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1.
Maintenance of adequate immunosuppression and avoidance of side-effects are the goals of long-term management of all organ-transplanted patients. We here report the final results of a prospective, randomized trial comparing early cyclosporine monotherapy versus double-drug therapy (cyclosporine and steroids) in adult liver transplantation patients. One hundred four patients were randomized 3 months after transplantation either to continue (Group I = 50 patients) or to stop steroids (Group II = 54 patients). Patients on a double-drug regimen were maintained long term on methylprednisolone at a dose of 0.1 mg/kg/d. Target cyclosporine trough levels were between 150 and 250 ng/mL in both groups. Our main points of interest were the prevalence of acute and chronic rejections and steroid-related side-effects in the two groups of patients. Mean follow-up was 41 +/- 16 months (range, 4-68 months). Patient actuarial survival 2 and 5 years after randomization was similar in the two groups (82% vs. 83% and 82% vs. 77%). The prevalence of acute rejections after randomization was, respectively, 8% and 4%. A single episode of chronic rejection was observed only in a patient on long-term steroid therapy. Side-effects of steroid therapy were less frequent in patients weaned off steroids, and when considering hypertension and diabetes, the differences between the two groups were statistically significant. Early cyclosporine monotherapy is a safe undertaking in liver transplantation because it allows a significant reduction of steroid-related side-effects without increasing the risk of acute and chronic rejection. After 5 years, patient survival was similar in patients with or without steroids.  相似文献   

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A novel complex mutation consisting of a small deletion/insertion (3958del5ins4) was found in the breast cancer-1 gene (BRCA-1) in three unrelated French breast and/or ovarian cancer families. These mutations occurred at the same nucleotide position of the 3' end of exon 11. The wild-type sequence, CTCAG, was deleted and replaced by AGGC in the three families. The consequence is the generation of a stop codon, TAG, resulting in a truncated protein. We propose two different mechanisms to explain the generation of this complex mutation: (i) the simultaneous occurrence of a deletion and an insertion in a stem-loop structure and (ii) the abortive integration of a human transposable element (Tigger 1) that deleted 5 nucleotides and inserted a 4-nucleotide "scar", corresponding to the 5' extremity of the transposon.  相似文献   

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BACKGROUND: The long-term complications of immunosuppressive therapy such as diabetes, hypercholesterolemia, and hypertension are a major source of morbidity in liver transplant recipients. In this prospective, randomized, open-label study we completely withdrew prednisone (PRED) 14 days after liver transplantation in an effort to decrease these metabolic complications. Patients were maintained on mycophenolate mofetil (MMF) in combination with either cyclosporine (CsA; Neoral formulation) or tacrolimus (TAC). Thus, we also were able to compare CsA to TAC in patients not receiving PRED with respect to efficacy, toxicity, and effect on posttransplant metabolic complications. METHODS: A total of 71 patients were randomized to receive either TAC-MMF (n=35) or CsA-MMF (n=36) after liver transplantation and were analyzed for patient and graft survival. Fifty-eight patients continued the immunosuppressive protocol for at least 6 months after transplantation and were analyzed for the incidence of acute rejection and the prevalence of diabetes, hypertension, and hypercholesterolemia. RESULTS: The 6-month patient survival rates were 94.4% for CsA-MMF and 88.6% for TAC-MMF. Corresponding 6-month graft survival rates were 88.7% and 85.71% with no immunologic graft losses in either group. The incidence of biopsy-proven acute rejection was 46% for CsA-MMF and 42.3% for TAC-MMF. Six patients were converted from CsA to TAC (four for recurrent rejection) and seven patients were converted from TAC to CsA (four for neurotoxicity). Only one patient (in the TAC-MMF group) developed new-onset posttransplant diabetes. In contrast, four of eight patients in the CsA-MMF group who were diabetic before transplant became nondiabetic in the first 3 months after transplant. The mean serum cholesterol level was significantly lower in the TAC-MMF group than in the CsA-MMF group (145.2+/-41.8 mg/dl and 190.3+/-62.2, respectively; P<0.001) and the incidence of hypertension was lower in the TAC-MMF group (12% vs. 30.3% in the CsA-MMF group, P<0.01). Both groups had a lower incidence of metabolic complications compared with a historical group (n=100) maintained on CsA and PRED (10 mg/day at 6 months). CONCLUSIONS: MMF in combination with either TAC or CsA allows withdrawal of PRED 14 days after liver transplantation with a moderate rejection rate and no immunologic graft losses. Early PRED withdrawal decreases posttransplant diabetes, hypercholesterolemia, and hypertension, but patients maintained on TAC have lower serum cholesterol levels and a lower incidence of hypertension than CsA-treated patients.  相似文献   

