No abstract

SUMMARY:Mutations in the Xq28 gene G4.5 lead to dilated cardiomyopathy (DCM). Differential splicing of G4.5 results in a family of proteins called "tafazzins" with homology to acyltransferases. These enzymes assemble fatty acids into membrane lipids. We sequenced G4.5 in two kindreds with X-linked DCM and in two unrelated men, one with idiopathic DCM and the other with DCM of arrhythmogenic right ventricular dysplasia. We examined the ultrastructure of heart, liver, and muscle biopsy specimens in these three DCM types; we used gas chromatography to compare fatty acid composition in heart, liver, and muscle autopsy specimens of two patients of kindred 1 with that of controls. In X-linked DCM, G4.5 had a stop codon (E188X), a nonsense mutation, in kindred 1 and an amino acid substitution (G240R), a missense mutation, in kindred 2. In the two men with isolated DCM, G4.5 was not mutated. Ultrastructural mitochondrial malformations were present in the biopsy tissues of the patients with DCM. Cardiac biopsy specimens of both kindreds with X-linked DCM exhibited greatly enlarged mitochondria with large bundles of stacked, compacted, disarrayed cristae that differed from those of the two types of isolated DCM. Autopsy tissue of patients with X-linked DCM had decreased unsaturated and increased saturated fatty acid concentrations. Seven of 13 published G4.5 missense mutations, including the one presented here, occur in acyltransferase motifs. Impaired acyltransferase function could result in increased fatty acid saturation that would decrease membrane fluidity. Mitochondrial membrane proliferation may be an attempt to compensate for impaired function of acyltransferase. Cardiac ultrastructure separates X-linked DCM with G4.5 mutations from the two types of isolated DCM without G4.5 mutations. Electron microscopy of promptly fixed myocardial biopsy specimens has a role in defining the differential diagnosis of DCM. Mutational analysis of the G4.5 gene also serves this purpose. (Lab Invest 2002, 82:335-344).

Deranged magnesium concentrations in serum and cardiovascular structures have been implicated in the pathophysiology of hypertension, ischemic heart disease, arrhythmias, and sudden death. This study was conducted to determine the status and interrelation of serum and tissue concentrations of magnesium in patients with congestive heart failure, a clinical setting purportedly predisposed to the development of depleted levels of this cation. Magnesium concentrations of serum, circulating mononuclear cells, skeletal muscle, and myocardium were measured in 23 patients with heart failure on standard therapy. Two patients were hypomagnesemic (<1.6 meq/l). Poor or no correlations were found between serum and tissue magnesium concentrations and among the magnesium concentrations of the three tissues studied. Strong direct correlations were, however, noted between magnesium and potassium concentrations of the tissues examined. The prevalence of hypomagnesemia in this typical ambulatory heart failure population is relatively low (9%o) and serum, circulating mononuclear cell, skeletal muscle, and myocardial magnesium concentrations correlate poorly with each other. Serum, circulating mononuclear cell, and skeletal muscle magnesium concentrations are thus of little predictive value in assessing the status of myocardial magnesium in humans with heart failure. (Circulation 1989;80:573-580) M agnesium, a biologically essential cation, has recently received considerable attention in clinical medicine, especially with regard to the role of its depletion in cardiovascular pathophysiology. Decreased magnesium stores have been implicated in the development and complications of atherosclerosis, myocardial infarction, hypertension, and dysrhythmias.1,2 Severe magnesium deficiency in animals has been shown to cause direct myocardial damage.3Patients with congestive heart failure would seem to be a group adversely susceptible to altered magnesium metabolism because these patients often have underlying myocardial damage and dysrhythmias and are receiving diuretics chronically. Diuretic therapy increases urinary magnesium losses and may cause depletion of total body and regional

An in vivo evaluation of isobutyl 2-cyanoacrylate as an osseous adhesive was done in an effort to answer two questions: Used in limited amounts, can this monomer maintain the reduction of an unstable intra-articular osteochondral fracture while allowing for fracture healing around the sites of adhesive placement? Used in limited amounts, in this monomer toxic to adjacent viable bone? Osteochondral fractures were created in 32 dog knees. In 16 knees, the fracture reduction was secured with three small drops of adhesive placed around the periphery of the fracture surface. In 16 control knees no adhesive was used. Eighty-one percent of the fractures in the adhesive-treated group united compared to 56% of the control group. Although the difference in number of fractures that healed in the two groups is not definitely statistically significant and no conclusion was drawn as to effectiveness of the adhesive, osseous healing was noted to proceed around the sites of adhesive placement and the monomer appeared nontoxic to adjacent bone.