Search PubMed⌕ Search

Biomedical subjects

D Cooper

Publications and source records attributed to D Cooper.

At least 55 records · Page 3Linked to original sources
PubMed1998

A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study.

CONTEXT: Current guidelines recommend that individuals infected with the human immunodeficiency virus type 1 (HIV-1) be treated using combinations of antiretroviral agents to achieve sustained suppression of viral replication as measured by the plasma HIV-1 RNA assay, in the hopes of achieving prolonged remission of the disease. However, until recently, many drug combinations have not led to sustained suppression of HIV-1 RNA. OBJECTIVE: To compare the virologic effects of various combinations of nevirapine, didanosine, and zidovudine. DESIGN: Double-blind, controlled, randomized trial. SETTING: University-affiliated ambulatory research clinics in Italy, the Netherlands, Canada and Australia (INCAS). PATIENTS: Antiretroviral therapy-naive adults free of the acquired immunodeficiency syndrome with CD4 cell counts between 0.20 and 0.60x10(9)/L (200-600/microL). INTERVENTION: Patients received zidovudine plus nevirapine (plus didanosine placebo), zidovudine plus didanosine (plus nevirapine placebo), or zidovudine plus didanosine plus nevirapine. MAIN OUTCOME MEASURE: Plasma HIV-1 RNA. RESULTS: Of the 153 enrolled patients, 151 were evaluable. At week 8, plasma HIV-1 RNA levels had decreased by log 2.18, 1.55, and 0.90 in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.05). The proportions of patients with plasma HIV-1 RNA levels below 20 copies per milliliter at week 52 were 51%, 12%, and 0% in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.001). Viral amplification was attempted in 59 patients at 6 months. Viral isolation was unsuccessful in 19 (79%) of 24, 10 (53%) of 19, and 5 (31%) of 16 patients in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively. Among patients from whom virus could be amplified, resistance to nevirapine was found in all 11 patients receiving zidovudine plus nevirapine and in all 5 patients receiving triple drug therapy. Rates of disease progression or death were 23% (11/47), 25% (13/53), and 12% (6/51) for the zidovudine plus nevirapine, zidovudine plus didanosine, and triple drug therapy groups, respectively (P=.08). CONCLUSIONS: Triple drug therapy with zidovudine, didanosine, and nevirapine led to a substantially greater and sustained decrease in plasma viral load than the 2-drug regimens studied. Our results also suggest that suppression of viral replication, as demonstrated by a decrease in the plasma HIV-1 RNA load below the level of quantitation of the most sensitive test available, may at least forestall the development of resistance.

Adult↗
PubMed1998

Functional redundancy and gustatory development in bdnf null mutant mice

In the mouse nasopalate papilla and in the trenches of the foliate and vallate papillae, taste buds accumulated primarily during the first 2 weeks after birth. Null mutation for brain-derived neurotrophic factor caused extensive death of embryonic taste neurons, with the secondary outcome that most taste buds failed to form. However not all taste neurons died; functional redundancy rescued a variable number. The primary research objective was to identify the likely site of the taste neuron rescue factor that substituted for BDNF. In this quest taste bud abundance served as a useful gauge of taste neuron abundance. The proportion of taste buds that developed was variable and uncorrelated among the nasopalate, vallate, and foliate gustatory papillae within each bdnf null mutant mouse. Thus, in spite of shared IXth nerve innervation, the vallate and foliate papillae independently varied in residual gustatory innervation. This variation rules against the rescue of gustatory neurons by system-wide factors or by factors acting on the IXth ganglion or nerve trunk. Therefore it is likely that surviving BDNF-deprived taste neurons were stochastically rescued by a redundant neurotrophic factor at the level of the local gustatory epithelium. These findings broaden the classic expectation that target tissue supplies only a single neurotrophic factor that can sustain sensory (taste) neurons.

Journal Article↗
PubMed1998

The morphogenesis of mouse vallate gustatory epithelium and taste buds requires BDNF-dependent taste neurons

The developmental absence of brain-derived neurotrophic factor (BDNF) in null mutant mice caused three interrelated defects in the vallate gustatory papilla: sparse innervation, a reduction in the area of the gustatory epithelium, and fewer taste buds. On postnatal day 7, the stunted vallate papilla of bdnf null mutant mice was 30% narrower, the trench walls 35% reduced in area, and the taste buds 75% less abundant compared with wild-type controls. Quantitative assessment of innervation density was carried out to determine if the small trench walls and shortage of taste buds could be secondary consequences of the depletion of gustatory neurons. The diminished gustatory innervation was linearly associated with a reduced trench wall area (r=+0.94) and fewer taste buds (r=+0.96). Residual taste buds were smaller than normal and were innervated by a few surviving taste neurons. We conclude that BDNF-dependent taste neurons contribute to the morphogenesis of lingual gustatory epithelia and are necessary for both prenatal and postnatal mammalian taste bud formation. The gustatory system provides a conspicuous example of impaired sense organ morphogenesis that is secondary to sensory neuron depletion by neurotrophin gene null mutation.

