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Biomedical subjects

S Z Hirschman

Publications and source records attributed to S Z Hirschman.

At least 37 records · Page 2Linked to original sources

Malignant external otitis. Comparison of monotherapy vs combination therapy.

Twenty patients with adult-onset diabetes mellitus and malignant external otitis (MEO) were treated at the Mount Sinai Medical Center, New York, over a seven-year period (August 1976 to October 1983). A retrospective analysis compared patients who received an antipseudomonal cephalosporin as monotherapy (group A) with those who received conventional antipseudomonal therapy (group B). Pseudomonas aeruginosa was isolated in all patients. Differences (group B less than group A) included insulin dependence, underlying vascular disease, total number of cranial nerve palsies or paresis, and surgical procedures. The overall clinical outcome was similar in both groups; 64% of patients in group A (7/11) and 70% in group B (7/10) were cured at a follow-up period of five to 57 months. A more favorable outcome was found in patients with less extensive infection in both groups. Monotherapy compared favorably with conventional antipseudomonal therapy for the treatment of patients with MEO and moderate infection.

Aged↗

Pharmacokinetic properties of mezlocillin in ambulatory elderly subjects.

Twelve healthy ambulatory elderly subjects (mean age, 73-78 years) randomly received either a 4-g or 5-g dose of mezlocillin intravenously. One week later the regimen was repeated and patients crossed over to the other dose. Peak serum concentrations were 165 mg/L and 281 mg/L for the 4-g and 5-g doses, respectively. For both doses, differences in t1/2 beta (1.32 hr vs 1.13 hr), AUC (275 mg.hr/L vs 403 mg.hr/L), CL (207 mL/min vs 174 mL/min), CLR (59 mL/min vs 45 mL/min), CLNR (152 mL/min vs 130 mL/min) were not statistically significant. The differences in Varea (22.4L vs 168.8L, P less than or equal to .01) and Cmax (216.6 mg/L vs 317 mg/L, P less than or equal to .05) were statistically significant. Comparison with pharmacokinetic parameters obtained in younger subjects following the 5-g dose reveals that in the elderly the AUC, Varea, and CLNR are higher whereas the CL and CLR are lower. The elderly demonstrated an increase in nonrenal clearance compared with young subjects that is not fully compensatory. The increased AUC in the elderly group suggests that clinical studies examining mezlocillin doses and dose intervals in the treatment of serious infections are warranted in infected elderly patients.

Aged↗

Infections associated with transhepatic biliary drainage devices.

To determine the infectious complications associated with transhepatic biliary drainage devices, an analysis of the records of 38 patients who underwent placement of a pigtail catheter (n = 11), a Ring catheter/feeding tube (n = 13), or a Carey-Coons endoprosthesis (n = 15) was carried out. Nineteen infectious events occurred in 38 patients with 39 biliary devices. Infections consisted of bacteremia, cholangitis with and without documented bacteribilia, and intrahepatic abscesses and were frequently associated with obstruction (66.7 percent of infectious episodes). The most frequent organisms isolated from blood were Escherichia coli and Pseudomonas aeruginosa, and the most frequent organisms isolated from bile were P. aeruginosa, Klebsiella pneumoniae and Streptococcus faecalis. Trends for more frequent occurrence of neoplasms involving the gallbladder or biliary tract, recent surgical procedures and catheter manipulations in infected as compared with noninfected patients, and a delayed time to infection were noted in patients with an endoprosthesis.

Adult↗

Pharmacokinetics of cefoperazone in ambulatory elderly volunteers compared with young adults.

Two groups of 10 healthy ambulatory subjects, i.e., a group of 10 persons less than or equal to 30 years of age (mean age, 27.6 years) and a group of 10 persons greater than or equal to 65 years of age (mean age, 70 years), were randomized in a single-trial crossover design to receive 1 and 2 g of cefoperazone with a 1-week washout between doses. The elderly subjects had both decreased estimated creatinine clearances and decreased albumin concentrations in serum. Cefoperazone concentrations in serum of elderly persons were significantly higher at each interval from 30 min to 6 h for the 2-g dose. Compared with that in younger persons, the total clearance in elderly subjects was significantly lower for both the 1- and 2-g doses, the renal clearance was significantly lower for the 2-g dose, and the area under the curve was significantly higher for the 2-g dose in the elderly persons. The half-life at beta phase was higher in the elderly persons at both the 1- and 2-g doses but not significantly so. Changes in total clearance and area under the curve and higher levels in serum in the elderly persons suggest a longer duration of antimicrobial activity in this age group.

Adult↗

Pulmonary toxoplasmosis in AIDS.

