Granuloma annulare and necrobiosis lipoidica in a patient with HNF1A-MODY

SUMMARY Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic forms of diabetes mellitus with distinct clinical features. Clinical dermatological phenotypes in MODY patients are very rare in literature. This report describes a patient with HNF1A-MODY presenting with necrobiosis lipoidica (NL) and granuloma annulare (GA). A 39-year-old asymptomatic woman, with atypical diabetes diagnosed at age 17, has a confirmed HNF1A mutation on exon 2 (c.392G>A, p.R131Q), classified as Pathogenic by the ACMG guidelines. She has reasonable metabolic control using oral anti-diabetic medications and has no chronic diabetic complications. Clinical and histologic diagnoses of both NL and GA were made. We discuss these conditions and their association with MODY.

Does [18F]F-FDG-PET/MRI add metabolic information to magnetic resonance image in childhood-onset Takayasu's arteritis patients? A multicenter case series

Abstract Background: The observation that 2-deoxy-2[18F]fluoro-D-glucose-positron emission tomography/magnetic resonance imaging ([18F]F-FDG-PET/MRI) revealed high-grade arterial wall FDG uptake, without arterial wall thickening with contrast-enhancement, in a considerable number of c-TA patients in our previous study, encouraged us to compare patients with both PET and MR angiography (MRA) positives, with those with PET positive but MRA negative. Our aim was to evaluate the relevance of these two imaging modalities together. Methods: A three-center cross-sectional study with 17 patients who fulfilled the EULAR/PRINTO/PReS criteria for c-TA and who underwent [18F]F-FDG-PET/MRI was previously performed. Herein we compared patients/vessels with positive PET (arterial wall 18F-FDG uptake higher than liver) and positive MRA (arterial wall thickening with contrast-enhancement)—group 1, with those with positive PET but negative MRA—group 2. Results: Median disease duration of 17 c-TA patients was 10.4 years. Nine patients were classified as group 1 and six as group 2. Median of metabolic inflammatory volume (MIV) of all arterial segments was significantly higher in group 1 (2346 vs. 1177 cm3; p = 0.036). Fifty-four (19%) from 284 available arterial segments presented positive findings in vessel wall in one or both images. Positive findings were concordant between PET and MRA in only 13% arterial segments (group 1); most changes (28-59.6%) that were discordant between both images, were positive in PET and negative in MRA (group 2). Conclusions: Our study demonstrated that [18F]F-FDG-PET/MRI added information about inflammation in vessel wall of c-TA patients. Prospective multicenter studies are needed in order to get solid data to guide immunosuppressive tapering and withdrawal.

Searching for mutations in the HNF1B gene in a Brazilian cohort with renal cysts and hyperglycemia

ABSTRACT Objective To verify the presence of variants in HNF1B in a sample of the Brazilian population selected according to the presence of renal cysts associated with hyperglycemia. Subjects and methods We evaluated 28 unrelated patients with clinical suspicion of HNF1B mutation because of the concomitant presence of diabetes mellitus (DM) or prediabetes and renal cysts. Genotyping was accomplished using Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA). In positive cases, available relatives were recruited. Results We found two patients with HNF1B mutations. The first presented the variant p.Pro328Leufs*48(c.983delC) and had DM, renal cysts, and hypomagnesemia. The second presented a heterozygous whole gene deletion in HNF1B, DM, renal cysts, body and tail pancreatic agenesis, and hypomagnesemia; this alteration was also found in his two siblings and his father. Conclusion The recruitment of suspected cases of HNF1B gene mutations in Brazilians due to hyperglycemia and renal cysts presents two positive cases. Our cases contribute to the annotation of clinical and biochemical phenotypes of this rare form of maturity-onset diabetes of the young (MODY).

