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The objective of this study was to determine whether a dopamine agonist could improve mental status among children in a low-response state following traumatic brain injury. In an 8-week, prospective, double-blind, randomized trial, 10 children and adolescents ages 8 to 21 years (X = 16.7 years) with traumatic brain injury sustained at least 1 month previously and remaining in a low-response state (Rancho Los Amigos Scale level ≤ 3) received pramipexole or amantadine. Medication dosage was increased over 4 weeks, weaned over 2 weeks, and then discontinued. At baseline and weekly during the study, subjects were evaluated with the Coma Near Coma Scale, Western NeuroSensory Stimulation Profile, and Disability Rating Scale. Scores improved significantly from baseline to the medication phase on the Coma Near Coma Scale, Western NeuroSensory Stimulation Profile, and Disability Rating Scale (P < .005). The weekly rate of change was significantly better for all three measures on medication than off medication (P < .05). Rancho Los Amigos Scale levels improved significantly on medication as well (P < .05). There was no difference in efficacy between amantadine and pramipexole. No unexpected or significant side effects were observed with either drug This clinical trial supports the benefit of two dopamine agonists in the restoration of functional arousal, awareness, and communication. These drugs can be helpful in accelerating eligibility for acute rehabilitation among children and adolescents who have sustained significant brain injuries. [ABSTRACT FROM AUTHOR]

The relative contribution of the angiotensin II type 1 and 2 receptors (AT1-R and AT2-R) in postmyocardial infarction (MI) remodeling remains incompletely understood. We studied five groups of C57BI/6 mice after 1 h of left anterior descending artery occlusion-reperfusion: 1) wild type, untreated (n = 12); 2) wild type, treated with the AT1-R blocker losartan (10–20 mg·kg-1·day-1 in drinking water) from day 1 to day 28 post-MI (n = 10); 3) cardiac overexpression of the AT2-R [AT2-transgenic (TG); n = 14]; 4) AT2-TG treated with losartan (n = 13); and 5) AT2-TG and null for the AT1a-R [AT2-TG/AT1 knockout (KO); n = 10]. Cardiac magnetic resonance imaging (CMR) measured ejection fraction and left ventricular end-diastolic and endsystolic volume (EDVI and ESVI) and mass indexed to weight on days 0, 1, 7, and 28 post-MI. Infarct size was measured on day 1 by late gadolinium-enhanced CMR. Regional myocyte hypertrophy and collagen content were measured on day 28 post-MI. Infarct size was similar among groups. Systolic blood pressure was lowest in AT2-TG/AT1KO. By day 28 post-MI, when corrected for baseline differences, EDVI and ESVI were higher and ejection fraction was lower in wild type than other groups. Ejection fraction was highest and EDVI and mass index were lowest in AT2-TG/AT1KO at day 28. The AT2-TG/AT1KO demonstrated less fibrosis in adjacent regions. Regional myocyte hypertrophy was similar in all groups. The AT1-R and AT2-R are intricately intertwined in post-Ml remodeling. Pharmacological blockade of AT1-R is equivalent to AT2-R overexpression in attenuating post-MI remodeling. Genetic knockout of the AT1a-R is additive to AT2-R overexpression, due, at least in part, to blood pressure lowering. [ABSTRACT FROM AUTHOR]

