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Biomedical subjects

H Donabedian

Publications and source records attributed to H Donabedian.

At least 19 recordsLinked to original sources
PubMed2003

Quorum sensing and its relevance to infectious diseases.

Quorum sensing allows bacteria to detect the density of their own species and alter their metabolism to take advantage of this density. Quorum sensing is used by a wide variety of bacteria including human pathogens. Quorum sensing genes are important for the pathogenic potential of Pseudomonas aeruginosa and Staphylococcus aureus, as well as other invasive bacteria. An understanding of quorum sensing may lead to new therapeutic strategies.

Bacterial Infections↗
PubMed1998

Clot formation by group A streptococci.

Group A streptococci of several different M serotypes can cause human plasma to clot in nutrient-poor media. Addition of glucose to the medium prevents clot formation. Once formed, clots are stable for several days and can be lysed on addition of exogenous streptokinase or urokinase. Clot lysis can also be achieved by addition of glucose to a clot containing wild-type group A streptococci but not clots containing an isogenic mutant in which the ska gene was inactivated.

Blood Coagulation↗
PubMed1995

Prevention of subsequent urinary tract infections in women by the use of anti-adherence antimicrobial agents: a double-blind comparison of enoxacin with co-trimoxazole.

A prospective, double-blinded crossover study was carried out to test whether a brief course of antibiotic therapy could eliminate bacteria adherent to uroepithelial cells and thus prolong the interval between urinary tract infections (UTIs). Thirty-two women with frequent Gram-negative urinary tract infections were randomized to receive either co-trimoxazole or enoxacin twice a day for 10 days to treat their UTI. Their urines were collected for 30 days after the onset of their UTI and quantitatively analyzed for bacteria, antibiotics, and bacteria adherent to uroepithelial cells (UECs). A subsequent infection caused the patient to be treated with the alternative antibiotic. A third infection terminated the study. Both regimens were indistinguishable in the rate of elimination of bacteria and in their inhibition of bacterial adherence to UECs for up to five days after stopping treatment. The interval between infections was inversely correlated with the number of adherent bacteria per UEC 30 days after the onset of the first UTI. Both regimens were equally effective in preventing subsequent UTI and the effect of 10 days therapy on the inhibition of bacterial adherence to UEC's did not extend beyond five days after stopping treatment.

Bacterial Adhesion↗
PubMed1994

Disseminated cutaneous and meningeal sporotrichosis in an AIDS patient.

We report the first proven case of Sporothrix meningoencephalitis in an AIDS patient. The patient had dramatic, wide-spread ulcerative and infiltrative disease with progressive meningoencephalitis in spite of amphotericin and itraconazole therapy. Sporothrix was cultured from premortem cerebrospinal fluid and seen in the meninges and in brain vessels at autopsy.

AIDS-Related Opportunistic Infections↗
PubMed1994

Inappropriate use of oxygen: loss of a valuable healthcare resource.

Oxygen (O2) use is well established in hospitalized patients with hypoxemia. However, its value in patients without hypoxemia is not well documented. The authors conducted a retrospective study to evaluate the excess use of O2 and the resulting loss of resources. They established criteria for O2 use by faculty consensus. Ninety-six patients (102 admissions) receiving O2 between August and October 1991 were identified. Principal discharge diagnoses included cardiac diseases (37%), pulmonary diseases (26.5%), and miscellaneous (36.5%). Cumulative oxygen use was 9,742 hours. Appropriate O2 amounted to 3,272 hours (34%), and inappropriate O2 use was 6,470 hours (66%). The billing for O2 use was $38,468, of which $25,880 constituted inappropriate use. In 1991, there were 7,743 admissions, with oxygen charges of $1.06 million. Extrapolation of the data shows billing for inappropriate oxygen was $697,000. The authors conclude that inappropriate use of oxygen results in significant loss of resources. Educational efforts to decrease this loss and evaluate its impact on patient outcome is needed.

Adolescent↗
PubMed1994

Enhancing faculty participation and interest in quality improvement in academic centers.

Continuous quality improvement (CQI) is necessary in maintaining and improving the quality of medical care delivered. However, quality assurance (QA) in the past was performed superficially to meet requirements of the Joint Commission on Accreditation of Health Care Organizations and other regulatory agencies. Academic faculty participation in QA activity was also limited. Faculty often assume that meaningful quality process demands excessive efforts and time unrewarded with career advancement, promotion, or monetary compensation. In addition, unstructured QA leads to duplication of data and loss of educational opportunity. We reorganized the QA process in internal medicine using the CQI concept to: (a) improve academic faculty participation, (b) incorporate educational concepts, (c) stimulate interest in outcome research and CQI, and (d) integrate cost containment. A reorganized CQI format has stimulated enthusiastic participation of faculty and residents, and has generated conferences and grand rounds pertinent to medical care, outcome research, and cost containment. We conclude that academic faculty should play leadership roles in the CQI process and include teaching models. Improved and increased academic faculty participation could be realized, when educational values, research activities, and cost analysis are incorporated into the CQI process.

