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9,178,124
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Field trials of a vaccine against bovine mastitis. 1. Evaluation in heifers.
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A vaccine was developed against bovine mastitis based on inactivated, highly encapsulated Staphylococcus aureus cells; a crude extract of Staph. aureus exopolysaccharides; and inactivated, unencapsulated Staph, aureus and Streptococcus spp. cells. This vaccine was tested on 30 heifers during a 7-mo period. The 30 heifers were randomly assigned to three groups of 10 heifers each. The prepartum group received two injections of the vaccine at 8 and 4 wk before calving, and the postpartum group received two injections at 1 and 5 wk after calving. The control group received two injections of a placebo at 8 and 4 wk before calving. The vaccine or the placebo was administered subcutaneously in the brachiocephalicus muscle of the neck. The frequencies of intramammary infections caused by Staph. aureus were reduced from 18.8% for heifers in the control group to 6.7 and 6.0% for heifers in the prepartum and postpartum groups, respectively. This protective effect was maintained for at least 6 mo. The relative risk of mastitis caused by Staph. aureus was 0.31 and 0.28 for heifers in the prepartum and postpartum groups, respectively, compared with that for heifers in the control group. The results of the trial indicated the effectiveness of the vaccine in decreasing the incidence of intrammammary infections caused by Staph. aureus. A slight but nonsignificant increase occurred in fat production in the milk of vaccinated cows. The vaccine had no observable effect on somatic cell count or streptococcal infections.
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9,178,125
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Field trials of a vaccine against bovine mastitis. 2. Evaluation in two commercial dairy herds.
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A vaccine against bovine mastitis was developed. The vaccine was based on inactivated, highly encapsulated Staphylococcus aureus cells; a crude extract of Staph. aureus exopolysaccharides; and inactivated unencapsulated Staph. aureus and Streptococcus spp. cells. In this study, the vaccine was evaluated in 164 cows from two commercial dairies (A and B) during a 4-mo period. Two doses of the vaccine were administered subcutaneously to 82 cows in the brachiocephalicus muscle of the neck within a 4-wk interval. The results of this trial revealed significantly fewer intramammary infections caused by Staph. aureus at various levels of severity (clinical, subclinical, and latent) in cows that were vaccinated. The odds ratios of all types of intrammammary infections caused by Staph. aureus for dairies A and B, which were determined by a logistic model, were 1.84 and 1.89, respectively, for quarters of vaccinated cows and quarters of control cows. The colony counts for Staph. aureus in milk from infected quarters of vaccinated cows were significantly lower than those in milk from infected quarters of control cows. Also, the somatic cell counts per milliliter in milk from vaccinated cows were significantly decreased when the initial somatic cell count was < 500,000 cells/ml at the start of the trial. The vaccine had no observable effect on fat production in milk or on streptococcal infections.
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9,178,126
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The effects of early antibiotic treatment following diagnosis of mastitis detected by a change in the electrical conductivity of milk.
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Mastitis was induced experimentally by infusion of Streptococcus uberis or Staphylococcus aureus into the mammary glands of lactating dairy cows. Clinical mastitis was identified when clots appeared in foremilk (conventional diagnosis) or was predicted by changes in the electrical conductivity of foremilk (early diagnosis). The responses to intramammary antibiotic treatment that was initiated after early diagnosis of mastitis and after conventional diagnosis were compared. Early treatment significantly limited the severity of the disease and, in many cases, prevented the appearance of any visible signs of infection. Milk yield was less depressed, and the somatic cell count (SCC) was lower, when treatment was initiated earlier. The SCC of the quarter at the time mastitis was predicted was approximately 2 x 10(6) cells/ml for both pathogens, which was significantly less than when clots appeared at conventional diagnosis, approximately 4 x 10(6) and 12 x 10(6) cells/ml for Staph. aureus and Strep. uberis, respectively. The time required for SCC to recover to < 4 x 10(5) cells/ml was significantly less, approximately half, for both pathogens following early detection and early initiation of treatment. When treatment was administered in response to early detection, the bacteriological and clinical cure was almost complete, and the amount of antibiotic used was < or = 50% less. Obvious benefits for milk yield and quality and the health of the cow would result when changes in the electrical conductivity of milk are used to predict clinical mastitis and when treatment is initiated early.
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9,178,127
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Evaluation of alternative equations for prediction of intake for Holstein dairy cows.
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Six prediction equations for dry matter intake (DMI) were evaluated for accuracy with independent data. The equations were selected based on ease of parameter measurement and practical on-farm use. The equations were assessed for accuracy of predicting individual weekly DMI for primiparous (n = 105) and multiparous (n = 136) cows; three-fourths of these cows were supplemented with a sustained-release form of bovine somatotropin (bST). Large variations in accuracy were identified across the six prediction equations for effects of parity and bST. Prediction accuracy of all equations for cows in wk 1 to 24 of lactation was better for primiparous cows than for multiparous cows. Precision of prediction equations was poor for cows in wk 8 through 12 of lactation and for cows in > 40 wk of lactation. The equation for DMI with the best accuracy measured by a low total lactation mean square prediction error was the modified equation of the National Research Council: DMI (kilograms per day) = -0.293 + 0.372 x fat-corrected milk (kilograms per day) + 0.0968 x body weight 0.75 (kilograms). However, the overall mean bias (predicted minus observed) of the prediction of weekly DMI of a single cow was high for all equations, including the modified equation of the National Research Council. For wk 2, 4, 8, 10, and 20 of lactation, the mean bias for the modified equation was +6, +3.4, -1.3, -2.1, and -2.8 kg/d. The accuracy of prediction was lower for cows treated biweekly with bST. High yielding cows and cows treated biweekly with bST had higher milk yields in relation to body weight, and standardized prediction equations for DMI were less accurate.
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9,178,128
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Development and evaluation of equations for prediction of feed intake for lactating Holstein dairy cows.
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Improved prediction equations for dry matter intake (DMI) of Holstein cows that consume high energy diets were developed using regression techniques applied to a comprehensive database. The equations for predicting DMI, which were dependent on parity, accounted for the effects of milk yield, milk protein, body weight (BW), BW change, days pregnant, ambient temperature, relative humidity, and night cooling. A simplified prediction equation of DMI for farm application was developed and based on milk protein yield and BW at calving. An ambient temperature and a lag adjustment factor for early lactation were developed to improve accuracy of prediction of DMI of dairy cows in early lactation. The developed equations for DMI were evaluated against six independent data files. These equations accounted for 55 to 98% of the variation of the weekly group DMI of the independent validation data. The remainder of the variation in intake was attributed to diet, management, and undescribed animal factors. The equations developed in this study had a mean proportional bias of 5.6% and a mean square prediction error of 5.45 kg2/d. Predicted intake using the new equations was within 3 to 8% of actual intake. The new equations must be applied to situations in which Holstein dairy cows are fed highly digestible diets because dietary fill effects are not considered in these equations. The relationship of milk protein yield and DMI warrants further investigation.
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9,178,129
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Dietary variety via sweetening and voluntary feed intake of lactating dairy cows.
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The effects of choice of diets on feed intake were studied using 12 lactating Holstein cows. A switchback design was used that had three periods and two sequential blocks. Diets were 1) a control total mixed ration (TMR), which consisted of alfalfa haylage, corn silage, and a concentrate mixture based on ground corn and soybean meal (25:25:50 on a dry matter basis) and 2) a sweetened TMR in which a brown sugar food product constituted 1.5% of the dietary dry matter. Treatments consisted of the control TMR fed on both sides of divided feed bunks, the sweetened TMR fed on both sides of divided feed bunks, or both TMR fed on alternating (daily) sides of divided feed bunks in tie stalls. Periods were 2 wk in duration, and cows averaged 67 and 53 d of lactation at the start of blocks 1 and 2, respectively. The dry matter intake, body weight, milk yield, and percentages of milk fat, protein, and solids not fat were similar when either TMR was fed alone. A choice of control TMR or sweetened TMR did not affect any of these variables. The dry matter intake, body weight, milk yield, and milk protein percentage were affected by block; however, these effects were probably caused by differences between the blocks in environment and stage of lactation. The results of this experiment might have been affected by the composition of the control TMR, its similarity to the sweetened TMR, availability of both diets simultaneously when a choice was offered, and use of a TMR instead of separate feeds or simpler mixtures.
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9,178,130
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Influence of particle size on the effectiveness of beet pulp fiber.
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Sixteen Holstein cows in midlactation were used in a design based on a replicated 4 x 4 Latin square with the last period removed to determine the influence of particle size of beet pulp neutral detergent fiber (NDF) on its effectiveness as a replacement for alfalfa NDF. Diets were a low forage, low fiber diet [12.1 g of alfalfa NDF/100 g of dry matter (DM)], a normal forage diet (low forage plus 7.8 g of additional alfalfa NDF/100 g of DM), and two low forage diets with 5.3 g of NDF/100 g of DM from either whole or finely ground dried sugar beet pulp. Replacement of alfalfa fiber with beet pulp fiber increased milk protein yield because of the tendencies toward increased milk yield and protein concentration. However, milk fat concentration and yield were unaffected. The addition of beet pulp fiber, either whole or ground, to the basal low forage, low fiber diet did not affect yields of milk, protein, or fat, but milk protein concentration tended to be lower for cows fed the beet pulp diets than for cows fed the basal diet. Reducing the particle size of beet pulp increased DM intake but did not affect any of the milk yield measurements. Particle size reduction of beet pulp did not reduce its effectiveness as a fiber source as measured by changes in milk fat content.
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9,178,131
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Effect of percentage of dietary forage neutral detergent fiber and source of starch on performance of lactating Jersey cows.
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Five Jersey cows were used in a 5 x 5 Latin square design to determine the effects of decreasing dietary forage neutral detergent fiber (NDF) and different sources of dietary starch on performance and nutrient digestibilities. The control diet was balanced to consist of 21% forage NDF and 43% nonfiber carbohydrates. Four other diets were balanced to contain 35% nonfiber carbohydrates and either 16 or 11% forage NDF; diets were arranged in a 2 x 2 factorial design with either corn or corn and wheat as the sources of starch. Dry matter intake decreased linearly as forage NDF decreased; however, most of the decrease occurred when forage NDF was reduced from 16 to 11%. Milk production, yield of 4% fat-corrected milk, and percentages of milk fat and protein were similar among diets. Digestibility of NDF and acid detergent fiber increased as forage NDF decreased, but fiber digestibilities decreased with the addition of wheat to the diets. Starch digestibility was similar among diets. Source and amount of starch may be equally important or more important than the percentage of forage NDF for maintaining nutrient digestibilities of the total tract. Forage NDF in the diets of high producing cows can be reduced to 16% when sources and concentrations of starch are adequately balanced.
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9,178,133
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Factors affecting body tissue mobilization in early lactation dairy cows. 1. Effect of dietary protein on mobilization of body fat and protein.
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Twenty Holstein cows were fed diets that were formulated with 16 or 19% crude protein (CP) that contained, respectively, 6 and 9% ruminally undegradable protein (RUP) (dry matter basis) to study the effect of increased RUP on tissue mobilization and production parameters. Cows were enrolled in the study from -14 to 114 d postpartum. Body composition measurements using the D2O dilution technique were made at -2, 5, and 12 wk postpartum. Maximum loss of body tissue occurred between wk 2 prepartum and wk 5 postpartum during which time cows fed both treatments mobilized a mean of 54 kg of body fat and 21 kg of body protein. Cows continued to mobilize 18 kg of body fat through wk 12 postpartum, but the amount of body protein was unchanged. One unit of change in body condition score corresponded to about 40 kg of empty body fat. Partitioning of empty body energy between empty body fat and protein indicated that, for each unit of change in body energy, 93% was lost or gained as body fat, and body protein accounted for only 7%. Increasing RUP in the diet had no effect on the postpartum amounts of empty body protein, empty body fat, or empty body energy. Milk production was 39.8 kg for cows fed the 16% CP diet and 42.4 kg for cows fed the 19% CP diet. There was an interaction of treatment by week postpartum. Both dry matter intake and milk production were lower during the first 6 wk postpartum but were greater thereafter for cows fed the 19% CP diet than for cows fed the 16% CP diet. Milk CP percentage was higher (3.08% vs. 2.89%), and milk CP yield tended to be greater (1.29 vs. 1.15 kg/d), for cows fed the 19% CP diet.
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9,178,132
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Effect of nigericin, monensin, and tetronasin on biohydrogenation in continuous flow-through ruminal fermenters.
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Four ionophores differing in cation selectivity were compared for their effect on microbial fermentation and biohydrogenation by ruminal bacteria in continuous culture. Monensin and nigericin are monovalent antiporters with selective binding affinities for Na+ and K+, respectively. Tetronasin is a divalent antiporter that binds preferentially with Ca2+ or Mg2+. Valinomycin is a monovalent uniporter and does not exchange K+ for H+. Steady-state concentrations of 2 micrograms/ml of monensin, nigericin, tetronasin, or valinomycin were maintained by constant infusion into fermenters. Molar percentages of acetate were lower, and those of propionate were higher, in the presence of monensin, nigericin, and tetronasin; all three ionophores also decreased CH4 production. Concentrations of valinomycin as high as 8 micrograms/ml had no effect on volatile fatty acids or CH4 production. Monensin, nigericin, and tetronasin inhibited the rate of biohydrogenation of linoleic acid. Continuous infusion of C18:2n-6 at a steady-state concentration of 314 micrograms/ml into fermenters receiving monensin, nigericin, or tetronasin resulted in lower amounts of stearic acid and higher amounts of oleic acid. Ionophores increased total C18:2 conjugated acids mainly because of an increase in the cis-9, trans-11-C18:2 isomer. If reflected in milk fat, ionophore-induced changes in ruminal lipids could enhance the nutritional qualities of milk.
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9,178,135
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Influence of undergradability of protein in the diet on intake, daily gain, feed efficiency, and body composition of Holstein heifers.
