Factor V Leiden,hormone replacement therapy,and risk of venous thromboembolic events in women with coronary disease

Oral contraceptive use in women with factor V Leiden is associated with increased rates of venous thromboembolic events (VTEs). However, the effects of hormone replacement therapy (HRT) in postmenopausal women with factor V Leiden are not known. A nested case-control study was conducted among women with established coronary disease enrolled in 2 randomized clinical trials of HRT, the Heart and Estrogen/Progestin Replacement Study (HERS) and the Estrogen Replacement and Atherosclerosis (ERA) trial. The Leiden mutation was present in 8 (16.7%) of 48 cases with VTE compared with only 7 (6.3%) of 112 controls (odds ratio [OR](Leiden) 3.3, 95% CI 1.1 to 9.8; P=0.03). In women without the factor V Leiden mutation, risk associated with HRT use was significantly increased (OR(HRT) 3.7, 95% CI 1.4 to 9.4; P<0.01). On the other hand, in women with the factor V Leiden mutation, the estimated risk associated with HRT was increased nearly 6-fold, although the CIs were wide and included unity (OR(HRT) 5.7, 95% CI 0.6 to 53.9; P=0.13). The OR for women with the Leiden mutation who were also assigned to HRT compared with wild-type women assigned to placebo was 14.1 (95% CI 2.7 to 72.4, P=0.0015). In women with the factor V Leiden mutation who were treated with HRT, the estimated absolute incidence of VTE was 15.4 of 1000 per year compared with 2.0 of 1000 per year in women without the mutation who were taking a placebo (P=0.0015). On the basis of these data, in women with coronary disease, the estimated number needed to screen for factor V Leiden to avoid an HRT-associated VTE during 5 years of treatment is 376. If factor V Leiden genotyping becomes less expensive, it could be cost effective to screen for the presence of the mutation before instituting HRT in women with coronary disease.     

Preparation of vaccines against H5N1 influenza

In response to the pandemic warning provided by the highly pathogenic H5N1 influenza virus infections in Hong Kong, there were world-wide attempts to develop vaccines. Three strategies were followed and although each was associated with some success, there were also some problems. Pre-clinical vaccine efficacy results are presented from one such strategy, that of using an apathogenic H5N3 avian strain for vaccine production.     

The time-course of metastases from breast cancer after mastectomy and breast-conserving surgery with and without isolated local-regional recurrence

We have examined time intervals between events in 390 metastatic breast cancer (MBC) patients whose distant failure developed within 10 years from initial surgery of Stage I/II disease. All of the patients underwent axillary dissection and mastectomy (n=295) or breast-conserving surgery (BCS, n=95), between 1983 and 1987. Distinctions have been made between distant failure with (n=79) and without (n=311) isolated local-regional recurrence (LRR). The median survival time after first relapse was significantly longer with intrabreast (30 months) and chest wall (24 months) than with distant relapse (15 months), but with axillary (17 months) or with supraclavicular (17 months) relapse survival was similar. The delay between LRR and distant metastasis was shorter with axillary (7 months) and supraclavicular (9 months) than with breast (20 months) and chest wall (12 months) recurrences. The median postmetastatic survival time by site of first relapse was significantly shorter with supraclavicular (6 months) and axillary (9 months) than with distant site relapse (15 months) but with intrabreast (12 months) or with chest wall (11 months) recurrence survival was similar. In MBC, regional recurrences are associated with a shorter interval between events than with local recurrences. The shortened intervals for patients with regional recurrence suggest that metastases existed at the time of initial surgery. The question of whether prevention of local or regional recurrence or both improves cause-specific survival after mastectomy or BCS needs to be answered in randomized studies.     