Academic Medical Centers↗
PubMed1992

Norwegian scabies in a patient with AIDS.

Depression of cellular and humoral immunity can result in an overwhelming infection with the mite Sarcoptes scabiei. Infections in which the densities of mites are very high are known as Norwegian, or crusted, scabies. Cases of Norwegian scabies have been reported sporadically in patients with AIDS, but the appearance of the rash on these patients can be very misleading because of the diffuse papular or psoriasiform presentation. Such patients may readily transmit scabies to others. Since the disease is curable, it should be considered in the differential diagnosis of any persistent papular or psoriasiform rash on a patient with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Novel abnormality in subpopulations of circulating lymphocytes. T gamma delta and CD2-, 3+, 4-, 8- lymphocytes in histoplasmosis-associated immunodeficiency.

A patient, who had developed anergy after disseminated histoplasmosis and who had gone on to develop a cardiomyopathy, demonstrated an unusually large proportion of T lymphocytes bearing the gamma and delta chains of the T cell receptor (TCR-gamma/delta). These gamma delta + cells composed over half of the circulating lymphocytes and were clearly divisible into two subgroups based on the level of expression of the gamma and delta chains and their ability to bind one of the monoclonal antibodies reactive with the TCR-delta chain. In addition, the patient showed an abnormally high proportion of circulating lymphocytes having the CD2-, 3+, 4-, 8- phenotype which has been only recently described. The pattern of lymphocyte subpopulations changed over the 9 years that the patient was followed since his original infection and appears to characterize a novel abnormality.

Antibodies, Monoclonal↗
PubMed1989

Long-term suppression of Salmonella aortitis with an oral antibiotic.

An aneurysm of the aortic arch infected with Salmonella choleraesuis is presumed to be inevitably fatal unless the patient receives corrective surgery and antibiotic therapy. I report such a case in a patient who refused surgery and who has been maintained free of infectious symptoms for over 26 months using trimethoprim-sulfamethoxazole administered orally.

Administration, Oral↗
PubMed1988

Rupture of a pulmonary artery mycotic aneurysm associated with candidal endocarditis.

Candidal endocarditis can develop if candidemia occurs during Swan-Ganz catheterization. Candida endocarditis may persist for many months and is fatal unless the infected valve is resected. Herein is reported the first case of rupture of a mycotic pulmonary artery aneurysm caused by chronic candidal endocarditis. The endocarditis followed Swan-Ganz catheterization and aneurysm progressed despite appropriate medical and surgical therapy.

Amphotericin B↗
PubMed1987

Inhibition of neutrophil shape change by an inhibitor of chemotaxis.

Human mononuclear cells exposed to staphylococcal peptidoglycan in serum-free culture rapidly produce an inhibitor of neutrophil chemotaxis which we have previously described. We found that this inhibitor of chemotaxis has its most potent effect on the inhibition of neutrophil shape change from a spherical to a polarized configuration. In order to quantify this shape change inhibition, we developed an assay using flow cytometric techniques. Neutrophils exposed to a chemoattractant simultaneously change their shape and decrease their forward angle light scattering intensity (delta FLS) with a correlation coefficient of 0.886 (p less than 0.001). In 51 experiments, neutrophils pretreated with the inhibitor of chemotaxis decreased their FLS by only 6.8 +/- 1.3 channels, while neutrophils pretreated with medium or control culture supernatants decreased theirs by 26.4 +/- 1.9 and 20.5 +/- 3.0 channels respectively (p less than 0.001). The factor which causes inhibition of shape change was indistinguishable from the inhibitor of chemotaxis by physical properties and chromatography. We conclude that this inhibitor of chemotaxis may act by inhibiting a physiologic step at or before shape change.

Chemical Phenomena↗
PubMed1987

Expansion of a T lymphocyte subpopulation (CD3+,4-,8-) after immunodepression associated with disseminated histoplasmosis.

A major subpopulation of T lymphocytes bearing a high density of CD3 (T3/Leu 4) with no detectable CD4 (T4/Leu 3a) or CD8 (T8/Leu 2a) was found in a patient with cardiomyopathy. Previously the patient had developed disseminated histoplasmosis which had been associated with a profound anergic state. The proportion of CD3+ lymphocytes that bore the phenotype CD3+,4-,8- has been increasing in the absence of reactivation of the histoplasmosis. The CD3+,4-,8- lymphocytes bound anti-CD2 but did not bind WT31, a monoclonal antibody specific for the alpha beta heterodimer of the T cell antigen receptor.