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Thirty-two Holstein heifers with body weights (BW) between 213 and 231 kg were randomly assigned to one of four treatments for the 50-d trial. Treatments consisted of four percentages of rumen-undegradable protein (RUP) (31, 43, 50, and 55% of total N) at 100% of National Research Council recommendations for total digestible nutrients and crude protein. Total mixed diets composed of corn silage, ground barley straw, soybean meal, blood meal, urea, and minerals were formulated for a mean daily BW gain of 0.60 kg. Ration RUP percentage was varied by shifting protein sources. Mean dry matter intake (grams per kilogram of BW0.75) was 97.6, 84.4, 77.8, and 73.5 for 31% RUP (soybean meal), 43% RUP (blood and soybean meal), 50% RUP (blood meal with urea), and 55% RUP (blood meal) treatments, respectively. Daily gain was 0.84, 0.89, 0.91, and 0.96 kg/d, respectively. Intake of digestible energy (megacalories per kilogram of BW0.75 per day) was 0.28, 0.24, 0.22, and 0.21, respectively, and feed efficiency (megacalories of digestible energy per kilogram of BW gain) was 20.6, 16.1, 15.2, and 13.3, respectively. Dry matter intake (grams per kilogram of BW0.75), digestible energy intake, feed efficiency, daily BW gain, and hip height differed with respect to treatment. There were no differences in growth, wither height, or heart girth because of treatments. Changes in percentage of empty body fat as estimated by urea space procedures was 6.73, 4.67, 6.67, and 7.32, respectively, and did not differ with respect to treatments. These results indicate that increasing the RUP percentage in the diets of growing heifers improves feed efficiency and increases BW gain.
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9,178,134
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Milk production and composition responses to the source of protein supplements in diets containing wheat middlings.
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Two 3 x 3 Latin square trials were conducted to determine the effect of the source of supplemental protein in diets containing wheat middlings on milk production and composition. Cottonseed meal or meat and bone meal was substituted for a portion of the soybean meal and provided 24.5% of the total dietary crude protein. Trial 1 was conducted during fall 1989, and trial 2 was conducted during summer 1993. During trial 1, no differences in production or composition of milk were found for primiparous cows fed the various protein supplements. Multiparous cows tended to have higher dry matter intakes and produced more milk with lower milk fat percentages when fed meat and bone meal than when fed soybean meal or cottonseed meal. No differences were found among supplements for other milk components or for the production of energy-corrected milk. In trial 2, primiparous cows tended to produce more milk, and multiparous cows tended to produce less milk, when fed meat and bone meal than when fed soybean meal. No differences were found for dry matter intake, milk composition, or production of energy-corrected milk. Cottonseed meal was equal to soybean meal in supporting milk production. Meat and bone meal tended to support higher productions of milk than did soybean meal, but production of energy-corrected milk was similar for both.
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9,178,136
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Metabolism of water, sodium, potassium, and chlorine by high yielding dairy cows at the onset of lactation.
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We studied the balance of Na+, K+, Cl-, and water in six high yielding (> 39 kg/d of milk) cows between wk 2 to 1 prepartum and at 2 and 7 wk postpartum during winter in Israel. Cows were fed complete diets; Na+ and Cl- contents exceeded dietary recommendations, and K+ content was equal to dietary recommendations. Milk yield was related positively and significantly to retention of Cl- and K+, indicating that ions that are the main constituents of sweat can limit the ability of cows to express full genetic potential. The highest ion retention was recorded for cows that had the highest dry matter intake and, hence, the highest ion intake. Retention of Cl- was highest for cows that were most efficient in retaining Cl- in the kidney. In hot climates, increasing the concentrations of ions in the diet of early lactation cows according to the actual dry matter intake could prevent or reduce the severity of ion deficiencies. Water turnover rate of the cows was dependent on dry matter intake, milk yield, and respiratory-cutaneous water loss. The milk-free water balance (water turnover rate minus water secreted in milk) could be very efficiently predicted for lactating and nonlactating cows by the following equation: milk-free water balance (kilograms per day) = digestible energy intake (megacalories per day) x 0.58 + respiratory-cutaneous loss (kilograms per day) x 0.97 (n = 18; R2 = 0.97). This formula provides a tool to assess the evaporative-cutaneous water loss from feed and water intake measurements to evaluate the severity of heat stress.
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9,178,137
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Predictability of bull merit from genetic evaluations of sires and maternal grandsires using an animal model.
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The ability of animal model evaluations to predict the genetic potential of a bull from his sire and maternal grandsire was investigated. Theoretical coefficients were derived for different combinations of progeny records on the bull, sire, and maternal grandsire. Coefficients > 0.50 for sires and > 0.25 for maternal grandsires were associated with bulls with few daughters. Ten animal model evaluations of Holsteins, July 1989 to January 1994, were used to estimate coefficients realized in three populations: 1) all AI bulls (n = 6924), 2) current AI bulls (n = 1344), and 3) elite AI bulls (n = 6116). The PTA were analyzed for milk, fat, and protein yields, and for fat and protein percentages. Birth year of sons nested within the birth year of their sire was included as a random effect with a first-order autoregressive process for the regression model used to estimate the realized coefficients for sires and maternal grandsires. After adjustment for the genetic trend for estimates of sires, the correlation coefficient between predicted merit of sons from 2 consecutive yr ranged from 0.34 to 0.87. The PTA of bulls from first-crop evaluation were accurately predicted from PTA of sire and maternal grandsire for yield and percentage traits.
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9,178,138
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Dominance models with method R for stature of Holsteins.
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Estimates of variance components were obtained with method R for several additive and dominance models. The data included 301,960 records for first parity and 280,040 records for later parities of Holsteins. The single-record model included effects of management, regression on inbreeding percentage, age at calving, stage of lactation, and additive and dominance effects. The repeatability model included these effects in addition to permanent environment. For the single-record model, estimates were 46% of the total variance for additive variance, 12% of total variance for dominance variance, and -0.06 for the regression coefficient on inbreeding. In the repeatability model, the variance for permanent environment was estimated at 5%; other estimates were similar. When the dominance effect was eliminated, the estimate of the variance for permanent environment increased to 17% for the repeatability model. Elimination of stage of lactation increased regression on inbreeding to 0.09 and the estimate of dominance variance to 17% in the single-record model. The same change increased the estimate of additive variance to 64% for the repeatability model. Elimination of regression on inbreeding or stage of lactation had a small effect on the estimates. The presence or absence of the dominance effect had little influence on additive variance. In the absence of dominance, the estimate of the permanent environment effect included the dominance effect. Estimates of variances with method R are very sensitive to age adjustments. With the adjustments, the estimates of the dominance and additive variances are consistent.
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9,178,139
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Effects of method of colostrum feeding and colostrum supplementation on concentrations of immunoglobulin G in the serum of neonatal calves.
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Holstein heifer and hull calves (n = 52) at Ames Plantation (Grand Junction, TN) and Piedmont Research Station (Salisbury, NC) were blocked by sex and assigned randomly to receive 3.8 L of maternal colostrum in one feeding, 1.9 L in two feedings at a 10- to 12-h interval, or 1.9 L in two feedings at a 10- to 12-h interval plus 272 g of colostrum supplement at the first feeding. The colostrum supplement was mixed with 0.95 L of warm water and fed immediately following colostrum. Serum immunoglobulin G (IgG) concentrations were unaffected by the number of feedings and averaged 20.0 and 16.6 g/L at 24 and 48 h, respectively. Calves that were fed the colostrum supplement at the first feeding had lower serum IgG concentrations at 24 h (16.0 g/L) than did calves that were fed two colostrum feedings without supplementation (21.0 g/L); however, serum IgG concentrations at 48 h did not differ among treatments. Dry matter intake and body weight gain were unaffected by feeding method. Calves may be fed high quality colostrum in one or two feedings without affecting IgG absorption.
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9,178,140
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Uterine health and disorders.
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Nonspecific uterine infections reduce the reproductive efficiency of cows and the profit potential of dairy farms. Fortunately, most cows do not develop severe uterine infections. The term uterine infection indicates that the uterus is contaminated with pathogenic organisms. Actinomyces pyogenes, either alone or with other bacteria, is often associated with uterine infections. When A. pyogenes was isolated from uterine fluids after d 21 postpartum, cows developed severe endometritis and were infertile at first service. However, the exact causes of uterine infections are unknown but are associated with several factors. Cows with dystocia, retained placenta, twins or still-births, and various metabolic disorders are more likely to develop metritis than are other cows. Aberrant immune function before and after calving seems to predispose cows to severe uterine infections. Few cows die from uterine infections, but cows with uterine infections are more likely to be culled for poor reproductive performance. Also, uterine infections can reduce milk production, and some treatments contaminate milk. Because they are nonspecific, uterine infections are difficult to prevent; attention to sanitation and periparturient hygiene, especially during assisted calving, may be the best defense. Evidence that aberrant immuno function predisposes cows to uterine infections indicates that methods for regulating immune function in periparturient cows have the potential for preventing or treating uterine infections.
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9,178,141
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Ovarian follicular cysts in dairy cows.
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Ovarian follicular cysts are anovulatory follicular structures that occur in 10 to 13% of dairy cows. This review focuses upon the dynamics of cyst growth, development, and persistence as well as on associated endocrine and cellular mechanisms. During the estrous cycle of cows, two to four waves of follicular growth occur. From a cohort of recruited follicles, one is selected for continued growth and dominance while the other undergo atresia and regress. In contrast, cysts have long been thought to be static structures that persist for extended periods. Although cysts can persist for extended periods, most regress over time and are replaced during subsequent follicular waves. The next dominant follicle either ovulates or develops into a new cyst. The recruitment of a cohort of follicles from which a cyst develops and the growth rate of cysts to ovulatory size are similar to ovulatory follicular waves, but the cyst continues to grow for a longer period. The interval between waves of follicular growth is longer for cows with cysts than for cows with normal estrous cycles. Each wave is preceded by a transient increase in circulating FSH. Near the time of cyst development and persistence, the concentration of FSH is not different from that during normal estrous cycles. Serum concentrations of LH and estradiol-17 beta are higher in cows that develop cysts than in cows that do not. Conversely, hypothalamic content of GnRH is lower in cows with cysts. Thus, cysts are dynamic structures, and their development and lifespan are likely associated with altered hypothalamic-hypophysial-ovarian function.
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9,178,142
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Bovine acidosis: implications on laminitis.
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Bovine lactic acidosis syndrome is associated with large increases of lactic acid in the rumen, which result from diets that are high in ruminally available carbohydrates, or forage that is low in effective fiber, or both. The syndrome involves two separate anatomical areas, the gastrointestinal tract and body fluids, and is related to the rate and extent of lactic acid production, utilization, and absorption. Clinical manifestations range from loss of appetite to death. Lactic acid accumulates in the rumen when the bacteria that synthesize lactic acid outnumber those that utilize lactic acid. The systemic impact of acidosis may have several physiological implications, including laminitis, a diffuse aseptic inflammation of the laminae (corium). Although a nutritional basis for the disease exists, etiology includes a multitude of interactive factors, such as metabolic and digestive disorders, postpartum stress, and localized trauma, which lead to the release of vasoactive substances that trigger mechanisms that cause degenerative changes in the foot. The severity of laminitis is related to the frequency, intensity, and duration of systemic acidotic insults on the mechanisms responsible for the release of vasoactive substance. The critical link between acidosis and laminitis appears to be associated with a persistent hypoperfusion, which results in ischemia in the digit. Management of acidosis is critical in preventing laminitis. High producing dairy herds attempting to maximize energy intake are continually confronted with subclinical acidosis and laminitis. Management of feeding and husbandry practices can be implemented to reduce incidence of disease.
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9,178,151
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Inflammatory myopathies and systemic disorders: a review of immunopathogenetic mechanisms and clinical features.
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The inflammatory myopathies are a heterogeneous group of muscle diseases characterized by muscle degeneration mediated by inflammatory processes. They may be idiopathic, as in polymyositis, dermatomyositis and inclusion body myositis, or associated with systemic disorders such as malignancies, overlap syndromes, and retroviral infection. The pathogenesis of each disease is discussed together with more recent molecular and cellular immunology findings. Salient diagnostic, clinical and pharmacological features are also reviewed.
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9,178,145
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A preliminary report on the use of relon mesh in the repair of eventrations with large parietal defects. An experimental study in rats.
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This experimental study in rats was designed to investigate the tolerability and the mode of healing when commercial relon mesh is used in the repair of large abdominal-wall defects. A defect was created to simulate anatomical derangement of the abdominal wall and a surgical correction was performed using relon mesh. The mesh was implanted intraperitoneally in 18 Wistar albino rats. The animals were killed under anaesthesia 4, 6, 8, 12, 15 or 30 days later and the intra-abdominal viscera were examined macroscopically for adhesions and other evidence of inflammatory reactions. Skin healing usually occurred within 7-8 days of surgery. Microscopic studies were used to confirm the gross findings and showed that maturation of granulation tissue, fibrocyte invasion with encapsulation of the mesh and the appearance of newly formed vessels occurred 2 weeks after surgery. Within 4 weeks a strong layer of connective tissue was present. The relon mesh was tolerated well. These results indicate that the use of relon mesh may provide a cheap alternative means of repairing large abdominal-wall defects.
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9,178,152
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Ocular flutter and truncal ataxia may be associated with enterovirus infection.
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We report on three patients who presented a rare, uniform clinical syndrome consisting of ocular flutter and truncal ataxia. In all patients the symptoms followed an upper respiratory infection and resolved without sequelae within a few weeks. Previous reports have emphasized the apparent relationship of this entity to infectious disease, but the infectious agent remained uncertain. In one patient we could find a significant rise in antibody titres to enterovirus. We are not aware of any other similar documented case.
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9,178,154
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Movement disorders in Japanese encephalitis.
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Movement disorders in Japanese encephalitis (JE), although reported, have not been analyzed systematically. In this study, we report an analysis of movement disorders in 14 out of 17 JE patients, correlated with the radiological findings. All patients had at least a four fold rise of IgG antibodies against JE in a haemagglutination inhibition test. The patients' ages ranged between 2 and 54 years and 4 of them were women. Extrapyramidal signs, such as hypokinesia, hypophonia and masking of the face, were present in all patients by the first month as the patients came out of the coma-except for 1 patient. Eight patients had axial and 3 tongue dyskinesia; rigidity was present in 6 and tremor in 2 patients. At 3 months, these symptoms improved considerably in 6 patients. Cranial CT scan revealed thalamic involvement in 10, which was bilateral in 9 patients. Two patients had brain stem and one had cerebellar involvement. Cranial MRI was carried out in 9 patients and revealed additional findings in lentiform nucleus, midbrain and pons in 3 each and cerebellum in 4 patients. Bilateral thalamic involvement on MRI was seen in all the patients, including two patients whose CT scans were normal. SPECT studies using 99mTc-ECD revealed bilateral thalamic hypoperfusion in all (n = 7) and frontal hypoperfusion in 3 patients. In JE, movement disorders are common and may be due to thalamic involvement in isolation or in combination with basal ganglia or midbrain or both.
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9,178,153
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Differences in factors associated with silent and symptomatic MRI T2 hyperintensity lesions.
