-Objective: To describe the clinical presentation a group of patients with juvenile onset of Huntington disease. Method: All patients were interviewed following a stru c t u red clinical questioner. Patients were genotyped for the trinucleotide cytosine-adenine-guanine (CAG) repeat in the Huntington Disease gene. High resolution brain MRI was perf o rmed in all patients. Results: We identified 4 patients with juvenile onset of disease among 50 patients with Huntington disease followed prospectively in our N e u rogenetics clinic. Age at onset varied from 3 to 13 years, there were 2 boys, and 3 patients had a paternal inheritance of the disease. Expanded Huntington disease allele sizes varied from 41 to 69 trinucleotide repeats. The early onset patients presented with rigidity, bradykinesia, dystonia, dysarthria, seizures and ataxia. MRI showed severe volume loss of caudate and putamen nuclei (p=0.001) and reduced cerebral and c e rebellum volumes (p=0.01). Conclusion: 8% of Huntington disease patients seen in our clinic had juvenile onset of the disease. They did not present with typical chorea as seen in adult onset Huntington disease. There was a predominance of rigidity and bradykinesia. Two other important clinical features were s e i z u res and ataxia, which related with the imaging findings of early cortical atrophy and cerebellum volume loss.KEY WORDS: n e u rodegenerative disord e r, dynamic mutations, genotype-phenotype correlation, basal ganglia, atrophy. Apresentação clínica da forma juvenil da doença de HuntingtonRESUMO -Objetivo: D e s c rever o quadro clínico de um grupo de pacientes com forma juvenil da doença de Huntington. Método: Os pacientes foram entrevistados seguindo um questionário clínico estru t u r ado; genotipados para a repetição do trinucleotídeo citosina-adenina-guanina (CAG) no gene da doença de Huntington; e realizaram exame de RM de alta re s o l u ç ã o . Resultados: Identificamos 4 pacientes com doença de Huntington de início juvenil dentre 50 pacientes com doença de Huntington seguidos pro s p e ctivamente em nosso ambulatório de neurogenética. A idade de início variou entre 3 e 13 anos (2 meninos e 2 meninas). Três pacientes tiveram herança paterna da doença. O tamanho do alelo expandido da doença de Huntington variou entre 41 a 69 repetições de trinucleotídeos. As principais manifestações clínicas no início da doença foram rigidez, bradicinesia, distonia, disartria, crises epilépticas e ataxia. A RM mostro u acentuada atrofia dos núcleos caudado e putamem (p=0.001) e redução do volume cerebral e cere b e l a r (p=0.01). Conclusão: 8% dos pacientes com doença de Huntington acompanhados em nosso ambulatório apresentaram início juvenil da doença. Estes pacientes não apresentaram a manifestação típica de coréia o b s e rvada em adultos. Houve predomínio de rigidez, bradicinesia, crises epilépticas e ataxia, o que tem relação com a atrofia cortical e cerebelar precoce na RM.
A rapid, sensitive and specific method to quantify bromazepam in human plasma using diazepam as the internal standard (IS) is described. The analyte and the IS were extracted from plasma by liquid-liquid extraction using diethyl ether-hexane (80 : 20, v/v). The extracts were analyzed by high-performance liquid chromatography (HPLC) coupled to electrospray tandem mass spectrometry (MS/MS). Chromatography was performed isocratically on a Genesis C(18) analytical column (100 x 2.1 mm i.d., film thickness 4 microm). The method had a chromatographic run time of 5.0 min and a linear calibration curve over the range 5.0-150 ng ml(-1) (r(2) > 0.9952). The limit of quantification was 5 ng ml(-1). This HPLC/MS/MS procedure was used to assess the bioequivalence of two bromazepam 6 mg tablet formulations (bromazepam from Medley SA Indústria Farmacêutica as the test formulation and Lexotan from Produtos Roche Químico e Farmacêutico SA as the reference formulation). A single 6 mg dose of each formulation was administered to 24 healthy volunteers (12 males and 12 females). The study was conducted using an open, randomized, two-period crossover design with a 3 week washout interval. Since the 90% CI for C(max), AUC(last), AUC(0-240 h) (linear) and AUC((0- infinity )) ratios were all inside the 80-125% interval proposed by the US Food and Drug Administration, it was concluded that the bromazepam formulation from Medley is bioequivalent to the Lexotan formulation for both the rate and the extent of absorption.
