Insulin resistance Type A and short 5th metacarpals.

BACKGROUND/AIMS: Insulin resistance is associated with a number genetic syndromes and a variety of defects of insulin action. METHODS: We describe three members of an extended family spanning two generations with insulin resistance Type A and short 5th metacarpals. The proband had secondary amenorrhoea, male pattern hair distribution, acne, hirsutism, deep voice, acanthosis nigricans, polycystic ovaries, diabetes, features of acromegaly, raised creatine kinase and triglyceride levels and short 5th metacarpals. Her growth hormone, adrenal steroid and testosterone levels were normal. The proband's daughter had severe acne, hirsutism, acanthosis nigricans, polycystic ovaries, raised triglyceride, glucose and testosterone level short metacarpals and normal insulin receptor gene. The proband's son had a muscular build, raised creatine kinase, hypertriglyceridaemia and short 5th metacarpals. His fasting insulin levels were normal but pro-insulin was raised. RESULT/CONCLUSION: There are many familial and genetic syndromes associated with insulin resistance. This family was diagnosed as having insulin resistance Type A. This family does not conform entirely to any of the previously described syndromes and a number of family members have the phenotype of short 5th metacarpals, which appears to be associated with the features of insulin resistance Type A.     

Combined percutaneous antegrade and cystoscopic retrograde approach in the treatment of distal ureteric fistulae

Purpose To determine the efficacy of a cystoscopic approach, as definitive treatment of ureteral fistulae, after failure of antegrade ureteral stent insertion.Methods Of 43 ureter fistulae encountered over 4 years, 10 postoperative and/or postradiotherapy fistulae could not be stented via an antegrade approach alone. A cystoscopic approach was used, with the antegrade approach available as back-up, if necessary.Results In two patients the ureteral orifice could not be visualized cystoscopically, thus precluding the retrograde approach. In the eight remaining patients, the retrograde approach alone never allowed successful stenting. In six patients, combined antegrade and retrograde approaches permitted stent insertions. In three of those six patients, a complex catheterization procedure was necessary. In two patients the combined approach failed altogether. Therefore, 6 of 10 patients underwent a successful stenting procedure with the combined approach; all ultimately closed the fistula.Conclusion Antegrade stent insertion remains the treatment of choice for ureteral leaks. If the antegrade approach fails, the retrograde approach alone is not likely to be successful. Instead, a combination of both approaches often does succeed.     

Binding of nucleosomes to a cell surface receptor: Redistribution and endocytosis in the presence of lupus antibodies

In the present study, we sought evidence for a surface nucleosome receptor in the fibroblastic cell line CV-1, and questioned whether anti-double-stranded (ds)DNA and/or anti-histone autoantibodies could recognized and influence the fate of cell surface-bound nucleosomes. ¹²⁵I-labeled mononucleosomes were shown to bind to the cell layer in a specific, concentration-dependent and a saturable manner. Scatchard analysis revealed the presence of two binding sites: a high-affinity site with a Kd of ～ 7nM and a low-affinity site (Kd ～ 400 nM) with a high capacity of 9 × 10⁷ sites. Visualization of bound mononucleosomes by fluorescence revealed staining on both the cell surface and the extracellular matrix (ECM). Purified mononucleosome-derived dsDNA (180–200 bp) was found to compete for binding of ¹²⁵I-mononucleosomes on the low-affinity site, to stain exclusively the ECM in immunofluorescence, and to precipitate three specific proteins of 43, 180 and 240 kDa from ¹²⁵-I-labeled cell lysates. Nucleosomes were found to precipitate not only the 180-kDa dsDNA-reactive component, but also a unique protein of 50 kDa, suggesting that this protein is a cell surface receptor for nucleosomes on these fibroblasts. Once bound on the cell surface, mononucleosomes were recognized and secondarily complexed by lupus anti-dsDNA or anti-histone antibodies (i.e. anti-nucleosome antibodies), thus forming immune complexes in situ. The presence of these complexing auto-antibodies was found dramatically to enhance the kinetics of mononucleosome internalization. Following the internalization of the nucleosome-anti-nucleosome complexes by immunofluorescence, we observed the formation of vesicles at the edge of the cells by 5–10 min which moved toward the perinuclear region by 20–30 min. By means of double-fluorescence labeling and proteolytic treatment, these fluorescent vesicles were shown to be in the cytoplasm, suggesting true endocytosis of nucleosome-anti-nucleosome immune complexes. As shown by confocal microscopy, at no stage of this endocytic process was there any indication that coated pits or coated vesicles participated. Co-distribution of the endocytic vesicles with regions rich in actin filaments and inhibition of endocytosis of nucleosome-anti-nucleosome complexes by disruption of the micro-filament network with cytochalasin D suggest a mechanism mediated by the cytoskeleton. Taken together, our data provide evidence for the presence of a surface nucleosome receptor. We also show that anti-dsDNA and anti-histone antibodies can form nucleosome-anti-nucleosome immune complexes in situ at the cell surface, and thus dramatically enhance the kinetics of nucleosome endocytosis.     

Formalin-fixed and paraffin-embedded nodal non-Hodgkin's lymphomas demonstrate the same chromosome changes as those found in frozen samples: a comparative study using interphase fluorescence in situ hybridization.