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The factors and symptomatology associated with different types of hyperintensity lesions on MRI were investigated. The study population consisted of 139 subjects who were recruited from 450 outpatients who had a neurological diagnosis in 1994. The subjects underwent brain magnetic resonance imaging between 1994 and 1995 and were divided into three groups (control, asymptomatic, and symptomatic) on the basis of T2 hyperintensity lesions, as well as a history of or neurological signs of stroke, or both. The demographic characteristics and risk factors were studied, and the T2 hyperintensity lesions were analysed semi-quantitatively. Results showed that: (1) the control and asymptomatic groups did not differ in terms of risk factors and demographic characteristics with the exception of age; (2) the symptomatic group was characterized by a significantly higher incidence of hypertension and electrocardiographic abnormalities, as well as significantly more numerous risk factors when compared with the other two groups; (3) the symptomatic patients also had higher proportion of men and higher levels of systolic blood pressure and blood glucose than the control patients, and more frequent hypertriglyceridaemia and higher triglyceride level than the asymptomatic patients; (4) the symptomatic group had a greater lesion distribution in the posterior basal ganglia-internal capsule and the infratentorial regions than did the asymptomatic group. We concluded that the asymptomatic and symptomatic groups should not be considered identical entities.
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9,178,155
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Magnetic stimulation in Alzheimer's disease.
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Alzheimer's disease (AD) is a common cause of dementia in which some clinical motor abnormalities have been described. We used transcranial magnetic stimulation in order to test the hypothesis that the change in the motor cortex might cause modifications in motor excitability. Fourteen mildly to moderately affected AD patients were compared with 11 controls matched for age, height and sex. The motor evoked potential threshold value for the relaxed abductor digiti minimi was lower in the AD patients than in the control group for both left and right hemispheres (P < 0.05). No statistically significant difference was found comparing the left and the right hemispheres thresholds in each population. The mean interside threshold differences were small and not significantly different between patients and controls. The spinal motor neuron excitability, as evaluated by F/M and H/M waves amplitude ratios, showed no difference between the groups, reinforcing the motor cortex increased excitability hypothesis to explain this difference. Degeneration of inhibitory gabaergic terminals might be the basis for the increased cortical excitability in the motor cortex of the Alzheimer patients; postsynaptic changes in the GABAA receptors might also affect inhibitory gabaergic transmission. The increased excitability found by transcranial magnetic stimulation in the motor cortex is important for understanding the emergence of seizures and myoclonus in this disease.
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9,178,150
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Budd-Chiari syndrome: a review of ten cases.
|
The cases of ten patients with Budd-Chiari syndrome who were admitted to our medical centre between 1974 and 1986 were reviewed. There were three survivors; the remaining seven died after their disease had taken a rapid downhill course. The clinical course of Budd-Chiari syndrome and the various modalities of medical and surgical treatment are outlined.
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9,178,143
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Effect of the calcium channel blocker nilvadipine on urinary albumin excretion in hypertensive microalbuminuric patients with non-insulin-dependent diabetes mellitus.
|
A 24-week study was conducted to evaluate the effects of the dihydropyridine calcium channel blocker nilvadipine on urinary albumin excretion in eight microalbuminuric hypertensive patients with non-insulin-dependent (type II) diabetes mellitus. Blood pressure and urinary albumin excretion measurements before the administration of nilvadipine (8 mg) were compared with those after 4, 8, 12 and 24 weeks of treatment. No significant changes were observed in the mean values of haemoglobin A1C. Systolic blood pressure was significantly reduced from 174 +/- 23 mmHg before treatment to 144 +/- 13 mmHg after 24 weeks of treatment (P < 0.02). Diastolic blood pressure was significantly reduced from 93 +/- 11 mmHg at baseline to 79 +/- 8 mmHg after 24 weeks of treatment (P < 0.05). Urinary albumin excretion was significantly reduced from 65.4 +/- 37.4 mg/g creatinine at baseline to 51.6 +/- 41.1 mg/g creatinine (P < 0.05) after 4 weeks, and to 39.1 +/- 26.9 mg/g creatinine (P < 0.02) after 24 weeks of treatment. These data suggest that in hypertensive microalbuminuric patients with non-insulin-dependent diabetes mellitus, treatment of hypertension with the calcium blocker nilvadipine may slow the progression of diabetic nephropathy.
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9,178,144
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Investigation of the influenza-like symptoms associated with recombinant human erythropoietin therapy.
|
The mechanism by which fever and influenza-like symptoms occur, after the administration of recombinant human erythropoietin (rHuEPO) to patients on continuous ambulatory peritoneal dialysis, was investigated. Peripheral blood mononuclear cells, obtained from two patients with fever and/or influenza-like symptoms related to the administration of rHuEPO for the treatment of anaemia were cultured with or without rHuEPO (100, 200, and 300 U/ml). Production of interleukin-1 beta and tumour necrosis factor-alpha was higher in cultures with rHuEPO than in cultures without rHuEPO, although the dose relationships were not clear. These findings suggest that increased production of interleukin-1 beta and tumour necrosis factor-alpha 1, induced by administration of rHuEPO, may cause fever and influenza-like symptoms.
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9,178,156
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Serial magnetisation transfer ratios in gadolinium-enhancing lesions in multiple sclerosis.
|
The magnetisation transfer (MT) ratio of eight multiple sclerosis lesions has been studied serially. Initially, when the lesions showed gadolinium enhancement, there was a marked reduction in their MT ratio compared with normal white matter. Follow-up a mean of 11 months later (range 3-23 months), when the lesions no longer enhanced, revealed a consistent and usually marked recovery of the MT ratios towards normal. The MT ratio is thought to reflect the structural integrity of tissues with an important contribution from myelin and axons. MT imaging is a promising tool for elucidating pathophysiology and monitoring treatment in multiple sclerosis.
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9,178,157
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Source of cerebral microembolic signals in occlusion of the internal carotid artery.
|
There are several possible sources of cerebral embolic ischaemia distal to an occlusion of the internal carotid artery (ICA). Our aim was to identify the source of microembolic signals in the ipsilateral middle cerebral artery (MCA) by taking simultaneous bitemporal transcranial Doppler ultrasound recordings of the ipsilateral MCA and the contralateral ACA to find the route of potential microembolic material to MCA.
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9,178,158
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Value of nerve biopsy in the diagnosis and follow-up of leprosy: the role of vascular lesions and usefulness of nerve studies in the detection of persistent bacilli.
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Nerve biopsy specimens from 53 patients with leprosy and neuropathy were taken from the sural, the dorsal branch of the ulnar, or the superficial radial nerves and processed for light and electron microscopy. There was inflammation in 40 cases (75%), 7 with a granulomatous reaction, various stages of fibrosis in 35 (66%), and endoneurial vascular neoformation in 7. In two cases, small focal infarcts were associated with marked endoneurial inflammation compressing the vessels, in addition to endoneurial lymphocytic vasculitis. Most had an axonal neuropathy of varying degree, some with total fibre loss, others with predominant small myelinated and unmyelinated fibre loss. Signs of demyelination and remyelination were the main findings in 9 cases (17%). Bacilli were present in endothelial, perineurial, Schwann cells and in macrophages. On two occasions, they lost their alcohol acid resistance, were suspected in semithin sections, and confirmed ultrastructurally. The biopsy was decisive for the diagnosis of leprosy in 15 cases (28%), most without skin lesions. We evaluated the effectiveness of the treatment in 20 (37.7%), 12 without and 8 with bacilli, despite negativity in the skin. The diagnosis of leprosy based on skin lesions was confirmed with the nerve biopsy in 9 cases, 6 had an inflammatory neuropathy suggestive of leprosy in the absence of bacilli, and 3 had nonspecific changes in the sural nerve since the neuropathy was in the upper limbs. We conclude that nerve biopsy is indicated for the diagnosis of leprosy in cases without clinically visible skin lesions and to evaluate the effectiveness of the treatment. In these cases the ultrastructural studies are important for recognition of the bacilli. Vascular lesions may play an important role in the progression of the nerve damage, including the occurrence of focal nerve infarcts which, to our knowledge, have not been previously reported in association with leprosy.
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9,178,147
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Staphylococcus aureus in the anterior nares and subungual spaces of the hands in atopic dermatitis.
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We examined the prevalence of Staphylococcus aureus in the anterior nares and the subungual spaces of the hands of patients with atopic dermatitis to determine whether the presence of S. aureus at these sites may contribute to the aggravation of the dermatitic skin lesions. The prevalence of S. aureus in the anterior nares of patients with atopic dermatitis was over five times higher than that in the anterior nares of patients with other skin diseases or in healthy adult controls, and the prevalence of S. aureus in the subungual spaces was 10 times higher in patients with atopic dermatitis than in those with other skin diseases or in controls. Both the anterior nares and the subungual spaces of the hands are important reservoirs of S. aureus in atopic dermatitis. The phage type of S. aureus strains isolated from the anterior nares is similar to that of the strains isolated from the subungual spaces.
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9,178,146
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Role of transforming growth factor-beta 1 and -beta 2 in ddY mouse nephropathy.
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We investigated the glomerular distribution of transforming growth factor-beta (TGF-beta 1 and TGF-beta 2) protein and the expression of its mRNA, and related factors, in ddY mice, aged 5-60 weeks, before and after the onset of nephropathy, TGF-beta 1 protein expression was observed from the age of 20 weeks onwards, peaking at 50 weeks, and then declining. Expression of TGF-beta 2 protein gradually increased from 5 to 60 weeks. TGF-beta 1 and TGF-beta 2 mRNA were both detected from 5 to 60 weeks. The mesangial matrix expansion index (MMEI) was significantly higher in mice with nephropathy than in those without nephropathy, as was the expression of TGF-beta 1 and TGF-beta 2 proteins (P < 0.05). TGF-beta 2 was significantly positively correlated with the MMEI (P < 0.05). Infiltration of CD68-positive monocytes/macrophages gradually increased until 60 weeks, and was significantly correlated with the expression of TGF-beta 1 (P < 0.05) and TGF-beta 2 (P < 0.01). These findings indicate that TGF-beta 1 and TGF-beta 2 were overexpressed in ddY mice with overt nephropathy compared with pre-nephropathic mice. TGF-beta 2 may be an important mediator of mesangial matrix expansion in ddY mouse nephropathy.
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9,178,148
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The use of prostaglandin E2 for cervical ripening in patients requiring induction of labour.
|
A total of 290 women who required induction of labour for medical or obstetric reasons were given single or multiple doses of prostaglandin E2 gel (0.5 mg) to induce cervical ripening. Onset of labour occurred in 185 (63.8%) of the women treated with the gel, without any further treatment. The overall Caesarean section rate was 27.2% (79/290) and was significantly higher among those with an initially low Bishop score than in those with a higher initial score (34.7% versus 22.1%; P = 0.025). Prostaglandin E2 gel appears to be of considerable clinical benefit, especially where no other options are available except Caesarean section or a very long, difficult labour that may result in significant fetal distress.
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9,178,149
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Efficacy of a combined diloxanide furoate-metronidazole preparation in the treatment of amoebiasis and giardiasis.
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A combined formulation of diloxanide furoate and metronidazole was used to treat amoebiasis and giardiasis (cysts and vegetative forms) in 54 patients. Of these 34 patients had amoebiasis, 19 had giardiasis and one had mixed infection. Each patient took one tablet (containing 500 mg diloxanide furoate and 400 mg metronidazole), three times daily for 5 days, and the response to therapy was checked by clinical examination and by examination of fresh stools on days 3, 5 and 10. Abdominal pain was completely relieved in 91% and 84% of patients with amoebiasis and giardiasis, respectively, while parasitic clearance was 100% in both groups. Tolerance to the drug was adequate.
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9,178,159
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Carotid artery dissections presenting as isolated posterior cerebral artery infarctions.
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A spontaneous dissection of the carotid artery is a well-known cause of cerebral infarction, mostly due to an embolus from the affected vessel segment. For haemodynamic and anatomical reasons the territories of the middle and anterior cerebral arteries are usually involved. We report two cases of carotid artery dissections resulting in infarctions exclusively in the territory of the posterior cerebral artery. The underlying anatomical conditions were a fetal origin of the posterior cerebral artery and an embolic supra-ophthalmic occlusion of the internal carotid artery. To our knowledge similar cases have not previously been documented.
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9,178,160
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Peroneal nerve neuropathy in cancer patients: a paraneoplastic syndrome?
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To investigate the occurrence of symptomatic peroneal neuropathy (PN) in cancer patients, as well as that of cancer in PN patients and to seek possible factors in the aetiology of PN.
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9,178,166
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Transgenic animal models of familial amyotrophic lateral sclerosis.
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Amyotrophic lateral sclerosis (ALS) occurs in both sporadic and familial forms, which have very similar clinical presentation and course. Approximately 20% of the familial cases of ALS are caused by mutation of the SODI gene encoding Cu, Zn superoxide dismutase (SOD). Over 30 different SODI gene mutations have been found in patients. Most are missense mutations that cause the substitution of one amino acid for another. The failure to find deletions in familial ALS suggests that the mutant protein is required for pathogenesis. Studies in transgenic mice indicate that familial ALS is caused by gain-of-function mutations in the SODI gene. These enhance formation of free radicals by the mutant enzyme. When expressed at high levels in transgenic mice, mutant human Cu,Zn SOD causes a clinical disease that resembles human ALS. Selective degeneration of motor neurones in the spinal cord and brainstem is accompanied by progressive motor impairment. Pathogenesis in the transgenic model of familial ALS is a sequential, two-step process in which damage mediated by free radicals accumulates to a threshold that triggers catastrophic motor neurone loss through glutamate-mediated, excitotoxic mechanisms. Evidence in support of this hypothesis comes from therapeutic studies with antioxidants and inhibitors of glutamatergic neurotransmission.
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9,178,165
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Glutamate, excitotoxicity and amyotrophic lateral sclerosis.
