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BACKGROUND: Mycophenolate mofetil (MMF) is rapidly hydrolyzed to its active metabolite mycophenolic acid (MPA), which is excreted by the kidney after undergoing glucuronidation to MPAG. MPAG has been shown to accumulate in patients with renal failure. MPA is extensively and avidly bound to human serum albumin. In vitro inhibition of the pharmacologic target, inosine monophosphate dehydrogenase, is dependent on free MPA. It has been demonstrated that high MPAG concentrations decrease MPA protein binding in vitro. In addition, the uremic state is associated with altered protein binding of many drugs. METHODS: We assessed free MPA, total MPA, and MPAG kinetics in a patient with renal failure receiving MMF for a pancreas transplant, who presented with signs of MMF toxicity. MPA, MPAG, and free MPA were measured by high performance liquid chromatography and a validated 14C-MPA ultrafiltration methodology. RESULTS: The MPAG area under the concentration curve (AUC) in this patient was extremely high (5899 microg x hr/ml). The total MPA AUC of 36.8 microg x hr/ml was within the range usually obtained in stable renal patients. The free fraction of MPA and the free MPA AUC were markedly elevated (13.8% and 5.07 microg x hr/ml, respectively). CONCLUSIONS: Patients with severe renal insufficiency may have markedly increased free MPA levels that may not be reflected in total MPA concentrations. These patients may be at increased risk for MMF-related toxicity.  相似文献   

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In the present study, the potential of a diphenylphosphorylazide-crosslinked type I bovine collagen membrane was evaluated in the healing of mandibular bone defects applying the biological concept of guided bone regeneration. The experiment was carried out on 25 Wistar rats. After exposing the mandibular ramus bilaterally, 5 mm diameter full-thickness circular bone defects were surgically created. While the defect on one side was covered by the membrane (experimental), the defect on the other side was left uncovered (control) before closure of the overlying soft tissues. The rats were sacrificed in groups of 5 after 7, 15, 30, 90, and 180 days of healing. Although at early stages of healing similar amounts of bone formation were observed in the experimental and control defects, after 1 month of healing, most of the experimental defects were completely closed with new bone, while in the control defects, only limited amounts of new bone were observed at the rims and in the lingual aspect of the lesions. In the 90- and 180-day animals, all experimental defects were completely closed, while in the control defects, no statistically significant increase in bone regeneration was observed. The increase in percentage of bone regeneration in the experimental defects was statistically significant between the 15-day specimens as compared with the 7-day specimens (P < 0.01) and likewise between 30-day and 15-day specimens (P < 0.001). It can be concluded that a DPPA-crosslinked collagen membrane yields biocompatibility, ad hoc mechanical hindrance, and handling characteristics suitable for guided bone regeneration applications in this experimental model.  相似文献   

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The authors present the results of selective bronchial and parietal arteriography of pulmonary systemic hypervascularization, in 83 cases. They emphasize the advantages of previous pulmonary venous angiography and overall aortography for the success of selective injections. Failures are evaluated at 6 to 7%. On occasions, a medullary branch was opacified. No medullary accidents were noted. The angiographic appearances of the lesions encountered are described. A comparative study of the angiographic results of non-tumoral acquired lesions was carried out in those patients with hemoptysis and in those who were free from them.  相似文献   

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OBJECTIVES: The present study was designed to investigate which characteristics of anginal symptoms or exercise test results could predict the favorable anti-ischemic effect of the beta-adrenergic blocking agent metoprolol and the calcium antagonist nifedipine in patients with stable angina pectoris. BACKGROUND: The characteristics of anginal symptoms and the results of exercise testing are considered of great importance for selecting medical treatment in patients with chronic stable angina pectoris. However, little information is available on how this first evaluation may be used to select the best pharmacologic approach in individual patients. METHODS: In this prospective multicenter study, 280 patients with stable angina pectoris were enrolled in 25 European centers. After baseline evaluation, consisting of an exercise test and a questionnaire investigating patients' anginal symptoms, the patients were randomly allocated to double-blind treatment for 6 weeks with either metoprolol (Controlled Release, 200 mg once daily) or nifedipine (Retard, 20 mg twice daily) according to a parallel group design. At the end of this period, exercise tests were repeated 1 to 4 h after drug intake. RESULTS: Both metoprolol and nifedipine prolonged exercise tolerance over baseline levels; the improvement was greater in the patients receiving metoprolol (p < 0.05). Multivariate analysis revealed that low exercise tolerance was the only variable associated with a more favorable effect within each treatment group. Metoprolol was more effective than nifedipine in patients with a lower exercise tolerance or with a higher rate-pressure product at rest and at ischemic threshold. None of the characteristics of anginal symptoms or exercise test results predicted a greater efficacy of nifedipine over metoprolol. CONCLUSIONS: The results of a baseline exercise test, but not the characteristics of anginal symptoms, may offer useful information for selecting medical treatment in stable angina pectoris.  相似文献   

