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Biomedical subjects

D A Cooper

Publications and source records attributed to D A Cooper.

At least 127 records · Page 7Linked to original sources
PubMed1997

Olestra ingestion and retinyl palmitate absorption in humans.

This study examined the effect of olestra, a zero-calorie fat replacement, on the absorption of retinyl palmitate in humans. After a 30-d adaptation period during which they consumed 10 g olestra/d in potato chips under free-living conditions, 68 healthy male subjects were housed in a metabolic ward and given a single dose of retinyl palmitate (0.33 RDA) containing a trace amount of 3H-retinyl palmitate with a breakfast that contained 0, 8, 20 or 32 g of olestra and about 38 g of triglyceride. Blood was collected at defined intervals for 48 h and plasma analyzed for 3H-retinyl esters by HPLC and liquid scintillation spectrometry. There was no significant effect on retinyl palmitate absorption as determined from the area under the plasma 3H-retinyl esters concentration-time curve. However, an area under the plasma concentration-time curve in the 32-g olestra group that was 81% (mean value) or 70% (median value) of the area under the curve for the placebo group suggested that olestra may have affected retinyl palmitate absorption. Inclusion or exclusion of 13 high responders did not change the results.

Adult↗
PubMed1997

Olestra ingestion and dietary fat absorption in humans.

The effect of olestra, a zero-calorie fat replacement, on the absorption of dietary fat was determined with a dual-isotope technique in 67 healthy male subjects. After a 30-d adaptation period in which they consumed potato chips which delivered either 10 g/d olestra or 10 g/d triglyceride under free-living conditions, the subjects were housed in a metabolic ward and given 0, 8, 20 or 32 g olestra in potato chips. The chips were eaten as part of a breakfast containing about 38 g of fat, about 0.16 mg of 14C-triolein, and a nonabsorbable marker, 51CrCl3. Feces were collected for 7 d, and aliquots of the two daily collections containing the highest levels of 51Cr were oxidized. The CO2 was collected, and 14C content was determined by liquid scintillation spectrometry. The fractional absorption of 14C-triolein was calculated from the average ratios of 14C/51Cr dosed and measured in the feces. Olestra had a slight but significant dose-response effect on triglyceride absorption: the highest olestra dose (32 g) reduced absorption by 1.2%. This effect is not nutritionally significant with respect to either availability of essential fatty acids or energy intake.

Adult↗
PubMed1997

Evaluation of the potential for olestra to affect the availability of dietary phytochemicals.

It has been hypothesized that phytochemicals found in fruits and vegetables are responsible for the inverse association observed between diets high in fruits and vegetables and risk of certain chronic diseases and cancer. This paper assesses the potential for olestra to affect the absorption of dietary phytochemicals and estimates the effect of olestra on the availability of carotenoids when olestra-containing snacks and foods containing carotenoids are eaten in free-living diets. Experimental data compiled on the effects of olestra on the availability of 29 compounds, mainly nutrients and oral medications, showed that olestra affects the availability of only molecules having octanol-water partition coefficients greater than approximately 7.5. Partition coefficients compiled for 382 dietary phytochemicals showed that only two classes of phytochemicals, phytosterols and carotenoids, contain molecules with octanol-water partition coefficients in the range in which olestra could potentially affect bioavailability. The potential effect on the bioavailability of phytosterols would be <10% and would not be expected to be of concern inasmuch as the hypothesized benefit of consuming pharmacological amounts of phytosterols is to reduce cholesterol availability, a function also of olestra. A 5.9% reduction in the average effective beta-carotene intake was calculated for individuals eating olestra-containing snack foods in free-living diets. The calculation was made by assuming that carotenoid bioavailability would be reduced to the extent measured in human clinical studies each time olestra-containing snacks and carotenoid-containing foods are eaten together and that all snacks eaten are made with olestra. Among individuals with low carotenoid intakes (the lowest 10%) the calculated reduction was 6.0%; for heavy snack eaters (the top 10%) it was 9.5%. These effects on carotenoid bioavailability are similar to those that can occur with other dietary factors.

Adolescent↗
PubMed1997

Fertility and reproductive choice in women with HIV-1 infection.

