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Biomedical subjects

W D Hardy

Publications and source records attributed to W D Hardy.

At least 37 records · Page 2Linked to original sources
PubMed1992

Therapeutic algorithm for treatment of cytomegalovirus retinitis in persons with AIDS. A roundtable summary.

Foscarnet and ganciclovir appear to be of similar effectiveness in halting active infection when given as induction therapy and in forestalling progression of disease when given as maintenance therapy in persons with AIDS who have cytomegalovirus (CMV) retinitis. The primary dose-limiting toxicity of foscarnet is nephrotoxicity, whereas that of ganciclovir is neutropenia. The availability of two effective agents with different toxicities permits selection of initial treatment for CMV retinitis based on individual patient characteristics and provides an alternative for therapy if drug intolerance or viral resistance develops. An approach to treatment of first-episode and recurrent CMV retinitis based on patient and drug characteristics is presented. Case reports detailing the use of foscarnet and ganciclovir and problems encountered in patient management are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1992

The effect of zidovudine treatment on serum neopterin and beta 2-microglobulin levels in mildly symptomatic, HIV type 1 seropositive individuals.

Sixty-one subjects with mildly symptomatic human immunodeficiency virus (HIV) infection were included in a double-blind, randomized, placebo-controlled trial of zidovudine (part of AIDS Clinical Trials Group protocol 016, ACTG 016) to evaluate changes in the serum immune activation markers neopterin and beta 2-microglobulin (beta 2M) as early markers of the antiviral effect of zidovudine on HIV type 1 (HIV-1) infection. The mean values of serum neopterin and beta 2M levels in 27 placebo-treated subjects tended to increase with time. The mean value of neopterin in 34 subjects receiving zidovudine decreased at 4 weeks (15.76 nmol/L before treatment to 12.73 nmol/L, p = 0.001). The maximum reduction was seen at 8 weeks of treatment (10.78 nmol/L, p less than 0.0001). Subsequently, the mean value of serum neopterin increased but remained below the pretreatment value for more than a year. Serum beta 2M levels decreased (from 3.01 to 2.69 mg/L at 4 weeks, p = 0.01) and reached the lowest level at 8 weeks (2.45 mg/L, p = 0.0002) in zidovudine recipients. The mean beta 2M level returned to pretreatment value at approximately 24 weeks of the treatment. There was a close correlation between changes from baseline in serum neopterin and beta 2M during the first 16 weeks of the zidovudine therapy, but not later. Subjects with greater reductions of serum neopterin or beta 2M tended to maintain lower levels of these markers with continued zidovudine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Complex↗
PubMed1992

Eleven lymphoid phenotypic markers in HIV infection: selective changes induced by zidovudine treatment.

HIV infection induces substantial changes in the expression of many lymphocyte phenotypic markers as well as depletion of CD4 lymphocyte numbers. A comprehensive study was undertaken to determine whether seven lymphocyte phenotypic changes associated with HIV infection (increased CD38, HLA-DR, CD57, and CD71 and decreased CD11b, CD45RA, and leu-8) are altered by zidovudine (ZDV) administration. Levels of the four major lymphoid subsets (CD4, CD8, B, and NK cells) and changes in the serum activation markers neopterin and beta 2-microglobulin (beta 2M) were also measured. Elevated pretreatment expression of CD38 and CD71 was reduced significantly toward normal at 2 weeks by ZDV; however, CD38 and CD71 returned to pretreatment levels at different rates. The kinetics of CD38 reduction and the return to pretreatment levels were similar to those of serum neopterin and beta 2M. HLA-DR decreased in many but not all subjects. CD4 lymphocytes showed a transient increase, most evident at 8 weeks of treatment. Lymphoid phenotypes that did not show significant changes after ZDV therapy included CD57, CD11b, CD45RA, and leu-8 markers as well as CD8 T cells, CD20 B cells, and CD56 NK cells. The fact that some lymphocyte phenotypic markers change toward normal with ZDV treatment and others do not indicates that complex processes underlie immune perturbations of HIV infection. Several phenotypic markers (CD38, CD71, and HLA-DR) that are susceptible to short-term effects of ZDV (but with changes that differ from CD4 T cell changes) are surrogate marker candidates for evaluation in anti-HIV treatment.

Biomarkers↗
PubMed1991

Development of the immunofluorescent antibody test for detection of feline leukemia virus infection in cats.

Studies of the immunodetection of various microorganisms by various assay systems indicated that the most specific and sensitive assays are immunofluorescence, radioimmunoassay, and immunoblot analysis (western blot), followed by sensitive but less specific ELISA and agglutination assays and, finally, by even less sensitive but very specific virus isolation and double immunodiffusion techniques. The first test for the clinical detection of FeLV infection in pet cats was the immunofluorescent antibody (IFA) test, which was introduced in 1972. The FeLV test is used for detection for FeLV infection and not as a test for leukemia or any other feline disease. The IFA test was compared with an immunodiffusion (ID) test and with tissue culture isolation (TCI) of the virus in 26 cats to establish a standard for FeLV tests. Excellent correlation was observed between the IFA and the ID tests (100%).

