A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis

We have examined the prothrombin gene as a candidate gene for venous thrombosis in selected patients with a documented familial history of venous thrombophilia. All the exons and the 5'- and 3'-UT region of the prothrombin gene were analyzed by polymerase chain reaction and direct sequencing in 28 probands. Except for known polymorphic sites, no deviations were found in the coding regions and the 5'-UT region. Only one nucleotide change (a G to A transition) at position 20210 was identified in the sequence of the 3'-UT region. Eighteen percent of the patients had the 20210 AG genotype, as compared with 1% of a group of healthy controls (100 subjects). In a population-based case-control study, the 20210 A allele was identified as a common allele (allele frequency, 1.2%; 95% confidence interval, 0.5% to 1.8%), which increased the risk of venous thrombosis almost threefold {odds ratio, 2.8; 95% confidence interval, 1.4 to 5.6}. The risk of thrombosis increased for all ages and both sexes. An association was found between the presence of the 20210 A allele and elevated prothrombin levels. Most individuals (87%) with the 20210 A allele are in the highest quartile of plasma prothrombin levels (> 1.15 U/mL). Elevated prothrombin itself also was found to be a risk factor for venous thrombosis.     

Graded comprehensive cardiopulmonary exercise testing in the evaluation of dyspnea unexplained by routine evaluation

The evaluation of dyspnea is problematic when a cause is inapparent after initial diagnostic studies. We examined the results and role of cardiopulmonary exercise testing (CPET) in 50 patients with a mean 23 months of dyspnea and normal FEV1 and FVC. The CPET studies were interpreted by a panel and a consensus reached. Subsequent tests ordered by the primary physician were reviewed, and a final diagnosis was agreed on by the panel. Seven of 50 patients had cardiac limitation, 17 of 50 had pulmonary limitation, 14 of 50 had obesity and/or deconditioning, 1 of 50 had gastroesophageal reflux, and 16 of 50 had either psychogenic dyspnea or no identifiable disease. Five patients had more than one clinical diagnosis accounting for 55 diagnoses in the 50 patients. Those with a normal CPET had a higher VO2max and O2 pulse than those with cardiac disease, deconditioning, or hyperactive airways disease (HAD) (p < 0.05). Electrocardiographic changes identified cardiac disease while studies demonstrating ventilatory limitation identified a pulmonary process. In 24, deconditioning could not be distinguished from cardiac limitation. Of these, 14 responded to exercise training and/or weight loss, whereas 3 had cardiac disease, 7 had HAD, and 4 had psychogenic dyspnea (4 had more than one clinical diagnosis). In the 13 patients with normal CPET results, one had gastroesophageal reflux, two had HAD, four had psychogenic dyspnea, and six had no identifiable disease. We conclude that a diagnosis can be made in most patients with chronic dyspnea; however, further studies including bronchoprovocation are often required. Cardiopulmonary exercise testing is useful in identifying a cardiac or pulmonary process, but it is insensitive in distinguishing cardiac disease from deconditioning.     

Oxidant damage to erythrocyte membrane in glucose-6-phosphate dehydrogenase deficiency: correlation with in vivo reduced glutathione concentration and membrane protein oxidation

Chronic nonspherocytic hemolytic anemia has been observed in a recently described glucose-6-phosphate dehydrogenase (G6PD) variant, G6PDWayne. The mechanical properties of these erythrocytes and other G6PD variants were examined. The deformability of G6PD-deficient erythrocytes was normal, as determined by osmotic scan ektacytometry, and was not significantly affected by hemolytic crisis. In the common varieties of G6PD deficiency, the mechanical stability of the red blood cell (RBC) membrane was greater than normal, but G6PDWayne membranes were abnormally susceptible to shear-induced fragmentation. There was no evidence for a concurrent genetic defect in spectrin, because self-association constants and tryptic digests were normal. The fragility of G6PDWayne membranes appeared to be a consequence of oxidative damage to membrane thiol groups associated with a low glutathione (GSH) level in these RBCs. Associations among GSH level, thiol oxidation, and membrane instability were also found when a larger group of G6PD-deficient RBCs were examined. In normal erythrocytes, 1-chloro-2,4-dinitrobenzene was used to reduce GSH levels by 50%. Membrane thiol oxidation and membrane fragility both increased when these cells were kept at 4 degrees C for 3 to 5 days. Our findings suggest that chronic depletion of GSH leads to the destabilization of membrane skeleton through oxidation of membrane protein thiols.     

On Synchronous Robotic Networks—Part II: Time Complexity of Rendezvous and Deployment Algorithms

This paper analyzes a number of basic coordination algorithms running on synchronous robotic networks. We provide upper and lower bounds on the time complexity of the move-toward-average and circumcenter laws, both achieving rendezvous, and of the centroid law, achieving deployment over a region of interest. The results are derived via novel analysis methods, including a set of results on the convergence rates of linear dynamical systems defined by tridiagonal Toeplitz and circulant matrices.     

