The association between seated immobility and local lower-limb venous coagulability in healthy adult volunteers: a simulation of prolonged travel immobility.

This is the first study to examine the hypothesis that prolonged sitting is associated with procoagulant changes in the local lower-limb venous system. A comparison was made with upper-limb venous changes. Changes in markers of thrombin generation, fibrinolysis, endothelial perturbation and haemoconcentration were analysed as 10 healthy adult male participants sat for 8 h. The change in foot volume was estimated. Subjective venous thromboembolism assessment was undertaken hourly, along with 2-week and 4-week safety follow-up for clinical events.Expected increases in median prothrombin fragments 1 and 2, thrombin-antithrombin complex and D-dimer were not observed in either limb. An increase greater than 45% in the median tissue plasminogen activator and plasminogen activator-1 molar ratio (t-PA/PAI-1), and a decrease greater than 15% in median soluble thrombomodulin were noted in both limbs. Median haematocrit decreased minimally (1%) in the lower limbs, while the foot volume increased by 4%. Subjects experienced vague symptoms after 6 h of sitting, but none developed symptomatic venous thromboembolism. Upper and lower-limb changes in biomarkers did not correlate, except those in t-PA/PAI-1 ratio and plasminogen activator-1. Significant correlation was found between changes in the lower-limb t-PA/PAI-1 ratio and right foot volume.This study originally reveals that even in the lower limbs, prolonged daytime cramped sitting is not associated with significant procoagulant changes in healthy adult male volunteers, and confirms a previous observation that local lower-limb venous changes are not identically reflected in the upper limbs.     

Primary carcinoma of gallbladder in Yazd, Iran: A 14-year study (1992–2006)

Aim: To investigate the clinico‐pathological profile and stage of disease at presentation of patients with carcinoma of the gallbladder diagnosed during 1992–2006 in Iran. Methods: During this study period 34 consecutive patients with gallbladder carcinoma were identified using a pathology‐based tumor database. The data extracted for each study patient included their gender, age at diagnosis, signs and symptoms, presence of gallstones and histopathological pattern of the gallbladder carcinoma and the UICC/AJCC TNM staging system was used for labeling the stages of the disease. Results: The median age of the 34 patients studied was 69.50 with most between 61 and 70 years of age. The age range of the men was between 53 and 80 years with a median age of 71.50 years and that of the women was between 33 and 79 years with a median age of 68.50 years. The most common symptom was pain in the right hypochondrium. More women had gallstones (15/34) than men (3/10). Adenocarcinoma was the most common histopathological type (91.18%) with the commonest subtype being papillary (47.06%). Eighteen patients had stage IB and stage IIA (52.94%) carcinomas whereas stages IIB and III were observed in six (17.6%) and seven cases (20.6%), respectively. Only three cases (8.82%) were seen in stage IV. The follow up of gall bladder carcinoma (GBC) patients in this study ranged from 6 to 60 months. However, there was a progressive reduction of patients attending follow‐up oncology clinic, particularly by those who had stages III and IV of the disease. Conclusion: Most patients (52.94%) presented with early disease (stage IB and IIA) which carries a good prognosis. Early detection of GBC and a national consensus for the evidence‐based management of GBC in Iran should be the major components of a strategy aimed at improving therapeutic outcome.     

The use of recombinant-activated factor VII in von Willebrand disease: a case series.

Spontaneous and surgery-associated bleeding in patients with von Willebrand disease (vWD) cannot always be controlled with desmopressin or replacement therapy. This paper presents results on the use of recombinant-activated factor VII (rFVIIa) in patients with vWD included in the internet registry Haemostasis.com. Twenty-eight reports on the use of rFVIIa in vWD were identified from the database and included in this analysis. The bleeding episodes were classified as mild (n = 7), moderate (n = 16), or severe (n = 2), and were unspecified in three cases. The median dose of rFVIIa administered was 94 microg/kg body weight (40-127.3 microg/kg). Bleeding stopped in 23 of 27 evaluable patients (85%) and markedly decreased in three patients; the total response rate was 96% (26/27 patients). Response did not correlate with the type of vWD, the site or severity of the initial bleed, or the rFVIIa dose. Other replacement therapies were infrequently used, and their use was similar in the 24 h before and after rFVIIa administration. Eighteen patients also received antifibrinolytic treatment, but its impact on response was not recorded. Only one adverse event (mild fever) was observed. These cases suggest a role for rFVIIa as a safe and effective therapy for vWD.     