Objective: The purpose of this series is to report our experience in managing ureteral trauma, focusing on the importance of early diagnosis, correct treatment, and the impact of associated injuries on the management and morbid-mortality. Materials and Methods: From January 1994 to December 2002, 1487 laparotomies for abdominal trauma were performed and 20 patients with ureteral lesions were identified, all of them secondary to penetrating injury. Medical charts were analyzed as well as information about trauma mechanisms, diagnostic routine, treatment and outcome. Results: All patients were men. Mean age was 27 years. The mechanisms of injury were gunshot wounds in 18 cases (90%) and stab wounds in two (10%). All penetrating abdominal injuries had primary indication of laparotomy, and neither excretory urography nor computed tomography were used in any case before surgery. The diagnosis of ureteric injury was made intra-operatively in 17 cases (85%). Two ureteral injuries (10%) were initially missed. All patients had associated injuries. The treatment was dictated by the location, extension and time necessary to identify the injury. The overall incidence of complications was 55%. The presence of shock on admission, delayed diagnosis, Abdominal Trauma Index > 25, Injury Severity Score > 25 and colon injuries were associated to a high complication rate, however, there was no statistically significant difference. There were no mortalities in this group. Conclusions: A high index of suspicion is required for diagnosis of ureteral injuries. A thorough exploration of all retroperitoneal hematoma after penetrating trauma should be an accurate method of diagnosis; even though it failed in 10% of our cases.
A rapid, sensitive and specific method to quantify nevirapine in human plasma using dibenzepine as the internal standard (IS) was developed and validated. The method employed a liquid-liquid extraction. The analyte and the IS were chromatographed on a C(18) analytical column, (150 x 4.6 mm i.d. 4 microm) and analyzed by tandem mass spectrometry in the multiple reaction monitoring mode. The method had a chromatographic run time of 5.0 min and a linear calibration curve over the range 10-5000 ng ml(-1) (r(2) > 0.9970). The between-run precision, based on the relative standard deviation for replicate quality controls was 1.3% (30 ng ml(-1)), 2.8% (300 ng ml(-1)) and 3.6% (3000 ng ml(-1)). The between-run accuracy was 4.0, 7.0 and 6.2% for the above-mentioned concentrations, respectively. This method was employed in a bioequivalence study of two nevirapine tablet formulations (Nevirapina from Far-Manguinhos, Brazil, as a test formulation, and Viramune from Boehringer Ingelheim do Brasil Química e Farmacêutica, as a reference formulation) in 25 healthy volunteers of both sexes who received a single 200 mg dose of each formulation. The study was conducted using an open, randomized, two-period crossover design with a 3 week washout interval. The 90% confidence interval (CI) of the individual ratio geometric mean for Nevirapina/Viramune was 96.4-104.5% for AUC((0-last)), 91.4-105.1% for AUC((0-infinity)) and 95.3-111.6% for C(max) (AUC = area under the curve; C(max) = peak plasma concentration). Since both 90% CI for AUC((0-last)) and AUC((0-infinity)) and C(max) were included in the 80-125% interval proposed by the US Food and Drug Administration, Nevirapina was considered bioequivalent to Viramune according to both the rate and extent of absorption.
Solid tumors typically contain high levels of fibrillar collagen. The increased stromal collagen deposition usually promotes cancer progression since biochemical and biophysical cues from tumor-associated collagen fibers stimulate neoplastic cells. Few studies have investigated the relationship between Merkel cell carcinoma (MCC) and the extracellular matrix (ECM), but there are no works evaluating collagen.This is an observational, analytical, retrospective study including 11 patients with MCC. Primary tumor-stained sections were evaluated by second harmonic generation microscopy and texture analysis.Peritumoral texture features (area fraction, mean gray value, entropy, and contrast) showed much lower values than normal skin (P < .0001) revealing extensively altered structure of peritumoral collagen fibers. These differences were not significant between tumors with unfavorable and favorable known prognostic factors.Profound changes in collagen fibers present in the stroma accompanying primary MCC may contribute to the aggressive behavior of this tumor. Our results indicate that whatever MCC histological subtype, size or anatomical location, MCC promotes the same type of ECM for its development. As an outlook, therapies using ECM macromolecules or fibroblasts (the architects of ECM remodeling) as target could be useful in the treatment of MCC.
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