OBJECTIVE: To measure fertility and birth rates and to describe the reproductive histories of women diagnosed with HIV-1 infection in Australia. METHODS: The medical records of 294 women with HIV-1 infection in four states of Australia were reviewed. Expected fertility and birth rates were calculated using national statistics. RESULTS: In the study population, 152 (52%) women had at least one pregnancy prior or subsequent to HIV-1 diagnosis. At maternal HIV-1 diagnosis, 71 (24%) women had a total of 106 children aged under 15 years. During the study period, 246 women were aged 15, 44 years and 58 (23%) of these became pregnant after HIV-1 diagnosis. Women whose exposure to HIV-1 was injecting drug use were twice as likely to become pregnant and more likely to have multiple pregnancies than women who did not report injecting drug use. The annual general fertility rate was 30 per 10,000 compared with 63 per 10,000 for the Australian female population aged 15-44 years, and the birth rate in women with HIV-1 infection was one-half that of the general female population. Of pregnancies confirmed after HIV-1 diagnosis, 47% were voluntarily terminated, a rate more than double that of the general population. All multiple terminations were among women whose exposure to HIV-1 was injecting drug use. CONCLUSIONS: Fertility and birth rates among women with HIV-1 infection are lower than the general population and the rate of termination higher. The results of this study provide a basis for the management of women with HIV-1 infection who are considering pregnancy.

Adolescent↗
PubMed1997

Increased frequency of CCR-5 delta 32 heterozygotes among long-term non-progressors with HIV-1 infection. The Australian Long-Term Non-Progressor Study Group.

BACKGROUND: The beta-chemokine receptor CCR-5 is used as a coreceptor by macrophage-tropic strains of HIV-1 to gain entry into CD4+ cells. OBJECTIVE: To determine the effect of a common 32 base-pair deletion mutation in the CCR-5 gene (CCR-5 delta 32) on progression of HIV infection to AIDS, and to assess the level of heterozygosity for this mutation in a well-defined group of long-term non-progressors (LTNP). PARTICIPANTS: Sixty-four HIV-1-infected LTNP (CD4+ T lymphocyte count > 500 x 10(6)/l after 8 years) were compared with 95 individuals infected within a similar period (1983-1986) but who had rapidly progressed to AIDS and death, and with a further 120 HIV-positive individuals with CD4+ counts < 500 x 10(6)/l. METHODS: The presence of the CCR-5 delta 32 mutation was assessed using polymerase chain reaction with primers spanning the 32 base-pair deletion. CD4+ and CD8+ counts, plasma HIV-1 RNA, p24 antigen and beta 2-microglobulin levels in LTNP carrying the CCR-5 delta 32 mutation were compared with LTNP lacking the mutation. RESULTS: A marked increase in the frequency of CCR-5 delta 32 heterozygosity was found among LTNP (35.9%) compared with rapid progressors (12.6%; P = 0.0005) and patients selected on the basis of a CD4+ T-cell count < 500 x 10(6)/l (12.5%; P = 0.0004). LTNP heterozygous for CCR-5 delta 32 had a significantly higher CD8+ T-cell count than those without the mutation (1218 versus 972 x 10(6)/l; P = 0.044). No significant correlation was observed between heterozygosity and CD4 count, viral load, p24 antigen or beta 2-microglobulin within the LTNP group. CONCLUSIONS: This study provides the strongest evidence to date for the importance of a single copy of the CCR-5 delta 32 mutation in long-term non-progression of HIV infection, which may involve, in part, CD8+ T lymphocytes.

Disease Progression↗
PubMed1997

Incidence of HIV infection in a cohort of homosexually active men.

The purpose of this study was to estimate the incidence of human immunodeficiency virus (HIV) in a cohort of homosexually active men in Sydney. In 1984-85 the Sydney AIDS Prospective Study enrolled homosexually active men, who were followed by six-monthly visits, although regular contact with most participants ceased in the early 1990s. In 1993-94 a major effort was made to establish the HIV status of all participants who had attended more than once. Of the 1075 men enrolled, 528 (49 per cent) were negative at enrollment and had at least one further documented HIV test. The annual incidence rate of HIV infection was highest in the early years of the study, 1984 (9.6 per cent) and 1986 (5.0 per cent), and remained low from 1987 (1.9 per cent) to 1994 (0.0 per cent). The incidence of HIV infection was higher among men aged under 34 years at enrollment and men who reported more than four sexual partners in the six months before enrollment, but these associations disappeared by 1987. The decrease in HIV incidence is consistent with findings from other cohorts followed for this length of time.

Adolescent↗
PubMed1997

Scytalidium dimidiatum and Lecythophora hoffmannii: unusual causes of fungal infections in a patient with AIDS.

Immunocompromised patients are susceptible to infections by fungi that seldom cause disease in humans. We describe a human immunodeficiency virus-infected patient who had simultaneous infections with two fungi which are rare causes of serious infection: Lecythophora hoffmannii, causing chronic sinusitis, and Scytalidium dimidiatum, causing skin lesions, lymphangitis, and lymphadenitis. The clinical and pathologic findings are discussed.

