ADC mapping and (1)H MR spectroscopy reveal abnormally high free-water concentrations in the WM of patients with merosin-deficient CMD.

This series of patients demonstrated that there was no correlation between the extent of WM abnormality on MRI and the clinical status and degree of merosin deficiency (partial or total). Bilateral WM involvement was seen to be more prominent in the parietal, frontal, and temporal regions of the brain. The brain stem and internal and external capsules were less affected. Cerebellar WM involvement is rare. Changes on follow-up imaging studies did not correlate with the clinical status of the patient.

-We describe five patients with Schwartz-Jampel syndrome (SJS) examined at the outpatient service for neuromuscular disorders at our Institution from 1996 to 1999 with the objective of emphasizing the characteristic dysmorphic phenotype of SJS and its different clinical forms. Two cases presented SJS-type 1A, two had SJS-type 1B and one manifested SJS-type 2. Two boys with 3 and 13 years of age had generalized stiffness and the characteristic facial as well as osteoarticular changes from birth. Other two boys with 11 and 7 years had less marked dysmorphic changes at birth and manifested myotonia, as a limiting factor, during the second year of age. A girl with two months of age had severe myotonia from birth leading to feeding diffuculties. In all cases the diagnosis was based on dysmorphic features, and on electromyographic changes showing continuous electrical activity of muscle fibers. All were treated with carbamazepine, 20-30 mg/Kg since diagnosis. The four boys (all with normal intelligence) improved of myotonia in daily activities, markedly in three, and moderately in one. The girl did not improve and showed global development delay: by the last follow-up (at 20 months of age) she did not sit unsupported, and had mental retardation. Carbamazepine in SJS-type 1 improves general daily performance and psychological status of the patients.KEY WORDS: Schwartz-Jampel syndrome, myotonia, carbamazepine. Síndrome de Schwartz-Jampel: relato de cinco casosRESUMO -Descrevemos cinco pacientes com a síndrome de Schwartz-Jampel (SSJ) avaliados no Ambulatório de Doenças Neuromusculares da Divisão de Neurologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, de 1996 a 1999, com o objetivo de salientar o peculiar fenótipo dismórfico e as diferentes formas clínicas da SSJ. Dois meninos apresentavam SSJ-tipo 1A, mais branda e mais tardia, dois outros meninos apresentavam SSJ-tipo1B, de início mais precoce e dismorfismos mais limitantes, e uma menina apresentava SSJ-tipo 2, forma neonatal, com grave comprometimento, inclusive da sucção. Em todos, o diagnóstico foi baseado nos aspectos clínicos dismórficos, tanto faciais como esqueléticos, e no encontro de anormalidade eletromiográfica caracterizada como atividade elétrica contínua da fibra muscular. Todos receberam carbamazepina, em doses anticonvulsivantes de 20 a 30 mg/Kg, desde a realização da eletromiografia, que foi mantida nas consultas de seguimento, após períodos variando de 15 meses a 4 anos. Os quatro meninos, todos frequentando escola, apresentaram atenuação da síndrome miotônica; esta atenuação foi acentuada em três, notando-se nítida melhora da postura anormal, e moderada em um, que refere menor limitação nas atividades da vida diária. O quadro da menina com SSJ-tipo 2 não se modificou e a paciente manifestou retardo global do desenvolvimento, não tendo adquirido a marcha nem a linguagem por ocasião da última avaliação aos 20 meses de idade. A boa resposta dos sintomas à carbamazepina na SSJ-tipo 1 deve ser enfatizada, poi...

No abstract

Anaphylactic shock can be defined as an acute syndrome, and it is the most severe clinical manifestation of allergic diseases. Anaphylactoid reactions are similar to anaphylactic events but differ in the pathophysiological mechanism. Nitric oxide (NO) inhibitors during anaphylaxis suggest that NO might decrease the signs and symptoms of anaphylaxis but exacerbate associated vasodilation. Therefore, blocking the effects of NO on vascular smooth muscle by inhibiting the guanylate cyclase (GC) would be a reasonable strategy. This study aimed to investigate the effects of NO/cGMP pathway inhibitors methylene blue (MB), N o-nitro-L-arginine methyl ester hydrochloride (L-NAME), and indigo carmine (IC) in shock induced by compound 48/80 (C48/80) in rats. The effect was assessed by invasive blood pressure measurement. Shock was initiated by C48/80 intravenous bolus injection 5 min before (prophylactic) or after (treatment) the administration of the inhibitors MB (3 mg/kg), L-NAME (1 mg/kg), and IC (3 mg/kg). Of the groups that received drugs as prophylaxis for shock, only the IC group did not present the final systolic blood pressure (SBP) better than the C48/80 group. Regarding shock treatment with the drugs tested, all groups had the final SBP similar to the C48/80group. Altogether, our results suggested that inhibition of GC and NO synthase in NO production pathway was not sufficient to revert hypotension or significantly improve survival.

Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control.

