Antineutrophil cytoplasmic antibodies in patients with Graves’ disease: association of antimyeloperoxidase autoantibodies with propylthiouracil therapy

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitic disorders have been reported in patients with Graves disease during propylthiouracil (PTU) therapy. To investigate whether ANCA are found in serum samples from patients with Graves disease, and whether PTU therapy is associated with ANCA positivity, levels of serum ANCA were examined in Graves-disease patients receiving either PTU (n = 49) or 1-methyl-2-mercaptoimidazole (methimazole, MMI) (n = 50), and in untreated Graves-disease patients (n = 32) by enzyme-linked immunosorbent assay (ELISA). Serum samples from patients with Hashimotos thyroiditis (n = 46) were also analyzed. Antimyeloperoxidase (MPO) autoantibodies (MPO-ANCA) were present in 10 (20.4%) of 49 Graves-disease patients receiving PTU therapy, whereas MPO-ANCA were not detected in Graves-disease patients receiving MMI, in untreated Graves-disease patients, or in Hashimotos thyroiditis patients. The MPO-ANCA-positive sera showed a perinuclear staining pattern which was detected by indirect immunofluorescence microscopy using a human polymorphonuclear leukocyte–cytospin preparation. Furthermore, Western blot analysis revealed that MPO-ANCA in the Graves-disease patients, as well as MPO-ANCA in patients with idiopathic pauci-immune necrotizing and crescentic glomerulonephritis, recognize the 105-kD protein of native MPO. These results indicate that MPO-ANCA in Graves-disease patients are strongly associated with PTU therapy, and not simply related to the autoimmune thyroid disease. This study also suggests that the presence of MPO-ANCA alone may not be sufficient for the development of vasculitic disorders.     

Mechanical properties and imaging characteristics of remanufactured intravascular ultrasound catheters

Intravascular ultrasound (IVUS) as a routine device in interventional cardiology is handicapped by its high price. 19 factory-made, remanufactured IVUS catheters which consist of sterilized, used phased-array IVUS transducers inserted into a new catheter shaft were compared with 23 new IVUS catheters. 3 mechanical and 4 imaging characteristics were assessed on a 5 point scale (1 = unacceptable, 5 = excellent). Mechanical as well as imaging properties of remanufactured IVUS catheter were comparable to new catheters with excellent ratings for each of the evaluated characteristics in 38 to 94% of remanufactured catheters and 50 to 96% of new catheters. The initial failure rate for remanufactured IVUS catheters was 31.6% vs. 4.3% for new catheters (P < 0.05). Overall failure rate was 47.3% for remanufactured catheters vs. 8.7% for new catheters (P < 0.05). The failure was due to an electronic connecting problem occurring during mechanical stress to the IVUS catheter. In conclusion, remanufactured IVUS catheters offer mechanical and imaging characteristics which are comparable to new catheters. Improvements in the remanufacturing process to resolve the high rate of electronic connecting problems may make this a promising approach to substantially lower the price of IVUS catheters.     

Crohn’s disease complicated by adult-onset Still’s disease

A 31-year-old man with Crohns disease developed arthritis, spiking fever, and skin rash indistinguishable from that of adult-onset Stills disease. He was admitted to our hospital because of a periumbilical intestinal skin fistula. Crohns disease had been diagnosed in 1991, and had required intestinal resection twice, and schizophrenia had been diagnosed in 1993. He developed polyarthritis and spiking fever, accompanied by a macular skin rash on both forearms. Marked hepatosplenomegaly and bilateral pleural effusion were detected on computed tomography examination. These findings are indistinguishable from those of adult-onset Stills disease. Because his mental status had deteriorated following high-dose prednisolone on a previous admission, he was treated with an immunosuppressive agent on this occasion, with the treatment being successful. This is the first report of adult-onset Stills disease complicating Crohns disease. In patients with Crohns disease, polyarthritis and skin rash can easily be misdiagnosed as enteropathic arthritis with erythema nodosum associated with the Crohns disease. Although adult-onset Stills disease may not be fatal, early diagnosis is important because it can, in rare cases, result in life-threatening complications.     

