Diagnosis and treatment of lipodystrophy: a step-by-step approach.

AIM: Lipodystrophy syndromes are rare heterogeneous disorders characterized by deficiency of adipose tissue, usually a decrease in leptin levels and, frequently, severe metabolic abnormalities including diabetes mellitus and dyslipidemia. PURPOSE: To describe the clinical presentation of known types of lipodystrophy, and suggest specific steps to recognize, diagnose and treat lipodystrophy in the clinical setting. METHODS: Based on literature and in our own experience, we propose a stepwise approach for diagnosis of the different subtypes of rare lipodystrophy syndromes, describing its more frequent co-morbidities and establishing the therapeutical approach. RESULTS: Lipodystrophy is classified as genetic or acquired and by the distribution of fat loss, which can be generalized or partial. Genes associated with many congenital forms of lipodystrophy have been identified that may assist in diagnosis. Because of its rarity and heterogeneity, lipodystrophy may frequently be unrecognized or misdiagnosed, which is concerning because it is progressive and its complications are potentially life threatening. A basic diagnostic algorithm is proposed. Effective management of lipodystrophy includes lifestyle changes and aggressive, evidence-based treatment of comorbidities. Leptin replacement therapy (metreleptin) has been found to improve metabolic parameters in many patients with lipodystrophy. Metreleptin is approved in the United States as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy and has been submitted for approval in Europe. CONCLUSIONS: Here, we describe the clinical presentation of known types of lipodystrophy, present an algorithm for differential diagnosis of lipodystrophy, and suggest specific steps to recognize and diagnose lipodystrophy in the clinical setting.

An Uncommon Association of Familial Partial Lipodystrophy, Dilated Cardiomyopathy, and Conduction System Disease.

A 46-year-old African American woman presented with severe respiratory distress requiring intubation and was diagnosed with nonischemic cardiomyopathy. She had the typical phenotype of familial partial lipodystrophy 2 (FPLD2). Sequence analysis of LMNA gene showed a heterozygous missense mutation at exon 8 (c.1444C>T) causing amino acid change, p.R482W. She later developed severe coronary artery disease requiring multiple percutaneous coronary interventions and coronary artery bypass surgery. She was later diagnosed with diabetes, primary hyperparathyroidism, and euthyroid multinodular goiter. She had sinus nodal and atrioventricular nodal disease and had an implantable cardioverter defibrillator implantation due to persistent left ventricular dysfunction. The device eroded through the skin few months after implantation and needed a re-implant on the contralateral side. She had atrial flutter requiring ablation. This patient with FPLD2 had most of the reported cardiac complications of FPLD2. This case is presented to improve the awareness of the presentation of this disease among cardiologists and internists.

Angioedema de intestino delgado secundario a inhibidor de la enzima convertidora de la angiotensina / Angioedema of the small bowel secondary to treatment with angiotensin converting enzyme inhibitor

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Doenças do sistema digestório de caprinos e ovinos no semiárido do Brasil / Diseases of the digestive system of sheep and goats in the semiarid region of Brazil

As doenças do sistema digestório de caprinos e ovinos na região semi-árida do nordeste do Brasil foram avaliadas através de um estudo retrospectivo de 2.144 atendimentos de pequenos ruminantes no Hospital Veterinário da Universidade Federal de Campina Grande, Patos, Paraíba, no período de janeiro de 2000 a dezembro de 2011. Os registros foram revisados para determinar a ocorrência e as principais características clínicas, epidemiológicas e patológicas dessas enfermidades. De um total de 512 casos (23,9%) de distúrbios digestivos, 367 (71,7%) ocorreram em caprinos e 145 (28,3%) em ovinos. As helmintoses gastrintestinais e a coccidiose foram as doenças mais frequentes, com um total de 330 casos. Os distúrbios da cavidade ruminoreticular (acidose, indigestão simples, timpanismo, e compactação ruminal) totalizaram 94 casos. O abomaso foi afetado primária e secundariamente por úlceras. Casos de obstrução e compressão do trato gastrointestinal também foram observados. Malformações como atresia anal e fenda palatina foram registradas em ambas as espécies, sendo esta última associada à ingestão de Mimosa tenuiflora. Entre as doenças infecciosas foram observados cinco casos de ectima contagioso, dois casos de paratuberculose e dois casos de pitiose gastrointestinal. Em sete animais suspeitou-se de enterotoxemia e 31 casos foram diagnosticados como enterite inespecífica. A não utilização de práticas de controle integrado de parasitas e a utilização de alimentos inadequados durante o período de escassez de forragem contribuiu para a ocorrência de um grande número de doenças. A prática de conservação de forragens poderia reduzir substancialmente a ocorrência de distúrbios digestivos na região semiárida.

