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Biomedical subjects

D L Cohn

Publications and source records attributed to D L Cohn.

At least 91 records · Page 5Linked to original sources

Counterimmunoelectrophoresis for detection of human serum antibody to HTLV-III.

We examined the usefulness of a counterimmunoelectrophoresis (CIE) technique for detecting antibodies to HTLV-III using sera that previously had been assessed for antibodies to HTLV-III by the standard enzyme-linked immunosorbent assay (ELISA). We selected a subset of 53 sera from patients with the acquired immune deficiency syndrome (AIDS) or the generalized lymphadenopathy syndrome (GLS) in which 81.1% were initially ELISA-positive, and 96.2% were positive by Western blot technique. In our standard HTLV-III CIE technique, 58.5% were positive and repeat testing increased the yield to 67.9%. Varying several parameters of the standard CIE assay did not improve sensitivity. We also studied 20 ELISA-negative and 10 ELISA-borderline sera from normal controls; all were negative by CIE. These results indicate that CIE may be used for detection of human serum antibodies to HTLV-III, but that the present assay was less sensitive than the HTLV-III ELISA.

Acquired Immunodeficiency Syndrome↗

Progressive encephalitis three months after resolution of cutaneous zoster in a patient with AIDS.

A 37-year-old homosexual man with the acquired immune deficiency syndrome (AIDS) developed progressive, ultimately fatal, neurological deficits 12 weeks after a course of cutaneous zoster. Premortem radiological procedures and cerebrospinal fluid analyses were nondiagnostic. At postmortem examination, several opportunistic infections associated with AIDS were recognized. Throughout the brain, necrotic and demyelinative lesions were present, suggestive of progressive multifocal leukoencephalopathy. However, light microscopical examination showed numerous Cowdry type A intranuclear inclusions in astrocytes, oligodendrocytes, and neurons near the periphery of the lesions. Herpes zoster encephalomyelitis was diagnosed and confirmed by electron microscopy, peroxidase-antiperoxidase staining, and by Southern blot analysis of DNA extracted from brain tissue. This case provides insight into the pathogenesis of zoster-associated encephalomyelitis and suggests another agent to be considered in the differential diagnosis of encephalopathy in patients with AIDS and other disorders of immunological impairment.

Acquired Immunodeficiency Syndrome↗

The relationship of abnormalities of cellular immunity to antibodies to HTLV-III in homosexual men.

A comprehensive evaluation of the cellular immune system (total T-cell, helper cell, suppressor cell, and natural killer cell numbers; in vitro interleukin-2 production, T-cell responses to mitogens and antigens, serum beta 2 microglobulin levels, and delayed hypersensitivity skin tests) was performed on 36 HTLV-III seronegative and 16 HTLV-III seropositive healthy homosexual men, 48 asymptomatic homosexual men with the chronic lymphadenopathy syndrome, 41 patients with AIDS, and 29 heterosexual controls without any known risk factors for AIDS. Our studies demonstrate that HTLV-III seronegative homosexual men have normal cellular immunity and are comparable to heterosexual controls. The abnormalities of lymphocyte subsets observed in HTLV-III seropositive healthy homosexual men are comparable to subjects with chronic lymphadenopathy. Assays of lymphocyte function, with the exception of delayed type hypersensitivity (DTH) skin tests, are similar in each group except patients with AIDS. Subjects with chronic lymphadenopathy were less responsive to DTH skin tests and HTLV-III seropositive healthy homosexuals were comparable to chronic lymphadenopathy subjects. We conclude that immunologic abnormalities in homosexual men are attributable to infection with HTLV-III.

Acquired Immunodeficiency Syndrome↗

Mycobacterium avium-M. intracellulare isolates from patients with or without acquired immunodeficiency syndrome.

Susceptibility testing and serotyping were performed on 57 isolates of Mycobacterium avium-M. intracellulare from patients with acquired immunodeficiency syndrome (AIDS) and 75 isolates from patients without AIDS. Susceptibility patterns and serotypes of AIDS isolates were significantly different from those of non-AIDS isolates. These results may partially explain the poor therapeutic response of M. avium-M. intracellulare infections in AIDS patients.

Acquired Immunodeficiency Syndrome↗

Altered excretion of modified nucleosides and beta-aminoisobutyric acid in subjects with acquired immunodeficiency syndrome or at risk for acquired immunodeficiency syndrome.

Urinary excretion of modified nucleosides and beta-aminoisobutyric acid, subsequently referred to as markers, was determined in populations of patients with acquired immunodeficiency syndrome (AIDS) or at risk for development of AIDS. Our results show that asymptomatic adult male homosexuals excreted elevated amounts of markers as compared to male heterosexuals. This aberrant excretion was more pronounced in asymptomatic adult male homosexuals with antibodies to HTLV-III. Significantly greater excretion of 1-methylinosine, N4-acetylcytidine, and N2-methylguanosine was observed in asymptomatic adult male homosexuals with antibodies to HTLV-III than in asymptomatic male homosexuals without antibodies to HTLV-III. Increased amounts of markers were also excreted by subjects with the generalized or chronic lymphadenopathy syndrome, AIDS related complex (ARC), or AIDS. In these subjects, the most pronounced differences between groups were between subjects with chronic lymphadenopathy syndrome and those with ARC; subjects with ARC excreted greater amounts of seven of the ten urinary markers. There were few differences between subjects with ARC and those with AIDS, Kaposi's sarcoma, or AIDS with opportunistic infections. This observation may be useful for identifying subjects who are at risk of developing AIDS. A prospective study to test this hypothesis is under way.

Acquired Immunodeficiency Syndrome↗

Parasites of the laboratory woodchuck (Marmota monax).

