Citations

AbstractOBJECTIVE:Olfaction is often sacrificed to gain access to the cranial base in anterior craniofacial surgery. We describe the long-term results of olfactory function in patients who underwent anterior craniofacial surgery and a cribriform plate osteotomy to preserve olfaction.METHODS:Between 1992 and 2004, 28 patients underwent 29 cribriform plate osteotomies in an attempt to preserve olfaction during anterior craniofacial surgery performed through modified extended transbasal approaches. Patients' charts and office notes were reviewed retrospectively. Formal olfactory testing was available in 5 patients, but most data were based on patients' subjective reports of olfaction. Olfactory preservation was defined by the subjective ability to detect fumes such as coffee, chocolate, roses, and orange juice regardless of the intensity of the sensation. Follow-up was based on phone calls to patients.RESULTS:Four patients were lost to follow-up and excluded. Therefore, follow-up was available in 24 patients after 25 procedures. On the basis of patients' subjective reports, olfaction was spared in 22 patients after 23 procedures (92%) and was confirmed objectively in the five patients formally tested. After surgery, only two patients were anosmic.CONCLUSION:Olfaction can be preserved in selected patients undergoing anterior craniofacial surgery. At least 1 cm of nasal mucosa should remain attached to the cribriform plate, which can be achieved by including the nasal bone in the osteotomy of the orbital bar. A medial orbital canthopexy is therefore necessary after these procedures.

The protozoan parasite Toxoplasma gondii relies on calcium-mediated exocytosis to secrete adhesins on to its surface where they can engage host cell receptors. Increases in intracellular calcium occur in response to Ins(1,4,5)P3 and caffeine, an agonist of ryanodine-responsive calcium-release channels. We examined lysates and microsomes of T. gondii and detected evidence of cADPR (cyclic ADP ribose) cyclase and hydrolase activities, the two enzymes that control the second messenger cADPR, which causes calcium release from RyR (ryanodine receptor). We also detected endogenous levels of cADPR in extracts of T. gondii. Furthermore, T. gondii microsomes that were loaded with 45Ca2+ released calcium when treated with cADPR, and the RyR antagonists 8-bromo-cADPR and Ruthenium Red blocked this response. Although T. gondii microsomes also responded to Ins(1,4,5)P3, the inhibition profiles of these calcium-release channels were mutually exclusive. The RyR antagonists 8-bromo-cADPR and dantrolene inhibited protein secretion and motility in live parasites. These results indicate that RyR calcium-release channels that respond to the second-messenger cADPR play an important role in regulating intracellular Ca2+, and hence host cell invasion, in protozoan parasites.

AbstractFrom 1951 through December, 1985, a total of 89 patients underwent total pancreatectomy for ductal adenocarcinoma. Of the 89 patients, 54 were male and 35 were female; their average age was 60.0 years. Histologic grading (Broders') demonstrated that 56% of the patients had a grade 2 tumor and 38%, a grade 3 tumor. None of the patients had grade 4 tumors. Peripancreatic lymph nodes were positive in 47% of the patients at the time of resection. Multicentricity was noted in 32.5% of patients. The operative mortality was 10.1%; however, for the patients who had surgery after January, 1980, the operative mortality was 6.2%. At the completion of the study, 78 patients had died and 11 were alive. The principal cause of death was recurrent malignancy. The median duration of survival, including the duration of survival in patients who had operative deaths, was 1.03 years. The influence of sex, tumor grade and size, multicentricity, and nodal status was evaluated multivariately with Cox's proportional hazard model.

Unauthorized self-administration of hypoglycemic agents produces a unique clinical situation. Because the symptoms and laboratory findings are consistent with a functioning adenoma of the pancreas, there is a significant hazard of unnecessary surgery. By appropriate laboratory tests, however, the alert physician may be able to justify suspicion that the disorder is self-induced. Accurate diagnosis may be further facilitated by recognizing certain similarities in these patients. Review of published reports and study of three cases newly presented have revealed these characteristics with enough consistency for proposal of a psychiatric syndrome. In hypoglycemia, factitial causation is suggested by the combination of female sex, single status, medical knowledge derived from experience as a diabetic or from vocational or family contacts, and features of the hysterical personality.