Adult↗
PubMed1985

Pathogenesis and treatment of endocarditis.

The rabbit model has been invaluable for in vivo studies in the pathogenesis and treatment of bacterial endocarditis. Both of the features of the mature bacterial vegetations in this rabbit model, i.e., absence of phagocytosis and decreased metabolic activity, provide evidence to support the concept that a rapidly bactericidal antimicrobial agent provides the optimal approach to the successful treatment of endocarditis. Imipenem, a carbapenem with a very broad spectrum of in vitro activity, has been shown to be rapidly bactericidal in animals and highly effective in the treatment of experimental bacterial endocarditis. In addition, twenty-six patients with endocarditis, caused largely by Staphylococcus aureus, have been successfully treated with imipenem/cilastatin.

Animals↗
PubMed1985

Human mononuclear cells exposed to staphylococci rapidly produce an inhibitor of neutrophil chemotaxis.

Serum-free cultures of human peripheral blood mononuclear cells from normal volunteers produce an inhibitor of neutrophil chemotaxis when exposed to heat-killed staphylococci. Human neutrophils were exposed to 100-fold dilutions of supernatants from 6-hr cultures, washed repeatedly, and assayed for chemotactic responsiveness with a radiolabel assay. Dilutions of supernatants from cell cultures exposed to staphylococci resulted in a mean chemotaxis of 856 +/- 83 cpm (n = 21), while that for medium-treated neutrophils was 1,354 +/- 100 cpm (n = 21, P less than .001), and supernatants from cultures without staphylococci produced chemotaxis of 1,107 +/- 132 cpm (n = 14, P greater than .05 vs. medium-treated). Fifty-three experiments on tissue from 26 donors showed that after 6 hr the mean inhibition (+/- SE) of chemotaxis at 1:100 dilution was 26.4% +/- 3.3% (P less than .001 vs. medium-treated). It was found that the peptidoglycan fraction of the staphylococci was sufficient to induce production of inhibitor by the cooperative action of T cells and monocytes. The inhibitor is a protein with a molecular mass of 30-45 kilodaltons. It is not toxic to the neutrophils and does not affect secretion, adhesion, phagocytosis, or the ability to kill Staphylococcus aureus. This potent inhibitor of neutrophil chemotaxis may play a role in the modulation of neutrophil function during bacterial infections.

Cell Movement↗
PubMed1985

Empirical use of imipenem as the sole antibiotic in the treatment of serious infections.

Seventy-three patients with eighty-five infections were treated with imipenem as the sole antimicrobial agent. Some of these infections were caused by pseudomonads and enterococci resistant to other cephalosporins. The vast majority of the Gram-positive and the Gram-negative bacteria that were isolated had a minimal inhibitory concentration (MIC) of less than 1 mg/l, and all MICs for initial isolates were below the levels of imipenem that were achieved in plasma and other body fluids with a dose of 500 mg every 6 h. The outcomes of 67 infectious episodes were satisfactory, four outcomes were failures and 14 were not evaluable. During the two years of this study, only a few strains of Staphylococcus epidermidis and of Pseudomonas aeruginosa emerged which were resistant to imipenem.

Adolescent↗
PubMed1983

The hyperimmunoglobulin E recurrent-infection (Job's) syndrome. A review of the NIH experience and the literature.

The hyperimmunoglobulin E recurrent-infection syndrome (HIE) entails a disorder of recurrent bacterial infections of the skin and sinopulmonary tract commencing in infancy or early childhood in the presence of serum levels of IgE which are at least 10 times normal (greater than 2,000 IU/ml). Variable concomitants of HIE are coarse facies, chronic eczematoid rashes, cold cutaneous abscesses, mild eosinophilia, mucocutaneous candidiasis, and a neutrophil chemotactic defect. The bacteria which commonly infect these patients are Staphylococcus aureus and Haemophilus influenzae although Streptococcus pneumoniae and enteric gram-negative rods are seen in some cases. Other than pneumonias, deep-seated infections are unusual, although osteomyelitis, arthritis, and visceral abscesses are seen. Bacteremia and sepsis are rare. Therapy should involve prolonged intravenous antibiotics and early surgery to treat infections which usually seem deceptively benign. HIE patients' neutrophils display a variable chemotactic defect, and their mononuclear cells variably produce an inhibitor of neutrophil chemotaxis. The production of the inhibitor correlates with the in vitro chemotactic defect. The basis of the propensity for recurrent infections is still speculative, and the further study of this syndrome should add new dimensions to our understanding of host defenses against bacterial invaders.

Abscess↗