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Biomedical subjects

M A Fletcher

Publications and source records attributed to M A Fletcher.

At least 37 records · Page 2Linked to original sources
PubMed1999

Disease progression, adherence, and response to protease inhibitor therapy for HIV infection in an Urban Veterans Affairs Medical Center.

Indinavir therapy has demonstrated promise in the treatment of HIV-1 infection in clinical trials; however, its efficacy in a U.S. Veterans Affairs Medical Center, where access to therapy is generally unimpeded, is unknown. A review of the Miami cohort was conducted for the year beginning May 1996 to evaluate response to indinavir plus two nucleoside analogues. Of 483 HIV-1-positive patients (97% male; mean age, 46.7+/-9.7 years), 266 were offered indinavir based on their having CD4 counts <200 cells/microl or viral loads >10,000 copies/ml. Of these patients, 36% were adherent and experienced significant reductions in viral loads (-93,325+/-147,911 copies/ml) and elevations in CD4+ (111+/-103 cells/microl) and CD8+ (225+/-338 cells/microl) T cell counts. Adherent patients with baseline CD4 counts <100 cells/microl were 4.5 times more likely to have follow-up viral loads >10,000 copies/ml than those with CD4 >200 cells/microl. Adherent patients with CD4 counts <100 cells/microl did not show evidence of immune "exhaustion" because they were equal to those with CD4 counts >200 cells/microl in their capacity to replenish CD4 cells. Nonadherence to the regimen resulted in loss of therapeutic benefit and suggested that strategies to enhance adherence may become an essential component of treatment.

Adult↗
PubMed1999

Cardiopulmonary and CD4 cell changes in response to exercise training in early symptomatic HIV infection.

PURPOSE: The purposes of the present study were to assess the effects of a 12-wk laboratory based aerobic exercise program on cardiopulmonary function, CD4 cell count, and physician-assessed health status among symptomatic pre-AIDS HIV-infected individuals (N = 28) and to assess the degree to which ill health was associated with exercise relapse. METHODS: Responses to graded exercise test, physician-assessed health status, and CD4 cell counts were determined at baseline and 12-wk follow-up for participants randomly assigned to exercise or control conditions, and reasons for exercise noncompliance were recorded. RESULTS: Approximately 61% of exercise-assigned participants complied (> 50% attendance) with the exercise program, and analyses of exercise relapse data indicated that obesity and smoking status, but not exercise-associated illness, differentiated compliant from noncompliant exercisers. Compliant exercisers significantly improved peak oxygen consumption (VO2peak; 12%), oxygen pulse (O2pulse; 13%), tidal volume (TV; 8%), ventilation (VE; 17%), and leg power (25%) to a greater degree than control participants and noncompliant exercisers (all P < 0.05). Although no group differences in health status were found, a significant interaction effect indicated that noncompliant exercisers' CD4 cells declined (18%) significantly, whereas compliant exercisers' cell counts significantly increased (13%; P < 0.05). CONCLUSION: We conclude that although aerobic exercise can improve cardiopulmonary functioning in symptomatic HIV-infected individuals with minimal health risks, attention to factors associated with exercise adherence is warranted.

Adult↗
PubMed1998

A bereavement support group intervention is longitudinally associated with salutary effects on the CD4 cell count and number of physician visits.

A randomized, controlled, clinical trial was conducted to examine the impact of a semistructured, 10-week, once weekly, 90-min/session bereavement support group intervention on immunological, neuroendocrine, and clinical health status in human immunodeficiency virus type 1-seropositive (HIV-1+) and HIV-1-seronegative (HIV-1-) homosexual men, compared to a standard of care control condition. A total of 119 homosexual men (74 HIV-1+ and 45 HIV-1-) were assessed at baseline, 10 weeks, and 6 months follow-up. At the 6-month follow-up assessment, the intervention groups exhibited significant beneficial effects compared to controls on changes in CD4 cell, total T-lymphocyte, and total lymphocyte counts, when baseline levels, antiretroviral medication use, CDC stage of disease, and other potentially confounding factors were accounted for. There was no statistically significant effect on the CD4/CD8 ratio or on the CD8 cell count. The effect on CD4 cell count was associated with group attendance and with changes in plasma cortisol level. Plasma cortisol levels decreased significantly among intervention subjects, compared to controls. A significantly reduced number of health care visits over the 6-month follow-up period among the intervention subjects supported the clinical relevance of the immunological changes observed for both HIV-1+ and HIV-1- individuals. These results indicate that behavioral interventions may have salutary immunological and clinical health effects following bereavement among HIV-1-infected individuals. The effect in HIV-1- individuals suggests that this bereavement support group intervention might have similar salutary effects in the general population. Potential effects of such interventions on clinical HIV disease progression are of interest and should be studied.

