[The department of internal medicine: change in historical structure].
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Biomedical subjects
Publications and source records attributed to M Levy.
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The pharmacokinetics and effects on platelet function of dipyrone (1.0 g; 2.5 g; i.v.) and ketorolac tromethamine (30 mg; i.m.) were studied in a three-way crossover study in twelve healthy subjects. The biosynthesis of thromboxane A2 in clotting whole blood ex vivo as well as collagen-induced platelet aggregation were determined before and up to 48 h after administration. Both prostanoid biosynthesis and platelet aggregation were inhibited by ketorolac tromethamine for a significantly longer period of time than by both doses of dipyrone. The changes in platelet functions correlated well with the serum concentrations of ketorolac or 4-methylaminoantipyrine and 4-aminoantipyrine. Using the sigmoidal Emax model the mean serum concentration (SD) of ketorolac, 4-methylaminoantipyrine and 4-aminoantipyrine inhibiting platelet TXB2 generation by 50% (EC50) in vitro was found to be 0.088 +/- 0.031, 1.2 +/- 0.3 and 10.2 +/- 3.4 micrograms ml-1, respectively. In conclusion the recovery of platelet function after dipyrone administration is faster as compared to ketorolac tromethamine. This is in line with clinical observations and may be an advantage when these drugs are given as postoperative analgesics at the doses tested.
OBJECTIVE: To test the effect of atrial natriuretic peptide (ANF) in dogs with acute pulmonary edema in the absence of urinary sodium retention. ANF is normally a potent natriuretic agent, although this effect is attenuated in generalized edema or acute renal failure. DESIGN: Animal study. SUBJECTS: Twenty-nine dogs. INTERVENTION: Induction of acute pulmonary edema with intravenously administered alloxan and administration of ANF according to five protocols. OUTCOME MEASURES: Natriuretic effect of ANF before and after the induction of pulmonary edema during the protocols. RESULTS: In six control animals, induction of pulmonary edema was associated with diuresis (mean 0.38, standard error of the mean [SEM] 0.003 mL/min before alloxan administration v. mean 0.75, SEM 0.11 mL/min after); natriuresis (mean 60, SEM 8 mumol/min before v. mean 103, SEM 12 mumol/min after); and a decline in blood pressure (mean 114, SEM 7 mm Hg before v. mean 93, SEM 9 mm Hg after) and in the glomerular filtration rate (mean 52, SEM 3.3 mL/min before v. mean 36, SEM 3.7 mL/min after). When isoncotic dextran solution was infused in dogs with pulmonary edema, blood pressure was maintained but the glomerular filtration rate still declined by 42% and there was natriuresis. When the renal arteries were clamped for 5 minutes during the infusion of alloxan, diuresis and natriuresis were prevented, but the glomerular filtration rate still declined, although blood pressure was maintained. ANF administered intravenously during pulmonary edema induced a further significant natriuresis in all experimental protocols. Catalase, administered intravenously as a bolus just before the alloxan infusion, prevented pulmonary edema and the associated renal changes. CONCLUSIONS: Although alloxan appears to be directly nephrotoxic, renal damage caused by this compound does not impair the natriuretic effect of ANF in acute pulmonary edema.
The Aerodium hover sport facility in Eilat has been in operation for the past 4 years and 33 patients have been treated for injuries caused by falls while hovering. The Aerodium is a new sport facility in Israel, similar to others in the US and Switzerland. It includes a 4-meter-wide wind tunnel with air pushed vertically upwards toward its center. Air flow velocity is adjustable and ranges between 120 and 140 km/hr, with a maximum of approximately 180 km/hr. Participants wear special suits and jump into the center of the column of air to hover. The hover suits are very wide, and puff up like a balloon; the sleeves and leggings have vents through which air escapes. Participants hover with their arms spread out and their legs slightly spread apart. The inexperienced hover at a height about 2 m. and the more experienced at heights of up to 5 m. During falls the person hovering lands on air mattresses surrounding the air column. Failure to follow rules and procedures, usually while changing limb position during hovering, can unbalance the inexperienced participant and lead to uncontrolled spins and falls.