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OBJECTIVE: To compare outcome and costs between laparoscopic and open hernia repair. DESIGN: Prospective randomised study. SETTING: One university and two district hospitals in Sweden. SUBJECTS: 200 men aged 25-75 years. MAIN OUTCOME MEASURES: Operating time, hospital stay, complications, and time to recovery. A cost-minimisation-analysis was used in which the total costs were calculated for a defined period of time for each option. RESULT: The one year follow-up rate was 98%. Mean (SD) operation times in the laparoscopic and open groups were 72 (30) and 62 (25) minutes, respectively (p = 0.009). Hospital stay and complication rates did not differ between the groups. Among employees the mean (SD) periods off work in the laparoscopic and open groups were 10 (8) and 23 (21) days, respectively (p = 0.0001). The mean direct costs of the laparoscopic operation were increased by SEK 4037 (US$ 483) but the savings in indirect costs resulting from earlier return to work were SEK 11392 (US$ 1364). CONCLUSIONS: Laparoscopic hernia repair gave the employed patients faster recovery and return to work, and was the most cost-effective strategy provided that both direct and indirect costs were included.  相似文献   

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To assess the long-term outcome of kidney/pancreas transplantation, patients were identified who had good graft function at one year posttransplant and a minimum of 3 years' follow-up. Fifty recipients from 1987-92 met these criteria. Records were reviewed for graft survival, graft function, readmissions, and medical complications. Psychosocial adjustment and quality of life were assessed using the SCL-90-R and SIP surveys, respectively. Patient, kidney, and pancreas survivals were 94%, 86%, and 85% at five years (Kaplan-Meier), with a mean follow-up of 4.3 years. The 3 deaths were due to 2 sudden arrests at home (presumed to be cardiac events) and 1 episode of sepsis. Other graft losses were due to rejection, except for one case of sepsis. The remaining patients are normoglycemic (glucose 92 +/- 23 mg/dl) and have a creatinine of 1.8 +/- 0.6 mg/dl. Mortality after the first year was 0.9%/year. Estimated kidney and pancreas half-lives were 15 +/- 2 and 23 +/- 7 years, respectively. Hospitalization, acute rejection, graft pancreatitis, dehydration, and severe infections all decreased dramatically after the first year. While CMV was the most common infection in the first year, foot infections predominated thereafter. Retinal hemorrhage was infrequent. Sudden death (presumably cardiac) was the chief cause of mortality, while peripheral vascular disease resulted in several amputations. Fractures were common, suggesting the need for increased attention to bone demineralization. Psychosocial and quality of life evaluations were within normal limits. In conclusion, most complications specifically related to transplantation occur in the first year, but underlying disease renders these patients susceptible to a variety of cardiovascular, bone, and other disorders.  相似文献   

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BACKGROUND: Advanced hyperparathyroidism refractory to active vitamin D continues to be a problem and frequently forces the nephrologist to resort to parathyroidectomy. One particular aspect is persisting advanced hyperparathyroidism after renal transplantation. Published information on this point is fragmentary. DESIGN: Retrospective analysis. PATIENTS: Between 1983 and 1995 a total of 456 patients with renal secondary hyperparathyroidism were subjected to parathyroidectomy (PTX) of whom 103 were transplanted or had at least a history of renal transplantation. The present analysis concerns 37 patients who had a functional renal graft at the time of PTX and were followed for up to 13 years. PTX was performed after an average of 36.7 months after renal transplantation. OUTCOME: Thirteen patients experienced rejection and became dialysis-dependent. Twenty-four patients had stable function of the renal graft. Seven patients died during follow-up. Hypoparathyroidism post-PTX developed in 4/37 patients, but could be overcome by replantation of cryoconserved parathyroid tissue. FREQUENCY ESTIMATE: A total of 2632 renal transplants were performed in the catchment area. As a minimum estimate 3.91% of patients with a functional graft required PTX. RECOMMENDATION: Parathyroidectomy should be considered early in cases with advanced secondary renal hyperparathyroidism, since renal transplantation does not necessarily guarantee reversibility of parathyroid overactivity.  相似文献   

