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J J Schentag

Publications and source records attributed to J J Schentag.

At least 181 records · Page 10Linked to original sources
PubMed1983

Liquid-chromatographic assay of cefmenoxime in serum and urine.

This is a simple, precise liquid-chromatographic procedure for determining cefmenoxime in patients' serum and urine. p-Anisic acid is used as the internal standard. Protein is precipitated from 0.5 mL of serum or dilute urine with 100 microL of perchloric acid. The clear supernate is injected directly onto a mu-Bondapak CN reversed-phase column. The mobile phase is acetate buffer, pH 3.8 (25 degrees C). The flow rate is 2.5 mL/min. Column effluent is monitored at 254 nm. Extraction recovery from serum averaged 74.6%. Calibration curves were linear from 0.5 mg/L, the lower limit of quantification, to 100 mg/L. We present cefmenoxime concentrations in serum from a patient being treated for pneumonia. The procedure was evaluated in the clinical setting to determine its applicability to the study of cefmenoxime pharmacokinetics in critically ill patients.

Aged↗
PubMed1983

Antibiotic penetration in liver infection: a case of tobramycin failure responsive to moxalactam.

A 23-year-old man sustained a severe liver laceration which subsequently became infected with Enterobacter aerogenes. Blood cultures were positive for this organism and the patient experienced sepsis. Over the course of 18 days, his bilirubin and serum creatinine increased from normal to 40 and 2.7 mg/dl, respectively. Tobramycin, clindamycin, and penicillin failed to control the infection despite in vitro sensitivity of the organism to tobramycin. Moxalactam was started as a last resort, and the symptoms of infection resolved in 12 h. Both hepatic and renal function returned to normal, and the patient was discharged without complications. Moxalactam concentrations in wound fluid exceeded serum concentrations and the usual minimum inhibitory concentration of the infecting organism. A likely explanation for response to moxalactam, in face of tobramycin failure, was that moxalactam was able to reach the site of infection.

Adult↗
PubMed1982

HPLC determination of D and L moxalactam in human serum and urine.

A high-pressure liquid chromatographic procedure was developed to determine the D and L isomers of moxalactam in human plasma and urine. After protein precipitation with hydrochloric acid the sample was extracted with ethyl acetate. It was then back extracted into tromethamine buffer (pH 8.0) and washed with octanol. Extraction recovery from plasma ranged from 73-81%. An aliquot of the tromethamine buffer was then injected onto a C18-muBondapak column. The mobile phase was 3% acetonitrile in 0.05 M ammonium acetate pH 6.5 buffer. Samples were quantitated by UV detection at 275 nm and 0.01 aufs. The lower limit of detection was 0.5 microgram/ml for each isomer. Preliminary stability studies were performed to assess proper sample handling and storage conditions. The procedure was evaluated in a clinical setting to demonstrate its applicability to the study of moxalactam pharmacokinetics in critically ill patients.

Cephalosporins↗
PubMed1982

Relationship between concentration and anticoagulant effect of heparin in plasma of hospitalized patients: magnitude and predictability of interindividual differences.

The anticoagulant effect of heparin as reflected by the slope (S) of the relationship between heparin concentration and natural log of activated partial thromboplastin time (APTT) was determined in citrated plasma of 31 hospitalized, 21- to 80-yr-old patients (including many typical candidates for heparin therapy). Also determined were level of factors II, V, VII to XII, albumin, individual globulins, calcium, antithrombin III, fibrinogen, alpha-1-acid glycoprotein, alpha-1-antitrypsin, and alpha-2-macroglobulin and prothrombin time and hematocrit. Baseline APTT was 24.1 to 60.3 sec and S was 1.80 to 4.27 ml/u. S correlated with baseline APTT, hematocrit, total protein, functional antithrombin III, prothrombin time, beta-globulin, and factors II, VII, X, XI, and XII. A multiple linear regression equation with baseline APTT, total protein concentration, and factor XI as independent variables was "best" for predicting the S of these patients (r = 0.807, P less than 0.0001). A multiple linear regression equation with baseline APTT and hematocrit as independent variables, obtained in a previous study on healthy subjects, overpredicted the patients' S values. An equation with baseline APTT and gamma-globulins as independent variables yielded the best correlation predicted and actual S values for the combined group of patients and normal subjects (r = 0.715, P less than 0.0001). Our observations indicate that it may be possible to predict the heparin concentration-anticoagulant effect (APTT) relationship for individual patients before institution of heparin therapy.