Percutaneous absorption of explosives and related compounds: an empirical model of bioavailability of organic nitro compounds from soil

The percutaneous absorption potentials of (14)C-labeled 2,4,6-trinitrotoluene (TNT), trinitrobenzene, 2,4-dinitrotoluene (2,4-DNT), 2,6-dinitrotoluene (2,6-DNT), 2-amino-4,6-dinitrotoluene, 4-amino-2,6-dinitrotoluene, 2,4-diamino-6-nitrotoluene, 2,6-diamino-4-nitrotoluene, N-methyl-N,2,4,6-tetranitrobenzamine, hexahydro-1,3,5-trinitro-1,3,5-triazine, octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine, and 2,2-thiobis(ethanol) were determined from two soil types, Yolo having 1.9% carbon and Tinker having 9.5% carbon. TNT skin absorption from another low-carbon soil (Umatilla) was also determined. Approximately 10 microg/cm(2) of radiolabeled compound was applied in 5 microl of acetone or 10 mg/cm(2) of soil to excised pigskin mounted in skin penetration-evaporation chambers. Absorption from acetone served as a control. Radiolabel recovered from the dermis and tissue culture media (receptor fluid) was summed to determine the percentage of absorption from the soils. For each compound, percentage absorptions of radiolabel were highest from acetone solution and lowest from Tinker soil, with the results from Yolo soil being intermediate. Skin absorptions of TNT from Yolo and Umatilla soils were similar. For TNT in all vehicles, the penetration rate of radiolabel into the receptor fluid was highest during the 1- to 2-h interval after dosing. HPLC analysis of TNT radiolabel in receptor fluid at maximum flux indicated extensive conversion to monoamino derivatives and other metabolites. For 2,4-DNT and 2,6-DNT applications in Yolo soil, percentage absorptions approached those obtained from acetone applications. After 2,4-DNT and 2,6-DNT applications (acetone and soils), HPLC analysis of radiolabel in receptor fluid during the period of maximum flux revealed no significant metabolites. Skin absorption of the nitro compounds from soils was found to correlate with the compound's water solubility and vapor pressure. These findings formed the basis of an empirical model to predict skin bioavailability.     

Development of a new method to characterize (SMBV) antigen formulations using surface plasmon resonance technology

Supra Molecular Biovectors (SMBV) are nanoparticles composed by a polysaccharidic core surrounded by a lipid bilayer. They are designed for drug delivery and vaccine and can be administrated by nasal route. The association rate and the stability of association between active principle (AP) or antigens (Ag) with SMBV can be evaluated using the plasmon resonance technology using a BIAcore X system and a HPA hydrophobic sensor chip. AP, Ag and/or adjuvant molecule solutions are injected over SMBV saturated HPA sensor chip surface. Using a very small quantity of material, this technique allows us to quickly have an overview of complex formulations using SMBV. It is also the fastest screening technique to select the best SMBV for each Ag and the best formulation process.     

Outcome of elderly patients with appendicitis: effect of computed tomography and laparoscopy

HYPOTHESIS: Elderly patients who have appendicitis have a greater morbidity and mortality rate when compared with younger patients. We hypothesized that recent changes in the diagnosis and management of appendicitis in elderly patients might affect the outcome. DESIGN: Retrospective review. SETTING: Large metropolitan teaching hospital. PATIENTS: All patients aged 70 years and older who underwent appendectomy for appendicitis between January 1, 1991, and December 31, 2000, were divided into groups 1 (those treated from January 1, 1991, through December 31, 1995) and 2 (those treated from January 1, 1996, through December 31, 2000). MAIN OUTCOME MEASURES: Age, sex, preoperative evaluation, operative duration and findings, postoperative course, duration of hospital stay, and mortality rate. Continuous and categorical variables were analyzed using t and chi(2) tests, respectively. RESULTS: Ninety-five patients met inclusionary criteria. The mean age (78 years), sex, preoperative suggestion of appendicitis (group 1, 39 [83%] of 47 patients; group 2, 45 [94%] of 48 patients), and duration of the preoperative hospitalization over 24 hours (group 1, 11 patients [23%]; group 2, 9 patients [19%]) were similar in both groups. There was an increasing use of diagnostic computed tomography (group 1, 13 patients [28%]; group 2, 32 patients [67%]; P<.001) and laparoscopy (group 1, 14 patients [30%]; group 2, 23 patients [48%]; P =.02) between the 2 study periods associated with no significant difference in the duration of hospitalization, frequency of appendiceal perforation or abscess, occurrence of complications, or mortality. The length of operating time increased in the second period (ie, January 1, 1996, through December 31, 2000). CONCLUSIONS: Appendicitis in elderly patients continues to be a challenging surgical problem. While computed tomography may represent a useful diagnostic tool and laparoscopic appendectomy may be appropriate therapy for selected patients, neither has affected outcome when measured for morbidity and mortality rates. Overall results might improve with earlier consideration of the diagnosis in elderly patients with abdominal pain, followed by prompt surgical consultation and operation.     