Context Despite evidence that patients with acute lung injury (ALI) have pulmonary surfactant dysfunction, trials of several surfactant preparations to treat adults with ALI have not been successful. Preliminary studies in children with ALI have shown that instillation of a natural lung surfactant (calfactant) containing high levels of surfactant-specific protein B may be beneficial. Objective To determine if endotracheal instillation of calfactant in infants, children, and adolescents with ALI would shorten the course of respiratory failure. Design, Setting, and Patients A multicenter, randomized, blinded trial of calfactant compared with placebo in 153 infants, children, and adolescents with respiratory failure from ALI conducted from July 2000 to July 2003. Twenty-one tertiary care pediatric intensive care units participated. Entry criteria included age 1 week to 21 years, enrollment within 48 hours of endotracheal intubation, radiological evidence of bilateral lung disease, and an oxygenation index higher than 7. Premature infants and children with preexisting lung, cardiac, or central nervous system disease were excluded. Intervention Treatment with intratracheal instillation of 2 doses of 80 mL/m2 calfactant or an equal volume of air placebo administered 12 hours apart. Main Outcome Measures Ventilator-free days and mortality; secondary outcome measures were hospital course, adverse events, and failure of conventional mechanical ventilation. Results The calfactant group experienced an acute mean (SD) decrease in oxygenation index from 20 (12.9) to 13.9 (9.6) after 12 hours compared with the placebo group's decrease from 20.5 (14.7) to 15.1 (9.0) (P = .01). Mortality was significantly greater in the placebo group compared with the calfactant group (27/75 vs 15/77; odds ratio, 2.32; 95% confidence interval, 1.15-4.85), although ventilator-free days were not different. More patients in the placebo group did not respond to conventional mechanical ven... [ABSTRACT FROM AUTHOR]

OBJECTIVE: Endoscopic treatment of ampullary lesions has been well described, though it remains uncertain if specific features predict malignancy, and whether identifiable factors are associated with successful endoscopic resection of benign lesions.METHODS: Fifty-six consecutive patients undergoing endoscopic evaluation of ampullary neoplasia between March 2000 and May 2004 were included in the study. Clinical presentation, underlying medical conditions, endoscopic treatment, endoscopic ultrasound (EUS) to define extent of local involvement, pathology results, and outcome were documented. Data elements for analysis included EUS findings, lesion lifting with submucosal injection, age, gender, tumor size, and endoscopic intervention. Analyses were performed to determine the ability to predict malignancy and the ability to extirpate benign lesions.RESULTS: Thirty-one males and 25 females were included; mean age was 62 yr. Final diagnoses included 29 adenomas, 20 adenocarcinomas, 4 adenomyomas, 2 paragangliomas, and 1 neuroendocrine tumor. Thirty of 35 patients with benign lesions had extirpation with a mean of two endoscopic procedures. Complications of endoscopic resection included cholangitis (), bleeding (), and pancreatitis (). The presence of malignancy was associated by multivariate analysis with the inability to obtain a cleavage plane with saline injection. Univariate analysis also identified EUS T stage as a predictor of malignancy. In benign lesions, none of the analyzed variables predicted successful endoscopic resection.CONCLUSION: In ampullary lesions, failure to achieve a cleavage plane with submucosal injection is the strongest predictor of malignancy followed by EUS T stage. Endoscopic treatment of benign ampullary neoplasia is effective; no factor was predictive of successful extirpation.(Am J Gastroenterol 2004;99:1–5) [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy of a lifestyle intervention program that can be readily translated into clinical practice for obese patients with type 2 diabetes.Research Design and Methods: The study consisted of a 12-month randomized controlled trial of 147 health plan members with type 2 diabetes and obesity (BMI >or=27 kg/m(2)). Participants were randomized to lifestyle case management or usual care. Case management entailed individual and group education, support, and referral by registered dietitians; intervention cost was US dollars 350 per person. Individuals treated with usual care received educational material. Both groups received ongoing primary care. Outcomes were difference between groups for change in weight (kilograms), waist circumference (centimeters), HbA(1c), fasting lipid levels, use of prescription medications, and health-related quality of life.Results: Case management resulted in greater weight loss (P < 0.001), reduced waist circumference (P < 0.001), reduced HbA(1c) level (P = 0.02), less use of prescription medications (P = 0.03), and improved health-related quality of life (P < 0.001) compared with usual care. The 12-month group difference in weight loss and waist circumference was 3.0 kg (95% CI -5.4 to -0.6) and -4.2 cm (-6.8 to -1.6). HbA(1c) differences were greatest at 4 months (-0.59%, P = 0.006) but not significant by 12 months (-0.19%, P = 0.45). Participants in the case management group lowered their use of medications, primarily diabetes medications, by 0.8 medications per day more than participants treated with usual care (P = 0.03). In seven of nine quality-of-life domains, the case management group improved compared with usual care (P < 0.05).Conclusions: Moderate-cost dietitian-led lifestyle case management may improve diverse health indicators among obese patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

