Triple-blind clinical trial with placebo control to evaluate the efficacy of a heparin of low molecular weight (bemiparin) for treating slow-responding ulcers in diabetic foot in primary care

OBJECTIVES: To establish the degree of efficacy of bemiparin treatment over 3 months in the improvement of slow-responding ulcers in diabetic foot. Also, to evaluate the safety of bemiparin and quality of life and to compare the evolution of retinopathy and nephropathy against placebo. DESIGN: Stage III clinical trial to evaluate efficacy and safety in a new indication of a medicine already on the market, parallel in two branches, randomised, triple-blind, and controlled with placebo. SETTING: Health care centres in Mallorca, Spain. PARTICIPANTS: 42 patients per branch, over 18, with type-1 or 2 DM of over 3 years evolution, and one or more first or second-degree ulcers on the Wagner scale, distal to the knee, that did not heal in three months of health care. Randomised allocation in blocks of four.Interventions. The experimental drug was bemiparin (heparin of low molecular weight), injected subcutaneously at 3500 IU/day for the first 10 days and 2500 IU/day up to 90 days. As control, physiological serum was injected sub-cutaneously in a similar volume for masking. MAIN MEASUREMENTS: An "effect"was defined as a reduction of at least 50% in its surface area and/or a favourable evolution in status to a degree between the control at the start of treatment and at three months. Other measurements included proteinuria, retinography and quality of life (SF-36). Analysis of efficacy through principle of intention to treat.     

Smoking and the risk of gastric cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC)

Smoking has recently been recognised as causally associated with the development of gastric cancer (GC). However, evidence on the effect by sex, duration and intensity of smoking, anatomic subsite and cessation of smoking is limited. Our objective was to assess the relation between tobacco use and GC incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC). We studied data from 521,468 individuals recruited from 10 European countries taking part in the EPIC study. Participants completed lifestyle questionnaires that included questions on lifetime consumption of tobacco and diet in 1991-1998. Participants were followed until September 2002, and during that period 305 cases of stomach cancer were identified. After exclusions, 274 were eligible for the analysis, using the Cox proportional hazard model. After adjustment for educational level, consumption of fresh fruit, vegetables and preserved meat, alcohol intake and body mass index (BMI), there was a significant association between cigarette smoking and gastric cancer risk: the hazard ratio (HR) for ever smokers was 1.45 (95% confidence interval [CI] = 1.08-1.94). The HR of current cigarette smoking was 1.73 (95% CI = 1.06-2.83) in males and 1.87 (95% CI = 1.12-3.12) in females. Hazard ratios increased with intensity and duration of cigarette smoked. A significant decrease of risk was observed after 10 years of quitting smoking. A preliminary analysis of 121 cases with identified anatomic site showed that current cigarette smokers had a higher HR of GC in the cardia (HR = 4.10) than in the distal part of the stomach (HR = 1.94). In this cohort, 17.6 % (95% CI = 10.5-29.5 %) of GC cases may be attributable to smoking. Findings from this large study support the causal relation between smoking and gastric cancer in this European population. Stomach cancer should be added to the burden of diseases caused by smoking.     

Amygdalar atrophy in panic disorder patients detected by volumetric magnetic resonance imaging

It has been suggested that the pathophysiology of panic disorder (PD) may involve abnormalities in several brain structures, including the amygdala. To date, however, no study has used quantitative structural neuroimaging techniques to examine amygdalar anatomy in this disorder. Volumetric magnetic resonance imaging (MRI) studies of the amygdalas, hippocampi, and temporal lobes were conducted in 12 drug-free, symptomatic PD patients (six females and six males), and 12 case-matched healthy comparison subjects. Volumetric MRI data were normalized for brain size. PD patients were found to have smaller left-sided and right-sided amygdalar volumes than controls. No differences were found in either hippocampi or temporal lobes. These findings provide new evidence of changes in amygdalar structure in PD and warrant further anatomical and MRI brain studies of patients with this disorder.     

Granulocyte colony-stimulating factor in the treatment of high-risk febrile neutropenia: a multicenter randomized trial

BACKGROUND: Granulocyte colony-stimulating factors (G-CSFs) have been shown to help prevent febrile neutropenia in certain subgroups of cancer patients undergoing chemotherapy, but their role in treating febrile neutropenia is controversial. The purpose of our study was to evaluate-in a prospective multicenter randomized clinical trial-the efficacy of adding G-CSF to broad-spectrum antibiotic treatment of patients with solid tumors and high-risk febrile neutropenia. METHODS: A total of 210 patients with solid tumors treated with conventional-dose chemotherapy who presented with fever and grade IV neutropenia were considered to be eligible for the trial. They met at least one of the following high-risk criteria: profound neutropenia (absolute neutrophil count <100/mm(3)), short latency from previous chemotherapy cycle (<10 days), sepsis or clinically documented infection at presentation, severe comorbidity, performance status of 3-4 (Eastern Cooperative Oncology Group scale), or prior inpatient status. Eligible patients were randomly assigned to receive the antibiotics ceftazidime and amikacin, with or without G-CSF (5 microg/kg per day). The primary study end point was the duration of hospitalization. All P values were two-sided. RESULTS: Patients randomly assigned to receive G-CSF had a significantly shorter duration of grade IV neutropenia (median, 2 days versus 3 days; P = 0.0004), antibiotic therapy (median, 5 days versus 6 days; P = 0.013), and hospital stay (median, 5 days versus 7 days; P = 0.015) than patients in the control arm. The incidence of serious medical complications not present at the initial clinical evaluation was 10% in the G-CSF group and 17% in the control group (P = 0.12), including five deaths in each study arm. The median cost of hospital stay and the median overall cost per patient admission were reduced by 17% (P = 0.01) and by 11% (P = 0.07), respectively, in the G-CSF arm compared with the control arm. CONCLUSIONS: Adding G-CSF to antibiotic therapy shortens the duration of neutropenia, reduces the duration of antibiotic therapy and hospitalization, and decreases hospital costs in patients with high-risk febrile neutropenia.     

