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Biomedical subjects

L Weinstein

Publications and source records attributed to L Weinstein.

At least 145 records · Page 8Linked to original sources

Pharmacokinetics of the penicillins in man.

The purpose of this article is to review and summarise those aspects of the pharmacokinetic behaviour of the penicillins that may be of particular interest to the clinician. While these antibiotics differ markedly in their acid stability and oral absorption, misleading inferences may be drawn from simple inspection of the maximal serum concentrations produced by a given dose administered orally. A more accurate picture emerges when serum protein binding and intrinsic activity of the drugs are taken into account. All of the penicillins are readily and actively secreted by the renal tubles and most are eliminated, almost completely unchanged, in the urine. The majority are excreted in small quantities in the bile, but this is a major route for elimination of nafcillin from the body. Distribution of the penicillins in 'non-specialised' sites is excellent. In contrast, penetration of the central nevous system and eye are poor, and of the prostate, minimal. Inflammation reduces the barries to penetration of these areas. However, quantitative data related to this phenomenon in man are few. Probenecid actively competes with the 'export' pump of the meninges and renal tubular cells. This results in an increase in concentrations of the penicillins in the blood and cerebrospinal fluid. The effect of this agent on active secretion of these antibiotics from the eye and biliary tract is minimal. While elimination of the penicillins from the body takes place largely via renal excretion, penicillin V and oxacillin are extensively degraded as well. In contrast to the situation with respect to 'natural' and 'broad-spectrum' penicillins, the serum half-life of the isoxazolyl congeners and nafcillin is only minimally prolonged in the presence of renal failure. These agents are only weakly haemodialyzable, while the other penicillins are rapidly removed from the circulation by this procedure.

Administration, Oral↗

Penetration of clindamycin phosphate into the abnormal human biliary tract.

Clindamycin phosphate, 600 mg, was given intravenously to 14 patients undergoing biliary tract surgery. Seven had complete obstruction of the common bile duct. Concentrations of total and active (nonesterified) antibiotic were measured in serum, gall bladder and common duct bile, gall bladder wall, and liver. Persons with patent common ducts had high levels of active drug at all hepatobiliary sites; concentrations were two and one half to three times higher in bile and liver than in serum. Persons with obstruction of the common duct had no measurable drug in bile and had reduced levels in gall bladder wall; however, concentrations in the liver were slightly higher than those in the group without obstruction. The results of this study suggest that, even in the presence of common duct obstruction, the concentrations of active clindamycin in the liver may be sufficient to limit the spread of intrahepatic infections due to susceptible organisms.

Anti-Bacterial Agents↗

Alcoholism as a political problem in Chile.

Chile has a very serious alcohol problem. 20% of the population over 15 years of age are problem drinkers, - 15% are excessive drinkers, and 5% are alcoholics. Excessive drinking, particularly inebriety, is considered to be the core of the alcohol problem. During Allende's government, there was an increasing concern for the national patterns of drinking. Workers began to become conscious that drinking seriously limited social and political participation. And patterns of alcohol abuse among men predict stimulated conservative attitudes in women. This paper discusses the concept of alcoholism as a disease, considering that alcohol addiction is a part of a wider problem, alcohol culture, which, in the context of the situation in Chile in 1972, had to be seen ideologically as opposed to the revolutionary process.

Alcoholism↗

Infectious diseases.

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Communicable Diseases↗

The synergistic effect of calcium and prostaglandin F2alpha in second trimester abortion. A pilot study.

A clinical use of the basic science phenomenon that prostaglandin is synergistic with calcium in increasing uterine contractility has been demonstrated. Twenty-five women had midtrimester abortions induced with intraamniotic calcium gluconate followed by prostaglandin F2alpha. All patients aborted within 21 hours with minimal toxicity. The mean injection-to-abortion interval was 13.5 hours in the group of women without a preinjection laminaria and 10.1 hours in patients when a laminaria was included in the protocol.