Adult↗
PubMed1998

Mild cognitive impairment and risk of mortality in HIV-1 infection.

HIV-1-associated cognitive impairment has only been preliminarily investigated for associations with mortality. The authors examined 119 HIV-1-positive homosexual men (asymptomatic: n = 96; early symptomatic: n = 23). At follow-up (to 3.5 years), there were 105 survivors and 14 nonsurvivors. Those at the 25th percentile in response speeds and in long-term memory retrieval accuracy were at 6.4 (P < 0.02) and 3.5 (P < 0.05) times increased mortality risk, respectively, of those at the 75th percentile--independent of baseline CDC clinical stage, CD4 cell count, hemoglobin level, antiretroviral and prophylactic medication use, and sociodemographics. Cognitive impairment should be identified early--for maximization of both functional status and survival time.

AIDS Dementia Complex↗
PubMed1998

Human diploid cell strains (HDCS) viral vaccines.

Since the development in 1961 by Hayflick and Moorhead of a human diploid cell strain (HDCS) culture system for isolating viruses, HDCS-derived human vaccines have been licensed worldwide for polio IPV and OPV (multiple strains), rabies (Pitman-Moore L503 3M strain); rubella (RA27/3 strain); measles (Edmonston-Zagreb strain); varicella-zoster (Oka strain); mumps (Rubini strain) and hepatitis A (HM-175, CR-326-F', and GBM strains). Many of these widely-used vaccines now have at least a 20-year record of safety after extensive, ongoing pharmacovigilance. Serious vaccine-associated events are rare, and appear to reflect the activity of the live viruses replicated in the HDCS or of the inactivated viruses or other proteins added during manufacture. There is no credible association of reactions to the HDCS substrate or a hypothetical contaminant derived from it.

Cell Line↗
PubMed1997

HIV-1 infection in women is associated with severe nutritional deficiencies.

Nutritional deficiencies may contribute to immune dysregulation, and have been shown to be sensitive markers of HIV-1 disease progression. Only limited information exists, however, regarding the nutritional profile of HIV-1-seropositive drug abusers. Immune and nutritional measurements were obtained in a subsample of 125 subjects from a larger cohort of drug users being followed for HIV-1 infection and cofactors of disease progression. Nutritional deficiencies, particularly vitamins A, E, and zinc, were widespread with up to 86% of the drug users exhibiting at least one nutritional alteration. Although immune parameters (CD4 count, CD8 count, beta2-microglobulin) were similar in the HIV-1-infected men and women, women had significantly poorer overall nutritional status, as measured by plasma proteins, which are considered to be sensitive markers of malnutrition. A comparison of individuals with advanced disease (CD4 count <200/mm3) revealed significantly lower levels of plasma prealbumin (p < .01), selenium, (p < .05), and greater deficiency of vitamins A (p < .01) and E (p < .05) in women than in men. The greater severity of nutritional deficiencies noted in HIV-1-infected women may be an important determinant of disease progression and survival.

Adult↗
PubMed1997

High risk of HIV-related mortality is associated with selenium deficiency.