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The "glutamate hypothesis" is one of three major pathophysiological mechanisms of motor neurone injury towards which current research effort into amyotrophic lateral sclerosis (ALS) is directed. There is great structural and functional diversity in the glutamate receptor family which results from combinations of 14 known gene products and their splice variants, with or without additional RNA editing. It is possible that motor neurones express a unique molecular profile of glutamate receptors. Abnormal activation of glutamate receptors is one of five main candidates as a final common pathway to neuronal death. In classical acute excitotoxicity, there is influx of Na+ and CI-, and destabilisation of intracellular Ca2+ homeostasis, which activates a cascade of harmful biochemical events. The concept of secondary excitotoxicity, where cellular injury by glutamate is triggered by disturbances in neuronal energy status, may be particularly relevant to a chronic neurodegenerative disease such as ALS. Data are now beginning to emerge on the fine molecular structure of the glutamate receptors present on human motor neurones, which have a distinct profile of AMPA receptors. Two important molecular features of motor neurones have been identified that may contribute to their vulnerability to neurodegeneration. The low expression of calcium binding proteins and the low expression of the GluR2 AMPA receptor subunit by vulnerable motor neurone groups may render them unduly susceptible to calcium-mediated toxic events following glutamate receptor activation. Eight lines of evidence that indicate a disturbance of glutamatergic neurotransmission in ALS patients are reviewed. The links between abnormal activation of glutamate receptors and other potential mechanisms of neuronal injury, including activation of calcium-mediated second messenger systems and free radical mechanisms, are emphasised. Riluzole, which modulates the glutamate neurotransmitter system, has been shown to prolong survival in patients with ALS. Further research may allow the development of subunit-specific therapeutic targeting of glutamate receptors and modulation of "downstream" events within motor neurones, aimed at protecting vulnerable molecular targets in specific populations of ALS patients.
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9,178,167
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The Riluzole Early Access Programme: descriptive analysis of 844 patients in France. ALS/Riluzole Study Group III.
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Recent controlled trials in outpatients with amyotrophic lateral sclerosis (ALS) indicate that riluzole prolongs tracheostomy-free survival. After 12 months' treatment, riluzole 50 mg, 100 mg and 200 mg daily reduced the risk of death or tracheostomy (relative to placebo) by 24%, 34% and 31%, respectively (by 28%, 43% and 43%, respectively, after adjustment for known prognostic factors). This survival advantage (6-9 patients require treatment with riluzole to avoid 1 death/tracheostomy annually) compares favourably with that achieved therapeutically in breast cancer and coronary artery disease. Some 6000 ALS patients are currently receiving riluzole 50 mg twice daily within the Riluzole Early Access Program. In France, this programme is being implemented as an open-label multicentre trial to assess patients' functional status and quality of life. To date, 844 patients have been enrolled, and they will be followed up for 12 months on riluzole. Baseline demographic and clinical characteristics of this study population are presented here.
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9,178,168
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Health outcome and quality-of-life measurements in amyotrophic lateral sclerosis.
|
Quality of life has been used as a primary outcome measure in the treatment of cancer and cardiovascular disease, and as a secondary outcome measure in therapy of Parkinson's disease. However, it has been relatively neglected in studies of amyotrophic lateral sclerosis (ALS). Although there is need for the development of an ALS-specific quality-of-life measure, it will be necessary, nonetheless, to continue to use generic measures in order to ensure comparability of measurement between disease states. An argument is put forward for the use of quality-of-life measures as a primary end-point in future clinical trials in ALS. A distinction is drawn between the demonstration of biological efficacy and clinically useful benefit. The most likely instruments to prove useful are briefly discussed.
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9,178,169
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Impact of riluzole on the relationship between patient and physician.
|
To date, there has been little systematic research on the patient-physician relationship in amyotrophic lateral sclerosis (ALS). Important factors in this relationship are the emotional state, or mood, of the patients and their expectations of successful therapeutic intervention. In many patients there is a gradual deterioration of mood with disease progression-a view supported by studies comparing the initial and late phases of the disease. The few studies examining patients' expectations of therapy revealed a strong desire to be informed about the disease and its course without destroying every hope. In the later stages of the disease patients expected compassion and help with immediate problems. To our knowledge there has been no systematic study on the attitude of physicians towards ALS patients. The lack of effective treatment and the wish to avoid full information about the poor prognosis are almost unique problems involved in dealing with ALS patients. The new option to treat with a drug that slows disease progression provides some alleviation for the physician. Riluzole, at least, partially meets this expectation. Although its efficacy is too limited to satisfy fully the wishes of patients and physicians, it is the first available drug that has been shown to slow disease progression. Thus, it may bring to an end the feeling that there is nothing that can be done for these patients. In our experience this provides relevant alleviation in the management of ALS patients.
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9,178,170
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Oral exfoliative cytology: review of methods of assessment.
|
The use of oral exfoliative cytology in clinical practice declined due to the subjective nature of its interpretation and because there may be only a small number of abnormal cells identifiable in a smear. The more recent application of quantitative techniques, together with advances in immunocytochemistry, have refined the potential role of cytology, stimulating a reappraisal of its value in the diagnosis of oral cancer. This review considers the influence of the quantitative analysis of cytomorphology, DNA analysis and other tumour markers applied to oral exfoliative cytological samples. These studies indicate that oral cytology may provide an important adjunct in the assessment of the patient with a potentially cancerous oral lesion.
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9,178,171
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Enhancement of calcyclin gene RNA expression in squamous cell carcinoma of the oral mucosa, but not in benign lesions.
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Oral cancer is a neoplasm with some known causes. Proliferation genes are significant among its few pathogenetic and prognostic factors. Calcyclin is a cell-cycle-related gene, the function of which is still unclear. Its expression and that of Haras and histone-H3 have been investigated in an assessment of their pathogenetic role in squamous cell carcinoma. RNA extracted from the pathological and normal mucosa of patients with squamous cell carcinoma (SCC) and benign lesions was reverse transcribed and amplified by the polymerase chain reaction (PCR). The expression of all three genes in the pathological mucosa was enhanced in SCC only. This suggests that they may be involved in its pathogenesis and provides another parameter for the differentiation of malignant and benign lesions.
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9,178,172
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Expression of p53, Ki-67 and cytokeratin-4 (CK4) in oral papillomas.
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P53 is overexpressed in more than 50% of all human cancers. A previous study suggested that p53 was also overexpressed in oral papillomas. This study was carried out to investigate whether p53 expression was correlated with expression of the cellular proliferation marker Ki-67 and the epithelial differentiation marker cytokeratin-4 (CK4) in oral papillomas. Formalin-fixed paraffin-embedded sections of 30 oral papilloma specimens and 30 unmatched normal oral mucosal specimens were processed for immunohistochemistry, using an avidin-biotin-peroxidase procedure and monoclonal antibodies. A semiquantification analysis on p53 and Ki-67 labeling indices was performed. Twenty-eight of 30 (93%) papilloma specimens were positive for p53. The percentage of p53-positive cells in the basal layer was 60.4 +/- 14.8 (mean +/- SD, n = 28), and that of Ki-67-positive cells was 26.7 +/- 14.4. There was no correlation between expression of p53 and that of Ki-67. Expression of CK4 was inversely correlated with the expression of Ki-67 but not correlated with the expression of p53.
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9,178,174
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Dynamic distribution of basic fibroblast growth factor during epulis formation: an immunohistochemical study in an enhanced healing process of the gingiva.
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Basic fibroblast growth factor (bFGF) is thought to play an important role in wound healing. However, its histological localization, both in normal and pathological conditions in the oral mucosa, has not been well documented. We have studied the immunolocalization of bFGF in normal gingiva and gingival epulis specimens corresponding to different organizing stages. In normal gingiva, bFGF was detected in subpopulations of macrophages, mast cells and most endothelial cells in the lamina propria. Granulation tissue in epulides was histopathologically classified into six organizing stages. In stages 1 and 2, a small number of bFGF-positive macrophages was seen at the periphery of ulcer bases. In stages 3 and 4, histologically characterized by prominent capillary proliferation, large numbers of bFGF-positive macrophages and mast cells were located within granulation tissue. A positive reaction for bFGF was also found in some endothelial cells and in myxoedematous stroma that was rich in heparan sulfate proteoglycan. In stages 5 and 6, when fibrosis was accelerated, bFGF-positive macrophages and mast cells decreased in number and were localized only at the periphery of the fibrous tissue. These findings suggest that maximum amounts of bFGF are synthesized and released from some macrophages and mast cells into the extracellular matrix during neovascularization of granulation tissue.
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9,178,173
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Expression and mutations of p53 in salivary gland tumours.
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A series of 219 salivary gland tumours (103 carcinomas and 116 benign tumours) were analysed for p53 protein expression using immunohistochemistry, and for mutations in p53 gene using non-radioactive single strand conformation polymorphism (SSCP). p53 expression was present in 36% (42/116) of the benign tumours and in 54% (56/103) of the carcinomas. The highest prevalence of p53 expression was found in adenoid cystic carcinomas (69%), followed by mucoepidermoid carcinomas (67%). Of the benign tumours, pleomorphic adenomas showed the highest prevalence of p53 positivity (41%). In malignant tumours, expression of p53 bore no correlation to local recurrence, metastatic disease or survival of the patients. Exons 5 through 9 were analysed and four mutations were found in 20 cases of p53-immunopositive tumours and two in 20 p53-negative tumours. Each of the exons 5, 6 and 8/9 had two mutations, whereas no mutations were detected in exon 7.
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9,178,176
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Oral candidiasis in HIV infection: predictive value and comparison of findings in injecting drug users and homosexual men.
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The objectives of this study were to compare the relationship of oral candidiasis to HIV status, cohort and CD4+ lymphocyte values in injecting drug users and homosexual men and to examine its impact on prognosis. An oral examination was added to an ongoing longitudinal study of HIV infection. Data obtained at 6-month intervals included smoking, illicit drug use, medication use, symptoms and medical diagnoses, physical examination findings and laboratory data. In this study HIV+ subjects were much more likely to present with oral candidiasis than were HIV- subjects (OR = 6.3, P < 0.01). Injecting drug users, regardless of serostatus, were more likely than homosexual men to present with oral candidiasis (OR = 3.0, P = 0.001). In both cohorts oral candidiasis was associated with low CD4+ lymphocyte counts and percent ages, and Kaplan-Meier survival estimates showed that subjects with oral candidiasis had a poorer prognosis than those without candidiasis, even after controlling for CD4+ lymphocyte count.
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9,178,175
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The in vitro adhesion of Candida albicans to buccal epithelial cells (BEC) from diabetic and non-diabetic individuals after in vivo and in vitro application of nystatin.
|
Buccal epithelial cells (BEC) from 12 patients with diabetes mellitus and 12 age- and sex-matched non-diabetic subjects were tested in vitro for adhesion of Candida albicans following exposure to nystatin both in vitro and in vivo. Adhesion was significantly reduced (P < 0.002) to cells from both the diabetic and non-diabetic subjects after in vitro exposure to nystatin, but the reduction in adhesion was variable (5.0-50.7% in control subjects and 0.5-48.4% in diabetic subjects) and equivalent between the two groups. In vivo exposure to nystatin produced no overall significant reduction in candidal adhesion to cells from either diabetic or control subjects.
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9,178,177
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Autopsy findings in the tongues of 20 patients with AIDS.
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An extensive examination of the tongue was performed at autopsy in 20 consecutive patients who had died with AIDS. Abnormalities in the tongue were detected in 18 (90%) of the cases; the commonest lesions were ulceration (11), candidosis (8) and small foci of hyperkeratosis (10). The most extensive lesions were caused by Aspergillus infection (1), non-Hodgkin's lymphoma juxtaposed with Kaposi's sarcoma (1), herpetic infection (1) and candidosis (5). The disease causing death was identified in the tongue in two cases. There was a surprisingly low prevalence of oral hairy leukoplakia, which may be related to anti-viral or retroviral therapy.
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9,178,178
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Synthesis and biological evaluation of new 3-aralkylamino-2-aryl-2H-1, 2,4-pyridothiadiazine 1,1-dioxides as potential CCK-receptor ligands.
|
A series of 2-aralkyl-4H-pyridothiadiazine 1,1-dioxides and 3-aralkylamino-2-aryl-2H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides structurally related to quinazolinone CCK receptor antagonists were synthesized and evaluated as CCK-A and CCK-B receptor ligands. The compounds were effective as cholecystokinin-ligands in the micromolar range of concentration, c.f. the cholecystokinin receptor antagonists asperlicin, lorglumide or benzotript, and were thus less potent than the best quinazolinones previously reported. Although the compounds were unsuitable for drug use, the work contributed to our understanding of the chemistry of unusual 2,3-disubstituted pyridothiadiazinedioxides.
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9,178,179
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Investigation of physicochemical changes to L-asparaginase during freeze-thaw cycling.
|
L-Asparaginase derived from Erwinia chrysanthemi which is being investigated as an alternative to E. coli for the treatment of lymphoblastic leukaemia has been found in our laboratory to lose activity upon exposure to consecutive freeze-thaw cycles. An investigation was undertaken using several techniques to characterize fully the physicochemical changes L-Asparaginase is undergoing during freeze-thaw cycling leading to the loss of its activity. A total protein assay suggested that the loss of some enzyme activity was a result of protein precipitation. Circular dichroism (CD) studies showed a decrease of alpha-helical structure with a concomitant increase in beta sheet and random coil content, suggesting alterations in the secondary structure leading to unfolding, the first step of denaturation processes. The elution profiles obtained from size-exclusion chromatography (SEC) studies indicated the formation of several species during the process of freezing and thawing. Sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) studies showed bands corresponding to 1-3 kDa and 32 kDa, suggesting that some of the species are fragments and shortened monomers resulting from cleavage of monomers. The molecular weight distribution obtained using SEC-linked light scattering indicated a substantial fraction of polydispersed fragments ranging from 900 Da to 3 kDa and a small fraction of aggregates corresponding to 300 kDa. A scheme was proposed to explain the cascade of events leading to the loss of soluble protein and accompanying loss of enzyme activity. Tetramers of the enzyme dissociate into monomers some of which are cleaved into small fragments. The shortened monomers then aggregate and precipitate.
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9,178,180
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Effect of cationic surfactant on transport of model drugs in emulsion systems.
|
Excess surfactant present in emulsions can influence the rates of transport of incorporated drugs by micellar solubilization, alteration of the partitioning process and by drug-surfactant complexation. Cetyltrimethylammonium bromide (CTAB), a cationic surfactant was selected to investigate these phenomena as it forms relatively stable mineral oil-water (O-W) emulsions and has the potential for ionic interaction. Phenylazoaniline, benzocaine, benzoic acid and phenol were chosen as model drugs for this study. The emulsion critical micelle concentration (CMC) for CTAB determined using a combination of a membrane equilibrium technique and surface-tension measurement was 1.0% w/v in 10% v/v% O-W emulsion systems. Ionic interaction between model drugs and surfactants and drug hydrophobicity affected their transport rates in the emulsion systems. The transport rates of the lipophilic drugs (benzocaine and phenylazoaniline) and the ionized hydrophillic drug (benzoic acid, pH 7.0) in the emulsion systems increased with increasing CTAB concentration up to 0.5% w/v micellar concentration and then decreased at higher concentrations. The rate of transport of phenol was not affected by the presence of micellar phase. Ionic interaction between surfactant and model drugs affected transport rates of model drugs in emulsion systems. The micellar phase was considered to affect the overall transport rates of model drugs.
