Pentoxifylline. Adjunctive therapy in the treatment of pedal frostbite

Frostbite injury to the extremities has the potential for disastrous effects. Prompt recognition and treatment are paramount. The use of Pentoxifylline to minimize tissue damage in the treatment of frostbite is a viable addition to the traditional therapy of rewarming soaks, pain management, and vesicle débridement. The most well known action of Pentoxifylline is its ability to increase RBC flexibility, allowing easier vascularization. This explains its indication for PVD, arterial disease, and intermittent claudication. As is explained previously, however, Pentoxifylline has multiple actions that will enhance tissue survival. The dosage of Pentoxifylline in controlled release tablet form is one 400 mg tablet three times a day with meals. The duration of treatment should be from two to six weeks. As this drug has many actions and therefore possibilities, more research is warranted with regards to its use not only with frostbite, but with other pathological processes.     

Vaccination with irradiated autologous tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor augments antitumor immunity in some patients with metastatic non-small-cell lung carcinoma.

PURPOSE: We demonstrated that vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates potent, specific, and long-lasting antitumor immunity in multiple murine models and patients with metastatic melanoma. To test whether this vaccination strategy enhances antitumor immunity in patients with metastatic non-small-cell lung cancer (NSCLC), we conducted a phase I clinical trial. PATIENTS AND METHODS: Resected metastases were processed to single-cell suspension, infected with a replication-defective adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines consisted of 1 x 10(6), 4 x 10(6), or 1 x 10(7) cells, depending on overall yield, and were administered intradermally and subcutaneously at weekly and biweekly intervals. RESULTS: Vaccines were successfully manufactured for 34 (97%) of 35 patients. The average GM-CSF secretion was 513 ng/10(6) cells/24 h. Toxicities were restricted to grade 1 to 2 local skin reactions. Nine patients were withdrawn early because of rapid disease progression. Vaccination elicited dendritic cell, macrophage, granulocyte, and lymphocyte infiltrates in 18 of 25 assessable patients. Immunization stimulated the development of delayed-type hypersensitivity reactions to irradiated, dissociated, autologous, nontransfected tumor cells in 18 of 22 patients. Metastatic lesions resected after vaccination showed T lymphocyte and plasma cell infiltrates with tumor necrosis in three of six patients. Two patients surgically rendered as having no evidence of disease at enrollment remain free of disease at 43 and 42 months. Five patients showed stable disease durations of 33, 19, 12, 10, and 3 months. One mixed response was observed. CONCLUSION: Vaccination with irradiated autologous NSCLC cells engineered to secrete GM-CSF enhances antitumor immunity in some patients with metastatic NSCLC.     

Spinal instrumentation for primary pyogenic infection report of 31 patients

The role of spinal instrumentation in the presence of infection is still controversial. Radical debridements of infected vertebrae and disc material and bone grafting usually leaves the spine unstable without some surgical stabilisation. We reviewed 31 cases of primary pyogenic spinal infection treated by radical debridement, bone grafting and posterior (30) or anterior (1) spinal instrumentation. The indication for surgery was the failure of conservative treatment (8), progressive neurological deficit (19) or the lack of diagnosis (3). The clinical, laboratory and radiological parameters were assessed pre and postoperatively. The mean period of follow-up was 3.8 years (1-12 years). The neurological deficit was progressive in 19 patients, following surgery all these patients were improved. The neurological deficit was established in one patient; following surgery, his neurological deficit did not improve. The infection was eradicated in all our patients. The following complications were encountered: (1) three patients developed deep wound infection, which responded to repeated debridement; (2) one death resulted from nosocomial septicaemia, (3) reoperation was carried out on one patient for implant failure and on another for a dislodged anterior bone graft. We conclude that spinal instrumentation may be indicated when after radical debridement of infected vertebrae and disc material and bone grafting the stability of the spine is still compromised. According to the location of the infection and the availability of suitable implants, anterior or posterior instrumentation may be necessary. With appropriate antimicrobial agents, the outcome has been satisfactory in our patients.     

Critical decisions in the management of endoscopic perforations of the colon

The ideal management of suspected colon perforation following colonoscopy remains elusive because the incidence is only 0.1 to 2.0 per cent. The patient with obvious perforation deserves immediate exploration, but the patient with equivocal findings poses a diagnostic dilemma. We propose an algorithm based on the results of water-soluble contrast enema that allows for rapid, definitive surgical decision-making. If perforation is confirmed, early operation allows for primary repair without resection or colostomy, or if no perforation is identified, medical management can be undertaken with confidence. This algorithm should ensure that the surgical management of this potentially lethal complication is not unnecessarily delayed.     

Endothelins and their inhibition in the human skin microcirculation: ET[1-31], a new vasoconstrictor peptide

AIMS: Endothelin-1 (ET-1([1-21])) is an extremely potent vasoconstrictor in the human skin microcirculation and is generated from larger precursor peptides. The aims of the present study were to assess the vasoactive effects of these precursors as well as endothelin blockade in the human skin microcirculation, in vivo. METHODS: Six healthy volunteers received intradermal injections of a range of doses of big ET-1([1-38]), ET-1([1-31]), ET-1([1-21]), BQ-123 (ET(A) receptor antagonist), BQ-788 (ET(B) receptor antagonist), phosphoramidon [endothelin converting enzyme (ECE) inhibitor] or saline control (0.9%). Skin blood flow (SBF) was measured using standard laser Doppler flowmetry. RESULTS: Big ET-1([1-38]), ET-1([1-31]) and ET-1([1-21]) reduced SBF when compared with saline control (P < 0.01 for all). Big ET-1([1-38]) and ET-1([1-31]) were less potent than ET-1([1-21]) as defined by skin vasoconstriction. Phosphoramidon, BQ-123 and BQ-788, given alone, all caused vasodilatation in the human skin microcirculation (P < 0.01 for all). CONCLUSIONS: In the human skin microcirculation, big ET-1([1-38]) and ET-1([1-31]) are less potent vasoconstrictors than ET-1([1-21]). The effects of big ET-1([1-38]) and phosphoramidon suggest the presence of endogenous ECE activity in the skin. In contrast to skeletal muscle resistance vessels, ET-1([1-21]) contributes to the maintenance of skin microvascular tone through both ET(A) and ET(B) receptor-mediated vasoconstriction.