Evidence from experimental animal studies show that sex hormones influence the glucocorticoid response to a variety of inflammatory and noninflammatory stimuli. In this study we assessed gender differences in the response of ACTH and cortisol in normal young male and female humans following intravenous infusion of human IL-6 in various dosages. Males presented a significantly stronger ACTH production in response to IL-6 than females. Peak cortisol response, however, was similar in males and females. Cortisol/ACTH ratios were significantly higher in females than in males, both at baseline and after each of the IL-6 dosages. These results suggest that an effective glucocorticoid response requires similar levels of IL-6 in males and females. However, they also suggest that the adrenals of males and females have different sensitivities to ACTH (higher in females) and possibly also to direct IL-6 stimulation.
OBJECTIVE: Mutations of the PROP1 gene lead to combined pituitary hormone deficiency (CPHD), which is characterized by a deficiency of GH, TSH, LH/FSH, PRL and, less frequently, ACTH. This study was undertaken to investigate the molecular defect in a cohort of patients with CPHD. DESIGN, PATIENTS AND MEASUREMENTS: A multicentric study involving 46 cases of CPHD (17 familial cases belonging to seven kindreds and 29 sporadic cases) selected on the basis of clinical and hormonal evidence of GH deficiency, central hypothyroidism and hypogonadotrophic hypogonadism, in the absence of an identified cause of hypopituitarism. Mutations of PROP1 were investigated by DNA sequencing. Clinical, hormonal and neuroradiological data were collected at each centre. RESULTS: PROP1 mutations were identified in all familial cases: five kindreds presented a c. 301-302delAG mutation, one kindred presented a c. 358C --> T (R120C) mutation and one presented a previously unreported initiation codon mutation, c. 2T --> C. Of the 29 sporadic cases, only two (6.9%) presented PROP1 germline mutations (c. 301-302delAG, in both). Phenotypic variability was observed among patients with the same mutations, particularly the presence and age of onset of hypocortisolism...
Os bezoars gastrointestinais são achados relativamente raros, apresentando uma variação regional na sua distribuição relacionada com diferenças na ingestão de alimentos ricos em fibras. A sua verdadeira incidência é desconhecida. A sua ocorrência apresenta uma tendência crescente, em provável relação com a maior taxa de cirurgias gastroduodenais realizadas no último século, consideradas factores de risco para a sua formação. Os autores apresentam o caso de um doente com antecedentes de cirurgia gastroduodenal, com quadro clínico caracterizado por vómitos alimentares, dor e distensão abdominal, paragem de emissão de fezes, anorexia e perda ponderal. O estudo complementar levantou a suspeita da existência de dois bezoars, um gástrico e um intestinal, a qual foi confirmada por laparotomia.Gastrointestinal bezoars are relatively uncommon findings and its distribution has a regional variation that correlates with differences in fibre enriched alimentary products ingestion. Its true incidence is unknown but its occurrence shows a growing tendency, which is probably related with the higher number of gastroduodenal surgeries performed in the past century, considered to be risk factors for bezoar formation. The authors present the case of a patient with a past history of gastric and duodenal surgery...
BACKGROUND & AIMS: Hereditary diffuse gastric cancer (HDGC) families carry CDH1 heterozygous germline mutations; their tumors acquire complete CDH1 inactivation through "2nd-hit" mechanisms. Most frequently, this occurs via promoter hypermethylation (epigenetic modification), and less frequently via CDH1 mutations and loss of heterozygosity (LOH). We quantified the different 2nd hits in CDH1 occurring in neoplastic lesions from HDGC patients.
METHODS: Samples were collected from 16 primary tumors and 12 metastases from 17 patients among 15 HDGC families; CDH1 mutations, LOH, and promoter hypermethylation were analyzed. E-cadherin protein expression and localization were determined by immunohistochemistry.
RESULTS: Somatic CDH1 epigenetic and genetic alterations were detected in lesions from 80% of HDGC families and in 75% of all lesions analyzed (21/28). Of the 28 neoplastic lesions analyzed, promoter hypermethylation was found in 32.1%, LOH in 25%, both alterations in 17.9%, and no alterations in 25%. Half of the CDH1 2nd hits in primary tumors were epigenetic modifications, whereas a significantly greater percentage of 2nd hits in metastases were LOH (58.3%; P = .0274). Different neoplastic lesions from the same patient frequently displayed distinct 2nd-hit mechanisms. Different 2nd-hit mechanisms were also detected in the same tumor sample.
CONCLUSION: The 2nd hit in CDH1 frequently occurs via epigenetic changes in HDGC primary tumors and LOH in metastases. Because of the concomitance and heterogeneity of these alterations in neoplastic lesions and the plasticity of hypermethylated promoters during tumor initiation and progression...
PURPOSE: To evaluate the efficacy of a selective cyclooxygenase-2 (COX-2) inhibitor in rat bladder cancer chemoprevention, as well as to assess the relevance of inflammation, proliferation and oxidative stress in tumor growth and in its prevention.
