Search PubMed⌕ Search

Biomedical subjects

D T Durack

Publications and source records attributed to D T Durack.

At least 91 records · Page 5Linked to original sources
PubMed1983

Cunninghamella: a newly recognized cause of rhinocerebral mucormycosis.

Cunninghamella, a zygomycete in the order Mucorales, is an extremely rare cause of human infection. Of the five reported cases of human disease caused by this fungus, none involved rhinocerebral infection. Here, the authors document what appears to be the first case of rhinocerebral mucormycosis caused by Cunninghamella bertholletiae in an elderly man who had diabetes with sideroblastic anemia and hemochromatosis. The disease was rapidly fatal. The mycology and classification of this organism are presented, and the previous case reports in the literature are reviewed.

Aged↗
PubMed1983

Pharmacokinetics of N-formimidoyl thienamycin and influence of a renal dipeptidase inhibitor in experimental meningitis.

We studied the pharmacokinetics of N-formimidoyl thienamycin with and without a renal dipeptidase inhibitor in plasma and cerebrospinal fluid (CSF) of rabbits. Thienamycin reached a maximal concentration of 0.6 +/- 0.06 mg/l in the CSF of normal rabbits. When the meninges were inflamed, the mean CSF concentration of N-formimidoyl thienamycin was 3.2 +/- 1.5 mg/l, five times higher than in normal rabbits. This concentration would kill most bacteria that cause meningitis. The renal dipeptidase inhibitor alone had no detectable antibacterial activity. When administered with N-formimidoyl thienamycin, it exerted only minor effects on the pharmacokinetics in either plasma or CSF of normal or infected rabbits.

Animals↗
PubMed1983

Cryptococcemia.

Previous reports have emphasized that cryptococcemia is almost uniformly fatal. To define the clinical course and prognostic and therapeutic implications of cryptococcemia, we studied 15 patients treated at this medical center over the past 7 years. Cryptococcemia was strongly associated with corticosteroid therapy, especially when the dosage had recently been increased. Meningitis was common (but not invariably present) in these patients, characteristically with a large burden of organisms in the cerebrospinal fluid. Cryptococcemia developed during hospitalization in one-third of our patients; this high rate of nosocomial infection emphasizes that C. neoformans infection should be considered in febrile, immunocompromised patients even when the initial work-up is negative. Most of these patients were treated with amphotericin B plus 5-fluorocytosine. Although the one-year survival rate of 4/15 (29%) was dismal, no patient died from uncontrolled cryptococcal infection. Other infections, which developed before, during or after cryptococcemia was diagnosed, were the major immediate cause of morbidity and mortality. The progress of underlying diseases and the outcome of concomitant infections in these patients were more important determinants of survival than was cryptococcemia itself.

Adrenal Cortex Hormones↗
PubMed1983

Therapeutic significance of penicillin tolerance in experimental streptococcal endocarditis.

Tolerance to penicillin exists among the viridans group of streptococci, but its therapeutic significance is unknown. We studied the effect of penicillin alone and in combination with streptomycin, in vivo and in vitro, on three strains of dextran-producing Streptococcus sanguis serotype II which possess widely various degrees of penicillin tolerance. In rabbits with experimental endocarditis, treatment with procaine penicillin (250 mg/kg intramuscularly twice daily for 5 days) decreased the number of viable organisms in valvular vegetations from 8.82 log10 +/- 0.98 CFU/g in untreated controls to 5.31 +/- 1.19 for a highly tolerant strain, 4.22 +/- 1.05 for a less tolerant strain, and 1.79 +/- 1.72 for a nontolerant strain (P less than or equal to 0.01 for comparison between any of the four groups). None of 36 rabbits infected with tolerant strains were cured by 5 days of treatment with penicillin, but 10 of 23 animals infected with the nontolerant strain were cured (P = 0.00002). When streptomycin was given in combination with penicillin, rabbits infected with the nontolerant strain were cured within 3 days, and rabbits infected with the tolerant strain were cured within 5 days. These findings indicate that tolerance can exert a critical influence on the response of S. sanguis to penicillin therapy in vivo and that the combination of penicillin plus streptomycin exerts a synergistic effect against tolerant as well as nontolerant organisms.

