Familial parathyroid tumours-comparison of clinical profiles between syndromes.

INTRODUCTION: Primary hyperparathyroidism (PHPT) caused by parathyroid tumours is mostly sporadic, with a genetic cause identified in 5-10% of cases. Familial parathyroid tumours can be included in complex syndromes, such as multiple endocrine neoplasia (MEN) type 1, 2A and 4 or hyperparathyroidism-jaw tumour syndrome (HPT-JT). OBJECTIVE: Characterisation of the familial parathyroid tumours followed-up at our centre and comparison of the different clinicopathological manifestations between the syndromes. METHODS: Retrospective analysis of 48 patients with familial parathyroid tumours harbouring RET (n = 11), CDC73 (n = 20) and MEN1 (n = 17) germline mutations was performed. RESULTS: Cases of PHPT in MEN2A syndrome presented with lower serum PTH (sPTH) and serum calcium (sCa) levels at diagnosis (sPTH = 108.0 (IQR 53.3) pg/mL, sCa = 10.6 ± 1.1 mg/dL) than MEN1 (sPTH = 196.9 (IQR 210.5) pg/mL, sCa = 11.7 ± 1.2 mg/dL) (p = 0.01, p = 0.03, respectively) or HPT-JT cases (sPTH = 383.5 (IQR 775.8) pg/mL, sCa = 12.9 ± 1.8 mg/dL) (p = 0.01; p < 0.001, respectively). There was a statistical difference in sCa levels between MEN1 and HPT-JT (p = 0.02), but not between sPTH (p = 0.07). The predominant first manifestation of the syndrome in MEN1 was gastroenteropancreatic neuroendocrine tumour (GEP-NET) in 47.1% of the cases, in MEN2A was medullary thyroid cancer (90.9%) and in HPT-JT was PHPT in 85% patients. In MEN1 syndrome, the number of affected parathyroid glands was significantly higher than in MEN2A (p < 0.001) and HPT-JT (p = 0.01). CONCLUSION: The first manifestation of the syndrome in MEN1 cases was GEP-NET and not PHPT. Although presenting at similar ages, patients with MEN2A exhibit less severe biochemical and clinical PHPT at diagnosis than the other familial syndromes.

Erectile dysfunction association with physical activity level and physical fitness in men aged 40-75 years.

The aim of this study is to evaluate the association between physical activity level and physical fitness with erectile dysfunction in men aged 40-75 years. We examined 180 men aged 40-75 years. The individuals were evaluated for age, presence of dyslipidemia and smoking and for anthropometric parameters for the characterization of body mass index. For assessing the level of physical fitness, a test was performed to measure the indirect maximum oxygen consumption. The evaluation of erectile function was made by the International Index of Erectile Function questionnaire and assessment of physical activity level by the International Physical Activity questionnaire in its short version. This study showed that younger men with higher physical activity and better physical fitness are less likely to suffer from erectile dysfunction. Multivariable analysis through logistic regression showed that age (odds ratio (OD)=1.15; 95% confidence interval (95% CI)=1.07-1.23), physical activity (OD=10.38; 95% CI=3.94-27.39) and physical fitness (OD=4.62; 95% CI=1.75-12.25) were independent variables associated with erectile dysfunction. This study reinforces the concept that healthy habits have a direct effect on erectile function.

Anticonvulsant and sodium channel-blocking properties of novel 10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide derivatives.

