The effect of mannitol versus dimethyl thiourea at attenuating ischemia/reperfusion-induced injury to skeletal muscle.
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OBJECTIVE: Mannitol is used as a treatment for skeletal muscle ischemia/reperfusion (I/R) injury in humans, despite the fact that its effectiveness in vivo is still disputed. The purpose of this study was to determine the efficacy of mannitol in attenuating I/R injury at the microcirculatory level. METHODS: The study was designed as an experimental study with male Wistar rats. The main outcome measures were intravital microscopy, which was used to measure capillary perfusion, capillary and venular red blood cell velocity (VRBC), and leukocyte-endothelial interactions in the extensor digitorum longus muscle of the rat hind limb before and after ischemia. In addition, tissue injury was assessed during reperfusion with the fluorescent vital dyes bisbenzimide and ethidium bromide. Dimethyl thiourea (DMTU), a highly effective therapeutic agent of experimental I/R injury, was used as a positive control. RESULTS: No-flow ischemia (2 hour) resulted in a 40% drop in capillary perfusion, a decline in capillary and venular VRBC, and increased leukocyte venular adherence and tissue infiltration. Tissue injury increased to a constant level during reperfusion. Mannitol attenuated capillary malperfusion during the first 60 minutes of reperfusion and prevented a decline in capillary VRBC. However, mannitol did not reduce tissue injury or leukocyte adherence and infiltration during reperfusion. By comparison, DMTU not only prevented the perfusion deficits and the increases in leukocyte venular adherence and tissue infiltration but significantly reduced the magnitude of tissue injury. CONCLUSION: Our findings suggest that mannitol may be of limited value for the prevention of early reperfusion-induced injury after no-flow ischemia in skeletal muscle. By comparison, DMTU was highly efficacious by not only reducing microvascular perfusion deficits but by also reducing leukocyte-endothelial cell interactions and the incidence of cellular injury. (+info)
Sex differences in prognosis for children with acute lymphoblastic leukemia.
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PURPOSE: Whether recent improvements in the treatment of childhood acute lymphoblastic leukemia (ALL) have nullified the adverse prognosis associated with male sex remains unclear. Therefore, we analyzed the survival experience and presenting clinical and laboratory features of boys and girls with newly diagnosed ALL who were treated at our institution over the past three decades. PATIENTS AND METHODS: One thousand one hundred fifty-one boys and 904 girls were treated in 13 consecutive Total Therapy studies between 1962 and 1994. An overview analysis was used to investigate the impact of sex on overall and event-free survival, both for the entire cohort and for subgroups defined by treatment era and blast-cell immunophenotype. Stratified analyses were performed to adjust for treatment protocol and known risk factors, and in the modern treatment era, for protocol, immunophenotype, and the DNA content of leukemic cells (ie, DNA index). The pharmacokinetics of methotrexate, teniposide, and cytarabine, as well as the thiopurine methyltransferase activity of erythrocytes, were compared between boys and girls treated on a single protocol. RESULTS: Compared with girls, boys were more likely to have T-cell ALL (20.9% v 10.7%, P < .001) and seemed less likely to have a favorable DNA index (17.8% v 25.1%, P = .072). There were no other statistically significant differences between the two sexes with respect to presenting features, including leukemic-cell genetic abnormalities, nor were there significant sex differences in the pharmacokinetics of methotrexate, teniposide, or cytarabine or in erythrocyte thiopurine methyltransferase activity. Girls clearly fared better than boys (P < .001) on protocols used during the early era of treatment (10-year event-free survival +/- 1 SE, 43.1%+/-2.1% v 31.5%+/-1.7%). Although prognosis improved for both sexes in the modern era, the difference in outcome between girls and boys persisted (P = .025) (10-year event-free survival, 73.4%+/-3.7% v 63.5%+/-4.0%). However, stratification of modern-era patients by protocol, immunophenotype, and DNA index mitigated statistical evidence of a sex difference in overall survival (P = .263) and event-free survival (P = .124). CONCLUSION: Although boys and girls alike have benefited from improvements in ALL therapy, these gains have not completely eliminated the sex difference in prognosis that has persisted since the early 1960s. The apparent difference in outcome is partially explained by differences between boys and girls in the distributions of ALL immunophenotype and DNA index. (+info)
Outcome for cancer patients requiring mechanical ventilation.
