Impairment of the metabolism of dipyrone in asymptomatic carriers of the hepatitis-B virus does not occur in rapid acetylators

OBJECTIVE: We previously found that, compared with healthy subjects. asymptomatic hepatitis-B virus (HBV) carriers displaying slow acetylator phenotype demonstrate a significant prolongation of the elimination half-life of 4-methylaminoantipyrine (MAA) and a decrease in the clearance of formation of 4-aminoantipyrine (AA) and 4-formylaminoantipyrine (FAA). However, the formation of 4-acetylaminoantipyrine (AAA) was unchanged. The present study was designed to examine the effect of the asymptomatic HBV carrier state on the metabolism of dipyrone. as a model drug, in rapid acetylators. METHODS: The plasma and urine concentrations of the metabolites of dipyrone were measured in eight asymptomatic HBV carriers and eight healthy subjects who had normal liver function tests, all displaying the rapid acetylation phenotype and genotype, after the administration of a 1.0-g oral dose of dipyrone. RESULTS: The following pharmacokinetic parameters were evaluated: peak plasma concentration, time to peak plasma concentration, elimination rate constant, area under the plasma concentration-time curve (0-->infinity), amount excreted (0-->infinity), renal and non-renal clearances for MAA and the clearances of formation for AA, FAA and AAA. No significant differences were found between the two subject groups. CONCLUSION: The effect of hepatic viral carrier state on drug metabolism may vary according to metabolic pathways and genetic polymorphism.     

The Speech Generating Device (SGD) Mentoring Program: Supporting the Development of People Learning to Use an SGD

Mentoring in speech generating device (SGD) use by adults who use an SGD proficiently offers the potential to improve the device usage of people learning an SGD. The aim of the present study was to examine the impact of SGD mentoring on the mentees’ SGD usage. Three mentors, aged 23, 31, and 54 years, and 3 mentees, aged 13, 14, and 32 years, participated. A nonconcurrent multiple baseline across participants design was used to assess the outcomes. Mentee conversation samples were analyzed for the number of total words, the number of different words, and the number of bound morphemes produced in mentoring sessions. Improvements were made in these measures across the mentees following commencement of mentoring sessions with a trained SGD mentor. These results provide preliminary evidence of SGD mentoring success.     

Pediatric obesity: are we under-diagnosing? Assessing pediatric obesity at an urban community health clinic

Pediatric care providers are often discouraged by the scope and magnitude of our current childhood overweight epidemic. Numerous studies have shown the adverse consequences of pediatric obesity, ranging from short-term physical and psychosocial consequences to long-term consequences that manifest in adulthood. In this study we investigated rates of overweight and at-risk for overweight children in a community health center in urban Honolulu, Hawai'i which serves a large multi-cultural and multi-ethnic population with a large presence of Asians and Pacific Islanders. This was done by conducting a chart review of the pediatric patients in the clinic. Twenty-four children had been formally diagnosed and recorded in their charts as obese/overweight during the last 2 years, out of 4,640 pediatric patients seen (less than 0.5%). However, according to this study roughly 140 overweight children are seen monthly at this clinic, indicating a prevalence of more than 50%. Samoan and Micronesian children were found to be primarily impacted.     

Celecoxib leads to G2/M arrest by induction of p21 and down-regulation of cyclin B1 expression in a p53-independent manner

A unique in vitro system has been developed in our lab that consists of normal enterocytes derived from the rat ileum (IEC-18 cells) and their transformed derivatives with c-K-ras (R1 cells), anti-sense bak (B3 cells) and cyclin D1 (D1 cells). R1 and B3 cells express high level of COX-2 protein and PGE2. IEC 18 and D1 cells express negligible amount of COX-2, and produce very low level of PGE2. A relatively low dose of celecoxib (5-10 microM) induced G2/M arrest, followed by induction of apoptosis in the transformed but not in the normal cells. Down-regulation of cyclin B1 and up-regulation of p21 expressions independent of p53 might have cause this cell cycle block. Growth inhibition was related to COX-2 function with 90-95% reduction in PGE2 production. These findings may be of clinical importance, since low concentration of celecoxib can be achieved in human serum following standard anti-inflammatory (100-200 mg bid) regime.     