In contrast to toxoplasmosis in non-AIDS immunocompromised hosts, AIDS patients rarely have been reported to be infected at extra-CNS sites. We report the case of a 45-year-old homosexual male with AIDS who presented with pneumonitis caused by Toxoplasma gondii following a previous illness consistent with CNS toxoplasmosis.

Acquired Immunodeficiency Syndrome↗

Pharmacokinetics of mezlocillin in patients with hepatobiliary dysfunction.

The pharmacokinetics of mezlocillin were investigated in 26 patients with alcoholic liver disease. Serum concentrations of mezlocillin were measured following intravenous administration of 3 g doses over 30 min. The mean peak serum concentration (+/- standard deviation) of mezlocillin at the end of infusion was 138.8 +/- 55.7 mg/l and the mean terminal half-life (T 1/2 beta) was 2.10 +/- 0.9 h. The 24 h urinary recovery of mezlocillin was 35.4 +/- 12.4% of the administered dose. Serum clearance was found to be inversely correlated with alkaline phosphatase and with total bilirubin. The T 1/2 beta was related to the following clinical measurements: age, SGOT and prothrombin time. This relationship suggests it may be prudent to adjust the dosage and the dosage interval of mezlocillin in patients with hepatobiliary dysfunction.

Adult↗

Varying nuclear staining intensity of hepatitis B virus DNA in human hepatocellular carcinoma.

An in situ hybridization technique with biotinylated hepatitis B virus (HBV)-DNA probes was used to localize HBV-related DNA sequences in cells of human hepatocellular carcinoma (HCC). Formalin fixed, paraffin-embedded liver biopsies of 11 patients with HCC studied; nuclear HBV-DNA hybridization was observed in 7 of the patients. Sensitivity and specificity of the method were determined by examining appropriate controls. The number of cells exhibiting nuclear fluorescence and intensity of fluorescence varied from tumor to tumor. In two instances liver tissue adjacent to HCC exhibited nuclear staining. HBV-DNA nuclear staining did not correlate with tumor localization of HBsAg or HBcAg, nor with type or with differentiation of the tumor. The use of biotinylated HBV-DNA probes offers a powerful and reproducible technique to localize HBV-related DNA sequences even in formalin-fixed, paraffin-embedded tumor tissue, and also to compare the presence of HBV-DNA with that of viral antigens stained in parallel sections. The frequent localization of HBV-DNA in nuclei of HCC cells fortifies the important epidemiologic association between infection and HCC. The random cellular localization of HBV-DNA sequences in HCC suggests that HBV-DNA may be incorporated, or perhaps replicated, unequally in tumor cells.

Adult↗

Mycobacterial meningitis. Retrospective analysis from 1970 to 1983.

The clinical presentation and course of tuberculous meningitis in 21 patients treated between 1970 and 1983 are analyzed. Tuberculous meningitis may present as acute, subacute, or chronic meningitis. Although characteristic cerebrospinal fluid findings of lymphocytic pleocytosis, low glucose level, and elevated protein level occur in the majority of cases, there are many atypical presentations. The protein level, glucose level, and white blood cell count may be normal, and there may be a predominance of polymorphonuclear cells rather than lymphocytes in the cerebrospinal fluid. Poor prognostic factors in this series were age greater than 65, underlying diseases, and stage 3 presentation. Incorrect or inadequate therapy had a disastrous outcome. Nontuberculous mycobacteria rarely are involved in central nervous system disease. Tuberculous meningitis must be considered in the differential diagnosis of any patient with fever and change in sensorium. A deteriorating mental status and falling cerebrospinal fluid glucose level in the presence of negative findings on bacterial culture and india ink preparation should lead to strong consideration for empiric initiation of anti-tuberculous therapy.

Adult↗

Comparative in vitro activity of coumermycin against methicillin-resistant Staphylococcus aureus.

Coumermycin was the most active agent in vitro against methicillin-resistant Staphylococcus aureus when compared with fusidic acid, imipenem, rifampin, trimethoprim-sulfamethoxazole, and vancomycin. The MICs of coumermycin ranged from 0.002 to greater than 4 micrograms/ml and from 0.5 to greater than 4 micrograms/ml for inocula of 10(4) and 10(6) CFU/ml, respectively. The combination of coumermycin with either cephalothin or ciprofloxacin showed some synergy; antagonism was found with gentamicin.

Aminocoumarins↗

Properties of hepatitis B e antigen synthesized by rat cells transfected with circular viral DNA.

Transfection of Buffalo rat liver cells with closed circular hepatitis B virus DNA resulted in the synthesis of both hepatitis B e and surface antigens. A 14000 mol. wt. peptide bearing hepatitis B e antigenic determinants was isolated from cell culture fluids. Native hepatitis B e antigen was present in multimeric forms in the cell culture fluids and was associated with protein phosphokinase activity. The multimeric forms of hepatitis B e antigen may serve both structural and enzymic functions for the hepatitis B virion with its small genome.