A series of esters of the major metabolite of oxcarbazepine (2), 10, 11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide, were synthesized and evaluated for their anticonvulsant and brain sodium channel-blocking properties. The compounds were assayed intraperitoneally and per os in rats against seizures induced by maximal electroshock (MES). Neurologic deficit was evaluated by the rotarod test. The enantiomeric acetates (R)-11 and (S)-12 were the most active of the series against MES-induced seizures with oral ED(50) values at t(max) of 10.9 +/- 2.3 and 4.7 +/- 0.9 mg/kg, respectively. After intraperitoneal administration, carbamazepine (1) behaved more potently than 2 and all other new dibenz[b, f]azepine-5-carboxamide derivatives in the MES test; compounds 2 and 12 were equally potent. In the rotarod test, low doses of 1 produced considerable motor impairment, which did not occur with 2, enantiomeric alcohols (S)-6, (R)-7, and racemic alcohol 8, or racemic acetate 10 or (R)-11. The potencies of the racemic and enantiomerically pure alcohols 8, (S)-6, and (R)-7 derived from 2 in the MES and rotarod test were found to be similar between them, and consequently they exhibit similar protective index values. All three forms of the alcohol and their corresponding acetates (pairs 8 & 10, 6 & 12, and 7 & 11) were found to differ in the MES or rotarod tests; the ED(50) value for (S)-6 against MES-induced seizures was nearly 3-fold that for (S)-12. The protective index also differed markedly between all stereoisomers of the alcohol and their corresponding acetates, most pronouncedly for compound (S)-12 which attained the highest value (12.5) among all compounds tested. Blockade of voltage-sensitive sodium channels was studied by investigating [(3)H]batrachotoxinin A 20-alpha-benzoate ([(3)H]BTX) binding. Acetates (R)-11 and (S)-12 were more potent than the standards 1 and 2 at inhibiting the binding of [(3)H]BTX to sodium channels and the influx of (22)Na(+) into rat brain synaptosomes. It is concluded that acetates (R)-11 and (S)-12 are not simple metabolic precursors of alcohols (R)-7 and (S)-6 in rodents but that they possess anticonvulsant and sodium channel-blocking properties in their own right.

Immunological responsiveness to M. leprae and BCG antigens in 98 leprosy patients and their household contacts

The cellular immune response to M. leprae and BCG antigens was evaluated in 98 leprosy patients and 143 household contacts lacking clinical manifestation of the disease. The proliferative responses and release of Interferon-gamma by peripheral blood mononuclear cells were assessed and both patients and contacts were classified as low or high responders to M. leprae. The high responder contacts constitued 54.8% of the population analyzed, a three times higher proportion when compared to the controls, indicating the possible existence of active infection among them. The correlation coefficient between the immunological response to M. leprae and BCG was found to be higher within the contact group than in the patients, suggesting that cross-reactivity defense mechanisms against mycobacteria exist even before the onset of clinical detectable disease

[Correlation of skin tests and the production of gamma-interferon in leprosy patients]. / Correlação entre testes cutâneos e produção de Y-IFN en pacientes com hanseníase.

The responsiveness of 25 leprosy patients to an in vitro correlate of cell-mediated immunity to M. leprae antigen, (the production of Y-IFN by peripheral blood mononuclear cells) was compared to their response to skin tests routinely used to evaluate cell-mediated immunity to a number of antigens including M. leprae. The results indicate that among the polar lepromatous patients (LL) there was a clear correlation between low responses in the in vitro assay (Y-IFN production), negative skin test to the specific antigen (Mitsuda reaction) and low responses to skin tests to a related antigen (PPD). There was no correlation in the other clinical groups with skin tests to other unrelated antigens.

Immunological responsiveness to M. leprae and BCG antigens in 98 leprosy patients and their household contacts.

1. The cellular immune response to M. leprae and BCG antigens was evaluated in 98 leprosy patients and 143 household contacts lacking clinical manifestation of the disease. 2. The proliferative responses and release of Interferon-gamma by peripheral blood mononuclear cells were assessed and both patients and contacts were classified as low or high responders to M. leprae. 3. The high responder contacts constituted 54.8% of the population analyzed, a three times higher proportion when compared to the controls, indicating the possible existence of active infection among them. 4. The correlation coefficient between the immunological response to M. leprae and BCG was found to be higher within the contact group than in the patients, suggesting that cross-reactivity defense mechanisms against mycobacteria exist even before the onset of clinically detectable disease.

Linfogranuloma venereo. Estudo de casos e teste de Frei. / Lymphogranuloma venereum: study of cases and Frei's test

Foi realizado teste de Frei em 55 pacientes distribuidos em tres grupos: portadores de linfogranuloma venereo, pacientes com outras doencas sexualmente transmitidas e grupo controle. A reacao de Frei foi interpretada de acordo com a condicao epidemiologica de cada grupo. O objetivo principal do trabalho e estimar a incidencia da infeccao subclinica no grupo de pacientes com outras doencas sexualmente transmitidas, somando-se observacoes de linfogranuloma venereo