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...     

Local excision of carcinoma of the rectum: Indications

To discuss indications for local excision of adenocarcinoma of the low rectum, two different series of patients were analysed. Series I consisted of 60 patients treated by local excision from 1969 to 1985 in whom local recurrence developed. Series II consisted of 59 patients who underwent resection for non high grade tumors 3.5 cm from 1980 to 1990 in whom lymph node spread was studied. A distinction is made between tumors which are obvious cancers and malignant polyps, and the discussion of indications for local excision is orientated to the former. The results of local excision have been disappointing but a number of compromise selections for local excision have been necessary. Endorectal ultrasound has emerged as the most important method of assessing the depth of invasion of the tumor. Stratifying the depth of the tumor is at present the most important prognostic indicator for lymph node metastasis and local recurrence in non high grade tumors. If the muscle layer is invaded by tumor, local metastasis will occur in 17% of patients. It is likely that only tumors involving superficial layers of muscle are suitable for local excision, but this needs further study. Mucinous carcinomas and the presence of lymphatic invasion are contra-indications to local excision. The shape and size of tumors are not independent prognostic indicators. The techniques available for local excision alter the indications. Salvage operations for recurrence after local excision have proved disappointing.

---

Resumen Con el objeto de revisar las indicaciones para la resección local del carcinoma del recto distal, se analizaron dos series diferentes de pacientes. La serie I incluyó 60 pacientes tratados mediante resección local (1969–1985), en quienes se analizó la recurrencia local. La serie II incluyó en 59 pacientes cuyos tumores eran de 3.5 cm, no de alto grado histológico, que fueron tratados principalmente mediante resección (1980–1990) y en quienes se estudió la extensión linfática. Se establece la distinción entre tumores que obviamente son cánceres y pólipos malignos, y la discusión sobre indicaciones está orientada hacia los primeros. Los resultados de la resección local han sido desalentadores, pero ha sido necesaria una serie de compromisos para la selección de pacientes para resección local. La ultrasonografía endo-rectal ha surgido como el método más importante para determinar el grado de invasión del tumor. La estratificación de la profundidad del tumor es actulamente el principal indicador de pronóstico para metástasis ganglionares y recurrencia local en tumores no de alto grado. Si la capa muscular está invadida por tumor, el análisis de los pacientes de la serie I y de la serie II indica que se presentan metástasis locales en 17%. Es probable que sólo los pacientes con tumores que afectan las capas musculares superficiales sean candidatos para resección local, pero ésto requiere estudio adicional. Los carcinomas mucinosos y la presencia de invasión local constituyen contraindicación para resección local. La forma y el tamaño de los tumores no aparecen como indicadores independientes de pronóstico. Las técnicas disponibles para resección local alteran sus indicaciones. Las operaciones de salvamento para recurrencia después de resección local han probado ser desalentadores, y señalan la importancia de los criterios originales de selección para resección local, puesto que ésta puede ser la primera y la última operación capaz de erradicar el tumor.

---

Résumé Pour préciser les indications de l'exérèse locale des adénocarcinomes du bas rectum, deux séries ont été comparées: une première série de 60 patients (I), traités par exérèse locale entre 1969 et 1985, et une deuxième série de 59 patients (II), traités entre 1980 et 1990, qui avaient des tumeurs de diamètre inférieur ou égal à 3.5 cm dont le degré de différenciation était faible, et qui avaient eu une résection avec étude des ganglions lymphatiques. On a séparé les cancers évidents des polypes cancérisés; la discussion n'a porté que sur le premier group de patients. Les résultats de l'exérèse locale sont décevants mais cette technique est la seule envisageable chez un certain nombre de patients. L'échographie endorectale apparaît l'examen le plus important dans l'évaluation de la profondeur de l'envahissement local de la tumeur. La classification selon l'extension en profondeur de la tumeur est, à l'heure actuelle, l'indicateur pronostique le plus important en ce qui concerne l'envahissement lymphatique et la récidive locale des tumeurs de faible degré de malignité. L'envahissement de la couche musculaire, que ce soit dans la série I ou II, correspond à un taux de métastase locale de 17%. Il est probable que seules les tumeurs superficielles soient susceptibles de bénéficier d'une exérèse locale, mais ceci doit être confirmé. Le cancer mucineux et la présence d'un envahissement lymphatique sont des contreindications à une exérèse locale. La taille et la forme des tumeurs ne semblent pas intervenir comme facteurs pronostiques. Les techniques disponibles pour l'exérèse locale influent sur les indications. Les interventions de sauvetage après exérèse locale sont décevantes.

     

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.     

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.