Patient Preferences for the Management of High-Grade Dysplasia in Barrett’s Esophagus

Surgical esophagectomy, intensive endoscopic surveillance, and mucosal ablative techniques, particularly photodynamic therapy (PDT), have been proposed as possible management strategies for Barretts high-grade dysplasia (HGD). Each option has advantages and disadvantages, and no firm consensus exists for the preferred strategy at this time. The purpose of this pilot study was to gain insight into patient preferences in Barretts HGD management. Twenty patients with Barretts esophagus were enrolled in a questionnaire study. The three possible management options for Barretts HGD including each options potential benefits and harms were presented to the subject in a formalized presentation that was designed to be easily comprehendible by patients. The subjects rated each strategy using a health-related quality of life instrument and chose one of the management strategies assuming they were found to have HGD. The average feeling thermometer rating scale values for the management strategies were as follows: endoscopic surveillance, 79; esophagectomy, 46; and PDT, 60. When asked to choose a strategy, 14 (70%) chose endoscopic surveillance, 3 (15%) chose esophagectomy, and 3 (15%) chose PDT. These findings were statistically significant (P = 0.0024). The patients who chose endoscopic surveillance felt comfortable with endoscopy, while the most common concern about esophagectomy, and PDT was the risk of death and the unknown risk of recurrence, respectively. In summary, when patients with Barretts esophagus were presented with three options to manage HGD, the majority chose endoscopic surveillance. Familiarity with endoscopic surveillance was the predominant reason for the choice.     

Reconnaissance de l’antigène et différenciation des lymphocytes T

Résumé Cest au cours de leur développement intrathymique que les lymphocytes acquièrent la capacité de reconnaître une grande variété dantigènes associés au molécules dhistocompatibilité du Soi. Cette propriété est dune part liée à lacquisition de récepteurs de reconnaissance de lantigène, les récepteurs T, dont la biosynthèse sopère à un stade précoce du développement intrathymique. Elle est dautre part la conséquence de processus sélectifs intrathymiques, qui favoriseront lémergence de lymphocytes capables de reconnaître les produits dhistocompatibilité du Soi tout en prévenant la production de thymocytes autoréactifs. Seront ici évoqués les principales étapes du développement lymphocytaire, en insistant sur la génération du répertoire lymphocytaire et sa sélection intrathymique.     

Efficacy of Topical Metronidazole (10 Percent) in the Treatment of Anorectal Crohn’s Disease

PURPOSE The aim of this study was to investigate the efficacy of 10 percent topical metronidazole in the treatment of symptomatic anorectal Crohns disease.METHODS Patients with symptomatic anorectal Crohns disease were studied in a prospective, nonblinded, nonrandomized study to evaluate the efficacy of topical 10 percent metronidazole. Perianal Crohns Disease Activity Index and each component (pain, discharge, induration, sexual dysfunction, and type of pathology) were recorded before treatment and at four weeks. Visual analog pain score (0–10) was recorded before treatment and at weekly intervals for up to four weeks.RESULTS Fourteen patients were studied prospectively for four weeks. Mean Perianal Crohns Disease Activity Index decreased from 8.8 ± 0.9 before treatment to 4.1 ± 0.7 after four weeks treatment (P < 0.0001). Visual analog pain scores decreased from 5.4 ± 0.7 before treatment to 2.4 ± 0.5 at one week (P < 0.001) and to 1.0 ± 0.4 after four weeks treatment (P < 0.0001). Of the Perianal Crohns Disease Activity Index components, significant decreases were noted in pain and discharge (P < 0.0001) and induration (P < 0.001).CONCLUSION For patients with perianal Crohns disease, topical 10 percent metronidazole decreases the Perianal Crohns Disease Activity Index and anorectal pain.     

