Substrate stabilization: genetically controlled reciprocal relationship of two human enzymes.

5-Phosphoribosyl-l-pyrophosphate, a substrate shared by adenine phosphoribosyltransferase and hypoxanthine-guanine phosphoribosyltransferase, accumulates in human erythrocytes lacking hypoxanthine-guanine phosphoribosyltransferase. 5-Phosphoribosyl-l-pyrophosphate added to purified adenine phosphoribosyltransferase stabilizes it against heat inactivation. The increased activity of adenine phosphoribosyltransferase seen in erythrocytes deficient in hypoxanthine-guanine phosphoribosyltransferase may result from substrate stabilization of this enzyme in vivo.

Parasympathetic innervation of the meibomian glands in rats.

PURPOSE: To determine the location of parasympathetic neurons that innervate the meibomian glands in rats. METHODS: The B subunit of cholera toxin (CTB), fast blue, and a retrograde transneuronal tracer, the Bartha strain of pseudorabies virus (PRV-Ba), were injected into the upper eyelids of adult Sprague-Dawley rats after sectioning the ipsilateral branches of the facial nerve and resecting the superior cervical ganglia. Brains and orbital tissues were processed for the immunohistochemical detection of PRV-Ba and CTB. In selected cases, series of brain sections were double labeled for PRV-Ba and tyrosine hydroxylase to determine the relationship between the A5 noradrenergic cell group and superior salivatory nucleus, or for PRV-Ba and choline acetyltransferase to establish the neurochemical phenotype of parasympathetic preganglionic neurons. RESULTS: Labeled ganglionic cells were diffusely distributed within the ipsilateral pterygopalatine ganglion (PPG) and along the more proximal portions of the greater petrosal nerve (GPN). Labeled preganglionic neurons were cholinergic and were located immediately dorsolateral to the rostral-most portion of the facial nucleus and caudal superior olive, where they intermingled with A5 noradrenergic cells. CONCLUSIONS: The meibomian glands and other structures within the lid margin are subject to parasympathetic regulation by ganglion cells diffusely distributed within the PPG and along more proximal portions of the GPN. Cholinergic parasympathetic preganglionic neurons that project to meibomian gland-innervating ganglion cells are located immediately lateral, dorsal, and rostral to the facial motor nucleus in the region commonly referred to as the superior salivatory nucleus.

Stimulation of human purine synthesis de novo by fructose infusion.

In order to clarify the mechanism of hyperuricemia and hyperuricosuria resulting from rapid infusion of fructose in man, the effects of an intravenous infusion of 125-200 g of fructose given over 3-4 hr on the rate of purine synthesis de novo was measured in one individual with osteoarthritis and four patients with gout. The incorporation of 1-minus 14C glycine into urinary uric acid was measured, and the pool size and turnover of urate were assessed by renal excretion of simultaneously administered 15-N urate. Fructose caused an expansion of body urate pool in all subjects, while urate turnover was increased in four. The rate of incorporation of 14-C glycine into urinary uric acid corrected for extrarenal disposal was increased in all cases (21%-430%). In two patients, rates of incorporation of 14-C glycine into urinary creatinine were increased by 10% and 11%, while rates of incorporation into uric acid were increased 84% and 159%, respectively, as a result of fructose infusion. Specific enhancement of the rate of purine synthesis de novo was suggested by these findings. The rate of infusion appeared more important than total dose in determining the magnitude of this effect. Whether the increased rate of purine synthesis was a result of direct stimulation by a fructose metabolite or was secondary to fructose-induced purine nucleotide depletion is uncertain, since the kinetics of glycine incorporation were consistent with either mechanism. Erythrocyte PP-ribose-P concentrations, however, were diminished during infusion rather than increased as might be expected if fructose infusion stimulated purine synthesis by increasing availability of this regulatory substrate.

Medical-legal consultation in gastroenterology.

Medical-legal consultation is a challenging adjunct to gastroenterology practice, encountering a wide range of problems. Cases in this series involved both medical malpractice and other liability issues, but only a minority of cases involve dendoscopic complications. Consultants can develop skills to efficiently perform independent medical examinations, give depositions and testimony in court. The expert must be informed, detached, and follow guidelines of ethical behavior in providing his or her opinions. The 1993 ruling by the Supreme Court in the Daubert case sets new standards for scientific testimony by expert witnesses.

Oral labetalol versus oral clonidine in the emergency treatment of severe hypertension.

This study was designed to compare the clinical efficacy and safety of oral clonidine and oral labetalol in the treatment of severe hypertension in an emergency department setting. Thirty-six patients with severely elevated blood pressure (mean baseline blood pressure 199/132 mm Hg) without acute end-organ dysfunction were treated with either oral labetalol or oral clonidine in a randomized double-blind prospective study. Labetalol was administered as an initial dose of 200 mg, followed by hourly 200 mg doses up to 1,200 mg. Clonidine was administered as an initial dose of 0.2 mg, followed by hourly 0.1 mg doses up to 0.7 mg. Labetalol reduced diastolic blood pressure in 94% of the patients within 6 hours, with a mean reduction in blood pressure of 54/37 mm Hg. Clonidine reduced diastolic blood pressure in 83% of the patients within 6 hours, with a mean reduction in blood pressure of 57/32 mm Hg. The authors conclude that oral labetalol was comparable to clonidine in efficacy, had a similar incidence of side effects, and offered the clinician a useful alternative for the treatment of severe hypertension in an emergency department setting. Further studies are indicated to determine appropriate dosing regimens for oral labetalol in the acute treatment of severe hypertension.

Liver histology in patients receiving low dose pulse methotrexate for the treatment of rheumatoid arthritis.

The liver histology of 52 patients treated with intermittent low dose pulse methotrexate for rheumatoid arthritis was evaluated using a modification of the Roenigk grading system. Patients studied had had an average of 3.2 years of treatment or had received 1.7 g methotrexate. No patient had cirrhosis; 15 (29%) patients had evidence of mild fibrosis. Histological abnormalities were not predicted by liver function test changes, with the exception that hypoalbuminaemia occurred in 60% of those with grade IV (modified criteria) findings. The need for liver biopsy in patients with rheumatoid arthritis treated with methotrexate before two years or 1500 mg of treatment has not been established. Whether serial liver biopsies will be needed beyond this time has yet to be determined.