Animals↗
PubMed1982

Multicenter collaborative trial of intravenous acyclovir for treatment of mucocutaneous herpes simplex virus infection in the immunocompromised host.

Intravenous acyclovir was evaluated in the treatment of 97 immunocompromised patients with mucocutaneous herpes simplex virus infection in a randomized, double-blind, placebo-controlled trial. Acyclovir recipients had significantly shorter periods of virus shedding (p less than 0.0002) and lesion pain (p less than 0.01), and more rapid lesion scabbing (p less than 0.004) and lesion healing (p less than 0.04). The most common adverse reaction was a low incidence of peripheral vein irritation; no serious toxicity could be definitely attributed to acyclovir treatment even in these seriously ill patients. Intravenous acyclovir offers both safe and effective treatment for mucocutaneous herpes simplex virus infection in the immunocompromised host.

Acyclovir↗
PubMed1982

Treatment of experimental cryptococcal meningitis with amphotericin B, 5-fluorocytosine, and ketoconazole.

Ketoconazole, amphotericin B, 5-fluorocytosine, and combinations of these drugs were compared as therapy for chronic cryptococcal meningitis in steroid-treated rabbits. Two hours after treatment of rabbits with meningitis with single drugs the mean cerebrospinal fluid concentration of 5-fluorocytosine was 4.4 microgram/ml, that of amphotericin B was less than 0.3 microgram/ml, and that of ketoconazole ranged from less than 0.2 to 0.8 microgram/ml. Serial quantitative cultures indicated that amphotericin B was the best single-drug regimen. Ketoconazole provided little or no additive effect when used in combination with fluorocytosine or therapeutic doses of amphotericin for two weeks. However, the combination of ketoconazole plus amphotericin B was at least as effective as amphotericin B plus 5-fluorocytosine over a two-week treatment regimen. The addition of ketoconazole to subtherapeutic dose of amphotericin B significantly increased the killing of cryptococci in cerebrospinal fluid.

Amphotericin B↗
PubMed1982

Lack of in vivo and in vitro bactericidal activity of N-formimidoyl thienamycin against enterococci.

The minimal bactericidal concentrations of N-formimidoyl thienamycin (N-f-thienamycin) against 21 strains of enterococci isolated from patients with infective endocarditis were determined by macro- and microdilution methods. By a macrodilution technique with the minimal bactericidal concentration defined as greater than or equal to 99.9% killing of an initial inoculum, all 21 strains of enterococci were found to have minimal bactericidal concentration/minimal inhibitory concentration ratios of greater than or equal to 32. The mean minimal inhibitory concentration was 1.5 micrograms/ml (range, 0.5 to 4 micrograms/ml), and the minimal bactericidal concentration was greater than or equal to 128 micrograms/ml. The disparity between the results of our study and those published elsewhere, which reported that N-f-thienamycin is bactericidal in vitro against enterococci, may represent the relative insensitivity of the microdilution method in determining greater than or equal to 99.9% killing. The lack of in vitro bactericidal activity of N-f-thienamycin against enterococci was confirmed in vivo in the rabbit model of experimental endocarditis. N-f-Thienamycin was no more effective than penicillin alone in the treatment of experimental enterococcal endocarditis and was less effective than the combination of penicillin and gentamicin. The results indicate that N-f-thienamycin should not be used alone in the treatment of enterococcal endocarditis.

Animals↗
PubMed1982

The neuroleptic malignant syndrome.

