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Biomedical subjects

M A Fletcher

Publications and source records attributed to M A Fletcher.

At least 73 records · Page 4Linked to original sources
PubMed1994

Umbilical venous catheterizations: audit by the Study Group for Complications of Perinatal Care.

The Study Group for Complications of Perinatal Care, through 13 of its participating neonatal intensive care units, conducted a prospective audit to describe contemporary use of umbilical venous catheters (UVCs) over 3 months in 1951 admissions. Frequency of UVC attempts was 15.5% for all patients and greatest (50%) in patients of 1000 g or less birthweight (BW), with a wide range of frequency by institution and by BW grouping. Institutions with more 1500 g or less BW infants tended to use UVCs more frequently. The most common reason for placement was general intravascular access. A variety of fluids were infused, and in most cases heparin was employed. Mean duration of use was 4.4 days for all patients and longest (5.5 days) in infants in the 1001 to 1500 g BW group. The most common reason for UVC removal was lack of further need. UVCs appear to be used more commonly and for a longer duration than is currently recommended. There is a need for a prospective, randomized trial to assess the risks properly and maximize the benefits of UVC usage.

Canada↗
PubMed1994

Umbilical arterial catheter use: report of an audit conducted by the Study Group for Complications of Perinatal Care.

The Study Group for Complications of Perinatal Care through 13 of its participating neonatal intensive care units conducted an audit of umbilical artery catheter (UAC) use over 3 months. Of 1941 patient admissions, 582 (30%) had a UAC inserted and left in place for a mean of 4.9 days. The mean supplemental oxygen concentration (FIO2) at removal was 0.35 with over 55% of UACs remaining in place until FIO2 was less than 0.26. Institutional practices varied widely for positioning the catheter tip, use of heparin, and types of infusates, as did the frequency of adverse events that prompted removal of the UAC. Most institutions with multiple physicians found less consistency in practice patterns within their own units than presumed prior to the audit. Just two institutions preferred catheter placement in the abdominal aorta (low) with the others selecting a low site only after detecting a malposition below the initially sought thoracic level. All but one group routinely used heparin, although in varying concentrations and total doses. Patient weight and catheter duration were inversely correlated, with smaller patients having catheters left in place for significantly longer periods (P < 0.01). Similarly, smaller patients had a higher likelihood of catheter removal because of an adverse event; the adverse events were not necessarily related to longer duration. A significant relationship existed between positioning a catheter tip in the abdominal aorta and removal for adverse events (P < 0.05).

Catheterization, Peripheral↗
PubMed1994

Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression.

Among a group of 70 individuals who met the criteria established by the Centers for Disease Control and Prevention (Atlanta) for chronic fatigue syndrome (CFS), 12%-28% had serum levels exceeding 95% of control values for tumor necrosis factor (TNF) alpha, TNF-beta, interleukin (IL) 1 alpha, IL-2, soluble IL-2 receptor (sIL-2R), or neopterin; overall, 60% of patients had elevated levels of one or more of the nine soluble immune mediators tested. Nevertheless, only the distributions for circulating levels of TNF-alpha and TNF-beta differed significantly in the two populations. In patients with CFS--but not in controls--serum levels of TNF-alpha, IL-1 alpha, IL-4, and sIL-2R correlated significantly with one another and (in the 10 cases analyzed) with relative amounts (as compared to beta-globin or beta-actin) of the only mRNAs detectable by reverse transcriptase-coupled polymerase chain reaction in peripheral-blood mononuclear cells: TNF-beta, unspliced and spliced; IL-1 beta, lymphocyte fraction; and IL-6 (in order of appearance). These findings point to polycellular activation and may be relevant to the etiology and nosology of CFS.

Adult↗
PubMed1994

Clinical and immunological changes in AIDS patients following adoptive therapy with activated autologous CD8 T cells and interleukin-2 infusion.