Heat-killed Mycobacterium bovis-Bacillus Calmette-Guerin prevents experimental respiratory tract eosinophilia in mice

INTRODUCTION: The increased prevalence of asthma has become a major public health issue worldwide. It has been proposed that this increase is due to the steady decline of infectious diseases such as tuberculosis. AIM OF THE STUDY: Supporting this view was, the suppressive effect of live Bacillus Calmette-Guerin (BCG) infection on allergen (ovalbumin) induced airway eosinophilia was published previously. METHODS: Next the authors compared the effects of live, heat killed BCG and purified protein derivative of Mycobacterium tuberculosis (PPD) on a murine model of ovalbumin induced airway eosinophilia. RESULTS: The results showed that both live and heat killed BCG, but not PPD strongly suppressed airway eosinophilia. This inhibition was correlated with the reduced number of Th2 cells in the lung. CONCLUSION: Their data support the hypothesis that the application of bacterial antigens may be a safe vaccination method against asthma in the future.     

Energy intake during a typical Himalayan trek

People taking part in commercial treks are exposed to high altitude (HA) while eating ad libitum, a situation that has been related to under eating and body weight loss. We investigated this phenomenon in westerners taking part in a typical Himalayan trek. Body weight, energy intake (EI), macronutrient composition of the diet, and acute mountain sickness symptoms (AMS) were measured in seven healthy individuals (aged 45 +/- 12 yr and BMI 24.6 +/- 4.4 kg/m(2)) during a 19-day trek to Makalu Base Camp. Comparisons were made between three periods of the trek: a 5-day climb below 2500 m (low altitude 1: LA1), an 8-day period between 3500 m and 5200 m (high altitude: HA), and a 4-day descent below 2500 m (low altitude 2: LA2). Body weight was significantly reduced at the end of the trek (p < 0.01). A decrease in total EI was observed at HA (p < 0.05). This was followed by an increase in EI upon return to LA2 (p < 0.001). Neither EI nor macronutrient composition of the diet was associated with the presence of AMS. In conclusion, a decrease in EI was observed in HA, which does not seem to be macronutrient specific.     

Positive peritoneal cytology in early-stage endometrial cancer does not influence prognosis

The aim of this study was to assess the prognostic importance of positive peritoneal cytology in early-stage endometrial cancer. All 278 stage I and 53 stage IIIA (without cervical involvement) endometrial cancer patients operated between 1980 and 1996, recorded at the Geneva Cancer registry, were included. Stage IIIA cancers were recategorised into 'cytological' stage IIIA (positive peritoneal cytology alone, n=33) and 'histological' stage IIIA (serosal or adnexal infiltration, n=20). Survival rates were analysed by Kaplan-Meier method and compared using log-rank test. The prognostic importance of cytology was analysed using a Cox model, accounting for other prognostic factors. The 5-year disease-specific survival of cytological stage IIIA cancer was similar to stage I (91 vs 92%) and better than histological stage IIIA cancer (50%, P<0.001). After adjustment for age, myometrial invasion, differentiation and radiotherapy, cytological stage IIIA patients were still at similar risk to die from endometrial cancer compared to stage I patients (hazard ratio (HR) 0.7, 95% confidence interval (CI): 0.18-2.3), while histological stage IIIA patients were at a four-fold increased risk to die from their disease (HR 4.2, 95% CI: 1.7-10.3). This population-based study shows that positive peritoneal cytology in itself has no impact on survival of patients with localised endometrial cancer. Based on the present and previous studies, FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) might consider reviewing its classification system.