Adult↗
PubMed1982

Mental status, the intensive care unit, and cimetidine.

A blinded, prospective study of the association between cimetidine treatment and altered mental status (MS) was evaluated in 217 surgical intensive care patients stratified by the degree of renal or hepatic dysfunction or both. The cimetidine and noncimetidine groups did not differ in blood chemistries, physiologic-metabolic data, or concurrent medications. There was a correlation between treatment with cimetidine and changes in MS (p less than 0.0001). The MS changes with cimetidine ranged from 33% for neither hepatic nor renal dysfunction to 80% for both renal and liver impairment. The magnitude of MS change was influenced by disease and serum concentration, with patients with both renal and liver disease having the greatest MS change at the highest serum concentrations. The type of MS change was also disease specific. All MS change cleared within 24 to 36 hours of stopping the drug. It appears that both dosage and underlying disease state are important factors determining the nature and severity of cimetidine-associated mental status changes.

Adult↗
PubMed1982

Rate of methicillin penetration into normal heart valve and experimental endocarditis lesions.

Methicillin concentrations were measured in serum, normal heart valves, damaged heart valves, myocardium, and extravascular fluid from 12 New Zealand white rabbits to assess the influence of valvular damage on methicillin penetrations. Fibrin scarring of the aortic valve was induced by the placement of a polyethylene catheter through the aortic leaflet for 4 days. Each rabbit was then given a 40-mg/kg intravenous bolus dose of methicillin. Serum concentrations were collected, and animals were sacrificed 5, 15, 30, and 60 min after the dose. Normal and damaged heart valves from six different rabbits were desiccated to evaluate the fluid content of each. The time course of methicillin in damaged aortic valves was similar to that in serum and followed a bioexponential decline. The pharmacokinetic profile of methicillin in normal heart muscle and normal heart valves was clearly different from that of serum and damaged heart valves. Damaged valves showed a rapid and complete equilibrium with serum, whereas normal heart valve and muscle methicillin concentrations were consistently lower than serum concentrations at all times after the rapid bolus dose. The greater extravascular fluid content in damaged heart valves (P less than 0.001) compared with that in normal heart valves may be associated with the greater extent of penetration into damaged heart valves. Equilibrium between serum and damaged valves may be achieved more rapidly because the damaged area is composed of platelet and fibrin matrix and lacks the membrane integrity of normal heart valve tissue.

Animals↗
PubMed1982

Clinical and pharmacokinetic characteristics of aminoglycoside nephrotoxicity in 201 critically ill patients.

We studied 201 critically ill patients during 267 courses of gentamicin (139 courses) or tobramycin (128 courses) therapy. Clinical and pharmacokinetic data were obtained on 240 of 267 courses (120 courses each of gentamicin and tobramycin). Two judgments of nephrotoxicity and its cause were made independently in this study, using a clinical and a pharmacokinetic definition of nephrotoxicity. The two sets of criteria were generally in good agreement, as all but 10 of 41 patients who were judged nephrotoxic by pharmacokinetic criteria were independently judged nephrotoxic by the clinical definition. Groups of patients judged nontoxic did not differ from groups judged nephrotoxic in age, sex, weight, initial creatinine clearance, total dose given, duration of treatment, initial aminoglycoside trough serum levels, number of dosage adjustments, concurrent use of furosemide, or concurrent cephalosporins. Prior aminoglycosides (usually gentamicin) had been used more frequently in the nontoxic group (P less than 0.05). Two major conclusions of this study are at variance with those of previous investigators; (i) we found no clinical parameters of value in predicting nephrotoxicity in critically ill patients; and (ii) aminoglycoside serum concentrations, once in the therapeutic range, were of limited value in prevention of aminoglycoside nephrotoxicity in our patients.

