Reliability of mechanical and phased-array designs for serial intravascular ultrasound examinations

Background: Both mechanical and multi-element intravascular ultrasound designs have potential advantages and limitations that may impact on their value for clinical and research purposes. Determination of the reproducibility of measurements is critical before a given system can be used in studies such as regression of atherosclerosis trials. Methods: We performed serial intravascular ultrasound imaging with catheters using mechanical and phased-array designs in stented and non-stented coronary arteries in dogs and in patients. Results: Both systems correlated well for areas (r 0.90, p < 0.0001) and diameters (r 0.84, p < 0.0001) in dogs and in patients. There was a slight difference between multi-element and mechanical designs for measurements of area (mean difference in dogs and in patients: –0.24 and 0.96 mm², p < 0.055) and diameter (–0.08 and 0.16 mm, p < 0.0001). The reproducibility of the multi-element system for reanalysis of the same frames and for analysis of serial pullbacks was similar to the same measurements with the mechanical system (r 0.96 for all measurements). The differences in absolute and relative variability between the mechanical and phased-array designs, both for reanalysis of same frames and serial pullbacks, were very small. Conclusions: Although multi-element and mechanical intravascular ultrasound designs are not strictly interchangeable, their similar reproducibility and the small differences in measurements demonstrate that both designs are acceptable alternatives for trials of regression of atherosclerosis. Determination of the variability for serial pullbacks of both designs was also important to assess the statistical power of such trials.     

Variations in Digestive Physiology of Rats After Short Duration Flights Aboard the US Space Shuttle

The purpose of this work was to assess the influence of microgravity on several endogenous and microbial parameters of digestive physiology. On the occasion of two Spacelab Life Sciences missions, SLS-1 (a 9-day space flight) and SLS-2 (a 14-day space flight), Sprague-Dawley rats flown aboard the US space shuttle were compared to age-matched ground-based controls. In both flights, exposure to microgravity modified cecal fermentation: concentration and profile of short-chain fatty acids were altered, whereas urea and ammonia remained unchanged. Only in SLS-1 was there an induction of intestinal glutathione-S-transferase. Additional analyses in SLS-2 showed a decrease of hepatic CYP450 and of colonic goblet cells containing neutral mucin. After a postflight recovery period equal to the mission length, only modifications of the hepatic and intestinal xenobiotic metabolizing enzymes still persisted. These findings should help to predict the alterations of digestive physiology and detoxification potential likely to occur in astronauts. Their possible influence on health is discussed.     

Calcium-sensing receptor autoantibodies are relevant markers of acquired hypoparathyroidism

We investigated the presence of autoantibodies (aAbs) directed against the parathyroid gland in 17 patients with spontaneous isolated acquired hypoparathyroidism. Fourteen patients with acquired hypoparathyroidism (AH) associated with type I or II autoimmune polyendocrinopathy syndrome were also tested in comparison with a control group of 68 subjects without AH, including patients with other autoimmune diseases and healthy blood donors. aAbs against parathyroid tissue were screened using an indirect immunofluorescence technique on primate parathyroid tissue and human parathyroid adenoma. aAbs against the calcium-sensing receptor (CaSR) were analyzed using an immunoblotting assay with the recombinant extracellular domain of the human CaSR as antigen. Seven of the 31 patients with AH were positive for CaSR aAbs. Five of the positive sera were obtained from the group with isolated AH. The two other positive sera were from patients with autoimmune polyendocrinopathy syndrome. The sensitivity of the immunoblotting technique was higher than that of both the radioimmunological test using the extracellular domain of the CaSR and the indirect immunofluorescence technique. There were no positive sera in the control group. In conclusion, using an immunoblotting assay, we demonstrate the presence of CaSR aAbs in about one third of the patients with isolated AH, pointing out the value of detecting such aAbs to assess the autoimmune origin of the disease.     

Rheumatoid flat foot and deformity of the first ray

OBJECTIVE: To study the relationship between flat foot and forefoot deformities in rheumatoid arthritis (RA) in order to improve understanding of the progression of deformity and thus provide more appropriate treatment. METHODS: Anteroposterior and lateral weight-bearing radiographs were obtained of 308 feet of patients with RA and 202 feet of patients with neck pain (control feet). RESULTS: In women with RA, we observed with disease duration an increased frequency of flat foot that was correlated with first ray deformity (chiefly metatarsus primus adductus) and severe stages of disability. Flat foot increased very markedly after 3-4 years of disease duration. In control women, flat feet were more frequent after the age of 50 years. CONCLUSION: In RA the inflammatory and mechanical factors leading to foot deformity must receive early medical treatment to avoid progressive hindfoot deformities that lead to disability.     

A prospective national study on colonoscopy and sigmoidoscopy in 2000 in France

AIM: The aim of this study was to evaluate the practice of colonoscopy and sigmoidoscopy in France in 2000. METHODS: A prospective study was conducted in November 2000 using questionnaires sent to all gastroenterologists practicing in France (N=2858) who were asked to reply to items concerning colonoscopies and sigmoidoscopies performed on two workdays chosen in advance. The response rate was 32.8%. Data were extrapolated to establish estimates for the entire year. RESULTS: An estimated 894000 colonoscopies and 115320 sigmoidoscopies were performed in 2000. Single-use material was used in 22.1% of the procedures. Indications for endoscopy were mainly hematochezia (21.6%), gastrointestinal symptoms (35%) and surveillance of patients with a history of previous polypectomy (15%). Colorectal cancer screening was the indication for 20% of colonoscopies. Abnormal findings were reported for 54.8% of the endoscopies (polyps for 287218 procedures and cancer for 32799). Failure was noted in 4.9% of colonoscopies. The complication rate was 0.48%. Most polyps were adenomas (64.4%) or hyperplasic polyps (28.1%). The overall estimated number of colonoscopies with polypectomy was 224133. CONCLUSION: In 2000 there was an increased rate of colonoscopy for colorectal cancer screening (20%) but an overall decrease (2.5%) in the total number of colonoscopies compared to 1999. Abnormal findings were disclosed by 54.8% of the procedures. Extrapolation from these data indicates that colonoscopic screening enabled the diagnosis of 32799 colorectal cancers.     