OBJECTIVES: (1) To determine the safety and feasibility of repetitive reinfusions of activated autologous CD8 cells followed by low-dose continuous interleukin (IL)-2 infusion in patients with AIDS. (2) To study the relationships between clinical responses, surface marker phenotypic distributions and cytokine expression patterns of both cultured CD8 cells and lymphocytes in the peripheral blood compartment. DESIGN: Six adult patients with Centers for Disease Control and Prevention group IV HIV-1 disease ranging from mild to severe, were studied. All patients were receiving zidovudine prior to and during the study period, and had initial CD4 and CD8 cell counts > 50 and 200 x 10(6)/l, respectively. METHODS: Autologous CD8 T cells (10(8)-10(10)) were reinfused five times after ex vivo culture and stimulation with phytohemagglutinin and recombinant (r) IL-2. The fifth such infusion was followed by 5 days of rIL-2 infusion. Phenotypes and cytokine expression patterns of the expanded cells were determined as well as serum levels of immune mediators throughout the study. RESULTS: Patients showed stable CD4 and CD8 cell counts, p24 antigenemia, and minimal toxicity over the 24-week protocol study. Clinical improvement was observed in lymphadenopathy (six out of six), oral hairy leukoplakia (three out of four), and Kaposi's sarcoma (KS; two out of two) in the patients studied. In vivo induction of detectable levels of bioactive acid-stable interferon (IFN)-alpha, but not of other cytokines studied, upon activated CD8 cell reinfusion was associated consistently with improvement of oral hairy leukoplakia. However, partial regression of KS was observed after the CD8 cell infusion cycles and without IFN-alpha induction. In one of the two patients studied, KS regression was associated with decreased IL-1 alpha serum levels. In the other patient, who had failed previous IFN-alpha therapy, KS regression was observed after a decline in reinfused CD8 cell-associated gene expression of tumor necrosis factor (TNF)-beta. Both IL-1 alpha and TNF-beta are growth factors for KS cells. CONCLUSIONS: These observations demonstrate the feasibility and safety of ex vivo CD8 cell activation, expansion, and reinfusion, and rIL-2 infusion in AIDS patients. The findings in this Phase I trial suggest potential clinical efficacy and encourage Phase II trials. The correlations obtained between clinical and immunological states could contribute to an understanding of the relationship between CD8 T-cell function and HIV-1-associated disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Distress, denial, and low adherence to behavioral interventions predict faster disease progression in gay men infected with human immunodeficiency virus.

This study examined psychological prediction of 2-year disease progression in gay men after finding out their human immunodeficiency virus (HIV) serostatus. Psychological and immune status of asymptomatic gay men who did not know their HIV serostatus was monitored during the 5 weeks before and after serostatus notification. The men were randomly assigned to an exercise. cognitive-behavioral stress-management intervention, or control group. At 2-year follow-up for the 23 men who turned out to be seropositive. 9 had developed symptoms, including 5 with acquired immune deficiency syndrome--4 of whom died. Distress at diagnosis, denial (5 weeks post-diagnosis minus pre-diagnosis). and low adherence during interventions were significant predictors of 2-year disease progression. Denial and adherence remained significant predictors of disease progression even after controlling for CD4 number at entry. Furthermore. change in denial was significantly correlated with immune status 1 year later; l-year immune status was significantly correlated with 2-year disease progression. The present study therefore demonstrates significant relations between psychological variables on the one hand and both immune measures and HIV-1 disease progression on the other. We conclude that distress, denial, and low protocol compliance predict subsequent disease progression.

Journal Article↗
PubMed1994

Exercise and psychoneuroimmunology.

Psychoneuroimmunology is the study of the interrelationships among psychological, neuroendocrine, and immunological parameters and is concerned with how these relationships may affect an individual's health. Substantial evidence indicates that exercise is associated with improvements in mental health, neuroendocrine, and immune functioning. We synthesize these effects of exercise and propose an "exercise and psychoneuroimmunology" model by which exercise may benefit the psychologic and immunologic sequelae of several chronic diseases. For the past several years we have been investigating exercise training interventions, based on our model, for individuals infected with the human immunodeficiency virus type 1 (HIV-1). These studies indicate that a moderate exercise training program may attenuate the adverse stressor-induced psychologic and immunologic changes for asymptomatic HIV-1 seropositive individuals. In addition, our research indicates that continued aerobic exercise training may result in increased CD4 cell counts, immune surveillance, and a potential for a slowing of disease progression. Other researchers have demonstrated similar beneficial effects of exercise for individuals infected with HIV-1 who are at more advanced stages of disease. Exercise within the context of psychoneuroimmunology appears to be a very promising approach to the treatment of illness and promotion of health.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Effect on lymphocyte subsets of clotting factor therapy in human immunodeficiency virus-1-negative congenital clotting disorders. The Transfusion Safety Study Group.