Abortion, Induced↗

Hemolytic disease of the neonate secondary to anti-Fya.

A case of hemolytic disease secondary to anti-Fya in a neonate requiring exchange transfusion is presented. A review of the literature reveals 18 previous cases, with 32 per cent requiring exchange transfusion and a 16 per Fya-b- or Fya-b+ blood can be obtained for exchange transfusion if indicated.

Amniocentesis↗

Eczema herpeticum. Treatment with methylene blue and light.

Kaposi varicelliform eruption due to herpes simplex virus (eczema herpeticum) is a serious disease in infants, with occasional fatal outcome. Photoinactivation therapy consisting of local application of methylene blue followed by light exposure resulted in rapid improvement both clinically and virologically. Methylene blue, at a concentration of 10(-5)M was found to be viricidal to herpesvirus in the light but not in the dark.

Administration, Topical↗

Transient bacteremia associated with barium enema.

A group of 175 patients had barium enema. Pour-plate blood cultures were obtained immediately before and after the procedure and 5, 10, 15, and 30 minutes later. Bacteremia was demonstrable in 20 (11.4%) patients. In some, blood cultures were positive for as long as 15 minutes after barium enema; all were negative at 30 minutes. Among the bacteria associated with the 20 episodes of bacteremia were Escherichia coli, Klebsiella, enterococci, Proteus morganii, Bacteroides, and Veillonella. The incidence of bacteremia among patients with ulcerative colitis, regional enteritis, rectal polyps, colonic or rectal carcinoma, nonspecific diarrhea, or other lower intestinal tract disorders was not much different from patients free of rectosigmoid disease. The results of this study suggest that a history of recent barium enema may be important in patients who have endocarditis.

Barium Sulfate↗

Pharmacokinetics of lincomycin and clindamycin phosphate in a canine model.

Linomycin and clindamycin phosphate were studed in a canine model in which acute biliary obstruction was produced during iv infusion of antibiotic. Hepatic and renal extraction, bilary and renal excretion, and concentrations in liver and kidney were measured. Total and nonesterified clindamycin were assayed. The antibiotics were taken up by the liver at similar rates; however; the rates of excretion and concentration in bile were significantly higher for lincomycin than for clindamycin. Biliary obstruction did not affect the concentration of either antibiotic in canalicular bile. Lincomycin was extracted by the kidneys and excreted into urine at a much higher rate than was clindamycin. Concentrations of nonesterified clindamycin in the hepatic vein were higher than those in the portal vein, an observation suggesting metabolic activation within the liver. This relation was reversed by bilary obstructon. The results in this canine model indicate a greater role for the kedney in the disposition of lincomycin than in that of clindamycin, major differences between the rates of biliary excretion of the two agents, and a probable change in the metabolism of clindamycin procued by acute bilary obstruction.

Animals↗

Transient bacteremia associated with percutaneous liver biopsy.

Transient bacteremia associated with percutaneous liver biopsy was studied by pour-plate blood cultures, which were obtained immediately before and after the procedure and 5, 10, 15, and 30 min later in 89 patients. Part of the liver tissue was also cultured in all patients. Histological diagnoses included hepatitis, cirrhosis, cholangitis, fatty liver, granulomata, metastatic liver disease, lymphoma, and miscellaneous disorders. All blood cultures obtained before liver biopsy were sterile. Bacteremia was demonstrable in 12 patients (13.48%). In most of these patients, blood cultures were positive for as long as 15 min after liver biopsy; all cultures were negative at 30 min. Among the bacteria associated with 12 episodes of bacteremia were Escherichia coli, Klebsiella, Bacteroides, enterococci, diphtheroids, Staphylococcus aureus, alpha-hemolytic Streptococcus, and Streptococcus pneumoniae. The patients with positive liver biopsies had a higher incidence of bacteremia (83.3%) than did the patients whose liver biopsies were sterile (8.r%); this difference is stastically significant (P smaller than 0.01). Thus, liver biopsy can be associated with transient bactermia.

