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H A Kessler

Publications and source records attributed to H A Kessler.

At least 55 records · Page 3Linked to original sources
PubMed1993

Characterizing the neuropsychological functioning of persons with human immunodeficiency virus (HIV) infection, Part II. Neuropsychological functioning of persons at different stages of HIV infection.

Neuropsychological impairment has been reported to occur in persons at all stages of infection with the human immunodeficiency virus (HIV). However, the findings of studies to characterize the incidence and pattern of impairment have been limited by inconsistent definitions of impairment and the failure to control for confounding variables, such as hematological abnormalities, history of head injury, or substance abuse. In the present study, neuropsychological tests were administered to 141 persons at four stages of HIV infection. Significant differences were found in the percentage of persons who showed impairment at each stage of infection. Further, participants' performance on the tests tended to decline across progressive stages of infection. These findings may help psychiatric nurses identify and manage the changes associated with HIV infection.

AIDS Dementia Complex↗
PubMed1993

Detection of HIV-1 provirus in bronchoalveolar lavage cells by polymerase chain reaction.

This study was undertaken to evaluate whether HIV-seropositive individuals harbor HIV provirus in cells obtained by bronchoalveolar lavage (BAL). BAL cells were obtained from 14 HIV-positive patients undergoing bronchoscopy for evaluation of acute pulmonary symptoms. Cells were fractionated into macrophage-enriched and lymphocyte-enriched populations. The quantity of HIV-1 proviral DNA in the unfractionated BAL cells and in each population of fractionated cells was determined following polymerase chain reaction (PCR) amplification. Detectable quantities (3-90 copies/100,000 cells) of HIV-1 proviral DNA were found in unfractionated BAL cells in 12 of 14 patients. In the other two patients, provirus was detected after a sevenfold enrichment of lymphocytes. Provirus was also detected in BAL macrophages from 8/14 patients although proviral content was significantly higher in the lymphocyte fraction (133 +/- 72 vs. 35 +/- 22 proviral copies, p = 0.03). No correlation was seen with the ability to detect provirus in lymphocyte- or macrophage-enriched fractions and clinical diagnosis (e.g., Pneumocystis carinii pneumonia). The data suggest that lymphocytes are the predominant cells that contain provirus found in the lungs, although macrophages may be infected in some patients.

AIDS-Related Opportunistic Infections↗
PubMed1992

AIDS: Part II.

Great strides have been made in the therapy of human immunodeficiency virus (HIV) infection. Currently approved drugs include zidovudine and didanosine. A third drug, dideoxycytidine (zalcitibine), has recently been filed for approval with the Food and Drug Administration. All these drugs work through inhibition of the reverse transcriptase enzyme. Zidovudine is the only drug that has shown clinical efficacy against HIV. Treatment of patients with advanced HIV disease (i.e., acquired immune deficiency syndrome [AIDS] or symptomatic infection with < 200 CD4+ lymphocytes per mm3), results in a prolongation and improved quality of life. Zidovudine is the only antiretroviral agent approved for the treatment of asymptomatic patients. Early intervention with zidovudine has been shown to delay progression to AIDS when patients' CD4+ lymphocyte counts decline to less than 500/mm3, irrespective of clinical signs or symptoms of HIV infection. Didanosine is currently indicated for the treatment of patients with advanced HIV disease who are intolerant to or failing zidovudine therapy. The major toxicity of zidovudine is bone marrow suppression with anemia and granulocytopenia (which occurs in from 1% to 45% of patients, depending on the clinical stage of disease and the dose of the drug). Didanosine and zalcitibine have both been associated with a severe peripheral neuropathy, which is generally reversible on cessation of the drug. In addition, didanosine has been implicated as a cause of pancreatitis that has been fatal in a small percentage of cases. The toxicities of didanosine and zalcitibine range from 1% to 10%, depending on dose, duration of therapy, and the presence of underlying HIV-related peripheral neuropathy or a previous history of pancreatitis. The clinical hallmark of HIV infection is the development of opportunistic infections and malignancies, which are a consequence of the profound immunodeficiency. The risk of an opportunistic infection increases significantly as the T-helper lymphocyte count declines to less than 20%, or 200 to 250/mm3. The spectrum of opportunistic infections ranges from viruses to protozoa. Patients with advanced HIV disease are also at increased risk of infection with nonopportunistic, community-acquired pathogens. Primary and secondary prophylaxis against the most common AIDS-defining opportunistic infection, Pneumocystis carinii pneumonia, is now recommended. Studies are currently underway to determine the efficacy of prophylaxis against other opportunistic pathogens. Treatment of opportunistic infections associated with AIDS has improved significantly over the past 5 years as new drugs and combination regimens of antimicrobials have been developed.(ABSTRACT TRUNCATED AT 400 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1992

