The Surgical and Functional Outcome of Limb-Salvage Surgery With Vascular Reconstruction for Soft Tissue Sarcoma of the Extremity

Background This study compared the surgical, oncological, and functional outcomes of patients undergoing limb-salvage surgery for extremity soft tissue sarcoma with vascular resection and reconstruction with the outcomes of those undergoing limb-salvage without vascular reconstruction. Methods Nineteen patients were identified from a prospective soft-tissue sarcoma database who underwent vascular resection and reconstruction as part of their limb-salvage surgery and who were followed up for at least 1 year or until death. Each of these 19 patients was case-matched to 2 additional patients on the basis of tumor location, size, and depth; patient age; and timing of radiation. To compare functional outcome, a subset of patients was case-matched with additional criteria including wound-complication status, motor nerve sacrifice, similar preoperative function as determined by the Toronto Extremity Salvage Score, and no metastases at diagnosis or the 1-year follow-up. Results Patients in the vascular reconstruction group were more likely to require a muscle transfer (53% vs. 18%; P = .008), experience a wound complication (68% vs. 32%; P = .03), experience deep venous thrombosis (26% vs. 0; P = .003), experience significant limb edema (87% vs. 20%; P = .001), and ultimately require an amputation (16% vs. 3%; P = .07). Patients who underwent vascular reconstruction had only slightly lower Toronto Extremity Salvage Score scores 1 year after surgery (78.5 vs. 84.2; P = .35). There were no significant differences in local or systemic tumor relapse between the two groups. Conclusions Vascular reconstruction is a feasible option in limb-salvage surgery for soft tissue sarcoma but is associated with an increased risk for postoperative complications, including amputation. Although function is not significantly worse after vascular reconstruction, the results are less predictable.     

Vaporized perfluorohexane attenuates ventilator-induced lung injury in isolated, perfused rabbit lungs

BACKGROUND: The authors tested the hypothesis that administration of vaporized perfluorohexane may attenuate ventilator-induced lung injury. METHODS: In isolated, perfused rabbit lungs, airway pressure-versus-time curves were recorded. At baseline, peak inspiratory pressure and positive end-expiratory pressure of mechanically ventilated lungs were set to obtain straight pressure-versus-time curves in both the lower and upper ranges, which are associated with less collapse and overdistension, respectively. After that, peak inspiratory pressure and positive end-expiratory pressure were set at 30 cm H2O and 0, respectively, and animals were randomly assigned to one of two groups: (1) simultaneous administration of 14% perfluorohexane vapor in room air (n = 7) and (2) control group-ventilation with room air (n = 7). After 20 min of cycling collapse and overdistension, tidal volume and positive end-expiratory pressure were set back to baseline levels, administration of perfluorohexane in the therapy group was stopped, and mechanical ventilation was continued for up to 60 min. Lung weight, mean pulmonary artery pressure, and concentration of thromboxane B2 in the perfusate were measured. In addition, the distribution of pulmonary perfusate flow was assessed by using fluorescent-labeled microspheres. RESULTS: Significantly higher peak inspiratory values developed in control lungs than in lungs treated with perfluorohexane. In addition, upper ranges of pressure-versus-time curves were closer to straight lines in the perfluorohexane group. Lung weight, mean pulmonary arterial pressure, and release of thromboxane B2 were significantly higher in controls than in perfluorohexane-treated lungs. Also, redistribution of pulmonary perfusate flow from caudal to cranial zones was less important in the treatment group. CONCLUSION: The authors conclude that the administration of perfluorohexane vapor attenuates the development of ventilator-induced lung injury in isolated, perfused rabbit lungs.     

Estrogen receptor (ER) gene polymorphism may predict the bone mineral density response to raloxifene in postmenopausal women on chronic hemodialysis

