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Biomedical subjects

T Barnett

Publications and source records attributed to T Barnett.

At least 19 recordsLinked to original sources

Sexual transmission risk perceptions and behavioural correlates of HIV concentrations in semen.

HIV transmission risk behaviours are related to perceived infectiousness and HIV-positive men who have undetectable blood viral loads may practise less protective behaviours. The current study extends previous research by reporting the association between perceived HIV transmission risks, risk behaviours and viral load in semen. Results showed significant associations between perceived risks for transmitting HIV, unprotected intercourse and viral load in semen. Further analyses showed that men with greater concentrations of HIV in their semen were practising higher rates of transmission risk behaviours while perceiving less risk for potentially transmitting HIV. We conclude that behavioural interventions are needed for HIV-positive men to inform them that HIV infectiousness cannot be inferred from peripheral blood viral loads and to support maintenance of HIV risk reduction behaviours.

Attitude to Health↗

Human immunodeficiency virus in semen and plasma: investigation of sexual transmission risk behavioral correlates.

Risks for sexually transmitted HIV may be related to concentrations of virus detected in semen and previous research shows a small to moderate association between viral load in blood and semen. This study examined the association between viral load in semen and plasma in a community sample of HIV-infected men and is the first study to examine semen viral load in relation to sexual transmission risk behaviors. A sample of 44 HIV-positive men recruited from community service agencies provided semen, blood, and urine samples and completed clinical interviews assessing health and behavior. We failed to find an association between viral load in semen and plasma, Spearman rho = 0.07, p > 0.1. When restricted to participants with detectable virus in semen and plasma, the correlation remained nonsignificant, rho = -0.16, p > 0.1. Men who had higher semen viral loads relative to their plasma viral load were distinguished by having engaged in significantly higher rates of unprotected intercourse as the insertive sex partner in the previous 3 months. Semen viral load was not, however, related to recent or current sexually transmitted infections (STIs). This study is among the first to examine sexual transmission risk behaviors as marker for HIV infectiousness. Results caution against inferring sexual transmission infectiousness based on plasma viral load and suggest that HIV-positive men who practice higher rates of insertive intercourse may be more infectious even in the absence of other STIs.

Adult↗

Relapse after allogeneic bone marrow transplantation for refractory anemia is increased by shielding lungs and liver during total body irradiation.

Patients with the refractory anemia (RA) subtype of myelodysplastic syndrome who undergo allogeneic bone marrow transplantation (BMT) have a low risk of relapse, but they have a high risk of nonrelapse mortality when prepared with conventional preparative regimens. To try to reduce nonrelapse mortality, we treated 14 RA patients with a modified approach to total body irradiation (TBI) followed by cyclophosphamide (CY) and HLA-identical sibling BMT. Median patient age was 44 years (range, 28 to 65 years). Patients received TBI with shielding of the right lobe of the liver and both lungs followed by electron beam boosts to shielded ribs. Total radiation exposure in nonshielded areas was 12 Gy (n = 10), 10 Gy (n = 3), or 6 Gy (n = 1). After TBI, patients received CY at 120 mg/kg over 2 days, followed by transplantation of unmanipulated bone marrow. All patients initially achieved engraftment with donor cells, although 2 patients had subsequent reemergence of host hematopoiesis without evidence of disease relapse. Five patients died of transplantation-related causes between 22 and 1262 days post-BMT. Four patients relapsed between 157 and 1096 days post-BMT. These 14 patients were compared with 46 historical controls with RA who received conventional CY/TBI or busulfan/CY preparative regimens. Patients in the experimental group had a similar nonrelapse mortality rate compared with the historical control group (29% versus 37%, respectively; P = .8), but a higher relapse rate (34% versus 2%, P = .0004) and a lower disease-free survival (38% versus 61%, P = .16). We conclude that this modified TBI approach is associated with an unacceptably high risk of relapse for patients with RA undergoing BMT.

Adult↗

Busulfan, melphalan, and thiotepa with or without total marrow irradiation with hematopoietic stem cell rescue for poor-risk Ewing-Sarcoma-Family tumors.