AIDS: Part I.

Acquired immunodeficiency syndrome (AIDS) is caused by infection with a pathogenic human retrovirus known as human immunodeficiency virus (HIV). Approximately 1 million people are currently infected with HIV in the United States, with 8 to 10 million infected individuals worldwide. The virus is transmitted predominantly through genital sexual contact, although orogenital spread has been rarely reported. Heterosexual transmission has been most common in the Third World, whereas male homosexual transmission has predominated in the United States and western Europe. Transmission through homosexual contact has been steadily declining over the past 5 years as transmission through illicit intravenous drug use and promiscuous unprotected heterosexual activity has increased. Sexually transmitted diseases that cause inflammatory or ulcerative lesions of the genital tract act as important cofactors in increasing the risk of transmission through sexual contact. Perinatal transmission of HIV occurs in approximately 30% of infants born to infected mothers. Transmission to infants through breast-feeding has also been documented. Health care workers have been infected with HIV through accidental high-risk percutaneous or mucous membrane exposures, albeit at a low transmission rate of 0.3%. Infection of patients by infected health care professionals is a rare event, having been reported only once in 10 years of the epidemic. Infection with HIV results in a chronic lifelong infection. The major targets for HIV are CD4+ T-helper lymphocytes and cells of monocyte/macrophage lineage. Infection of the T-helper lymphocyte ultimately results in the death of the cell. Over time (measured in years), a progressive destruction of the T-helper lymphocyte population occurs, which results in profound immune suppression. Infection of monocytes/macrophages is not cidal, but these cells do have functional alterations as a result of the infection, which may contribute to the immune deficiency. In addition, chronically infected tissue macrophages may act as an important reservoir for HIV, particularly in the central nervous system. Infection of the T-helper lymphocytes and monocytes/macrophages is mediated through attachment of HIV through a specific binding interaction between CD4 expressed in the plasma membrane of these cells and a surface glycoprotein on the virus, gp120. Once the virus nucleocapsid (core particle) enters the cytoplasm of the target cell, the viral RNA genome is reverse transcribed by a reverse transcriptase enzyme into proviral DNA. This proviral DNA migrates into the nucleus where it integrates into the host cellular genome, which results in a chronically infected cell.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1992

Reconstitution of long-term T helper cell function after zidovudine therapy in human immunodeficiency virus-infected patients.

Peripheral blood mononuclear cells from 12 asymptomatic patients infected with immunodeficiency virus (HIV) and 4 patients with AIDS were analyzed before and during therapy with zidovudine for T helper cell (Th) function. Th function improved by more than fourfold to one or more of three stimuli tested in 9 (75%) of 12 asymptomatic patients on zidovudine therapy and in 3 of 4 patients with AIDS. Only 6 (7.4%) of 80 untreated HIV-infected control patients showed spontaneous improvement in Th function (P less than 10(-6)). Improved Th function was detected as early as 5 weeks into therapy in 6 patients and continued to be evident for greater than 1 year after start of therapy in 6 patients and for greater than 2 years in 2 patients. No correlation was observed between improved Th function and changes in CD4+ or CD8+ cell numbers or in levels of serum HIV p24 antigen or beta 2-microglobulin. These results suggest inclusion of in vitro Th function as a useful marker in determining the efficacy of antiretroviral drug therapy of HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Pneumocystis carinii choroiditis in patients with AIDS: clinical features, response to therapy, and outcome.