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OBJECTIVES: This study sought to compare stenting of the primary infarct-related artery (IRA) with optimal primary percutaneous transluminal coronary angioplasty (PTCA) with respect to clinical and angiographic outcomes of patients with an acute myocardial infarction. BACKGROUND: Early and late restenosis or reocclusion of the IRA after successful primary PTCA significantly contributes to increased patient morbidity and mortality. Coronary stenting results in a lower rate of angiographic and clinical restenosis than standard PTCA in patients with angina and with previously untreated, noncomplex lesions. METHODS: After successful primary PTCA, 150 patients were randomly assigned to elective stenting or no further intervention. The primary end point of the trial was a composite end point, defined as death, reinfarction or repeat target vessel revascularization as a consequence of recurrent ischemia within 6 months of randomization. The secondary end point was angiographic evidence of restenosis or reocclusion at 6 months after randomization. RESULTS: Stenting of the IRA was successful in all patients randomized to stent treatment. At 6 months, the incidence of the primary end point was 9% in the stent group and 28% in the PTCA group (p=0.003); the incidence of restenosis or reocclusion was 17% in the stent group and 43% in the PTCA group (p=0.001). CONCLUSIONS: Primary stenting of the IRA, compared with optimal primary angioplasty, results in a lower rate of major adverse events related to recurrent ischemia and a lower rate of angiographically detected restenosis or reocclusion of the IRA.  相似文献   

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The aim of this prospective study, carried out in a consecutive series of 305 microsurgically clipped aneurysms, was to check the absence of an aneurysmal remnant on post-operative angiography, and if a remnant was found to quantify its size in order to consider additional clipping to avoid the risk of rebleeding. Out of the 305 aneurysms, 292 (96%) were located in the anterior and 13 (4%) in the posterior circulation. Post-operative angiography was performed on average two weeks after surgery. Determination of the presence or not of an aneurysmal remnant and its quantification was done by an independent observer (JCA). Aneurysmal remnants were classified into 5 grades: grade I: less than 50% of neck size, grade II: more than 50% of neck size, grade III: residual lobe of a multilobulated sac, grade IV: residual sac of less than 75% of aneurysmal size and grade V: residual sac of more than 75% of aneurysmal size. Correlations between presence (and size) of the remnant and anatomical-surgical data obtained from the operative report were studied. Clipping was considered incomplete in 18 of the 305 aneurysms (5.9%). The group with residual neck only (grade I = 8 cases, Grade II = 4 cases) amounted to 4% of the whole series, whereas the group with residual neck + sac (grade III = 4, grade IV = 1, Grade V = 1) to 1.9%. Only this latter group was amenable to re-operation for complementary clipping without creating a stenosis of the parent artery. Our results are in the range of those of other published series. Anatomical-surgical factors for predisposition to incomplete clipping are discussed. The rates of sac obliteration using microsurgical clipping are to be compared with those recently achieved by electrically detachable coiling. The classification which we have developed is proposed for future comparison with endovascular results.  相似文献   

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Calcium antagonist drugs were proposed for use in patients with recent aneurysmal subarachnoid hemorrhage (SAH) because of their ability to block the effects of a wide variety of vasoconstrictor substances on cerebral arteries in vitro. It was suggested that these agents might, therefore, be useful in ameliorating cerebral vasospasm and its ischemic consequences which frequently complicate SAH. This hypothesis was tested in an arm of a randomized double-blind placebo-controlled trial of high-dose intravenous nicardipine in patients with recently ruptured aneurysms. Participating investigators were required to send selected copies of all admission and follow-up angiograms obtained between Days 7 and 11 following hemorrhage (the peak period of risk for vasospasm) to the Central Registry of the Cooperative Aneurysm Study for blinded interpretation and review for the presence and severity of angiographic vasospasm. In centers with transcranial Doppler ultrasound (TCD) capabilities, middle cerebral artery (MCA) mean flow velocities were measured and recorded. Angiograms obtained between Days 7 and 11 were available for 103 (23%) of 449 patients receiving nicardipine and 121 (26%) of 457 receiving placebo. There was a balance of prognostic factors for vasospasm between the groups. Fifty-one percent of placebo-treated patients had moderate or severe vasospasm on "Day 7-11 angiograms" compared to 33% of nicardipine-treated patients. This difference is statistically significant (p < 0.01). Sixty-seven (49%) of 137 placebo-treated patients examined with TCD between Days 7 and 11 had mean MCA flow velocities exceeding 120 cm/sec compared to 26 (23%) of 112 nicardipine-treated patients (significant difference, p < 0.001). These data suggest that high-dose intravenous nicardipine reduces the incidence and severity of delayed cerebral arterial narrowing in patients following aneurysmal SAH.  相似文献   