Diseases of the digestive system of goats and sheep in the semiarid region of northeastern Brazil were evaluated by a retrospective study of 2,144 attendances of small ruminants in the Veterinary Hospital of the Federal University of Campina Grande, Patos, Paraíba, from January 2000 to December 2011. The records were reviewed to determine the occurrence, epidemiology, and the main clinicopathological features of the gastrointestinal diseases diagnosed during the studied period. Out of a total of 512 cases (23.9%) of gastrointestinal disorders in small ruminants, 367 (71.7%) occurred in goats and 145 (28.1%) in sheep. Gastrointestinal helminthiasis and coccidiosis were the most frequent diseases (330 cases). The disorders of the rumen and reticulum (acidosis, simple indigestion, bloat, and ruminal compaction) constituted 94 cases. The abomasum was affected by primary and secondary ulcers, and obstruction and compression of the gastrointestinal tract were also observed. Malformations, such as anal atresia and cleft palate were recorded in both species, the latter being associated with ingestion of Mimosa tenuiflora. Among the infectious diseases, five outbreaks of contagious ecthyma, two cases of paratuberculosis, and two cases of gastrointestinal pythiosis were observed. Suspected seven cases of enterotoxemia and nonspecific enteritis were identified. The lack of an integrated control of parasites and the use of inadequate food during the period of lack of forage contributes to the occurrence of a great number of gastrointestinal diseases in small ruminants in the studied area. The practice of conservation of fodder could substantially reduce the occurrence of digestive disorders in the semiarid region.

Topical EMLA for pain control during extracorporeal shock wave lithotripsy: prospective, comparative, randomized, double-blind study.

Patient collaboration in external shock wave lithotripsy (ESWL) is critical for its correct application, making proper analgesic selection indispensable. The aim of this study was to evaluate the efficacy of combined application of EMLA and intravenous (i.v.) pethidine compared with pethidine plus placebo cream in patients undergoing ESWL for ureteral and/or renal lithiasis. Prospective, controlled, randomized, double-blind study was conducted in patients receiving ESWL for renal and/or ureterolithiasis. The patients were randomly assigned to receive i.v. pethidine plus either EMLA cream (group A) or placebo hydrating cream (group B). Evaluated were type, location, and size of lithiasis, patient's sex, age, body mass index, comorbidity, Visual Analogue Scale (VAS) score of pain, and degree of lithiasis fragmentation. EMLA cream provided significantly better pain relief and lithiasis fragmentation and more completed ESWL treatment. Topical application of EMLA cream combined with i.v. pethidine improved VAS scores and lithiasis fragmentation and decreased the rate of withdrawal from ESWL procedure versus i.v. pethidine plus placebo therapy.

Histological and molecular features of lipomatous and nonlipomatous adipose tissue in familial partial lipodystrophy caused by LMNA mutations.

OBJECTIVES: Type 2 familial partial lipodystrophy (FPLD2) is a rare adipose tissue (AT) disease caused by mutations in LMNA, in which lipomas appear occasionally. In this study, we aimed to histologically characterize FPLD2-associated lipomatosis and study the expression of genes and proteins involved in cell cycle control, mitochondrial function, inflammation and adipogenesis. DESIGN AND PATIENTS: One lipoma and perilipoma fat from each of four subjects with FPLD2 and 10 control subjects were analysed by optical microscopy. The presence of inflammatory cells was evaluated by immunohistochemistry. Real-time RT-PCR and Western blot were used to evaluate gene and protein levels. RESULTS: Adipocytes from lipodystrophic patients were significantly larger than those of controls, in both the lipomas and perilipoma fat. Lipodystrophic AT exhibited CD68(+) macrophages and CD3(+) lymphocytes infiltration. TP53 expression was reduced in all types of lipomas. At protein level, C/EBPß, p53 and pRb were severely disturbed in both lipodystrophic lipomas and perilipoma fat coming from lipoatrophic areas, whereas the expression of CEBPα was normal. Mitochondrial function genes were less expressed in lipoatrophic fat. In both lipomas and perilipoma fat from lipoatrophic areas, the expression of adipogenes was lower than controls. CONCLUSIONS: Even in lipomas, the adipogenic machinery is impaired in lipodystrophic fat coming from lipoatrophic regions in FPLD2, although the histological phenotype is near-normal, exhibiting low-grade inflammatory features. Our results suggest that the p53 pathway and some adipogenic proteins, such as CEBPα, could contribute to the maintenance of this near normal phenotype in the remnant AT present in these patients.

