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Biomedical subjects

W Holloway

Publications and source records attributed to W Holloway.

12 recordsLinked to original sources

Evolution of antifungal susceptibility among Candida species isolates recovered from human immunodeficiency virus-infected women receiving fluconazole prophylaxis.

The effect of fluconazole on the susceptibility of Candida isolates recovered from women infected with human immunodeficiency virus (HIV) was evaluated in a randomized, double-blind, placebo-controlled trial. Women with CD4(+) cell counts of < or =300 cells/mm(3) received either fluconazole (200 mg/week) or placebo as prophylaxis. The antifungal susceptibility of specimens was evaluated. One patient who received fluconazole and 2 patients assigned to placebo had Candida albicans isolates recovered that were resistant to fluconazole (MIC, > or =64 microg/mL). Eleven patients assigned fluconazole and 4 patients assigned placebo had non-albicans Candida strains (all Candida glabrata) recovered that were resistant to fluconazole. There was significant azole cross-resistance among the non-albicans Candida species isolates. Although the rate of azole resistance did not significantly increase after fluconazole prophylaxis, there was a trend toward more in vitro azole resistance in C. glabrata isolates from patients assigned fluconazole. Moreover, the majority of resistant vaginal isolates of Candida species were recovered after initiation of open-label fluconazole use.

AIDS-Related Opportunistic Infections↗

Efficacy testing of recombinant human immunodeficiency virus (HIV) gp160 as a therapeutic vaccine in early-stage HIV-1-infected volunteers. rgp160 Phase II Vaccine Investigators.

A phase II efficacy trial was conducted with recombinant human immunodeficiency virus (HIV) type 1 envelope glycoprotein gp160 (rgp160) in 608 HIV-infected, asymptomatic volunteers with CD4+ cell counts >400 cells/mm3. During a 5-year study, volunteers received a 6-shot primary series of immunizations with either rgp160 or placebo over 6 months, followed by booster immunizations every 2 months. Repeated vaccination with rgp160 was safe and persistently immunogenic. Adequate follow-up and acquisition of endpoints allowed for definitive interpretation of the trial results. There was no evidence that rgp160 has efficacy as a therapeutic vaccine in early-stage HIV infection, as measured at primary endpoints (50% decline in CD4+ cell count or disease progression to Walter Reed stage 4, 5, or 6) or secondary endpoints. A transient improvement was seen in the secondary CD4 endpoint for the vaccination compared with the placebo arm, but this did not translate into improved clinical outcome.

AIDS Vaccines↗

Key adhesion molecules are present on long podia extended by hematopoietic cells.

BACKGROUND: We recently reported that CD34(+) hematopoietic cells and the KG1a cell line extend long, thin podia. These podia can dynamically extend and retract, often adhere to the substrate, and appear to connect cells up to 300 microm apart. The surface receptors found on these podia have not been described. METHODS: By using time-lapse fluorescent microscoscopy and immunostaining techniques, we describe a method for detecting surface receptors on these podia. This includes an in situ antibody staining procedure without fixing cells. RESULTS: We demonstrate, using CD34 selected mobilized peripheral blood cells and KG1a cells, that adhesion molecules known to play important roles in blood-cell migration and adhesion are present on these podia. These include: CD11a, CD18, CD29, CD34, CD45, CD49d, CD49e, and CD62L. Additionally, CD54 and CD44 were present on the podia extended by KG1a cells, but were not detectable on the primary CD34(+) cells. The integrin CD49d localized at the base of these podia in a time-dependent manner in KG1a cells. The frequency and morphology of these long podia on three myeloid leukemia-cell lines (KG1a, MV4-11, and AML-193) and a CD34-negative T-cell line (CEM) are also compared. KG1a and CEM cell lines extend long, dynamic podia that are similar to the podia on primary CD34(+) cells in morphology and adhesion molecule expression. The AML-193 and MV4-11 cell lines, however, did not extend these long podia. CONCLUSIONS: We describe a technique that provides a method of detecting surface receptors on thin cell membrane projections. These results support the likely role of these podia in cell migration and cell-cell communication.

Antigens, CD34↗

Evolution of vaginal Candida species recovered from human immunodeficiency virus-infected women receiving fluconazole prophylaxis: the emergence of Candida glabrata? Terry Beirn Community Programs for Clinical Research in AIDS (CPCRA).

