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21.
Stephen Hanessian 《ACS medicinal chemistry letters》2016,7(1):6-9
Current major advances in drug discovery
can be traced back to
pioneering contributions originating from academics over a century
ago. Living in a symbiotic yet noninvasive coexistence, the academic
community and the pharmaceutical industry have strived, each in their
own way, to develop the modern medicines that benefit humankind today.
The subject is presented from a historical and personal perspective. 相似文献
22.
Pulmonary hamartomas are usually an incidental finding and range in size from 1 cm to 8 cm in diameter in various series. We report a case of a massive pulmonary hamartoma (size 25.5 × 17.5 × 6.5 cm and weighing 1134 g) in a 61 year old male who presented with a short history of breathlessness. The tumour was arising from the medial border of the right lung and occupying most of the right chest extending in to the anterior mediastinum. The tumour was compressing the right lung and there was no evidence of infiltration into the surrounding structures. It was successfully treated by surgical resection and final histology was pulmonary hamartoma with predominantly adipose and leiomyomatous differentiation. 相似文献
23.
Stephen J Glatt Erik G J?nsson 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2006,(2):149-154
Previously we derived independent estimates of the effect of the dopamine D2 receptor (DRD2) Ser311Cys polymorphism on risk for schizophrenia using fixed- and random-effects meta-analyses. Both analyses identified a significant association between the Cys allele and schizophrenia, but neither included all available data. Furthermore, genotype data were not evaluated in either analysis, thus precluding any determination of the mode of inheritance. The present study was conducted to resolve discrepancies between the existing meta-analyses, and provide more comprehensive and accurate estimates of the nature and magnitude of the influence of the Ser311Cys polymorphism on risk for schizophrenia. All discrepancies between the two sets of previously meta-analyzed studies were identified and resolved to the mutual satisfaction of the authors, and the final dataset was analyzed independently by fixed- and random-effects meta-analyses. A total of 27 samples, comprising 3,707 schizophrenia patients and 5,363 control subjects, were included in the analyses of allelic association, while smaller numbers of studies and subjects were included in each of the genotypic association analyses. A significant effect of the Cys allele was observed under both fixed-effects (odds ratio [OR] = 1.4; P = 0.002) and random-effects (OR = 1.4; P = 0.007) models. Cys/Ser heterozygotes were at elevated risk for schizophrenia when compared to Ser/Ser homozygotes (fixed- and random-effects OR = 1.4, p(s) or= 0.948). There was no evidence of heterogeneity, excessive influence of any single study, or publication bias in any of the analyses, suggesting that the effect of this DRD2 polymorphism on schizophrenia risk is reliable and uniform across populations, and our estimates of its magnitude are robust and accurate. 相似文献
24.
Eric W. Dickson MD Gary V. Doern PhD Leo Trevino PhD Michelle Mazzoni PhD Stephen O. Heard MD 《Academic emergency medicine》2003,10(10):1019-1023
OBJECTIVES: Patients undergoing emergent endotracheal intubation are at increased risk for developing pneumonia. Although numerous strategies have been investigated to reduce ventilator-associated pneumonia (VAP), the incidence of VAP and its associated mortality remains high. This investigation tested the hypothesis that LiquiVent (Alliance Pharmaceutical, San Diego, CA-LV) delivered antibiotics (via spray-dried microspheres-SDM) would improve survival in a rat model of descending gram-negative pneumonia. METHODS: Wistar rats (n = 49) were randomized to receive prophylaxis with 1). nothing (controls); 2). intramuscular (IM) tobramycin, 3). intratracheal LV plus SDM shells (vehicle), 4). intratracheal LV plus SDM shells plus IM tobramycin, or 5). intratracheal LV plus SDM containing 1 mg/kg of tobramycin. All interventions were given 24 hours before a bacterial challenge with 10(8) colony-forming units of intratracheal Klebsiella pneumoniae. Mortality at ten days was the sole outcome measure. Survival in individual groups was compared with controls by Fisher's exact test with Bonferroni correction for multiple comparisons. RESULTS: All animals in the control group died of pneumonia within ten days of bacterial inoculation (0% survival). Prophylaxis with either IM tobramycin or SDM vehicle plus IM tobramycin provided no protection (0% survival). This is in sharp contrast to the cohort receiving pretreatment with tobramycin-containing SDM delivered via LV, in which 60% of the animals survived to study completion (p < 0.05). CONCLUSIONS: Prophylaxis with SDM containing antibiotics delivered in low-dose LV provided significant protection in a rat model of descending gram-negative pneumonia. These data support the hypothesis that perfluorocarbon-delivered intratracheal antimicrobials may be useful in the prevention of VAP. 相似文献
25.