-Ullrich congenital muscular dystrophy (UCMD), due to mutations in the collagen VI genes, is an autosomal recessive form of CMD, commonly associated with distal joints hyperlaxity and severe course. A mild or moderate involvement can be occasionally observ e d . Objective: To evaluate the clinical picture of CMD patients with Ullrich phenotype who presented decreased or absent collagen VI immunoreactivity on muscular biopsy. Results: Among 60 patients with CMD, two had no expression of collagen V and their clinical involvement was essentially diff e rent: the first (3 years of follow-up) has mild motor difficulty ; the second (8 years of follow-up) never acquired walking and depends on ventilatory support. A molecular stud y, perf o rmed by Pan et al. at the Thomas Jefferson University, demonstrated in the first a known mutation of Bethlem myopathy in COL6A1 and in the second the first dominantly acting mutation in UCMD and the first in COL6A1, previously associated only to Bethlem myopathy, with benign course and dominant inheri t a n c e . Conclusion: Bethlem myopathy should be considered in the diff e rential diagnosis of UCMD, even in patients without fingers contractures; overlap between Ullrich and Bethlem phenotypes can be supposed.KEY WORDS: Ullrich congenital muscular dystrophy, congenital muscular dystrophy, joint hyperlaxity, collagen VI, Bethlem myopathy. D i s t rofia muscular congênita com hiperextensibilidade articular distal (Ullrich) e miopatia de Bethlem: heterogeneidade clínica e genética RESUMO -A distrofia muscular congênita (DMC) com hiperextensibilidade articular distal (fenótipo Ullrich) a ssocia-se a mutações nos genes do colágeno VI e corresponde a um grave quadro congênito de herança autossômica recessiva e curso pro g ressivo, ocasionalmente mostrando menor gravidade. Objetivo: Av a l i a r o quadro clínico dos pacientes com DMC tipo Ullrich que apresentam imunoexpressão baixa ou ausente d o colágeno VI na biópsia muscular. Resultados: E n t re 60 pacientes com DMC, dois mostravam imunomarc ação negativa do colágeno VI. Mostravam-se clinicamente essencialmente diferentes: o primeiro, com 8 anos de idade e três de seguimento mostra leve dificuldade motora; o segundo, com 14 anos de idade e 8 de seguimento, não deambula e apresenta insuficiência respiratória. O estudo molecular, realizado na Thomas Jefferson University por Pan et al., revelou no primeiro, no gene COL6A1, mutação típica da miopatia de Bethlem, que tem curso benigno e herança autossômica dominante; e no segundo a primeira mutação de efeito dominante e do gene COL6A1, previamente associado apenas à miopatia de Bethlem. C o n c l u s ã o : A miopatia de Bethlem deve constar no diagnóstico diferencial da DMC tipo Ullrich, mesmo na ausência das típicas contraturas dos dedos; pode existir sobreposição dos fenótipos Ullrich e Bethlem.PA L AV R A S -C H AVE: distrofia muscular congênita; hiperextensibilidade art i c u l a r, colágeno VI, fenótipo Ullrich, miopatia de Bethlem.

o nc l u s i o n :T h e re is a greater relationship between merosin and the former proteins; among MP-CMD patients, no remarkable immunohistochemical/phenotypical correlations were found, although the reduced expre ssion of β-DG had showed statistically significant correlation with severe phenotype and marked fibro s i s on muscular biopsy.KEY WORDS: congenital muscular dystro p h y, merosin, dystro p h i n -g l y c o p roteins associated complex, sarc o g l ycan complex, dystroglycan complex.Complexo distro f i n a -g l i c o p roteínas associadas na distrofia muscular congênita: análise imunohistoquímica em 59 casos RESUMO -A distrofia muscular congênita (DMC) é doença muscular heterogênea, de início precoce e padrão histopatológico de distrofia. Diversos subtipos foram geneticamente identificados e os fenótipos ainda não identificados pertencem em geral ao subgrupo de DMC merosina-positiva (MP). Objetivo: Analisar a e x p ressão imuno-histoquímica das principais proteínas do complexo distro f i n a -g l i c o p roteínas associadas na biópsia muscular de pacientes com diferentes fenótipos de DMC, a fim de investigar uma eventual correlação com o quadro clínico e histopatológico. Método: Cinqüenta e nove pacientes com DMC foram avaliados clinicamente e sua biópsia muscular, histopatologica e imuno-histoquimicamente: 32 eram MP, 23 m e rosina-deficiente (MD), um mostrava fenótipo Ullrich e três síndrome de Wa l k e r-Wa r b u rg . R e s u l t a d o s : D i s t rofina e disferlina foram normais em todos; nove pacientes MD apresentavam déficit parcial de mero s ina, porém com a mesma gravidade clínica daqueles com deficiência total. Conclusão: A hipoexpressão de α-s a rcoglicana (SG) and α-d i s t roglycan (DG) se correlacionou estatisticamente com o grave fenótipo MD, assim indicando maior correlação entre a merosina e as referidas proteínas; entre os pacientes MP, apesar da hipoexpressão de β-DG ter se correlacionado significativamente com fenótipo e histopatologia mais g r ave, não houve correlação clínica/imuno-histoquímica valorizável.