More than kin, less than kind: one family and the many faces of diabetes in youth

SUMMARY Identification of the correct etiology of diabetes brings important implications for clinical management. In this report, we describe a case of a 4-year old asymptomatic girl with diabetes since age 2, along with several individuals in her family with different etiologies for hyperglycemia identified in youth. Genetic analyses were made by Sanger sequencing, laboratory measurements included HbA1c, lipid profile, fasting C-peptide, pancreatic auto-antibodies (glutamic acid decarboxylase [GAD], Islet Antigen 2 [IA-2], and anti-insulin). We found a Gly178Ala substitution in exon 5 of GCK gene in three individuals co-segregating with diabetes, and type 1 diabetes was identified in two other individuals based on clinical and laboratory data. One individual with previous gestational diabetes and other with prediabetes were also described. We discuss difficulties in defining etiology of hyperglycemia in youth in clinical practice, especially monogenic forms of diabetes, in spite of the availability of several genetic, laboratory, and clinical tools.

ADIPOQ and adiponectin: the common ground of hyperglycemia and coronary artery disease? / ADIPOQ e adiponectina: base comum da hiperglicemia e doença arterial coronariana?

Plasma adiponectin and the coding gene for adiponectin, ADIPOQ, are thought to explain part of the interaction between obesity, insulin resistance, type 2 diabetes (T2DM) and coronary artery disease (CAD). Here, we illustrate the role that adiponectin and ADIPOQ variants might play in the modulation of CAD, especially in the occurrence of hyperglycemia. Recent evidence suggests that total and high molecular weight (HMW) adiponectin levels are apparent markers of better cardiovascular prognosis in patients with low risk of CAD. However, in subjects with established or high risk of CAD, these levels are associated with poorer prognosis. We also provide recent evidences relating to the genetic control of total and HMW adiponectin levels, especially evidence regarding ADIPOQ. Accumulated data suggest that both adiponectin levels and polymorphisms in the ADIPOQ gene are linked to the risk of CAD in patients with hyperglycemia, and that these associations seem to be independent from each other, even if adiponectin levels are partly dependent on ADIPOQ.

Os níveis plasmáticos de adiponectina e o gene codante desta proteína, ADIPOQ, parecem explicar parte da interação de doenças como obesidade, resistência à insulina, diabetes melito tipo 2 (DM2) e doença arterial coronariana (DAC). Apresentamos as evidências do papel tanto dos níveis de adiponectina quanto das variantes no ADIPOQ na modulação da DAC, sobretudo na presença de hiperglicemia. Estudos recentes sugerem que níveis de adiponectina total e de alto peso molecular (HMW) são marcadores de bom prognóstico DAC, sobretudo em pacientes de baixo risco cardiovascular, enquanto nos pacientes de alto risco ou com doença já estabelecida podem se associar com pior prognóstico. Apresentamos também as evidências em relação ao possível controle genético dos níveis circulantes de adiponectina, tanto total quanto da isoforma de alto peso molecular, sobretudo em relação ao ADIPOQ. A análise global dos dados sugere que tanto os níveis circulantes de adiponectina quanto polimorfismos no gene ADIPOQ estão implicados na evolução de DAC em pacientes com hiperglicemia e que essas associações podem existir de forma independente.

Macroangiopatia diabética coronariana precoce no diabetes do jovem: relato de dois casos / Early-onset diabetic coronary macroangiopathy in young diabetes: two case reports

A macroangiopatia é multifatorial. No diabetes melito (DM) é mais grave e está frequentemente relacionada à nefropatia, sendo a principal causa de mortalidade em ambos os tipos de DM. Apesar disso, é pouco estudada no jovem com DM. Apresentamos dois casos de diabéticas jovens com coronariopatia precoce. Caso 1, 40a., branca, DM tipo 2 há 21a., tratada com sulfoniluréias até os 25a., foi insulinizada devido a gestação. Desenvolveu pré-eclâmpsia, porém o parto ocorreu a termo. Permaneceu com macroproteinúria (0,99g/24h), evoluindo para insuficiência renal (clearance 52,7mg/min) (tratamento conservador). Aos 36a., apresentou infarto agudo do miocárdio (IAM). Constatada lesão tri-arterial grave, sofreu revascularização. Caso 2, 34a., negra, DM tipo 1 há 24a., diagnóstico em cetoacidose diabética. Com mau controle metabólico crônico (HbA1c persistentemente acima de 4 pontos percentuais além do limite superior da normalidade), evoluiu com microalbuminúria (0,26g/24h) aos 22a., após gestação. Desenvolveu macroproteinúria (1,7g/24h) após a 2ª. gestação. Aos 31a. iniciou quadro de angina estável. Foi indicada revascularização após cinecoronariografia. Estes dois casos de macroangiopatia em pacientes com DM de diagnóstico na juventude mostram uma rápida progressão no desenvolvimento da coronariopatia, sugerindo uma abordagem multifatorial, agressiva e precoce, independente da sua etiologia.

