PubMed Health⌕ Search

Biomedical subjects

K McIntosh

Publications and source records attributed to K McIntosh.

At least 37 records · Page 2Linked to original sources
PubMed1996

Randomized study of the tolerance and efficacy of high- versus low-dose zidovudine in human immunodeficiency virus-infected children with mild to moderate symptoms (AIDS Clinical Trials Group 128). Pediatric AIDS Clinical Trials Group.

The current dosage of zidovudine for children is 180 mg/m2 every 6 h. To investigate whether a lower dosage was equally effective, human immunodeficiency virus (HIV)-infected children (3 months to 12 years) with mild to moderate symptoms were randomly assigned to receive either high-dose (180 mg/m2/dose) or low-dose (90 mg/m2/dose) zidovudine (double-blind). Treatments were compared with respect to neuropsychologic function, survival, clinical and laboratory evidence of disease progression, and safety and tolerance. Four hundred twenty-six HIV-infected children were enrolled; median time for receipt of study drug was 35 months. Zidovudine in either dose was well tolerated, with no difference in efficacy or tolerance by treatment group using any clinical or laboratory parameter. In children with mild to moderate disease, a reduction of zidovudine to 90 mg/m2/dose will result in substantial cost savings and should be the recommended dose.

AIDS Dementia Complex↗
PubMed1996

Age- and time-related changes in extracellular viral load in children vertically infected by human immunodeficiency virus.

BACKGROUND: It is known that plasma or serum viral load is high in vertically HIV-infected children during the first year of life, but the changes in these titers after the first birthday have not been described. Information on the natural history of circulating extracellular virus will be useful in elucidating the pathogenesis of pediatric HIV infection and in using viral load measurement to guide prognosis and therapy. METHODS: We measured serum RNA by reverse transcriptase-polymerase chain reaction and immune complex-dissociated p24 antigen enzyme-linked immunosorbent assay over time in 48 unselected children followed in our clinics and analyzed the findings in relation to age and clinical outcome. RESULTS: In first-available samples from the 48 children there was a gradual reduction in HIV RNA values with increasing age, with a slope of -0.21 log copy/ml/year (P < 0.001, R2 = 0.6022). This downward trend was seen in subsets of children with all degrees of immunodeficiency. The mean slope of repeated HIV RNA measurements in individual children was similarly in a downward direction (slope -0.11 (P = 0.007 for difference from zero)). The slope was more negative in children who were younger at baseline. Immune complex-dissociated p24 antigen values were much less predictable and predictive. CONCLUSIONS: Viral load in vertically infected children, measured by reverse transcriptase-polymerase chain reaction, falls very gradually over time, descending from very high titers at the end of the first year, and reaching values seen in horizontally infected adults at approximately 5 years of age.

Adult↗
PubMed1995

Vertical transmission of human immunodeficiency virus type 1: autologous neutralizing antibody, virus load, and virus phenotype.

OBJECTIVE: To evaluate immunologic and virologic correlates of vertical transmission of human immunodeficiency virus type 1 (HIV-1). DESIGN: Case-control study. PATIENTS: Women who were prospectively enrolled in a natural history study of HIV-1 infection in women and infants. Sixteen HIV-1-infected women whose infants became infected were matched by CD4+ cell percentage and use of zidovudine during pregnancy with women whose infants did not become infected. MEASUREMENTS: Maternal autologous neutralizing antibody, virus load determined by RNA-polymerase chain reaction (RNA-PCR), and virus phenotype. RESULTS: Most women in both groups had low titers of autologous neutralizing antibody, and no difference in neutralizing titers was observed (range, < 4 to 181 in both groups). The HIV-1 copy number in maternal plasma was not significantly different in the two groups but was inversely correlated with maternal CD4+ cell percentage (p < 0.005). Five women in the transmitting group and four in the non-transmitting group had syncytium-inducing (SI) phenotype virus. Two infected infants had SI phenotype virus. The SI phenotype virus was associated with a greater HIV-1 copy number in maternal plasma (p < 0.05) and an increase in the mortality rate for the infants (p < 0.01). CONCLUSIONS: In women matched for CD4+ cell percentage, low titers of autologous neutralizing antibody, high virus load, and SI phenotype virus were not associated with an increased risk of transmission of HIV-1 to their infants.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Cross-linking of Fc gamma receptors activates HIV-1 long terminal repeat-driven transcription in human monocytes.