(75/106051)
PURPOSE: To describe hospital survival for cancer patients who require mechanical ventilation. MATERIALS AND METHODS: A prospective, multicenter observational study was performed at five academic tertiary care hospitals. Demographic and clinical variables were obtained on consecutive cancer patients at initiation of mechanical ventilation, and information on vital status at hospital discharge was acquired. RESULTS: Our analysis was based on 782 adult cancer patients who met predetermined inclusion criteria. The overall observed hospital mortality was 76%, with no statistically significant differences among the five study centers. Seven variables (intubation after 24 hours, leukemia, progression or recurrence of cancer, allogeneic bone marrow transplantation, cardiac arrhythmias, presence of disseminated intravascular coagulation, and need for vasopressor therapy) were associated with an increased risk of death, whereas prior surgery with curative intent was protective. The predictive model based on these variables had an area under the receiver operating characteristic curve of 0.736, with Hosmer-Lemeshow goodness-of-fit statistics of 7.19; P = .52. CONCLUSION: This model can be used to estimate the probability of hospital survival for classes of adult cancer patients who require mechanical ventilation and can help to guide physicians, patients, and families in deciding goals and direction of treatment. Prospective independent validation in different medical settings is warranted. (+info)
Quality of life and performance in advanced head and neck cancer patients on concomitant chemoradiotherapy: a prospective examination.
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PURPOSE: To prospectively evaluate performance and quality of life (QOL) in advanced-stage head and neck cancer (HNC) patients on a curative-intent, concomitant-chemoradiotherapy (CT/XRT) (twice-daily radiation, fluorouracil, hydroxyurea, and cisplatin) regimen aimed at improving locoregional control, survival, and QOL. PATIENTS AND METHODS: Sixty-four patients were assessed before, during, and at 3-month intervals after treatment. Standardized measures of QOL (Functional Assessment of Cancer Therapy-Head and Neck), performance (Performance Status Scale for Head and Neck Cancer Patients and Karnofsky Performance Status Rating Scale), and patient-reported symptoms (McMaster University Head and Neck Radiotherapy Questionnaire) were administered. RESULTS: Acute treatment toxicities were severe, with declines in virtually all QOL and functional domains. Marked improvement was seen by 12 months; general functional and physical measures returned to baseline levels of good to excellent. Although up to a third of the patients continued to report problems with swallowing, hoarseness, and mouth pain, these difficulties were present in similar magnitudes before treatment. The following symptoms were more frequent at 12 months: dry mouth (58% v 17%), difficulties tasting (32% v 8%), and soft food diet (82% v 42%). Twelve-month diet was not related to pretreatment functioning, disease, treatment, or patient characteristics. Twelve-month QOL was best predicted by pretreatment QOL, with very little relationship to residual side effects or functional impairments. Small numbers of patients in four of the five disease sites precluded examination of outcome by site. CONCLUSION: These data support the feasibility of intense CT/XRT as primary treatment for advanced HNC. Results confirm acute toxicity but indicate that many of the treatment-related performance and QOL declines resolve by 12 months. The persistent inability to eat a full range of foods warrants further attention and monitoring. (+info)
Antegrade visceral revascularisation via a thoracoabdominal approach for chronic mesenteric ischaemia.
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OBJECTIVES: It has been suggested that patients with chronic visceral ischaemia are elderly and emaciated hence they may not tolerate antegrade visceral revascularisation via a thoracoabdominal approach. There are no studies to support this assumption. The purpose of this study is to assess the efficacy of this approach for the treatment of chronic visceral ischaemia. METHODS: Between 1988 and 1996, 10 patients underwent antegrade visceral revascularisation for chronic visceral ischaemia via a thoracoabdominal approach and were followed-up for a mean of 40 months. Eight patients were treated with aorto superior mesenteric artery bypass and implantation of the coeliac axis in the graft and two patients with aorto superior mesenteric bypass alone. Graft patency was monitored with duplex scanning. RESULTS: There were no postoperative deaths in this series. Two patients developed postoperative pulmonary infections and required intubation for a short period of time. All patients were discharged after a mean of 17 days (range 7-38). Follow up with duplex scanning revealed that all grafts were patent. One patient developed a high grade anastomotic stenosis which was followed by recurrence of the symptoms. This was dilated on three occasions by balloon angioplasty within a period of 17 months. On the last occasion a stent was placed and since the patient remains asymptomatic. CONCLUSIONS: Antegrade visceral revascularisation via a thoracoabdominal approach is a durable and effective method of relieving symptoms of chronic visceral ischaemia. The low morbidity in this series justifies larger studies in order to establish the true incidence of complications. (+info)
Outcome of the first 100 femoropopliteal angioplasties performed in the operating theatre.