To further characterize the clinical features, response to therapy, and outcome of Pneumocystis carinii choroiditis in patients with AIDS, we retrospectively reviewed the course of choroiditis for eight patients identified from two institutions through April 1991. Seven patients had prior Pneumocystis carinii pneumonia and had received aerosolized pentamidine prophylaxis for a median of 10 months; one patient had no prior history of pneumonia or prophylaxis. The median CD4+ lymphocyte count for six patients was 11 cells/mm3. Choroiditis was a preterminal diagnosis for three patients--two with associated disseminated pneumocystosis. Ocular manifestations improved or resolved with therapy for five of the six treated patients. All five subsequently received prophylaxis with dapsone (n = 2), dapsone/trimethoprim (n = 2), or aerosolized pentamidine (n = 1). Choroiditis recurred at 15 months in the one patient receiving aerosolized pentamidine. The median survival from time of diagnosis was 44 weeks. A literature review including an additional 40 cases support the conclusions that (a) Pneumocystis choroiditis is a rare complication of advanced HIV disease, occurring often in the context of systemic pneumocystosis; (b) ocular signs and symptoms may improve or resolve with specific antipneumocystis therapy; and (c) relapse may occur, particularly in those not receiving systemic prophylaxis.

AIDS-Related Opportunistic Infections↗
PubMed1991

A controlled trial comparing foscarnet with vidarabine for acyclovir-resistant mucocutaneous herpes simplex in the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group.

BACKGROUND AND METHODS: Most strains of herpes simplex virus that are resistant to acyclovir are susceptible in vitro to both foscarnet and vidarabine. We conducted a randomized trial to compare foscarnet with vidarabine in 14 patients with the acquired immunodeficiency syndrome (AIDS) and mucocutaneous herpetic lesions that had been unresponsive to intravenous therapy with acyclovir for a minimum of 10 days. The patients were randomly assigned to receive either foscarnet (40 mg per kilogram of body weight intravenously every 8 hours) or vidarabine (15 mg per kilogram per day intravenously) for 10 to 42 days. In the isolates of herpes simplex virus we documented in vitro resistance to acyclovir and susceptibility to foscarnet and vidarabine. RESULTS: The lesions in all eight patients assigned to foscarnet healed completely after 10 to 24 days of therapy. In contrast, vidarabine was discontinued because of failure in all six patients assigned to receive it. The time to complete healing (P = 0.01), time to 50 percent reductions in the size of the lesions (P = 0.01) and the pain score (P = 0.004), and time to the end of viral shedding (P = 0.006) were all significantly shorter in the patients assigned to foscarnet. Three patients had new neurologic abnormalities while receiving vidarabine. No patient discontinued foscarnet because of toxicity. Although initial recurrences of herpes simplex infection after the index lesion had healed tended to be susceptible to acyclovir, acyclovir-resistant infection eventually recurred in every healed patient, a median of 42.5 days (range, 14 to 191) after foscarnet was discontinued. CONCLUSIONS: For the treatment of acyclovir-resistant herpes simplex infection in patients with AIDS, foscarnet has superior efficacy and less frequent serious toxicity than vidarabine. Once the treatment is stopped, however; there is a high frequency of relapse.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Multiple patterns of alloantigen presenting/stimulating cell dysfunction in patients with AIDS.

The APC/stimulating cell (APC/SC) potential of PBMC from Walter Reed stage 1 and 2 patients and patients with AIDS was tested by using these PBMC as stimulators in an allogeneic MLR. The responding cells were PBMC from unrelated, HIV- donors that were either unfractionated or depleted of APC by plastic and nylon wool adherence. Using this approach, we observed no defect in the APC/SC potential of PBMC from Walter Reed stage 1 and 2 patients. However, PBMC from AIDS patients used as allogeneic stimulators exhibited three different patterns of APC/SC function: 1) no defect in alloantigen (ALLO) APC/SC potential; 2) a defect in ALLO APC/SC function that was detected only if the responder cells were depleted of APC (presenting cell defect); and 3) a defect in ALLO APC/SC function, irrespective of whether the responder cells were depleted of APC (stimulating cell defect). These results indicate that in addition to Th cell defects associated with AIDS, the PBMC from AIDS patients can also exhibit a defect in APC/SC function. This study provides an approach that permits the testing of Ag-presenting function in all AIDS patients, and is therefore not limited to testing patients for whom HIV-, HLA-identical T cells and APC are available.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Suppression of cytomegalovirus retinitis in persons with AIDS with high-dose intravenous acyclovir.