Journal Article↗
PubMed1998

Functional redundancy and gustatory development in bdnf null mutant mice.

In the mouse nasopalate papilla and in the trenches of the foliate and vallate papillae, taste buds accumulated primarily during the first 2 weeks after birth. Null mutation for brain-derived neurotrophic factor caused extensive death of embryonic taste neurons, with the secondary outcome that most taste buds failed to form. However not all taste neurons died; functional redundancy rescued a variable number. The primary research objective was to identify the likely site of the taste neuron rescue factor that substituted for BDNF. In this quest taste bud abundance served as a useful gauge of taste neuron abundance. The proportion of taste buds that developed was variable and uncorrelated among the nasopalate, vallate, and foliate gustatory papillae within each bdnf null mutant mouse. Thus, in spite of shared IXth nerve innervation, the vallate and foliate papillae independently varied in residual gustatory innervation. This variation rules against the rescue of gustatory neurons by system-wide factors or by factors acting on the IXth ganglion or nerve trunk. Therefore it is likely that surviving BDNF-deprived taste neurons were stochastically rescued by a redundant neurotrophic factor at the level of the local gustatory epithelium. These findings broaden the classic expectation that target tissue supplies only a single neurotrophic factor that can sustain sensory (taste) neurons.

Accessory Nerve↗
PubMed1998

The morphogenesis of mouse vallate gustatory epithelium and taste buds requires BDNF-dependent taste neurons.

The developmental absence of brain-derived neurotrophic factor (BDNF) in null mutant mice caused three interrelated defects in the vallate gustatory papilla: sparse innervation, a reduction in the area of the gustatory epithelium, and fewer taste buds. On postnatal day 7, the stunted vallate papilla of bdnf null mutant mice was 30% narrower, the trench walls 35% reduced in area, and the taste buds 75% less abundant compared with wild-type controls. Quantitative assessment of innervation density was carried out to determine if the small trench walls and shortage of taste buds could be secondary consequences of the depletion of gustatory neurons. The diminished gustatory innervation was linearly associated with a reduced trench wall area (r = +0.94) and fewer taste buds (r = +0.96). Residual taste buds were smaller than normal and were innervated by a few surviving taste neurons. We conclude that BDNF-dependent taste neurons contribute to the morphogenesis of lingual gustatory epithelia and are necessary for both prenatal and postnatal mammalian taste bud formation. The gustatory system provides a conspicuous example of impaired sense organ morphogenesis that is secondary to sensory neuron depletion by neurotrophin gene null mutation.

Animals↗
PubMed1998

Suppressed PHA activation of T lymphocytes in simulated microgravity is restored by direct activation of protein kinase C.

Utilizing clinostatic rotating wall vessel (RWV) bioreactors that simulate aspects of microgravity, we found phytohemagglutinin (PHA) responsiveness to be almost completely diminished. Activation marker expression was significantly reduced in RWV cultures. Furthermore, cytokine secretion profiles suggested that monocytes are not as adversely affected by simulated microgravity as T cells. Reduced cell-cell and cell-substratum interactions may play a role in the loss of PHA responsiveness because placing peripheral blood mononuclear cells (PBMC) within small collagen beads did partially restore PHA responsiveness. However, activation of purified T cells with cross-linked CD2/CD28 and CD3/CD28 antibody pairs was completely suppressed in the RWV, suggesting a defect in signal transduction. Activation of purified T cells with PMA and ionomycin was unaffected by RWV culture. Furthermore, sub-mitogenic doses of PMA alone but not ionomycin alone restored PHA responsiveness of PBMC in RWV culture. Thus our data indicate that during polyclonal activation the signaling pathways upstream of PKC activation are sensitive to simulated microgravity.

Antigen-Antibody Reactions↗
PubMed1998

Plasma esterase (ES) polymorphism in the tammar wallaby, Macropus eugenii.

The major plasma esterase in the tammar wallaby was identified as a carboxylesterase by inhibition studies and polymorphism with six variants was observed by isoelectric focusing (pH 4.2-4.9), followed by staining for esterase activity. Family studies demonstrated an inheritance of six codominant alleles, ESA,B,C,D,E,F, and population studies revealed marked differences in the allele frequencies in five Australian populations of tammar wallabies.

Animals↗
PubMed1998

Lack of reactivity to CMV pp65 antigenemia testing in a patient with CMV disease following allogeneic bone marrow transplant.