BACKGROUND: Survival following metastatic or recurrent Ewing sarcoma family tumors (ESFT) remains <25%. Myeloablative therapy with hematopoietic stem cell transplantation (HSCT) may improve survival for poor-risk ESFT. We describe the toxicity and efficacy of a myeloablative chemotherapy regimen, followed by a second myeloablative radiotherapy regimen as consolidation treatment for poor-risk ESFT. PROCEDURE: Sixteen patients with poor-risk ESFT were treated with myeloablative therapy followed by HSCT. All patients received busulfan, melphalan, and thiotepa (BuMelTT) as chemotherapy conditioning. Nine patients received total marrow irradiation (TMI) as a second myeloablative therapy, also followed by HSCT. Seven patients were excluded from TMI because of inadequate peripheral blood stem cell harvest, extensive prior radiation therapy, early disease progression, orpatient refusal. The disease status prior to my eloablative therapy was first complete response (CR1) in three patients, CR2 in nine, second partial response (PR2) in one, CR3 in one, and progressive disease (PD) in two. RESULTS: One patient died of regimen-related toxicity, one from late pulmonary toxicity, and one following allogeneic transplantation for myelodysplasia. Eight developed recurrent disease (median time to progression 6.8 months). Six survive without relapse from 27 to 66 months following BuMelTT (median follow-up 42 months), all of whom received both BuMelTT and TMI patients (3-year event-free survival 36%). CONCLUSIONS: Dual myeloablative therapy with BuMelTT and TMI was a feasible and promising treatment approach for patients with poor-risk ESFT. Inability to collect sufficient PBSC and extensive previous radiation therapy limit the ability to deliver TMI as a second HSCT conditioning regimen.

Adolescent↗

The HIV/AIDS epidemic in Ukraine: its potential social and economic impact.

Present and immediately foreseeable medical knowledge suggest that HIV infection cannot be avoided by vaccination and that an affordable cure for the resulting syndrome, AIDS, is a long way off. There is a strong possibility that Ukraine is confronted by an HIV epidemic which will spread into the general population and that the most common mode of transmission will be through heterosexual intercourse. The epidemic in the Ukraine is currently concentrated among intravenous drug users. It is estimated that between 60,000 and 180,000 people may currently be infected. In present economic and social circumstances there are many features of Ukrainian society that may add to the probability of the epidemic becoming widespread in the general population. It is likely that this process may have already commenced. The result of this will be numerous additional deaths and illness over the short (5 year) (19,000-23,000 deaths), medium (10-15 year) (61,000-111,000), and longer terms (>20 year) (in excess of 40,000-160,000 deaths). The research reported here was undertaken in 1997-8 and describes the potential medium to long term social and economic impact of an HIV/AIDS epidemic in Ukraine. Using the concepts of risk environment, susceptibility and vulnerability, it reports the problems which might be expected to develop in relation to care of excess orphans, the elderly, vulnerable households and regions as well as among those working in the "third sector", a social sector upon which exponents of the importance of developing sound "civil society" in "transitional economies" place heavy emphasis.

Acquired Immunodeficiency Syndrome↗

Endogenous circulating sympatholytic factor in orthostatic intolerance.

Sympathotonic orthostatic hypotension (SOH) is an idiopathic syndrome characterized by tachycardia, hypotension, elevated plasma norepinephrine, and symptoms of orthostatic intolerance provoked by assumption of an upright posture. We studied a woman with severe progressive SOH with blood pressure unresponsive to the pressor effects of alpha(1)-adrenergic receptor (AR) agonists. We tested the hypothesis that a circulating factor in this patient interferes with vascular adrenergic neurotransmission. Preincubation of porcine pulmonary artery vessel rings with patient plasma produced a dose-dependent inhibition of vasoconstriction to phenylephrine in vitro, abolished vasoconstriction to direct electrical stimulation, and had no effect on nonadrenergic vasoconstrictive stimuli (endothelin-1), PGF-2alpha (or KCl). Preincubation of vessels with control plasma was devoid of these effects. SOH plasma inhibited the binding of an alpha(1)-selective antagonist radioligand ([(125)I]HEAT) to membrane fractions derived from porcine pulmonary artery vessel rings, rat liver, and cell lines selectively overexpressing human ARs of the alpha(1B) subtype but not other AR subtypes (alpha(1A) and alpha(1D)). We conclude that a factor in SOH plasma can selectively and irreversibly inhibit adrenergic ligand binding to alpha(1B) ARs. We propose that this factor contributes to a novel pathogenesis for SOH in this patient. This patient's syndrome represents a new disease entity, and her plasma may provide a unique tool for probing the selective functions of alpha(1)-ARs.

Adrenergic alpha-1 Receptor Antagonists↗

Stable mixed hematopoietic chimerism in dog leukocyte antigen-identical littermate dogs given lymph node irradiation before and pharmacologic immunosuppression after marrow transplantation.