Surgical Debulking and Intraperitoneal Chemotherapy for Established Peritoneal Metastases From Colon and Appendix Cancer

Background: Aggressive treatment of peritoneal metastases from colon cancer by surgical cytoreduction and infusional intraperitoneal (IP) chemotherapy may benefit selected patients. We reviewed our institutional experience to assess patient selection, complications, and outcome.Methods: Patients having surgical debulking and IP 5-fluoro-2-deoxyuridine (FUDR) plus leucovorin (LV) for peritoneal metastases from 1987 to 1999 were evaluated retrospectively.Results: There were 64 patients with a mean age of 50 years. Primary tumor sites were 47 in the colon and 17 in the appendix. Peritoneal metastases were synchronous in 48 patients and metachronous in 16 patients. Patients received IP FUDR (1000 mg/m² daily for 3 days) and IP leucovorin (240 mg/m²) with a median cycle number of 4 (range, 1–28). The median number of complications was 1 (range, 0–5), with no treatment related mortality. Only six patients (9%) required termination of IP chemotherapy because of complications. The median follow-up was 17 months (range, 0–132 months). The median survival was 34 months (range, 2–132); 5-year survival was 28%. Lymph node status, tumor grade, and interval to peritoneal metastasis were not statistically significant prognostic factors for survival. Complete tumor resection was significant on multivariate analysis (P = .04), with a 5-year survival of 54% for complete (n = 19) and 16% for incomplete (n = 45) resection.Conclusions: Surgical debulking and IP FUDR for peritoneal metastases from colon cancer can be accomplished safely and has yielded an overall 5-year survival of 28%. Complete resection is associated with improved survival (54% at 5 years) and is the most important prognostic indicator.Presented in part at the 54th Annual Cancer Symposium of the Society of Surgical Oncology, Washington, DC, March 15–18, 2001.     

Dissociating memory processes involved in direct and indirect tests with ERPs to unfamiliar faces

Event-related potentials (ERPs) were recorded during indirect and direct memory tests for unfamiliar faces. In both tests, ERPs displayed the usual positive shift known as the ERP repetition effect. In the indirect test, this effect includes parietal effect (the usual N400 effect) and a right fronto-central effect. Both effects are also present in the direct test. Two additional effects are present only in the direct test. These effects are an early fronto-polar effect and a late posterior effect (the usual P600 effect). These findings are taken as support for the distinction between 'associative' processes elicited in both the direct and indirect tests, and 'episodic' processes elicited only in the direct test. This task dissociation could well provide a scalp correlate of the distinction between the neocortical and cortico-limbic systems that have been shown to contribute respectively to associative and episodic processing. In addition, it is proposed that the dissociation between the two frontal effects could be accounted for by a distinction between the processing of intrinsic vs. extrinsic contextual attributes as a function of the task requirements.     

How I Manage the Adult Potential Organ Donor: Donation After Neurological Death (Part 1)

The need for organ donation has become a growing concern over that last decade as the gap between organ donors and those awaiting transplant widens. According to UNOS, as of 8/2009, there were 102,962 patients on the transplant waiting list and only 6,004 donors in 2009 (UNOS.org. Accessed 4/8/2009). In 2008, an estimated 17 patients died each day awaiting transplant (OPTN.org). Though currently most organ donations come after brain death (DND or donation after neurological death), tissue donation (cornea, skin, bone, and musculoskeletal tissue), and donation after cardiac death (DCD) and are also possible. The term “extended criteria donor” refers to potential donors over 60 years of age or age 50–59 years plus 2 of the 3 following criteria: stroke as the cause of death, creatnine > 1.5 meq/dl, or a history of hypertension. Historically, extended criteria donors have had a lower organ yield per donor. In order to preserve the choice of organ donation for the family, intensive management of the potential organ donor is necessary. Since each potential donor could save seven lives or more, nihilism in the care of such patients can have far reaching ramifications. This article describes intensive care management practices that can optimize organ donation.     

Composite reconstruction of hypopharynx and esophagus

Extended surgical resection of the whole esophagus and associated hypopharynx may require composite reconstructions using a combination of pediculated and free tissue units. Twelve patients were assigned to composite reconstructions of the hypopharynx and esophagus for either metachronous carcinoma of the esophagus and head and neck (group I, n = 4), cervical anastomotic recurrence of esophageal carcinoma (group II, n = 3), or secondary reconstruction after the failure of a previous reconstruction of hypopharynx or esophagus (group III, n = 5). Pediculated tissues were the stomach (n = 10), colon (n = 1), or jejunum (n = 1). A free jejunal graft was constantly interposed between the pharynx and the mobilized organ. There were no hospital deaths. Swallowing function was restored in all patients except one who had cervical leakage as a result of partial necrosis of the free jejunal graft. Composite reconstruction permitted, even in groups I and II in which prognosis was extremely poor, prolonged survival and oral feeding, which proved beneficial in terms of the patients' quality of life.