Pre-emptive antiviral therapy based on the early detection of CMV infection is an important strategy for the prevention of CMV disease following allogeneic BMT. Accepted methods for early detection of CMV infection include viral culture of blood or bronchial lavage specimens or CMV pp65 antigenemia testing of peripheral blood specimens. We describe a patient with aplastic anemia with worsening liver transaminases after allogeneic bone marrow transplantation who had repeated negative tests for CMV pp65 antigenemia despite positive viral blood cultures. Re-examination of peripheral blood samples with a different pp65 antibody pool revealed the presence of high levels of CMV in peripheral blood leukocytes, confirming a lack of reactivity to the original antibody pool. Following institution of antiviral therapy, a prompt reduction in the number of pp65 antigen-positive peripheral blood leukocytes paralleled a reduction in abnormal transaminases. The practical implications of these findings are discussed.

Adult↗
PubMed1998

Effects of long-term oral treatment with leflunomide on allergic sensitization, lymphocyte activation, and airway inflammation in a rat model of asthma.

BACKGROUND: Short-term treatment with leflunomide is effective in suppressing antigen-specific antibody production and allergen-induced bronchoconstriction after sensitization. This agent may thus have a role in future primary prevention strategies in allergic disease. OBJECTIVE: The current study aimed to determine whether long-term oral treatment with leflunomide prevents allergic sensitization permanently. METHODS: After sensitization with ovalbumin, six groups of rats (n = 31) were treated daily with leflunomide or diluent for up to 30 days. Ovalbumin-specific IgE and IgG were determined weekly for at least 2 weeks after cessation of treatment. T lymphocytes from another 21 animals were stimulated ex vivo with ovalbumin or concanavalin A. RESULTS: Ovalbumin-specific IgE and IgG were lower during treatment with leflunomide compared with controls (P < 0.002) but increased after the cessation of treatment. Antigen-specific T-cell proliferation was decreased in cells obtained from leflunomide treated animals (P < 0.05), but not when stimulated with concanavalin A. Eosinophil (P < 0.0001) and neutrophil (P < 0.02) numbers in bronchoalveolar lavage 24 h after allergen challenge were lower in the leflunomide treated animals. CONCLUSIONS: Leflunomide prevents antigen-specific immunoglobulin production after sensitization during treatment, inhibits allergen-induced airway inflammation and diminishes antigen-specific T lymphocyte proliferation.

Administration, Inhalation↗
PubMed1998

A randomized, double-blind trial of valaciclovir prophylaxis for cytomegalovirus disease in patients with advanced human immunodeficiency virus infection. AIDS Clinical Trials Group Protocol 204/Glaxo Wellcome 123-014 International CMV Prophylaxis Study Group.

Cytomegalovirus (CMV) disease is a common complication of advanced human immunodeficiency virus (HIV) infection. Administration of oral valaciclovir, a valine ester of acyclovir, achieves sufficient plasma acyclovir levels to inhibit many clinical isolates. Acyclovir has been associated with enhanced survival in AIDS but not with CMV disease prevention. CMV-seropositive patients (1227) with CD4 cell counts <100/mm3 were enrolled in a randomized, double-blind trial. Valaciclovir, 8 g/day, was compared with acyclovir, 3.2 or 0.8 g/day, for CMV prevention; all three arms were compared for survival. The confirmed CMV disease rate was 11.7% among valaciclovir recipients and 17.5% in the pooled acyclovir arms, a 33% reduction in risk. Time to confirmed CMV disease was significantly longer for the valaciclovir group (P = .03). A trend toward earlier mortality for valaciclovir recipients was seen (P = .06). Toxicity and earlier medication discontinuation were more common in this group. Valaciclovir significantly reduces the risk of CMV disease. Further exploration of a better-tolerated dose is warranted.

AIDS-Related Opportunistic Infections↗
PubMed1998

Primary HIV-1 infection: a review of clinical manifestations, immunologic and virologic changes.

In the past few years, major advances have been made in the field of primary HIV-1 infection. Several studies have reevaluated the clinical syndrome. The emergence of new molecular laboratory techniques has permitted a detailed analysis of viral dynamics and subsequent immunologic changes. Measurements of subsets of T-lymphocytes have allowed greater insight into the early pathogenesis of HIV-1 disease. There is now evidence that HIV-1-specific cytotoxic T-lymphocytes occur early during primary HIV-1 infection and are probably the most important immune defense against HIV-1. However, HIV-1 immune escape mutants have been identified during primary infection, which may be one reason for the failure of the immune system to completely eradicate the virus. Cytokines have been shown to play a role in primary HIV-1 infection, and the therapy of primary infection has gained more interest due to the introduction of potent triple combinations, including protease inhibitors.

AIDS Serodiagnosis↗
PubMed1998

Effects of 14 d of covert substitution of olestra for conventional fat on spontaneous food intake.

