PubMed HealthSearch

Biomedical subjects

S Z Hirschman

Publications and source records attributed to S Z Hirschman.

At least 19 recordsLinked to original sources

Renal aspergilloma: an unusual cause of infection in a patient with the acquired immunodeficiency syndrome.

The case of a 36-year-old man with the acquired immunodeficiency syndrome (AIDS) and a renal aspergilloma is reported. Aspergillus infections are uncommon in patients with AIDS. Isolated renal aspergillomas have rarely been reported in the non-AIDS population (14 cases) and have never been reported in a patient with AIDS. The patient we describe was clinically symptomatic and initially treated medically, but he did not respond to intravenous amphotericin and oral itraconazole. He eventually required nephrectomy; however, there was local recurrence of the aspergilloma postoperatively. We comment on some issues in the spectrum of Aspergillus infections in AIDS and review the literature on the manifestations and treatment of renal aspergillomas.

Acquired Immunodeficiency Syndrome

Clostridium difficile diarrhea induced by cancer chemotherapy.

Four patients had diarrhea due to Clostridium difficile after receiving chemotherapy for cancer. None of the patients had received antibiotics for at least 4 weeks before the onset of diarrhea. At the time of admission of any of these four patients no outbreak of diarrhea was noted on the ward. Each patient was admitted with the acute onset of diarrhea after receiving chemotherapy, at different times of the year. Diarrhea was clinically important and was associated with dehydration, toxemia, and blood in the stool in all cases. Diagnosis of C difficile was confirmed by endoscopic examination, positive biopsy specimen, and positive test for toxin in the stool. All patients recovered after undergoing specific treatment. Drugs not believed to carry serious risk to the bowel mucosa may facilitate proliferation of C difficile. Patients with severe diarrhea after receiving chemotherapy, particularly those with blood in the stool, should be promptly tested for C difficile even in the absence of a history of antibiotic administration. Early and specific treatment can prevent additional morbidity and reduce cost of care.

Acute Disease

The hepatitis B virus and its DNA polymerase: the prototype three-D virus.

The hepatitis B virus (HBV), the causal agent of serum hepatitis, has a diameter of 42 nm and is comprised of an outer surface coat and a 27 nm core. A unique DNA-dependent DNA polymerase is associated with the core of the virus. The core also houses a circular DNA that contains both double-stranded and single-stranded regions. In the endogenous reaction, the DNA polymerase repairs the single-stranded gaps of the viral DNA. The surface protein of the virus, called hepatitis B surface antigen, contains both lipid and carbohydrate, and is often present in particulate form in the blood of infected patients. In Asia and Africa HBV infection is associated with subsequent development of primary hepatocellular carcinoma. Although most patients recover completely from acute illness, the hepatitis B virus may cause chronic infection. Recently, a virus similar to human HBV was discovered in woodchucks. HBV has not yet been propagated in a cell culture system and the mode of replication of this unusual virus in hepatocytes is still moot. Although reliable therapy has not yet been provided, the problem of this world-wide infection has led to many interesting approaches to both vaccine production and anti-viral chemotherapy.

Animals

Rhinocerebral mucormycosis: premortem diagnosis and therapy.

The diagnosis of rhinocerebral mucormycosis is most often made at autopsy. We report a series of nine patients in whom the diagnosis was established premortem. Six of the patients had underlying diabetes mellitus and three had acute leukemia. Facial or ocular pain was the complaint found in all patients, and frequently was the initial symptom. The diagnosis was established by examination and culture of infected tissue obtained by biopsy. In seven patients, identification of hyphal elements in smears of biopsy material allowed the immediate institution of amphotericin B therapy. Four of the seven patients treated with amphotericin B survived. All surviving patients had underlying diabetes mellitus and had undergone surgical debridement. Early diagnosis leading to immediate institution of appropriate therapy is most important for survival of patients with mucormycosis.

Acute Disease

Pharmacologic studies with cefaclor, a new oral cephalosporin.