A case of anti-Jo1 myositis with pleural effusions and pericardial tamponade developing after exposure to a fermented Kombucha beverage

The pathogenesis of the idiopathic inflammatory myopathies has been postulated to be an environmental trigger causing the expression of the disease in a genetically predisposed patient. We report a case of anti-Jo1 antibody-positive myositis which was associated with pleural effusions, pericardial effusion with tamponade, and mechanics hands, probably related to the consumption of a fermented Kombucha beverage. Kombucha mushroom, a symbiosis of yeast and bacteria, is postulated to be the trigger for our patients disease owing to the proximity of his symptoms to the consumption of the Kombucha beverage.Abbreviations ALT Alanine transferase - AST Aspartate aminotransferase - CPK Creatinine phosphokinase     

Differences of cellular composition and adhesion molecule expression in “leukemic” as compared with “normal” human long-term bone marrow cultures

Summary Human long-term bone marrow cultures (HLTBMCs) were established with bone marrow samples collected from 15 patients with acute myeloid leukemia (AML) and compared with HLTBMCs from eight healthy volunteers. During 6 weeks of culture, the cellular composition of HLTBMCs was quantitatively studied. The cells of the HLTBMCs were divided into three main categories: fibroblasts, macrophages, and other cells (endothelial cells, hematopoietic cells and undefined cells). HLTBMCs derived from healthy volunteers demonstrated a very consistent development. The number of fibroblasts increased during culture and the number of macrophages decreased, resulting in a steady state after 3 weeks of culture. In contrast, HLTBMCs derived from patients with AML showed a strikingly different pattern of irregular development and a steady state was not reached under our conditions. The APAAP technique was used to demonstrate expression of adhesion molecules. VLA2, VLA5, VLA6, LFA1, Mac1, p150/95, ₂-chain, HCAM, ICAM1, NCAM, and VCAM1 were more expressed on normal as compared with leukemic bone marrow stromal cells, although this reached significance only for ₂-chain and NCAM. VLA1, 3, and 4 were expressed in a higher percentage on leukemic stroma (not significant). More expression was seen on normal as opposed to leukemic macrophages for the adhesion molecules tested, except for VLA5. The differences reached significance for the majority of molecules tested. It is concluded that striking differences exist in cellular composition and adhesion molecule expression between HLTBMCs from healthy individuals and those from patients with AML. This may have an impact on the pathogenesis of AML.     

Mutations in the R-type pyruvate kinase gene and altered enzyme kinetic properties in patients with hemolytic anemia due to pyruvate kinase deficiency

Summary The biochemical properties of erythrocyte pyruvate kinase (PK) together with mutations found in the coding sequence of the R-PK gene in five patients with severe hemolytic anemia due to PK deficiency are described. The enzyme variants were designated PK Mosul (homozygote), PK Bukarest_1,2, PK Hamburg₁, PK Köln₁, and PK Essen (compound heterozygote). PK Mosul showed normal positive cooperative substrate binding, PK Bukarest_1,2 exhibited noncooperative behavior, and PK Hamburg₁ and PK Köln₁ displayed mixed cooperativity, whereas PK Essen was negative cooperative. PK Mosul was found to be homozygous for the mutation 1151 ACG to ATG, resulting in an amino acid substitution 384 Thr to Met. In one allele of PK Bukarest_1,2 a single nucleotide substitution GAG-TAG was found at nucleotide 721, causing a change of 241 Glu to a chain termination codon (PK Bukarest₁). Additionally, in the second allele of this patient a point mutation at position 1594 (CGG-TGG) occurs, changing 532 Arg to Trp (PK Bukarest₂). Direct sequencing showed the heterozygosity of the patient's mother (PK Bukarest₁/normal) at position 721 and of the patient's father (PK Bukarest₂ /normal) at position 1594. A point mutation at position 1529 (CGA-CAA), causing an amino acid substitution 510 Arg-Gln, was identified in PK Hamburg₁ and PK Köln₁. The second mutation in these variants was not detected. In PK Essen no mutation in the coding sequence was found at all. Screening for the mutation at position 1529 in further compound heterozygote patients and in normal subjects of Western European origin showed that this exchange is a common mutation responsible for PK deficiency in this population.Supported by theDeutsche Forschungsgemeinschaft, Grants no. La 527/1 and Ne 416/1.     