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OBJECTIVES: To examine the factors influencing outcome and restenosis in an initial series of 100 infrainguinal angioplasties. DESIGN: Prospective study of angioplasties of the superficial femoral and popliteal arteries performed over a 42-month period. MATERIALS AND METHODS: One hundred consecutive angioplasties in 96 patients performed in the operating theatre between January 1993 and June 1996 were followed prospectively with clinical, ABI, and duplex assessment. Forty-four procedures were for disabling claudication and 56 for critical ischaemia. Stents were deployed in 30 limbs. RESULTS: Angioplasty was successful in 84 of 100 limbs. Cumulative patency of the entire group at 3, 6, 12 and 18 months was 78%, 60%, 53%, and 49% respectively, while excluding initial failures, gave patencies of 95%, 69%, 63%, and 58%, respectively. Claudicants with a 1-year patency of 64% did significantly better than patients with critical ischaemia (44% p < 0.05). Angioplasties performed during the initial 21 months had a 1-year patency of 42%, while those performed in the final 21 months had a 74% patency (p = N.S.). The patency for stented arteries was 66% vs. 49% for angioplasty alone (p = N.S.). The 2-year limb salvage rate was 91% in patents with critical ischaemia. Forty-six per cent of restenoses were asymptomatic. CONCLUSIONS: The results suggest that while angioplasty is useful in treating infrainguinal arterial disease, there is a learning curve, resulting in a high restenosis rate for occlusive and multilevel disease, while concomitant placement of stents may be beneficial. (+info)
The surgical management of acute limb ischaemia due to native vessel occlusion.
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OBJECTIVES: Data from the STILE study have indicated that for patients with subacute limb ischaemia due to native vessel occlusion, surgery is both more effective, and durable than thrombolysis. The purpose of this study was to evaluate the outcome of an aggressive surgical approach in patients presenting with acute limb-threatening ischaemia. DESIGN: Details of patients presenting with salvageable acute limb ischaemia due to native artery occlusion over a 6-year period in a University hospital vascular unit setting were obtained from the vascular audit and the outcome of the surgical management of these patients was analysed. RESULTS: One hundred and seventy-four consecutive patients underwent surgery for acute native vessel limb ischaemia (76% lower, 24% upper limb). Fogarty thrombectomy or embolectomy was initially performed in 153 (89%) patients. Of these, 37 (24%) immediately underwent a further procedure: 28 (18%) had on-table thrombolysis and 14 (9%) underwent vascular reconstruction. Twenty-six patients (15%) underwent further limb salvage surgery within 30 days. Life table analysis demonstrated a limb salvage rate of 88% and 76% at 30 days and 2 years, respectively. Patient survival was 75% and 48% at the same time intervals. CONCLUSIONS: These results demonstrate that a role for aggressive surgical intervention still exists, resulting in high limb salvage rates. (+info)
Relationship of femorodistal bypass patency to clinical outcome. Iloprost Bypass International Study Group.
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OBJECTIVE: To investigate the relationship between bypass patency, limb survival and clinical symptoms after femorodistal bypass procedures. DESIGN: Multicentre, prospectively planned 12-month postoperative follow-up. PATIENTS AND METHODS: Five hundred and seventeen patients undergoing femorodistal bypass surgery for severe ischaemia. Clinical symptoms, bypass patency were recorded at regular intervals up to 12 months postoperatively. RESULTS: Complete follow-up data was obtained on 498 patients (96%). Fifty-six (17%) of the 341 patients with patent bypasses had either rest pain or ulcers or had undergone major amputation at 12 months. Of the 167 patients with an occluded bypass, 22 patients (13%) had improved clinical symptoms and a total of 59 patients (35%) had avoided major amputation at 12 months. The clinical outcome for patients classified preoperatively as Fontaine stage IV was significantly worse than for those in stage III preoperatively despite similar bypass patency rates. CONCLUSIONS: There is a fair correlation between technical and clinical outcome after femorodistal bypass surgery at 12 months, but there are significant numbers of patients with occluded bypasses who have a good clinical outcome and of patients with patent bypasses who have a poor clinical outcome. The reporting of symptoms in addition to bypass patency would aid the interpretation of surgical results. (+info)