Aminoglycosides↗
PubMed1982

Excretion of cephalothin and cefamandole by the normal pancreas and in acute pancreatitis in dogs.

Nine mongrel dogs were studied to evaluate the excretion of cefamandole (five dogs) and cephalothin (four dogs) in the pancreatic fluid. Each dog was studied before and after the induction of pancreatitis, with 2 weeks between studies. After intravenous administration of a 25-mg/kg dose of either cephalosporin, serum and pancreatic fluid concentrations were monitored for 6 h. Both cephalothin and cefamandole were excreted in bactericidal concentrations in the normal pancreas and in acute pancreatitis. Clearance of cefamandole (290 ml/min) and cephalothin (348 ml/min) were similar pre- and postinduction of pancreatitis. Serum albumin concentration was less during the post-pancreatitis phase compared with the prepancreatitis phase. Penetration of cephalothin was reduced in pancreatitis, whereas cefamandole penetration increased in pancreatitis.

Acute Disease↗
PubMed1982

Two-compartment comparison of gentamicin and tobramycin in normal volunteers.

The objective of this study was to determine whether differences in tissue accumulation observed upon multiple dosing of aminoglycosides in hospitalized patients could be identified in appropriate single-dose studies in normal volunteers. Ten volunteers received single intravenous doses of 1.0 mg of gentamicin and tobramycin per kg of body weight in randomized crossover fashion. Multiple serum and urine samples were collected during the next 30 days. Serum aminoglycoside concentrations and urinary excretion rates were fitted to a two-compartment pharmacokinetic model, and parameters were derived. Tobramycin exhibited a higher clearance (P less than 0.08) and a lower volume of distribution at steady state (P less than 0.1), neither of which was significant. Tobramycin also showed a significantly lower predicted amount of drug in the body at steady state (P less than 0.05). These differences are consistent with observations made in patients receiving multiple doses. Single-dose studies appear to be capable of discriminating pharmacokinetic characteristics relevant to the comparative nephrotoxic potential of these two aminoglycosides.

Aged↗
PubMed1982

Renal handling of gentamicin by normal and ischemic canine kidneys.

The purpose of this study was to examine the pharmacokinetics of gentamicin renal uptake in dogs and assess the role of chronic renal ischemia. A stenosing silver clip was place on the left renal artery of four mongrel dogs. Six months later, each dog received an infusion of gentamicin and inulin. Blood and urine samples were collected serially. In each dog, the ischemic left kidney was smaller and had a lower RPF and CCR. The decrease in CCR was highly correlated with the decrease in RPF. Measured gentamicin kidney concentrations were found to be in good agreement with predicted values based on the amount reabsorbed and the kidney weight. Within each animal (control vs. ischemic kidney), there was a significant correlation between the filtered load of gentamicin and both the renal reabsorption and excretion of gentamicin. These relationships exhibited high R2 values, demonstrating that the induced ischemia did not alter the filtration or reabsorbtive mechanisms of gentamicin within the animal, but only decreased the filtered load. Between animals, gentamicin excretion was proportional to filtered load, but gentamicin reabsorption had the lowest r2 value, explaining only 49% of the observed variance. The unexplained variance encountered in gentamicin reabsorption between animals establishes that there are important determinants of renal tissue concentration that are independent of filtration or filtered load. This study suggests that a reduction in glomerular filtration is not an important risk factor for elevated gentamicin renal tissue concentrations, provided that serum concentrations are controlled within the therapeutic range.

Absorption↗
PubMed1981

ICU nurses rate their work places.

An investigation of 10 critical care units recorded nurses' perceptions of the positive and negative aspects of their work settings.

Attitude of Health Personnel↗
PubMed1981

Age, disease, and cimetidine disposition in healthy subjects and chronically ill patients.