Stable mixed donor/host hematopoietic chimerism can be accomplished in dog leukocyte antigen (DLA)-identical littermate dogs given sublethal (200 cGy) total-body irradiation (TBI) before and immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP) after transplant (Blood 89:3048, 1997). Studies were based on the hypothesis that drugs that prevent graft-versus-host disease (GVHD) after transplant also suppress host-versus-graft (HVG) reactions and thereby enhance engraftment. Here, we asked whether pretransplant TBI provided marrow space for the graft to home or caused host immunosuppression. To address the questions, recipients were given pretransplant irradiation to cervical, thoracic, and abdominal lymph nodes (except pelvis), DLA-identical littermate marrow grafts, and MMF/CSP posttransplant. Six dogs that received 450 cGy irradiation showed initial engraftment. Two rejected their grafts after 8 and 18 weeks, 1 died with GVHD and engraftment, and 3 are alive as mixed chimeras after 57 to 97 weeks. Four dogs given 200 cGy irradiation also showed initial engraftment, but rejected their grafts after 10 to 18 weeks. Mixed chimerism was present in nonirradiated marrow and lymph node spaces and involved granulocytes, T cells, and monocytes. While other explanations are possible, results seem consistent with the hypothesis that pretransplant radiation provides host immunosuppression, and grafts can create their own marrow space. These data set the stage for the development of novel transplant regimens that substitute immunosuppressive for cytotoxic agents.

Animals↗

Prevalence and correlates of physical activity behaviors among elementary schoolchildren in multiethnic, low income, inner-city neighborhoods in Montreal, Canada.

PURPOSE: To describe the prevalence and correlates of physical inactivity and of participation in organized sports at and outside school among elementary schoolchildren in multiethnic, low income, urban neighborhoods in Montreal, Canada. METHODS: As part of the evaluation of a school-based heart health promotion program, baseline data on physical activity behaviors and potential correlates of these behaviors, were collected from 2285 students aged 9-13 in all 130 grade 4 to 6 classes in 24 inner-city elementary schools from May to June 1993. RESULTS: One-fifth of boys (20.5%) and 24.4% of girls were inactive; 40.0% and 33.3% of boys and girls respectively, participated in school sports teams; 82.5% and 74.7% participated in organized sports outside school. Declines in activity levels with age were apparent in both genders. Children who participated in organized sports programs at and outside school, those with higher perceived self-efficacy for physical activity, and those with more parental support for engaging in physical activity were more active. Children of Asian family origin were less active. Socioeconomic status was related to participation in organized sports outside school. CONCLUSIONS: To reach children in socio-economically disadvantaged areas and to prevent age-related declines in activity levels, interventions promoting physical activity should focus on increasing availability and access to community-based organized sports programs at and outside school. Also they should include components to increase parental support and to improve perceived self-efficacy for physical activity.

Adolescent↗

Inhibition of skin carcinomas but not papillomas by sphingosine, N-methylsphingosine, and N-acetylsphingosine.

The sphingoid base backbones of sphingolipids are highly bioactive compounds that affect cell growth, differentiation, diverse cell behaviors, and programmed cell death. Therefore, the efficacy of sphingosine (SPH) and the analogs N-acetylsphingosine (NAS), N-methylsphingosine (NMS), octylamine (OCT), and sterylamine (STR) in the prevention of skin cancer was assessed in female Sencar mice by measuring effects on the induction of epidermal ornithine decarboxylase (ODC) activity and hyperplasia by 12-O-tetradecanoylphorbol-13-acetate (TPA) and effects on the induction of skin tumors by 7, 12-dimethylbenz[a]anthracene (DMBA) and TPA. ODC was measured in the shaved dorsal skin of mice treated topically with 0.05-20 mumol of these compounds 30 minutes before application of 8.5 nmol of TPA in 0.2 ml of acetone. ODC activity was inhibited by > or = 5 mumol of SPH and STR, > or = 10 mumol of NAS and NMS, and 20 mumol of OCT. In contrast, the induction of hyperplasia was not inhibited by application of these compounds 30 minutes before TPA. Two carcinogenesis studies were conducted with 10 nmol of DMBA as the initiator and 3.2 nmol of TPA (2x/wk for 15 wk) as the promoter. In the first study, NAS, NMS, OCT, and STR (0.05 and 0.5 mumol) were applied before each TPA application. Papilloma incidence and multiplicity were not inhibited, but NAS (0.05 mumol) and NMS (0.05 and 0.50 mumol) increased cancer-free survival. In the second experiment, SPH, NAS, and NMS (0.05 and 0.5 mumol) were applied 30 minutes before each TPA treatment and twice weekly for 10 weeks after the final TPA treatment. Papilloma incidence and multiplicity were not inhibited; however, the proportion of mice without carcinoma was increased by both doses of SPH and by 0.5 mumol of NAS. Thus low doses of sphingolipids that were not effective in inhibiting ODC activity, reducing hyperplasia, or preventing epidermal papilloma development were, nonetheless, effective in inhibiting carcinoma development.