Bacteroides↗

Extraction of antibiotics from the circulation by liver and kidney: effect of probenecid.

An experimental canine model was designed to measure directly the uptake, storage, and excretion of antibiotics by the liver and kidney. At equilibirum the rate of uptake of penicillin G, cephalothin, and nafcillin by these organs was about 80% of the rate of intravenous infusion of each antibiotic. Penicillin G and cephalothin were extracted mainly by the kidneys, and nafcillin by the liver. Injection of probenecid virtually abolished the difference in concentration of antibiotic between afferent and efferent vessels of the liver and kidney after 30-45 min. Renal tubular secretion of penicillin G and cephalothin was suppressed, and their levels in renal tissue were increased. These findings militate against any primary limitation by probenecid of access of antibiotic to the renal parenchyma. A marked sustained increase (60%-70%) in the rate of portal flow followed injection of probenecid, and the concomitant percentage of nafcillin extracted by the liver declined significantly. Because of the circulatory changes, a specific effect of probenecid on acess of nafcillin to the liver could not be proved.

Animals↗

Predictability of blood levels of gentamicin in man.

Data from 42 patients were analyzed to determine the predictability of the peak serum level and the t1/2 of gentamicin on the bases of age, sex, body weight, serum concentration of creatinine, and blood hematocrit. Renal function was normal in 21 patients and impaired in 21. The most striking finding was the relatively poor predictability of t1/2 of gentamicin from serum concentration of creatinine. The overall correlation coefficient was 0.749 (P less than 0.001) in contrast to values of greater than 0.9 reported by others. tthere was a significant correlation of the t1/2 of gentamicin with the reciprocal of hematocrit (r * 0.647, P less than 0.001). Linear regression equations taking account of sex, serum creatinine concentration, and reciprocal of hematocrit provided a somewhat higher correlation coefficient (0.821) with the t1/2 of gentamicin than did the equation including serum creatinine concentration alone but were still not fully satisfactory. Thus the pharmacokinetics of gentamicin may not be adequately predictable from standardized equations or nomograms.

Adolescent↗

Renal tubular transport of penicillin G and carbenicillin in the rat.

The pattern of transport of penicillin G and carbenicillin was examined directly in the rat kidney by means of micropuncture studies. Samples of plasma, tubular fluid, and urine were assayed for antibiotic content by an agar diffusion technique. Secretion accounted for 67% of the penicillin G but for only 37% of the carbenicillin present in the proximal tubule. No further net secretion of either agent could be detected in the distal nephron. Net secretion of penicillin G decreased from 67% in the distal tubule to 60% in the urine (P less than 0.05%); this reduction correlated with reabsorption of water from the collecting ducts. Both penicillin G and carbenicillin were secreted by the proximal tubule of the rat nephron, but the latter was secreted at a lower rate than the former. A significant fraction of penicillin G was reabsorbed from the collecting ducts under conditions of maximal antidiuresis.

Animals↗

Effect of diuretics on urinary excretion of cephalothin in humans.

Diuretics and antibiotics are frequently used concomitantly. The possibility of drug interactions led us to study the effects of several diuretics on the renal elimination of cephalothin. Five healthy volunteers received a constant infusion of 500 mg of sodium cephalothin per h for 9 h on 4 consecutive days. Each day, after the third hour of infusion, the subjects were given one of the following in varying order: (i) furosemide (1 mg/kg, intravenous), (ii) mercaptomerin (250 mg, intramuscular), (iii) mannitol (25 g, intravenous), or (iv) no diuretic (control day). Fluid losses were replaced hourly. Serum and complete urine collections were obtained each hour and assayed for creatinine and cephalothin (bioassay). Clearances (milliliter per minute) and urinary excretions (milligram per hour) of cephalothin did not differ either when the diuretic day values were compared with control day, or when pre- and postdiuretic results on the same day were compared. Creatinine clearances were not affected by diuretics except for a transient rise after furosemide.

Adult↗