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9,178,181
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Oral sustained-release cisplatin preparation for rats and mice.
|
A new oral sustained-release solid-dispersion preparation of cisplatin (cis-diamminedichloroplatinum(II): cisplatin) has been developed for administration to small experimental animals such as mice. This preparation was obtained by formulating cisplatin with the water-insoluble polymer ethylcellulose and with stearic acid in different ratios. In-vitro dissolution studies showed that cisplatin release characteristics were zero-order for the formulation cisplatin-ethylcellulose-stearic acid (1:10:5) and levels equilibrated 7 h after the start of the experiment. The availability of cisplatin from this preparation was evaluated both in rats and mice. The cisplatin preparation (20 mg kg-1) was administered orally to rats and the resulting curve of serum cisplatin levels against time was compared with that obtained after intravenous infusion (20 mg kg-1) to rats. By comparing the areas under serum concentration-time curves (AUCs), the bioavailability of cisplatin was estimated to be 31%. The mean residence time (MRT) of cisplatin solid dispersion was 6.13 +/- 0.43 h, whereas the MRT of cisplatin administered by intravenous infusion was 3.89 +/- 0.05 h. Serum cisplatin levels were maintained above 0.3 mg mL-1 (believed from our clinical studies to be the minimum effective concentration) for 24 h. The curve of serum cisplatin level against time suggested that cisplatin was released from the solid dispersion preparation in a sustained-release fashion. Similar levels were also maintained in mice for 24 h. The MRT of the cisplatin preparation was 10-16 h in mice, which is longer than that obtained after oral administration of the physical mixture. The serum free-cisplatin concentration was determined to be 0.10 mg mL-1 in mice serum in which the total cisplatin concentration was 0.30 mg mL-1. The free fraction of cisplatin in mice serum was the same as that in human patient serum. Pathological examination showed that this new sustained-release oral cisplatin preparation did not have any side effects on the gastrointestinal tract. These results suggest usefulness of this new solid-dispersion preparation for oral cisplatin therapy in lung cancer patients.
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9,178,183
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Experiences with the rectal use of trimethoprim.
|
The possibility of rectal use of trimethoprim was studied. The in-vitro liberation of the drug from 24 different suppository bases was examined and the results used to select bases for in-vivo examination. The in-vitro liberation from the suppositories containing 50-200 mg trimethoprim was studied by the method of dynamic diffusion, and the released drug content was measured spectrophotometrically. The in-vivo examinations were performed in anaesthetized rats. The concentration of trimethoprim in blood was determined by bioassay. The absorption of the drug in the form of oral suspension, rectal solution and suppository was also studied. The pharmacokinetic parameters obtained after blood-level curve fitting were compared by use of the MedUSA 1.6 program. The best in-vivo results were achieved with the lipohydrophilic Witepsol W 35 vehicle containing 10% polysorbate 20 and 10% polysorbate 61 (bioavailability = 63.8%) and with Witepsol W 35 containing 10% polysorbate 60 (bioavailability = 63.8%). The results for hydrophilic Macrogol 1540 vehicle containing 5% of Macrogol 400 were only slightly worse (bioavailability = 52.9%). In the case of the lipohydrophilic Witepsol W 35 vehicle with 10% polysorbate 20 and 10% polysorbate 61 content a significant negative exponential relationship was found between the administered doses and their respective bioavailability values; this tendency was also observed during in-vitro examinations. When incorporated in the appropriate vehicle trimethoprim was absorbed well. With three vehicles the extent of absorption exceeded that for oral administration on the same model (bioavailability = 38.8%). Trimethoprim rectal suppositories, which are formulated with the vehicles having the best in-vitro and in-vivo results, are suitable for clinical pharmacological investigation.
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9,178,182
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Encapsulation, stability and in-vitro release characteristics of liposomal formulations of colchicine.
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The severe toxicity and low therapeutic index of colchicine limit its therapeutic use. Encapsulation in liposomes might reduce these toxic effects. The objective of this study was to determine the factors influencing encapsulation of colchicine in liposomes and to optimize the encapsulation parameters. Colchicine was encapsulated in multilamellar liposomes and large unilamellar liposomes prepared using various phospholipids. The effects of method of preparation, type of vesicle, charge, and concentration of cholesterol on encapsulation of colchicine in liposomes were investigated. Also, stability of colchicine under stress conditions and at various temperatures, and in-vitro release characteristics were determined. A significant difference in encapsulation of colchicine in multilamellar liposomes was observed when prepared by two different methods. Induction of charge on the liposome surface increased encapsulation of colchicine in multilamellar liposomes, but did not affect large unilamellar liposomes. The liposome preparations could withstand simulated transport conditions and frequent changes in temperature. Particle size and concentration of colchicine did not change significantly during storage at various temperatures for six months. In order to retain encapsulated colchicine in liposomes, storage at or below room temperature was found to be suitable. In-vitro release of colchicine from large unilamellar liposomes was biphasic and was influenced by two rate-limiting barriers, the dialysis membrane and the liposome bi-layers. For optimum encapsulation and stability of colchicine liposomes were prepared from a mixture of 1,2-distearoyl-sn-glycero-3-phosphocholine, cholesterol and either stearylamine or dicetyl phosphate.
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9,178,184
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Some effects of Cassia italica on the central nervous system in mice.
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This work examines some effects of the crude ethanolic extract of the medicinal plant Cassia italica, given at single oral doses of 0.25, 0.5 or 1 g kg-1, on the central nervous system in mice. Several models of nociception have been used to examine the analgesic effect of the extract. HPLC fingerprinting of the extract was performed to ensure uniformity of the extract material used. In treated mice, the extract caused dose-related inhibition of acetic acid-induced abdominal constriction, and in the formalin test of antinociception the extract reduced formalin-induced pain in the second (late) but not in the first (early) phase of the pain. Treatment with the extract at doses of 0.5 and 1 g kg-1 significantly increased the reaction time in the hot-plate and warm-water tail-flick tests. Naloxone was ineffective in antagonizing the analgesic effect of C. italica on tail-flick and abdominal constriction tests, possibly indicating that the effect occurs via non-opiate pathways. The C. italica extract caused slight dose-related impairment of motor control which was significant only at a dose of 1 g kg-1. Treatment at the three doses used did not affect the rectal temperature of normothermic mice, but was effective in significantly reducing the rectal temperature of hyperthermic rats, 0.5 and 1 h (but not 6 h) after administration of the extract at doses of 0.5 and 1 g kg-1. The extract also produced progressive diminution in the ambulatory and total activity of treated mice for up to 2 h after administration. It is concluded that the crude ethanolic extract of C. italica has CNS depressant properties, manifested as antinociception and sedation.
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9,178,187
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Characteristics of cefdinir uptake by rabbit small intestinal brush-border membrane vesicles.
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Aminocephalosporins with peptide-like structures have been shown to be absorbed by the intestinal peptide carrier. We investigated the transport mechanism of cefdinir, an oral monocarboxylic acid cephalosporin, using rabbit small intestinal brush-border membrane vesicles. Transport of cefdinir showed a slow and almost linear uptake rate for concentrations up to 30 mM with and without and inward H+ gradient. No overshoot phenomenon was observed in the presence of an inward H+ gradient. The uptake rate increased only slightly with decreasing extravesicular pH, and a protonophore had little effect on the uptake. Aminocephalosporins such as cephalexin only slightly inhibited cefdinir uptake even in the presence of an inward H+ gradient, and vice-versa. Monocarboxylic acids such as acetic acid and salicylic acid had little effect on cefdinir uptake. These findings suggest that in contrast with other oral cephalosporins cefdinir uptake through the brush-border membrane is slow and involves a mechanism similar to passive diffusion.
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9,178,185
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Electrical and mechanical modulations by oxygen-derived free-radical generating systems in guinea-pig heart muscles.
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The effects of free-radical generating systems and angiotensin-converting enzyme (ACE) inhibitors on the action potentials and contractile force in guinea-pig cardiac muscles were examined using conventional microelectrode and whole-cell voltage-clamp methods at 36 degrees C. Hydrogen peroxide (30-100 microM) prolonged 50%, 75% and 90% repolarization of action-potential duration (APD) approximately 15-25 min after its application. But the longer exposure reversed the APD shortening in a concentration-dependent manner. Other action-potential parameters were not altered to a significant extent. The contractile force was increased. Longer exposure inhibited the enhanced force (but it was still larger than control). The effects on the spontaneous action potential from right atrial muscle were almost the same. In whole-cell voltage-clamp experiments, H2O2 (100 microM) inhibited L-type Ca2+ current and enhanced delayed rectifier K+ current. The effects of light-activated rose bengal (10-100 nM) on the APD were similar to, but more potent than, those of H2O2. The response was observed rapidly after a light illumination. During exposure to rose bengal (100 nM), abnormal spontaneous action potentials or arrhythmias such as a bigeminy occurred, presumably because of early and delayed afterdepolarizations. The responses were irreversible. At 300 microM ACE inhibitors, captopril and enalapril, protected the changes induced by these free radicals. These results indicate that H2O2 has a dual, time-dependent, action on the APD and rose bengal with light illumination produced the responses rapidly. The oxygen-derived free radicals increased [Ca]i and then cellular Ca2+ overload occurred. These responses were protected by ACE inhibitors.
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9,178,189
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Inhibitory effects of N-acetylcysteine on superoxide anion generation in human polymorphonuclear leukocytes.
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It has been suggested that reactive oxygen species released by activated polymorphonuclear leukocytes (PMN) in man is one mechanism of tissue injury. Therapeutic action aimed at increasing antioxidant defence mechanisms is still a clinical challenge. This study examines the activity of N-acetylcysteine, a known antioxidant, in the protection of PMN exposed in-vitro to the chemoattractant peptide fMet-Leu-Phe (FMLP), the protein kinase C activator phorbol myristate acetate or the lipid peroxidation promoter t-butyl hydroperoxide. FMLP (3-300 nM) and phorbol myristate acetate (160 pm-160 nM) induced concentration-related superoxide anion generation. Pre-treatment with N-acetylcysteine (33-333 microM) resulted in concentration-related inhibition of superoxide production induced by FMLP (30 nM) or phorbol myristate acetate (16 nM);-log IC50 values were 3.97 +/- 0.07 and 3.91 +/- 0.10, respectively. Changes in intracellular calcium ion concentration ([Ca2+]i) induced by FMLP (30 nM) were studied in fura-2-loaded human PMN. FMLP produced a transient calcium response, i.e. a peak followed by decay to a residual value above baseline. N-Acetylcysteine (333 microM) did not affect either basal [Ca2+]i values or changes in [Ca2+]i values after treatment with FMLP. Activation by phorbol myristate acetate caused a reduction in glutathione levels from 5.94 +/- 0.86 (control) to 1.84 +/- 0.51 nmol/3 x 10(6) cells (P < 0.05 compared with control). Pre-treatment with N-acetylcysteine (333 microM) fully reversed the reduction in glutathione levels induced by phorbol myristate acetate (4.83 +/- 0.68 nmol/3 x 10(6) cells; P > 0.05 compared with control). Exposure to t-butyl hydroperoxide (0.5 mM, 30 min) markedly increased malondialdehyde levels (from 0.03 +/- 0.02 to 0.73 +/- 0.07 nmol/10(6) cells), and index of lipid peroxidation. Malondialdehyde levels were significantly reduced in PMN treated with N-acetylcysteine (333 microM; 0.55 +/- 0.04 nmol/10(6) cells; P < 0.05 compared with untreated cells exposed to t-butyl hydroperoxide). In conclusion, N-acetylcysteine reduces superoxide generation in response to FMLP and phorbol myristate acetate and partially protects against lipid peroxidation in PMN from man. The protection afforded by N-acetylcysteine is not related to alteration of the intracellular calcium signal but might be effected by replenishment of the intracellular glutathione levels.
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9,178,186
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A structure-relationship study of the uptake of aliphatic polyamine compounds by rat intestinal brush-border membrane vesicles.
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The effects of lipophilicity, ion-diffusion potential and membrane surface potential on the uptake of various aliphatic polyamine compounds by rat intestinal brush-border membrane vesicles (BBMV) have been investigated. A valinomycin-induced potassium-diffusion potential (inside-negative) stimulated the initial uptake of diamine compounds, and good correlation was observed between lipophilicity and the amount of diffusion-potential-dependent transport of the diamines. In contrast, because of their much lower lipophilicity, tri- and tetraamine compounds were not affected by the diffusion potential. Tetracaine, which can make the membrane surface potential more positive, inhibited the transport rate of 1,9-nonanediamine, spermidine and spermine by the BBMV. These data suggest that the transport mechanism of diamines is similar to that of monoamine compounds in respect to its dependence on ion-diffusion potential and on the membrane surface potential. The extent of the effect of ion-diffusion potential on the rate of transport of the diamines was closely related to the lipophilicity of the diamine. In contrast, only the surface potential contributed to the transport mechanism of lower lipophilic tri- and tetraamine compounds.
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9,178,188
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Effects of ATP on phosphoinositide hydrolysis and prostaglandin E2 generation in rabbit astrocytes.
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Extracellular ATP secreted from stimulated nerves plays a role in neurotransmission. This study examined the effects of extracellular ATP on phospholipase A2 and C signalling pathways in rabbit astrocytes. ATP caused prostaglandin E2 (PGE2) generation and phosphoinositide hydrolysis in a time- and concentration-dependent manner. A P2y purinoceptor-selective agonist, 2-methylthio-ATP also caused phosphoinositide hydrolysis, but not PGE2 generation. A P2x purinoceptor-selective agonist, alpha, beta-methylene-ATP did not cause either phosphoinositide hydrolysis or PGE2 generation. Although pertussis toxin had no effect on 2-methylthio-ATP-induced phosphoinositide hydrolysis, it markedly decreased ATP-induced PGE2 generation, with significant inhibition of phosphoinositide hydrolysis. Dexamethasone and indomethacin which potently inhibited ATP-induced PGE2 generation, caused partial inhibition of phosphoinositide hydrolysis, suggesting that pertussis toxin-sensitive component of ATP-induced phospholipase C activation is mediated by cyclo-oxygenase metabolites of arachidonic acid. These results suggest that a stimulation of P2y receptor results in phospholipase C activation in a pertussis toxin-insensitive manner, and that a P2 receptor other than the P2y or P2x subtypes is involved in ATP-induced phospholipase A2 activation via a pertussis toxin-sensitive G protein.
