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ULTRA was established on the 1st April 1990, to consider applications made by registered medical practitioners seeking approval to transplant an organ between 2 living unrelated persons in the United Kingdom.  相似文献   
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Ductal carcinoma in situ (DCIS) is considered a direct precursor of invasive ductal breast cancer (IDC). We combined tissue microdissection and comparative genomic hybridization to identify genetic changes in five DCIS lesions with no invasion and in two that were adjacent to IDC. Extensive genetic changes characterized pure DCIS cases with gains of 1q, 6q, 8q, and Xq as well as losses of 17p and chromosome 22 being most often involved. Except for the Xq gain, these changes are also common to IDC. Separate analysis of DCIS and IDC components in the same tumor revealed an almost identical pattern of genetic changes in one case, whereas substantial differences were found in another. We conclude that many of the common genetic changes in IDC may take place before development of invasive growth. However, a simple linear progression model may not always account for the DCIS-IDC transition.  相似文献   
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OBJECTIVE: To determine the outcome of DSM-III-R schizophreniform disorder with good prognostic features. METHOD: A 6-year follow-up of 20 cases was conducted with structured interviews (comprehensive assessment of symptoms and history) and assessments of functioning scales (global assessment of functioning, Strauss-Carpenter Scale). RESULTS: Thirty-five percent of the cases had major affective disorders, 35% had schizophreniform episodes and major affective disorders, 5% had schizophreniform episodes only, 10% developed schizophrenia, and 15% had no disorders. CONCLUSION: The findings suggest an association between schizophreniform disorder with good prognostic features and affective illness.  相似文献   
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PURPOSE: While advanced cardiac life support (ACLS) training is widely available, it is not mandatory for all anaesthetists. We hypothesised that adherence to ACLS guidelines during resuscitation of ventricular fibrillation (VFib) as assessed in a simulator environment would be poor by anaesthetists not trained in ACLS compared with those who had received training. METHODS: With approval by the ethics review board, 89 subjects participated in the study. The simulation system consisted of a computer controlled mannequin with lifelike qualities set in a mock operating room. Each subject was given a test scenario that contained several standard anaesthetic problems. A VFib cardiac arrest occurred after approximately one hour into the simulation. A perfect score (score = A) defined complete compliance with the ACLS guidelines, whereas minor deviations (score = B) included changes in energy levels, drug doses or treatment order. The failure to discontinue the anaesthetic, defibrillate or administer epinephrine were considered major deviations (score = C). RESULTS: Eight subjects followed the ACLS guidelines (9%, score = A), while 27 subjects showed minor (30%, score = B) and 54 subjects major deviations (61%, score = C). Sixty-two of the 89 participants (70%) had taken the ACLS course and achieved higher scores than did anaesthetists without such training (P < 0.05). Forty-two participants (47%) did not discontinue the anaesthetic, 10 (11%) never gave epinephrine and 5 (6%) never used the defibrillator. CONCLUSION: Adherence to ACLS guidelines was poor. A greater proportion of subjects without previous ACLS training had deviations from protocol than did subjects who had received training. We need to consider ways to ensure that anaesthetists obtain and retain resuscitation skills according to ACLS guidelines.  相似文献   
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The impact of oral treatment with insulin on disease development was studied in diabetes prone BB rats. Because of the positive outcome of a prior study in non obese diabetic (NOD) mice, BB rats received insulin in combination with a bacterial adjuvant. Porcine insulin was given orally twice weekly from 35-100 days of age, the E. coli preparation OM-89 was fed on alternate days. Other groups received vehicle, the bacterial adjuvant, or insulin alone. Both insulin containing oral dosing regimens induced a transient non significant delay in diabetes onset. Insulin alone, however did not decrease the final diabetes incidence. Oral dosing with insulin plus adjuvant caused exacerbation of disease development as judged from the decreased survival rate in comparison with the insulin treated group (p < 0.05). Intra-islet infiltration also increased (p < 0.005) compared with the insulin or vehicle treated groups. The effect correlated with enhanced interferon gamma (IFNgamma) and decreased interleukin 10 (IL-10) gene expression in the gut suggesting a shift towards proinflammatory T helper 1 (Th1) reactivity (p < 0.01). Although treatment with adjuvant alone also increased the degree of insulitis, an enhanced incidence of diabetes and a shift in cytokine expression was only seen in the group receiving insulin plus adjuvant. Taken together, the data suggest that treatment with a bacterial adjuvant and oral insulin may alter the gut immunoregulatory state such that disease promoting rather than protective immune responses are induced.  相似文献   