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Between January 1986 and May 1996, 870,313 children were tested in European neuroblastoma (NB) screening programmes. Among these children, 82 cases of NB (age range 4-24 months, median 11 months) were detected by screening. 83% of the patients had localised NB and 17% were diagnosed with generalised NB (stage 4, 10%; stage 4s, 7%). Unfavourable biological markers (MYCN amplification, loss of heterozygosity (LOH) 1p36, DNA di/tetraploidy) were observed in 14% of 76 biologically examined cases. The median follow-up time of all the patients was 21.5 months (range 1-101 months). To date, 69 patients are in complete remission (CR) and 2 patients have died due to therapy (stage 4, 1 patient; stage 3, 1 patient with unfavourable markers). Apart from screened patients, 16 other patients with NB were found who had previously had a normal screening test, i.e. 'false negative' patients (age range 10-41 months, median 31.5 months). The median interval between screening and diagnosis was 24.5 months (range 6-35 months). 11 of the 'false negative' patients suffered from generalised NB (stage 4) and 5 had localised NB at diagnosis. Unfavourable biological markers were observed in 7/12 patients. 5 patients have died, 2 achieved partial remission and 9 CR. 9 of the 11 patients with unfavourable biological markers diagnosed due to NB screening are currently in CR. It is very likely that, among the patients without unfavourable biological markers, we detected tumours which may have regressed spontaneously. These children may have undergone 'unnecessary,' but unavoidable, diagnostic procedures and therapy. To reduce the number of 'false negative' patients, a later screening could be helpful and should be evaluated.  相似文献   

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Presentation of a series of 6 cases of eosinophilic cystitis diagnosed in our hospital and recorded in 1988-1993, with an average follow-up of 2 years from time of diagnosis. The actual trend with regard to this particular form of chronic cystitis is to abandon the idea of considering it a "benign" disease, basically due to its increasingly less uncommon association to bladder and/or prostate tumoral pathology (in the recent literature and most particular in the present series). Also, a relative increase in the frequency of occurrence of this disease is noted, because of chemoprophylaxis of surface bladder tumour with Mitomycin-C, an association which is increasingly frequent. Based on these 6 cases, a review of the most recent literature on this topic is made.  相似文献   

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Our aim was to explore the current spectrum of contact allergens in schoolchildren, as a basis for diagnosis and prevention of allergic contact dermatitis. Results of patch tests in children 6-15 years old, performed in the years 1990-1995 by 22 centres of the German Contact Dermatitis Research Group and filed by the Information Network of Departments of Dermatology, were analysed and evaluated retrospectively, including epidemiologic data. Children with positive tests (62 out of 156 boys and 108 out of 260 girls tested) had a higher frequency of allergic contact dermatitis and a lower frequency of atopic dermatitis than patch test negative ones. 16 distinct allergens elicited positive reactions in > or = 1% of the children tested. Reactions to nickel sulfate occurred in 15.9% of all children tested, but in 25.0% of girls 14/15 years old, and in only 4.5% of boys 6-13 years old. Double-sensitizations with cobalt salts, potassium dichromate and palladium were seen. Mercury compounds were found in 2nd place (thimerosal: all children: 11.3%; 6-13 years old: 14.3%; 14/15 years old: 8.0%), followed by fragrance allergens. We conclude that contact allergy in children is related to their sex and age. Prophylaxis against nickel, mercury, and fragrance allergy needs to be improved. A shortened standard series may be sufficient for testing children.  相似文献   