Animals↗

The hepatitis B virus as a molecular model for chronic infection: synthesis of hepatitis B surface and e antigens in mouse L cells transfected with closed circular viral DNA.

Linear hepatitis B virus (HBV) DNA, excised from a recombinant plasmid with EcoR1, was purified by preparative electrophoresis on agarose gels and incubated with phage T4 ligase to form either monomeric or dimeric closed circles. Thymidine kinase deficient mouse L cells were cotransfected with thymidine kinase (tk) and circular HBV DNAs and grown in hypoxanthine medium. Colonies of tk-transformed cells, selected after 3-4 weeks of incubation and subcultured in HAT medium, synthesized either hepatitis B surface antigen (HBsAg) alone or HBsAg in combination with hepatitis B e antigen (HBeAg). The various cell colonies differed in plating efficiency, growth rates, cellular appearance, and extent of viral antigen synthesis. Southern hybridization analysis showed the presence of HBV-related sequences in high molecular weight DNA prepared from cells expressing viral antigens. Digestion of cellular DNAs with restriction endonucleases indicated integration of the entire viral genome.

Animals↗

Pharmacokinetics of amdinocillin in healthy adults.

The pharmacokinetics of amdinocillin (mecillinam) were determined in 10 healthy volunteers. Single doses of 10 and 15 mg/kg of body weight were administered intravenously and intramuscularly in a crossover study. Plasma concentrations of amdinocillin were determined by microbiological assay. Mean peak plasma concentrations were 49 and 87 micrograms/ml after intravenous doses of 10 and 15 mg/kg, respectively. The terminal half-life value of 0.89 h was similar for both doses. After intramuscular injections, the mean concentration of drug in plasma was 26.2 micrograms/ml for the 10-mg/kg dose and 29.6 micrograms/ml for the 15-mg/kg dose, with terminal half-lives of 0.96 and 0.86 h, respectively. The mean apparent volumes of distribution at steady state were 18 and 16 liters/100 kg for the intravenous doses of 10 and 15 mg/kg, respectively. Drug concentrations in plasma at 4 h were above the minimal inhibitory concentrations for gram-negative organisms categorized as susceptible to this drug.

Adult↗

Crossover study of the pharmacokinetics of ceftriaxone administered intravenously or intramuscularly to healthy volunteers.

The pharmacokinetics of ceftriaxone were investigated in six healthy adults. One-gram doses were administered either intramuscularly or intravenously in a crossover design study. Mean peak ceftriaxone concentrations in plasma of 79.2 and 123.2 micrograms/ml were achieved with intramuscular injection and intravenous infusion, respectively, with plasma half-lives of 5.4 and 5.8 h. The urinary recovery of ceftriaxone in the first 24 h was 37% after intravenous infusion and 25% after intramuscular injection.

Adult↗

Nuclear scanning in necrotizing progressive "malignant" external otitis.

The usefulness of radionuclear scanning in the treatment of 18 patients with necrotizing progressive "malignant" external otitis is discussed. A Tc 99-m bone scan, a valuable test since results are positive in early cases of osteomyelitis of the temporal bone and base of skull, showed increased uptake in all 18 patients. In 6 patients, Ga-67 citrate scans were obtained at the start of therapy and at 5-6 week intervals thereafter. The serial gallium scans were useful in evaluating the effectiveness of therapy since the uptake decrease with control of infection.

Aged↗

Expression of hepatitis B viral antigens in animal cells transfected with viral DNA.

Mouse L cells deficient in thymidine kinase (tk-) were transfected with either monomeric or dimeric circular HBV DNA and co-transformed with tk+ DNA derived from herpes simplex virus. Thymidine kinase transformed cell colonies were harvested and maintained as separate cell lines. Either HBsAg, HBeAg, or HBsAg and HBeAg were detected in culture fluids from the various cell colonies. Immunofluorescent stains of cells from colonies synthesizing HBsAg and/or HBeAg showed that these antigens were present in cytoplasm. The monomeric form of circular HBV DNA was more efficient in producing cells synthesizing large amounts of HBsAg and HBeAg than the dimeric form. The patterns of integration of HBV DNA differed between cells synthesizing HBsAg and those synthesizing HBsAg and HBeAg. This in vitro system for the expression of HBV DNA now allows a detailed study of the synthesis and function of HBeAg and the interaction of HBV DNA and the retroviral DNA present in mouse L cells. Furthermore, it may be possible to develop a hepatitis B virus vaccine based on HBeAg as the viral antigen.

Animals↗