Postmenopausal estrogen and progestogen therapy and the risk of uterine leiomyomas

OBJECTIVE: Leiomyomas are common benign neoplasms. Although hormone therapy is the most common and effective treatment for menopausal symptoms, little is known about its effect on leiomyomas. We examined the risk of a first diagnosis of leiomyomas in peri- and postmenopausal women associated with prior use of estrogen and progestogen therapy (EPT). DESIGN: A case-control study was conducted among enrollees from a nonprofit health plan. Cases had a first diagnosis of leiomyomas confirmed by surgery or ultrasound. Controls were women of the same age range without a diagnosis of leiomyomas selected at random from membership and outpatient files. Participants were interviewed regarding prior use of exogenous hormones, medical history, and reproductive history. This analysis was restricted to cases (n = 256) and controls (n = 276) who were peri- or postmenopausal and more than 40 years of age. Adjusted odds ratios (OR) and 95% CIs were estimated using logistic regression models. RESULTS: EPT use for more than 5 years was associated with a 1.7-fold increased risk of leiomyomas (95% CI, 0.9-3.3). Associations with EPT use were only present among women with a body mass index less than 24 kg/m; OR (ever-use), 2.3 (95% CI, 1.2-4.3); and OR (>or= 5 years use), 4.0 (95% CI, 1.6-10.3). CONCLUSION: Among peri- and postmenopausal women, prior EPT use was associated with an increased risk of a subsequent leiomyomas. This association seemed limited to the subset of women with low body mass index. Exogenous sources of estrogen and progestin in the setting of low adiposity may contribute to the development of leiomyomas.     

Are there racial differences in the way patients with psychotic disorders are treated at their first hospitalization?

BACKGROUND: It is now well documented that both black and white patients with severe mental illness are likely to use different types of treatment facilities, have different lengths of hospital stays, and receive different types and dosages of psychotropic medications. It is still uncertain, however, whether these differences exist at the early stages of treatment. METHOD: We examined treatment patterns for a countywide sample of patients with psychotic disorders recruited at their initial psychiatric hospitalization. Illness characteristics, prior treatment histories, admission conditions, and psychotropic medication use during this hospitalization were compared for both black and white patients. RESULTS: Black patients were less likely to have had out-patient treatment prior to their first hospitalization and were more likely to be hospitalized in public than in community psychiatric units than were white patients. Black patients were also more likely to be hospitalized primarily for a behavioral disturbance and escorted to the hospital by the emergency medical services or police, while white patients were more often hospitalized primarily for subjective suffering. These patterns were particularly significant for those with a non-schizophrenia diagnosis. However, there were few statistically significant differences between black and white patients on psychotropic medication use during the first hospitalization. CONCLUSIONS: Differences during the early stages of treatment between black and white patients with psychotic disorders appear to arise most prominently before, rather than during, their first hospitalization.     

Expansion of quasispecies diversity but no evidence for adaptive evolution of SHIV during rapid serial transfers among seronegative macaques

Four successive, rapid serial passages of the nonpathogenic, CCR5-tropic simian-human immunodeficiency virus SHIV(SF162) in rhesus macaques resulted in an increase in acute plasma viremia with each passage and the emergence of a pathogenic isolate SHIV(SF162P3) in one of the passage three transfer animals (macaque T353). To explore the mechanism(s) underlying increased virulence of SHIV(SF162) upon in vivo passage, the evolution of the HIV-1 envelope gene was characterized in plasma and PBMC samples obtained from animals before (week 1) and after (week 3) the time of virus transfer. We found no evidence in support of adaptive evolution of the HIV gp120 during rapid serial passage; however, the animals which later received passage virus had more diverse quasispecies. SHIV(SF162P3)-like gp120 sequences were first detected in macaque T353 at week 6, after seroconversion. These sequence changes increased in frequency and number at later time points. The first sequence change conferred neutralization escape but not an increase in viral infectivity that could account for the apparent increase in replicative capacity of the later passage viruses. Collectively, our data argue against any host-specific adaptation of the HIV-1 envelope gp120 as the basis for the generation of more aggressive SHIV variants during rapid serial transfers in seronegative macaques, and support the model of quasispecies diversity as a predictor of pathogenesis. Envelope sequence changes accumulate principally in response to immune pressure exerted by the host, generating viral variants that can persist in the presence of a strong host immune response.     