The parasite burden of captive and colony-born woodchucks maintained in laboratory animal facilities was determined and compared to woodchucks recently trapped. Microfilariae of Ackertia marmotae in blood or dermis were most commonly observed in trapped woodchucks. There was a linear decrease in woodchucks positive for microfilariae after introduction in the laboratory colony, but even after 39 months, 53% were positive. Microfilaremia or microfilariderma were never observed in colony born woodchucks. Eggs or oocysts of Obeliscoides cuniculi, Citellina triradiata and Eimeria sp. were found by fecal flotation. The O. cuniculi population declined exponentially in captive woodchucks following colony entry, and this nematode was never found in colony-born woodchucks. However, low rates of infection with Citellina and Eimeria sp. were found in the colony-born group. Ixodes cookei, Oropsylla sp., and Androlaelaps sp. ectoparasites were observed commonly in recently trapped woodchucks, but were not present in any woodchucks maintained in the colony. Clinical disease associated with parasitic infection was not observed.

Animals↗

Interleukin-2 production by persons with the generalized lymphadenopathy syndrome or the acquired immune deficiency syndrome.

We measured production of interleukin-2 (IL-2) by phytohemagglutinin-stimulated peripheral blood mononuclear cells from 27 heterosexual persons, 43 asymptomatic homosexual men, 34 homosexual men with generalized lymphadenopathy syndrome (GLS), and 21 patients with acquired immune deficiency syndrome (AIDS). Asymptomatic heterosexual and homosexual subjects produced comparable amounts of IL-2, but 8 of 11 AIDS patients with opportunistic infections and two of three AIDS patients with both opportunistic infections and Kaposi's sarcoma failed to produce detectable amounts of IL-2; all seven AIDS patients with only Kaposi's sarcoma produced IL-2. The titer of IL-2 produced by the AIDS patients correlated with the percentage of helper T lymphocytes (Leu 3a+ cells) but not with the percentage of suppressor T lymphocytes (Leu 2a+ cells). This observation is interpreted as indicating that failure to produce IL-2 by AIDS patients is most likely due to depletion of IL-2-producing cells, although an abnormality of T-cell function has not been excluded. In addition, three of eight AIDS patients who did not produce IL-2 produced supernatants that inhibited growth of IL-2-dependent cells in the presence of IL-2. These observations suggest that measurement of endogenous IL-2 production may be important in selecting patients for therapy with IL-2.

Acquired Immunodeficiency Syndrome↗

Health status of Southeast Asian refugees.

The rates of several diseases have been reported to be higher among Southeast Asian refugees compared with those of indigenous North Americans. When we prospectively evaluated 991 refugees new to the Denver metropolitan area for their health and immunization status over a 12-month period, 38% were found to be tuberculin-positive, 71% carried one or more enteric parasites, 15% were HBsAg-positive, 13% had anemia and 31% either presented without immunization records or required continuation of vaccination sequences begun in overseas camps. Age and ethnicity were important variables with regard to tuberculosis, hepatitis B and anemia. The rates of specific parasitic infestations varied among the four ethnic groups, though the overall rates of parasitosis remained constant across ethnic lines.

Adolescent↗

Oral rifampin and trimethoprim/sulfamethoxazole therapy in asymptomatic carriers of methicillin-resistant Staphylococcus aureus infections.

During a hospital outbreak of methicillin-resistant Staphylococcus aureus (MRSA) disease in 30 patients we studied the use of rifampin and trimethoprim/sulfamethoxazole (TMP/SMX) in managing asymptomatic carriers. The outbreak persisted despite control measures including "barrier" precautions, screening cultures, identification of affected persons and rapid hospital discharge of affected patients. The MRSA strain was susceptible to both rifampin and TMP/SMX and in vitro the combination was not antagonistic. Fourteen carriers received a five-day course of rifampin and TMP/SMX given by mouth. Twelve patients were evaluable. Cultures remained persistently positive in four patients, three of whom had foreign bodies that could not be removed. Among the eight with an initial response, two relapsed to the carrier state more than six months after treatment. During the study the outbreak resolved. These data suggest that rifampin and TMP/SMX may decrease the number of MRSA-colonized patients, but may not permanently eradicate the MRSA carrier state.

Adult↗

Tuberculosis screening. Evaluation of a food handlers' program.

An evaluation of a tuberculosis screening program for food handlers revealed an unexpectedly low cost ($45) per identifiable candidate for preventive treatment (324 of 6,090 individuals screened). Four new active cases of tuberculosis were identified, and a risk/benefit analysis projected a potential reduction of 19.4 new active cases over the subsequent ten-year period.

Adolescent↗

Postantibiotic suppression of bacterial growth.

Persistent suppression of bacterial growth following exposure of both gram-positive and gram-negative bacteria to numerous antimicrobial agents was studied. The persistent, or postantibiotic, effect was quantitated by periodic counts of colony-forming units after removal of the drug by washing, dilution, or inactivation with penicillinase. Although a postantibiotic effect was observed with all drugs studied, there were marked differences among drugs in their postantibiotic effects on certain organisms. With gram-positive organisms, concentrations of beta-lactam antibiotics near the minimal inhibitory concentration produced persistent effects lasting 1-3 hr. With gram-negative organisms much higher concentrations were required to elicit a postantibiotic effect. Inhibitors of protein and RNA synthesis produced the longest persistent suppression of growth, which was of comparable duration in gram-positive and gram-negative bacteria. Only a short persistent effect of gentamicin was observed with Staphylococcus aureus and Escherichia coli, but a postantibiotic effect lasting 1.6-2.6 hr was observed with Pseudomonas aeruginosa. The duration of the postantibiotic effect was related linearly to concentration of drug and duration of exposure up to a point of maximal response. Persistent effects following exposure to antibiotics were also demonstrated in 90% human serum.

Anti-Bacterial Agents↗