Gemcitabine and ISIS-2503 for patients with locally advanced or metastatic pancreatic adenocarcinoma: a North Central Cancer Treatment Group phase II trial.

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/m(2) 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.     

Delayed presentation of congenital diaphragmatic hernia in association with group B streptococcus infection in a preterm Omani neonate

We present an interesting case of a preterm Omani newborn that had delayed onset of congenital diaphragmatic hernia in association with group B streptococcus infection. The association and the pathogenesis are supported by literature review. The message to follow is that any neonate with prolonged course of streptococcal pneumonia, with unusual course, should be investigated for presence of congenital diaphragmatic hernia.     

Angiogenesis during tumor progression in the oral cavity is related to reduced apoptosis and high tumor cell proliferation

Angiogenesis, the growth of new blood vessels, is believed to aid tumor progression and metastasis. Tumor progression is also influenced by the extent of proliferation and apoptosis. This study, therefore, analyzed in lesions of the oral cavity, the significance of angiogenesis in relation to apoptosis, expression of apoptosis regulatory p53, bax and bcl-2 proteins as well as tissue proliferation defined by cyclin D1 expression. Results from this study suggest that angiogenesis increases as histological abnormality increases in the oral mucosa. The expression of apoptosis regulatory proteins also appears to be altered in a histologically dependent manner. The correlation seen between CD34 expression, cyclin D1 and TUNEL reactive cells suggests that increased angiogenesis, decreased apoptosis and deregulated proliferation occur simultaneously during tumor progression in the oral mucosa. Presence of a mutant p53, increased bcl-2 expression and altered bax expression are also involved in this complex process.     

Effects of smoking on health care costs

Smoking is the leading preventable cause of death in the United States. The US Centers for Disease Control and Prevention (CDC) estimate that smoking kills approximately 419,000 people in the United States each year. Cigarette smoking is the nation's leading cause of premature mortality, and is responsible for one-third of all deaths among working-age Americans. Smoking cigarettes is both psychologically and physiologically addictive. Smoking is an important risk factor for cardiovascular diseases, especially coronary artery disease, stroke, carcinoma of the lung, chronic bronchitis, chronic obstructive pulmonary disease, and emphysema. It also increases the risk for peripheral vascular disease and is associated with cancers of the larynx, oral cavity, esophagus, pancreas, and urinary bladder. Smoking by pregnant women can cause adverse health effects on their babies, like low birth weight and preterm delivery; increases the risk of miscarriage; and has also been found to be an important cause of sudden infant death syndrome. Careless smoking also can cause severe burn injuries and death. Many of these adverse effects of smoking occur in "second-hand" smokers.     

Gunshot injuries of the popliteal artery

BACKGROUND: Guidelines for the management of popliteal artery trauma emanate mainly from military experience. This study was undertaken to describe the management of popliteal injuries in a civilian vascular surgical unit with a large trauma workload. METHODS: A retrospective review of records of patients treated between 1983 and 1997 was undertaken. RESULTS: Some 117 popliteal artery gunshot injuries were treated (83 low velocity, 16 high velocity, 18 shotgun). Associated fractures occurred in 44 patients and 40 had popliteal vein injuries. Treatment of the arterial injury included vein graft interposition in 71, primary reanastomosis in 19, prosthetic graft interposition in four, lateral suture in one, vein patch in one and ligation in one patient; 84 fasciotomies were performed. No perioperative deaths occurred. There were 20 primary and 14 secondary amputations. Factors associated with amputation were high-velocity injuries, delay in revascularization in excess of 7 h, arterial transection, associated fracture, and compartment syndrome or muscle infarction. CONCLUSION: Civilian popliteal gunshot injuries are attended by a high amputation rate. Prompt resuscitation and revascularization appear to be the only correctable factors that may improve limb salvage rates.     

Randomized phase II trial of three schedules of pemetrexed and gemcitabine as front-line therapy for advanced non-small-cell lung cancer.

PURPOSE: A randomized three-arm phase II study was undertaken to evaluate the optimum administration schedule of pemetrexed and gemcitabine in chemotherapy-na?ve patients with non-small-cell lung cancer. PATIENTS AND METHODS: Patients were randomly assigned to three schedules of pemetrexed 500 mg/m2 plus gemcitabine 1,250 mg/m2, separated by a 90-minute interval, on a 21-day cycle as follows: schedule A, pemetrexed followed by gemcitabine on day 1 and gemcitabine on day 8; schedule B, gemcitabine followed by pemetrexed on day 1 and gemcitabine on day 8; and schedule C, gemcitabine on day 1 and pemetrexed followed by gemcitabine on day 8. RESULTS: One hundred fifty-two eligible patients (schedule A, n = 59; schedule B, n = 31, and schedule C, n = 62) received a median of five (schedule A), two (schedule B), and four (schedule C) treatment cycles. Overall, 66% of patients experienced grade 3 or 4 neutropenia. Common grade 3 and 4 nonhematologic toxicities were dyspnea (11%), fatigue (16%), and transaminase elevation (9%). Schedule A seemed less toxic compared with schedule C (grade 3 or 4 events: 86% v 94%, respectively; P = .19; grade 4 events: 39% v 48%, respectively; P = .30). Schedule B was closed at interim analysis for inferior efficacy. Schedule A, with a confirmed response rate of 31% (95% CI, 20% to 45%), met the protocol-defined efficacy criteria, whereas schedule C, with a confirmed response rate of 16.1% (95% CI, 11% to 34%), did not. Median survival time and time to progression were 11.4 and 4.4 months, respectively, with no observable difference between the arms. CONCLUSION: Pemetrexed and gemcitabine administered as outlined for schedule A met the protocol-defined efficacy criteria, was less toxic compared with the other treatment schedules, and should be further evaluated.     

Polarizing the T helper 17 response in Citrobacter rodentium infection via expression of resistin-like molecule α

Citrobacter rodentium infection is a murine model of pathogenic Escherichia coli infection that allows investigation of the cellular and molecular mechanisms involved in host-protective immunity and bacterial-induced intestinal inflammation. We recently demonstrated that following C. rodentium infection, the absence of Resistin-Like Molecule (RELM) α resulted in attenuated Th17 cell responses and reduced intestinal inflammation with minimal effects on bacterial clearance. In this addendum, we investigated the cytokine modulatory effects of RELMα and RELMα expression in the intestinal mucosa following C. rodentium infection. We show that in addition to promoting Th17 cytokine responses, RELMα inhibits Th2 cytokine expression and Th2-cytokine effector macrophage responses in the C. rodentium-infected colons. Second, utilizing reporter C. rodentium, we examined RELMα expression and macrophage recruitment at the host pathogen interface. We observed infection-induced macrophage infiltration and RELMα expression by intestinal epithelial cells. The influence of infection-induced RELMα on macrophage recruitment in the intestine is discussed.