To evaluate the efficacy and safety of high-dose intravenous acyclovir combined with oral zidovudine as suppressive therapy for cytomegalovirus retinitis in patients with AIDS, a single-arm, outpatient, open-label, phase II pilot study was performed. Between July 1989 and July 1990, 12 men with AIDS, cytomegalovirus retinitis, and salvageable vision received intravenous acyclovir, 10 mg/kg of body weight every 8 h, and oral zidovudine after successful induction therapy with intravenous ganciclovir, 5 mg/kg every 12 h for 14 days. Patients were evaluated weekly. Ten of 12 patients were followed to the time of retinitis progression; two were withdrawn from the study because of concomitant life-threatening infection. The median duration of acyclovir and zidovudine therapy before retinitis progression occurred was 32 days. None of the eight uninvolved eyes in the 10 evaluatable patients developed cytomegalovirus retinitis during study participation. These data suggest that high-dose intravenous acyclovir with zidovudine provides some benefit in suppressing cytomegalovirus retinitis.

Acquired Immunodeficiency Syndrome↗
PubMed1991

2',5'-oligoadenylate synthetase, neopterin and beta 2-microglobulin in asymptomatic HIV-infected individuals.

This study examined 2',5'-oligoadenylate (2,5A) synthetase activity in 26 individuals during the asymptomatic phase of HIV infection and its correlation with neopterin or beta 2-microglobulin. In HIV-antibody-positive (HIV-Ab+) asymptomatic people, both neopterin and beta 2-microglobulin levels in sera were significantly elevated; in contrast, 2,5A-synthetase activity in peripheral blood mononuclear cells was not significantly higher than in HIV-antibody-negative controls. The 2,5A-synthetase levels in symptomatic people (AIDS-related complex and AIDS) were significantly higher than in either asymptomatic or control individuals. However, within the group of HIV-infected asymptomatic individuals, all three markers were positively correlated. In this group, neopterin values were negatively correlated with the number of CD4+ lymphocytes while a positive correlation was found between 2,5A-synthetase and the number of CD8+ lymphocytes. Asymptomatic people with detectable serum HIV p24 antigen had significantly higher 2,5A-synthetase, neopterin, beta 2-microglobulin and number of CD8+ lymphocytes. This study suggests that elevated 2,5A-synthetase activity may reflect a different aspect of host response to HIV infection than do elevated neopterin or beta 2-microglobulin.

2',5'-Oligoadenylate Synthetase↗
PubMed1991

Combined APACHE II score and serum lactate dehydrogenase as predictors of in-hospital mortality caused by first episode Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome.

We retrospectively analyzed data from 75 hospitalized patients with a first episode of Pneumocystis carinii pneumonia to compare the ability of four parameters, including admission serum albumin, serum lactate dehydrogenase (LDH), alveolar-arterial oxygen gradient, and the APACHE II score, to predict mortality and response to initial antipneumocystis therapy. The eight patients who died due to pneumocystosis and the 12 who failed initial antipneumocystis therapy had significantly higher admission mean APACHE II scores and serum LDH levels and lower mean serum albumin levels than did the 65 who survived and the 61 who responded to initial therapy (p less than 0.05 for each). Differences in mean alveolar-arterial oxygen gradients were not statistically significant with respect to survival or response to initial therapy. In a stepwise discriminant analysis of parameters associated with mortality, APACHE II score and LDH level were statistically significant (p less than 0.0001 for each). In a stepwise discriminant analysis of parameters associated with response to initial therapy, APACHE II score and LDH level were again statistically significant (p less than 0.0001, respectively). The addition of the alveolar-arterial oxygen gradient and serum albumin level did not further increase the predictive ability of the discriminant analyses. When analyzed alone, neither the alveolar-arterial oxygen gradient nor the serum albumin were statistically significant in each discriminant analysis. The APACHE II score combined with the serum LDH may be more useful than other parameters, singly or combined, to more closely match patients with regard to severity of illness due to first episode Pneumocystis carinii pneumonia when comparing experimental new therapies with standard agents.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Successful treatment of acquired immunodeficiency syndrome-related Mycobacterium avium complex disease with a multiple drug regimen including amikacin.

