Outbreak of head pediculosis during SFINCSS-99 isolation experiment

This short case report presents the development and treatment of a head lice outbreak during a space simulation experiment. The confinement experiment was conducted from July 1999 to March 2000 at the State Research Center of the Russian Federation Institute for Biomedical Problems in Moscow. Following a symptom period of up to 9 wk before diagnosis and treatment, 3 wk of treatment were required to remove all nits from those infected. Recommendations are made with regard to prevention of such infections during space missions. Treatment altered performance and comfort of crews, took time out of other duties, and even affected relations between crewmembers. The case is made for the development of a public health agenda in space research and medical space programs.     

The pancake phenomenon contributes to the inaccuracy of margin assessment in patients with breast cancer

BACKGROUND: To determine the effect on margin evaluation for patients with breast cancer, we prospectively quantified the "flattening" of the breast specimen after surgical removal. METHODS: The volume and height of 100 consecutive breast biopsy specimens were recorded independently by the operating surgeon and the pathologist. Five factors were analyzed that were thought to contribute to changes in specimen dimensions: patient age, breast tissue density, mammographic lesion type, specimen size, and the use of compression during specimen radiography. RESULTS: After surgical removal, mean volume and height of the breast specimens decreased from 46 cm(3) to 29 cm(3) (30%) and from 2.6 cm to 1.4 cm (46%), respectively. Flattening of the breast specimens occurred in all subgroups studied. CONCLUSIONS: Breast specimens are flattened after surgical removal, losing almost 50% of their original height. This "pancake" phenomenon has important implications for the accuracy of margin analysis.     

How could management of rectoceles be optimized?

A posterior vaginal wall prolapse, also known as a rectocele, is a common condition and is an outpouching of the posterior vaginal wall and anterior rectal wall into the lumen of the vagina.1-5 Although more common in parous women, rectoceles of over 1 cm in size have been demonstrated in over 40% of nulliparous women. As rectoceles may be asymptomatic, their true prevalence is not clear. Many women with rectoceles present to their gynaecologist who may not ascertain any anorectal symptoms or perform a rectal examination. Conversely, colorectal surgeons often disregard a vaginal examination.6 Conventionally, gynaecologists have managed rectoceles, but increasingly colorectal surgeons are involved because of the prevalence of anorectal symptoms. There are many surgical techniques for the management of a symptomatic rectocele. There is, however, little data to suggest which is the most effective technique, or whether specific techniques are more appropriate in certain circumstances.7     

Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial

Context  Hormone replacement therapy (HRT) and antioxidant vitamins are widely used for secondary prevention in postmenopausal women with coronary disease, but no clinical trials have demonstrated benefit to support their use. Objective  To determine whether HRT or antioxidant vitamin supplements, alone or in combination, influence the progression of coronary artery disease in postmenopausal women, as measured by serial quantitative coronary angiography. Design, Setting, and Patients  The Women's Angiographic Vitamin and Estrogen (WAVE) Trial, a randomized, double-blind trial of 423 postmenopausal women with at least one 15% to 75% coronary stenosis at baseline coronary angiography. The trial was conducted from July 1997 to January 2002 in 7 clinical centers in the United States and Canada. Interventions  Patients were randomly assigned in a 2 x 2 factorial design to receive either 0.625 mg/d of conjugated equine estrogen (plus 2.5 mg/d of medroxyprogesterone acetate for women who had not had a hysterectomy), or matching placebo, and 400 IU of vitamin E twice daily plus 500 mg of vitamin C twice daily, or placebo. Main Outcome Measure  Annualized mean (SD) change in minimum lumen diameter (MLD) from baseline to concluding angiogram of all qualifying coronary lesions averaged for each patient. Patients with intercurrent death or myocardial infarction (MI) were imputed the worst rank of angiographic outcome. Results  The mean (SD) interval between angiograms was 2.8 (0.9) years. Coronary progression, measured in mean (SD) change, worsened with HRT by 0.047 (0.15) mm/y and by 0.024 (0.15) mm/y with HRT placebo (P = .17); and for antioxidant vitamins by 0.044 (0.15) mm/y and with vitamin placebo by 0.028 (0.15) mm/y (P = .32). When patients with intercurrent death or MI were included, the primary outcome showed an increased risk for women in the active HRT group (P = .045), and suggested an increased risk in the active vitamin group (P = .09). Fourteen patients died in the HRT group and 8 in the HRT placebo group (hazard ratio [HR], 1.8; 95% confidence interval [CI], 0.75-4.3), and 16 in the vitamin group and 6 in the vitamin placebo group (HR, 2.8; 95% CI, 1.1-7.2). Death, nonfatal MI, or stroke occurred in 26 HRT patients vs 15 HRT controls (HR, 1.9; 95% CI, 0.97-3.6) and in 26 vitamin patients and 18 vitamin controls (HR, 1.5; 95% CI, 0.80-2.9). There was no interaction between the 2 treatment interventions. Conclusion  In postmenopausal women with coronary disease, neither HRT nor antioxidant vitamin supplements provide cardiovascular benefit. Instead, a potential for harm was suggested with each treatment.      