We conducted a double-blind, placebo-controlled, within-subject crossover study to investigate the effects of covert substitution of olestra, a non-energy-containing fat replacer, for conventional fat on food selection and energy intake in lean and obese men and women. Fifty-one subjects [BMI (kg/m2): 19-36; age: 25-63 y] were studied during two 14-d treatment periods (olestra and placebo), with a 7-d washout between feeding periods. During the intervention periods all foods were provided to the subjects. The aim was to produce a 10% dilution of total energy intake by replacing conventional triacylglycerol with olestra. To accomplish this, subjects were required to consume core foods providing 20-35 g olestra (depending on estimated energy needs) or the same foods containing placebo triacylglycerol. Additional items could be selected from foods that varied in macronutrient composition. When the two treatment periods were compared, total energy intake was 8% lower and fat intake 11% lower during the olestra period than during the placebo treatment period (P < 0.0001). Overall, subjects compensated for 15% of the fat and 20% of the total energy replaced by olestra. In absolute terms, subjects consumed 32% of total energy from fat during the placebo period and 27% of total energy from fat during the olestra period. Neither carbohydrate nor protein intake (g/d) differed between periods. The results did not differ as a function of BMI (lean compared with obese) or sex. Over a 2-wk period, covert substitution of olestra for conventional fat led to reductions in dietary fat intake and total energy intake in all subjects.

Adult↗
PubMed1998

Improving the yield of blood cultures for patients with early Lyme disease.

This study was designed to improve the recovery of Borrelia burgdorferi from blood. With the techniques used, B. burgdorferi could be recovered from the blood of approximately 25% of patients with early Lyme disease associated with erythema migrans. Serum was a better source of culture material than whole blood. The volume of blood cultured correlated directly with yield, particularly for patients with a single erythema migrans lesion.

Adult↗
PubMed1998

Gay men who engage repeatedly in unprotected anal intercourse with casual partners: the Sydney Men and Sexual Health Study.

We set out to determine the frequency and correlates of gay men's repeated unprotected anal intercourse with casual partners (UAI-C), defined as UAI-C reported at each of 3 annual interviews. By May 1997, 659 men had completed 3 annual interviews for the Sydney Men and Sexual Health (SMASH) cohort study. For the 3 6-month periods prior to each interview, 127 men reported UAI-C during one period only; 45 reported it during 2 periods; and 20 men reported it during all 3 periods. These 20 men who had repeated UAI-C were compared with 497 men who had anal intercourse with casual partners but did not report on all 3 occasions that they had UAI-C. Logistic regression revealed that repeated UAI-C was associated with HIV-positive status, more casual partners, less favourable attitudes toward condoms and greater recreational drug use. Few gay men have repeated UAI-C but those who do run greater risk of HIV transmission.

Adult↗
PubMed1998

A survey of consultants treating upper aerodigestive tract cancer in the UK.

A study was undertaken to determine the current service provision for the treatment of upper aerodigestive tract (UAT) cancers in the UK. A postal questionnaire was sent to all consultant members of relevant specialist societies, with 1041 (74%) responding. Treatment of UAT cancer is widely dispersed with over 900 consultants from five major disciplines treating, on average, less than 10 cases per year. There were few regional or provider differences in the facilities and services available and in processes used for assessing patients. There is little systematic collection of data for audit or research and some consultants do not record stage. The involvement of other disciplines in the assessment process, use of joint clinics, counselling, specialist nursing and therapy services appears to be low. There is a need for rationalisation of head and neck cancer services; for more systematic collection of data for audit and research and for improvements in the use of joint clinics and support services.

Cancer Care Facilities↗
PubMed1997

Regulation of antigen-specific IgE, IgG1, and mast cell responses to ingested allergen by mucosal tolerance induction.

Mucosal administration of soluble protein Ags results in profound immunologic nonresponsiveness, characterized by reduced production of Th1 and Th2 cytokines and concomitant suppressed Ig production. It has been suggested that Th2 cells are required for the induction and maintenance of this tolerogenic state. In this study, we show that oral tolerance induction abrogates subsequent Th2-driven Ag-specific IgE and IgG1 responses, while intranasal tolerance induction only blocks the production of IgE, but not IgG1. Consistent with suppressed IgE serum levels, elevated IFN-gamma production was observed in the spleens of tolerized mice. Moreover, both oral and intranasal tolerance induction were found to inhibit intestinal mast cell responses upon subsequent priming and intragastric provocation. Transfer of total splenocytes or purified CD4+, but not CD8+, T cells from intranasally tolerized mice clearly suppressed ongoing Ag-specific IgE, but not IgG1, responses in primed recipients. In addition, coadministration of IFN-gamma-neutralizing Abs completely blocked the transfer of suppression to primed recipients. These results show that Th2 cells can be subjected to tolerance induction, by inducing cross-regulatory, IFN-gamma-producing CD4+ T cells. Moreover, our results point out differences in the regulation of T cell-dependent Ag-specific IgE and IgG1 responses.

Animals↗