Clinical and laboratory data of five cases of Emery-Dreifuss muscular dystrophy in three generations of a family are reported. Severity of the myopathic picture varied in the five patients considerably from almost noninvolvement to severe manifestations. In contrast, cardiomyopathy was severe not only in three adults but also in a 13-year-old boy. A review is given of 73 cases from the 6 major families reported in the literature. Most striking is the high incidence of sudden death. A wide variability in the severity of the myopathic picture was also evident.

Adult↗

PubMedDate not supplied

Merosin-negative congenital muscular dystrophy, occipital epilepsy with periodic spasms and focal cortical dysplasia. Report of three Italian cases in two families.

We report clinical, EEG and neuroimaging findings of three patients in two Italian families with merosin-negative congenital muscular dystrophy (CMD), drug-resistant occipital epilepsy, diffuse persistent cerebral white matter changes and focal cortical dysplasia. Clinical and epilepsy histories, EEG and neuroimaging findings were very similar in all patients. Seizures started in childhood and mainly consisted of periodic spasms, a particular type of partial seizure characterized by clusters of epileptic spasms. The motor expression of the spasms was very mild so that they had been frequently missed or misinterpreted as non-convulsive generalized absence seizures. Interictal EEG showed occipital spike-waves and bilateral synchronous slow spike-wave discharges. Ictal EEG showed prolonged periodic sequences of slow waves with associated fast rhythm complexes, characteristic of periodic spasms. Two patients had normal intelligence, one patient presented moderate mental retardation. Focal cortical dysplasia in the posterior areas of the brain, in addition to marked diffuse white matter alterations, was detected in the magnetic resonance images of all patients. Findings in these patients indicate that in merosin-negative CMD brain involvement can include cortical dysplasia, in addition to white matter changes. In such cases the brain damage can lead to a childhood-onset localization-related symptomatic occipital epilepsy. Epileptic seizures and cortical dysplasia can be, however, difficult to detect in CMD. The clinical semiology of epileptic seizures may in fact be modified because of muscular weakness. This implies that epilepsy may be misdiagnosed or even missed and EEG-polymyographic recordings may be necessary to identify it. Similarly, cortical dysplasia may be very localized and visible by neuroimaging only if it is carefully investigated on the basis of epileptological and EEG-polymyographic findings.

Child↗

PubMedDate not supplied

Bethlem myopathy: early-onset benign autosomal dominant myopathy with contractures. Description of two new families.

Bethlem myopathy is an apparently rare early-onset benign autosomal dominant limb-girdle myopathy with contractures of the fingers. To determine whether this disorder is unrecognized rather than rare we used muscle computerized tomography (CT) and isokinetic muscle testing and assiduously sought contractures of the fingers in relatives of two patients with the disease. CT showed that muscle impairment was mild but more diffuse than clinically apparent and showed an unexpected progressive degeneration of lumbar paravertebral muscles. The isokinetic test showed that the quadriceps was more involved that the hamstrings. In addition we found that contractures of the last four fingers progressed centripetally with age from the distal interphalangeal joints to the wrist. As a result we proved that 15 of the 21 examined subjects had the disease, 7 of them being unaware that anything was amiss. Careful examination may reveal that Bethlem myopathy is more common than is now thought.

Adolescent↗

PubMedDate not supplied

1-Methyl-beta-carboline-3-carboxylic acid, an unusual metabolite from cows fed with corn silage.

Explore the source record for details and available documents.

Animal Feed↗

PubMedDate not supplied

Chlorthalidone alone or in fixed combination with slow-release metoprolol in the management of arterial hypertension: a long-term study of 545 patients.

In a double-blind trial, 545 out-patients with essential hypertension received 25 mg/day chlorthalidone alone (274 patients) or in fixed combination with 200 mg/day slow-release metoprolol (271 patients) for 8 weeks. Both treatments significantly (P less than 0.001) decreased systolic and diastolic blood pressure; 45.6% of patients receiving chlorthalidone and 82.5% receiving combined therapy had a diastolic blood pressure of less than 95 mmHg. Patients not controlled by chlorthalidone or chlorthalidone plus metoprolol subsequently received chlorthalidone plus metoprolol (137 patients) or chlorthalidone plus metoprolol plus a third drug (34 patients), respectively, for 8 weeks. A total of 79.5% of patients receiving chlorthalidone plus metoprolol and 61.8% receiving chlorthalidone plus metoprolol plus a third drug had a diastolic blood pressure of less than 95 mmHg. Only 5.9% of patients experienced mild to moderate side-effects. Plasma potassium levels significantly (P less than 0.01) decreased during the first 8 weeks only. It is concluded that a diuretic alone or in fixed combination with a beta-blocker is effective in the long-term treatment of arterial hypertension.

Blood Pressure↗

PubMedDate not supplied

Nuclear envelope proteins and chromatin arrangement: a pathogenic mechanism for laminopathies.

The involvement of the nuclear envelope in the modulation of chromatin organization is strongly suggested by the increasing number of human diseases due to mutations of nuclear envelope proteins. A common feature of these diseases, named laminopathies, is the occurrence of major chromatin defects. We previously reported that cells from laminopathic patients show an altered nuclear profile, and loss or detachment of heterochromatin from the nuclear envelope. Recent evidence indicates that processing of the lamin A precursor is altered in laminopathies featuring pre-mature aging and/or lipodystrophy phenotype. In these cases, pre-lamin A is accumulated in the nucleus and heterochromatin is severely disorganized. Here we report evidence indicating that pre-lamin A is mis-localized in the nuclei of Emery-Dreifuss muscular dystrophy fibroblasts, either bearing lamin A/C or emerin mutations. Abnormal pre-lamin A-containing structures are formed following treatment with a farnesyl-transferase inhibitor, a drug that causes accumulation of pre-lamin A. Pre-lamin A-labeled structures co-localize with heterochromatin clumps. These data indicate that in almost all laminopathies the expression of the mutant lamin A precursor disrupts the organization of heterochromatin domains. Our results further show that the absence of emerin expression alters the distribution of pre-lamin A and of heterochromatin areas, suggesting a major involvement of emerin in pre-lamin A-mediated mechanisms of chromatin remodeling.

Aging, Premature↗