Cefaclor, a new oral cephalosporin, was administered to 18 normal human volunteers in either single or multiple doses of 250 and 500 mg. Mean serum concentrations of 6.09 and 12.8 microgram/ml were achieved 1 hour after single oral doses of 250 and 500 mg, respectively. The serum concentrations declined rapidly and no drug was detected at 4 hours. Very high concentrations of cefaclor were found in urine during the first 8 hours after ingestion of the drug. Forty-three per cent of the total dose was excreted in urine during the first 8 hours. There was no accumulation of drug in serum during the multiple-dose studies.

Administration, Oral

Differential activation of hepatitis B DNA polymerase by detergent and salt.

Three patterns of activity were evident when the differential activation of the DNA polymerase associated with serum Dane particles by nonionic detergent and salt was investigated. The patterns were obtained by plotting the increase in enzyme activity mediated by the detergent Nonidet P-40 (NP-40) in increasing concentrations of KCl compared to the activity observed in the absence of detergent. The pattern of differential activity of hepatitis B (HB) DNA polymerase in detergent and salt was altered by subjecting the HBAg preparations to shearing forces. Hepatitis B DNA polymerase activity was stable even in NP-40 concentrations as high as 10%. In addition to hepatitis B DNA polymerase, DNA polymerase activated by calf thymus DNA was found in pellets containing Dane particles. The latter DNA polymerase activity was also activated by NP-40 and was not decreased by DNAse; this DNA polymerase coprecipitated with hepatitis B antigen (HBAg) upon addition of anti-HBs. However, the DNA polymerase activated by calf thymus DNA was inhibited by 0.4 M KCl. Electron microscopic observations of serum Dane particles in 0.4 M KCl showed no alterations of morphology of these particles when compared to particles in low-salt buffer. The data indicated that KCl activated HB DNA polymerase by a different mechanism from that of shear or NP-40, which removed the surface antigen coat from the Dane particles.

DNA-Directed DNA Polymerase

Antibacterial activity of cefamandole in vitro.

Cefamandole, a new cephalosporin derivative, was found to have a broad spectrum of antimicrobial activity against a cross-section of both gram-positive and gram-negative bacteria isolated clinically. Gram-positive cocci, except for Streptococcus faecalis, were extremely susceptible to cefamandole; penicillin G-resistant Staphylococcus aureus also was highly susceptible. Minimal bactericidal concentrations for gram-positive cocci approximated the minimal inhibitory concentrations. Strains of Haemophilus influenzae were very susceptible to the drug. Most strains of Escherichia coli, Klebsiella species, and Proteus species were inhibited by low concentrations of cefamandole, Salmonella typhi, including ampicillin- and chloramphenicol-resistant strains, was inhibited by low concentrations of cefamandole. Susceptible bacteria became increasingly resistant as the inoculum size was increased. Strains of Pseudomonas were resistant to cefamandole.

Bacteria

Antimicrobial activity in vitro of netilmicin and comparison with sisomicin, gentamicin, and tobramycin.

The antimicrobial activity of netilmicin, a new semisynthetic aminoglycosidic aminocyclitol, was determined against 123 recent gram-negative clinical isolates susceptible to gentamicin and 60 isolates resistant to either sisomicin, gentamicin, or tobramycin. The minimal inhibitory concentrations and minimal bactericidal concentrations of netilmicin, sisomicin, gentamicin, and tobramycin against Pseudomonas, Escherichia coli, Klebsiella, Enterobacter, Proteus mirabilis, and indole-positive Proteus were, in general, quite similar. Gentamicin was the most active against Serratia. A total of 54, 67, and 88% of gentamicin-resistant Pseudomonas, Serratia, and Klebsiella, respectively, were susceptible to netilmicin. Strains of indole-positive Proteus, Acinetobacter, Providencia, and E. coli resistant to gentamicin were likely to be resistant also to netilmicin.

Aminoglycosides

Pharmacokinetics of cefamandole in patients with renal failure.

The pharmacokinetics of cefamandole were studied in four patients with stable renal failure, two patients undergoing peritoneal dialysis, and four patients undergoing hemodialysis. Peak concentrations of cefamandole in serum were achieved 1 to 2 h after intramuscular injection in the patients with stable renal impairment, and the concentrations declined slowly, with half-life values of 12.3 to 18 h. Cefamandole was removed only very slowly by peritoneal dialysis. Hemodialysis was more efficient in removing cefamandole, with serum half-life values ranging from 3.8 to 7.9 h. The mean apparent volume of distribution of cefamandole in these 10 patients was 21.92 liters, or 31% of the body weight.