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To determine the effect of pretransplant liver function on survival following orthotopic liver transplantation and to quantify the effects of cyclosporine administration on long-term renal function in patients undergoing liver transplant, we performed an analysis of a prospectively maintained database. Data from 569 consecutive patients undergoing liver transplantation alone who were treated with CsA for immunosuppression were used for this study. Actuarial graft and patient survival rates were calculated using Kaplan-Meier statistics. Glomerular filtration rates, serum creatinine, and the use of various immunosuppressives were analyzed for this study. The initial analysis demonstrated that patients presenting for liver transplant with hepatorenal syndrome have a significantly decreased acturial patient survival after liver transplant at 5 years compared with patients without hepatorenal syndrome (60% vs. 68%, P < 0.03). Patients with hepatorenal syndrome recovered their renal function after liver transplant. Patients who had hepatorenal syndrome were sicker and required longer stays in the intensive care unit, longer hospitalizations, and more dialysis treatments after transplantation compared with patients who did not have hepatorenal syndrome. The incidence of end-stage renal disease after liver transplantation in patients who had hepatorenal syndrome was 7%, compared with 2% in patients who did not have hepatorenal syndrome. To more fully examine the effect of pretransplant renal function on posttransplant survival, the non-hepatorenal syndrome patients were divided into quartiles depending upon their pretransplant renal function. The patients with the lowest pretransplant renal function had the same survival as the patients with the highest pretransplant renal function. In addition, there was no increased incidence of acute or chronic rejection in any of the groups. The patients with the lower pretransplant renal function were treated with more azathioprine to maintain renal function and had a negligible decrease in glomerular filtration rate following transplant. Conversely, patients with the highest level of renal function pretransplant had a 40% decline in renal function in the first year, but maintained stable renal function up to 4 years after transplant. We conclude that pretransplant renal function other than hepato-renal syndrome has no effect on patient survival after orthotopic liver transplant. Renal function after liver transplant is stable after an initial decline, despite continued administration of CsA.(ABSTRACT TRUNCATED AT 400 WORDS)
The small subunit (SSU) of Rubisco is synthesized in the cytosol in a precursor form. Upon import into the chloroplast, it is proteolytically processed at a Cys-Met bond to yield the mature form of the protein. To assess the importance of the Met residue for recognition and processing by the stromal peptidase, we substituted this residue with either Thr, Arg or Asp. The mutant precursor proteins were imported into isolated chloroplasts, and the products of the import reactions were analyzed. Mutants containing Thr or Arg residues at the putative processing site were processed to a single peptide, comigrating with the wild-type protein. N-terminal radio-sequencing revealed that these mutants were processed at the Cys-Thr and the Cys-Arg bond, respectively. After import of the Asp-containing mutant, four processed forms of the protein were observed. Analysis of the most abundant one, co-migrating with the wild-type protein, demonstrated that this species was also a product of correct processing, at the Cys-Asp bond. All the correctly processed peptides were found to be associated with the holoenzyme of Rubisco, and remained stable within the chloroplast, like the wild-type protein. The results of this study, together with previous ones, suggest that proper recognition and processing of the SSU precursor are more affected by residues N-terminal to the processing site than by the residue on the C-terminal side of this site.
