The effects of perinatal hypoxia on the behavioral,neurochemical, and neurohistological toxicity of the metabolic inhibitor 3-nitropropionic acid

3-nitropropionic acid (3-NPA) neurotoxicity and long-term effects of perinatal hypoxia were evaluated in 18 adult rats. Hypoxia-insulted (I) and noninsulted (NI) rats were delivered by cesarean section. Hypoxic insult was effected by submerging dissected uterine horns in warmed saline for 15 min. NI rats were delivered from the adjacent nonsubmerged horns. At postnatal day 90, I and NI rats were trained to perform tasks thought to measure behaviors dependent upon aspects of time estimation (TE), motivation, and learning. At 12 months of age, rats were injected i.p. with escalating doses of 3-NPA (5 mg/kg/day to a maximum of 30 mg/kg/day) immediately after each test session and sacrificed at the end of treatment. Additional male rats were used as untreated controls. Although 3-NPA produced a dose-dependent impairment of performance in each task, the effects were qualitatively similar for each group. A significant difference between I and NI rats was, however, observed in the TE task where NI rats completed less of the task at high doses of 3-NPA compared to I rats. Compared to untreated controls, dopamine concentrations were decreased in caudate nucleus of both I and NI rats after 3-NPA. Specific areas most frequently damaged included cerebral cortex, hippocampal subfield CA1, thalamus, caudate nucleus, and the cerebellum. Lesions usually were less extensive in the I rather than NI members of a littermate pair, suggesting a possible protective effect of perinatal hypoxia against subsequent 3-NPA neurotoxicity.     

The idiopathic musculoskeletal pain syndromes in childhood

Idiopathic musculoskeletal pain syndromes in children have a variety of manifestations; they can be diffuse or well localized, constant or intermittent, with or without autonomic symptoms and signs, completely incapacitating or not limiting activities, and they can tax the physician's diagnostic skill. A careful history and examination is usually all that is needed to make a diagnosis, although the differential diagnosis is large and might require laboratory and radiographic investigation. Pain and functional assessment help track the progress with therapy. Intense exercise therapy is associated with the best outcome. Psychologic issues should be evaluated to determine if further psychologic intervention is indicated. The medium-term outcome is probably good for most of these children, but the long-term prognosis is unknown. One must be aware that other manifestations of psychologic problems might emerge. By the time these children and their families see the rheumatologist they are desperate and can be frustrating to work with due to their difficulty in accepting any kind of psychologic element to the pain and its associated disability. Nevertheless, it is rewarding to help the children understand and work through their pain so they can resume normal lives.     

Metoclopramide-Induced Normalization of Impaired Gastric Emptying in Spinal Cord Injury

In a partial, two-way crossover study of gastric emptying (GE) in spinal cord injury (SCI), fasted, healthy, unmedicated male volunteers were given a 99mTc-labeled liquid meal on two occasions. Metoclopramide (10 mg) was administered intravenously to each subject before the second evaluation of GE. We used single and multiexponential models with linear and nonlinear least-squares regression techniques to study the time-course of the disappearance of 99mTc from the stomach. The GE pattern in all subjects was most accurately characterized by nonlinear analysis (NONLIN) and consisted of two components, an initial adynamic phase and a phase of rapid emptying. The GE t1/2 of a liquid meal decreased from 106.6 +/- 58.3 min (mean +/- SD) in all SCI subjects (quadriplegic plus paraplegic) prior to treatment to 21.6 +/- 8.2 min after the intravenous administration of metoclopramide (p less than 0.006). Significant correlations between GE t1/2 and injury duration (yr) or level of spinal injury were observed. Impaired gastric emptying in SCI can be pharmacologically modified by metoclopramide to resemble a normal gastric emptying profile. Metoclopramide-altered gastric emptying in SCI may be expected to result in changes in the therapeutic efficacy of orally administered drugs when drug absorption is dependent on gastric motility or emptying efficiency.     

Predictors of Change in Frequency of Crack Cocaine Use in a Street-Recruited Sample

Crack cocaine users are at high risk for HIV, with higher frequency crack users engaging in higher rates of HIV-related sexual risk behaviors. This study will assess the variables impacting changes in crack use frequency. Out-of-treatment crack users were street recruited in East Harlem, NY. Subjects (n = 727) were 33% female, 91% minority, and 28% reported recent drug injecting. Baseline and 6-month follow-up interviews were administered. There was a significant reduction in crack use over time (p < .0001). Subjects were categorized according to five groups, based on their change in level of crack use between the two interviews, to predict those who stopped, maintained, or changed their level of use. Discriminant analyses identified six variables as the best predictors of the five groups, including having been in drug treatment since baseline and having been a drug injector (both related to reduced levels of crack use). The overall reduction in crack use for the sample masked the fact that important subgroups remained at high use levels or increased their use. The identification of subgroups who may be most resistant to reducing drug use can be helpful in developing more effective interventions.     