The use of botanical mixtures is commonplace in patients with prostate cancer, yet the majority of these products have not been rigorously tested in clinical trials. Here we use PC-SPES, a combination of eight herbs that has been shown to be effective in clinical trials in patients with prostate cancer, as a model system to demonstrate 'proof of principle' as to how gene expression profiling coupled with promoter assays can evaluate the effect of herbal cocktails on human prostate cancer. In addition, we demonstrate how such approaches may be used for standardization of herbal extract activity by comparing the gene profile of PC-SPES with that of PC-CARE, a product with a similar herbal composition. Since prior studies have shown that PC-SPES contains estrogenic organic compounds, and such compounds are known to affect prostate cancer, an important issue is whether these are the primary drivers of the gene profile. Our data suggest that gene expression profiles of LNCaP human prostate cancer cells in response to PC-SPES are different from those found when diethylstilbestrol (DES), a synthetic estrogen, is used, suggesting that the estrogenic moieties within PC-SPES do not drive this expression signature. In contrast, the expression profile of PC-CARE was almost identical to that of DES, highlighting that mixtures containing similar herbal compositions do not necessarily result in similar biological activities. Interestingly, these three agents cause similar in vitro morphological changes and growth effects on LNCaP. To validate the expression profiling data, we evaluated the protein expression and promoter activity of prostate-specific antigen (PSA), a gene induced by PC-SPES but repressed by DES. In order to gain a mechanistic understanding of how PC-SPES and DES affect PSA expression differently, LNCaP cells were transiently transfected with wild-type and mutagenized PSA promoter, ARE concatemers and appropriate controls. We provide evidence that androgen... [ABSTRACT FROM AUTHOR]

Objective: To test effectiveness of static magnetic fields of two different configurations, produced by magnetic sleep pads, as adjunctive therapies in decreasing patient pain perception and improving functional status in individuals with fibromyalgia. Design: Randomized, placebo-controlled, 6-month trial conducted from November 1997 through December 1998. Setting and subjects: Adults who met the 1990 American College of Rheumatology criteria for fibromyalgia were recruited through clinical referral and media announcements and evaluated at a university-based clinic. Interventions: Subjects in Functional Pad A group used a pad for 6 months that provided whole-body exposure to a low, uniform static magnetic field of negative polarity. Subjects in the Functional Pad B group used a pad for 6 months that exposed them to a low static magnetic field that varied spatially and in polarity. Subjects in two Sham groups used pads that were identical in appearance and texture to the functional pads but contained inactive magnets; these groups were combined for analysis. Subjects in the Usual Care group continued with their established treatment regimens. Outcome measures: Primary outcomes were the change scores at 6 months in the following measures: functional status (Fibromyalgia Impact Questionnaire), pain intensity ratings, tender point count, and a tender point pain intensity score. Results: There was a significant difference among groups in pain intensity ratings (p = 0.03), with Functional Pad A group showing the greatest reduction from baseline at 6 months. All four groups showed a decline in number of tender points, but differences among the groups were not significant (p = 0.72). The functional pad groups showed the largest decline in total tender point pain intensity, but overall differences were not significant (p = 0.25). Improvement in functional status was greatest in the functional pad groups, but differences among groups were not significant (p = 0.23). Conclusions: Although the functional pad groups showed improvements in functional status, pain intensity level, tender point count, and tender point intensity after 6 months of treatment, with the exception of pain intensity level these improvements did not differ significantly from changes in the Sham group or in the Usual Care group. [ABSTRACT FROM AUTHOR]

The article discusses a study on integrin adjunct therapy for the treatment of melanoma. It mentions that multivalent integrin binding reagents are able to mimic adhesion to extracellular matrices by clustering the integrins. It mentions the development of pentavalent fibronectin in the binding region of integrins and also mentions assessment of entry and stability of the fibrinectin in blood of mice.