New evidence for the role of TNF-alpha in liver ischaemic/reperfusion injury.

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) plays a key role in causing ischaemia/reperfusion (I/R) injury. I/R also causes activation of xanthine oxidase and dehydrogenase (XDH + XO) system that, via generated free radicals, causes organ damage. We investigated the effect of ischaemia, reperfusion and non-ischaemic prolonged perfusion (NIP) on TNF-alpha and XDH + XO production in an isolated perfused rat liver model. MATERIALS AND METHODS: Rat livers underwent 150 min NIP (control group) or two hours of ischaemia followed by reperfusion (I/R group). TNF-alpha (TNF-alpha mRNA and protein level), XDH + XO production and bile secretion were determined in tissue and effluent at baseline, at 120 min of ischaemia, after 30 min of reperfusion (I/R group) and after 120 and 150 min of prolonged perfusion (control). RESULTS: Unexpectedly, neither ischaemia nor reperfusion had any effect on TNF-alpha production. TNF-alpha in effluent was 11 +/- 4.8 pg mL(-1) at baseline, 7 +/- 3.2 pg mL(-1) at the end of ischaemia, and 13 +/- 5.3 pg mL(-1) after 30 min of reperfusion. NIP, however, caused a significant increase of TNF-alpha synthesis and release. TNF-alpha effluent level after 120 and 150 min of perfusion was 392 +/- 78.7 pg mL(-1) and 408 +/- 64.3 pg mL(-1), respectively. TNF-alpha mRNA in tissue was also significantly elevated compared to baseline levels (1.31 +/- 0.2 P < 0.001 and 1.38 P < 0.002, respectively). Decrease of liver function (expressed by bile secretion) during I/R and NIP was accompanied by significant XDH + XO elevation. CONCLUSION: This is the first evidence that NIP, and not I/R, is the decisive trigger for TNF-alpha production. This study leads to a better understanding of pathogenesis of liver I/R and perfusion damage.

Technical aspects of harvesting the radial artery with the harmonic scalpel.

BACKGROUND: Harvesting the radial artery (RA) with ultrasonic dissection with the Harmonic Scalpel reduces spasm induced by surgical handling. Topical exposure to phentolamine methanesulphonate (Regitine) exerts an additional effect of vasodilatation. METHODS: Between January and December 2002, the RA was harvested as a pediculated vessel with the Harmonic Scalpel in 145 consecutive patients undergoing myocardial revascularization. A fasciotomy of the pedicle was performed after harvest ing. A composite graft with the reverse free RA on the in situ left internal thoracic artery (ITA) was prepared before the construction of distal coronary anastomoses. The RA was then placed in a syringe filled with Regitine (0.07 microg/mL) for 10 minutes. \par RESULTS: The mean number of grafts/patient was 3.0. The mean number of RA anastomoses was 2.0/patient. Left ITA free flow was 105 +/- 34 mL/min. Regitine increased the RA free flow from 60 +/- 35 mL/min to 82 +/- 30 mL/min (P <.05). Fourteen patients underwent postoperative coronary angiography. All RA anastomoses were patent. CONCLUSION: The compound effect of RA harvesting with the Harmonic Scalpel and topical treatment with the alpha- blocking agent Regitine increases the RA free flow and significantly decreases intraoperative spasticity.

A randomized, controlled clinical trial of the homeopathic medication TRAUMEEL S in the treatment of chemotherapy-induced stomatitis in children undergoing stem cell transplantation.

BACKGROUND: Stomatitis is a common consequence of chemotherapy and a condition for which there is little effective treatment. Although the management of patients with other chemotherapy-related toxicities has improved in recent years, the incidence of stomatitis is increasing because of more intensive treatment and is often a dose limiting factor in chemotherapy. The authors assessed the efficacy of a homeopathic remedy, TRAUMEEL S(R), in the management of chemotherapy-induced stomatitis in children undergoing bone marrow transplantation. METHODS: A randomized, placebo-controlled, double-blind clinical trial was conducted in 32 patients ages 3-25 years who had undergone allogeneic (16 patients) or autologous (16 patients) stem cell transplantation. Of the 30 evaluable patients, 15 were assigned placebo, and 15 were assigned TRAUMEEL S both as a mouth rinse, administered five times daily from 2 days after transplantation for a minimum of 14 days, or until at least 2 days after all signs of stomatitis were absent. Stomatitis scores were evaluated according to the World Health Organization grading system for mucositis. RESULTS: A total of five patients (33%) in the TRAUMEEL S treatment group did not develop stomatitis compared with only one patient (7%) in the placebo group. Stomatitis worsened in only 7 patients (47%) in the TRAUMEEL S treatment group compared with 14 patients (93%) in the placebo group. The mean area under the curve stomatitis scores were 10.4 in the TRAUMEEL S treatment group and 24.3 in the placebo group. This difference was statistically significant (P < 0.01). CONCLUSIONS: This study indicates that TRAUMEEL S may reduce significantly the severity and duration of chemotherapy-induced stomatitis in children undergoing bone marrow transplantation.