Efficacy of postexposure immunization with live attenuated varicella vaccine in the household setting--a pilot study

The aim of the present study was to examine the efficacy of postexposure vaccination with Varilrix in the household setting. A randomized, double-blind, placebo-controlled design was used. Twenty-two children received the varicella vaccine and 20, a placebo. The relative risk of developing varicella with a placebo compared with the vaccine was 1.1 (95% confidence interval 0.55-2.21). The risk of developing moderate to severe disease was eight times greater in the placebo group (RR=8), indicating an 80% protective effect against moderate/severe disease. The varicella vaccine Varilrix may not be effective in preventing varicella when administered after household exposure, although it is highly effective in ameliorating the disease in those who acquire it under these circumstances.     

Peripheral neuropathy in pediatric systemic lupus erythematosus

Peripheral neuropathy is an uncommon manifestation of systemic lupus erythematosus and has not yet been characterized in pediatric patients. We report the clinical and electrophysiologic features of peripheral neuropathy in one child and three adolescents with lupus erythematosus. There were three females and one male. The peripheral neuropathy followed the onset of lupus erythematosus by a mean of 3 years. The onset of the neuropathy correlated with lupus erythematosus activity and presented with either severe pain or dropfoot. Nerve conduction studies revealed sensory and motor polyneuropathy in all patients and mononeuritis multiplex in two patients. Only one patient had associated central nervous system involvement at that time. All patients were positive for IgM and IgG anticardiolipin antibodies. Patients were treated with steroids, gabapentin, carbamazepine, azathioprine, and cyclophosphamide. Response to treatment was variable: two patients recovered and two had a partial response. Although an unusual manifestation, peripheral neuropathy should be kept in mind as part of the neurologic spectrum in lupus erythematosus. It is not necessarily associated with central nervous system disease. A role for antiphospholipid antibodies in the pathogenesis is suggested.     

Processing of low-probability sounds by cortical neurons

The ability to detect rare auditory events can be critical for survival. We report here that neurons in cat primary auditory cortex (A1) responded more strongly to a rarely presented sound than to the same sound when it was common. For the rare stimuli, we used both frequency and amplitude deviants. Moreover, some A1 neurons showed hyperacuity for frequency deviants--a frequency resolution one order of magnitude better than receptive field widths in A1. In contrast, auditory thalamic neurons were insensitive to the probability of frequency deviants. These phenomena resulted from stimulus-specific adaptation in A1, which may be a single-neuron correlate of an extensively studied cortical potential--mismatch negativity--that is evoked by rare sounds. Our results thus indicate that A1 neurons, in addition to processing the acoustic features of sounds, may also be involved in sensory memory and novelty detection.     

Ambulatory blood pressure monitoring in children with isolated haematuria

Ambulatory blood pressure monitoring (ABPM) was performed in 29 children, ages 8.5-10.5 years (mean 11.6+/-3.0) with isolated haematuria (IH) and in 27 age, sex, weight and height matched healthy controls (C). Isolated haematuria was defined as >or=5 RBC/HPF on three separate urinalyses over a 3-month period with normal renal function, a normal appearing ultrasound examination of the kidneys and the absence of hypercalciuria. Haematuria had been documented for at least 3 years prior to ABPM. Daytime and nighttime periods were 0800-2200 and 2200-0800 hours, respectively. The total number of successful blood pressure readings was 21.8 and 20.7 per subject (90.0 and 86.1% of all attempted measurements) in IH and C, respectively. Mean 24-h, daytime and nighttime heart rate, mean arterial pressure, and systolic and diastolic blood pressure in IH did not differ from that of controls. Nocturnal dipping was present in all IH patients and was of equal magnitude to C (9.5 vs 8.4 and 13.7 vs 10.3% for average systolic blood pressure (SBP) and diastolic blood pressure (DBP) dips, respectively). We conclude that normal blood pressure values, as well as the circadian rhythm of blood pressure, are maintained in children with IH of at least 3 years' duration.