RESULTS: The main findings were: (I) the incidence of carcinoma was: control: 0% (0/8); BBN: 65% (13/20); CEL: 0% (0/8) and BBN + CEL: 12.5% (1/8); (II) the mean tumor volume per rat with tumor and per tumor were significantly lower in the BBN + CEL group (21.2 and 5.3 +/- 0.4 mm(3)) vs. BBN (138.5 +/- 7.5 and 112.5 +/- 6.4 mm(3)); (III) the incidence of pre-neoplasic (hyperplasia and dysplasia) and neoplasic (papillary tumors and carcinoma in situ-CIS) lesions were notoriously reduced in the CEL + BBN treatment; (IV) CEL significantly reduced serum TGFbeta1 and CRP and increase TNFalpha and IL-1beta (p < 0.001); (V) CEL reduced MDA formation in serum (p < 0.001) and liver (p < 0.05) and also showed a trend to reduction in kidney.
METHODS: Drug treatments were performed during the first 8 w, followed by 12 w for tumor expression/prevention, in the following groups: control-vehicle; carcinogen-0.05% of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN); celecoxib (CEL)-10 mg/kg/day and preventive CEL + BBN. The bladders were analyzed for number and volume of tumor and nature of urothelium lesions. Serum was assessed for markers of inflammation...
O tratamento da artrite reumatóide assenta no trabalho de uma equipa multidisciplinar constituída por reumatologistas, ortopedistas, fisiatras e anestesistas, entre outros. A intervenção cirúrgica representa, apenas, uma das etapas da planificação do tratamento global do doente.
A cirurgia na artrite reumatóide deve ser reservada para os doentes que não respondam satisfatoriamente a um tratamento médico bem conduzido, e deve ser efectuada, de um modo geral, nos estádios iniciais da doença, por forma a permitir alcançar o melhor resultado.
Se assim não acontecer, se o doente não for operado em tempo útil, estabelecem-se lesões das partes moles irreversíveis, cujo tratamento conduz, naturalmente, a um resultado menos conseguido, apesar das modalidades cirúrgicas de elevada eficácia terapêutica que actualmente dispomos.
Com a cirurgia pretende-se, de um modo geral e numa ordem de prioridades decrescentes, aliviar/suprimir a dor, melhorar a função, prevenir as destruições, corrigir as deformidades e melhorar a estética. O objectivo final a conseguir é a reintegração sócio-profissional do doente, nas melhores condições que for possível.
A determinação das prioridades cirúrgicas é um problema específico da artrite reumatóide. A decisão de onde...
The weak central coherence hypothesis represents one of the current explanatory models in Autism Spectrum Disorders (ASD). Several experimental paradigms based on hierarchical figures have been used to test this controversial account. We addressed this hypothesis by testing central coherence in ASD (n = 19 with intellectual disability and n = 20 without intellectual disability), Williams syndrome (WS, n = 18), matched controls with intellectual disability (n = 20) and chronological age-matched controls (n = 20). We predicted that central coherence should be most impaired in ASD for the weak central coherence account to hold true. An alternative account includes dorsal stream dysfunction which dominates in WS. Central coherence was first measured by requiring subjects to perform local/global preference judgments using hierarchical figures under 6 different experimental settings (memory and perception tasks with 3 distinct geometries with and without local/global manipulations). We replicated these experiments under 4 additional conditions (memory/perception*local/global) in which subjects reported the correct local or global configurations. Finally, we used a visuoconstructive task to measure local/global perceptual interference. WS participants were the most impaired in central coherence whereas ASD participants showed a pattern of coherence loss found in other studies only in four task conditions favoring local analysis but it tended to disappear when matching for intellectual disability. We conclude that abnormal central coherence does not provide a comprehensive explanation of ASD deficits and is more prominent in populations...
To provide new insights into the pathophysiology, prevention and diagnosis of cerebral venous thrombosis (CVT) associated with iatrogenic cerebrospinal fluid (CSF) leaks and/or external CSF drainage.
Case report and literature review.
We describe the case of a 30-year-old woman who developed a CSF fistula after lumbar spinal surgery. The treatment included rest, hydration, caffeine, and continuous lumbar CSF drainage. After closure of the fistula, the patient complained of severe orthostatic headache. Thrombosis involving the superior sagittal sinus, the right transverse sinus, the right sigmoid sinus, and the right jugular vein was diagnosed after neurological deterioration.
A few reports have associated CVT with various forms of spinal meningeal injury. However, it has been rarely documented following spinal surgery complicated by accidental durotomy and/or external lumbar CSF drainage. CSF hypovolemia may precipitate CVT in patients having prothrombotic risk factors. Patients who have or had CSF leaks and/or lumbar CSF drains who present with symptoms of intracranial CSF hypotension should remain in the horizontal position to prevent CVT. In that context, the diagnosis of CVT depends on a high degree of suspicion.