Patients with hemophilia A without human immunodeficiency virus type 1 (HIV-1) infection have lower CD4+ counts and CD4+/CD8+ ratios than controls. This is usually interpreted as a therapy-induced immunodeficiency. Our data re-examine the effect of therapy on peripheral blood mononuclear cell immunophenotypic subpopulations in all congenital clotting disorders. Since late 1985 we have prospectively observed HIV-1 uninfected persons with all types and severity of disorder. Controls were household members without clotting disorders or HIV-1 infection. Analyses of immunophenotype and treatment included a longitudinal random effects model. Compared with controls, age-adjusted CD4+ counts were significantly lower in treated patients (P < .0001) and in patients with all types of clotting disorders who were seldom or never treated (P = .0005). Significantly lower values among both treated and untreated clotting disorder subjects (P < .05) were likewise found for total lymphocytes, several other T-cell subsets, and the CD4+/CD8+ ratio. For most indexes, including the CD4+ count and CD4+/CD8+ ratio, the type of clotting deficiency was not a significant variable. Comparing persons who had no or minimal therapy with those having the most showed increases in CD8+ (P = .0017) and CD20+ CD21- counts (P = .0255), and a lower CD20+ CD21+/CD20+ ratio (P = .0106) in the latter. Controls and persons with clotting disorders differ in CD4+ count. Among those with clotting factor disorders, there is no difference attributable to type of clotting disorder or factor therapy. Large amounts of treatment increased CD8+ and CD20+ CD21- counts, but were not associated with a change in CD4+ count.

Antigens, CD↗
PubMed1993

Lipopolysaccharide detoxification by endotoxin neutralizing protein.

Endotoxin neutralizing protein (ENP), a recombinant form of the anti-lipopolysaccharide factor that was isolated from amebocytes of the American horseshoe crab, Limulus polyphemus, detoxifies lipopolysaccharide (LPS) both in vitro and in vivo. Using the Limulus amebocyte lysate assay, LPS was detoxified by ENP at a 1 to 1 weight ratio (1:1). When isolated rat aortic rings were preincubated for 16 hr with either LPS or LPS/ENP (1:5), only aortas in the LPS/ENP group contracted normally under norepinephrine stimulation. To show that detoxification of a lethal amount of LPS (18 mg/kg, LD50 at 48 hr) persists in vivo, LPS/albumin (1:1) or LPS/ENP (1:1) mixtures were preincubated (30 min, 37 degrees C) and then injected intravenously into rats. In the 8 hr after injection, LPS/ENP challenged rats, in contrast to their LPS/albumin injected counterparts, had significantly fewer physical signs of acute LPS toxicity (P < 0.001). At 48 hr after challenge, all LPS/ENP treated rats survived (P < 0.01 vs LPS/albumin), and with significantly less weight loss (P < 0.001 vs LPS/albumin challenged survivors). At necropsy, the LPS/ENP group was free of typical LPS-induced gross organ lesions, notably in the liver, spleen, gut-associated lymphoid tissue (GALT), and small intestine. By microscopic examination, lymphocytic necrosis in the spleen and GALT of the LPS/ENP treated survivors was significantly milder than that in the LPS/albumin challenged survivors, although the degree of hepatocellular necrosis and small intestinal enteritis was similar. LPS-neutralizing proteins such as ENP may be useful in treating LPS toxicity.

Amino Acid Sequence↗
PubMed1993

The esterified plasma fatty acid profile is altered in early HIV-1 infection.

Previous studies have shown that alterations in micronutrient utilization occur in patients with Acquired Immune Deficiency Syndrome. In this study, total plasma fatty acid composition was measured in 36 homosexual men infected with the Human Immunodeficiency Virus 1 (HIV-1) and in 17 HIV-1 seronegative homosexual men in order to evaluate differences associated with early HIV-1 infection. Immunologic assessment included CD4 cell number count and lymphocyte blastogenesis in response to the mitogens phytohemagglutinin (PHA) and pokeweed (PWM). The mean total amount of omega 6 polyunsaturated fatty acids (18:2 and 20:4) was significantly lower in the HIV-1 seropositive subjects (38 +/- 8.1% SD) as compared to HIV-1 seronegative subjects (43 +/- 4.2%; P = 0.0027). This was also reflected in a higher level of total saturated fatty acids (16:0 and 18:0) in HIV-1 seropositive subjects (30 +/- 2.2% vs. 26 +/- 2.8%; P = 0.0001). The ratio of linoleic to arachidonic acid (18:2 to 20:4) was higher in the HIV-1 seropositive group (6.76 +/- 4.88) compared to the HIV-1 seronegative group (4.86 +/- 1.37; P = 0.0213). The response to PHA in seropositive subjects correlated inversely with total plasma omega 6 fatty acids (r = -0.36; P = 0.027), and directly with the 18:2 to 20:4 ratio (r = 0.33; P = 0.046). CD4 cell counts and the response to PWM did not correlate with plasma fatty acid levels in HIV-1 seropositive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Structural features of two T-cell-specific genes that suggest a potential role in HTLV-I-associated pathology.

The Rpt-1 gene product is an intranuclear protein expressed by CD4+ T-cells, which may regulate expression of the interleukin-2 receptor. Structural analysis of Rpt-1 reveals structural motifs that are shared by a group of transcriptional regulatory proteins with oncogenic potential. We suggest that altered expression of Rpt-1 may be associated with HTLV-I-dependent T-cell leukemias.

