Muscle and nerve pathology in Dunnigan familial partial lipodystrophy.

OBJECTIVE: To characterize muscle and nerve pathology in Dunnigan familial partial lipodystrophy (FPLD). METHODS: We used conventional histology, immunohistochemistry, messenger RNA (mRNA) expression, gene sequencing, and clinical studies of 13 patients with neuromuscular involvement. RESULTS: The clinical findings consisted of muscle hypertrophy (12/13), severe myalgias (9/13), and multiple nerve entrapment syndromes (8/13). Skeletal muscle histology demonstrated marked Type 1 and 2 muscle fiber hypertrophy and nonspecific myopathic changes, whereas numerous paranodal myelin swellings (tomacula) were found in sural nerve biopsies. We found that myostatin mRNA expression was reduced in patients with FPLD vs controls. We sequenced the myostatin gene in our subjects, but found no mutations. We then investigated whether or not SMAD, the intracellular mediator of myostatin signaling, might be impaired in patients with FPLD. We found that in FPLD muscle, a large number of SMAD molecules adhered to the nuclear membrane and were not found within the nucleus, compared with normal muscle or muscle from a patient with a non-FPLD lamin A/C disease. CONCLUSION: The myopathy and neuropathy associated with Dunnigan familial partial lipodystrophy are distinct from other lamin A/C disorders. We hypothesize that the lipodystrophy-associated mutation interferes with SMAD signaling, linking this type of lipodystrophy to the phenotypically similar myostatin deficiency.

Spontaneous intracerebral hemorrhage and multiple infarction in Williams-Beuren syndrome.

A 7-year-old boy diagnosed with Williams-Beuren syndrome was admitted for spontaneous right hemispheric intracerebral hemorrhage. Cerebral angiography did not reveal any source of bleeding. After a short period of clinical improvement under conservative treatment, the boy deteriorated rapidly. CT showed the beginning of a complete infarction of both hemispheres. Operative evacuation of the bleeding and bilateral osteoclastic decompression had no perceptible influence on the clinical course. To the present day, the boy has remained in a vegetative state. Reports in the literature suggest that Williams syndrome with cerebral infarction is associated with a markedly poorer prognosis when there is additional intracerebral bleeding.

Late neurological deterioration 30 years following conservative treatment of a lower cervical spine fracture--a case report.

A today 44 years old man suffered from a compression and subluxation fracture of C 4 and C 5 vertebral body during a swimming accident in 1971. The primary therapy was conservative and the patient was rehabilitated. Since 1997 the patient showed a slowly progressive right hemiparesis with signs of cervical myelopathy. The diagnostic procedures revealed a severe deformity of the cervical spine with myelon compression. We performed an operation with replacement of C4 and C5 and dorsal stabilization at the same time. This very impressive case shows the risk of a late and slowly onset of myelopathic deterioration while latent bony instability persist post traumatic. The authors think in agreement with the actual literature that the early operative stabilization of instable fractures of the lower cervical spine is inevitable. According to the grade of neurological and bony damage the operation should not be performed later than 8-12 hours after injury.

Local immunosuppression with budesonide after liver transplantation in the rat: a preliminary histomorphological analysis.

BACKGROUND: In this study we have analyzed the local immunosuppression with budesonide, a topically selective glucocorticosteroid, in rats after orthotopic liver transplantation. Because of its high first-pass hepatic clearance budesonide can be given orally, achieving high intrahepatic and low systemic concentrations. METHODS: Using an acute rejection model from Dark Agouti (DA) to Lewis rats, the histomorphological degree of rejection was assessed on histological sections at the ninth postoperative day. RESULTS: Livers of the DA to Lewis study group without immunosuppression revealed severe allograft rejection with vast cellular infiltrates, massive endothelialitis, and hepatocyte necrosis. In the three budesonide study groups (250 microg, 500 microg, and 1 mg/kg/day) a moderate to mild liver allograft rejection was seen. Rejection was most prominent in the 250 microg group, whereas the 1 g group showed almost no signs of rejection, similar to the Lewis to Lewis control group. Aspartate and alanine transaminase (sGOT, sGPT) as well as alkaline phosphatase serum levels correlated with the degree of rejection, achieving highest levels in the DA to Lewis group without immunosuppression. Animals treated with 1 g of budesonide had serum levels similar to Lewis to Lewis control animals. CONCLUSIONS: These results implicate a beneficial effect of local immunosuppression with budesonide in rats based on the histomorphological degree of liver allograft rejection.

La receta retenida: un problema médico-legal / The prescription retention: a medical-legal problem

Se investigó el conocimiento que poseen los médicos y químico-farmacéutico (QF) del uso de la receta retenida (RR) y la legalidad vigente, que regula el expendio de fármacos controlados. Se realizó un estudio descriptivo, prospectivo, que consistió en una prueba de simulación, en farmacias del área oriente de Santiago y se encuestó a QF y médicos durante el mes de diciembre de l990. Del estudio se concluye que en más de un tercio de las farmcias l RR no es recibida por el QF como establece la ley. Sólo se rechazaron un l5.6 por ciento de las recetas incompletas presentadas. Un 78.3 por ciento de los QF desconocen la mayoria de los requisitos legales que debe cumplir la RR la RR no cumple el objetivo para el cual se creó: evitar la venta indiscriminada de ciertos medicamentos y la farmacodependencia