[Radiofrequency ablation as an alternative treatment for organ confined renal tumor]. / Ablación con radiofrecuencia como alternativa de tratamiento para el tumor renal localizado.

INTRODUCTION: We report our early clinical experience associated with radiofrequency (RF) ablation in patients with renal cell carcinoma (RCC) and evaluate the efficacy, tolerability and complications. MATERIAL AND METHODS: Retrospective review of patients treated in our hospital with kidney ecoguide RF. All of them diagnosed with renal tumor and not candidates for surgery because of bilateral tumor, significant comorbidity or refusal to surgical treatment. We use an Amitech® 220 Watts generator with an electrode tip 3 cm. Straight knitting needles and hooks. Controls were performed with axial tomography at 24h, 7 days, 1, 3 and 6 months and every 6 months thereafter. RESULTS: 11 tumors, 9 patients. The mean age was 76 years (63-85 years). The average tumor size was 3.5 cm (2.2-5.8 cm). In 2 tumors was needed prior chemoembolization. In other two new RF session was needed. 9 tumors with treatment considered effective. Mean follow-up was 17.5 months (3-52 months). One patient had local recurrence at 14 months and needed a laparoscopic radical nephrectomy and two patients developed lung metastases 41.5 months after RF. There were no clinically relevant complications. CONCLUSIONS: In our experience, we believe that RF is considered an alternative treatment for renal tumors with clinical stage T1 or T2 very symptomatic in patients in whom surgery is not possible, with acceptable results in the medium term, a good tolerance, reduced consumption of hospital resources and low complication rate.

Ablación con radiofrecuencia como alternativa de tratamiento para el tumor renal localizado / Radiofrequency ablation as an alternative treatment for organ confined renal tumor

Introducción: Presentamos nuestra serie inicial de tumores renales tratados mediante radiofrecuencia (RF) continua percutánea y evaluamos la eficacia, la tolerabilidad y las complicaciones de la técnica. Material y métodos: Revisión retrospectiva de los pacientes tratados en nuestro hospital con RF renal ecoguiada. Todos diagnosticados de tumor renal y no candidatos a cirugía por tumor bilateral, comorbilidad importante o rechazo al tratamiento quirúrgico. Utilizamos un generador Amitech® de 220W con una punta de electrodo de 3 cm, agujas de punta recta y en gancho. Los controles fueron realizados mediante una tomografía computarizada toracoabdominopélvica a las 24h, a los 7 días, al mes, a los 3 meses y a los 6 meses, y cada 6 meses después. Resultados: Se hallaron 11 tumores en 9 pacientes. La media de edad fue de 76 años (63–85). La media de tamaño tumoral fue de 3,5cm (2,2–5,8). En 2 tumores se necesitó de quimioembolización previa y en otros dos se necesitó una nueva sesión de RF. Hubo 9 tumores con tratamiento considerado como eficaz. La media de seguimiento fue de 17,5 meses (3–52). Un paciente tuvo persistencia de enfermedad a los 3 meses con necesidad de nefrectomía radical laparoscópica y otros dos tuvieron metástasis pulmonares a los 26,5 meses de media. No hubo complicaciones relevantes clínicamente. Conclusiones: En nuestra experiencia, estimamos que la RF es un tratamiento considerado como una alternativa para los tumores renales de estadio clínico T1 o T2 muy sintomáticos, en pacientes en los que no es posible la cirugía, con unos resultados aceptables a medio plazo, una buena tolerancia, un escaso consumo de recursos hospitalarios y un bajo índice de complicaciones (AU)