Cytogenetic studies in lymphomas classically require fresh or frozen tissue, whereas in many instances only paraffin-embedded biopsies are available. We applied an interphase FISH assay on nuclei extracted from thick paraffin sections to determine accuracy of molecular cytogenetics in such samples. Twenty-three lymphoma samples and 4 reactive lymph nodes were tested with various commercially available DNA probes, and hybridization patterns were compared with those obtained on frozen nuclei counterparts. Successful hybridization with all probes tested was observed for 23/27 (85%) paraffin-embedded tissues and for all (100%) frozen samples, and cut-off levels defining positivity were superimposable for both situations. Chromosome changes were detected in the same way, without any false-positive or false-negative cases. Hybridization signals observed on dewaxed samples were either those classically expected to define the relevant chromosome change or were atypical: all atypical changes could be demonstrated also into nuclei from the frozen counterpart. Moreover, all typical and atypical chromosome changes observed on frozen nuclei were also detected in paraffin-embedded tissues. Our study shows that our interphase FISH assay performed on paraffin-embedded samples is a valuable alternate to conventional methods to ascertain diagnosis of lymphomas as to include patients into therapeutic trials.     

White matter hyperintensities and their association with suicidality in depressed young adults

INTRODUCTION: Researchers and clinicians have increasingly recognized that biological markers may help identify patients who are at risk for suicide. The objective of this retrospective, cross-sectional study was to compare the prevalence and location of white matter hyperintensities (WMH) in young inpatients with major depressive disorder (MDD) with and without histories of suicide attempts. METHODS: T2-weighted magnetic resonance images (MRI) of 102 young psychiatric inpatients with MDD were rated for the presence of WMH. Medical charts were reviewed to ascertain history of suicide attempt, demographic and clinical variables. Fisher's Exact Tests and logistic regression modeling were used to test the association between WMH and suicidality. RESULTS: Bivariate analysis showed that the prevalence of periventricular WMH was significantly higher in subjects with past suicide attempts (Fisher's Exact Test, p=0.02). Logistic regression analyses controlling for age, sex, and several clinical risk factors supported this finding (odds ratio=5.7; 95% confidence interval: 1.6, 21.2). LIMITATIONS: Due to the retrospective, cross-sectional design of our study, we are unable to determine if the WMH preceded or followed past suicide attempts. The generalizability of our findings is limited since this group of inpatients is more severely ill than the general psychiatric population. CONCLUSIONS: The increased prevalence of periventricular WMH in young adults with MDD and a history of suicide attempt, compared to similarly depressed adults without such a history, is consistent with our findings in children and youth, and suggests there might be neurobiological in addition to psychosocial risk factors for suicide.     

Promoting a Culture of Prevention in Albania: the “Si Je?” Program

Prevention Science - Albania is a small country on the Balkan Peninsula that recently implemented an innovative primary healthcare program called “Si Je?” (How are you?) which allowed...     

Hospital comparisons using a Euro Health Data Base for resource management and strategic planning

A European approach for resource management and strategic planning has been implemented in the HOSCOM project of AIM by defining information standards needed across countries, as well as a methodology to measure resources and costs at the institutional and interinstitutional level. A Euro Health Data Base (EHDB) has been obtained in order to test data availability and comparability as well as to validate models through macrocomparisons using case-mix (DRG's, refined grouping, disease staging) and microcomparisons based on three diseases (cardiac valve replacement, diabetes mellitus and hip fracture). The EHDB's presently based on 274 164 medical record summaries sampled from 7 countries allowed us to build prototypes (using Clipper, Prolog and SQL) in order to export uniform aggregates in the different countries, with standard software tools for statistical comparisons. It showed the present feasibility of using case-mix based on the European Minimum Basic Data Set (MBDS) and the difficulty of obtaining uniform data on resources and costs other than length of stay across countries. Medical data confidentiality was assured but not yet population-based representativity. Given the present state of the EHDB, problems have been clearly identified in order to be solved by international research and development projects in the near future.     

Análisis coste-efectividad de samario-153 (Quadramet®) en el tratamiento del dolor en pacientes con cáncer de próstata y metástasis óseas

Objective. To evaluate the cost-effectiveness of samarium [¹⁵³Sm-EDTMP] (Quadramet®) compared to conventional therapy in the treatment of pain in patients with prostate cancer and bone metastases. Method. A decision tree model for the treatment of bone pain due to metastases was adapted to the Spanish context. The model represents the standard treatment patterns in Spain for the study population. The time-course of the model is 4 months and it computes an estimate for the cost of pain control per patient. The effectiveness data for the model derive from a randomised trial. The current treatment patterns have been established according to the consensus opinions of a group of medical experts. Results. The cost of pain control per patient is ? 12,515.39 for conventional therapy and ? 5,595.52 for samarium-153 (Quadramet®) therapy. The incremental cost-effectiveness analysis shows that samarium-153 (Quadramet®) is a dominant therapy. It presents lower costs and higher efficacy than the conventional strategy. The sensitivity analyses showed these results to be robust. Conclusion. Samarium-153 (Quadramet®) is costeffective in treating pain in patients with prostate cancer and bone metastases.     

Acquired Left Ventricular Submitral Aneurysms in the Course of Takayasu Arteritis in a Child

A 9‐year‐old black African boy was hospitalized for heart failure revealing a severe left ventricular dysfunction associated with dilated cardiomyopathy, two submitral aneurysms, occlusion of the circumflex artery and a giant coronary artery aneurysm on the proximal left anterior descending artery. The boy was coinfected with human immunodeficiency virus and Mycobacterium tuberculosis. Though rare, association of Takayasu arteritis and submitral aneurysm leads to rethinking the pathogenesis of submitral aneurysm and suggests that some of them may be acquired. In our case, a common inflammatory process, possibly triggered by tuberculosis or HIV, may underlie Takayasu and submitral aneurysms.