Cephalosporins

Antimicrobial activity of cefamandole against Salmonella typhi.

A patient with Salmonella typhi bacteremia was sucessfully treated with cefamandole, a new cephalosporin derivative. Infection has not recurred during 6 months of follow-up observation. Minimum inhibitory concentrations and minimum bactericidal concentrations of cefamandole, cephalothin, ampicillin, and chloramphenicol were compared against 26 strains of S. typhi. All the strains were susceptible to cefamandole in vitro. Seven of the strains were resistant to chloramphenicol, and another seven were resistant to both chloramphenicol and ampicillin. Cefamandole appears to warrant further clinical trial for the treatment of typhoid fever.

Adult

Pharmacokinetic study of netilmicin.

Netilmicin at a dose of 2 mg/kg was infused intravenously into 10 healthy volunteers. A peak serum concentration of 16.56 mug/ml was obtained at the end of the infusion. Thirty-nine percent of the infused dose was excreted in the urine during the first 8 h after infusion. The pharmacokinetic parameters of netilmicin were derived by analyzing the elimination data according to a two-compartment model.

Adult

Hepatic dysfunction in acute measles infection of adults.

Hepatitis has rarely been recognized as a complication of acute measles infection. Two adult patients are reported in whom abnormal liver function was a prominent clinical feature during acute measles infection. Hepatic function returned to normal in both patients as the measles infection resolved. Hepatitis may be a salient clinical manifestation of acute measles infection of adults.

Acute Disease

Pharmacokinetic parameters of sisomicin.

Sisomicin in doses of 1 mg/kg was administered intramuscularly to 10 healthy volunteers, and 1 week later the same volunteers received sisomicin at the same dose intravenously. A peak serum concentration of sisomicin of 3.08 mug/ml was obtained 1 h after intramuscular injection, and a peak serum concentration of 7.12 mug/ml was achieved 30 min after a 30-min intravenous infusion. The sisomicin elimination data were analyzed according to a two-compartment model. Pharmacokinetic parameters derived from the intramuscular and intravenous studies were quite similar.

Adult

Comparison of activity of sisomicin and gentamicin in mouse protection tests with gram-negative bacilli.

The efficacy of sisomicin and gentamicin was compared in mouse protection studies against strains of Escherichia coli, Klebsiella sp., Enterobacter aerogenes, Serratia marcescens, Proteus mirabilis, and Pseudomonas aeruginosa. There was no significant difference in mortality of the mice in any of the protocol groups when five different dosages of sisomicin and gentamicin given by three separate schedules were compared for each bacterial inoculum in each antibiotic protocol. The mean protective dose values of sisomicin were at least one-half those of gentamicin for each protocol against Pseudomonas aeruginosa.

Animals

Pharmacological studies with cefamandole in human volunteers.

Serum and urine concentrations were measured after administration of 0.5-and 1-g doses of cefamandole intramuscularly and intravenously to healthy volunteers. Intramuscular doses of 0.5 and 1 g yielded serum concentrations at 1 h of 14.7 and 35.6 mug/ml, respectively. Significant antibacterial concentrations persisted through h 8. Intravenous doses of 0.5 and 1 g resulted in respective peak serum levels of 21 mug/ml at 45 min and 103 mug/ml at 15 min; these serum levels rapidly declined. Very high urine concentrations were achieved during the first 8 h after injection.

Adult

Integrator enzyme hypothesis for replication of hepatitis-B virus.

A hypothetical model for the replication of hepatitis-B virus is presented. It is suggested that the D.N.A. polymerase associated with Dane particles facilitates integration of viral D.N.A. into the genome of the liver cell. The viral D.N.A. is then replicated with the host genome. The hypothesis accounts for certain curious experimental and clinical observations and makes several predictions which are amenable to laboratory investigation.

Cell Membrane