Generic antiretroviral efficacy in AIDS-associated Kaposi's sarcoma in sub-Saharan Africa

Generic antiretroviral drugs are pivotal in the implementation of WHO's '3 by 5' programme. However, clinical experience with generics in sub-Saharan Africa is insufficiently documented. We report on 50 patients with HIV-associated Kaposi's sarcoma treated with generic fixed-dose highly active antiretroviral therapy. At 52 weeks, 74% achieved an undetectable viral load of < 50 copies/ml, 86% achieved < 400 copies/ml, and a 3.1 log10 decline from baseline. Side-effects were minimal. The outcomes support the use of generic antiretroviral therapy.     

Assessment of risk factors for emergence distress and postoperative behavioural changes in children following general anaesthesia

BACKGROUND: Emergence distress commonly occurs in children recovering from the immediate effects of general anaesthesia. This study was performed to (1) examine whether parental presence in the operating room during emergence from anaesthesia reduces the incidence or severity of emergence distress behaviour, and (2) assess psychosocial risk factors, including child temperament and sleep behaviour, for development of emergence distress. METHODS: A randomized and controlled trial of parental presence at emergence was conducted in 100 ASA class I and II children having general anaesthesia for inguinal or penile surgery. Children in the study group had a parent present at induction and emergence of anaesthesia, while children in the control group had a parent present only at induction. Emergence and postanaesthesia care unit (PACU) behaviour was monitored using both the Operating Room Behaviour Rating Scale (ORBRS) and a 7-point Likert type cooperation scale. RESULTS: One-way anovas showed no significant differences between the control group and the study group on emergence distress behaviour. The frequency of negative postoperative behavioural changes at 1 and 4 weeks postsurgery was low in both groups. Children described as clingy/dependent (chi2 = 5.57, P < 0.06) and children with frequent temper tantrums (chi2 = 7.44, P < 0.02) were more likely to have emergence distress behaviour. CONCLUSIONS: Parental presence during emergence from anesthesia did not decrease the incidence or severity of emergence distress behaviour in children. Young children and children with a history of temper tantrums or separation anxiety may be more likely to develop such behaviour.     

Is autism a disorder of fatty acid metabolism? Possible dysfunction of mitochondrial beta-oxidation by long chain acyl-CoA dehydrogenase

Long chain acyl-CoA dehydrogenase (LCAD) has recently been shown to be the mitochondrial enzyme responsible for the beta-oxidation of branched chain and unsaturated fatty acids [Biochim. Biophys. Acta 1393 (1998) 35; Biochim. Biophys. Acta 1485 (2000) 121]. Whilst disorders of short, medium and very long chain acyl dehydrogenases are known, there is no known disorder of LCAD deficiency in humans. Experimental LCAD deficiency in mice shows an acyl-carnitine profile with prominent elevations of unsaturated fatty acid metabolites C14:1 and C14:2 [Hum. Mol. Genet. 10 (2001) 2069]. A child with autism whose acyl-carnitine profile also shows these abnormalities is presented, and it is hypothesized that the child may have LCAD deficiency. Additional metabolic abnormalities seen in this patient include alterations of TCA energy production, ammonia detoxification, reduced synthesis of omega-3 DHA, and abnormal cholesterol metabolism. These metabolic changes are also seen as secondary abnormalities in dysfunction of fatty acid beta-oxidation, and have also been reported in autism. It is hypothesized that LCAD deficiency may be a cause of autism. Similarities between metabolic disturbances in autism, and those of disorders of fatty acid beta-oxidation are discussed.     

Concurrent sexual partnerships among African Americans in the rural south

PURPOSE: To investigate concurrent sexual partnerships among heterosexual African Americans, 18 to 59 years old, in rural North Carolina. METHODS: Household interviews with persons randomly selected from the NC driver's license file were conducted to identify overlap among the 3 most recent sexual partnerships. RESULTS: Concurrency prevalence in the past 5 years was 53% (men) and 31% (women). Most (61%) respondents believed that a recent partner had had a concurrent partnership. Multivariate analysis revealed strong associations between concurrency and male gender, being unmarried, age of sexual debut, and incarceration of a sex partner. CONCLUSIONS: Concurrent partnerships may increase rates of heterosexual HIV among blacks in the rural Southeastern United States. Future research should examine the context that supports this network pattern.     