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BACKGROUND: The Intracoronary Stenting and Antithrombotic Regimen (ISAR) Trial is a randomized study in which antiplatelet therapy is compared with anticoagulant therapy after coronary stent placement, showing a significantly lower rate of noncardiac and cardiac events with antiplatelet therapy. The present study is a report of the analysis of a prospective risk stratification protocol in the ISAR Trial and the association with the incidence of adverse cardiac events and stent vessel occlusion. METHODS AND RESULTS: In all 517 patients randomized in the ISAR Trial, risk stratification was done with a list of 18 clinical, procedural, and angiographic variables: 165 patients with two or fewer criteria were classified as low risk, 148 patients with three criteria were classified as intermediate risk, and 204 patients with four or more criteria were classified as high risk. Within a 30-day follow-up, cardiac event rate (death, myocardial infarction, repeat intervention) was 6.4% for high-risk, 3.4% for intermediate-risk, and 0% for low-risk patients (P<.01). Stent vessel occlusion occurred in 5.9%, 2.7%, and 0%, respectively (P<.01). There was no significant difference between anticoagulant and antiplatelet therapy in the low- and intermediate-risk groups. In high-risk patients, however, the cardiac event rate was 12.6% with anticoagulant therapy and 2.0% with antiplatelet therapy (P=.007), and the rate of stent vessel occlusion was 11.5% and 0%, respectively (P<.001). CONCLUSIONS: This risk stratification protocol can help to identify patients at risk for adverse cardiac events and stent vessel occlusion. Patients in the high-risk group had the most benefit from antiplatelet therapy. These data suggest that antiplatelet therapy is the therapy of choice after coronary stenting specifically for patients with acute ischemic syndromes, difficult procedures, or suboptimal final results.  相似文献   

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There is no single task that nurses do more often than make decisions, yet many clinicians feel inadequately prepared to address and resolve ethical issues. The Intravenous Nurses Society Code of Ethics provides practice guidelines for intravenous nursing specialists who need to make these often difficult decisions. The availability of an ethical decision-making model can assist the IV nurse in providing ethical quality care, regardless of the clinical setting in which care is delivered.  相似文献   

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Patients who were stable 1 to 6 months after a cardiac event underwent routine exercise testing with thallium scintigraphy. The prognosis of patients with good exercise capacity (Bruce stage 3) was similar whether or not ischemia was demonstrated and similar to patients with reduced exercise capacity and no ischemia, whereas the presence of both ischemia and a reduced exercise tolerance identified patients with a significantly poorer prognosis.  相似文献   

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This study documents age trends, interrelations, and correlates of intellectual abilities in old and very old age (70–103 years) from the Berlin Aging Study (N?=?516). Fourteen tests were used to assess 5 abilities: reasoning, memory, and perceptual speed from the mechanic (broad fluid) domain and knowledge and fluency from the pragmatic (broad crystallized) domain. Intellectual abilities had negative linear age relations, with more pronounced age reductions in mechanic than in pragmatic abilities. Interrelations among intellectual abilities were highly positive and did not follow the mechanic-pragmatic distinction. Sociobiographical indicators were less closely linked to intellectual functioning than sensory-sensorimotor variables, which predicted 59% of the total reliable variance in general intelligence. Results suggest that aging-induced biological factors are a prominent source of individual differences in intelligence in old and very old age. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

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A synthetic cell-binding peptide (P-15) combined with anorganic bovine-derived hydroxyapatite bone matrix (ABM) was compared to demineralized freeze-dried bone allograft (DFDBA) and open flap debridement (DEBR) in human periodontal osseous defects in a controlled, monitored, multi-center trial. Following appropriate initial preparation procedures, flap surgery with defect and root debridement was performed. Three osseous defects per patient were treated randomly with one of three procedures after surgical preparation. Appropriate periodontal maintenance schedules were followed, and at 6 to 7 months re-entry flap surgery was performed for documentation and finalization of treatment. Analysis of variation (ANOVA) and t test analyses of patient mean values from 31 patients revealed that the combination ABM/P-15 grafts demonstrated significantly better mean defect fill of 2.8 +/- 1.2 mm (72.3%) versus a mean defect fill of 2.0 +/- 1.4 mm (51.4%) for defects treated with DFDBA (P <0.05) and a mean defect fill of 1.5 +/- 1.3 mm (40.3%) (P <0.05) for defects treated with DEBR. Other hard tissue findings showed similar clinically superior results with the use of ABM/P-15. Relative defect fill results showed 87% positive (50% to 100% defect fill) responses with ABM/P-15, 58% positive responses with DFDBA, and 41% positive responses with DEBR. There were 8 to 9 times more failures (minimal response) with DFDBA and DEBR (26% to 29% frequency) than with ABM/P-15. Soft tissue findings showed no significant differences among treatments except for greater clinical attachment level gain with ABM/P-15 compared to DEBR. These results suggest that the use of the P-15 synthetic cell-binding peptide combined with ABM yields better clinical results than either DFDBA or DEBR. Further studies are needed to determine the relative roles of the ABM and/or the P-15 in these improved results.  相似文献   

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