Body mass index, allergic rhinitis and asthma in children.

Objective To assess the possible relationship of bodyweight and body mass index (BMI) to childhood asthma and allergic rhinitis. Setting Chilaw divisional secretariat area. Design Prospective observational study. Method Children aged 13-14 years in 20 out of 22 schools were assessed from April to June 2003 using the internationally validated ISAAC questionnaire on asthma and allergies. The children and parents filled the questionnaire. Height and weight of children were measured using a standardized procedure. Reference ranges for the normal BMI data were obtained from reference growth charts of Ministry of Health. Data was analysed using Epi info version 6.0. Results Total number of children recruited was 866. 185 (21%) gave a positive response to ever having had wheezing. Allergic rhinitis was found in 233 [27%]. Only 97 [11%] had both asthma and allergic rhinitis. The BMI was 85th centile in 41 (4.7%). Conclusion No significant association was found between BMI and asthma/allergic rhinitis in 13-14 year old school children in the Chilaw area.

Effect of antihypertensive agents on stellate cells during liver regeneration in rats

BACKGROUND: Although most studies have focused on the hepatocytes, all the hepatic cells participate in the regenerative process, among them the stellate cells. The stellate cells are mesenchymal cells involved in local neurotransmission and paracrine regulation of several liver functions. Acute hepatic tissue loss promotes the proliferation and activation of stellate cells from a quiescent state to myofibroblast-like cells. AIM: Investigate the effects of antihypertensive agents on the stellate cell population during the liver regenerative phenomenon in rats. METHODS: Adult male Wistar rats received lisinopril, losartan, bradykinin, or saline solution in a proportional volume, intraperitoneally, before and after 70 percent partial hepatectomy. Animals from the experimental and saline groups were sacrificed at 36 hours after partial hepatectomy. The alpha-smooth muscle actin labelled stellate cells population was counted in the periportal and pericentral zones of the liver specimen. RESULTS: The labelled stellate cells were more numerous in the control group both in the periportal and pericentral zones at 36 hours after partial hepatectomy than at the other times. The population of stellate cells was significantly lower in the losartan group and higher in the bradykinin and lisinopril groups than in the control group. CONCLUSIONS: These results suggest that losartan can inhibit and bradykinin and lisinopril can stimulate the stellate cell population during liver regeneration in rats. These cells synthesize several substances to stimulate liver regeneration.

Audit of stroke care at the Institute of Neurology, National Hospital of Sri Lanka, 1994-1997.

OBJECTIVE: To audit the process of stroke care. DESIGN: Retrospective case record evaluation using an audit package designed by the Royal College of Physicians of London. SETTING: Institute of Neurology, National Hospital of Sri Lanka, Colombo. PATIENTS: 263 patients with stroke admitted over a period of 3 years. MEASUREMENTS: Documentation of 60 audit items related to 13 aspects of stroke care. RESULTS: The process of care was considered 'very good' for only 11 (18.3%), and 'good' for only 9 (15%) of the audit items. Care was 'average' for 5 (8.3%), 'poor' for 9 (15%) and 'very poor' for 26 (43.3%) of the items. CONCLUSIONS: Stroke care was suboptimal in many aspects. Care related to rehabilitation oriented neurological assessments, initiation of secondary preventive measures, rehabilitation planning and discharge planning were especially deficient. Competing interests: none declared. Some of the data reported in this paper have been presented at the Annual Scientific Sessions of the Sri Lanka Medical Association, 1998.