Elevation of the levels of circulating immune complexes frequently accompanies HIV-1 infection and is a prognostic indicator of clinical progression from asymptomatic infection to AIDS. Here we report that cross-linking of Fc gamma RI or Fc gamma RII by adherent human IgG or by specific anti-Fc gamma R mAb activates HIV-1 gene expression in the human monocytic cell line BF24 and increased HIV RNA expression in monocytes from HIV infected patients as assayed by reverse transcription-PCR. In THP-1 cells, Fc gamma R cross-linking induced NF-kappa B, which is known to bind to the regulatory region of the long terminal repeat (LTR) of HIV-1 and to activate HIV-1 transcription. Anti-TNF-alpha antibody but not anti-IL-1 beta antibody strongly inhibited both the induction of HIV-1-LTR-driven transcription and the induction of NF-kappa B by Fc gamma R cross-linking. These results indicate that Fc gamma R can mediate a TNF-alpha-dependent induction of HIV-1 gene transcription and suggest that immune complexes may contribute to the pathophysiology of HIV-1 infection by augmenting viral replication in monocytes.

Acquired Immunodeficiency Syndrome↗
PubMed1995

The prenatal exclusion test for Huntington's disease: experience in the west of Scotland, 1986-1993.

Information about the prenatal exclusion test for Huntington's disease (HD) has been given to an unselected series of couples who attended the genetic counselling clinic from 1986 onwards. Ten couples underwent 13 prenatal tests during this period with expressed intention of stopping a pregnancy if the result indicated a high risk (almost 50%) that the fetus carried the HD gene. Nine fetuses at nearly 50% risk of carrying the HD gene were identified but only six such pregnancies were terminated. In each of three high risk pregnancies which continued, the mother made a "final hour" decision not to undergo the scheduled, first trimester termination. In our experience, late reversal of a previous decision to undergo first trimester pregnancy termination for a genetic indication is uniquely frequent among couples who have undergone the prenatal exclusion test for HD.

Adult↗
PubMed1995

Vertical Transmission of HIV-1. Correlation with maternal viral load and plasma levels of CD4 binding site anti-gp120 antibodies.

Almost all childhood HIV-1 is now acquired through vertical transmission. Identifying factors that affect the rate of transmission may lead to the initiation of specific preventive strategies. In this study, antibody levels against different neutralizing epitopes on the envelope glycoprotein of HIV-1 (gp120) were measured in HIV-1-infected pregnant women that either transmitted HIV-1 to their infants (18 women) or did not (29 women). Differences in levels of antibodies directed against the monomeric gp120 molecule and against the V3 loop region of gp120 were not significantly different between the two groups studied. However, significant differences were observed in the levels of CD4 binding site antibodies, as determined by the ability of diluted maternal plasma to inhibit binding of the CD4 binding site monoclonal antibody F105 (mAb F105) to monomeric gp120. In addition, more nontransmitting mothers had low viral load as defined by having two or more negative HIV-1 viral cultures during pregnancy compared with transmitters. This pilot study suggests that in addition to higher viral load, low levels of CD4 binding site antibodies correlate with increased risk of HIV-1 vertical transmission. Passive immunotherapy with broadly neutralizing CD4 binding site antibodies should be considered as a strategy to reduce this risk.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Gastrostomy tube supplementation for HIV-infected children.

OBJECTIVE: Malnutrition is common in pediatric human immunodeficiency virus (HIV) infection, and little is known of effective nutritional interventions. We sought to determine whether enteral supplementation with gastrostomy tube feedings would provide improvements in weight, height, body composition, immune parameters, morbidity, and mortality. METHODS: We collected clinical data on 23 HIV-infected children who were fed chronically by gastrostomy tube. The main outcome measures included weight, height, triceps skinfold thickness (TSF), arm-muscle circumference (AMC), hospital days, caloric intake, and CD4-positive T-lymphocyte count. Each of these parameters was measured or evaluated at four points: 6 months before nasogastric tube feeding, at the time nasogastric tube feeding was initiated, at the time gastrostomy tube feeding was initiated, and 6 months after gastrostomy tube feedings began. RESULTS: Weight z score [-2.1 (0.14) to -1.58 (0.14)] and weight-for-height z score [-0.98 (0.16) to -0.15 (0.17)] improved with gastrostomy tube feedings. There was a trend toward improvement in weight z score with nasogastric tube feedings. Caloric intakes increased progressively with nasogastric and gastrostomy tube feedings. No improvement in height, TSF, AMC, hospital days, or CD4 counts was seen in the follow-up period. However, children who had the greatest increase in weight had the most improvement in fat stores (TSF) (r = .65, P = .002) and a decrease in hospital days after the gastrostomy tube was placed (r = -.48, P = .025). Higher age-adjusted CD4 counts and lower weight-for-height z scores at the time of enteral supplementation were significant predictors of a positive response to gastrostomy tube feedings (r = .85, P = .0001). Children who responded favorably had a 2.8-fold reduction in the risk of dying for every positive unit change in weight z score (P = .005). CONCLUSION: Gastrostomy tube supplementation for HIV-infected children can improve weight and fat mass when other oral methods fail. Weight gain is coincident with greater caloric intakes. HIV-infected children with higher CD4 counts and lower weight-for-height z scores are likely to respond favorably to gastrostomy tube feedings. Early nutritional intervention is indicated for HIV-infected children.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Oral administration of acetylcholine receptor: effects on experimental myasthenia gravis.