Intimate Partner Violence and Monogamy among Women in Methadone Treatment

It is now becoming clear how important it is to understand womens HIV risk in the context of their sexual relationships with male partners, particularly among more vulnerable populations of women such as drug-involved women and women with physically abusive partners. Drawing from in-depth interviews with a sample of 38 ethnically diverse women, this study explores the meanings of monogamy and concurrent sexual partnerships in the relationships of women in methadone treatment with a history of physical abuse. Moreover, the ways in which having a history of intimate partner violence influences womens desire and ability to insist on monogamy is addressed. The womens narratives indicated that the majority valued monogamy and reported practicing it; however, many women were indifferent to this ideal or were unable to challenge non-monogamous partners for fear of severe reprisals. In addition, mens suspicions about violations of monogamy on the part of the women often resulted in extreme violence.     

Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment

Summary Glomerular basement membrane thickness (GBMT) has been measured in streptozotocin diabetic rats treated with insulin. The study included 3 groups of 8 rats each: 1) a well-controlled group of diabetic rats under insulin treatment with a plasma glucose level reasonable close to normal values, 2) a poorly-controlled group also under insulin treatment with constant high plasma glucose values, and 3) an age and weight matched non-diabetic control group. After 6 months of diabetes, GBMT was measured applying an intercept method on 3 glomerular cross sections from each of the 24 animals. The measurements showed that mean GBMT was 132.2. nm in the non-diabetic control rats and 131.6 nm in the well-controlled diabetic rats. In the poorly-control-led group the mean GBMT was 140.4 nm, i.e. statistically significantly increased when compared to each of the two other groups, 2p=0.022 and 0.012 respectively.The results demonstrate that good blood glucose control in rats preserves normal GBMT.     

Enzyme replacement and beyond

During the last decade, enzyme replacement therapy for lysosomal storage diseases became a reality with the demonstration of its safety and effectiveness in type 1 Gaucher disease. Currently, enzyme replacement and several other potential therapeutic strategies are being developed for selected lysosomal storage diseases, including Fabry disease due to the deficient activity of -galactosidase A (-Gal A). The development and clinical evaluation of these new therapies require a stepwise process, each step being rigorously reviewed and approved by national or international regulatory agencies. For lethal disorders that affect small populations, such as many inherited metabolic diseases, this process can be accelerated by orphan drug and fast track regulations. As an example of the drug development process, the development of recombinant human -Gal A (r-hGal A) replacement for Fabry disease is presented, including the preclinical studies in the Fabry mouse model, and the clinical phase 1/2, phase 3, and phase 3 extension studies, which demonstrate the safety and efficacy of this new therapy.     

Oral glucose tolerance and ambient temperature in non-diabetic subjects

Summary When either a 960-kcal, 140-g carbohydrate meal, or a 75-g glucose load was ingested by non-diabetic Caucasians, the 2-h venous plasma glucose concentration was higher by 0.82 and 1.25 mmol/l, respectively, if the ambient temperature was 33 °C rather than 23 °C. It is likely that this is a result of relative arterialisation of the venous blood. Even at 23 °C room temperature, use of the hot hand technique to obtain arterialised venous blood increases post-load glucose levels in contralateral antecubital veins. If these observations apply to those acclimatised to the heat, they could affect the diagnosis of both diabetes and impaired glucose tolerance in the tropics.     