Amino Acid Sequence↗
PubMed1993

Effects of retroviral infections on immune function in African-American intravenous drug users.

OBJECTIVES: To determine the effect of retrovirus infection and co-infection, and intravenous substance use, on immune function in African-Americans. DESIGN: A cohort of South Florida street-recruited African-American intravenous drug users formed the study population. The cohort consisted of 90 HIV-negative & human T-lymphotropic virus (HTLV)-negative, one HIV-negative & HTLV-I-positive, 11 HIV-negative & HTLV-II-positive, 79 HIV-positive & HTLV-negative, one HIV-positive & HTLV-I-positive and 21 HIV-positive & HTLV-II-positive individuals. The results reported are for the cross-sectional, baseline assessment of immune parameters. METHODS: Lymphocyte phenotypic distributions and functional markers, including proliferative response to mitogens and natural killer cell cytotoxicity, were determined. Serum immunoglobulin (Ig) levels were determined as a measure of B-cell activity. RESULTS: HTLV-II infection was associated with increases in CD8 lymphocyte count and serum Ig, but with no other significant immunologic changes. The distribution of CD4 and CD8 percentages, CD4:CD8 ratio, phytohemagglutinin (PHA) and pokeweed mitogen (PWM) reactivity, IgA and IgG for the four retrovirus serostatus groups suggested the possibility of interactive effects in the co-infected group, as demonstrated by a trend toward lower medians for CD4 and for PHA and PWM response and higher medians for IgG, IgA and CD8. Retrovirus-seronegative intravenous drug users had significantly impaired immune status compared with non-drug-using control individuals. CONCLUSIONS: Immunologic dysfunction attributable to HTLV-II infection was minor compared with HIV infection in this population. Study subjects who were co-infected with HIV and HTLV demonstrated more impairment of immune function than individuals with single retrovirus infections.

Adult↗
PubMed1992

Ring finger in the peroxisome assembly factor-1.

The peroxisome assembly factor-1 (PAF-1) is reported here to contain the signature subsequence for a ring finger motif in its carboxyl-terminus. This conserved subsequence in PAF-1 may be the key to a gene expression regulatory pathway important in peroxisome biogenesis.

Amino Acid Sequence↗
PubMed1992

Effect of age on human immunodeficiency virus type 1-induced changes in lymphocyte populations among persons with congenital clotting disorders. Transfusion Safety Study Group.

Children other than neonates infected with human immunodeficiency virus type 1 (HIV-1) have low rates of progression to acquired immunodeficiency syndrome (AIDS). Through 1989, 5.3% of 95 infected hemophiliacs aged 5 to 13 years developed AIDS, compared with 20.3% of 364 aged greater than or equal to 25 years. We asked whether the HIV-1 impact on peripheral blood mononuclear cell subpopulations differed with age using pairwise comparisons of uninfected and infected male children and adult hemophiliacs. Infected children had lesser reductions of total lymphocytes than adults, but proportionately lower numbers of CD2+, CD4+, CD2+CD26+, and CD4+CD29+ counts. CD4+CD45RA+ cell counts were greater than twofold higher in uninfected and infected children than adults; with infection, the CD4+CD45RA+/CD4+ proportion increased by 1.4-fold in adults, but was unchanged in children. Infected adults had highly significantly increased total CD8+ counts; both age groups had elevated CD8+HLA-DR+ counts. Infected children had significantly higher total B-cell counts than infected adults, with a disproportionately lower number of resting B cells (CD20+CD21+). During 2 years of follow-up, infected children and adults had lymphocyte changes in the same directions and these were proportionately equal. The lower rate of HIV-1 progression in children may be partly associated with differences in lymphocyte populations compared with adults; functional properties of immune cells may be equally or more important.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Active coping style is associated with natural killer cell cytotoxicity in asymptomatic HIV-1 seropositive homosexual men.

The aim of this study was to examine the hypothesis that a psychosocial model was associated with natural killer cell cytotoxicity (NKCC) in HIV-1 infection. A sample of 62 HIV-1 seropositive homosexual men at CDC stages II and III were given a psychosocial battery assessing life stressors, social support, and coping style. A regression model quantifying these variables along with control variables for alcohol use, substance use and nutritional status was estimated. Active coping style was directly and positively associated with NKCC, and trends toward a negative relationship of life stressors and a buffering effect of social support on lives stressors were also observed. The results suggest that (1) control variables should be included with psychosocial models and that (2) psychosocial factors, especially active coping, may have a deterrent effect on loss of NK cell function. Active coping style may merit a specific focus in future research of life stressors and the immune system.

Adaptation, Psychological↗