Animals↗
PubMed1991

Ten-year study comparing enzyme-linked immunosorbent assay with the immunofluorescent antibody test for detection of feline leukemia virus infection in cats.

Immunodetection tests for feline retroviruses are powerful tools used in modern veterinary practice. Veterinarians must fully understand the characteristics--strengths and weaknesses--of the FeLV tests so that the information gained from them can be used properly. Any FeLV ELISA or immunofluorescent antibody (IFA) test is a method for detection of FeLV infection (the virus) and is not a diagnostic test for leukemia or other feline disease. From previous studies, it was determined that the most accurate test for detection of persistent FeLV infection is the IFA test, which detects FeLV antigens in cytoplasm of leukocytes in the blood of infected cats. In the study reported here, 1,142,600 FeLV IFA tests were performed between June 1972 and December 1990. During this period 19.8% of the IFA test results were positive and 78% were negative. Evaluation was not possible for the remaining 2.2% of the tests because of lack of enough leukocytes in the smears to evaluate, or nonspecific staining reactions. In 1979, 7 years after introduction of the IFA test, in-hospital FeLV ELISA were introduced, which enabled veterinarians to test for FeLV in their hospitals. Ever since that time, continual discrepancies have been reported between results of FeLV ELISA and IFA tests, particularly between positive ELISA results and their IFA test confirmation. A 10-year comparison was made between practitioner-performed in-hospital FeLV ELISA (n = 20, 240 tests) results and FeLV IFA test performed by a commercial laboratory. All samples tested by ELISA were submitted (for confirmation of results) by veterinarians from the United States, Canada, Europe, Japan, and Australia.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed1991

General principles of retrovirus immunodetection tests.

Because infecting retroviruses contain protein and glycoprotein antigenic determinants that can be readily distinguished from host cell determinants, the development of immunologic detection systems, immunodetection tests, or immunoassays capable of identifying antigens of some retroviruses (oncoretroviruses) in blood, body fluids, or cells is possible. Conversely, detection of antibodies produced by animals against some infecting retroviruses can also be used to identify current infections of lentiretroviruses and some oncoretroviruses. Studies of various microorganisms by various immunodetection systems indicate that the most specific and sensitive assays are immunofluorescence, radioimmunoassay, and immunoblot (western blot) analysis, followed by sensitive but less specific ELISA and agglutination assays, and finally by even less sensitive but very specific isolation in culture and double immunodiffusion techniques. The first test used routinely for clinical detection of any retrovirus was the immunofluorescent antibody test, introduced in 1972, for detection of FeLV infection in pet cats. Since then, tests for human retroviruses, the human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2 and the human T-cell lymphotropic virus types I and II (HTLV-I and HTLV-II) have been introduced for routine use in human medicine. Recently, retroviral tests for a second feline retrovirus, the feline immunodeficiency virus (FIV) have been introduced in veterinary medicine. General principles of sensitivity, specificity, true-positive and -negative rates, false-positive and -negative rates, and positive and negative predictive values apply to all methods used for detection of retroviral infections.

Animals↗
PubMed1991

Humoral recall responses in HIV infection. Levels, specificity, and affinity of antigen-specific IgG.

To evaluate the integrity of humoral immunologic memory among persons with HIV infection, we measured the levels, specificity, and functional affinity of circulating antibodies to vaccine-related recall Ag, tetanus (TT) and diphtheria toxoids (DT), and to naturally acquired measles virus, in sera from 17 HIV-seronegative control subjects, 17 asymptomatic HIV-seropositive patients, and 10 patients with AIDS. Preimmunization levels of TT- and measles-specific IgG were similar in all groups, although DT-specific IgG was lower in AIDS patients. Four wk after immunization with TT3 and DT, all groups showed significantly increased specific antibody levels (p less than 0.02). The asymptomatic HIV+ patients and control subjects achieved similar peak serum levels of TT-specific IgG (102 +/- 32 and 169 +/- 36 micrograms/ml, respectively). In contrast, the AIDS patients had lower peak values of both TT- and DT- specific IgG (p less than 0.05). Peak levels correlated directly with the number of CD4+ T cells (p less than 0.05). However, 80 to 100% of all participants tested, independent of HIV status, showed higher levels of TT- and DT-specific IgG 6 mo after immunization compared with preimmunization levels. The antitoxoid antibodies were specific as they did not cross-react with other Ag in competitive inhibition experiments. In addition, all groups exhibited antibodies to TT and DT both pre- and postimmunization of equivalent functional affinity (avidity) (Kd = 10(-10)-10(-11) mol/liter). We conclude that, in contrast to the profoundly depressed humoral responses to new Ag, persons with asymptomatic HIV infection retain humoral immunity to certain recall Ag. These levels of specific IgG to three recall Ag are not proportional to elevated levels of total serum IgG in HIV-infected patients. In addition, many patients with HIV respond to challenge with recall Ag by producing significant amounts of high affinity IgG that may persist over time.