Coagulation in sepsis

Activation of the coagulation cascade during invasive infection can result in purpura fulminans, with rapid progression of tissue ischemia, or may manifest as abnormal clotting indices alone. Although severe derangements in coagulation are associated with organ dysfunction and increased mortality, the contribution of coagulopathy to the pathophysiology of sepsis remains incompletely understood. Over the past decade, investigators have evaluated several therapeutic anticoagulant strategies in sepsis, and manipulation of the coagulation system has emerged as a key concept in the current management of this disease. Clinical observations during treatment of septic patients with the endogenous anticoagulant activated protein C have stimulated additional study of interactions between endothelial injury, coagulation, and inflammation. This review describes clotting abnormalities during sepsis and discusses the clinical experience with therapeutic strategies intended to oppose excessive coagulation.     

Actin-binding proteins in a postsynaptic preparation: Lasp-1 is a component of central nervous system synapses and dendritic spines

CNS synapses are complex sites of cell-cell communication. Identification and characterization of the protein components of synapses will lead to a better understanding of the mechanisms of neurotransmission and plasticity. We applied multidimensional protein identification technology (MudPIT) to purified, guanidine-solubilized postsynaptic fractions to identify novel synaptically localized molecules. We identified several actin-associated proteins known to regulate actin polymerization and control cell motility in nonneural cells that have not previously been associated with CNS synaptic function. One of these is lasp-1, an actin-associated LIM and SH3 domain-containing protein. We show that lasp-1 is strongly expressed by CNS neurons and is concentrated at synaptic sites. Overall, the preponderance of actin-associated proteins in postsynaptic density fractions, and specifically those involved in actin reorganization, suggests that there are many modes by which the state of synaptic F-actin polymerization and, hence, synaptic physiology are affected.     

A community-based approach to promoting walking in rural areas

BACKGROUND: Ecologic models are often recommended to promote physical activity, yet sparse data exist on their effectiveness. DESIGN: A quasi-experimental design examined changes in walking behavior in six rural intervention communities in the Missouri "bootheel" region and in six comparison communities in Arkansas and Tennessee. SETTING/ PARTICIPANTS: The communities ranged in population from 2399 to 17,642; interventions focused on adults aged >/=18 years. INTERVENTION: Interventions were developed with community input and included individually tailored newsletters, interpersonal activities that stressed social support, and community-wide events such as walk-a-thons. MAIN OUTCOME MEASURES: Primary outcomes were rates of walking-trail use, total number of minutes walked in the past week, and total minutes walked for exercise. RESULTS: Among persons who used trails at baseline (16.9% of the total population), 32.1% reported increases in physical activity since they began using the trail. From community-wide samples, two subgroups indicated a positive net change in rates of 7-day total walking: people with high school degrees or less and people living in households with annual incomes of <==$20,000. However, no studied group showed a statistically significant net intervention effect. CONCLUSIONS: Although there was an increase in the rate of walking-trail use, a community-wide change in walking rates in rural communities was not documented. Results of this study should provide guidance for future projects.     

Training graduate-level pediatric psychology researchers at Case Western Reserve University: meeting the challenges of the new millennium

OBJECTIVE: To describe the challenges in training graduate-level pediatric psychology researchers for successful careers and to discuss solutions. METHODS: We reviewed experiences in training graduate students at Case Western Reserve University to identify key challenges in research training and potential strategies to meet them. RESULTS: We identified the following key challenges: stimulating graduate students' career interest in pediatric psychology research; teaching students about the pragmatic challenges of conducting research in pediatric settings, specialized research design, and data analytic issues; helping students to develop essential research skills; developing opportunities for student research-related collaborations; helping students develop professional identities as researchers; and developing and supporting their research careers beyond graduate school. CONCLUSIONS: Useful strategies for meeting these challenges include involving an interdisciplinary faculty in research training; developing specialized training methods that focus on critical research skills such as writing and data analysis; peer support; and involvement with multiple mentors who are successful researchers. Pediatric psychologists should also develop opportunities for the next generation of researchers by facilitating research job options and leadership opportunities.