AIDS-Related Opportunistic Infections↗
PubMed1997

Herpes zoster and the stage and prognosis of HIV-1 infection.

OBJECTIVES: To examine the incidence of herpes zoster in HIV-1 infection. To assess the prognostic significance of the occurrence of herpes zoster and progression to AIDS or death DESIGN AND METHODS: 146 homosexually active men with known times of HIV-1 seroconversion were identified through the Sydney AIDS Prospective Study and the clinic records of a private medical practice with large caseload of HIV infected homosexual men. Medical records were reviewed for a history of herpes zoster, CD4+ lymphocyte counts, and HIV-1 disease status. Cox's proportional hazards model was used to determine whether herpes zoster predicted progression to AIDS or death. RESULTS: After a mean follow up of 54 months, 30 men (20%) had an episode of herpes zoster and three of these men had one recurrence. The overall incidence of herpes zoster was 44.4 episodes per 1000 person years (95% CI 30.0-63.5). Herpes zoster was not found to be a marker of deteriorating immune functions as measured by CD4+ lymphocyte counts. CD4+ counts did not differ significantly between those with and without zoster at 1 year (551 v 572.10(6)/1, p = 0.79), 2 years (451 v 557, p = 0.11), and 3 years (424 v 481, p = 0.50) following HIV-1 seroconversion. There was no statistically significant difference in progression to AIDS (RR = 1.89, 95% CI 0.80-4.46, p = 0.15) or death (RR = 0.90, 95% CI 0.31-2.65, p = 0.85) from HIV-1 sero-conversion in those who did and those who did not develop herpes zoster. CONCLUSION: The incidence of herpes zoster was consistent with the findings of other studies. There was no association between the occurrence of herpes zoster and progression of HIV-1 disease.

AIDS-Related Opportunistic Infections↗
PubMed1997

Olestra affects serum concentrations of alpha-tocopherol and carotenoids but not vitamin D or vitamin K status in free-living subjects.

Normal, healthy, free-living adults ingested either 18 g/d olestra, with or without 1.1 mg tocopheryl acetate/g olestra, or 18 g/d triglyceride placebo, for 16 wk in a double-blind, placebo-controlled study. Serum concentrations of alpha-tocopherol, alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin, retinol and cholesterol were measured biweekly. Serum 25-hydroxyvitamin D concentration, prothrombin time, partial thromboplastin time and plasma concentration of functional prothrombin (Simplastin-Ecarin assay) were measured at wk 0, 8 and 16. Relative to the placebo group, serum alpha-tocopherol concentration was reduced 6% for the group given 18 g/d olestra. Addition of tocopheryl acetate to olestra partially offset the effect of olestra. For the group given 18 g/d olestra plus 1.1 mg tocopheryl acetate/g olestra, serum alpha-tocopherol concentration was 4% less than the placebo value. Olestra reduced serum concentration of beta-carotene by 27%; the other carotenoids were similarly affected. Serum cholesterol concentration was reduced approximately 4.5% in the olestra groups, relative to placebo, but the differences were not significant. Serum triglycerides, serum 25-hydroxyvitamin D, prothrombin time, partial thromboplastin time or the plasma concentration of under-gamma-carboxylated prothrombin were unaffected by olestra. Clinical observations and laboratory measures indicated no health-related effects of olestra; mild-to-moderate transient gastrointestinal symptoms such as bloating, cramping, loose stools and diarrhea were reported by all groups.

Adult↗
PubMed1996

CD8+ lymphocyte responses to antiretroviral therapy of HIV infection.

CD8+ T lymphocytes may mediate important host responses to human immunodeficiency virus (HIV) infection by human leukocyte antigen (HLA)-restricted cytotoxicity and production of soluble HIV suppressor factors. CD8+ lymphocytes are also important for the suppression of many latent pathogens responsible for opportunistic disease in HIV-infected patients. There has been no systematic analysis of the responses of CD8+ lymphocyte counts to antiretroviral therapy. We compared CD8+ lymphocyte responses in seven trials of nucleoside or non-nucleoside analog reverse transcriptase inhibitors and in two trials of ritonavir, a HIV protease inhibitor. Nucleoside analog and non-nucleoside analog reverse transcriptase inhibitor monotherapy resulted in no substantial changes in CD8+ counts relative to baseline or placebo. Combination nucleoside analog therapy resulted in variable peak responses (-145 to +240 cells/mm3), which remained significantly above baseline for 0 to 12 weeks. In contrast, ritonavir monotherapy caused a peak increase of 892 CD8+ cells/mm3, which remained significantly above baseline for 32 weeks. There was a significant correlation (Rs 0.61, p = 0.01) between the peak CD4+ cell and CD8+ responses to each therapy, but no significant correlation between the peak viral load responses and peak CD8+ cell responses. These findings suggest that the greater CD8+ response seen with ritonavir may be due to its specific inhibition of HIV protease and also that the CD8+ response is dependent on new CD4+ cell production. The CD8+ lymphocyte proliferation observed with protease inhibitor therapy could result in improved suppression of HIV replication by the immune system and should be confirmed in a prospective trial comparing protease inhibitors with both nucleoside and non-nucleoside analog therapies.