Following an overnight fast and 2 days of abstention from caffeine, a single 1.0-g oral dose of antipyrine was administered to 20 obese but otherwise healthy subjects (group A) and 11 healthy volunteers (group B). Weight, Body Mass Index (BMI) and % of Ideal Body Weight (IBW) were significantly greater in the obese than in the lean group. (Mean 110.4 vs 62.7 kg; 38.5 vs 22.3 kg.m-2 and 181 vs 106% respectively). In a subgroup of 6 obese subjects (group C) antipyrine was given again 11.3 months later after a 29.8 kg mean weight loss. Antipyrine apparent volume of distribution (V) and elimination half-life (t1/2) were significantly greater in the obese than in the lean group (V 49.9 vs 34.3 l respectively; t1/2 15.5 vs 12.0 h respectively), but its clearance rate (CL0) values were similar. V corrected for total body weight was significantly reduced in group A than in group B (0.45 vs 0.55 l.kg-1 respectively). Stratified comparison of antipyrine pharmacokinetics between obese and lean subjects according to age, gender and smoking habits did not alter the overall results. In group C, weight reduction was associated with a significant decrease in antipyrine V (from 51.8 to 47.5 l) and t1/2 (from 15.1 to 12.7 h), and a non-significant increase in antipyrine CL0. We conclude that in severely obese subjects, antipyrine total V is mildly increased but V corrected for total body weight is significantly decreased. In addition, obesity is associated with a slight prolongation of antipyrine t1/2 whereas its CL0 is unaltered. These findings may indicate that obesity, even in its extreme form, has a negligible effect on the oxidative metabolic capacity of the liver.
BACKGROUND AND OBJECTIVES: Dipyrone is an analgesic, antipyretic, and anti-inflammatory drug. After oral administration it is hydrolyzed to 4-methylaminoantipyrine and further metabolized to 4-aminoantipyrine, 4-formylaminoantipyrine, and 4-acetylaminoantipyrine. This study investigated the disposition of dipyrone metabolites in 12 hospitalized patients with cirrhosis (age, 25 to 65 years) and 27 healthy subjects of two age groups (young, 21 to 40 years; elderly, 73 to 90 years). METHODS: Subjects received 1 gm dipyrone orally, and blood samples were drawn and urine collected over 72 hours. Plasma and urine concentrations of the four metabolites were determined by HPLC. RESULTS: 4-Methylaminoantipyrine terminal elimination half-life (t1/2 beta) in patients with cirrhosis was prolonged compared with young and elderly subjects (mean +/- SEM, 10.6 +/- 0.6 versus 3.1 +/- 0.2 and 4.9 +/- 0.6 hours, p < 0.001), and the nonrenal clearance was reduced compared with the young subjects (1.069 +/- 0.243 versus 2.165 +/- 0.154 ml/min/kg, p < 0.005). 4-Formylaminoantipyrine was undetectable in two patients and in the remaining 10 patients, t1/2 was longer than in the young subjects (26.4 +/- 4.3 versus 10.8 +/- 0.7 hour, p < 0.01), whereas the elderly had intermediate values (18.1 +/- 2.8 hours). Clearance for production of 4-formylaminoantipyrine was reduced in the patients with cirrhosis than in the young and elderly subjects (0.109 +/- 0.024 versus 0.363 +/- 0.031 and 0.340 +/- 0.053 ml/min/kg, p < 0.001). The acetylation phenotype was determined to evaluate the pharmacokinetic parameters of 4-aminoantipyrine and 4-acetylaminoantipyrine. Prolongation of the 4-aminoantipyrine t1/2 and decrease in its clearance for production was found for the patients with cirrhosis, both slow and rapid acetylators, compared with the young and elderly subjects (p < 0.01). 4-Acetylaminoantipyrine t1/2 was also prolonged for patients with cirrhosis, slow and rapid acetylators, compared with the young subjects (p < 0.005). In the slow acetylators, clearance for production of 4-acetylaminoantipyrine did not differ between the patients with cirrhosis and the young subjects (p < 0.5); however, a difference was found for the rapid acetylators (p < 0.001). CONCLUSION: Our results show that the disposition of 4-methylaminoantipyrine, 4-aminoantipyrine, 4-formylaminoantipyrine, and 4-acetylaminoantipyrine is reduced by chronic liver disease after a single oral dose of dipyrone.