Disease due to Mycobacterium avium complex (MAC) in patients with the acquired immunodeficiency syndrome (AIDS) typically occurs late in the course of AIDS and is usually disseminated with evidence of multiorgan involvement. Most patients are persistently bacteremic. Previously published studies have noted a poor response to antimycobacterial chemotherapy. We describe successful treatment of MAC disease in an AIDS patient with a multiple drug regimen, including amikacin, clofazimine, rifampin, ethambutol, and ciprofloxacin. This patient, whose presentation and MAC disease course distinctly differ from most published experience, remains clinically and microbiologically MAC-disease free 25 months after initiation of therapy. We describe four additional AIDS patients with MAC disease who had a favorable clinical and microbiological response to this regimen without developing serious adverse effects after periods ranging from 4 to 12 months. We suggest a prospective, controlled clinical trial using this regimen for treatment of MAC disease in patients with AIDS may be warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Decreased oxidative burst activity of monocytes from asymptomatic HIV-infected individuals.

Although changes in function of monocytes from AIDS patients have previously been reported, the functional deficits that could occur in monocytes from asymptomatic HIV-seropositive individuals has not been extensively investigated. The goal of this study was to evaluate the oxidative burst response and cell surface marker expression of monocytes from this group. Both the oxidative burst, as measured by 2',7'-dichlorofluorescin diacetate oxidation, and cell surface markers were evaluated on CD14+ (Leu-M3) monocytes by two-color flow cytometry. A significantly lower oxidative burst capacity was observed in asymptomatic, seropositives after phorbol myristate acetate and calcium ionophore stimulation when compared to seronegative controls. However, differences in oxidative burst between the two groups were not observed after stimulation with heat-aggregated IgG. The oxidative burst of monocytes from seropositive HIV antigen+ or antigen- subjects was not significantly different. The most significant difference in monocyte surface markers between seropositive and seronegative controls was a decrease in the proportion of complement receptor 3+ (CD11b+) cells while slightly decreased numbers of CD13+ and CD33+ monocytes were observed. The decreased expression of CD11b+ cells in seropositives was found entirely within the seropositive, HIV antigen+ group. Similarly, when monocytes from seropositive HIV antigen+ and antigen- were compared, significantly lower numbers of CD4+ and HLA-DR+ cells were noted. These results indicate that significant changes in monocyte function and surface markers occur early during the course of HIV infection and are associated with the expression of serum HIV antigen.

Antigens, CD↗
PubMed1990

Isolation of HIV-1 from monocytes of individuals negative by conventional culture.

To improve isolation of human immunodeficiency virus (HIV) from purified monocytic cell populations, a differential culture technique was applied to blood from HIV-seropositive individuals, culture-negative for HIV by routine culture. When 206 individuals were grouped by percentage of CD4+ lymphocytes, increases in viral isolation rates were significantly associated with declines in percentage of CD4+ cells (P less than .0001). Of 158 asymptomatic individuals, 78% had greater than 400 CD4+ lymphocytes/mm3. Only 19% were culture-positive using routine methods. Separation of peripheral blood mononuclear cells (PBMC) into purified lymphocyte and monocyte subpopulations for 12 asymptomatic patients and subsequent HIV culture of each purified subpopulation using three different indicator cell lines resulted in 100% virus recovery from purified monocytes cultured in the U-937 promonocytic cell line. Culture of purified lymphocytes in U-937 cells did not increase the isolation rate, whereas culture of patient PBMC in U-937 indicator cells and in allogeneic monocytes resulted in a 50% increase in HIV isolation. A monocytic indicator cell line added to routine culture methods may improve virus recovery from asymptomatic individuals.

Acquired Immunodeficiency Syndrome↗