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We used broad-range bacterial PCR combined with DNA sequencing to examine prospectively cerebrospinal fluid (CSF) samples from patients with suspected meningitis. Fifty-six CSF samples from 46 patients were studied during the year 1995. Genes coding for bacterial 16S and/or 23S rRNA genes could be amplified from the CSF samples from five patients with a clinical picture consistent with acute bacterial meningitis. For these patients, the sequenced PCR product shared 98.3 to 100% homology with the Neisseria meningitidis sequence. For one patient, the diagnosis was initially made by PCR alone. Of the remaining 51 CSF samples, for 50 (98.0%) samples the negative PCR findings were in accordance with the negative findings by bacterial culture and Gram staining, as well as with the eventual clinical diagnosis for the patient. However, the PCR test failed to detect the bacterial rRNA gene in one CSF sample, the culture of which yielded Listeria monocytogenes. These results invite new research efforts to be focused on the application of PCR with broad-range bacterial primers to improve the etiologic diagnosis of bacterial meningitis. In a clinical setting, Gram staining and bacterial culture still remain the cornerstones of diagnosis.  相似文献   
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BACKGROUND: Traditionally, patients presenting with uncomplicated dyspepsia have been managed using empiric antisecretory therapy, followed by endoscopy in the event of persistent symptoms or complication. Since Helicobacter pylori is now accepted as an important and potentially reversible cause of ulcer disease, it is important to reevaluate the management of dyspepsia. The goal of this study is to evaluate seven outpatient strategies for the management of dyspeptic patients using a cost-utility analysis. METHODS: The study design was that of a cost-utility analysis. The model assumes that an adult patient with signs of dyspepsia but no signs of complication presents to the outpatient office of a primary care physician. Seven strategies are modeled: empiric antisecretory therapy; empiric H pylori eradication using oral omeprazole (20 mg [corrected] twice daily), clarithromycin (500 mg twice daily), and amoxicillin (1000 mg twice daily); use of either upper endoscopy, an upper gastrointestinal barium study (an upper GI), or the serum titer for H pylori as a diagnostic test to identify patients for H pylori eradication; or use of an initial diagnostic test followed by the serum titer for H pylori. The primary outcome was the cost per quality-adjusted life year (QALY) for each strategy for a 1-year period from presentation; secondary outcomes included the probability of symptomatic ulcer recurrence, cost per ulcer cure, and mortality. RESULTS: Three strategies were similarly cost-effective: empiric H pylori eradication ($1198 per QALY), use of a serum H pylori titer as an initial diagnostic test ($1214 per QALY), and empiric antisecretory therapy ($1288 per QALY). Empiric antisecretory therapy, however, was associated with significantly more symptomatic ulcer recurrences and deaths than any other strategy. CONCLUSIONS: This cost-utility analysis suggests that two strategies are reasonable for patients presenting with dyspepsia: (1) empiric H pylori eradication and (2) use of a serum H pylori titer to identify patients who might benefit from H pylori eradication. The latter strategy may be preferable because it is less likely to lead to antibiotic resistance. Strategies utilizing an upper GI or upper endoscopy (either with or without serum H pylori titer) or empiric antisecretory therapy do not improve outcomes and are associated with greater cost, morbidity, and/or mortality.  相似文献   
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Nitric oxide (NO) is reported to cause neuronal damage through various mechanisms. The present study tests the hypothesis that NO synthase inhibition by N(omega)-nitro-L-arginine (NNLA) will result in decreased oxygen-derived free radical production leading to the preservation of cell membrane structure and function during cerebral hypoxia. Ten newborn piglets were pretreated with NNLA (40 mg/kg); five were subjected to hypoxia, whereas the other five were maintained with normoxia. An additional 10 piglets without NNLA treatment underwent the same conditions. Hypoxia was induced with a lowered FiO2 and documented biochemically by decreased cerebral ATP and phosphocreatine levels. Free radicals were detected by using electron spin resonance spectroscopy with a spin trapping technique. Results demonstrated that free radicals, corresponding to alkoxyl radicals, were induced by hypoxia but were inhibited by pretreatment with NNLA before inducing hypoxia. NNLA also inhibited hypoxia-induced generation of conjugated dienes, products of lipid peroxidation. Na+,K+-ATPase activity, an index of cellular membrane function, decreased following hypoxia but was preserved by pretreatment with NNLA. These data demonstrate that during hypoxia NO generates free radicals via peroxynitrite production, presumably causing lipid peroxidation and membrane dysfunction. These results suggest that NO is a potentially limiting factor in the peroxynitrite-mediated lipid peroxidation resulting in membrane injury.  相似文献   
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