Alpers-Huttenlocher Syndrome

Alpers-Huttenlocher syndrome is an uncommon mitochondrial disease most often associated with mutations in the mitochondrial DNA replicase, polymerase-γ. Alterations in enzyme activity result in reduced levels or deletions in mitochondrial DNA. Phenotypic manifestations occur when the functional content of mitochondrial DNA reaches a critical nadir. The tempo of disease progression and onset varies among patients, even in identical genotypes. The classic clinical triad of seizures, liver degeneration, and progressive developmental regression helps define the disorder, but a wide range of clinical expression occurs. The majority of patients are healthy before disease onset, and seizures herald the disorder in most patients. Seizures can rapidly progress to medical intractability, with frequent episodes of epilepsia partialis continua or status epilepticus. Liver involvement may precede or occur after seizure onset. Regardless, eventual liver failure is common. Both the tempo of disease progression and range of organ involvement vary from patient to patient, and are only partly explained by pathogenic effects of genetic mutations. Diagnosis involves the constellation of organ involvement, not the sequence of signs. This disorder is relentlessly progressive and ultimately fatal.     

Heavy Smokers Perform More Poorly than Nonsmokers on a Simulated Task of Gambling

The Gambling Task (GT) has demonstrated sensitivity to a type of decision-making that differentiates individuals manifesting substance use disorders from those without such disorders. However, studies have not yet compared the GT performance of “heavy smokers” to the performance of never-smokers. In the present study, the GT performance of “heavy smokers” (n = 39) and never-smokers (n = 32) recruited from the community was compared in an experimental design. Analysis of covariance showed that “heavy smokers” performance on the GT was significantly worse than that of never-smokers (p < .01). Implications, the study's limitations and future directions are discussed.     

Two dimensional Doppler echocardiographic/M mode echocardiographic and phonocardiographic method for study of extracardiac heterograft valved conduits in the right ventricular outflow tract position

Significant concern exists over the long-term results of right ventricular outflow tract repair using heterograft valved conduits. Because these conduits and valves are difficult to image using ultrasound, a serially applicable two dimensional Doppler echocardiographic, M mode echocardiographic and phonocardiographic method for noninvasive investigation was developed and applied in 15 children. The method provides two dimensional echocardiographic imaging of valve contour and motion, as well as M mode and phonocardiographic analysis and quantitative range-gated Doppler information about the timing of flow through the conduit. Conduit diameter in two dimensional echocardiographic images correlated well with known conduit size (r = +0.96). A thickened and stenosed heterograft valve was predicted in two patients before hemodynamic investigation. This new method provides serially obtainable information to aid in the management of children and infants with a valved conduit placed for repair of congenital heart malformations and aids in planning the timing of hemodynamic follow-up studies.     

Cardiac transplantation in patients over 50 years of age

Sixty-two patients underwent cardiac transplantation at the University of Arizona from March 1979 to March 1985. Thirteen patients (11 men and 2 women) were over 50 years of age at the time of transplantation and 49 were under the age of 50. The mean age (+/- SEM) of the patients over 50 was 53 +/- 1 years. Eight of these patients were treated with conventional immunosuppressive therapy (azathioprine, prednisone and rabbit antithymocyte globulin) and five, beginning in January 1983, were treated with cyclosporine, prednisone and rabbit antithymocyte globulin. Early mortality (0 to 90 days) was 16% in the group over 50 versus 18% for those under 50. The late mortality (greater than 90 days) was 36 and 33%, respectively. In both groups, rejection and infection were the principal causes of death. The incidence of infection was 1.9 +/- 0.5 episodes per patient in those patients over 50 and 1.9 +/- 0.4 in those under 50. The incidence of rejection was 1.3 episodes per patient-year in patients over 50 and 1.7 episodes per patient-year in those under 50. Actuarial survival at 1 year was 72 +/- 14% in the group over 50 and 66 +/- 7% in the group under 50 years of age. These data indicate that the results of cardiac transplantation for patients over 50 do not differ significantly from those for patients under 50. Therefore, it is concluded that a rigidly defined age criterion for cardiac transplant recipients is not acceptable. Each potential recipient must be evaluated in terms of individual risk and benefit from the procedure.     

Antiplatelet or anticoagulant therapy after coronary artery bypass surgery. A meta-analysis of clinical trials

PURPOSE: To determine the efficacy of antiplatelet or anti-coagulant therapy in preventing graft occlusions after coronary artery bypass surgery. DATA IDENTIFICATION: Studies published from 1966 to 1988 were identified through a computerized search using MEDLINE, by searching the bibliographies of all identified articles, and by consulting with the cardiologists and cardiothoracic surgeons in the Veterans Administration Cooperative Study Group on Antiplatelet Therapy After Coronary Artery Bypass Surgery. STUDY SELECTION: All studies selected were randomized, controlled clinical trials comparing at least one active drug with a placebo or nonplacebo control group. DATA EXTRACTION: Key data were extracted from each article, including the percentage of patients in each treatment group with one or more grafts occluded, the percentage of patients with completed postoperative catheterizations, timing of postoperative catheterization, and timing of start of treatment. These data were easily obtained from each article and did not require multiple observers. RESULTS OF DATA ANALYSIS: All studies had positive treatment-effect sizes in favor of active treatment, although some studies did not achieve statistical significance. A meta-analysis combining all treatment effects clearly shows that active treatment is beneficial (overall effect size = 0.30; CI, 0.21 to 0.38). Efficacy improves with early initiation of treatment. CONCLUSIONS: Early initiation of antiplatelet or anticoagulant drugs reduces the incidence of graft occlusions after coronary artery bypass surgery.