A case of hereditary sensory and autonomic neuropathy (HSAN) type II.

We describe a case of hereditary sensory and autonomic neuropathy (HSAN) type II in a child with a penetrating foot ulcer, acral sensory impairment, and anhidrosis. This is the first documentation of HSAN in Sri Lanka.

Efeito de agentes anti-hipertensivos sobre as células estreladas durante a regeneraçäo hepática em ratos / Effect of antihypertensive agents on the starry cells during hepatic regeneration in rats

O efeito de um inibidor da enzima conversora da angiotensina (lisinopril), de um antagonista do receptor da angiotensina II (losartan) e da bradicinina na população de células estreladas (CE) durante o fenômeno regenerativo hepático foi estudado. Ratos machos Wistar receberam lisinopril, losartan, bradicinina ou solução salina em volumes proporcionais, intraperitonealmente, antes e após hepatectomia parcial a 70 por cento (HP). Cinco animais de cada grupo experimental e controle foram sacrificados sob anestesia com éter em 36 horas após a HP. A população de CE marcadas para alfa-actina de músculo liso foi estimada nas zonas periportal e pericentral das amostras hepáticas. A população de CE foi menor no grupo tratado com losartan, e maior nos grupos tratados com bradicinina e lisinopril que no grupo controle. Estes resultados sugerem que o losartan pode inibir, e a bradicinina e o lisinopril podem estimular a população de CE durante a regeneração hepática em ratos.

A case of eosinophilic meningitis.

A case of eosinophilic meningitis is reported, a condition not previously reported from Sri Lanka. We propose Angiostrongylus cantonesis to be the most likely causative agent in this patient.

Cerebral ventricle sites involved in the central hypertensive response to acetylcholine in unanesthetized rats

It is well known that the injection of acetylcholine (ACh) into the lateral ventricles of the brain (ICV) causes blood pressure increases in unanesthetized rats. However, the actual brain nuclei involved in the mediation of the pressor response to ACh are yet unknown. We report doserelated pressor responses when ACh was injected into the III ventricle or the cerebral aqueduct of similar magnitude to those observed after ICV injection of ACh. No blood pressure effects were observed after the injection of ACh into the IV ventricle. Obstructions of selected ventricular spaces with plugs of Nivea cream were performed to identify the ventricular area involved in the pressor response to ICV-injected ACh. Obstructions of the III ventricle or the aqueduct were similarly effective in significantly reducing the pressor response to ACh injected into the lateral ventricle. Obstructions of the IV ventricle did not affect the pressor response to ICV-injected ACh. The results with the injection of ACh into different ventricular spaces and the occlusion of delimited portions of the ventricular spaces suggest: 1) That prosencephalic, diencephalic as well as rhombencephalic nuclei play a minor role in the mediation of the pressor response to ICV-injected ACh, and 2) that the major site involved in the pressor response to ACh is located in a brain area close to the cerebral aqueduct.

Epidemiology of Chagas' heart disease

Chagas' disease is a major public health problem in Latin America. About 16 million persons are affected and 90 million others are exposed to the risk of being infected by the parasite. The knowledge of epidemiological aspects of the disease allowed to delineate the strategies for the control of the disease related with the vectorial transmission. However, these strategies have had no priority in all endemic countries. Rural-urban migration in most endemic areas carried infected individuals to urban centers increasing the problem of Chagas' disease by blood transfusion. In Brazil the control program has reached good results in the last years and in several states the vectorial transmission was controlled. More recently, hemotherapic practices are performed using screening procedures but this practice must be improved in order to eliminate the possibility of Chagas' disease transmission by another ways (congenital, accidental, oral, etc.). An adequate health care to the infected persons must be improved in order to diminish the social costs of the severe cardiopathy which has been responsible for the adults premature deaths.