BACKGROUND/AIMS: It has been suggested that activity of pancreatic enzymes and concentrations of tumoral markers in cyst fluid may help to distinguish pseudocyst, serous, and mucinous cystadenomas. The aim of this study was to prospectively assess the reliability of preoperative biochemical and tumor marker analysis in cyst fluids obtained by fine-needle aspiration for pathological diagnosis. METHODS: Cyst fluid was obtained preoperatively by fine-needle aspiration, and biochemical and tumoral marker values were measured. The diagnosis of cystic tumors (7 serous cystadenomas and 12 mucinous tumors) was established by surgical specimen analysis. Thirty-one pancreatic pseudocysts complicating well-documented chronic pancreatitis were also studied. RESULTS: Carbohydrate antigen 19.9 levels of > 50,000 U/mL had a 75% sensitivity and a 90% specificity for distinguishing mucinous tumors from other cystic lesions. Carcinoembryonic antigen levels of < 5 ng/mL had a 100% sensitivity and an 86% specificity for distinguishing serous cystadenomas from other cystic lesions. Amylase levels of > 5000 U/mL had a 94% sensitivity and a 74% specificity for distinguishing pseudocysts from other cystic lesions. CONCLUSIONS: High carbohydrate antigen 19.9, low carcinoembryonic antigen, and high amylase levels in cyst fluid are very indicative of mucinous tumors, serous cystadenomas, and pseudocysts, respectively.
Cardiovascular responses to three laboratory stressors (i.e., postural change, treadmill exercise, forehead cold) were evaluated in 106 children (72 Whites, 34 Blacks) who varied in family history (FH) of early myocardial infarction (53 positive FH, 53 negative FH). Subjects were evaluated on two occasions separated by one year. In general, regardless of ethnicity, gender or FH, stability of resting blood pressures (BP) and heart rates were comparable to existing data. Resting cardiac output (CO) and total peripheral resistance (TPR) stability estimates were comparable or higher than the BP estimates across groups except for the +FH subjects and males who showed poor stability to one or both parameters. Moderate stability was observed for all parameters in response to forehead cold and low to moderate stability was observed in HR, CO, and TPR postural change reactivity. The only consistent pattern of significant differences in stability estimates involved ethnicity. African-Americans exhibited significantly higher coefficients compared to Whites in TPR at rest and during postural change and forehead cold. Reasons for the low to moderate resting and reactivity stability estimates are discussed.
BACKGROUND: Desonide, a class 6 nonfluorinated topical corticosteroid, has been available for more than two decades. Hydrocortisone is widely used in the treatment of dermatoses in children. OBJECTIVE: Our purpose was to compare the safety and efficacy of desonide ointment and 1.0% hydrocortisone ointment in children with atopic dermatitis. METHODS: One hundred thirteen children (mean age, 4.8 years) with mild to moderate atopic dermatitis were enrolled in a multicenter, randomized, investigator-masked, parallel-group study. Treatments were applied twice daily for 5 weeks and extended to 6 months in 36 of the patients. Signs of atrophy were evaluated. Efficacy was determined by measuring global improvement, erythema, lichenification, excoriations, oozing or crusting, pruritus, and induration. RESULTS: No differences in safety were observed between hydrocortisone and desonide. The investigator's global assessment of improvement significantly favored desonide over hydrocortisone during 3 months of treatment (p < 0.05). CONCLUSION: Desonide ointment showed greater efficacy, produced more rapid improvement, and demonstrated an equivalent cutaneous safety profile when compared with 1% hydrocortisone ointment for up to 6 months.
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This article outlines strategies on how to approach equine endocrine disorders based on clinical signs and clinical pathologic data. In the 1987 Veterinary Clinics of North America: Equine Practice article on evaluating equine endocrine function, Beech stated that the numbers of hormonal assays available to use in horses was limited. Unfortunately, not much has changed since then. With the advent of convenient assay kits for many hormones and cofactors available in human medicine, it is possible to submit samples to laboratories for measurement of a wide range of endogenous substances. Caution must be used when interpreting the results in equine patients. Assay kits that have not been validated for use in horses may yield results that have no clinical meaning. Using veterinary endocrinology laboratories with equine experience is the best way to assure meaningful results from diagnostic testing (Table 1). If this is not possible, submitting age, breed, and sex-matched controls along with samples from the patient horse will provide some measure of a reference range. Normal values or reference ranges from species other than the horse cannot be used to interpret the results of equine samples.
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