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M F Sakr

Publications and source records attributed to M F Sakr.

10 recordsLinked to original sources

FK 506 pre-treatment is associated with reduced levels of tumor necrosis factor and interleukin 6 following hepatic ischemia/reperfusion.

Using a rat model, the effect of pre-treatment with FK 506 on hepatic ischemia/reperfusion injury was investigated. All control animals died within 72 h of the ischemia/reperfusion injury. Pre-treatment of the animals with FK 506 (0.3 mg/kg in 0.5 ml saline) administered intravenously improved survival. The most striking protection against fatal ischemia/reperfusion injury was achieved in rats that were given FK 506 6 and 24 h prior to the induction of the hepatic ischemic insult (70% and 80% 10-day survival rates, respectively). The hepatoprotective effect of FK 506 was assessed further in a second experiment in which the serum levels of tumor necrosis factor (TNF) and interleukin 6 (IL-6) were measured. These results suggest that a 60-min period of hepatic ischemia and subsequent reperfusion triggers the release of both TNF and IL-6, and that FK 506 pre-treatment (6 h before the ischemic episode) significantly inhibits the production and/or release of these two cytokines compared to untreated controls. These data provide additional information concerning the immunosuppressive and hepatoprotective activities of FK 506. Based upon these data, it is probable that FK 506 attenuates hepatic ischemia/reperfusion injury, at least in part, by reducing TNF and IL-6 levels.

Animals↗

FK 506 ameliorates the hepatic injury associated with ischemia and reperfusion in rats.

The effect of FK 506 on regeneration of the liver was studied in rats after a two-thirds partial hepatectomy after 60 min of ischemia of the unresected liver. The animals were divided into three distinct groups of 10 rats each. Group 1 (controls) received 0.5 ml saline solution intravenously 30 min after the induction of ischemia. Groups 2 and 3 were injected with FK 506 (0.3 mg/kg) intravenously 30 min after and 24 min before the induction of hepatic ischemia, respectively. The hepatic content of ATP and serum levels of ALT and lactate dehydrogenase were determined on each animal. In addition, the histological appearance and mitotic activity of the remnant liver was determined at regular 24-hr intervals after hepatic ischemia. All 10 control animals died within 72 hr. Treatment with FK 506 resulted in improved survival in groups 2 and 3 (30% and 80%, respectively). The improved survival seen in the FK 506-treated animals was reflected by a restoration of hepatic ATP content, a reduction in the serum levels of ALT and lactate dehydrogenase, an amelioration of hepatic necrosis and neutrophilic infiltration and an increase in the mitotic activity of the liver. These results suggest that FK 506 ameliorates the hepatic injury associated with ischemia/reperfusion and has a potent stimulatory effect on liver cell regeneration that may make it valuable as a hepatoprotective agent when administered to organ donors before graft harvesting.

Adenosine Triphosphate↗

FK 506 ameliorates the hepatic injury associated with ischemia.

Ischemic damage of the allograft liver is a major problem in clinical liver transplantation. Therefore the identification of hepatoprotective agents is a high priority at most liver transplantation programs. FK 506, a potent new immunosuppressive agent has been reported to possess hepatotrophic activity. To evaluate the putative hepatotrophic activity of FK 506 on experimental hepatic ischemia, rats were subjected to a subtotal hepatectomy following experimental ischemia and subsequent rat survival was assessed. FK 506 (0.3 mg/Kg) administered intravenously 24 hours prior to the induction of hepatic ischemia, reduced the subsequent mortality rate from 100% among controls given saline to only 20% (P less than 0.001). This observation demonstrates that FK 506 enhances the regenerative response of the liver to ischemic injury and may, in addition to its immunologic activity have hepatotrophic activity as well.

Animals↗

The use of the 'TRAM' flap in some oncological problems.