Cimetidine induces reversible dose-related central nervous system (CNS) toxicity. Trough serum concentrations and the development of CNS toxicity correlate. We compared cimetidine kinetics in 12 healthy subjects and 31 patients. Six of the latter had normal renal and liver function, five had renal disease only, 12 had liver disease only, and eight had both renal and liver disease. Postmortem tissue distribution was assessed in 11 patients, and expressed as tissue:serum ratio. Average cimetidine total clearance (ClB) in milliliters per minute for each group was as follows: patients with renal and liver disease (182 +/- 105), renal disease only (193 +/- 24), liver disease only (463 +/- 145), normal patients (510 +/- 93), and healthy subjects (583 +/- 140). Renal function was the major determinant for ClB, and the relationship was described by ClB = 4.2(CCr) + 140, r = 0.87, where CCr is creatinine clearance. Cimetidine clearance was affected little by age. Tissue:serum ratios from highest to lowest were as follows: kidney greater than stomach greater than liver greater than bone greater than brain greater than fat. Central and steady-state distribution volumes were not influenced by age or disease. There was enchanced CNS penetration in liver disease patients; their cerebrospinal fluid (CSF):serum ratio was twice the normal. Our kinetic studies identify patient characteristics likely to result in elevated blood levels, and suggest that the greatest risk of CNS toxicity is in those with liver disease.

Adolescent↗
PubMed1981

Effect of bile induced pancreatitis on tobramycin excretion in pancreatic fluid.

The objective of this study has been to lay the groundwork for a re-evaluation of the place of antibiotics in acute pancreatitis. This section has been devoted to determining if antibiotics excreted by the normal pancreas are excreted similarly in acute pancreatitis. Ten mongrel dogs were studied, each acting as its own control. Day 1: Operation--construction of pancreatic fistula. Day 2: Study of antibiotic excretion. Day 14: Operation--induction of acute focal pancreatitis. Day 15: Study of antibiotic excretion. Antibiotic concentrations in pancreatic fluid were studied by injecting tobramycin intravenously (5 mg/kg). Serum levels and excretion of the drug in the pancreatic secretion were then monitored over the next six hours. Results showed excretion of tobramycin reached bactericidal concentrations in pancreatic fluid from the normal and inflamed pancreas, with no significant differences (p = 0.2) between the excretion rates. The place of antibiotics in acute pancreatitis is discussed. Based on usual pathogens isolated in pancreatic abscesses, and their usual sensitivity patterns, tobramycin with Cephamandole are the antibiotics of choice in acute pancreatitis, and a clinical trial is indicated to evaluate their place in reducing complications and deaths in the disease.

Acute Disease↗
PubMed1981

Amikacin and gentamicin accumulation pharmacokinetics and nephrotoxicity in critically ill patients.

Twenty-five critically ill adults receiving blood level-adjusted doses of amikacin were prospectively studied with serum, urine, and, when possible, tissue amikacin concentrations. These data were fitted to a two-compartment pharmacokinetic model. Prolonged urine collections or postmortem tissues (or both) were used to confirm predicted tissue accumulation. Nephrotoxicity was also investigated. Patients were defined as having renal damage if they showed an increase in serum creatinine of greater than 0.5 mg/100 ml, an increase in urine beta 2-microglobulin of greater than 50 mg/day, and presence of urinary casts of greater than 500/ml. Renal damage was attributed to amikacin if there was, in addition to the above, tissue accumulation of amikacin of greater than 600 mg. These patients were matched with 25 patients treated with gentamicin during the same time period. There were no statistical differences between the gentamicin- and amikacin-treated patients in age, sex, weight, base-line creatinine clearance, concurrent cephalosporins or diuretics, treatment duration, site of infection, normalized (amikacin/gentamicin dosing ratio of 3:1) total dose, mortality, or tissue accumulation. More amikacin-treated patients (19 of 25) than gentamicin-treated patients (9 of 25) received prior aminoglycosides (P less than 0.01). The only pharmacokinetic parameter that differed between amikacin and gentamicin was a greater K21 for gentamicin. Nephrotoxicity was observed in 4 gentamicin was a greater K21 for gentamicin. Nephrotoxicity was observed in 4 gentamicin-treated patients (16%) and 5 amikacin-treated patients (20%). At a 3:1 dosing ratio, there were no significant differences between amikacin and gentamicin two-compartment pharmacokinetics and nephrotoxic potential in matched critically ill patients, but the trend of these data showed greater amikacin tissue accumulation. However, at an amikacin/gentamicin dosing ratio of 4:1, their tissue accumulation potential appeared to be almost identical.

