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51.
Dr. Lutz Lindemann-Sperfeld Klaus-Dieter Rudolf Michael Steen Ivan Marintschev Wieland Otto 《Trauma und Berufskrankheit》2003,5(2):198-207
Complex injuries of the foot are often overlooked, especially in the multiple injured patient, and they then lead to major loss of function. When the mechanism of injury suggests involvement of the foot, a clinical examination of the lower extremities should be included in the primary diagnostic procedures implemented in the multiply injured patient, followed by radiological examination once the patient's condition is stable. The condition of the soft tissues is of decisive importance in the prognosis of complex foot injuries, regardless of whether the damage to the foot is one component of a polytrauma or an isolated injury, which can also be life threatening. The diagnostic examinations selected should be adapted to the severity of the injuries in the particular multiply injured patient. Successful therapy involves stable internal fixation of injuries to bones and joints, though the external fixation options should be considered in the first instance, and carefully selected methods of temporary and definitive soft tissue reconstruction. The aim of treatment is the best possible reconstruction of the foot as a functional weight-bearing unit with intact soft tissue cover and a natural form. Good results can be achieved when there is close interdisciplinary cooperation between trauma (orthopedic) and plastic surgeons. Patient with severe injuries of this kind should be transferred to a trauma center as the first step toward this end. 相似文献
52.
Dual blockade of the renin-angiotensin system in type 1 patients with diabetic nephropathy. 总被引:7,自引:0,他引:7
Peter Jacobsen Steen Andersen Kasper Rossing Birgitte V Hansen Hans-Henrik Parving 《Nephrology, dialysis, transplantation》2002,17(6):1019-1024
BACKGROUND: Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in patients with diabetes. Approximately 30% of type 1 patients with diabetic nephropathy (DN) have albuminuria >1 g/day, and blood pressure >135 and/or >85 mmHg despite antihypertensive therapy with recommended doses of ACE inhibitor (ACEI) and diuretics. We tested the effect of dual blockade of the renin-angiotensin system (RAS) in these patients. METHODS: We performed a randomised double blind crossover trial with 2 months treatment with Irbesartan 300 mg o.d. and placebo added on top of previous antihypertensive treatment. We included 21 type 1 patients with DN responding insufficiently to ACEI and diuretics, as defined above. At the end of each treatment period, albuminuria, 24-h blood pressure and glomerular filtration rate (GFR) were measured. RESULTS: Addition of 300 mg Irbesartan to the patients' usual antihypertensive therapy induced a mean reduction in albuminuria of 37% (95% CI 20-49, P<0.001); from 1574 mg/24 h (95% CI 1162-2132) to 996 mg/24 h (95% CI 699-1419), a reduction in 24-h blood pressure of 8 mmHg systolic (95% CI -2 to 18) and 5 mmHg diastolic (95% CI 1-9) (P=0.11 and 0.01, respectively) (from placebo, mean (SE) 146 (4)/80 (2) mmHg). GFR remained unchanged. Serum potassium increased (mean 4.3 to 4.6 mmol/l, P=0.02). Intervention to reduce serum potassium was needed in two patients with GFR <35 ml/min/1.73 m(2). Otherwise the dual blockade with Irbesartan was safe and well tolerated. CONCLUSIONS: Dual blockade of the RAS may offer additional renal and cardiovascular protection in type 1 patients with DN responding insufficiently to conventional antihypertensive therapy, including recommended doses of ACEI and diuretics. 相似文献
53.
Christian J Streck Paxton V Dickson Catherine Y C Ng Junfang Zhou John T Gray Amit C Nathwani Andrew M Davidoff 《Clinical cancer research》2005,11(16):6020-6029
PURPOSE: Type I IFNs (IFN-alpha/beta) have shown significant antitumor activity in preclinical models but limited efficacy and significant toxicity in clinical trials. We hypothesized that the antitumor activity of type I IFNs could be enhanced by chronic, low-dose systemic delivery and sought to test this in murine neuroblastoma models. EXPERIMENTAL DESIGN: Continuous liver-generated expression of human IFN-beta (hINF-beta) was achieved through a gene therapy-mediated approach using adeno-associated virus vectors encoding hIFN-beta (AAV hINF-beta). Orthotopic localized retroperitoneal and disseminated models of neuroblastoma were established using three different xenografts. Immunohistochemical analysis and ELISA were used to evaluate the antiangiogenic effect of therapy. RESULTS: The development of both localized orthotopic (retroperitoneal) and disseminated neuroblastoma was prevented in all mice expressing hINF-beta. Continued growth of established retroperitoneal tumors, treated with AAV hINF-beta as monotherapy, was significantly restricted, and survival for mice with established, disseminated disease was significantly prolonged following administration of AAV hINF-beta. Analysis of treated tumors revealed a significant antiangiogenic effect. Mean intratumoral vessel density was diminished and expression of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor were both decreased. Finally, combination therapy in which AAV hIFN-beta was used together with low-dose cyclophosphamide resulted in regression of both established retroperitoneal and disseminated disease. CONCLUSIONS: AAV-mediated delivery of hIFN-beta when used as monotherapy was able to restrict neuroblastoma growth due in part to inhibition of angiogenesis. When used in combination with conventional chemotherapy, AAV hIFN-beta was able to effect complete tumor regression. 相似文献
54.
