Diazepam tolerance effects on vestibular function testing, Part I: Saccadic parameters during electronystagmography

OBJECTIVES: Benzodiazepines, particularly diazepam (DZ), are used in clinical practice to suppress acute vestibular symptoms. There have been limited studies looking at the effects of tolerance to DZ on parameters designed to measure the integrity of the vestibular system and its interaction with the oculomotor and balance systems. METHODS: In a double-blinded, repeated-measures design, we randomized 30 young healthy men into one of two treatment groups (diazepam and placebo) and assessed with electro-oculography the effects of clinical divided doses of DZ on saccadic eye movements and sedation over 16 days. RESULTS: Only sedation and saccadic latency were significant (p < .05) for treatment group, indicating selective effects on different central nervous system mechanisms. No significant effect for time was seen in any of the variables measured. Bonferroni t-test comparisons of the DZ group among 3 days were significant (p < .017) between baseline and day 3 for saccadic latency and accuracy and between day 3 and day 16 for self-ratings of sedation. CONCLUSIONS: Saccadic latency and accuracy and sedation ratings appear to be more sensitive to changes over time and less affected by subject variability than saccadic eye velocity. It remains questionable whether patients who have been on DZ for acute or extended periods of time need to discontinue the drug 48 hours before testing.     

Stimulation of hepatic phenylalanine hydroxylase activity but not Pah-mRNA expression upon oral loading of tetrahydrobiopterin in normal mice

Tetrahydrobiopterin (BH4) supplementation in patients with BH4-responsive phenylalanine hydroxylase (PAH) deficiency is an alternative to low-phenylalanine diet. To further investigate hepatic BH4-responsiveness, oral administration of 50 mg BH4/kg/day for 5 weeks was performed in wild-type mice. We observed a 2-fold increase in PAH protein by quantitative Western blot analysis and a 1.7-fold increase in enzyme activity, but no change in Pah-mRNA expression by quantitative real-time PCR analysis in treated mice compared to controls. Our findings support the proposed chemical-chaperone effect of BH4 to protect PAH.     

Death and taxes are more than just a certainty

This article discusses a tax provision referenced under Internal Revenue Code Section 691(a) known as "Income in Respect of a Decedent" (IRD) and includes many circumstances applicable to physicians. "IRD" refers to income that accrued to the decedent but was not included in taxable income.     

Epidermal H(2)O(2) accumulation alters tetrahydrobiopterin (6BH4) recycling in vitiligo: identification of a general mechanism in regulation of all 6BH4-dependent processes?

It has been shown in vivo that patients with the depigmentation disorder vitiligo accumulate hydrogen peroxide (H(2)O(2)) accompanied by low catalase levels and high concentrations of 6- and 7-biopterin in their epidermis. Earlier it was demonstrated that epidermal 4a-OH-tetrahydrobiopterin dehydratase, an important enzyme in the recycling process of 6(R)-L-erythro 5,6,7,8 tetrahydrobiopterin (6BH(4)), has extremely low activities in these patients concomitant with a build-up of the abiogenic 7-isomer (7BH(4)), leading to competitive inhibition of epidermal phenylalanine hydroxylase. A topical substitution for the impaired epidermal catalase with a pseudocatalase effectively removes epidermal H(2)O(2), yielding a recovery of epidermal 4a-OH-tetrahydrobiopterin dehydratase activities and physiologic 7BH(4) levels in association with successful repigmentation demonstrating recovery of the 6BH(4) recycling process. Examination of recombinant enzyme activities, together with 4a-OH-tetrahydrobiopterin dehydratase expression in the epidermis of untreated patients, identifies H(2)O(2)-induced inactivation of this enzyme. These results are in agreement with analysis of genomic DNA from these patients yielding only wild-type sequences for 4a-OH-tetrahydrobiopterin dehydratase and therefore ruling out the previously suspected involvement of this gene. Furthermore, our data show for the first time direct H(2)O(2) inactivation of the important 6BH(4) recycling process. Based on this observation, we suggest that H(2)O(2) derived from various sources could be a general mechanism in the regulation of all 6BH(4)-dependent processes.     

Polyarteritis nodosa in older children.

Polyarteritis in the older child is thought to be a rare disease. This study describes 11 children, 3 to 12 years of age, with polyarteritis seen over a five-year period. Fever, abdominal pain, hypertension, and leukocytosis were found in almost all. Renal disease occurred in eight. Examination of muscle, gut, or kidney tissue was an effective means of diagnosis. The pathological changes were the same as those seen in adults. There seemed to be an association between polyarteritis and group A streptococcal infection. Ten patients had a salutary response to high-dose prednisone administration.