Kenneth F. Swaiman

Echocardiographic incidence of cardiac rhabdomyoma in tuberous sclerosis

Cardiac rhabdomyoma occurs frequently in patients with tuberous sclerosis (TS). Although there have been case reports of detection of cardiac rhabdomyoma by 2-dimensional echocardiography, no study has examined the frequency of cardiac rhabdomyoma detected by cardiac ultrasound in patients with TS. Echocardiography was performed in 16 consecutive patients with TS. Physical examination revealed normal cardiac findings in each. Discrete areas of increased acoustic density were found in 8 of the 16 patients (50%). The maximum diameters ranged from 3 to 20 mm. Multiple areas were found in 3 of 8. The left ventricle was involved in 5 of the 8. Six masses were intracavitary and 8 were intramyocardial. No atrial masses were seen. Left ventricular size and function were normal. Although other tumors cannot be excluded, the diagnosis of cardiac rhabdomyoma is almost certain in these young patients with TS. The male predominance and the high incidence of intracavitary and left ventricular masses are similar to those in reported autopsy series, also supporting the diagnosis of cardiac rhabdomyoma. The prognosis and potential for growth of these masses are not known, but can be determined by longitudinal follow-up. Cardiac ultrasound should be considered for all patients with TS regardless of physical findings.

Neurologic characteristics of childhood lupus erythematosus

Records of 108 patients with lupus erythematosus beginning in childhood (1953-1990) were reviewed; 25 had recorded neurologic findings. This is the largest group of childhood lupus erythematosus patients with neurologic disease that has been reported. The average age of children at the time of diagnosis of lupus was 154 months. There were 22 girls and 3 boys in the group. All patients met at least four of the 1982 American Rheumatism Association criteria for the classification of systemic lupus erythematosus. Average age at onset of neurologic difficulties was 168 months. In 4 patients, the neurologic symptoms preceded the diagnosis: 1 month (spastic diplegia), 1 month (bilateral weakness and spasticity), 24 months (chorea), and 26 months (chorea), respectively. Four patients had neurologic symptoms coincident with the diagnosis of lupus erythematosus. In those patients whose symptoms followed the diagnosis of lupus erythematosus, the average elapsed time until symptoms appeared was 33 months; the single lowest and highest outliers were discounted. Most frequent findings were headache (16/25) and behavioral aberrations (10/25). All behavioral manifestations were depression except in 1 patient. Other prevalent findings included hemichorea or chorea (7/25), cerebrovascular accident with hemiplegia or diplegia (7/25), seizures (5/25), visual loss (3/25), and cranial neuropathy (2/25). Vertigo and myelopathy occurred in 1 patient each. All patients were treated primarily with corticosteroids and azathioprine; in the presence of active disease, the drug dosages were increased with significant improvement in neurologic symptoms. Resolution usually occurred from days to months; most improved in a few days to a few weeks; 3-4 months was the longest period until symptoms subsided.

A method for large-scale production of mouse brain cortical cultures

Fetal cerebral cortex can be grown for several weeks in dissociated cell culture using a relatively simple protocol for culture preparation. It is possible to establish large numbers of very similar cultures which serve as an effective test system for studies of toxicity and mechanism of action of neuroactive compounds. Light microscopic and ultrastructural studies document the neuronal component of the cultures as well as the developmental sequence. Cell counts, protein concentration and choline acetyltransferase activity demonstrate the reproducibility of the cultures from dish to dish.

Sea‐blue histiocytes, lymphocytic cytosomes, movement disorder and 59Fe‐uptake in basal ganglia Hallervorden‐Spatz disease or ceroid storage disease with abnormal isotope scan?

we studied two siblings with Hallervorden-Spatz syndrome. Fe-uptake and disappearance studies of the brain utilizing a narrow-field-of-view collimator indicated iron retention in the basal ganglia. Ferrokinetic studies utilizing 31Cr or 59Fe are within normal limits. Hematologic abnormalities heretofore unreported in Hallervorden-Spatz syndrome included sea-blue histiocytes in bone marrow and cytoplasmic inclusions in circulating lymphocytes, consisting of vacuoles, fingerprint profiles, multilaminar profiles, granular osmiophilic deposits, curvilinear bodies, and increased numbers of tubular arrays. These findings demonstrate extracerebral manifestations of Hallervorden-Spatz syndrome that may aid diagnosis and shed light on the etiology.

