Thirty years of Batten disease research: present status and future goals.

From a meager beginning in 1968, when Batten disease or neuronal ceroid lipofuscinosis was practically unheard of, tremendous advances have been made. It is now recognized worldwide as the most common neurodegenerative disease in children and young adults. It is recognized as a genetic disease. The infantile form has been localized to chromosome 1 p32 and the juvenile form, to 16p12.1; the gene for the late infantile is on chromosome 11p15 and for a variant form of the late infantile, the gene lies on chromosome 15q21-23. Finally, the molecular basis of the late infantile form is probably a pepstatin-insensitive lysomal peptidase. The future is to identify carriers, prevent the disease, and develop treatment by gene and enzyme replacement.

Perspective of biochemical research in the neuronal ceroid-lipofuscinosis.

The search for biochemical abnormalities in the neuronal ceroid-lipofuscinoses (NCL) or Batten disease was initiated with the discovery of normal levels of gangliosides in juvenile amaurotic idiocy. The primary goal of most biochemical studies has been to discover the unique biochemical marker for carriers and at-risk individual. Ceroid, the singular pathomorphologic trait of NCL, was isolated and shown to differ from a similar but normal product of aged cells, lipofuscin. In spite of the availability of stored product, the chemical analysis of ceroid has not elucidated the unique biochemical defect in the NCL, as has been the case for other lysosomal storage disorders. The NCL were thought to be a result of lipid peroxidation because ceroid is also found in disorders of impaired vitamin E metabolism or results from a diet deficient in the antioxidant, vitamin E. In addition, tissue analysis indicated losses of polyunsaturated fatty acids in affecteds and carriers, as well as the presence of a secondary product of lipid peroxidation, 4-hydroxynonenal, in affected and carrier NCL dogs. With the exception of a fluorescent compound isolated from retinal ceroid, studies aimed at discovering the disease-specific fluorophores of ceroid have been largely inconclusive. The discovery of elevated dolichols in urine and brain tissue of NCL patients led to another hypothesis, that the basic biochemical defect in NCL involved the metabolism of dolichols and retinoids. However, the more recent view is that dolichol metabolism is secondary to the unknown NCL lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Concomitant administration of terazosin and atenolol for the treatment of essential hypertension.

The safety and efficacy of once-daily terazosin hydrochloride administered concomitantly with once-daily atenolol for the treatment of essential hypertension were evaluated in this double-blind, multiclinic, placebo-controlled study. After each patient received 50 mg of atenolol daily for eight weeks, patients with a supine diastolic blood pressure (DBP) of 95 to 110 mm Hg and whose supine DBP had decreased at least 5 mm Hg were randomized to receive either terazosin (plus atenolol) or placebo (plus atenolol) for ten weeks. Patients assigned to the terazosin hydrochloride treatment group received increasing dosages (1,2,5, and 10 mg daily) [corrected] of terazosin at two-week intervals until the maximum dose was reached or until the supine DBP was decreased to less than 90 mm Hg. Terazosin-treated patients (n = 43) had significant mean decreases from the baseline in supine BP (systolic/diastolic = -8.8/-8.5 mm Hg) and standing BP (-10.9/-9.5 mm Hg), whereas the decreases in BP in the placebo-treated patients (n = 49; supine, -2.3/-2.6 mm Hg; standing, -1.4/-1.3 mm Hg) were not significant. When terazosin and placebo were compared, the differences in BP were significant. Terazosin-treated patients had significantly greater decreases in mean percent change of total cholesterol (-4.8%) and low-density lipoprotein plus very-low-density lipoprotein cholesterol (-6.3%) levels, compared with the placebo-treated patients (+0.6% and +1.1%, respectively). Concomitant administration of terazosin and atenolol to patients with essential hypertension was found to be safe and efficacious.

Batten disease: past, present, and future.

The name Batten disease (or neuronal ceroid lipofuscinosis) is used to unify the spectrum of clinical and pathological conditions covered by the names infantile, late infantile, juvenile, and adult variants with their respective eponyms. The past was largely devoted to clinical diagnosis. The present is devoted to specific diagnostic tests. The future will be devoted to prevention and treatment. Treatment may consist of specific drug treatment, enzyme replacement, or gene replacement. Early diagnosis is important in order to provide genetic counseling and to establish family support for those patients who have a protracted, progressive disabling and ultimate fatal course.

Gastric bezoars: treatment and prevention.

Gastric bezoars may occur in the normal stomach as a result of ingestion of various objects which do not pass through the pylorus. Most gastric bezoars occur as a complication of previous gastric surgery in which there is a loss of normal pyloric function, hypoperistalsis, and low gastric acidity. They may also occur as a complication of cimetidine therapy. Symptoms include epigastric fullness, regurgitation, nausea and vomiting, and epigastric pain. A simple treatment utilizing an ordinary Teledyne Water Pik jet stream through a gastroscope is described to break up a large phytobezoar. This method is probably the treatment of choice and should be used more widely.

Comparison of fecal blood loss after use of aspirin and diflunisal.

Diflunisal 1,000 mg/day, aspirin 4.0 g/day, or placebo were given to 36 healthy volunteers for 14 days to determine fecal blood loss. There was a significant increase in fecal blood loss from baseline in the aspirin group compared to both the diflunisal and placebo groups. A slight but significant increase in fecal blood loss in the diflunisal group at Week 1 was reported; however, there was no significant increase at Week 2. Use of diflunisal was not associated with any consistent blood loss or serious adverse reactions.

Effect of a new antacid on basal and meal-stimulated gastric secretion.

Our study of the comparative neutralizing effectiveness of four antacids on the acidity and pH of the basal gastric secretion in 32 patients showed that using the conventional doses of two tablets of Rolaids, two tablets of Di-Gel, 15 ml. of Maalox liquid or two tablets of Conquel, they are equal in their acid neutralizing capacity. The duration of action for 45-60 minutes. Conquel, in a dose of two tablets, was a potent buffer for the peptone-meal stimulated secretion. The duration of action lasted for longer than two hours.

Potassium chloride preparations and fecal blood loss. A parallel study with a 10 percent solution and a non-enteric-coated waxy-matrix tablet.

Concentrated potassium chloride produces ulceration of the gastrointestinal mucosa. Dilute solutions are frequently not acceptable to the patient. A tablet containing potassium chloride crystals suspended in a waxy matrix has been developed to avoid these drawbacks. We measured fecal blood loss by a radioactive chromium technique on 20 subjects during five days while they were given potassium chloride, 40mEq/day; ten subjects took a 10% solution; the others the waxy-matrix tablet. Fecal blood loss did not differ significantly between these groups. Mean fecal blood losses in both groups were slightly increased during the potassium chloride administration but never exceeded acceptable normal limits.