Sleep loss and fatigue in residency training: a reappraisal

Reduced sleep time is commonplace for many interns and residents. Recent studies, however, suggest that sleep loss and fatigue result in significant neurobehavioral impairments in healthy young adults. We reviewed studies addressing the effects of sleep loss on cognition, performance, and health in surgical and nonsurgical residents. We describe the effectiveness of countermeasures for sleepiness, including recent work-hour restrictions. A more complete understanding of the issues of sleep loss during residency training can inform innovative strategies to minimize the effects of sleepiness and fatigue on patient care and resident safety.      

Neuropsychiatric complications of antiretroviral therapy.

Neuropsychiatric adverse effects related to potent antiretroviral therapy are among the complications that can lead to poor adherence, treatment interruptions, or change of antiretroviral therapy regimens. For a historical perspective, we review early literature and case reports with CNS adverse effects attributed to antiretrovirals. The variability of the cerebrospinal fluid penetration of individual antiretrovirals may contribute to their potential for behavioural and psychiatric manifestations.The majority of neuropsychiatric complications related to potent antiretroviral therapy have been associated with the use of the efavirenz. Updates on the risk of neuropsychiatric manifestations with efavirenz use in patients with a history of psychiatric disorders or substance abuse are reviewed. We include a critical review of recently published data on the long-term CNS adverse effects with efavirenz. Special attention is given to the results of recent investigations on the relationship between the pharmacogenomics of genes responsible for efavirenz metabolism and the plasma concentration of efavirenz. It is important to note that there is no established direct correlation of efavirenz concentrations and symptoms. It is not recommended for practitioners to adjust efavirenz doses in order to prevent or alleviate CNS adverse effects. Patients may be placed at risk for virological failure and resistance if they receive suboptimal doses of efavirenz. The aim of this article is to give a concise review and an update on recent literature concerning neuropsychiatric effects of antiretroviral use in HIV-infected patients. Our intent is to present practitioners with data that can be used in a practical way to both educate and improve outcomes in the HIV-infected patient population.     

Toxicological safety evaluation of DNA plasmid vaccines against HIV-1, Ebola, Severe Acute Respiratory Syndrome, or West Nile virus is similar despite differing plasmid backbones or gene-inserts.

The Vaccine Research Center has developed a number of vaccine candidates for different diseases/infectious agents (HIV-1, Severe Acute Respiratory Syndrome virus, West Nile virus, and Ebola virus, plus a plasmid cytokine adjuvant-IL-2/Ig) based on a DNA plasmid vaccine platform. To support the clinical development of each of these vaccine candidates, preclinical studies were performed to screen for potential toxicities (intrinsic and immunotoxicities). All treatment-related toxicities identified in these repeated-dose toxicology studies have been confined primarily to the sites of injection and seem to be the result of both the delivery method (as they are seen in both control and treated animals) and the intended immune response to the vaccine (as they occur with greater frequency and severity in treated animals). Reactogenicity at the site of injection is generally seen to be reversible as the frequency and severity diminished between doses and between the immediate and recovery termination time points. This observation also correlated with the biodistribution data reported in the companion article (Sheets et al., 2006), in which DNA plasmid vaccine was shown to remain at the site of injection, rather than biodistributing widely, and to clear over time. The results of these safety studies have been submitted to the Food and Drug Administration to support the safety of initiating clinical studies with these and related DNA plasmid vaccines. Thus far, standard repeated-dose toxicology studies have not identified any target organs for toxicity (other than the injection site) for our DNA plasmid vaccines at doses up to 8 mg per immunization, regardless of disease indication (i.e., expressed gene-insert) and despite differences (strengths) in the promoters used to drive this expression. As clinical data accumulate with these products, it will be possible to retrospectively compare the safety profiles of the products in the clinic to the results of the repeated-dose toxicology studies, in order to determine the utility of such toxicology studies for signaling potential immunotoxicities or intrinsic toxicities from DNA vaccines. These data build on the biodistribution studies performed (see companion article, Sheets et al., 2006) to demonstrate the safety and suitability for investigational human use of DNA plasmid vaccine candidates for a variety of infectious disease prevention indications.