Introduction: We report our early clinical experience associated with radiofrequency (RF) ablation in patients with renal cell carcinoma (RCC) and evaluate the efficacy, tolerability and complicactions. Material and methods: Retrospective review of patients treated in our hospital with kidney ecoguide RF. All of them diagnosed with renal tumor and not candidates for surgery because of bilateral tumor, significant comorbidity or refusal to surgical treatment. We use an Amitech® 220 Watts generator with an electrode tip 3cm. Straight knitting needles and hooks. Controls were performed with axial tomography at 24h, 7 days, 1, 3 and 6 months and every 6 months thereafter.Results11 tumors, 9 patients. The mean age was 76 years (63–85 years). The average tumor size was 3.5cm (2,2–5,8cm). In 2 tumors was needed prior chemoembolization. In other two new RF session was needed. 9 tumors with treatment considered effective. Mean follow-up was 17.5 months (3–52 months). One patient had local recurrence at 14 months and needed a laparoscopic radical nephrectomy and two patients developed lung metastases 41.5 months after RF. There were no clinically relevant complications. Conclusions: In our experience, we believe that RF is considered an alternative treatment for renal tumors with clinical stage T1 or T2 very symptomatic in patients in whom surgery is not possible, with acceptable results in the medium term, a good tolerance, reduced consumption of hospital resources and low complication rate (AU)

Reduced adipogenic gene expression in fibroblasts from a patient with type 2 congenital generalized lipodystrophy.

AIMS: Beradinelli-Seip congenital generalized lipodystrophy is a rare autosomal recessive disorder characterized by near-complete absence of adipose tissue, Herculean appearance, insulin resistance, hypoleptinaemia and diabetes mellitus. The aim of this study was to investigate the in vitro effects of pioglitazone on the expression of genes involved in adipogenesis in fibroblasts from a patient with this condition due to a seipin mutation. METHODS: Primary cultures of fibroblasts from the skin of the patient were obtained. Fibroblasts were treated with classic adipose differentiation medium, with and without pioglitazone. Several adipogenes were evaluated by real-time reverse transcriptase-polymerase chain reaction and western blotting. Intracellular localization of prelamin A was studied by immunofluorescence microscopy. RESULTS: The expression of the adipogenic genes PPARG, LPL, LEP and SLC2A4 was reduced in lipodystrophic fibroblasts, while treatment with pioglitazone increased the expression of these genes. Moreover, and unexpectedly, we found an accumulation of farnesylated prelamin A in lipodystrophic fibroblasts. CONCLUSIONS: The process of adipocyte differentiation is compromised in patients with Beradinelli-Seip congenital lipodystrophy owing to diminished expression of the regulatory genes involved, which pioglitazone treatment partially rescues. Prelamin A accumulation establishes a link with other types of familial lipodystrophies, as familial partial lipodystrophy.

Pseudoaneurisma de arteria renal tras nefrectomía parcial laparoscópica. Diagnóstico, tratamiento y revisión bibliográfica / Renal artery pseudoaneurysm after partial nephrectomy. Diagnosis, treatment and literature review

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[Malignant fibrous histiocytoma of the bladder. A literature review]. / Histiocitoma fibroso maligno de vejiga. Revisión bibliográfica.

OBJECTIVES: Malignant fibrous histiocytoma (MFH) is an uncommon urinary tract tumor. This paper is intended to provide an update on its diagnostic criteria, pathological and immunohistochemical characteristics, histological classification, prognostic factors, and alternative treatments. MATERIALS AND METHODS: All published articles on MFH of the urinary bladder have been reviewed and a descriptive study has been done. RESULTS: Twenty-nine cases of MFH of the bladder have been reported. The most common morphological variants are storiform-fascicular (41%) and inflammatory (36%) MFH. Non-myxoid variants have a poorer prognosis. Stage T3 MFH was found in 72% of cases at the time of diagnosis. MFH local recurrence and distant metastasis rates were 50% and 25% respectively after surgical treatment only. CONCLUSIONS: MFH of the bladder is a tumor with high local and distant recurrence rates and a low survival rate, and therefore requires early and aggressive treatment. Radical cystectomy with lymphadenectomy and adjuvant radiotherapy is considered to be the treatment of choice, eventually associated to chemotherapy.