Amikacin↗
PubMed1981

Methicillin distribution in serum and extravascular fluid and its relevance to normal and damaged heart valves.

We evaluated the distribution of methicillin into normal and damaged heart valves and the accuracy with which subcutaneous plastic chambers reflected tissue uptake of this antibiotic. A total of 24 male New Zealand rabbits were given constant infusion doses of methicillin through central venous catheters. Five of these animals had their aortic and mitral valves damaged by catheterization of the left ventricle. A total of 19 rabbits had perforated plastic chambers inserted subcutaneously 7 to 10 days before methicillin infusion. In all animals more than 80% of the total infused dose of methicillin was accounted for in the serum, urine, and tissues. In the 12 animals infused to steady state (less than 7 h), the steady-state serum concentrations (11 to 120 micrograms/ml) were equal to the concentrations attained in either peritoneal or tissue chamber fluids. In the 12 animals sacrificed before 7 h, tissue chamber concentrations lagged behind serum and heart tissue concentrations in attaining steady state. Steady-state concentrations in normal heart valves and heart muscles failed to increase proportionally to increased constant infusion doses (8.7 to 87.2 mg/kg per h). The steady-state methicillin concentrations in fibrin-scarred heart valves were invariably higher than the steady-state concentrations in the normal right heart of the same animals (P less than 0.05). Tissue uptake of methicillin was altered in scarred heart valves as compared to normal heart valves, and large-volume subcutaneous tissue chambers misrepresented the uptake rate of methicillin into heart tissues and valves.

Animals↗
PubMed1981

Comparative nephrotoxicity of gentamicin and tobramycin: pharmacokinetic and clinical studies in 201 patients.

A total of 201 critically ill patients were studied during 267 courses of gentamicin or tobramycin treatment (139 gentamicin courses and 128 tobramycin courses). Of these 267 courses, pharmacokinetic and clinical data were obtained for 240 (120 gentamicin and 120 tobramycin). The data collected for pharmacokinetic analysis included measurements of serial blood and urine levels, urinary excretion of beta 2-microglobulin, protein levels, and granular casts. A two-compartment model was used to assess tissue accumulation, and in 89 courses the predicted accumulation was confirmed by cumulative urine collection or postmortem tissue analysis. As groups, the patients given gentamicin and tobramycin did not differ in age, weight, creatine clearance, total dose given, duration of treatment, initial aminoglycoside through serum levels, number of dosage adjustments, concurrent use of furosemide, or concurrent cephalosporins. Previous aminoglycoside treatment (usually gentamicin) had occurred more frequently in the tobramycin treated patients (P less than 0.01), and more males than females received tobramycin (P less than 0.05). Pharmacokinetic assessments of renal damage were based on both changes in glomerular filtration rate (serum creatinine levels, creatinine clearance) and renal tubular damage (beta 2-microglobin, casts), but only patients with elevated aminoglycoside tissue levels leading to renal tubular damage and subsequent creatinine clearance decreases were considered to have experienced aminoglycoside nephrotoxicity. In the pharmacokinetic analysis of nephrotoxicity, 29 gentamicin courses (24%) and 12 tobramycin courses (10%) were complicated by nephrotoxicity (P less than 0.01). The 201 study patients were also evaluated independently for clinical nephrotoxicity (defined as a serum creatinine level increase of 0.5 mg/dl or more). Clinical nephrotoxicity occurred at rates of 37% in the gentamicin-treated group and 22% in the tobramycin-treated group (P less than 0.02). In these similar groups of critically ill patients, tobramycin was less nephrotic than gentamicin.

Aged↗