26.
OBJECTIVE: This study was conducted to compare an otolaryngologist's experience with a cohort of epilepsy patients implanted with a vagal nerve stimulator (VNS) to previously published data. METHODS: Demographics, preoperative seizure frequency, medications, and complications were retrospectively collected from patients implanted by the senior author. Postoperative medications and seizure frequency were obtained from referring neurologists. RESULTS: Seventeen patients were implanted over a 24-month period. Average age was 28.3 years. Patients presented with petit mal (n = 3), tonic-clonic (n = 6), complex partial (n = 5), and grand mal (n = 8) seizures. Mean follow-up postimplantation was 13.5 months. Most patients had at least a 50% reduction of seizure frequency, with 3 patients being seizure free. There were no postoperative infections. One patient had left vocal cord immobility. The most common side effect was voice disturbance during device activation. CONCLUSION: Otolaryngologists are well equipped to perform VNS implantation and to diagnose and treat possible laryngeal side effects. EBM rating: C-4. 相似文献
27.
28.
The worldwide burden of hepatitis B mandates accurate and timely diagnosis of patients infected with the hepatitis B virus (HBV) and the use of treatment strategies derived from evidence-based guidelines. HBV is a DNA virus that produces a series of viral protein products circulating HBV DNA. Serologic and nucleic acid testing are critical to disease prevention and treatment objectives. Information from such testing helps determine patients' infectivity and immune status, appropriate monitoring strategies, and the efficacy of treatment, as well as providing data that contributes to a better understanding of the natural history and epidemiology of the disease. This article reviews the clinical use of state-of-the-art serologic and nucleic acid tests, including the relevance of hepatitis B e antigen and antibody and HBV DNA measurements as markers of disease activity. Viral load can be used to distinguish between active and inactive disease, define response to therapy, and detect the development of antiviral resistance. Some recent reports have suggested that high viral load is associated with poorer patient outcomes (eg, more rapid progression to cirrhosis and a higher incidence of hepatocellular carcinoma). Durable suppression of HBV DNA is evolving to become the primary goal of therapy, although all currently licensed medications have used histology as the primary end point of therapy. Suggested frequencies for HBV DNA monitoring are presented. 相似文献
29.
30.
Elaina F. George Arnold Komisar Stephen C. Scharf Adrienne Ferracci Stanley Blaugrund 《The Laryngoscope》1998,108(5):627-629
A retrospective chart review of 43 patients who underwent technetium 99m (Tc-99m) sestamibi scans from June 1995 to January 1997 was performed. Only those who underwent subsequent parathyroid exploration with excision were included in the study. Twenty subjects (13 women and seven men) were included in the study. Ages ranged from 21 to 84 years (mean, 58 years). All patients had laboratory values and clinical findings consistent with primary hyperparathyroidism. Two patients had preoperative magnetic resonance imaging (MRI) scans (one patient with recurrent disease), and one had a preoperative computed tomography (CT) scan. The remaining patients had the sestamibi scan as the only preoperative localization study. There were 18 pathologic diagnoses of parathyroid adenoma and two of parathyroid hyperplasia. Sestamibi failed to correctly identify the location of the parathyroid lesion in two cases. In 18 cases the preoperative sestamibi scan correctly localized the lesion, a predictive value of 90%. We conclude that the Tc-99m sestamibi scan is an accurate preoperative tool that can be used as a single modality to localize parathyroid adenomas. 相似文献