To determine the independent contribution of specific immunologic and nutritional factors on survival in HIV-1 disease, CD4 cell count, antiretroviral treatment, plasma levels of vitamins A, E, B6, and B12 and minerals selenium and zinc were considered in relation to relative risk for HIV-related mortality. Immune parameters and nutrients known to affect immune function were evaluated at 6-month intervals in 125 HIV-1-seropositive drug-using men and women in Miami, FL, over 3.5 years. A total of 21 of the HIV-1-infected participants died of HIV-related causes during the 3.5-year longitudinal study. Subclinical malnutrition (i.e., overly low levels of prealbumin, relative risk [RR] = 4.01, p < 0.007), deficiency of vitamin A (RR = 3.23, p < 0.03), vitamin B12 deficiency (RR = 8.33, p < 0.009), zinc deficiency (RR = 2.29.1, p < 0.04), and selenium deficiency (RR = 19.9, p < 0.0001) over time, but not zidovudine treatment, were shown to each be associated with HIV-1-related mortality independent of CD4 cell counts <200/mm3 at baseline, and CD4 counts over time. When all factors that could affect survival, including CD4 counts <200/mm3 at baseline, CD4 levels over time, and nutrient deficiencies were considered jointly, only CD4 counts over time (RR = 0.69, p < 0.04) and selenium deficiency (RR = 10.8, p < 0.002) were significantly associated with mortality. These results indicate that selenium deficiency is an independent predictor of survival for those with HIV-1 infection.

Adult↗
PubMed1997

Cognitive-behavioral stress management decreases dysphoric mood and herpes simplex virus-type 2 antibody titers in symptomatic HIV-seropositive gay men.

This study tested the effects of a 10-week group cognitive-behavioral stress management (CBSM) intervention on mood and immunologic parameters in HIV-seropositive gay men whose disease had progressed to a symptomatic stage. Men were randomized to either CBSM or a modified waiting-list control group. The CBSM intervention significantly decreased self-reported dysphoria, anxiety, and total distress. Individuals who practiced relaxation more consistently had significantly greater drops in dysphoria. The intervention also decreased herpes simplex virus-Type 2 (HSV-2) immunoglobulin G antibody titers. The control group showed no significant changes in either mood or antibody titers. Individual difference analyses revealed that decreases in dysphoria significantly predicted lower HSV-2 antibody titers by the end of the 10-week period. Neither group displayed changes in HSV-Type 1 antibody titers or in CD4+ or CD8+ cell numbers.

Adult↗
PubMed1997

Coping self-efficacy buffers psychological and physiological disturbances in HIV-infected men following a natural disaster.

The importance of coping self-efficacy (CSE) appraisals on psychological and physiological functioning for HIV seropositive patients facing a severe environmental stressor was tested comparing 37 HIV-infected gay men and 42 healthy male control participants following Hurricane Andrew. Results suggested that greater levels of CSE were related to lower emotional distress and posttraumatic stress disorder (PTSD) symptoms in both groups. In addition, greater CSE was associated with lower norepinephrine to cortisol ratios in the HIV group but not in the healthy control group. Results are discussed in relation to the coping process for HIV-infected individuals specifically and chronically ill populations in general who face severe environmental stressors.

Adaptation, Psychological↗
PubMed1997

Change in CD4+ cell enumeration following aerobic exercise training in HIV-1 disease: possible mechanisms and practical applications.

Growing evidence suggests that routine physical activity, by individuals who are HIV-1 infected, may have significant impact on several important components of good health. Some of the physical benefits noted are: an increase in cardiopulmonary fitness, improved muscle function, and weight gain, while psychological benefits consisting of improved mood states and increased active coping behaviors have been observed. However, the emphasis of this paper is on the effects of exercise training on the enumeration of CD4+ cells in HIV/AIDS. A review of all the available literature revealed: (1) no decline in CD+ cell counts seen in any of the studies, regardless of the initial stage of disease, level of CD4+ cells, or symptomatology; (2) a trend toward an increase in the number of CD4+ cells in all but one study, with the more significant increases seen in those subjects at earlier stages of disease; and (3) the importance of homogeneous study samples when investigating the effects of exercise in a dynamic disease, such as HIV/AIDS. With regard to possible mechanisms, psychological stress has been implicated among the cofactors contributing to the immunological decline in HIV-1 disease. Good evidence was presented which supports the stress management role of exercise training as a means to explain the buffering of these suppressive stressor effects, thereby facilitating a return of the CD4+ cell count to more normal levels. We therefore believe that the observed elevation in the number of CD4+ cells actually represents a normalization of CD4+ cells. With regards to practical application, collectively these studies provide reason to encourage HIV-1 infected individuals to begin an exercise training program, preferably while they are in the early stages of disease, and in compliance with the suggested guidelines.