Antibody Affinity↗
PubMed1991

Treatment of refractory oral candidiasis with fluconazole. A case report.

We describe a patient with the acquired immunodeficiency syndrome who had persistent oral esophageal pseudomembranous candidiasis clinically refractory to nystatin, clotrimazole, and ketoconazole. In vitro resistance to clotrimazole was demonstrated as well. The patient received temporary relief with intravenous amphotericin B therapy, but this was associated with serious adverse effects, including transfusion-requiring anemia, azotemia, and severe thrombophlebitis. Despite two courses of intravenous amphotericin B therapy, the patient's highly symptomatic, recurrent oral and esophageal candidiasis continued. The patient was then treated with fluconazole and obtained immediate relief without associated adverse effects.

Acquired Immunodeficiency Syndrome↗
PubMed1991

A health status questionnaire using 30 items from the Medical Outcomes Study. Preliminary validation in persons with early HIV infection.

Many current health status instruments either are too long to use in many acquired immune deficiency syndrome (AIDS) clinical trials or omit important concepts. In this study, human immunodeficiency virus (HIV)-relevant items developed for the Medical Outcomes Study (MOS) from subscales for cognitive function, energy/fatigue, health distress, and a single quality of life item were added to a portion of the MOS Short-form General Health Survey. The resulting 30-item questionnaire reliably and distinctly measured ten aspects of health and took less than 5 minutes to complete. To test its validity, this modified measure was used to compare the health of 73 subjects with asymptomatic HIV infection and 44 with early AIDS-related complex (ARC). Compared with ARC subjects, asymptomatic individuals reported superior overall health, less pain, and better physical function, role function, cognitive function, and quality of life (rank-sum, P less than 0.02). Asymptomatic subjects' scores were higher on most subscales than the age-adjusted scores of MOS outpatients with hypertension, diabetes, recent myocardial infarction, or depression; ARC patients scored closest to hypertensive patients. This instrument, containing a subset of the MOS measures of health-related quality of life, may be a useful outcome measure for AIDS clinical trials.

AIDS-Related Complex↗
PubMed1991

Combined ganciclovir and recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of cytomegalovirus retinitis in AIDS patients.

Ganciclovir is effective in halting or delaying the progression of cytomegalovirus (CMV) retinitis in patients with acquired immune deficiency syndrome (AIDS). However, the development of neutropenia necessitates the interruption of ganciclovir therapy in 40-50% of AIDS patients. In an ongoing randomized, controlled trial, AIDS patients with CMV retinitis are receiving standard ganciclovir therapy or ganciclovir plus recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). rHuGM-CSF is administered by daily subcutaneous injections and is given in ascending doses based on the neutrophil response in the individual patient. Preliminary data obtained from 36 evaluable patients (21 receiving ganciclovir alone, 15 receiving ganciclovir plus rHuGM-CSF) suggest that rHuGM-CSF administration is associated with a trend toward a decrease in the proportion of patients developing an absolute neutrophil count (ANC) of less than 750 cells/microliter (40% vs. 59%), in the overall incidence of such neutropenic episodes (20 vs. 68), and in the duration of ganciclovir treatment interruption due to the development of an ANC of less than 500 cells/microliter (5.5 days vs. 10.1 days). rHuGM-CSF administration has been generally well tolerated, and no consistent proliferative effect of this agent on human immunodeficiency virus infection has been observed. Definitive conclusions regarding the coadministration of rHuGM-CSF and ganciclovir await completion of the trial.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The safety and efficacy of zidovudine (AZT) in the treatment of subjects with mildly symptomatic human immunodeficiency virus type 1 (HIV) infection. A double-blind, placebo-controlled trial. The AIDS Clinical Trials Group.