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9,178,190
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2',5'-Dihydroxychalcone as a potent chemical mediator and cyclooxygenase inhibitor.
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Eleven chalcone derivatives have been tested for their inhibitory effects on platelet aggregation in rabbit platelet suspension and the activation of mast cells and neutrophils. Arachidonic acid-induced platelet aggregation was potently inhibited by almost all the compounds and some also had a potent inhibitory effect on collagen-induced platelet aggregation and cyclooxygenase. Some hydroxychalcone derivatives showed strong inhibitory effects on the release of beta-glucuronidase and lysozyme, and on superoxide formation by rat neutrophils stimulated with the peptide fMet-Leu-Phe (fMLP). We found that the anti-inflammatory effect of 2',5'-dihydroxychalcone was greater than that of trifluoperazine. 2'5'-Dihydroxy and 2',3,4,5'-tetrahydroxyl chalcones, even at low concentration (50 microM), tested in platelet-rich plasma from man almost completely inhibited secondary aggregation induced by adrenaline. These results suggest that the anti-platelet effects of the chalcones are mainly a result of inhibition of thromboxane formation.
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9,178,191
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Effect of a chymotrypsin-like inhibitor, TPCK, on histamine release from cultured human mast cells.
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The involvement of endogenous proteases in the secretory process from human mast cells remains to be clarified. A chymotrypsin-like protease inhibitor, N-tosyl-L-phenylalanylchloromethyl ketone (TPCK), blocked both FceRI- and A23187-mediated histamine release from cultured human mast cells at concentrations above 1 microM. At 10 microM, the concentration that completely inhibited FceRI-mediated histamine release, TPCK did not inhibit the chymase activity of the lysate or that in intact cells. The addition of TPCK to cells 30 min before challenge did not affect FceRI- or A23187-mediated Ca2+ mobilization. These findings suggest that a TPCK-sensitive molecule distinct from chymase is involved in a late stage of the process of histamine release from mast cells in man.
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9,178,192
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Some histamine-related compounds interacting with the benzylamine-oxidizing activity of rat white adipocytes.
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In rat white adipocytes histamine is oxidized by a semicarbazide-sensitive amine oxidase which has benzylamine or preferential substrate (Bz-SSAO). To determine whether Bz-SSAO could control the extracellular levels of histamine and other histamine-related compounds active in lipid mobilization, a series of histaminergic compounds was screened as possible substrates or inhibitors of Bz-SSAO activity. Histaminergic compounds with imidazolo or thiazolo groups are oxidized by rat white-adipocyte Bz-SSAO whereas S-isothiourea derivatives, with two- or three-carbon-atom alkyl chains between the isothiourea and the N,N-dimethyl residue are, instead, inhibitors of the enzyme. Amtamine has been identified as a selective, high affinity substrate for rat white adipocyte Bz-SSAO. This enzymatic degradation might represent a catabolic pathway for the drug. These results show that the histaminase property of the rat white-adipocyte enzyme Bz-SSAO also extends to other histamine derivatives active at histamine receptors.
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9,178,193
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Contribution of cytochrome P450 3A pathway to bromocriptine metabolism and effects of ferrous iron and hypoxia-re-oxygenation on its elimination in the perfused rat liver.
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The contribution of the cytochrome P450 3A pathway to bromocriptine metabolism, and the effects of ferrous iron and hypoxia-re-oxygenation on its elimination, were evaluated with the perfused rat liver. Outflow profiles of bromocriptine after bolus administration were estimated by moment analysis and dispersion model analysis. Kinetic parameters were not significantly changed by troleandomycin, a P450 3A inhibitor. The inhibition of bromocriptine metabolism by troleandomycin was 5.7 +/- 2.4%. These findings indicate that cytochrome P450 3A does not play an important role in bromocriptine elimination with the perfused rat liver. Elimination rate constant (ka) values were significantly increased by ferrous iron perfusion or hypoxia-re-oxygenation. Free-radical generation can, therefore, affect bromocriptine elimination. Our observations suggest that bromocriptine might be eliminated by scavenging of free radicals in the liver.
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9,178,194
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Pharmacological activity of feverfew (Tanacetum parthenium (L.) Schultz-Bip.): assessment by inhibition of human polymorphonuclear leukocyte chemiluminescence in-vitro.
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The bioactivity of feverfew (Tanacetum parthenium) leaf extracts has been analysed, by use of a human polymorphonuclear leukocyte (PMNL) bioassay, to assess the relative contributions of solvent extraction and parthenolide content to the biological potency of the extract. Extracts prepared in acetone-ethanol (system 1) contained significantly more parthenolide (mean +/- s.d. 1.3 +/- 0.2% dry leaf weight) than extracts in chloroform-PBS (phosphate-buffered saline; system 2; 0.1 +/- 0.04% dry leaf weight) or PBS alone (system 3; 0.5 +/- 0.1% dry leaf weight). Extract bioactivity, measured as inhibition of phorbol 12-myristate 13-acetate-induced, 5-amino-2,3-dihydro-1,4-phthalazinedione (luminol)-enhanced PMNL, chemiluminescence, followed a similar trend. Extracts inhibited phorbol 12-myristate 13-acetate-induced oxidative burst by amounts which, if solely attributable to parthenolide, indicated parthenolide concentrations for the respective solvent systems of 2.2 +/- 0.6%, 0.2 +/- 0.1% and 0.9 +/- 0.1% dry leaf weight. The mean ratio of parthenolide concentration to the parthenolide equivalent/PMNL-bioactivity value, for acetone-ethanol and PBS extracts were both 1:1.7. Parthenolide, although a key determinant of biological activity for T. parthenium leaf extracts based on the PMNL-bioassay, seems not to be the sole pharmacologically-active constituent. The identical and elevated bioactivity-parthenolide ratios for both organic and aqueons-phase leaf extracts suggest that a proportion of the other bioactive compounds have solubilities similar to that of parthenolide.
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9,178,195
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A sulphonoglycolipid from the fern Polypodium decumanum and its effect on the platelet activating-factor receptor in human neutrophils.
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The South American fern Polypodium decumanum, traditional name calaguala, has documented clinical use in oral treatment of skin disorders, including psoriasis. The inflammatory mediator platelet-activating factor (PAF), has been implicated in the pathogenesis of psoriasis. A constituent of a calaguala extract has been shown to have inhibitory activity in a PAF-induced exocytosis model in human neutrophils. The compound was identified as the sulphoquinovosyl diacylglycerol 1,2-di-O-palmitoyl-3-O-(6-sulpho-alpha-D-quinovopyranosyl)-glycero l by spectroscopic means. When subsequently studied in an in-vitro model for [3H]PAF binding in neutrophils from man the compound caused dose-dependent displacement of [3H]PAF from its receptor with an IC50 value of 2 microM. It is suggested that the compound acts through PAF receptor antagonism in intact human neutrophils.
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9,178,196
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Mechanisms involved in the antinociceptive effect in mice of the hydroalcoholic extract of Siphocampylus verticillatus.
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The antinociception caused by the hydroalcoholic extract of Siphocampylus verticillatus (Campanulaceae) has been investigated in chemical and thermal models of nociception in mice. We have also assessed some of the mechanisms underlying the antinociceptive effect of the extract. The hydroalcoholic extract of S. verticillatus (60-1000 mg kg-1, i.p. or p.o.) produced dose-related, significant and long-lasting (6 to 8 h) inhibition of acetic acid-induced abdominal constriction in mice, with ID50 values of 204 and approximately 1000 mg kg-1, respectively. In the formalin test, the extract (100-1000 mg kg-1), given either intraperitoneally or orally, resulted in graded inhibition of both phases of formalin-induced pain, being about 2- to 4-fold more potent in attenuating the second phase of the pain. The calculated mean ID50 (mg kg-1) values for the earlier and the later phases were: 491 and 186 and 640 and 441, respectively. In addition, the extract (60-1000 mg kg-1, i.p. or p.o.) caused marked and dose-related inhibition of capsaicin-induced neurogenic pain with mean ID50 values of 420 and 485 mg kg-1, respectively. The hydroalcoholic extract, at the same doses, did not significantly affect the performance of animals in the rota-rod test, nor did it have any analgesic effect in the tail-flick or hot-plate tests. The treatment of animals with naloxone (5 mg kg-1, s.c.) significantly reversed the analgesic effect of both morphine (5 mg kg-1, s.c.) and the extract (300 mg kg-1, i.p.) when assessed against acetic acid-induced abdominal constrictions. The treatment of animals with L-arginine (600 mg kg-1, i.p.) significantly attenuated the antinociceptive effects of NG-nitro-L-arginine (L-NOARG) (75 mg kg-1, i.p.), of the hydroalcoholic extract (600 mg kg-1, i.p.) or of morphine (5 mg kg-1, s.c.), when analysed against the formalin test. In addition, adrenalectomy of animals 7 days before the tests significantly reversed the antinociception caused by the hydroalcoholic extract (300 mg kg-1, i.p.) in the formalin-induced pain. These data show that the hydroalcoholic extract of S. verticillatus has significant and long-lasting oral antinociception when assessed against both neurogenic and inflammatory models of nociception in mice. The precise mechanism responsible for the analgesic effect of the extract still remains unclear, but a great part of this effect seems to be partly related to an opioid-like action and involvement of the L-arginine-nitric oxide pathway. Finally, the antinociception caused by the hydroalcoholic extract of S. verticillatus is modulated by adrenal hormones.
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9,178,197
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Analysis of rabbit vascular responses to DBI, an ingol derivative isolated from Euphorbia canariensis.
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We have analysed the effects of 7,12-O-diacetyl-8-O-benzoil-2,3-diepiingol (DBI), an ingol derivative isolated from E. canariensis, on isometric tension developed by isolated rabbit basilar and carotid arteries. Concentration-response curves to DBI (10(-8) - 3 x 10(-5) M) were obtained cumulatively in both arteries at resting tension and active tone (KCI, 50 mM). At resting tension, DBI induced a concentration-dependent contraction, which was not inhibited in Ca(2+)-free medium. H7 (1-(5-isoquinoline sulphonyl)-2-methylpiperazine dichloride) (10(-4) M) inhibited the DBI-induced contraction both in basilar and in carotid arteries. Calmidazolium (10(-4) M) inhibited the maximum contraction of the carotid artery to DBI, and completely abolished the response in the basilar artery. In pre-contracted basilar arteries DBI induced a concentration-dependent relaxation that was not modified by incubation with NG-nitro-L-arginine (L-NOARG; 10(-5) M) or indomethacin (10(-5) M). In the carotid artery with active tone DBI induced further contractions, which were not significantly modified by L-NOARG (10(-5) M) and were potentiated by indomethacin (10(-5) M). These results suggest that DBI contracts rabbit basilar and carotid arteries by a mechanism that is independent of extracellular Ca2+ and involves the participation both of protein kinase C and of calmodulin. DBI relaxes basilar but not carotid arteries by a mechanism independent of the liberation of nitric oxide and prostacyclin. In the carotid artery prostacyclin but not nitric oxide partially counteracts the contractile action of DBI.
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9,178,210
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The quality management jigsaw.
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The current scene in Australia, as in a large part of the developed world, in relation to the subject of quality management in health care, is characterized by confusion, blurred objectives, patchy involvement and very high opportunity costs. Much of the confusion is caused by a failure to understand or use correctly the bewildering array of terminology that characterizes what is becoming a new discipline in its own right. A series of simple definitions permits the reader to understand what the author is attempting to say. The paper also provides a conceptual framework for the implementation of quality management in hospitals: a jigsaw of activity which hospitals have some difficulty conceptualizing and without which hospitals will never be able to respond seriously to the challenge of assuring quality.
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9,178,211
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The impact of screening for risk factors associated with postnatal depression at the first prenatal visit.
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Although 10-15% of Australian women suffer from postnatal depression (PND), few efforts have been made, prenatally, to predict which women may develop the condition. The objective of this study was to evaluate the impact on patients, staff and services of an intervention designed to identify women at risk for PND. Women were screened at their first prenatal visit for factors associated with PND, and were asked to complete a questionnaire at their next clinic visit to assess the impact of the screening questions and the usefulness of a PND information kit. To assess the impact of the intervention on the prenatal clinic routine, all staff associated with the intervention were interviewed individually and their responses were tape recorded and analysed for themes. Patients reported a high level of satisfaction with the intervention. Staff responded well to the new procedure and offered constructive comments to improve the process.
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9,178,212
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Nosocomial infection indicators in Australian hospitals: assessment according to hospital characteristics.
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The relationship of bed size and hospital type (private or public) was studied using Hospital-Wide Medical Indicator data on nosocomial infections submitted to the Australian Council on Healthcare Standards Care Evaluation Program by hospitals presenting voluntarily for accreditation in 1993. The aim was to determine if this process could simplify the establishment of hospital peer groups for comparison of risk in the absence of knowledge of patient illness severity indices. After adjusting for potential confounders in a logistic model, hospital type was found to be a significant predictor for the occurrence of infection in clean and contaminated wounds. Bed size was a significant predictor for the occurrence of hospital-acquired bacteraemia in private and public hospitals. The increase in the risk of developing hospital acquired bacteraemia with increasing number of beds was significant as a trend (P < 0.0001) in private as well as public hospitals. The results suggest that hospital type and bed size are initial indices for 'flagging' peer group variation and prompting a more detailed internal review.
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9,178,213
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Changes in psychotropic medication use in nursing homes over a 9-month period.
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A 1993 survey of nursing home residents in one part of Sydney was repeated 9 months later. Details of psychotropic medication given to the 1433 residents who survived and remained in the same 38 nursing homes were examined. There were modest reductions in the percentage of residents taking neuroleptics, anxiolytics and hypnotics, but there was an increase from 16.0% to 17.6% in the percentage of residents taking antidepressants. About 65% of those taking psychotropic medication at the initial survey remained on exactly the same dose 9 months later. Most of those taking neuroleptic or antidepressant medication were given relatively small daily doses. Intervention studies are desirable to examine how best to improve prescribing practices.
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9,178,214
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Comprehensive audit of quality-of-care and quality-of-life for patients with diabetes.
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This comprehensive audit was conducted in a three-person general practice with an age-sex-disease register to evaluate care for patients with diabetes using metabolic indicators and validated measures of quality-of-life and patient satisfaction. Medical records were reviewed using criteria derived from guidelines published by Diabetes Australia and New South Wales Health. Self-administered questionnaires mailed to patients included the Diabetes Quality-of-Life measure (DQOL), the Well-Being Questionnaire (WBQ) and the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Record audit for 71 patients with diabetes demonstrated poor control and monitoring. Frequent attenders were no more likely to have had a HgA1c performed than less frequent attenders (P = 0.72). While patient satisfaction with care was high, numerical values for quality-of-life were lower than published overseas norms, indicating a need to support better care in general practice and further research to determine Australian norms.