The present study was conducted to evaluate the use of the transverse rectus abdominis myocutaneous (TRAM) flap in immediate autologous soft tissue coverage of the large wound defect that results from some oncological problems and would be impossible to close by direct primary sutures. The study included patients with locally advanced breast cancer (LABC) (n = 24), post-mastectomy local recurrence (n = 10), post-mastectomy irradiation ulcer (n = 4), recurrent fibrosarcoma of the chest wall (n = 1), and a huge ulcerating malignant melanoma of the groin region (n = 1). All patients were female except for the patient with melanoma. Their ages ranged between 39-73 years with an average of 56.2 years. The lower TRAM flap was used in 24 patients and the middle in only six. Mesh re-inforcement of the abdominal wall was adopted in 14 patients (35%). The mean operating time was 2.5 h and the average postoperative hospital stay was 9.7 days (range, 7-12 days). Six patients (15%) had partial flap necrosis which healed after debridement and secondary sutures, and eight patients had wound sepsis (20%). No patient suffered from abdominal herniation, although four patients (10%) had an epigastric bulge postoperatively. During the 48.5 month follow-up period (range 36-56 months), three cases of local recurrence and four cases of distant metastases were encountered in the patients with LABC. Three of the latter died at 7, 11 and 12 months postoperatively. Based on these data, it may be concluded that the results of the TRAM flap for immediate coverage of the large post-extirpation defect in different oncological problems have been encouraging. No flaps were lost, no abdominal herniation was encountered, and overall complications were minimal.

Abdominal Muscles↗

Risk factors in surgery of gastroduodenal ulcer disease in patients with schistosomal portal hypertension.

The present study was conducted to determine the risk factors associated with surgical treatment of peptic ulcer disease (PUD) in patients with schistosomal hepatic fibrosis (SHF). The medical records of 32 patients treated at the Department of Surgery, Alexandria Faculty of Medicine between 1984 and 1994 were reviewed and data were analyzed. Twenty-five patients were male and seven were female, with a mean age of 43.3 +/- 24. Fifteen patients belonged to Child A and 13 to Child B. Twenty-one patients were variceal non-bleeders and 11 were bleeders. The ulcer was pyloric or duodenal in 30 patients and gastric in only two. Twenty-four patients were operated upon electively mostly for pyloric obstruction (n = 15) and eight patients emergently; five for perforation and three for bleeding. Hepatic insufficiency, renal function impairment and gastrointestinal bleeding were the most detrimental postoperative complications that occurred, either alone or in combination, in 13 patients (40.6%). Eight patients died (25%) of liver failure (n = 5), gastrointestinal bleeding (n = 2) and multiple systems organ failure (n = 1). Urgency of the operation and Child B were of significance for predicting mortality in contrast to age, sex, liver size, bleeding varices and ulcer location. Based on these data, it may be concluded that 1) operations for PUD in patients with schistosomal portal hypertension are expected to have high postoperative morbidity and mortality; 2) mortality rate significantly increases by emergency operations, presence of postoperative complications and in modified Child B patients; 3) Liver function must be optimized preoperatively; and 4) the most simple and expeditious procedure must be performed to minimize postoperative complications and hepatic decompensation.

Adult↗

Protective effect of cyclosporine A (CyA) against the hepatic injury associated with ischemia and reperfusion.

The putative hepatoprotective effect of cyclosporine A (CyA) against the hepatic injury associated with ischemia and reperfusion was studied in rats after a two-thirds hepatectomy following a 60-minute period of ischemia of the unresected liver. Animals were divided into three distinct groups of 10 rats each Group 1 (controls) received 0.5 ml saline solution intravenously (i.v.) while group 2 animals were injected with CyA (5 mg/kg) i.v., 24 hours before the induction of hepatic ischemia. The hepatic ATP content and serum levels of ALT and LDH were determined in each animal. Rats in group 3 were subjected to two-thirds hepatectomy only without the induction of ischemia. All controls died within 72 hours (group 1). Pretreatment of CyA improved the 7-day survival to 60% (p < 0.01). All group 3 animals survived through seven days. The improved survival seen in CyA pretreated animals as compared to controls was reflected by a restoration of hepatic ATP content and reduction in the serum levels of ALT and LDH postoperatively. Based on these results, it may be concluded that CyA ameliorates the hepatic injury associated with ischemia and reperfusion and allows the liver to recover and regenerate. Subsequently, survival is enhanced.

Alanine Transaminase↗