OBJECTIVE: To evaluate the efficacy and safety of zidovudine early in the treatment of human immunodeficiency virus type 1 (HIV) infection. DESIGN: A double-blind, randomized, placebo-controlled trial with subject stratification by pretreatment CD4 T lymphocyte counts. SETTING: Multicenter trial at AIDS Clinical Trial units. SUBJECTS: Seven hundred eleven subjects with mildly symptomatic HIV infection. INTERVENTION: Three hundred fifty-one subjects were assigned to placebo and 360 to zidovudine, 200 mg orally every 4 hours. The median duration of follow-up was 11 months. MEASUREMENTS AND MAIN RESULTS: Fifty-one subjects developed the acquired immunodeficiency syndrome (AIDS), advanced AIDS-related complex, or death as a first critical event. For the stratum of subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 before treatment, 34 events occurred in placebo recipients and 12 in zidovudine recipients (P = 0.0002; relative risk [RR] estimate, 3.23 [95% CI, 1.67 to 6.24]). For the stratum of subjects with 500 to 799 CD4 T lymphocytes/mm3 before treatment, 2 events occurred in placebo recipients and 3 in zidovudine recipients. Candidiasis at study entry independently increased the risk for having an event (P = 0.005; RR estimate, 2.3 [95% CI, 1.29 to 4.12]); HIV antigenemia at study entry also increased this risk (P = 0.01; RR estimate, 2.1 [95% CI, 1.2 to 3.8]). Significant differences between the treatment groups in CD4 T-lymphocyte counts occurred in subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 after 4 weeks of therapy (P = 0.002). Differences persisted through week 52. Less prominent changes occurred in subjects with 500 or more CD4 T lymphocytes/mm3. Serum levels of HIV antigen decreased significantly in zidovudine recipients. Serious anemia and neutropenia occurred in 5% and 4% of zidovudine recipients, respectively, and in 0% and 1% of placebo recipients, respectively. CONCLUSION: Zidovudine delayed progression of HIV disease and produced little toxicity in subjects with mildly symptomatic HIV disease and less than 500 CD4 T lymphocytes/mm3.

AIDS-Related Complex↗
PubMed1990

Hemorheologic abnormalities in patients with human immunodeficiency virus infection and ophthalmic microvasculopathy.

The severity of conjunctival microvascular changes and the presence of cotton-wool spots were compared to factors that may affect blood flow (hematocrit level, red cell aggregation, fibrinogen level, plasma viscosity, circulating immune complexes, and quantitative immunoglobulin levels) in 22 human immunodeficiency virus-infected individuals. The severity of conjunctival disease was associated with increased zeta sedimentation ratios (a measure of red cell aggregation) and fibrinogen levels. The presence of cotton-wool spots was also associated with higher fibrinogen levels. Plasma viscosity and quantitative IgG levels were above normal levels in most patients, although a relationship to disease severity was not established. Altered blood flow may contribute to vascular damage and ocular ischemic lesions in patients with human immunodeficiency virus infection.

Adult↗
PubMed1990

Feline immunodeficiency virus and feline leukemia virus infections and their relationships to lymphoid malignancies in cats: a retrospective study (1968-1988).

Sera from 353 cats with naturally occurring feline leukemia virus (FeLV) infection were collected in Boston, Los Angeles, New York City, and Seattle between 1968 and 1988. These sera were retrospectively assayed by enzyme-linked immunosorbent assay for antibodies to feline immunodeficiency virus (FIV). Fifty-one (14.4%) of the FeLV-positive sera had antibodies to FIV, indicating dual oncovirus and lentivirus infections. FIV infections were confirmed by Western blot analysis, antibodies against the 15 and 27 kDa proteins being used as definitive markers. FIV infection was diagnosed in one cat sampled in 1968 and in eight other cats sampled before 1975 in New York City. Illnesses exhibited by coinfected cats were similar to those of cats infected with FeLV only. Two unrelated cats with multicentric fibrosarcomas were found to be simultaneously infected with FIV, FeLV, and feline sarcoma virus. FIV was less contagious than FeLV in 73 cats residing in an exposure household between 1977 and 1980 as determined by evaluation of sera collected sequentially. In this household, 15 resident cats became FeLV infected whereas no cats contracted FIV infection. Comparison of serologic results from 53 cats with leukemia/lymphoma and matched controls confirmed a strong correlation between FeLV viremia and leukemia/lymphoma. A significant correlation between FIV infection and lymphoproliferative malignancies was also found independent of FeLV infection.

Animals↗
PubMed1989

Feline lymphomas: immunological and cytochemical characterization.

The immunological and cytochemical phenotypes of five primary feline lymphomas and six feline lymphoma lines are reported. Thymic lymphomas induced by the Rickard strain of FeLV (FeLV-R) are of prothymocyte or (immature) cortical thymocyte origin, as these express terminal deoxynucleotidyl transferase, the guinea pig erythrocyte rosette receptor, Ia antigens, partial cortisone sensitivity, and nonspecific esterase. Lymphomas associated with other strains of FeLV form rosettes with guinea pig erythrocytes, frequently have Ia antigens and cytoplasmic nonspecific esterase, and probably originate from helper T-cells, monocyte/macrophages, or null cells. These data belie previous conclusions that FeLV leukemogenesis is restricted to mature T-cells; rather, the considerable heterogeneity in the surface and cytochemical phenotype of feline lymphomas probably reflects transformation of multipotent lymphoid or monocytoid precursors in the bone marrow by FeLV.

Animals↗