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9,178,215
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Pregnancy outcome score: a clinical indicator of the childbirth process.
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Clinical indicators associated with the process of childbirth are either gross (e.g. perinatal mortality rate) or measures of intervention (e.g. Caesarean section rate). Morbidity and process are rarely, if ever, addressed. We developed and piloted a simple pregnancy outcome score as a comparative indicator of outcome. This scoring system is easy to apply, and there was a positive and significant correlation between the pregnancy outcome score and the risk status of the patients.
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9,178,216
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Orthopaedic surgery outcomes assessment model.
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This paper reviews the motives and methods for applying an outcomes assessment model in the orthopaedic department at our hospital. Various strategic applications of health status measurement are demonstrated. The methods used in the process of designing this model are highlighted which may assist design of outcomes assessment models in other fields. A variety of surgical interventions were incorporated into this model including lower limb arthroplasties, total shoulder arthroplasty and all shoulder soft tissue surgery.
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9,178,217
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Difference in quick phases induced by horizontal and vertical vestibular stimulations: role of the otolithic input.
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Quick phases (QPs) induced by horizontal and vertical sinusoidal vestibular stimulations were studied in rabbits, cats, and humans. In all the animals, large and frequent horizontal QPs were observed following yaw stimulation in prone position. By contrast, QPs were almost absent during roll stimulation in rabbits, and they were small and oblique during pitch stimulation in cats and humans. As a result of these differences, the range of gaze displacement induced by vestibular stimulations was greater in the horizontal plane than in the vertical one. We also found that the trajectory of the QPs in rabbits was kept horizontal even when the yaw rotation was off vertical axis of +/- 45 degrees in the sagittal plane. Moreover, in the rabbit, the rare horizontal QPs induced by roll stimulation did not change their orientation at various pitch angles of roll stimulation axis. The QPs were also analyzed following roll stimulation of the rabbit in supine position. In this condition, in which the otolithic receptors were activated in the opposite way compared to prone position, large vertical QPs were elicited. We concluded that these results provide evidence that the otolithic signal plays a role in controlling occurrence and trajectory orientation of the QPs.
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9,178,218
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Kinematic analysis of locomotion in unilateral vestibular neurectomized cats.
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The vestibular syndrome following unilateral lesion of the vestibular system and the subsequent behavioral compensation over time have been well documented in many species. However, the locomotor pattern changes and the behavioral strategies used to preserve balance have still not been described. This study was aimed at quantitatively describing posturolocomotor behavior in cats tested before and after unilateral vestibular neurectomy (UVN) by the rotating beam test, which provides locomotor tasks of various difficulty. The position of head, neck, and trunk and the trajectory of the forelimbs and hindlimbs were recorded in 5 cats by 3D motion analysis. Step length and frequency walking velocity, and body height were computed. Results showed that normal cats adapted their locomotor patterns to the speed of beam rotation by increasing step length and/or frequency, that is, by increasing walking velocity, but without drastically changing their body posture. By contrast, UVN cats typically lowered their body centers of gravity and modified their locomotor patterns according to the locomotor task. Mean walking velocity was decreased in the low range of beam rotation as a result of smaller step length and lower frequency, and it was increased in the high range by opposite effects on these step cycle parameters. Modifications of the locomotor parameters were a function of the direction of beam rotation, showing significant reduction of step length, frequency, and velocity in the low range of counterclockwise compared to clockwise beam rotation, that is, during rotations toward the lesioned side. Phase plane plots of foot linear velocity with respect to foot linear displacement along the horizontal longitudinal axis displayed two different limit cycles, adapted to easy (low range of beam rotation) and more difficult (high range of rotation) walking conditions, in the normal cat. These dynamic profiles of the trajectories of the limbs during the step cycle were not greatly modified after vestibular lesion, but the phase plane typically observed in the high range for the normals was also found in the low range for the UVN cats. Thus, locomotor equilibrium function in the cat is strongly impaired following UVN, but locomotor balance can still be achieved in the UVN cats by the development of adaptive posturolocomotor strategies compensating for the lack of vestibular inputs.
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9,178,221
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Head-trunk coordination during hops using one or two feet in children and adults.
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The main purpose of this study was to investigate the development of head-trunk coordination during single hops using one foot or two feet in children of two ages (5.5 to 6 and 7 to 7.5) and adults (n = 6/group). The kinematics of the subjects' hops were analyzed by means of an automatic optical TV-image processor called the ELITE system. The absolute angular dispersion of the head, trunk, and leg about the pitch and the roll axis were measured. Head and trunk pitch and roll anchoring indexes were calculated in order to compare the stabilization of a given segment with respect both to external space and to the underlying anatomical segment. Results were analyzed separately for 3 phases: take-off, flight, and landing. Only the last two phases, flight and landing, are presented in this paper, and the following was found: 1) During flight, under both unipedal and bipedal conditions, head and trunk stabilization in space about the pitch axis occurred in children as well as in adults, suggesting an articulated operation of the head-trunk unit. In contrast, during landing, in children and adults, head stabilization in space tended to disappear while trunk stabilization in space was still present, suggesting an en bloc operation of the head-trunk unit. Similarly, pelvis stabilization in space about the roll axis occurred in all subjects during both flight and landing under unipedal conditions, where lateral balance control is of primary importance. Taken together, these results suggest that head stabilization in space is phase dependent, while trunk stabilization is phase independent. The trunk, including the pelvis, may thus constitute a stable reference frame from which anteroposterior and lateral balance control is organized during hops. 2) For head-trunk coordination, whatever the component of rotation, the two groups of children differed from adults, but did not differ from each other, suggesting that, while jumping, the transition between 6 and 7 years of age in the organization of balance control takes place in the coordination of the lower limbs during the preparatory phase of the take-off.
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9,178,219
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Visual object localization through vestibular and neck inputs. 1: Localization with respect to space and relative to the head and trunk mid-sagittal planes.
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Object localization in space signals in the absence of an external reference (visual, auditory, haptic) involves a signal of the head in space (vestibular). The present study asks whether signals of body position relative to the support surface (proprioceptive) are involved as well, by investigating the role of vestibular-neck interaction (dissociating head and trunk position). Normal human subjects saw a light spot (object) and continuously nulled displacement steps of the spot. They did so before and after vestibular and/or neck rotational stimulation in the horizontal plane, reproducing a predesignated object localization in space (i), relative to the head mid-sagittal (ii), and relative to the trunk mid-sagittal (iii). The predominant frequency contained in the stimuli was varied (0.05, 0.1, and 0.4 Hz). (I) Object localization in space upon whole-body rotation (vestibular stimulus) at high frequency was veridical, whereas that at low frequency fell short. Almost identical results were obtained for trunk rotation about the stationary head (neck stimulus). In contrast, when combining the stimuli in the form of head rotation on the stationary trunk, the results were veridical, independent of stimulus frequency. Additional findings obtained with a large variety of vestibular-neck stimulus combinations suggest a linear summation of vestibular and neck signals. (II) Object localization with respect to the head was approximately veridical, being independent of vestibular and neck stimulation. However, this only applied if subjects were not biased by a head-in-space motion illusion of neck origin. (III) Object localization with respect to the trunk was veridical in all conditions tested. The findings support a recently developed concept, according to which humans evaluate the kinematic state of a visual object in space by (a) relating it to that of the body support by means of an essentially ideal proprioceptive coordinate transformation, and (b) relating, in turn, the kinematic state of the support to a vestibularly derived notion of space, using a proprioceptive coordinate transformation that "knows" the vestibular transfer characteristics. One important aspect is that object localization in space always is veridical during head and trunk rotation relative to a stationary support (for example, the ground) despite non-ideal vestibular transfer characteristics. Additional findings in patients with chronic loss of vestibular function confirm this concept.
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9,178,222
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Locomotor head-trunk coordination strategies following space flight.
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During locomotion, angular head movements act in a compensatory fashion to oppose the vertical trunk translation that occurs during each step in the gait cycle. This coordinated strategy between head and trunk motion serves to aid gaze stabilization and perhaps simplifies the sensory coordinate transformation between the head and trunk, allowing efficient descending motor control during locomotion. Following space flight, astronauts often experience oscillopsia during locomotion in addition to postural and gait instabilities, suggesting a possible breakdown in head-trunk coordination. The goal of the present investigation was to determine if exposure to the microgravity environment of space flight induces alteration in head-trunk coordination during locomotion. Astronaut subjects were asked to walk (6.4 km/h, 20 s trials) on a motorized treadmill while visually fixating on a centrally located earthfixed target positioned either 2 m (FAR) or 30 cm (NEAR) from the eyes. In addition, some trials were also performed during periodic visual occlusion. Head and trunk kinematics during locomotion were determined with the aid of a video-based motion analyzing system. We report data collected preflight (10 days prior to launch) and postflight (2 to 4 hours after landing). The coherence between pitch head and vertical trunk movements during gaze fixation of both FAR and NEAR targets was significantly reduced following space flight indicating decreased coordination between the head and trunk during postflight locomotion. Astronauts flying on their first mission showed greater alterations in the frequency spectra of pitch head movements as compared to their more experienced counterparts. These modifications in the efficacy of head movement control may account for the reported disruption in gaze performance during locomotion and may contribute to postflight postural and gait dysfunction.
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9,178,229
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MR imaging and spectroscopy using hyperpolarized 129Xe gas: preliminary human results.
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Using a new method of xenon laser-polarization that permits the generation of liter quantities of hyperpolarized 129Xe gas, the first 129Xe imaging results from the human chest and the first 129Xe spectroscopy results from the human chest and head have been obtained. With polarization levels of approximately 2%, cross-sectional images of the lung gas-spaces with a voxel volume of 0.9 cm3 (signal-to-noise ratio (SNR), 28) were acquired and three dissolved-phase resonances in spectra from the chest were detected. In spectra from the head, one prominent dissolved-phase resonance, presumably from brain parenchyma, was detected. With anticipated improvements in the 129Xe polarization system, pulse sequences, RF coils, and breathing maneuvers, these results suggest the possibility for 129Xe gas-phase imaging of the lungs with a resolution approaching that of current conventional thoracic proton imaging. Moreover, the results suggest the feasibility of dissolved-phase imaging of both the chest and brain with a resolution similar to that obtained with the gas-phase images.
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9,178,226
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A review of adaptive change in musculoskeletal impedance during space flight and associated implications for postflight head movement control.
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We present a review of converging sources of evidence which suggest that the differences between loading histories experienced in 1-g and weightlessness are sufficient to stimulate adaptation in mechanical impedance of the musculoskeletal system. As a consequence of this adaptive change we argue that we should observe changes in the ability to attenuate force transmission through the musculoskeletal system both during and after space flight. By focusing attention on the relation between human sensorimotor activity and support surfaces, the importance of controlling mechanical energy flow through the musculoskeletal system is demonstrated. The implications of such control are discussed in light of visual-vestibular function in the specific context of head and gaze control during postflight locomotion. Evidence from locomotory biomechanics, visual-vestibular function, ergonomic evaluations of human vibration, and specific investigations of locomotion and head and gaze control after space flight, is considered.
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9,178,230
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Improved sensitivity to overlapping multiplet signals in in vivo proton spectroscopy using a multiecho volume selective (CPRESS) experiment.
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A method for volume selective proton spectroscopy is presented based on a multiecho sequence with short refocusing interval tcp. It is demonstrated, that by appropriate choice of tcp on the order of 4-6 ms, signals from overlapping multiplets like the glutamine and glutamate (Glu/Gln) resonances in spectra of the human brain are considerably increased compared with a conventional PRESS volume selection scheme. Thus proton spectra from J-coupled multiplet signals can be acquired with TE on the order of 20-30 ms avoiding the baseline problems arising at shorter echo times due to broad resonances. This allows to selectively acquire spectra from substances with longer T2 without the confounding effects from J-coupling occurring in conventional volume selection techniques.
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9,178,220
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Visual object localization through vestibular and neck inputs. 2: Updating off-mid-sagittal-plane target positions.
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The vestibular signal plays a significant role in sensing changes in head orientation during rotations and in determining the magnitude of the rotations, but has only minor contributions in updating the internal representation of object positions with respect to the body after body rotations. The small contribution of the vestibular signal in egocentric object localization was evidenced in experiments in which the subjects reported the remembered position of eccentric earth-fixed targets after passive body rotations. The experiment reported here tested whether motor systems, such as the oculomotor system, make use of vestibular signals to generate accurate goal-directed motor responses toward a target whose position needs to be updated with respect to the body during and after whole-body rotations. The results showed that although subjects can produce saccadic eye movements of about the same magnitude as passive whole-body rotations (as previously reported by a number of researchers), they failed to generate accurate saccades toward the position of an extinguished peripheral visual target after the rotation. Overall, these results combined with those found in the literature suggest different central processes for determining changes in body orientation in complete darkness and for updating a target position with respect to the body during and after body rotations.
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9,178,231
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Evidence for 100% 13C NMR visibility of glucose in human skeletal muscle.
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The accuracy of the measurement of total muscle glucose by in vivo 13C NMR spectroscopy was tested in five normal volunteers during a euglycemic [1-13C]glucose infusion. The NMR visible concentration calibrated using an external reference was compared with that calculated from plasma glucose concentration, assuming that glucose remained extracellular. The NMR measurement always provided higher values than the calculation from plasma glucose: 0.51 +/- 0.035 (mean +/- SE) versus 0.38 +/- 0.005 mmol/liter of muscle on average. This systematic difference was interpreted as reflecting the presence of muscle glucose-6-phosphate, co-resonating with free glucose. Thus, glucose appeared to be virtually 100% NMR visible in human skeletal muscle.
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9,178,233
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Effect of brain, body, and magnet bore temperatures on energy metabolism during global cerebral ischemia and reperfusion monitored by magnetic resonance spectroscopy in rats.
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To record brain temperature for comparison with rectal and temporalis muscle temperatures in preliminary studies before MR spectroscopy experiments, a thermistor was inserted into the basal ganglia in eight anesthetized, ventilated, and physiologically monitored rats. The rats were placed in an MR spectrometer and subjected to 60 min of global cerebral ischemia and 2 h of reperfusion without radiofrequency (RF) pulsing. Body temperature was maintained at 37.5-38.0 degrees C (normothermia) or 36.5-37.0 degrees C (mild hypothermia). Brain temperature during ischemia, which dropped to 31.9 +/- 0.3 (hypothermia) and 33.6 +/- 0.5 degrees C (normothermia), correlated with temporalis muscle temperature (r2 = 0.92) but not with body or magnet bore temperature measurements. Ischemia reduced brain temperature approximately 1.7 degrees C in rats subjected to mild hypothermia (1 degree reduction of body temperature). Parallel MR spectroscopy experiments showed no significant difference in energy metabolites between normothermic and hypothermic rats during ischemia. However, the metabolic recovery was more extensive 20-60 min after the onset of reperfusion in hypothermic rats, although not thereafter (P < 0.05). Mild hypothermia speeds metabolic recovery temporarily during reperfusion but does not retard energy failure during global ischemia in rats.
