Management of metabolic complications associated with antiretroviral therapy for HIV-1 infection: recommendations of an International AIDS Society-USA panel

OBJECTIVE: Alterations in glucose and lipid metabolism, lactic acidemia, bone disorders, and abnormal body fat distribution have been recognized recently as frequent complications associated with HIV-1 infection and potent antiretroviral therapy, but limited data are available regarding the appropriate management of these disorders. These recommendations were developed to guide physicians actively involved in HIV care in the management of metabolic complications that occur primarily within the context of potent antiretroviral therapy. PARTICIPANTS: A 12-member panel representing international expertise in HIV-1 patient care, antiretroviral therapy, and endocrine and metabolic disorders was selected in the spring of 2000 by the International AIDS Society-USA, a not-for-profit physician education organization. Panel members met in closed meetings beginning in May 2000. All work was funded by the International AIDS Society-USA; the panel members are not compensated for their participation. EVIDENCE: The panel reviewed published results of clinical, epidemiologic, and basic science studies and data and abstracts presented at research conferences, primarily from 1997 to 2002. The panel also considered studies of the pathophysiology and treatment of similar metabolic abnormalities in noninfected persons. Emphasis was placed on results from prospective, randomized, controlled clinical trials when available. PROCESS: For each metabolic complication, 1 or more member(s) reviewed and presented all available evidence to the panel, and then wrote a summary of the evidence and preliminary recommendations. Final recommendations were determined by full group consensus. The summaries were combined into a single working document and all panel members edited and approved all subsequent drafts. CONCLUSIONS: Carefully controlled studies to determine the incidence, etiology, risk factors, and most appropriate treatments for metabolic complications in HIV-1 infection are urgently needed. In the absence of these data, and to prevent acute illness and mitigate long-term risks, the panel recommends routine assessment and monitoring of glucose and lipid levels and assessment and monitoring of lactic acidemia and bone abnormalities if clinical signs or symptoms are detected. With the exception of body fat distribution abnormalities, specific treatments for these complications are also recommended. Successful long-term antiretroviral therapy will require diligent monitoring and preemptive treatment of metabolic complications to optimize the risk-benefit ratio of antiretroviral therapies.     

A prospective study of the factors influencing entry to alcohol and drug treatment

Much is known about factors related to entering alcohol and drug treatment, but most research comprises cross-sectional snapshots in time. It is not known whether the reasons for entering treatment endure when problem drinkers are studied over time. This study contrasts characteristics predicting treatment entry in a cross-sectional analysis at baseline with a longitudinal perspective at 1- and 3-year follow-up interviews. Sociodemographic characteristics were less important in the longitudinal analysis. In contrast to the social consequences important at the baseline interview, physiologic symptoms of alcohol dependence and interventions by medical professionals were prominent at later interview points. The findings have implications for interventions by health professionals, both for the development of early interventions targeting individuals to treatment and for a continuing care service model.     

Computing heading in the presence of moving objects: a model that uses motion-opponent operators

Psychophysical experiments have shown that human heading judgments can be biased by the presence of moving objects. Here we present a theoretical argument that motion differences can account for the direction of bias seen in humans. We further examine the responses of a computer simulation of a model for computing heading that uses motion-opponent operators similar to cells in the primate middle temporal visual area. When moving objects are present, this model shows similar biases to those seen with humans, suggesting that such a model may underlie human heading computations.     

Injectable hydroxyapatite paste as an option for ocular implantation after evisceration

OBJECTIVE: To investigate the feasibility of small incision evisceration with an injectable ocular implant that is biocompatible and preserves globe size. DESIGN: Experimental animal study. METHODS: The axial length of the eyes of 12 rabbits was determined by ultrasound before surgery. Subsequently, 12 eyes of 12 separate rabbits were eviscerated and injected with hydroxyapatite (HA) paste (BoneSource; Stryker Leibinger, Kalamazoo, MI). Three rabbits each were killed at 2 weeks, 6 weeks, 3 months, and 6 months after evisceration, and measurements of globe size were compared with measurements of the fellow eye. Histologic examination of the eviscerated eyes was performed. MAIN OUTCOME MEASURES: The axial length and lateral globe measurements of the eviscerated eye were compared with the fellow eye. The eviscerated eye was examined histologically and the degree of inflammation, vascularization, and ossification was noted for each period of observation. RESULTS: The mean preoperative difference in axial length between the control (fellow eyes) and the subsequently eviscerated eyes was 0.15 +/- 0.04 mm (mean +/- standard error of mean). The average axial and lateral globe measurements of the operated eye were 0.8 +/- 0.4 mm less than the fellow eye 2 weeks after surgery, and this difference increased to 3.1 +/- 0.7 mm 6 months after surgery. Histologic examination showed a decrease in granulomatous inflammation and an increase in vascularization of the implanted HA over the time of observation with early osseous metaplasia. CONCLUSIONS: Small incision evisceration is possible with ocular volume replacement with an injectable orbital implant. Injectable HA paste shows promise as an option for implantation after eye evisceration; however, further studies are required to establish the stability of this material for this application.     

Perceptions and needs of patients with migraine: a focus group study

OBJECTIVE: This study's purpose was to identify the areas that people find most difficult in living with migraines and, in that regard, what kinds of assistance would be most helpful to them and to other people who have migraine headaches. STUDY DESIGN: Four focus groups, each consisting of 4 to 8 participants, were held. Discussions, which were recorded and organized according to category and theme, focused on problems in living with migraines and effective treatment of migraines. POPULATION: Participants were 24 people who had been experiencing 1 to 2 migraines a month, each lasting 1 to 2 days, for at least 6 months. RESULTS: Five themes emerged: (1) impact on family, (2) misunderstanding by others, (3) effect on work, (4) physician care issues, and (5) issues related to medical insurance and drug companies. A majority of participants identified early treatment as the most important consideration for new migraine sufferers. Many participants preferred to have a relationship with their physicians in which they developed a treatment plan together rather than receiving generic educational materials. CONCLUSIONS: Results suggest that patients are interested in understanding their migraines and securing relevant information in addition to obtaining pain relief. Patients desired collaborative relationships with their physicians and a team approach to treatment. Suggestions for physicians who treat patients who have migraines are reviewed.     

