Double-blind cross-over placebo controlled study of flunarizine in patients with therapy resistant epilepsy

Twenty-five patients with long-standing therapy resistant epilepsy were studied in an eight-month double-blind cross-over add-on trial with a daily dose of 15 mg flunarizine. In five patients the seizure frequency decreased 50% or more. The mean seizure frequency reduction in the patients on flunarizine was 35%. Particularly the control of secondary generalized seizures improved. Flunarizine did not significantly alter the plasma levels of the regular anticonvulsant drugs. Minimal adverse side effects were reported equally in the flunarizine and the placebo group. In three patients depressive symptoms improved and two patients became free of postictal headaches. Flunarizine appears to be a safe adjuvant anticonvulsant.     

Hepatic resection for metastatic disease

Hepatic resection for metastatic disease is reviewed in 30 patients (mean age 58.9 years). The primary site was the colorectum in 25; the other primary tumours were leiomyosarcoma, plasmacytoma, and adenocarcinoma (all of gastric origin), ocular melanoma and an unknown primary. Operative procedures included 7 wedge resections, 5 segmentectomies and 21 lobectomies (11 right, 4 extended right and 6 left). Major complications in seven patients included intraoperative hemorrhage in three, two of whom died, bile-duct injury in two, small-bowel infarction in one and cerebrovascular accident in one. Operative death rate was 6.7% (2 of 30). Thirteen patients were alive and free of disease a mean of 24 months after hepatic resection while 5 more were alive with disease at a mean of 36.9 months. Life-table analysis projected a 5-year survival of 50.3% for those with colorectal primaries, with no apparent difference in survival between patients with single (55.0%) and multiple (54.0%) metastases. Improved survival was projected for patients with metachronous (66.6%) versus synchronous (45.0%) tumours, primary Dukes' class A or B (66.1%) versus Dukes' class C (46.0%) tumours and those having wedge resection or segmentectomy (66.6%) versus lobectomy or extended lobectomy (48.0%). Hepatic resection for metastatic disease can be done with acceptable morbidity and mortality and the expectation of substantially prolonged survival particularly in patients with metachronous lesions or Dukes's A or B colorectal primary lesions.     

Intraventricular neurocytoma, a recently recognized pathological entity: report of two cases and review of the literature.

Neurocytoma has only recently been recognized as a distinct pathological entity. Previously a rare tumor, it is now being recognized with increasing frequency. It typically presents in an intraventricular location in young adults. Many neurocytomas were originally diagnosed by light microscopy as oligodendrogliomas. More recently they have been shown to have ultrastructural and immunohistochemical features of neuronal differentiation. This paper presents two cases of intraventricular neurocytomas and reviews the recent literature.     

Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy

In a distinct autosomal recessive variant of epidermolysis bullosa, EB- MD, life-long skin blistering is associated with late-onset muscular dystrophy of unknown etiology. Electron microscopy of these patients' skin suggests that tissue separation occurs intracellularly at the level of the hemidesmosomal inner plaque, which contains plectin, a high molecular weight cytoskeletal associated protein, also expressed in the sarcolemma of the muscle. In this study, we report two patients with EB-MD, each with a homozygous deletion mutation in the plectin gene, PLEC1. In the first case, the proband and her similarly affected sister had a homozygous 9 bp deletion mutation, designated as 2719de19, which resulted in elimination of three amino acids, QEA, in a sequence of 23 amino acids entirely conserved between the mouse and human sequences. The proband in the second family demonstrated a single nucleotide deletion at position 5866, designated as 5866delC, which resulted in frameshift and a premature termination codon for translation 16 bp downstream from the site of deletion. The absence of plectin in the hemidesmosomes, as reflected by negative immunofluorescence with an anti-plectin antibody (HD-1), associated with fragility of basal keratinocytes, implicates plectin as critical for binding of intermediate keratin filament network to hemidesmosomal complexes. The function of plectin as a putative attachment protein also in the muscle would explain the clinical phenotype consisting of cutaneous fragility and muscular dystrophy in EB-MD.