Amines↗

Brain lactate and N-acetylaspartate in pediatric AIDS encephalopathy.

Two children with acquired immunodeficiency syndrome (AIDS) and progressive encephalopathy underwent MR spectroscopy before and after antiretroviral therapy. Initial MR spectroscopy of the basal ganglia region showed decreased N-acetylaspartate (NAA)/creatine (Cr) and a lactate peak. After therapy, there was improvement in NAA/Cr and an absence of the abnormal lactate peak. We suggest that decreased NAA/Cr in AIDS is reversible, that brain lactate might correlate with inflammation, and that MR spectroscopy can be useful in treatment trials.

AIDS Dementia Complex↗

Reliability of proxy reports of parental smoking by elementary schoolchildren.

PURPOSE: To investigate the reliability of reports of parental smoking by elementary schoolchildren aged 9-13 years, and to identify the correlates of disagreement between student proxy and parent self-reports. METHODS: As part of the evaluation of a school-based heart health promotion program, data on parental smoking status were collected from 1240 student-mother pairs and 898 student-father pairs. RESULTS: Agreement for parental smoking status was 93.1% among student-mother pairs and 86.4% among student-father pairs. Among student-mother pairs, reports by students aged 9 years were more likely to disagree with mothers' self-reports than those of older children (odds ratio (OR) = 3.1). Among student-father pairs, the only significant correlate of disagreement was living in a single-parent family headed by the mother (OR = 2.6). CONCLUSIONS: Children 10-years or older can provide reliable reports of the smoking status of cohabiting parents.

Adolescent↗

The "Yes, I Quit" smoking cessation course: does it help women in a low income community quit?

The objectives were to evaluate the impact of "Yes, I Quit" (a smoking cessation course tailored for women in a low income, low education community), and to identify baseline predictors of short and longer-term self-reported cessation. The impact was evaluated in a before-after study design with no comparison group. Baseline data were collected in self-administered questionnaires at the beginning of the first session of the course. Follow-up data were collected in telephone interviews at one, three and six months after the designated Quit Day. Self-reported quit rates among 122 participants were 31.1%, 24.7% and 22.3% at one, three and six months. Non-quitters reduced their consumption by 10.3, 8.3, and 7.1 cigarettes per day at one, three and six months. Multivariate logistic regression analyses showed that being in excellent/good health was significantly associated with cessation at one month (odds ratio (OR) = 2.4). Being married (OR = 13.0) and no other smokers in the household (OR = 3.6) were associated with three-month cessation. Only being married was associated with six-month cessation (OR = 6.8). "Yes, I Quit" produced quit rates among low income, low education participants comparable to those reported for cessation programs directed at the general population of smokers. Good health is associated with early cessation, while support from a spouse is important to maintaining a non-smoking status among quitters.

Adolescent↗

Dietary energy restriction does not inhibit pancreatic carcinogenesis by N-nitrosobis-2-(oxopropyl)amine in the Syrian hamster.

Dietary energy restriction was previously shown to be effective in preventing a wide range of experimentally induced cancers. Studies were conducted to assess the influence on pancreatic carcinogenesis of dietary energy restrictions (reduced fat and carbohydrate) of 10%, 20% or 40% in comparison with control in Syrian hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). Two carcinogenesis studies were conducted. One used a single treatment with 20 mg BOP/kg body weight and followed hamsters for 102 weeks following treatment, and the other used three weekly treatments of 20 mg BOP/kg body weight and followed hamsters for 45 weeks after treatment. Hamsters were fed control or energy restricted diet beginning the week following the last BOP treatment. Pancreatic carcinomas were induced in 9-18% of the hamsters in the first experiment and in 59-66% of the animals in the second. Dietary energy restriction did not influence carcinoma incidence in either study, and in the second experiment the multiplicity of tumors was higher in the 40% energy restriction (ER) group than in control hamsters. Plasma corticosterone was suppressed by BOP treatment, particularly in the 20% and 40% ER hamsters in the second experiment, and diet or BOP treatment did not significantly alter plasma cortisol. Pancreatic protein kinase Czeta measured by Western blot was highest in the cytosol and particulate fractions of the 40% ER hamsters in the first experiment. These results indicate that dietary energy restriction is not effective in the prevention of BOP induced pancreatic carcinogenesis in the Syrian hamster.

Animals↗