Reduction of translation initiation factor 4E decreases the malignancy of ras -transformed cloned rat embryo fibroblasts

Expression of the T24^ras oncogene induces malignancy (tumor growth, invasion and metastasis) in cloned rat embryo fibroblasts (CREF T24). In CREF T24, the rate of phosphorylation of eukaryotic translation initiation factor 4E (elF-4E) is increased, resulting in increased protein synthesis rates. We have recently shown that reducing the protein levels of elF-4E in CREF T24 (AS4E line) markedly decreases soft-agar colonization, increases tumor latency periods and increases tumor doubling times without significantly altering monolayer growth. In this study, cells with reduced elF-4E had delayed and reduced invasiveness and decreased experimental metastasis. Furthermore, reduced elF-4E levels correlated with decreased expression of the metastasis-associated 92-kDa collagenase type-IV and exon-6 variants of the CD44 adhesion molecule [CD44(6v)]. Reduced elF-4E levels correlated inversely with increased levels of the putative metastasis-suppressor protein nm23. Cell lines established from AS4E tumors and lung metastases exhibited increased levels of elF-4E protein and protein synthesis rates compared to the AS4E line. Tumor-derived AS4E had the shortened tumor latency periods of CREF T24 but displayed the slow tumor-growth rates of AS4E. Tumor-derived AS4E exhibited the metastatic capacity of CREF T24 controls. Furthermore, tumor- and lung-nodule-derived AS4E expressed levels of CD44 (6v) and the 92-kDa collagenase type IV comparable to CREF T24 and displayed reduced levels of nm23 relative to AS4E. These results demonstrate that elF-4E is an important effector molecule involved in oncogenic p2l^ras-induced malignant transformation. © 1995 Wiley-Liss, Inc.     

Why carve out? Determinants of behavioral health contracting choice among large U.S. employers

Many U.S. employers have carved substance abuse and mental health services out of their medical plans, changing the way millions of people access care. Employers that take this approach contract directly with specialized vendors, bypassing their general health plans. Since carving out may alter access and treatment, there is a need to understand why employers take this approach. This article reviews various hypotheses about why purchasers carve out and tests them using data from a survey of America's largest employers, the Fortune 500 firms. Size is the strongest predictor of an employer's decision to carve out behavioral health once other characteristics are controlled for. Employers that report they value coordination are less likely to carve out, while those that value special expertise are more likely to carve out. Employers are less likely to carve out enrollees in health maintenance organizations (HMOs) than those in other types of plans.     

Desmopressin does not reduce bleeding and transfusion requirements in congenital heart operations

Background. Desmopressin (DDAVP) has been evaluated in many randomized clinical trials as a means to reduce blood loss and transfusion of allogeneic blood in cardiac operation requiring cardiopulmonary bypass. Desmopressin reduces blood loss in adult patients with excessive bleeding after cardiac operation. Its usefulness in patients undergoing complex congenital heart repair with cardiopulmonary bypass is unproved.

Methods. Sixty patients younger than 40 years of age scheduled for complex congenital heart operation (44 redo, 16 primary) were enrolled in this prospective, randomized, double-blind trial. Desmopressin 0.3 μg/kg or placebo was administered 10 minutes after protamine administration. Transfusion requirements and postoperative blood loss were recorded. Differences were analyzed using analysis of variance with a p value of 0.05 or less used to denote statistical significance.

Results. There were no differences in demographic or surgical characteristics between the DDAVP or placebo groups. There was no difference in blood loss and transfusion requirements between the DDAVP and placebo groups. During the intraoperative postinfusion time period, the median blood loss for redo patients was 343 versus 357 mL/m² for placebo versus DDAVP, respectively, and for primary patients, the median blood loss was 277 versus 228 mL/m².

Conclusions. The prophylactic use of DDAVP to reduce excessive bleeding or transfusion requirements in patients undergoing complex congenital heart operations is not warranted.     

Microsatellite instability and expression of hMLH1 and hMSH2 proteins in ovarian endometrioid cancer.

Microsatellite instability and loss of heterozygosity has been implicated in ovarian carcinogenesis. The reported frequency of microsatellite instability in human ovarian cancer varies significantly owing to the use of heterogeneous tumor histotypes and various microsatellite markers in different laboratories. In this study, we determined the frequency of microsatellite instability in 74 ovarian endometrioid carcinomas using four microsatellite markers (BAT25, BAT26, D5S346, D17S250), and examined hMLH1 and hMSH2 protein expression. In all, 20% of the tumors were microsatellite instability high (two or more markers showing instability) and 12% were microsatellite instability low (one marker showed instability). Loss of hMLH1 and/or hMSH2 expression was found in nine of 15 microsatellite instability-high tumors. The microsatellite instability-high phenotype tended to occur more frequently in low-grade tumors (P=0.053), but did not correlate with clinical stage. Totally, 38% of cases also displayed loss of heterozygosity at D17S250; this loss of heterozygosity was associated with high clinical stage (P=0.097). Our results indicate that both microsatellite and loss of heterozygosity at D17S250 are involved in the development of ovarian endometrioid carcinoma.