Véronique Strijckmans Michel Bottlaender Humin Luo Michèle Ottavianil Daniel W. McPherson Christian Loc'h Chantal Fuseau Furn F. Knapp Bernard Mazière 《European journal of nuclear medicine and molecular imaging》1997,24(5):475-482
We studied the potential of three radiobrominated isomers of BrQNP, (Z(-,-)-[76Br]BrQNP,E(-,-)-[76Br]BrQNP andE(-,+)-[76Br]BrQNP), as suitable radioligands for imaging of central muscarinic cholinergic receptors in the human brain. These radioligands were stereospecifically prepared by electrophilic radiobromodestannylation of the respective tributylstannyl precursors using no-carrier-added [76Br]BrNH4 and peracetic acid. Preliminary pharmacological characterizations were determined by biodistribution, autoradiography, competition, displacement and metabolite studies in rats. The (-,-)-configuration presented important specific uptakes in brain muscarinic cholinergic receptor (mAChR)-rich structures and in heart, low metabolization rates and an apparent M2 selectivity. The (-,+)-configuration revealed more rapid clearance, lower uptake, a higher metabolization rate and an apparent M1 selectivity. Reversibility of the binding was confirmed for the three radiotracers. Positron emission tomography in the living baboon brain revealed high and rapid uptake in the brain and accumulation in the mAChR-rich structures studied. At 30 min p.i., theE(-,-)-radiotracer reached a plateau in cortex, pons and thalamus with concentrations of 29%, 24% and 19% ID/l, respectively.Z(-,-)-[76Br]BrQNP also accumulated in these structures, reaching a maximal uptake (27% ID/l) in the cortex 2 h p.i. At 5 min p.i. a plateau (17% ID/l) was only observed in the cortex for theE(-,+)-[76Br]BrQNP; by contrast, the other structures showed slow washout. After 3 weeks, the (-,-)-radiotracers were studied in the same baboon pretreated with dexetimide (1 mg/kg), a well-known muscarinic antagonist. In all the mAChR structures, the highly reduced uptake observed after this preloading step indicates that these radiotracers specifically bind to muscarinic receptors.Z(-,-)-[76Br]BrQNP, which is displaced in higher amounts from M2 mAChR-enriched structures, reveals an M2 affinity. The two isomers having the (-,-)-configuration are potential probes for investigating central muscarinic receptors. The absolute configuration on the acetate chiral centre influences their muscarinic subtype selectivity and thecis-trans isomerism of the vinyl moiety affects their specific fixation. 相似文献
55.
56.
Tim Strate Claus Schneider Emre Yekebas Wolfram T Knoefel Christian Bloechle Jakob R Izbicki 《Journal of investigative surgery》2003,16(1):13-21
This study was devised to identify sepsis-relevant parameters that early and reliably predict a lethal outcome in intra-abdominal sepsis. In 18 Duroc pigs, peritonitis was induced through standardized gastrotomy. Twelve hours later the defect was oversewn and the abdominal cavity lavaged thoroughly. Sepsis relevant parameters were measured before initiating therapy, and 30 min later animals were extubated and observed for a period of 6 days under adequate analgesia with free access to water and food. All parameters were correlated with survival postoperatively. In the treatment group, 7 out of 18 pigs (39%) died within the observation period. Endotoxin level at 30 min after initiation of therapy [17.9 EU/mL (+/- 12.1) vs. 110.9 EU/mL (+/- 21); p <.001] and Delta pHi [0.015 (+/- 0.011) vs. -0.039 (+/- 0.013); p =.016] were identified as the two parameters with highest predictive power regarding mortality in a multivariate analysis. In conclusion measurement of endotoxin and gastric tonometry should gain wider clinical application in septic patients. 相似文献
57.
58.
Markus Kohler Hans M. Eppenberger Imogen Cordt-Riehle Christian Michel 《Acta oncologica (Stockholm, Sweden)》1992,31(6):673-677
Urination frequency and cystic pressure resistance have been used as end-points to assess x-ray-induced changes of bladder function. Whole or half bladders of adult male rabbits were irradiated, caudally or cranially. The absorbed dose was 33 Gy, 36 Gy or 39 Gy, given in 5 daily fractions. Animals which received a whole bladder dose of 39 Gy or 36 Gy showed increased urination frequency and enhanced bladder pressure resistance during the whole follow-up time of 100 weeks, compared with the sham-irradiated controls. At half bladder irradiation, only the highest doses (39 Gy to the cranial part of the bladder and 39 Gy or 36 Gy to the caudal part) gave rise to a slight increase in frequency at about 20 weeks after exposure. 相似文献
59.
Association of human polyomavirus JC with peripheral blood of immunoimpaired and healthy individuals
Drries Kristina Sbiera Silviu Drews Klaus Arendt Gabriele Eggers Christian Drries Rdiger 《Journal of neurovirology》2003,9(1):81-87
JC virus (JCV) infection is regularly asymptomatic in healthy individuals. In contrast, in immunocompromised individuals, highly activated virus replication may lead to PML. Peripheral blood cells (PBCs) are found to habor JCV DNA in healthy and diseased individuals and it is discussed that they might be responsible for dissemination of the virus to the central nervous system (CNS) during persistence. To better understand the role of JCV DNA in PBCs for persistent infection and pathogenesis, the authors characterized the extent of JCV infection in Ficoll-gradient purified blood cells (peripheral blood mononuclear cells [PBMCs]) of healthy and human immunodeficiency virus type 1 (HIV-1)-infected individuals. Virus activation in PBMCs from healthy JCV-infected individuals was found at a rate of 0% to 38% at low polymerase chain reaction (PCR) sensitivity. In progressive multifocal leukoencephalopathy (PML) patients, a stronger signal was found, indicating increased virus activation. JCV DNA was regularly detected in T and B lymphocytes and in monocytes at low levels. However, granulocytes were shown to be the predominant reservoir of JCV DNA harboring high copy numbers. Although the overall distribution of viral genomes holds true for the population studied, in the individual, a markedly changed pattern of distribution can be found. 相似文献
60.