The abnormality in myasthenia gravis (MG) is a deficiency of acetylcholine receptors (AChRs) at neuromuscular junctions due to an antibody-mediated autoimmune attack. Although immunosuppressive drugs are usually beneficial in MG, they produce generalized suppression of the immune system. Treatment should specifically inhibit the immune response to AChR. Oral administration of an antigen may induce specific tolerance and has recently been tested for treatment of several cell-mediated experimental and human autoimmune diseases. In this study, we investigated the effects of oral administration of AChR in an experimental rat model of MG (EAMG), which is antibody mediated. Lewis rats were fed various doses of purified or unpurified Torpedo AChR, or a control antigen, ovalbumin (OVA). They were then immunized with AChR or OVA. We measured antibody responses to Torpedo AChR or OVA, autoantibody responses to rat AChR, cellular responses, cellular suppressive effects, and clinical status. Our results showed that AChR feeding prevented clinical signs of EAMG. It initially primed, then inhibited, antibody responses to foreign (Torpedo) AChR and self (rat) AChR, with a delayed onset. Cellular responses to AChR, measured by lymphocyte proliferation and interleukin-2 production, were markedly inhibited. The effects were dose dependent. Unpurified AChR given in comparable amounts was far less effective than pure AChR. OVA feeding had similar, but even more potent effects on humoral and cellular immune responses to OVA, but did not inhibit clinical EAMG or AChR responses. Moderate nonspecific suppression by splenic T cells from orally treated animals was demonstrated in vitro. We conclude that oral therapy is beneficial in EAMG and may prove effective in MG patients. Early priming and delayed inhibition suggest that a molecule with less immunogenic potential than intact AChR might be more effective as a therapeutic agent.

Administration, Oral↗
PubMed1994

Limitations of fractional shortening as an index of contractility in pediatric patients infected with human immunodeficiency virus.

Left ventricular fractional shortening (FS) is dependent on left ventricular preload and afterload, as well as contractility. Contractility may therefore not be accurately described by FS, especially in infants and children infected with human immunodeficiency virus (HIV), who tend to have abnormal left ventricular preload and afterload. We therefore examined the magnitude and clinical impact of the discrepancy between FS and contractility by assessment of 177 echocardiograms from 76 HIV-infected pediatric patients (median age, 1.9 years). The studies included simultaneous measurements of left ventricular FS, contractility, preload, and afterload. The correlation between contractility and FS was modest (r = 0.70; p < 0.001), and was weaker in children less than 2 years of age (r = 0.52) than in older children (r = 0.84). FS incorrectly predicted contractility in 46% of the studies; 43% with depressed FS (< 28%) had either normal (17/42) or enhanced (1/42) contractility. For 67% of echocardiograms, FS and contractility differed by > 1 SD, and for 36% the difference was > 2 SD. These differences remained after adjustment of FS for age or body surface area. Afterload was abnormal in 42% and preload in 21% of all echocardiograms. High preload predicted that FS would overestimate contractility (p = 0.002); high afterload predicted that FS would underestimate contractility (p < 0.001). The discrepancy between FS and contractility was larger among children who were younger, had more advanced HIV disease, or were not sedated during echocardiography. One third of children with congestive symptoms had normal contractility and depressed FS; the discrepancy was primarily due to loading conditions. We conclude that the high incidence of abnormal loading conditions in HIV-infected infants and children limits the usefulness of load-dependent FS for assessing contractility. Measurements of loading conditions and load-independent indexes, which more directly reflect contractility, allow a more accurate determination of myocardial status and may lead to better clinical management.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Blood culture in the first 6 months of life for the diagnosis of vertically transmitted human immunodeficiency virus infection. The Women and Infants Transmission Study Group.

Serial blood cultures over the first 6 months of life in 310 infants with vertical exposure to human immunodeficiency virus (HIV) in the Women and Infants Transmission Study were analyzed to determine their value for early diagnosis of HIV infection. Cultures were done at 0-7 days and 1, 2, 4, and 6 months of age: 55 infants were infected. Blood culture sensitivity in infected children was 24% (7/29) during the first week of life and 85%, 91%, 82%, and 88%, respectively, at 1, 2, 4, and 6 months. The sensitivity, specificity, and positive and negative predictive values of a single culture between 1 and 6 months of age were, respectively, 86.9%, 99.6%, 97.9%, and 97.5%. Two negative cultures between 1 and 6 months of age defined an uninfected infant with a specificity of 99.2%-100.0%. Blood culture done between 1 and 6 months of age in children of HIV-positive mothers is a sensitive and specific test for HIV infection, with high positive and negative predictive values.

Blood↗