The estrogen receptor (ER) gene has been considered as a candidate genetic marker for osteoporosis, and PvuII and XbaI polymorphisms of the ERalpha gene have been associated with low bone mineral density (BMD). We investigated whether ER polymorphism could predict the response of BMD in 28 postmenopausal women on hemodialysis with marked osteopenia or osteoporosis, randomized to receive raloxifene, a selective estrogen receptor modulator (SERM), or placebo for 1 year. BMD was assessed by dual X-ray absorptiometry and PvuII and XbaI restriction fragment-length polymorphism of the ER gene was determined using polymerase chain reaction. Baseline lumbar spine or femoral neck BMD parameters were not different between patients presenting either homozygous PP or xx when compared with heterozygous Pp or Xx genotypes. After 1 year, patients on raloxifene, presenting with PP or xx genotypes (but not those with Pp or Xx), showed a significantly higher mean lumbar spine BMD (0.942 +/- 0.18 vs. 0.925 +/- 0.17 g/cm2, p < .01) and lower serum pyridinoline (19.7 +/- 9.7 vs. 30.6 +/- 16.5 nmol/L, p < .02) when compared with baseline values. No changes were detected in the placebo-treated patients or in the femur neck sites. In conclusion, after 1 year on raloxifene, postmenopausal osteoporotic women on chronic hemodialysis, homozygous for the P or x (PP or xx) alleles of the ER, exhibited a better lumbar spine BMD response and decreased serum pyridinoline values when compared with heterozygous women (Pp or Xx), suggesting that ERalpha allelic variants may explain, at least in part, the different outcomes after treatment of osteoporosis with SERM.     

Design issues and outcomes in IBD clinical trials

Successful clinical trials in inflammatory bowel disease are based on precise definitions of study populations, standardized and well-defined interventions, reliable indices of disease activity, and clearly stipulated outcome measures. Interpretation of research results is often complicated by the differentiation of goals of therapy (remission induction and maintenance, quality of life) and the multitude of patient subsets. Choosing the correct patient subtype to enroll in a clinical trial is critical to the results of a study, its conclusions, and its applicability to the clinical setting. Validated, easy-to-use disease activity indices allow interpretation of results across trials. The use of biomarkers as surrogate clinical endpoints provides reproducibility, ease of statistical handling as a continuous variable, and consistent measurement of response to treatment. Despite these potential advantages, biomarkers of disease activity lack specificity and will need to be validated against clinically meaningful outcomes. Careful subject selection, standardization of disease activity indices, and precise outcome measurement are the keys to continued improvement of the inflammatory bowel disease research process.     

Relaxant effects of the essential oil of Eucalyptus tereticornis and its main constituent 1,8-cineole on guinea-pig tracheal smooth muscle

The effects of the essential oil of Eucalyptus tereticornis Sm. (EOET) on guinea-pig tracheal smooth muscle were investigated. EOET (10 - 1000 microg/mL) relaxed the tracheal basal tonus with an EC (50) value of 125.3 [52.2 - 300.9] microg/mL. Its maximal relaxation (40 +/- 6 %) was significantly lower than that evoked by aminophylline (209 +/- 34 %). The K (+)-(60 mM)-induced contractions were significantly reduced by both EOET (200 - 1000 microg/mL) and its main constituent 1,8-cineole (600 - 1000 microg/mL). Acetylcholine (1 microgM)-induced contractions were significantly enhanced by 1,8-cineole (10 - 1000 microg/mL). However, they were significantly enhanced and reduced by lower (200 - 400 microg/mL) and higher (800 - 1000 microg/mL) concentrations of EOET, respectively. Electrical field stimulation-induced contractions were significantly increased by EOET (100 - 600 microg/mL). In conclusion, EOET produces myorelaxant effects on guinea-pig isolated trachea, an effect that seems to result from a complex interaction between its monoterpenoid constituents.     

Chronic treatment with mianserin prevents DOCA-salt hypertension in rats--evidence for the involvement of central 5-HT2 receptors

Central 5-HT2A receptors have been implicated in central volume control by activating a central angiotensinergic pathway to cause the release of vasopressin. Interestingly, to induce DOCA-salt hypertension in rats vasopressin release is required. Thus the present experiments were carried out to determine whether continuous blockade of these receptors over 20 days, with the non-selective 5-HT2 receptor antagonist mianserin would prevent the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Mianserin, given i.c.v. 90 or 60 microg twice daily for 20 days prevented the development of hypertension in conscious rats receiving DOCA-salt but did not affect blood pressure in rats on salt alone. Further, the dose of 30 microg given i.c.v. twice daily had no effect nor did the vehicle, polyethylene glycol (PEG), on the development of the hypertension. Mianserin 90 microg twice daily i.c.v. was also shown to prevent the increase in fluid intake, urinary flow and sodium excretion caused by DOCA-salt treatment. These data indicate that this action of mianserin is not due to an intrinsic hypotensive action but an action which involves interference with the mechanism by which DOCA-salt treatment causes hypertension. Thus the data overall support the view that to induce hypertension with DOCA-salt a central 5-HT-containing pathway needs to be activated, which then activates 5-HT2 receptors to cause the release of vasopressin which has previously been shown to be responsible for the initiation of DOCA-salt treatment hypertension.