OXIDATIVE PHOSPHORYLATION IN MITOCHONDRIA OF DEVELOPING RAT BRAIN

Abstract— 1 Oxygen uptake, ADP/O ratios and respiratory control ratios (RCR) were studied by oxygen electrode techniques in mitochondria prepared from developing rat brain. 2 Oxygen consumption, ADP/O ratios and RCR based on mitochondrial protein concentration increased with maturation. Of the substrates employed, succinate supported oxygen uptake best and malate poorest. 3 The addition of exogenous NAD to the mitochondrial preparation had no effect on rate of oxygen uptake. 4 Lack of change in ADP/O ratio in the presence of glucose, a tricarboxylic acid cycle intermediate (α‐oxoglutarate), and ATP leads us to believe that there is no significant hexokinase activity in this preparation.

Iron uptake by glial cells.

Dynamic studies of iron metabolism in brain are generally unavailable despite the fact that a number of neurologic conditions are associated with excessive accumulation of iron in central nervous tissue. Cortical non-neuronal (glial) cultures were prepared from fetal mouse brain. After 13 days the cultures were exposed to radiolabeled iron. Brisk and linear total iron uptake and ferritin iron uptake occurred over 4 hours. When methylamine or ammonium chloride was added, (both known inhibitors of transferrin iron release because of their lysosomotropic properties), total iron uptake was diminished. Further studies indicated that meth-ylamine inhibits glial cell ferritin iron incorporation. Glial cell iron transport is similar to previously reported neuronal cell iron transport (1) but glial cell iron uptake proceeds at a faster rate and is more susceptible to the inhibition of certain lysosomotropic agents. The data reinforces the likelihood that iron uptake by nervous tissues is transferrin-mediated.

Early biochemical and EEG correlates of the ketogenic diet in children with atypical absence epilepsy

Early changes in blood chemistry and the electroencephalogram were monitored during the first three hours after initiating the medium chain triglyceride (MCT) diet in nine children with intractable atypical absence seizures. Serum glucose, insulin, triglycerides, cholesterol, free fatty acids, ketone bodies concentrations, and venous pH were assayed before and at timed intervals after MCT oil was administered orally. The concentration of serum ketones rose progressively over three hours, beta-hydroxybutyrate proportionately higher than acetoacetate. A statistically significant decrease in the group mean number of epileptiform discharges occurred following MCT therapy. Seizure frequency decreased by more than 50 percent in two-thirds of the children during the 10 week treatment period.

ELEVATED PLASMA PHENYLALANINE CONCENTRATION AND LYSINE INCORPORATION INTO RIBOSOMAL PROTEIN OF DEVELOPING BRAIN

Hyperphenylalaninemia was induced in 7‐day‐old rabbits over a 6‐hr period by intraperitoneal injection of phenylalanine.

The use of serum creatine phosphokinaseand other serum enzymes in the diagnosis of progressive muscular dystrophy

The early diagnosis of muscular dystrophy may be very difficult and the later less common forms may pose many diagnostic problems to the clinician. Serum creatine phosphokinase activity appears to be a valuable laboratory test to aid in the diagnosis of muscle disease. In determinations on serum from 200 patients with muscular disorders, the concentration of this enzyme was found to be increased only in patients with progressive muscular dystrophy or dermatomyositis.

THE EFFECT OF FOOD DEPRIVATION ON ENZYME ACTIVITY IN DEVELOPING BRAIN

Brain and body weights, contents of DNA and protein and activities of 1,6‐diphosphofructoaldolase (aldolase, EC 4.1.2.13), creatine phosphokinase (CPK, EC 2.7.3.2), and isocitric dehydrogenase (ICD, EC 1.1.1.42) in brain (minus cerebellum and brain stem) were studied in control and food‐deprived rats at 7, 14 and 21 days of postnatal age. Activities of all three enzymes per brain were less in the food‐deprived animals. In both groups of rats the ratios of aldolase/DNA and CPK/DNA increased with maturation, indicating that increasing activity per brain during maturation was the result of both increased activity per cell and increased numbers of cells. The ratio of ICD/DNA decreased with maturation but was essentially the same in both the food‐deprived and control groups. Increase of ICD activity per brain with maturation was attributable to increased numbers of cells. Food deprivation in immature animals resulted in lowered activities per brain for aldolase, CPK and ICD because of diminished cell multiplication.