Atherosclerosis is enhanced in arterial segments exposed to disturbed flow. Perturbed shear stress increases the expression of oxidation-sensitive responsive genes (such as ELK-1 and p -JUN) in the endothelium. Evidence suggests that polyphenolic antioxidants contained in the juice derived from the pomegranate can contribute to the reduction of oxidative stress and atherogenesis. The aim of the present study was to evaluate the effects of intervention with pomegranate juice (PJ) on oxidation-sensitive genes and endothelial NO synthase (eNOS) expression induced by high shear stress in vitro and in vivo . Cultured human coronary artery endothelial cells (EC) exposed to high shear stress in vitro and hypercholesterolemic mice were used in this study. PJ concentrate reduced the activation of redox-sensitive genes (ELK-1 and p -JUN) and increased eNOS expression (which was decreased by perturbed shear stress) in cultured EC and in atherosclerosis-prone areas of hypercholesterolemic mice. Moreover, oral administration of PJ to hypercholesterolemic mice at various stages of disease reduced significantly the progression of atherosclerosis. This experimental study indicates that the proatherogenic effects induced by perturbed shear stress can be reversed by chronic administration of PJ. This approach may have implications for the prevention or treatment of atherosclerosis and its clinical manifestations.

Purpose Gemcitabine remains the standard therapy for metastatic pancreatic adenocarcinoma (ACA), but has limited activity. ISIS-2503 is an antisense compound directed against H-ras with preclinical activity against pancreatic ACA in tumor models. The combination of ISIS-2503 and gemcitabine has been evaluated in a prior phase I study. Methods Patients with metastatic or locally advanced pancreatic ACA not amenable to surgery or local radiation received gemcitabine 1,000 mg/m2 intravenously over 30 minutes on days 1 and 8 and ISIS-2503 6 mg/kg/d as a continuous intravenous infusion over 14 days of an every-3-weeks cycle. Responses were monitored by radiologic imaging every 6 weeks. Results Forty-eight eligible patients were enrolled, 43 with metastatic disease. Median follow-up was 12.6 months (range, 2.2 to 16.8 months) for living patients. A median of four cycles of treatment was given (range, 1 to 18 cycles). All patients were assessable for response and toxicity. The 6-month survival percentage was 57.5% (95% CI, 44.9% to 73.5%) and the median survival was 6.6 months. The response rate was 10.4% (one complete response, four partial responses). Clinically significant toxicity was limited except for one fatal pulmonary embolism. Conclusion This study shows a promising response rate to the combination of gemcitabine and ISIS-2503 in patients with pancreatic ACA. The observed 6-month survival rate in these patients met our protocol-defined criteria for success. This regimen is tolerable, but is of unclear benefit. Additional studies evaluating the role of gemcitabine and ISIS-2503 in the treatment of pancreatic ACA should be considered.

Background and Purpose— Following publication of concerns about the results of the National Institute of Neurological Disorders and Stroke (NINDS) intravenous tissue plasminogen activator (t-PA) in acute stroke treatment trial, NINDS commissioned an independent committee “to address whether there is concern that eligible stroke patients may not benefit from t-PA given according to the protocol used in the trials and, whether the subgroup imbalance (in baseline stroke severity) invalidates the entire trial.” Methods— The original NINDS trial data were reanalyzed to assess the t-PA treatment effect, the effect of the baseline imbalance in stroke severity between the treatment groups on the t-PA treatment effect, and whether subgroups of patients did not benefit from receiving t-PA. Results— A clinically important and statistically significant benefit of t-PA therapy was identified despite subgroup imbalances in baseline stroke severity and an increased incidence of symptomatic intracerebral hemorrhage in t-PA treated patients. The adjusted t-PA to placebo odds ratio (OR) of a favorable outcome was 2.1 (95% CI, 1.5 to 2.9). Although these exploratory analyses found no statistical evidence that the t-PA treatment effect differed among patient subgroups, the study was not powered to detect subgroup treatment differences. Conclusions— These findings support the use of t-PA to treat patients with acute ischemic stroke within 3 hours of onset under the NINDS t-PA trial protocol. Health professionals should work collaboratively to develop guidelines to ensure appropriate use of t-PA in acute ischemic stroke patients.

The pathogenic mechanisms by which physical exercise influences atherosclerotic lesion formation remain poorly understood. Because vigorous physical training increases oxidative stress, this study tested the hypothesis that graduated and moderate physical exercise together with metabolic intervention ( l -arginine and antioxidants) may contribute to increased vascular protection. Exercise training in mice was induced by graduated swimming. In hypercholesterolemic male mice on an atherogenic high-cholesterol diet, graduated and moderate exercise lowered plasma cholesterol and decreased atherosclerotic lesions compared with sedentary control mice. Antioxidants (1.0% vitamin E added to the chow and 0.05% vitamin C added to the drinking water) and l -arginine (6% in drinking water) supplementation to exercising hypercholesterolemic mice further and synergistically reduced atherosclerosis compared with untreated exercised mice. Arterial oxidation-specific epitopes and systemic oxidative stress were reduced by metabolic intervention. Graduated chronic exercise elicited an increase in production of nitric oxide through increased endothelial nitric oxide synthase expression and ameliorated scavenger activities. Thus, metabolic intervention with l -arginine and antioxidants together with graduated and moderate exercise training reduce atherosclerotic lesion formation.