Pulmonary artery aneurysm in Behcet’s disease: a case report

The pulmonary artery is the second most common site of arterial involvement in Behcets disease. A 32-year-old man presented with bilateral ankle edema, abdominal discomfort, and hemoptysis. He had a history of recurrent oral and genital aphthous ulcerations for 1 year. The diagnosis of Behcets disease was made on the basis of the criteria published by the International Study Group for Behcets Disease. His chest X-ray revealed left hilar enlargement. A helical computed tomography (CT) scan showed a pulmonary aneurysm with intramural thrombosis in the left pulmonary artery and enlarged hepatic veins. Treatment with colchicine and cyclophosphamide was given for 24 months, and helical thoracic CT was performed again. Helical CT showed that the pulmonary aneurysm was reduced by treatment. Helical CT could be used in Behcets disease for the diagnosis and follow-up of pulmonary involvement.     

Takayasu’s arteritis and chronic autoimmune thyroiditis in a patient with type 1 diabetes mellitus

Takayasus arteritis is a rare, chronic inflammatory disease of unknown origin, affecting the walls of the aorta and its main branches, as well as coronary and pulmonary arteries. The inflammation of the arteries may lead to stenosis, occlusions, dilatations, and aneurysms of involved vessels. It is relatively common in Asia and the Far East but is rare in the Western Hemisphere. We present the case of a 36-year-old white woman with a history of type 1 diabetes mellitus and chronic autoimmune thyroiditis who complained of easy fatigability in the upper limbs, with absent arterial pulses in the upper limbs and audible bruits over both subclavian and left common carotid arteries. Intra-arterial digital subtraction angiography revealed complete or subtotal obliteration of the aortic archs branches, with the brain supplied with blood only by the left vertebral artery originating directly from the aortic arch. We diagnosed Takayasus arteritis with abnormal origin of the left vertebral artery. To the best of our knowledge, our case of Takayasus arteritis and chronic autoimmune thyroiditis in a type 1 diabetic patient with abnormal origin of the left vertebral artery is the first one ever described.     

Promoting healthy aging in cities: The Healthy Cities project in Europe

Health promotion is a growing field, spreading into various settings. Thispaper focuses on the city as a setting for health promotion and on theHealthy Cities project (HCP) of the Regional Office for Europe of theWorld Health Organization in particular. In the context of the HCP, variousactivities to promote the health of older citizens have been carried out inrecent years. These are illustrated in this paper through case studies.     

Scoring prevalence and severity in gonarthritis: the suitability of the Kellgren & Lawrence scale

In clinical and epidemiological studies the Kellgren & Lawrence (K&L) scale was mainly used in the past to determine the radiological prevalence and severity of gonarthritis. The dependency of this scoring system on the presence of osteophytes has been criticised, and owing to its varying reliability, its appropriateness in cross-sectional and longitudinal studies is questioned. It was the purpose of this study to test whether the dependency of the K&L scale on the presence of osteophytes is reflected in a higher correlation of the overall score with a separate scoring of osteophytes than with other radiological features. Furthermore we compared the inter- and intrarater reliability with the reliability of individual radiological features. Knee radiographs of 40 patients were graded according to the K&L scale and for the presence and severity of five separate radiological features of osteoarthritis. We found a moderate correlation of the K&L scale with the radiological features of osteophytes, joint space narrowing and flattening of condyles. The intra- and inter-rater reliability of the K&L scale was higher than the reliability of the individual radiological features. The K&L scale seems not to be strongly dependent on the presence of osteophytes, i.e. there is not a higher correlation of the overall score with that feature than with other radiological features.     