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9,178,225
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How to construct and move a cat's neck.
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Extensive information has been accumulated over the past several years about the head-neck sensory-motor system, in particular that relating to cats. Using still x-ray and cineradiographic analysis, the skeletal geometry of head-neck posture in three dimensions--when an animal is resting, actively orienting, or locomoting--is described. From these descriptions, cervical, vertebral, and craniocervical joint biomechanics for all three rotational dimensions are quantified. These behavioral data on muscle and skeletal movements have been incorporated in a biomechanical, functional anatomical model of the head-neck movement system. Individual as well as groups of neck muscles have been measured in detail and their kinematics determined. The role of a number of these muscles will be described for several reflex and voluntary behavioral contexts, including muscle co-contractions. Having established how each movement is accomplished, the neuronal sensory-motor reflex basis of head-neck system stabilization in space is addressed. The vestibular system is largely responsible for acquisition and maintenance of upright posture. The bilateral semicircular canals (horizontal, anterior, posterior) and otoliths (sacculus, utriculus) feed information differentially to specific neck muscles: these connections are reviewed with regard to the origin of the reflex are from each receptor to its destination of specific muscles. Behavioral data from normal animals, and from animals whose vestibular receptor systems are selectively lesioned, will be reviewed to complement the functional interpretation of the sensory-motor transformations. Finally, the requirements for space-time coordinated cat head-neck movements will be synthesized, based on biomechanics, muscle kinematics, canal/otolith connectivity, and selective lesion experiments.
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9,178,227
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Eye-head coordination toward auditory and visual targets in humans.
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Eye-head coordination during gaze orientation toward auditory targets in total darkness has been examined in human subjects. The findings have been compared, for the same subjects, with those obtained by using visual targets. The use of auditory targets when investigating eye-head coordination has some advantages with respect to the more common use of visual targets: (i) more eccentric target positions can be presented to the subject; (ii) visual feedback is excluded during the execution of gaze displacement; (iii) complex patterns of saccadic responses can be elicited. This last aspect is particularly interesting for examining the coupling between the eyes and the head displacements. The experimental findings indicate that during gaze orientation toward a visual or an auditory target the central nervous system adopts the same strategy of using both the saccadic mechanism and the head motor plant. In spite of a common strategy, qualitative and quantitative parameters of the resulting eye-head coordination are slightly different, depending on the nature of the target. The findings relating to patterns of eye-head coordination seem to indicate a dissociation between the eyes and the head, which receive different motor commands independently generated from the gaze error signal. The experimental findings reported in this paper have been summarized in a model of the gaze control system that makes use of a gaze feedback hypothesis through the central reconstruction of the eye and head positions.
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9,178,223
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The significance of motion sickness in the vestibular system.
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In order to clarify the significance of motion sickness in the vestibular system, we compared the findings of experimental motion sickness between different kinds of subjects, some of which were already reported. Subjects were healthy adults, healthy children between the ages of 4 and 15 years, and patients with congenital and acquired labyrinthine loss. They were asked to walk while wearing horizontally and vertically reversing goggles. Equilibrium ataxia as well as motion sickness were evoked by horizontal reversal, but not by vertical reversal in healthy subjects. Kindergarten children exhibited severe ataxia, but little nausea. The frequency of severe ataxia decreased during growth, inversely as the frequency of nausea syndrome increased. Although a patient with acquired loss became severely ataxic, a patient with congenital loss did not show any ataxia at all. The present study suggests that vestibular cues are indispensable to the ego-spatial relationship in the brain, and once the ego-spatial relationship becomes inadequate, discomfort acts as a safety device to brake uncontrollable actions. Then, perception of the outer world may automatically adjust voluntary actions by affecting motor commands. The importance of visual cues for representing an alternative framework may differ between congenital and acquired labyrinthine loss.
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9,178,224
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The control of head movements during human balance corrections.
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The assumption that the CNS regulates head stability during human balance corrections is explored in this review (an outgrowth of discussions initiated during the Head/Neck meeting held in Vail, Colorado, USA, July 1995). Two major questions were considered. First, how do the vestibulocollic (VCR) and cervicocollic (CCR) reflexes interact with intrinsic mechanical properties of the head neck system to control head position during balance corrections? Second, how is this interaction affected by factors such as vestibular loss, aging, and changes in behavioral goals or central set? The authors conclude that head velocities observed during balance corrections depend to a large extent on the movements of the head-neck mass-viscoelastic system whose properties could be altered by cocontracting the neck muscles. For experiments involving stance perturbations, much of the corrective response in neck muscles appeared to be triggered by trunk and leg proprioceptive signals, and a major role for the VCR was not established. Evidence consistent with a role for the vestibular system was found in other experimental paradigms in which the head was perturbed directly. In these paradigms the VCR modulates the amplitude of functionally stabilizing responses and damps mechanically induced instability of the head and neck.
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9,178,232
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Intracellular volume and apparent diffusion constants of perfused cancer cell cultures, as measured by NMR.
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Diffusion NMR spectroscopy was used to study intracellular volume and apparent water diffusion constants in different cell lines (DU145, human prostate cancer; AT3, rat prostate cancer; MCF-7, human breast cancer; RIF-1, mouse fibrosacroma). The cells were grown on various matrices (collagen sponge, collagen beads, polystyrene beads) which enabled continuous growth in perfused high density cell culture suitable for NMR studies. In perfused cell systems, the attenuation of the water signal versus the squared gradient strength was fitted by the sum of two decaying exponentials. For the slowly decaying component the apparent water diffusion constant at 37 degrees C was 0.22 (+/-0.02) x 10(-9) s/m2 for all cell lines at diffusion times > 100 ms. It continuously increased up to 0.47 (+/-0.05) x 10(-9) s/m2 when the diffusion time was decreased to 8 ms, indicating restricted diffusion. No significant effect of the matrices was observed. The fractional volume of the slow component as determined from the biexponential diffusion curve correlated with the relative intracellular volume, as obtained from the cell density in the sample and the cell size as measured by light microscopy. Therefore, this simple NMR approach can be used to determine intracellular volume in perfused cell cultures suitable for NMR studies. Using this information in combination with spectroscopic data, changes in intracellular metabolite concentration can be detected even when the cellular volume is changing during the experiment. The apparent diffusion constant for the fast diffusing component varied with growth matrix, cell density and cell type and also showed the typical characteristics of restricted diffusion (increase of apparent diffusion constant with time).
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9,178,234
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Quantitative lactate-specific MR imaging and 1H spectroscopy of skeletal muscle at macroscopic and microscopic resolutions using a zero-quantum/double-quantum coherence filter and SLIM/GSLIM localization.
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Quantitative lactate imaging and spectroscopy were performed on phantoms and on electrically stimulated, excised frog skeletal muscle at macroscopic and microscopic resolutions. Lactate selectivity was achieved by use of a zero-quantum/double-quantum coherence (ZQC/DQC) lactate filter, which suppressed all signals besides lactate, including water and lipid, to below noise level. Three-dimensional lactate data sets were acquired in 1-3 h; one of these spatial dimensions was frequency-encoded and the other two were phase-encoded. High-resolution images were reconstructed using the spectral localization by imaging (SLIM) and generalized SLIM (GSLIM) techniques. Lactate quantitation was achieved by employing an external lactate concentration standard and was verified by comparison to quantitative STEAM-localized and nonlocalized spectra that used total creatine as an internal concentration reference. Additionally, quantitatively accurate behavior of the SLIM and GSLIM techniques as applied to data sets of low signal-to-noise ratio and to macroscopically heterogeneous objects was verified using simulations and real muscle lactate data sets with known heterogeneity.
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9,178,228
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Do infants have motor responses to sudden surface rotations in prone position?
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This study investigated whether sudden rotation of the support surface (platform) triggers motor responses similar to reactions to sudden free fall in infants at very early age (2 to 5 weeks). Ten infants in prone position were exposed to sudden head-down rotation (mimicking the falling phase) and head-up rotation of the platform (mimicking landing phase) of 4 degrees or 6 degrees amplitude and 35 degrees/s velocity while EMGs and kinematics were recorded from the neck, trunk, and right arm. One infant, reassessed at 13 weeks, and one adult were tested for complementary developmental information. Sudden downward acceleration of the platform, induced either during head-down rotation or during the deceleration phase of head-up rotation, indeed mimicked falling and evoked in infants two-peaked EMG responses in the neck, trunk, and arm muscles, lasting in the latter over several hundred milliseconds. The activation pattern showed similarities to the adult and 13-week-old control subjects. The results suggested that the first burst may be ascribed to cutaneous pressure changes at the body and to vestibular signals triggering a startle-like response, whereas the second burst of the pattern in the arm is likely a candidate for an early substrate of the landing response normally seen during later stages of motor development. Head control appeared to be related more to its position with respect to the orientation of the trunk rather than to space in the infants and in the adult and might be due to the experimental paradigm, in which the surface accelerated away from the body and not, as during normal falling, when the body accelerates toward the support surface.
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9,178,235
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Effects of severe global ischemia on N-acetylaspartate and other metabolites in the rat brain.
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N-acetylaspartate (NAA) is found exclusively in neurons and their processes in the adult brain. Since the regional distribution of NAA may be imaged using magnetic resonance spectroscopic imaging (1H-MRSI), a regional measure of neuronal density may be noninvasively obtained. The technique may be particularly useful in the diagnosis of diseases where neurons are selectively injured, since these diseases do not result in definitive changes on conventional imaging studies. The goal of this study was to determine whether 1H-MRSI measurement of NAA defects neuronal loss following global ischemia. 1H-MRSI was performed in rats 24 h after global ischemia was induced by bilateral carotid occlusion plus hypotension. 1-H-MRSI showed that NAA was decreased by 28-74% in vulnerable regions, including the cortex, striatum, hippocampus, and, to a lesser extent, the thalamus. No change was observed in the brain stem or cerebellum. Regions where 1H-MRSI observed NAA was decreased also had histological evidence of selective neuronal necrosis and showed marked increase of lactate and alanine. These results show that 1H-MRSI detected loss of NAA in brain regions with selective neuronal loss, suggesting that 1H-MRSI measurements of NAA could detect neuronal loss in a variety of disease states where there is selective neuronal necrosis.
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9,178,236
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In vivo measurement of regional brain metabolic response to hyperventilation using magnetic resonance: proton echo planar spectroscopic imaging (PEPSI).
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A new rapid spectroscopic imaging technique with improved sensitivity and lipid suppression, referred to as Proton Echo Planar Spectroscopic Imaging (PEPSI), has been developed to measure the 2-dimensional distribution of brain lactate increases during hyperventilation on a conventional clinical scanner equipped with a head surface coil phased array. PEPSI images (nominal voxel size: 1.125 cm3) in five healthy subjects from an axial section approximately 20 mm inferior to the intercommissural line were obtained during an 8.5-min baseline period of normocapnia and during the final 8.5 min of a 10-min period of capnometry-controlled hyperventilation (end-tidal PCO2 of 20 mmHg). The lactate/N-acetyl aspartate signal increased significantly from baseline during hyperventilation for the insular cortex, temporal cortex, and occipital regions of both the right and left hemisphere, but not in the basal ganglia. Regional or hemispheric right-to-left differences were not found. The study extends previous work using single-voxel MR spectroscopy to dynamically study hyperventilation effects on brain metabolism.
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9,178,237
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A flexible magnetization transfer line shape derived from tissue experimental data.
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To summarize and compare magnetization transfer data from biological tissues, a method was developed to extract the average absorption lineshape of the semi-solid pool directly from magnetization transfer experimental data along with the four other parameters that characterize the two-pool model of exchange. Magnetization transfer data for several biological tissues were analyzed using this method and the resulting "flexible" lineshapes were compared with super-Lorentzian and "Kubo-Tomita" lineshapes. The use of flexible lineshapes noticeably improves the fit of the two-pool model to the data. The derived flexible lineshapes of all the tissues analyzed are physically realistic and show remarkably consistent behavior.
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9,178,238
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An MRI method for measuring T2 in the presence of static and RF magnetic field inhomogeneities.
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A magnetic resonance imaging method for measuring the T2 relaxation time constant is proposed. It is based on the assumption that, under very general conditions, the MR signal near a spin echo has a special symmetry arising from the refocusing nature of the 180 degrees RF pulse. A gradient echo sampling of the spin echo (GESSE) sequence is implemented to evaluate T2 by collecting multiple gradient echoes before and after the spin echo. This approach is a modification of the GESFIDE sequence proposed by Ma and Wehrli. However, our approach compares images that are not separated by any RF pulses and, as a result, is insensitive to slice profile imperfections. In addition, the calculated T2 value does not rely on any special assumptions about the MRI signal behavior in the presence of an inhomogeneous static magnetic field and, hence, is insensitive to the presence of static magnetic field inhomogeneities.
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9,178,239
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Evaluation of the early response in fMRI in individual subjects using short stimulus duration.
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Optical imaging studies have provided evidence of an initial increase in deoxyhemoglobin following the onset of neuronal stimulation/activation and demonstrated that this initial increase could be spatially more specific to the site of neuronal activity. These studies also raised the possibility of improving the specificity of fMRI by selective mapping of this early response. Previous MR studies reported the observation of this early response but were limited in scope and not in full agreement. This paper presents a more extensive study that (a) demonstrates the initial signal decrease in individual subjects and (b) examines its dependence on stimulus duration and subject. Binocular visual stimulation experiments were performed on 14 subjects using echo-planar imaging (EPI) with high temporal resolution. An initial signal decrease was consistently observed in regions that were more localized than those displaying the delayed positive response. In agreement with previous fMRI and optical imaging findings, the maximum signal decrease was 1-2% and occurred at approximately 2 s after the onset of the stimulus, depending on the subject. For stimulus longer then 3.0 s, the temporal dynamics and the amount of signal change of the early response was essentially independent of the stimulus duration, while the delayed response and the post-stimulus undershoot increased both in terms of magnitude and rise time as the duration of the stimulus increased; this observation is concordant with the recent optical imaging study.
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