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PubMed · 990855

The stricken.

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1976-11-20. The stricken.. https://pubmed.ncbi.nlm.nih.gov/990855/

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Laparoscopic cholecystectomy: are patients with biliary pancreatitis at increased operative risk?

BACKGROUND: Previous reports of laparoscopic cholecystectomy (LC) in patients with biliary pancreatitis suggested increased operative difficulty, high rates of conversion, and greater morbidity and mortality. METHODS: Between 1990 and 1997, LC was performed for biliary pancreatitis in 63 patients (Group I) and for other causes in 829 patients (Group II). RESULTS: Patients with biliary pancreatitis were significantly older (median age 57 vs 50 years, p = 0.009), with greater co-morbidity (ASA III/IV 24% vs 11%, p = 0.008). The groups were comparable with respect to the frequency of previous abdominal operations, acute inflammation of the gallbladder, and the frequency of bile duct calculi detected by intraoperative cholangiography. Moderate to severe adhesions involving the gallbladder were significantly more frequent in patients with biliary pancreatitis (46% vs 29%, p = 0.004). No significant differences were observed between the two groups with respect to intraoperative (1.5% Group I vs 6.0% Group II, p = 0.109) or postoperative complications (10% vs 8%, p = 0.426), conversion rate (0 vs 2.7%, p = 0.181), or duration of operation (median 92 vs 85 min, p = 0.33). CONCLUSION: Despite increased age and co-morbidity and more frequent adhesions, our data showed no evidence that intraoperative or postoperative complications were more frequent in patients with biliary pancreatitis than in other patients undergoing LC.

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Refractory Aspergillus pneumonia in patients with acute leukemia: successful therapy with combination caspofungin and liposomal amphotericin.

BACKGROUND: Pulmonary aspergillosis and other invasive fungal infections (IFIs) commonly complicate the management of patients with acute leukemia. Standard amphotericin-based therapies may be ineffective for many patients and the available salvage agents (itraconazole and caspofungin) are reported to possess only moderate activity against resistant infections. Laboratory evidence suggests a synergistic interaction between amphotericin and caspofungin. The authors treated a group of patients with amphotericin-refractory IFIs with the combination of caspofungin and amphotericin (or liposomal amphotericin). METHODS: A retrospective evaluation of patients with amphotericin-resistant IFIs was conducted. Diagnosis was based on clinical, radiographic, and when available, microbiologic data. Response to combination antifungal therapy was graded as either favorable or unfavorable. Favorable responses included improvement of both clinical and radiographic signs of fungal pneumonia. All other responses were graded as unfavorable. RESULTS: Thirty patients were included in this analysis. Twenty-six patients had acute leukemia. Based on recently published criteria, the IFIs were classified as proven in 6 patients, probable in 4 patients, and possible in 20 patients. The median duration and dose of amphotericin monotherapy were 12 days (range, 4-65 days) and 7.8 mg/kg (range, 4.2-66.1 mg/kg), respectively. The median duration of combination therapy was 24 days (range, 3-74 days). Eighteen patients (60%) experienced a favorable antifungal response. Twenty patients with acute leukemia received combination therapy for fungal pneumonias arising during intensive chemotherapy treatments. Favorable responses were observed in 15 of these patients (75%), and antifungal response did not depend on the response of the underlying leukemia. Survival to hospital discharge was significantly better (P < 0.001) in patients having a favorable response. Mild to moderate nephrotoxicity was noted in 50% of patients, necessitating the substitution of liposomal amphotericin. Mild elevation of alkaline phosphatase levels occurred in 30% of patients. Caspofungin was temporarily withheld from one patient who developed moderate but reversible biochemical hepatotoxicity. CONCLUSIONS: The antifungal combination of caspofungin and amphotericin can be administered safely to high-risk patients with hematologic malignancies. Although an absolute assessment of efficacy is limited by the design of this study, encouraging outcomes were noted for many patients. The authors plan to evaluate this regimen further in a randomized clinical trial.

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Expression of the long form of human FLIP by retroviral gene transfer of hemopoietic stem cells exacerbates experimental autoimmune encephalomyelitis.

Subsidence of inflammation and clinical recovery in experimental autoimmune encephalomyelitis (EAE) is postulated to involve apoptosis of inflammatory cells. To test this concept, we examined the effects of overexpressing the long form of human FLICE-inhibitory protein, a potent inhibitor of death receptor-mediated apoptosis, in myelin oligodendrocyte glycoprotein-induced EAE in DBA/1 mice. We found that overexpression of the long form of human FLICE-inhibitory protein by retroviral gene transfer of hemopoietic stem cells led to a clinically more severe EAE in these mice compared with control mice receiving the retroviral vector alone. The exacerbated disease was evident by an enhanced and prolonged inflammatory reaction in the CNS of these animals compared with control mice. The acute phase of EAE was characterized by a massive infiltration of macrophages and granulocytes and a simultaneous increase in TNF-alpha production in the CNS. In the chronic phase of the disease, there was a prolonged inflammatory response in the form of persistent CD4(+) T and B cells in the CNS and a peripheral Th1 cytokine bias caused by elevated levels of IFN-gamma and reduced levels of IL-4 in the spleen. Our findings demonstrate that death receptor-mediated apoptosis can be important in the pathogenesis of EAE and further emphasize the need for effective apoptotic elimination of inflammatory cells to achieve disease remission.

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