The effect of fluconazole prophylaxis on the vaginal flora of 323 human immunodeficiency virus-infected women was evaluated in a multicenter, randomized, double-blind, placebo-controlled trial. Women with CD4 cell counts of < or = 300/mm3 received either 200 mg of fluconazole per week or placebo. Vaginal surveillance cultures were performed every 3 months. After a follow-up of 29 months, Candida albicans was recovered from 53% of patients receiving fluconazole and 68% of patients assigned placebo. Fluconazole was associated with a 50% reduction in the odds of being colonized with C. albicans but with higher rates for non-albicans Candida species. Candida glabrata was recovered from 40 women assigned fluconazole and 29 assigned placebo (relative odds, 1.96; 95% confidence interval, 0.98-3.94). Fluconazole had an early and persistent effect on the vaginal mycoflora, with the emergence of C. glabrata vaginal colonization within the first 6 months. The effect of fluconazole prophylaxis can be attributed to the reduction in vaginal C. albicans colonization; however, C. glabrata colonization rapidly supervened.

AIDS-Related Opportunistic Infections↗

Two new pseudopod morphologies displayed by the human hematopoietic KG1a progenitor cell line and by primary human CD34(+) cells.

A primitive human hematopoietic myeloid progenitor cell line, KG1a, characterized by high expression of the CD34 surface antigen has been observed to extend long, thin pseudopodia. Once extended, these pseudopods may take on one of two newly described morphologies, tenupodia or magnupodia. Tenupodia are very thin and form in linear segments. They adhere to the substrate, can bifurcate multiple times, and often appear to connect the membranes of cells more than 300 micrometer apart. Magnupodia are much thicker and have been observed to extend more than 330 micrometer away from the cell. Magnupods are flexible and can exhibit rapid dynamic motion, extending or retracting in a few seconds. During retraction, the extended material often pools into a bulb located on the pod. Both morphologies can adhere to substrates coated with fibronectin, collagen IV, and laminin as well as plastic. The CD34 and CD44 antigens are also present on the surface of these podia. Primary human CD34(+) cells from fetal liver, umbilical cord blood, adult bone marrow, and mobilized peripheral blood extend these podia as well. The morphology that these pseudopods exhibit suggest that they may play both sensory and mechanical roles during cell migration and homing after bone marrow transplantation.

Adult↗

Influenza.

Explore the source record for details and available documents.

Aged↗

Two brains, one child: interhemispheric information transfer deficits and confabulatory responding in children aged 4, 7, 10.

In an investigation of developmental trends in the ability to transfer information between the cerebral hemispheres, 138 children, ages 4, 7, and 10, viewed pictures presented to either the right or left hemisphere and were asked to describe what was viewed. Responses were socored for the number of accurate pictorial features reported (inclusion score), confabulation (erroneous embellishment), perceptual, semantic, and syntactic errors. Misses (failure to provide a response) were also noted. A preponderance of errors were found, such that 4-year olds engaged in a significant degree of confabulatory responding following right vs. left presentation. A significant inverse relationship was found between inclusion and confabulation such that the larger the gap in information reported the greater was the tendency to insert (confabulate) erroneous material. In addition, all children were given a tactile-shape recognition task employing both transfer and non-transfer conditions and requiring tactile exploration and visual recognition. Significantly more errors were found on the transfer vs. non transfer task among the 4-year olds only. In that deficits in information transfer were not complete but only partial, and given that significant intra-hemispheric (non-transfer) errors were also discovered, it was concluded that the hemispheres of children age 4 are not completely but only partially disconnected, and that intra-hemispheric (cortical) immaturity plays a significant role in the production of processing deficits.

Cerebral Cortex↗

In vitro and clinical evaluation of ceforanide.

Ceforanide, a new cephalosporin antibiotic with a long half-life (three hours), was evaluated for its antimicrobial activity, pharmacology, and clinical efficacy. Fifty-two patients with 56 infections due to susceptible organisms received ceforanide, 0.5 g, 1 g, or 2 g, intramuscularly or intravenously every 12 hours for four to 60 days (average: 14.1 days). The in vitro studies of our clinical isolates showed that 12.0 micrograms/ml or less of ceforanide inhibited all Streptococcus pneumoniae, beta hemolytic streptococci group A, B, F, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Hemophilus influenzae. After a 1 gram intramuscular dose, the mean peak serum concentration at one hour was 44.0 micrograms/ml, and at 12 hours was 3.8 micrograms/ml. After a 1 gram intravenous dose, the mean peak serum concentration was 65.0 micrograms/ml, and the mean trough serum concentration at 12 hours was 9.6 micrograms/ml. The infections treated included ten pneumonias, ten urinary tract infections, seven bacteremias, two osteomyelitis, and 35 skin-soft tissue infections. Of the 56 evaluable infections treated, 52 had a clinical cure with only four failures. Ceforanide was well tolerated, with no patients developing thrombophlebitis, or liver or renal abnormalities. Three patients developed abnormal Coombs' reactions and one had diarrhea.

Adolescent↗