Acetamides↗
PubMed1996

Current clinical experience with nevirapine for HIV infection.

Nevirapine is a potent antiretroviral agent whose use, especially as monotherapy, may be limited by rapid onset of resistance as well as by hypersensitivity reactions. However, virologic features of nevirapine suggest that it may be useful in combination therapy with zidovudine or other antiretrovirals, including for patients infected with zidovudine-resistant strains HIV.

Antiviral Agents↗
PubMed1996

Alterations in the immune response of human immunodeficiency virus (HIV)-infected subjects treated with an HIV-specific protease inhibitor, ritonavir.

Effects of a human immunodeficiency virus (HIV) type 1 protease inhibitor, ritonavir, were evaluated in 21 patients enrolled in a phase I/II study. The magnitude and rates of CD4 and CD8 lymphocyte increase, changes in subsets of CD4 and CD8 lymphocytes, and proliferative responses to mitogen and antigens were analyzed. Significant increases were noted in CD4 and CD8 lymphocyte counts; numbers of CD4CD45RO lymphocytes increased significantly by week 1 of therapy. Increases in the CD4CD45RA subset were observed at week 4. Reductions in the percentage of CD4 and CD8 lymphocytes expressing CD38 were noted. Increases in proliferative responses to phytohemagglutinin were noted in 6 of 7 patients and correlated with duration of virus load suppression. Increased responses to recall antigens and to HIV-specific proteins were observed. Treatment with ritonavir produced alterations in the immune system that included changes in T cell subset distribution and increases in CD4 and CD8 lymphocyte numbers and of lymphocyte function.

ADP-ribosyl Cyclase↗
PubMed1996

Changes in biologic phenotype of human immunodeficiency virus during treatment of patients with didanosine.

Progression to AIDS in patients harboring human immunodeficiency virus type-1 (HIV-1) isolates expressing a syncytium-inducing (SI) phenotype is faster than in those in whom the virus expresses a non-SI (NSI) phenotype. Zidovudine monotherapy does not appear to alter this outcome. To examine the role of didanosine (ddI) monotherapy in phenotype expression, HIV-1 isolates from 73 patients receiving ddI for up to 72 weeks were analyzed. After 12 weeks, the number of isolates expressing an NSI phenotype was 29% higher than at the start of treatment. Patients receiving high-dose ddI (375 mg twice daily) were significantly more likely to express the NSI phenotype at 12 weeks than patients who received low-dose ddI (100 mg twice daily), even after adjustment for phenotype and CD4 cell count at baseline, suggesting that ddI may be selective against the faster-replicating virus. ddI at 375 mg twice daily significantly increases the probability of an NSI phenotype over the short term in patients with advanced HIV disease.

Antiviral Agents↗
PubMed1996

Virologic and immunologic benefits of initial combination therapy with zidovudine and zalcitabine or didanosine compared with zidovudine monotherapy. Wellcome Resistance Study Collaborative Group.

A randomized controlled study was done to determine whether initial combination therapy with zidovudine and zalcitabine or zidovudine and didanosine would delay the emergence of zidovudine-resistant virus. Human immunodeficiency virus (HIV)-1-infected patients with <300 CD4 cells/mm3 and <4 weeks of prior zidovudine therapy were randomized to zidovudine, zidovudine plus zalcitabine, or zidovudine plus didanosine. Combination therapy did not delay the emergence of zidovudine-resistant virus isolates. However, combination therapy resulted in a significant increase in CD4 cells through 72 weeks compared with zidovudine monotherapy and a greater and more sustained decline in serum HIV-1 RNA. Although this trial was not designed as a clinical end-point study, patients assigned to zidovudine plus didanosine combination therapy experienced a significant delay in time to first AIDS-defining event or death compared with those assigned to zidovudine monotherapy.

Adult↗