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BACKGROUND: Both ischemic and direct vascular injury (angioplasty) result in the elaboration of proinflammatory substances, including tumor necrosis factor alpha (TNF), which may regulate vascular smooth muscle cell (VSMC) proliferation and promote vessel stenosis. Interleukin-10 (IL-10) is a pleiotropic cytokine with potent antiinflammatory effects in many cells lines. We hypothesized that IL-10 could be used therapeutically to influence vascular remodeling by inhibiting TNF-induced VSMC proliferation. The purposes of this study were (1) to determine whether human myocardium produces endogenous TNF in response to ischemia-reperfusion, (2) to examine the effect of TNF on human arterial smooth muscle proliferation, and (3) to explore the potential therapeutic effect of IL-10 on unstimulated and TNF-stimulated VSMC proliferation. MATERIALS AND METHODS: Right atrial muscle was obtained from patients undergoing elective cardiac surgery. Atrial muscle was subjected to simulated ischemia and reperfusion in vitro and TNF was measured by immunoassay. Human aortic VSMCs were isolated and cultured. Proliferation assays were performed to determine the effect of TNF and IL-10 on VSMC growth. RESULTS: Ischemia-reperfusion resulted in an increase in atrial myocellular TNF (94.5 +/- 15.8 pg/g wet tissue versus control 12.9 +/- 4.4 pg/g wet tissue, P < 0.002). Compared with control, TNF stimulated concentration-dependent VSMC proliferation (P < 0.005). IL-10 alone did not influence VSMC growth. However, following TNF stimulation, IL-10 inhibited VSMC growth at a dose as low as 0.1 pg/ml (P < 0.005). CONCLUSIONS: Ischemia-reperfusion insult results in increased endogenous myocardial TNF accumulation. TNF stimulates VSMC growth which is abrogated by physiologically relevant levels of IL-10. This antiinflammatory cytokine may prove to be an effective therapeutic agent in regulating vessel wall remodeling following both ischemic and direct cardiovascular injury.  相似文献   

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The evidence is compelling that stroke units are effective when compared to management of patients on general medical wards. However, the evidence remains equivocal that better outcome is sustained in the longer term. This paper reports an investigation of cognitive and emotional outcome, environmental consequences, social activities, and physical outcome in 57 consecutive one-year survivors of a stroke discharged from a stroke and neurological rehabilitation unit. Satisfaction with inpatient and outpatient services was also investigated. Results were compared with previously reported studies of long-term outcome after stroke. Mean Barthel activities of daily living score at one year or more post-stroke was 16.8. Arm function was impaired in 43% of the participants in the study. Nearly half had cognitive and emotional problems, 19% communication problems, and 25% problems with access both inside and outside their house. All but four of the one-year survivors were less active after their stroke than before. More than 40% were dissatisfied with at least one aspect of inpatient and/or outpatient services. The long-term consequences of stroke in all areas investigated were considerable and in line with previous reports. Some suggestions for reducing these effects are made, including better information for patients about stroke and rehabilitation, improved access to psychology services, detailed assessment prior to hospital discharge of the patient's living environment and effective coordination with social services to improve access to their living environment.  相似文献   

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Studies were carried out to observe the species composition of mosquitos and to determine the vectors responsible for the transmission of filariasis in Grik, Perak, Malaysia. A total of 2,155 mosquitos belonging to 7 genera and 30 species were collected. Anopheles donaldi comprised 24.1% of the collection. Twelve out of 519 An. donaldi were infected with L3 larvae of Brugia malayi. The peak biting time was around 23.00-24.00 hours. The infective bites per month ranged from 0 to 6.3.  相似文献   

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Mesenchymal chondrosarcoma is a rare tumor that is distinctly different from classic chondrosarcoma. The prognosis of this tumor is poor, with a high incidence of locoregional and distant metastases. It shows a predilection for the head and neck, however mesenchymal chondrosarcoma of hyoid bone has rarely been reported. We experienced a case of mesenchymal chondrosarcoma of the hyoid bone in a 39-year-old woman. She underwent excision of the tumor by right hemihyoidectomy. Histologically, a combination of cellular zones composed of undifferentiated small cells and chondroid zones typically presented a bimorphic appearance. CD99 (DN16) immunohistochemical stain demonstrated that all undifferentiated small cells had strong reactivity with a distinct membranous pattern. There was microscopic tumor extension to the resection margin of the hyoid bone, however, no evidence of reccurence is noted at follow-up of 4 months with neck CT.  相似文献   

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