Morphometry versus densitometry — a comparison by use of casts of human coronary arteries

Geometric and densitometric methods for quantitative coronary arteriography have generally been compared by use of phantoms simulating arteries with circular lumina (Hole phantoms). We have used more adequate phantoms obtained by casting disease-free and atheromatous human coronary arteries. The phantoms, filled with contrast medium, were imaged digitally (1024 × 1024 × 10 matrix) under experimental conditions simulating routine coronary angiography. The angiographic diameters and the densitometric cross-sectional areas of 59 marked lumina were determined in single plane and orthogonal biplane raw images. Geometric calibration was performed by help of a 7F coronary catheter. For the densitometric calibration, we used a hole phantom attached to the image intensifier. The obtained luminal areas were compared to their true values determined previously by planimetry. The mean absolute error of single plane cross-sections obtained geometrically was 1.53 mm². Biplane imaging reduced it by a factor 2.4 to 0.64 mm². The corresponding mean absolute errors for densitometry were 0.56 mm² and 0.51mm². Single plane diameter measurements appear thus of very limited value for hemodynamic conclusions. In contrast, biplane geometric quantification was not markedly inferior to single plane and biplane densitometry.     

Study of porcine and human isophane (NPH) insulins in normal subjects

Summary The plasma glucose, C-peptide and insulin responses to subcutaneously administered highly purified porcine, semi-synthetic and biosynthetic human isophane (NPH) insulin and diluting medium as control in normal male subjects were evaluated. Porcine and semi-synthetic human NPH insulins were administered at two dose levels of 0.15 and 0.30 U/kg body weight and biosynthetic human NPH at 0.15 U/kg body weight only. At the low dose level the three insulin preparations resulted in a similar maximal hypoglycaemic effect within 3–5 h after administration. However, over the remainder of the 11 h post-injection period, the plasma glucose level was lower after semi-synthetic human insulin. In contrast, at the 0.30 U/kg dose level, there was no difference in the early or late hypoglycaemic response between porcine and semi-synthetic human NPH insulins of equivalent pharmaceutical formulation. The clinical relevance of these findings needs further evaluation. The data suggest that for the intermediate-acting NPH insulin preparations, both the species of insulin, nature and quantity of the retarding protein and their subsequent interaction may determine their time-action characteristics.     

The effect of hand osteoarthritis on grip and pinch strength and hand function in postmenopausal women

The aim of the study was to investigate the effect of osteoarthritis on hand function in postmenopausal women. One hundred patients with hand OA and 70 healthy volunteers as controls were evaluated. Grip and pinch strength measurements and Dreisers functional index were used for hand function. Pain was assessed by a visual analog scale, and tenderness was assessed by palpation and scored, depending on the severity of tenderness, as 0, 1 or 2. Heberdens and Bouchards nodules and joint involvement were also recorded. The number of patients with only distal interphalangeal joint involvement was 50 (50%), those with distal interphalangeal joint plus proximal interphalangeal joint involvement was 49 (49%), and those with carpometacarpal joint involvement numbered 18 (18%). The incidence of Heberdens and Bouchards nodules was 85% and 36%, respectively. Eighty-six (86%) patients were suffering from pain and 57 were found to have tenderness. Grip and pinch strength was significantly lower (p<0.05) and Dreisers functional index score was significantly higher (p<0.001) in the study group (particularly in grade 4 OA). Grip strength was lower in hand OA patients with distal interphalangeal joint plus proximal interphalangeal joint involvement than in those with only distal interphalangeal joint and carpometacarpal joint involvement. Pinch strength was also lower in patients with distal interphalangeal joint plus proximal interphalangeal joint plus carpometacarpal joint involvement. The patients with Heberdens and Bouchards nodules had lower grip and pinch strength than controls. Also, pain and tenderness had significant (p<0.05) effects on hand function. Dreisers total score ranged from 0 to 10 in 80 (80%) patients and from 11 to 20 in 20 patients. In conclusion, hand osteoarthritis contributes to hand dysfunction, mainly related to the severity of osteoarthritis, pain, joint involvement and the presence of nodules.Abbreviations CMC Carpometacarpal - DIP Distal interphalangeal - OA Osteoarthritis - PIP Proximal interphalangeal