Interference and enhancement effects on interaural time discrimination and level discrimination in listeners with normal hearing and those with hearing loss

It is known that many listeners with sensorineural hearing loss (SNHL) have difficulty performing binaural tasks. In this study, interference and enhancement effects on interaural time discrimination and level discrimination were investigated in 4 listeners with normal hearing (NH) and 7 listeners with SNHL. Just-noticeable differences were measured using 1/3-octave narrowband noises centered at 0.5 and 4 kHz. Noises were presented in isolation and together at equivalent sound pressure level (EqSPL) and equivalent sensation level (EqSL). Each noise served as target and distractor in the dual-band conditions. Congruent conditions included interaural differences in both noises that varied together, and incongruent conditions included an interaural difference in one noise with the second noise diotic. No significant enhancement effects were observed for either group in either task. Interference effects for the NH group were limited to the interaural level discrimination task in the 0.5-kHz target and 4-kHz distractor condition. Performance of participants with SNHL was similar to that of the NH group for interaural time discrimination with noises at EqSL but not EqSPL. In interaural level discrimination, listeners with SNHL demonstrated interference with a 4-kHz target and 0.5-kHz distractor. Results indicated that the relative levels of low- and high-frequency targets and distractors could affect binaural performance of individuals with SNHL but that in some conditions listeners with SNHL performed similarly to those with normal hearing. Implications of these results for binaural clinical tests and hearing aid fitting strategies are discussed.     

Autoimmune lymphoproliferative syndrome: a cause of chronic splenomegaly, lymphadenopathy, and cytopenias in children-report on diagnosis and management of five patients

Autoimmune lymphoproliferative syndrome (ALPS) usually manifests in early childhood with splenomegaly, lymphadenopathy, and cytopenias. In most patients, it results from mutations in genes that regulate lymphocyte apoptosis via the Fas pathway. Here, we report five children with ALPS. All five children had splenomegaly, cytopenias, and hypertriglyceridemia at presentation; four had lymphadenopathy. Mutations in the Fas receptor gene were demonstrated in three children. Clinical picture is variable: in only one child manifestations are severe enough to require immunosuppressive therapy. Diagnosis of ALPS can be challenging and increased awareness of the disease can result in more directed diagnostic approaches as well as earlier initiation of treatment.     

Palmoplantar hyperhidrosis: a therapeutic challenge

Excessive sweating from the palms and soles, known as palmoplantar hyperhidrosis, affects both children and adults. Diagnosis of this potentially embarrassing and socially disabling condition is based on the patient's history and visible signs of sweating. The condition usually is idiopathic. Treatment remains a challenge: options include topical and systemic agents, iontophoresis, and botulinum toxin type A injections, with surgical sympathectomy as a last resort. None of the treatments is without limitations or associated complications. Topical aluminum chloride hexahydrate therapy and iontophoresis are simple, safe, and inexpensive therapies; however, continuous application is required because results are often short-lived, and they may be insufficient. Systemic agents such as anticholinergic drugs are tolerated poorly at the dosages required for efficacy and usually are not an option because of their associated toxicity. While botulinum toxin can be used in treatment-resistant cases, numerous painful injections are required, and effects are limited to a few months. Surgical sympathectomy should be reserved for the most severe cases and should be performed only after all other treatments have failed. Although the safety and reliability of treatments for palmoplantar hyperhidrosis have improved dramatically, side effects and compensatory sweating are still common, potentially severe problems.     

Uncertainty intervention for watchful waiting in prostate cancer

Watchful waiting is a reasonable alternative to treatment for some older men with localized prostate cancer, but it inevitably brings uncertainty. This study tested the effectiveness of the watchful waiting intervention (WWI) in helping men cognitively reframe and manage the uncertainty of watchful waiting. Based on Mishel's Reconceptualized Uncertainty in Illness Theory (Image. 1990; 256-262), the WWI was tested with a convenience sample of 41 men. Experimental subjects received 5 weekly intervention calls from a nurse. Control subjects received usual care. Outcomes were new view of life, mood state, quality of life, and cognitive reframing. Repeated measures of analysis of variance were used to test the effectiveness of the WWI. The sample was 86% Caucasian and 14% African American, with an average age of 75.4 years. Intervention subjects were significantly more likely than controls to view their lives in a new light (P = .02) and experience a decrease in confusion (P = .04) following the intervention. Additionally, intervention subjects reported greater improvement in their quality of life than did controls (P = .01) and believed their quality of life in the future would be better than did controls (P = .01). This study's findings document the benefits of the WWI for patients living with uncertainty.