The neuroleptic malignant syndrome (NMS) comprises hyperpyrexia, altered consciousness, muscular rigidity, and autonomic dysfunction. It is a rare idiosyncratic reaction to major tranquilizers, including the phenothiazines, butyrophenones, and thioxanthenes; haloperidol and fluphenazine enanthate or fluphenazine decanoate are the drugs most commonly incriminated. The syndrome occurs after therapeutic rather than toxic doses of neuroleptic drugs and is unrelated to the duration of therapy. The NMS is attributed to a disturbance of dopaminergic systems within the basal ganglia and hypothalamus. Associated laboratory abnormalities include leukocytosis, with elevated serum creatine phosphokinase (CPK) and liver enzyme concentrations. The NMS, which is known to some psychiatrists and neurologists but to few internists, probably is underdiagnosed; therefore, its true incidence is unknown. The NMS should be included in the differential diagnosis of any febrile patient with a history of neuroleptic treatment. Because the mortality of NMS is about 20%, early diagnosis and withdrawal of the neuroleptic drug therapy is crucial. Supportive treatment in a medical intensive care unit may be required.

Antipsychotic Agents↗
PubMed1982

Leukocyte subpopulations in cerebrospinal fluid of normal rabbits.

Cerebrospinal fluid leukocytes from 48 apparently healthy New Zealand white rabbits were examined to define the number and types of cells present. The cerebrospinal fluid contained 0 to 7 leukocytes/mm3 (median 3/mm3). This small pool of mononuclear cells was comprised of 40 to 79% lymphocytes (median 67%) and 21 to 60% monocytes (median 33%). T lymphocytes were the predominant cell type, outnumbering B cells by approximately 100 to 1. In contrast to cerebrospinal fluid, normal rabbit blood contained nearly equal proportions of B and T cells (median 39% and 46% of lymphocytes, respectively). Three cerebrospinal fluid samples from apparently healthy rabbits had greater than 20 leukocytes/mm3.

Animals↗
PubMed1981

Purification of human eosinophil-derived neurotoxin.

Human and animal eosinophils contain a powerful neurotoxin that causes selective neuronal and axonal damage to white matter of cerebellum and spinal cord of experimental animals when injected intrathecally. This reaction is termed the "Gordon phenomenon." We purified the eosinophil-derived neurotoxin from eosinophil-rich leukocyte suspensions or eosinophil granules from four patients with various hypereosinophilic syndromes. A single protein with an average molecular weight of 18,400 was isolated by sequential chromatography on Sephadex G-50 columns and analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis of column fractions. The purified eosinophil-derived neurotoxin from the cells of these patients retained the potent neurotoxic activity of the crude eosinophil or eosinophil granule extracts in experimental animals. These animals developed the syndrome of stiffness and ataxia progressing to severe paralysis characteristic of the Gordon phenomenon. Histologic examination of the brains of animals injected with purified eosinophil-derived neurotoxin confirmed the characteristic widespread loss of Purkinje cells and severe spongiform vacuolation in the white matter of cerebellum, brain stem, and spinal cord. We have established the location of eosinophil-derived neurotoxin in the eosinophil granule and have shown that it is distinct from several other eosinophil proteins, the granule major basic protein, and the Charcot-Leyden crystal protein (lysophospholipase).

Animals↗
PubMed1981

Efficacy of ampicillin plus a beta-lactamase inhibitor (CP-45,899) in experimental endocarditis due to Staphylococcus aureus.

The efficacy of combined therapy with ampicillin and a beta-lactamase inhibitor, CP-45,899, for experimental endocarditis due to Staphylococcus aureus was evaluated. Three strains of beta-lactamase-producing S. aureus were used, and intramuscular doses of antibiotics were selected to produce serum levels in rabbits similar to those expected in humans. Sera from animals treated with ampicillin plus CP-45,899, but not from those treated with nafcillin plus gentamicin, had bactericidal activity against two nafcillin-resistant strains of S. aureus at 1 hr. The combination of ampicillin plus CP-45,899 was as effective as nafcillin in treatment of endocarditis due to one nafcillin-sensitive strain and was superior to nafcillin against two nafcillin-resistant strains (P less than 0.001). In a short-term treatment experiment using the nafcillin-sensitive strain, ampicillin plus CP-45,899 sterilized vegetations as rapidly as nafcillin plus gentamicin. Thus, ampicillin plus a beta-lactamase inhibitor may be effective treatment for bacteremic infections due to S. aureus, even when the strain is nafcillin-resistant.

Ampicillin↗