Clinical and biochemical phenotype in 11 patients with mevalonic aciduria

OBJECTIVE: Mevalonic aciduria is a consequence of the deficiency of mevalonate kinase, the first enzyme after 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the biosynthesis of cholesterol and nonsterol isoprenes. To establish the clinical and biochemical phenotype of mevalonic aciduria, the authors assembled their experience with 11 patients including attempts at therapeutic interventions. METHODS: Mevalonic acid in body fluids was determined by stable isotope dilution gas chromatography/mass spectroscopy with selected ion monitoring, ubiquinone-10 concentrations by reversed-phase high-pressure liquid chromatography. RESULTS: Varying degrees of severity of clinical illness were observed despite uniform, virtual absence of residual activity of the enzyme. The most severely affected patients have had profound developmental delay, dysmorphic features, cataracts, hepatosplenomegaly, lymphadenopathy, and anemia, as well as diarrhea and malabsorption, and have died in infancy. Less severely affected patients have had psychomotor retardation, hypotonia, myopathy, and ataxia. All patients have had recurrent crises in which there was fever, lymphadenopathy, increase in size of liver and spleen, arthralgia, edema, and a morbilliform rash. Neuroimaging studies revealed selective and progressive atrophy of the cerebellum. Mevalonic acid concentrations were found to be grossly elevated in body fluids of all patients. Concentrations of plasma cholesterol were normal or only slightly reduced. Concentrations of ubiquinone-10 in plasma were found to be decreased in most patients. Abnormalities such as hypoglycemia, metabolic acidosis, or lactic acidemia, the usual concomitants of disorders of organic acid metabolism, were conspicuously absent. CONCLUSIONS: These observations establish the broad range of clinical symptoms and biochemical findings in mevalonic aciduria. It is concluded that although patients with mevalonic aciduria have a recognizable phenotype of serious clinical manifestations, some patients are likely to remain undiagnosed and may be found in a variety of subspecialty clinics, including neurology, gastroenterology, cardiology, and genetics.     

Comparison of the retrograde and transseptal methods for ablation of left free wall accessory pathways

OBJECTIVES: The purpose of this study was to compare success rates, procedure and fluoroscopy times and complications for the transseptal and retrograde aortic approaches in a consecutive series of patients undergoing catheter ablation of left free wall accessory pathways. BACKGROUND: Radiofrequency catheter ablation of left-sided accessory pathways can be performed either by a retrograde, transaortic approach or by means of a transseptal puncture. METHODS: A total of 106 patients (mean age 33 years, range 4 to 79) underwent attempted catheter ablation of a single left-sided accessory pathway by either the retrograde or the transseptal approach, or both. In the first 65 patients, the retrograde aortic approach was the preferred initial method. In the most recent 51 patients, we first attempted the transseptal approach whenever a physician trained in the technique was available. Ultimately, 102 (96.2%) of 106 patients had successful ablation. RESULTS: Of 89 retrograde procedures, 85% resulted in elimination of accessory pathway conduction. Four retrograde procedures performed after failure of the transseptal approach were successful. Of the 13 patients with a failed retrograde procedure, 11 later underwent ablation using the transseptal approach. Twenty-six (85%) of 33 transseptal procedures were successful. All four patients with unsuccessful initial transseptal attempts were successfully treated with the retrograde method during the same session in the electrophysiology laboratory. Ten of 11 transseptal procedures after unsuccessful retrograde procedures were successful. Crossover from the retrograde to the transseptal approach was performed during a separate session in 9 of these 11. There was no difference in total procedure time (220 +/- 12.8 vs. 205 +/- 12.5 min) (mean +/- SEM) or fluoroscopy time (44.1 +/- 4.4 vs. 44.7 +/- 5.1 min) between the retrograde and transseptal methods. Ablation time was longer for the retrograde method (69.2 +/- 10.5 vs. 43.4 +/- 9.3 min) (p < 0.01). Of patients > or = 65 or < or = 16 years old, technical factors requiring crossover to the other technique or complications occurred in 7 (42%) of 17 patients undergoing the retrograde and 1 (11%) of 9 patients undergoing the transseptal approach (p < 0.01). The overall rate of complications was the same for both (6.7% for retrograde and 6.1% for transseptal). The most serious complication involved dissection of the left coronary artery with myocardial infarction during a retrograde procedure. CONCLUSIONS: The retrograde and transseptal approaches are complementary; if one method fails, the other should be attempted, yielding an overall success rate close to 100%. Because patients undergo heparinization immediately after the arterial system is entered during a retrograde procedure, failure of that approach requires crossover to the transseptal method during a separate session or reversal of heparin; if the transseptal method is tried first, crossover to the retrograde approach can be accomplished easily during the same session. To avoid complications related to access, the transseptal method should be the first used in children, the elderly and those with arterial disease or hypertrophic ventricles.     

Diabetic thoracic polyradiculopathy: ten patients with abdominal pain

OBJECTIVES: Abdominal pain caused by diabetic thoracic polyradiculopathy is unfamiliar to many gastroenterologists. The aim of this study was to describe the clinical characteristics and outcome of the disorder. METHODS: Ten patients (six women) with diabetic thoracic polyradiculopathy were cared for in 20 yr. Electromyographic evidence of nerve root denervation was found in seven patients. Nine patients were followed-up at least until recovery, including four until death. RESULTS: The patients were 42-79 yr of age, had diabetes of various duration, and often had other diabetic complications, including two with previous polyradiculopathy. Pain of various types occurred. It was often worse at night and aggravated by light pressure. Pain was either unilateral or bilateral and was often accompanied by weight loss. All patients had a cutaneous sensory abnormality, and four had localized abdominal wall paresis with protrusion. Spontaneous recovery was documented in nine patients, but two had recurrent polyradiculopathy. CONCLUSIONS: Gastroenterologists should be familiar with diabetic thoracic polyradiculopathy, because its early recognition may prevent unnecessary and expensive diagnostic evaluation for a visceral cause of pain.     

Subarachnoid hemorrhage: etiologic variants, pathogenetic features and morphology

8 etiological variants of subarachnoidal hemorrhage are considered, its complications (rupture into the ventricles, development of the arterial spasm, brain edema) and sequelae (aseptic leptomeningitis, external hydrocephaly). Three stages in the subarachnoidal hemorrhage course are distinguished. The analysis of the vascular alterations and ventricular ependyma in cases of the rupture into the brain ventricles is performed. The study of morphological substrates of the liquor circulation in both macro- and microscopical level is recommended in all cases of subarachnoidal hemorrhage.     

Molecular variation, evolution and geographical distribution of louping ill virus

The effect of lidocaine on the palmitoyl-L-carnitine (PALCAR)-induced mechanical and metabolic derangements was studied in Langendorff rat hearts, perfused aerobically at a constant flow rate and paced electrically. PALCAR (5 mumol/l) increased the left ventricular end-diastolic pressure, decreased the left ventricular developed pressure (i.e., mechanical dysfunction), and decreased the tissue levels of adenosine triphosphate and creatine phosphate (i.e., metabolic change). These mechanical and metabolic alterations induced by PALCAR were concentration-dependently attenuated by lidocaine (20, 50 or 100 mumol/l). Nevertheless, lidocaine (20, 50 or 100 mumol/l) did not affect the mechanical function and energy metabolism of the normal (PALCAR-untreated) heart. These results indicate that lidocaine has a cardioprotective action against the PALCAR-induced mechanical and metabolic derangements.