Alpha2-HS glycoprotein phenotypes and quantitative hormone and bone measures in postmenopausal women

Summary It has been suggested that inherited traits play a role in the development of osteoporosis by providing a background for the modulation of gene expression. In this study, we examine the influence of the different alleles of alpha₂-HS glycoprotein (AHSG), a protein of the bone matrix, on quantitative estrogens, estrone and estradiol, and bone measures, bone area and density. Estrogens provide a protective effect against fractures in older women and were thus included in the analyses. Isoelectric focusing of AHSG from sera followed by immunoblotting was used to type 163 white post-menopausal women participating in a clinical trial of the effects of walking on bone loss. Plasma hormones were measured by a combination of extraction, column chromatography, and radioimmunoassay; bone measures on the dominant radius were determined with computerized tomography. Analysis of variance was done on estrogen and bone measures after controlling for the effects of age and body mass index. The two major alleles of AHSG result in three phenotypes, designated AHSG 1-1, AHSG 2-1, and AHSG 2-2. The AHSG 1-1 homozygote showed a decreased concentration of estradiol, the AHSG 2-2 homozygote showed an increased concentration, and the AHSG 2-1 heterozygote was intermediate (P=0.001). Estrone demonstrated a similar pattern in residual analysis although it did not reach statistical significance.     

Pre-clinical Cushing's syndrome: an unexpected frequent cause of poor glycaemic control in obese diabetic patients

OBJECTIVE Autonomous cortisol secretion without clinical stigmata of Cushing's syndrome (CS) has been recently recognized and termed pre-clinical or sub-clinical CS. The common assumption is that CS is an extremely rare cause of uncontrolled diabetes; however, the prevalence of this entity has not been studied. We assessed the prevalence of pre-clinical CS among obese patients with uncontrolled diabetes. PATIENTS AND DESIGN (1) In a retrospective analysis, the medical records of 63 patients with endogenous CS were reviewed. (2) In a cross-sectional study, 90 obese patients (BMI >25 kg/m²) followed in a University Hospital and the local Health Fund endocrine and diabetes clinics, with poorly controlled diabetes (glycosylated haemoglobin >9%), underwent an overnight 1 mg dexamethasone suppression. In patients with non-suppressible cortisol levels (>140 nmol/l), Liddle's 2 and 8 mg dexamethasone suppression tests and imaging studies were performed. MEASUREMENTS The prevalence of poorly controlled diabetes, the major presenting symptom of CS, was assessed in the retrospective analysis. The prevalence of ‘true’ CS and the false positive rate in the overnight dexamethasone suppression test were calculated. The endocrine evaluation of the patients with pre-clinical CS and the effects of surgical cure on glycaemic control are described. RESULTS In the retrospective analysis, 11 (17.5%) had diabetes and 2 (3.2%) lacked the classic physical characteristics of the syndrome. In the cross-sectional study, 4 patients failed to suppress plasma cortisol (<140 nmol/l). In one patient the diagnosis of CS was not confirmed by a standard Liddle’s test and was therefore considered false positive. In the other 3, the diagnosis of CS was confirmed (prevalence of 3.3%, 95% confidence interval 1–9%). In all other patients the overnight cortisol suppression test was normal (cortisol level 47.3 ± 2.5 nmol/l (mean ± SEM)). After surgical treatment of CS, glycaemic control was markedly improved in all 5 patients (2 from retrospective and 3 from cross-sectional studies). CONCLUSIONS The prevalence of pre-clinical Cushing's syndrome in obese patients with poorly controlled diabetes appears to be considerably higher than previously believed. The overnight dexamethasone suppression test proved to be a simple, sensitive and highly specific screening test for Cushing's syndrome despite the presence of obesity and hyperglycaemia.