Histiocitoma fibroso maligno de vejiga. Revisión bibliográfica / Malignant fibrous histiocytoma of the bladder. A literature review

Objetivos: El histiocitoma fibroso maligno (HFM) es un tumor poco frecuente del tracto urinario. Pretendemos actualizar los criterios diagnósticos, las características anatomopatológicas e inmunohistoquímicas, la clasificación histológica, los factores pronóstico y las alternativas terapéuticas. Material y métodos: Revisión bibliográfica y estudio descriptivo de los casos de HFM de vejiga publicados en la literatura médica internacional. Resultados: Existen 29 casos publicados de HFM de vejiga y las variantes morfológicas más frecuentes son la estoriforme-fascicular (41%) y la inflamatoria (36%). Las variantes no mixoides comportan peor pronóstico. El 72% fue T3 en el momento del diagnóstico. La tasa de recurrencia local y a distancia del HFM de vejiga fue del 50 y del 25%, respectivamente, tras tratamiento exclusivamente quirúrgico. Conclusiones: El HFM de vejiga es un tumor con alta tasa de recurrencia local y a distancia, así como baja supervivencia, requiriendo un tratamiento precoz y agresivo. La cistectomía radical con linfadenectomía y radioterapia adyuvante, con eventual quimioterapia, se considera el tratamiento de elección (AU)

Objectives: Malignant fibrous histiocytoma (MFH) is an uncommon urinary tract tumor. This paper is intended to provide an update on its diagnostic criteria, pathological and immunohistochemical characteristics, histological classification, prognostic factors, and alternative treatments. Materials and methods: All published articles on MFH of the urinary bladder have been reviewed and a descriptive study has been done. Results: Twenty-nine cases of MFH of the bladder have been reported. The most common morphological variants are storiform-fascicular (41%) and inflammatory (36%) MFH. Non-myxoid variants have a poorer prognosis. Stage T3 MFH was found in 72% of cases at the time of diagnosis. MFH local recurrence and distant metastasis rates were 50% and 25% respectively after surgical treatment only. Conclusions: MFH of the bladder is a tumor with high local and distant recurrence rates and a low survival rate, and therefore requires early and aggressive treatment. Radical cystectomy with lymphadenectomy and adjuvant radiotherapy is considered to be the treatment of choice, eventually associated to chemotherapy (AU)

Site-dependent differences in both prelamin A and adipogenic genes in subcutaneous adipose tissue of patients with type 2 familial partial lipodystrophy.

BACKGROUND: Type 2 familial partial lipodystrophy (FPLD2) is characterised by loss of fat in the limbs and buttocks and results from mutations in the LMNA gene. AIM: To evaluate the role of several genes involved in adipogenesis in order to better understand the underlying mechanisms of regional loss of subcutaneous adipose tissue (scAT) in patients with FPLD2. METHODS: In total, 7 patients with FPLD2 and 10 healthy control participants were studied. A minimal model was used to calculate the insulin sensitivity (IS). scAT was obtained from abdomen and thigh by biopsy. Relative gene expression was quantified by real-time reverse transcription PCR in a thermal cycler. Prelamin A western blot analysis was carried out on scAT and prelamin A nuclear localisation was determined using immunofluorescence. Adipocyte nuclei were examined by electron microscopy. RESULTS: Patients with FPLD2 were found to have significantly lower IS. The expression of LMNA was similar in both groups. The expression of PPARG2, RB1, CCND3 and LPL in thigh but not in abdomen scAT was significantly reduced (67%, 25%, 38% and 66% respectively) in patients with FPLD2. Significantly higher levels of prelamin A were found in peripheral scAT of patients with FPLD2. Defects in the peripheral heterochromatin and a nuclear fibrous dense lamina were present in the adipocytes of patients with FPLD2. CONCLUSIONS: In FPLD2 participants, prelamin A accumulation in peripheral scAT is associated with a reduced expression of several genes involved in adipogenesis, which could perturb the balance between proliferation and differentiation in adipocytes, leading to less efficient tissue regeneration.