Acquired Immunodeficiency Syndrome↗
PubMed1997

A novel peptide-IgG conjugate, CAP18(106-138)-IgG, that binds and neutralizes endotoxin and kills gram-negative bacteria.

Although type-specific IgG directed to the O-polysaccharide antigen of bacterial lipopolysaccharide (LPS) is protective in most models of LPS or bacterial challenge, no currently available IgG binds to LPS from all gram-negative bacteria. The ability of a peptide-IgG conjugate, CAP18(106-138)-IgG, to bind and neutralize LPS, to kill gram-negative bacteria, and to protect in a sensitized mouse model of LPS toxicity was studied. CAP18(106-138)-IgG bound LPS from multiple gram-negative bacteria in four different binding assays. In a fluid-phase RIA, half-maximal binding of 5 microg/mL 3H-labeled LPS occurred at 5-10 microg/mL CAP18(106-138)-IgG, similar to binding with monoclonal type-specific IgG. CAP18(106-138)-IgG neutralized LPS, as assessed by LPS-induced coagulation of limulus amebocyte lysate and production of tumor necrosis factor in vitro, was bactericidal for a wide range of gram-negative bacteria, and decreased LPS-induced lethality in sensitized mice. Antibacterial peptide-IgG conjugates merit further study as a novel adjunctive therapy for gram-negative sepsis.

Animals↗
PubMed1997

Management of dermatologic complications of chronic graft versus host disease: a case study.

The purpose of this article is to illustrate a multidisciplinary team collaborative approach to the management of dermatologic complications related to chronic graft versus host disease (GVHD). GVHD is a complication of allogeneic bone marrow transplantation (BMT) and peripheral blood cell transplantation (BCT). The skin is affected in more than 80% of patients with chronic GVHD who received a BMT. Involvement can be limited or extensive and can seriously affect patient morbidity and mortality. Nursing care of the patient with chronic GVHD induces careful patient assessment, patient and family education, and interventions aimed at preventing or minimizing complications. A coordinated multidisciplinary team approach is essential for the successful management of chronic GVHD. Nurses play a critical role in coordinating the multiple disciplines involved in the care of patients with chronic GVHD.

Bone Marrow Transplantation↗
PubMed1996

Immunological correlates of disease severity in pediatric slow progressors with human immunodeficiency virus type 1 infection.

Pediatric slow progressors are a group of HIV-1-infected individuals who are homogeneous for route and length of infection and standard of care and are therefore amenable to cross-sectional population studies on the immunological correlates of disease progression. We report here that both clinical and immunological categorizations of pediatric slow progressors based on the 1994 CDC criteria for symptom and immunosupression severity levels yield similar immunological findings: declining proportions of CD4 T cells are associated with increasing proportions of CD8 and CD4-CD8- T cells and with declining IL-2, -5, and -10 production levels by peripheral blood cells in response to the T cell-dependent mitogen, phytohemagglutinin, but not to the T and B cell-dependent mitogen from pokeweed. The latter cross-sectional results point to potential prognostic and nosologic markers and therapeutic targets among HIV-infected pediatric slow progressors. Longitudinal studies will help to assess further the relevance of these findings.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Intrathecal synthesis of anti-sulfatide IgG is associated with peripheral nerve disease in acquired immunodeficiency syndrome.

Peripheral nervous system involvement in the acquired immunodeficiency syndrome (AIDS) can take the form of an acute or chronic inflammatory demyelinating polyneuropathy, polyradiculopathy, mononeuropathy multiplex, or autonomic neuropathy. There is no widely held consensus on the etiology of PNS or other neurological complications associated with HIV infection. We report here that PNS disease in HIV-infected individuals is associated with intrathecal synthesis of an antibody directed against sulfatide, a major component of myelin. The anti-sulfatide antibody is also present nonspecifically in serum. The antibody requires the presence of the 3-O-sulfogalactosyl residue for binding and recognizes preferentially the hydroxy fatty acid-containing form of sulfatide. Anti-sulfatide antibodies are therefore one of the humoral factors responsible for demyelinating diseases in AIDS patients.

Acquired Immunodeficiency Syndrome↗