Inflammatory carcinoma of the breast. Clinical review and summary of the Vanderbilt experience with multi-modality therapy

Inflammatory breast cancer is a distinct clinicopathologic entity that accounts for 1 percent of all cases of breast cancer. The diagnosis should be strongly suspected on the basis of the distinctive clinical findings, which include edema of the breast, inflammation, wheals, and a typical reddish-purple color of the overlying skin. Pathologic examination usually shows infiltration of the dermal lymphatics with carcinoma. Evidence of distant metastatic spread is more frequent than with other types of breast cancer and is seen in approximately 30 percent of patients. The five-year disease-free survival rate is less than 5 percent when local therapy alone (mastectomy and/or local radiotherapy) is used. The addition of combination chemotherapy to high-dose local radiotherapy has improved the five-year survival rate to approximately 30 percent. The potential for long-term survival is limited to the subgroup of patients with only local-regional disease at the time of diagnosis. Patients with inflammatory breast cancer should be treated with combined-modality therapy using combination chemotherapy and high-dose radiotherapy to the breast, since this approach is potentially curative. The fatalism formerly associated with this diagnosis is no longer warranted, particularly in patients with local-regional disease. Failure to employ intensive combined-modality treatment will deny some patients a chance for long-term survival.     

The birth,decline, and contemporary re-emergence of endovascular brachytherapy for prevention of in-stent restenosis

Despite the advent of drug-eluting stents and dual antiplatelet therapy in the interventional management of cardiovascular disease, restenosis rates remain high with significant sequelae. Endovascular brachytherapy—popular in the 1990s and early 2000s—has recently resurfaced as a cost-effective treatment option. In this work, we outline the history of endovascular brachytherapy starting with its earliest promise in the 1990s. We discuss the development of drug-eluting stents and dual antiplatelet strategies and their impact on the perceived benefit of endovascular brachytherapy. For the contemporary era, we propose novel roles for endovascular brachytherapy in complex coronary artery disease and in high-risk patients managed with drug-eluting stents. We discuss the impetus for reducing the requirement and duration of dual antiplatelet therapy using endovascular brachytherapy. We also review innovative opportunities for endovascular brachytherapy after bare-metal stent placement in both coronary and noncoronary territories and offer economic arguments in favor of endovascular brachytherapy. Trials of endovascular brachytherapy in these regimes are merited.     

Internet-Based Behavioral Activation Program for Depression and Problem Gambling: Lessons Learned from Stakeholder Interviews

International Journal of Mental Health and Addiction - Behavioral activation (BA) is a well-established treatment for depression, often used as an adjuvant for gambling disorder. Internet-based BA...     

Occupational Risk Factors for COPD Phenotypes in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study

Introduction: The contribution of occupational exposure to the risk of chronic obstructive pulmonary disease COPD in population-based studies is of interest. We compared the performance of self-reported exposure to a newly developed JEM in exposure-response evaluation. Methods: We used cross-sectional data from Multi-Ethnic Study of Atherosclerosis (MESA), a population-based sample of 45–84 year olds free of clinical cardiovascular disease at baseline. MESA ascertained the most recent job and employment, and the MESA Lung Study measured spirometry, and occupational exposures for 3686 participants. Associations between health outcomes (spirometry defined airflow limitation and Medical Research Council-defined chronic bronchitis) and occupational exposure [self-reported occupational exposure to vapor-gas, dust, or fumes (VGDF), severity of exposure, and a job-exposure matrix (JEM)-derived score] were evaluated using logistic regression models adjusted for non-occupational risk factors. Results: The prevalence of airflow limitation was associated with self-reported exposure to vapor-gas (OR 2.6, 95%CI 1.1–2.3), severity of VGDF exposure (P-trend < 0.01), and JEM dust exposure (OR 2.4, 95%CI 1.1–5.0), and with organic dust exposure in females; these associations were generally of greater magnitude among never smokers. The prevalence of chronic bronchitis and wheeze was associated with exposure to VGDF. The association between airflow limitation and the combined effect of smoking and VGDF exposure showed an increasing trend. Self-reported vapor-gas, dust, fumes, years and severity of exposure were associated with increased prevalence of chronic bronchitis and wheeze (P < 0.001). Conclusions: Airflow limitation was associated with self-reported VGDF exposure, its severity, and JEM-ascertained dust exposure in smokers and never-smokers in this multiethnic study.