A Randomized,Double-Blind,Parallel Study to Evaluate the Dose-Response of Three Different Vitamin D Treatment Schemes on the 25-Hydroxyvitamin D Serum Concentration in Patients with Vitamin D Deficiency

Many people worldwide are vitamin D (VTD) deficient or insufficient, and there is still no consensus on the dose of VTD that should be administered to achieve a 25(OH)D concentration of 20 or 30 ng/mL. In this study, we aimed to determine an adapted supplementation of VTD able to quickly and safely increase the vitamin D status of healthy adults with low 25(OH)D. One hundred and fifty (150) subjects were randomized into three groups, each to receive, orally, a loading dose of 50,000, 100,000 or 200,000 IU of VTD3 at Week 0, followed by 25,000, 50,000 or 100,000 IU at Week 4 and Week 8. Whereas 25(OH)D baseline values were not different between groups (p = 0.42), a significant increase was observed at Week 12 (p < 0.0001) with a mean change from baseline of 7.72 ± 5.08, 13.3 ± 5.88 and 20.12 ± 7.79 ng/mL. A plateau was reached after eight weeks. No related adverse event was recorded. This study demonstrated a linear dose-response relationship with an increase in 25(OH)D levels proportional to the dose administered. In conclusion, a loading dose of 200,000 IU VTD3 followed by a monthly dose of 100,000 IU is the best dosing schedule to quickly and safely correct the VTD status.     

Impairment of death-inducing signalling complex formation in CD95-resistant human primary lymphoma B cells

Multiple mechanisms exist by which tumour cells can escape CD95-mediated apoptosis. Previous studies by our laboratory have shown that primary B cells from non-Hodgkin's Lymphoma (B-NHL) were resistant to CD95-induced cell death. In the current study, we have analysed the mechanisms underlying CD95 resistance in primary human lymphoma B cells. We report that FADD (FAS-associated death domain protein) and caspase-8 were constitutively expressed in lymphoma B cells and that the CD95 pathway was blocked upstream to caspase-8 activation. However, caspase-8 was processed and functional after treatment with staurosporine (STS). We found that the expression levels of FLICE (FADD-like interleukin-1 beta-converting enzyme)-Inhibitory Protein (c-FLIP) and Bcl-2-related proteins were heterogeneous in B-NHL cells and were not related to CD95 resistance. Finally, we report the absence of a CD95-induced signalling complex [death-inducing signalling complex (DISC)] in lymphoma B cells, with no FADD and caspase-8 recruitment to CD95 receptor. In contrast, DISC formation was observed in CD95-resistant non-tumoural (NT) B cells. Therefore, we propose that the absence of DISC formation in primary lymphoma B cells may contribute to protect these cells from CD95-induced apoptosis.     

Evidence for hydrophobic region within heavy chains of mouse B lymphocyte membrane-bound IgM

The gel filtration behavior, in the presence of detergents, of membrane-bound IgM from normal mouse spleen B lymphocytes was compared to that of secretory IgM from mouse plasma cells. The proteins were labeled either by surface radioiodination or biosynthetically with radioactive amino acids. Cell lysates were fractionated on calibrated Sepharose 6B columns in the presence of the detergents Nonidet P-40 or deoxycholate. Eluted fractions were immunoprecipitated and the reduced or unreduced precipitates were analyzed by sodium dodecyl sulfate gel electrophoresis followed by radioautography. Surface (125)I-labeled 8S IgM exhibited a gel filtration pattern in Nonidet P-40 corresponding to much higher apparent molecular weight than that of secretory 8S IgM, a difference that almost disappeared when gel filtration was performed in the presence of deoxycholate, which forms much smaller micelles than does Nonidet P-40. Biosynthetically labeled lymphocytes contain two types of IgM molecules differing in their gel filtration behavior and fate: one identical to secretory 8S IgM of plasma cells and secreted in the medium during chase periods, and the other identical to surface (125)I-labeled IgM and remaining cell-associated. Because the surface-bound 8S IgM was not found to be associated with other labeled molecules, it is likely that the detergent-binding behavior of surface IgM is due to a hydrophobic segment carried by these Ig molecules. That lymphocytes synthesize two types of mu chains was also shown by the use of tunicamycin, an inhibitor of glycosylation. In its presence, two unglycosylated mu chains were observed: one identical in size to that made by tunicamycin-treated plasma cells, and the second slightly larger. Gel filtration in Nonidet P-40 of the cell lysates of tunicamycin-treated lymphocytes showed that the nonsecretory 8S IgM contains this second type of mu chains, whereas the IgM molecules of the secretory type contain plasma cell-like mu chains. It is suggested that membrane IgM mu chains contain a hydrophobic segment which is responsible for its association to the membrane.