Drying of persimmons (Diospyros kaki L.) and the following changes in the studied bioactive compounds and the total radical scavenging activities

Fresh persimmons were subjected to two different processes: sun-drying during 1 month and dehydration at 60 °C during 12 h. To assess the effect of this process on nutritional and health-related properties of persimmons dietary fibers, minerals, trace elements, polyphenols and the total radical scavenging activities (TRSAs) were determined before and after processing. It was found that the contents of dietary fibers, minerals and trace elements in fresh and dried persimmons fruits were comparable. Total polyphenols in fresh persimmons was higher than in dried fruits (1.3 vs. 0.9 and 0.8 mg/100 g FW, respectively) and percentage of inhibition was higher than in dried fruits (70% vs. 59% and 55% and 58% vs. 53% and 46% for 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) [ABTS] radicals, respectively (P>0.05 in all cases). In conclusion: (1) the differences in the contents of dietary fibers, minerals and trace elements in fresh and dried persimmons are not significant; (2) the contents of polyphenols and the level of the TRSA are higher in fresh persimmons than in dried fruits; however, both variables are also high in dried persimmons; (3) when fresh fruits are not available, proper dried persimmons could be used as a valuable substitute.     

Correlation between esophageal motility and 24-hour pH recording in patients with gastroesophageal reflux

The relationship between manometric and pH-metric data was studied in a group of 50 patients with symptoms of gastroesophageal reflux. Using a multiple regression analysis, we found that the total percentage of reflux was significantly correlated to the infradiaphragmatic length and resting pressure of the lower esophageal sphincter and also to the mean amplitude of the contractile waves of the distal esophagus, thus revealing the important role of these factors in the antireflux mechanism. When the patients were divided into groups according to their manometric characteristics and the values of the various pH-metric parameters between these groups compared using a one-way analysis of variance, we found that the amplitude of the contractile waves and the percentage of deglutitions without response were related not only to the total percentage of reflux but also to the number of reflux episodes of greater than 5 min duration and to the duration of the longest episode. This shows that prolonged exposure of the esophageal mucosa to the refluxed material may be due, in part, to an alteration in the capacity for esophageal clearing.     

Risk factors for osteoporosis in men

Three months after the launch of the MMR programme in the United Kingdom and the Republic of Ireland, a postal questionnaire was sent to all GP scheme trainees in both Northern Ireland and the Republic of Ireland. The response rate was 81%. All trainees were enthusiastic about promoting MMR immunisation; with 27% favouring compulsory immunisation. 9% had never seen a patient with measles. This did not alter their attitude towards the beneficial effects of MMR immunisation. Of pre-practice year trainees 26% felt their level of knowledge of immunisation was inadequate, 59% claimed to have received no education on immunisation during their vocational training to date. This may reflects deficiencies in their medical curriculum to-date. 95% of third-year trainees indicated that their practice experience had been the source of at least some of their education on immunisation. Only 46% of trainees in the Republic of Ireland were aware of their Department of Health's aims in launching the MMR immunisation campaign.     

In vivo surface analysis of titanium and stainless steel miniplates and screws

OBJECTIVE: To determine the results peranal excision for rectal carcinoma. DESIGN: Retrospective case series. SETTING: A university-affiliated hospital. PATIENTS: Of 178 patients who presented for curative resection of rectal carcinoma between 1975 and 1993, 19 (10.7%) were deemed suitable for local excision. There were 10 men and 9 women with a mean age of 71.2 years. The follow-up ranged from 13 to 184 months. INTERVENTION: Peranal excision. MAIN OUTCOME MEASURES: Histologic differentiation, gross morphology, depth of invasion and size of the carcinoma, adequacy of margins of excision, complications of operation, rates of recurrence, results of salvage therapy and 5-year survival. RESULTS: There were no intraoperative complications. Postoperative complications included urinary retention (one patient) and bleeding (one patient). There were five local recurrences (26%). Salvage operations were performed in three (60%) patients and were successful in two of them. The 5-year cancer-specific survival rate was 82%. The recurrence rate was higher in patients with inadequate margins of excision and ulcerative lesions. Neither size nor grade of the carcinoma correlated with recurrence. CONCLUSIONS: Local excision of rectal carcinoma can be performed successfully in selected patients. Diligent follow-up is required, because up to 60% of local recurrences can be treated successfully.     

Zoonotic Brugian lymphadenitis. An unusual case with florid monocytoid B-cell proliferation

Human infection with a zoonotic Brugia species in the United States is uncommon. Positive identification of the filarial nematode is required for histopathologic diagnosis. Many cases may go unrecognized because of the nonspecific clinical manifestations and the nondiagnostic histologic changes occurring in involved lymph nodes. A case of zoonotic Brugia lymphadenitis is described in a patient from Rhode Island, in which a small nongravid female worm was identified in a lymph node biopsy specimen. The lymph node also showed a spectrum of reaction changes including the presence of florid monocytoid B-cell proliferation, which has not been described in association with zoonotic Brugian filariasis.