Parasitismo natural de bufalinos em Botucatu, SP, Brasil: III. Dinâmica do parasitismo gastro-intestinal em vacas e suas crias / Natural parasitsm of buffalo cows in Botucatu, SP, Brazil: III. Dynamics of gastro-intestinal parasitism in cows and calves

Natural parasitism of buffalo cows in Botucatu, SP, Brazil - III. Dynamics of gastro-intestinal parasitism in cows and calves - Gastro-intestinal parasitism of 24 buffalo cows before parturition, and post-parturition, their infection and that of their respective calves during the following 30 weeks were studied. Willis, Hoffmann and whenever possible, the modified Gordon & Whitlock techniques were used for fecal examinations. Toxocara vitulorum eggs were the earliest forms encountered in calves feces, as follows: during the 1st week after birth, 58.33% of the calves were positive, and in the 4th week, 100% of these animals were positive. Eggs of Strongyloides sp were in the 1st week after birth in two of the calves and in the 5th week, all for them were positive. The next parasites to appear were the Coccidia of which oocysts were detected in the feces of two calves in the 2nd week after birth, and 58.33% of the calves were positive for these in the 3rd week, and in the 6th week, all calves shed oocysts in their feces. On the other hand, eggs of Strongylids were the last forms to appear in calves feces. However, despite their sporadic appearance in the feces, eggs of these parasites were observed continuously from the 11th week onwards, and at this point, the percentage of positive samples began to increase to reach its peak. Relatively to adult animals, eggs of T. vitulorum were observed in the feces of 11 cows, one or twice at most; eggs of Strongyloides sp were seen only once in the feces of four buffalo cows and eggs of Strongylids in 21 out of 24 cows. Oocysts of Coccidia were observed in 16 cows. Mechanisms of infestation of calves with these parasites are discussed

Chromosomes of Pomacea sp (Perry, 1811) (Mesogastropoda, Mollusca)

O estudo cariótípico em Pomacea sp é importante em virtude das grandes dificuldades taxonômicas apresentadas por este gênero e também por ser utilizado em experiências como controlador biológico da Biomphalaria glabrata, hospedeiro intermediário do Schistosoma mansoni. A técnica utilizada para a obtençäo de metáfase foi a de suspensäo celular, elabroada em nosso laboratório. O cariótipo foi obtido em preparaçöes realizadas com embriöes, no estágio de veliger jovem. Esta espécie possui o numero diplóide de 2n=28 cromossomos constituído de 9 pares metacêntricos, 4 pares submetacêntricos e 1 par subtelocêntrico. O braço curto do par subtelocêntrico se mostrou positivo ao AgNO3, local da constriçäo secundária (RON). A análise meiótica confirmou a presença de n=14 cromossomos

CNS catecholaminergic mechanisms in cardiovascular control

Existem evidências conclusivas da participaçäo de catecolaminas na mediaçäo central da pressäo arterial. A atuaçäo das catecolaminas estende-se a todos os segmentos do controle cardiovascular pelo SNC, envolvendo tanto a ativaçäo dos sistemas nervosos simpático e hipotalâmicos-neurohipofisário quanto modulaçäo da atividade vagal parassimpática. A seletividade dessa atuaçäo difusa é garantida pela multiplicidade de receptores envolvidos, possibilitando atuaçäo tanto inibitória quanto excitatória das catecolaminas em um mesmo neurônio. A ativaçäo desses receptores pode causar tanto elevaçäo da pressäo arterial como respostas hipotensoras, dependendo da espécie animal estudada, do sitio de administraçäo ou da utilizaçäo ou näo de anestésicos. Entretanto, existem evidências indicativas de que mecanismos alfa2-centrais estariam preferencialmente envolvidos na mediaçäo de respostas hipotensoras, enquanto mecanismos alfa1-atuariam mediando respostas hipertensoras. Por outro lado, o papel desempenhado por receptores ß-adrenérgicos centrais é ainda controvertido, envolvendo sua participaçäo tanto em respostas pressoras quanto depressoras