Polymorphisms in CYP2D6 have a Greater Effect on Variability of Risperidone Pharmacokinetics than Gender

Within‐subject coefficient of variation (CV_w) plays a decisive role in the determination of sample size in bioequivalence clinical trials. Highly variable drugs may require the participation of a large number of subjects. The aim of this study was to investigate whether gender and polymorphisms in CYP2D6 affect the CV_w of risperidone. Two single‐dose, two‐period crossover studies of risperidone (n = 70) were reanalysed to calculate CV_w for AUC_t and C_max. Subjects were classified into four different CYP2D6 phenotype groups [poor metabolizers (PM), intermediate metabolizers (IM), extensive metabolizers (EM) and ultrarapid metabolizers (UM)]. The effect of gender was evaluated in EM and IM. CV_w was lower in PM (13.3% for AUC_t and 10.9% for C_max) and UM (17.4% and 8.7%) than in EM (28.7% and 34.7%) and IM (33.2% and 27.3%). Variability was slightly lower in women (27.9% for AUC_t and 25.7% for C_max) than in men (33.3% and 37.2%, respectively). Genetic polymorphisms affect within‐subject variability more than gender and could considerably affect sample size calculation. Therefore, subjects participating in bioequivalence trials should be genotyped.     

Clinical features of ten cases of osteopoikilosis

A retrospective study was carried out of the ten cases of osteopoikilosis seen at this Orthopedic Unit over a 15-year period in order to determine the reasons why patients seek consultation, preliminary diagnosis, and associated lesions. Eight patients consulted for problems not related to the locomotor apparatus, and diagnosis was by chance; the other two presented joint pain. The preliminary diagnosis was osteoblastic metastasis in five patients and osteopoikilosis in the other five. None of the patients displayed skin or visceral involvement, but three presented bone alterations. Definitive diagnosis was made by measurement of biochemical markers of bone remodeling, radiography of both hands, and bone scan. Bone biopsy was performed in one case. Although rare, the radiographic symptoms of osteopoikilosis are sufficiently specific to avoid false diagnoses, which may give rise to rigorous and expensive studies for other important disorders.     

Clinical characteristics of familial versus sporadic Crohn's disease using the Vienna Classification

BACKGROUND: The etiology of Crohn's disease, an illness protean in its manifestations, may be better resolved through studies involving more homogenous subgroups of patients. Because a strong genetic influence exists, family history of inflammatory bowel disease may be a useful variable for patient classification if patients with familial and sporadic Crohn's disease are clinically different. Our study attempted to define any possible differences. METHODS: The medical records of 552 patients were reviewed, and patients were classified according to guidelines of the Vienna Classification. Patients were then divided based on family history of inflammatory bowel disease, and the familial and sporadic groups were compared. RESULTS: Overall, 422 (78.9%) patients were diagnosed before age 40 years (A1) and 114 (21.1%) at age 40 years or older (A2). There were 141 (26.3%) patients with disease involving the terminal ileum only (L1), 211 (39.4%) in the colon only (L2), 117 (21.9%) in the terminal ileum and colon (L3), and 66 (12.3%) in the upper gastrointestinal tract (L4). Disease behavior, as determined at the time of last visit or telephone contact, was nonstricturing, nonpenetrating (B1) in 149 (27.9%) patients, stricturing (B2) in 50 (9.3%) patients, and penetrating (B3) in 336 (62.8%) patients. Comparisons among the groups of 53 patients with first-degree relatives only, the 96 patients with either first-, second-, or third-degree relatives (familial CD group), and the 439 patients with sporadic disease demonstrated no differences in sex, age at diagnosis, or disease location. There was a difference in disease behavior between the familial and sporadic groups (p = 0.048) that failed to exist when nonstricturing, nonpenetrating cases were excluded. No such difference was observed between the first-degree relatives only group and the sporadic group (p > 0.10). CONCLUSIONS: Using the Vienna Classification, familial and sporadic Crohn's disease differed only in disease behavior. However, this difference failed to exist after patients with nonstricturing, nonpenetrating disease were excluded. Therefore, familial and sporadic groups appear to be quite similar clinically, and family history does not appear to be a variable useful for disease subclassification.     

Los altos volúmenes convectivos se asocian a la mejoría del perfil metabólico en los pacientes diabéticos en hemodiafiltración online

Background and objective

Online haemodiafiltration (OL-HDF) with high convective transport volumes improves patient survival in haemodialysis. Limiting the amount of convective volume has been proposed in patients with diabetes mellitus due to glucose load that is administered with replacement fluid. The objective of the study was to analyse the influence of substitution volume on the evolution of the metabolic profile and body composition of incident diabetic patients on OL-HDF.

Effect of purslane seed supplementation on inflammatory cytokines,oxidative stress and muscle damage in response to high-intensity intermittent exercise in national athlete runners

Sport Sciences for Health - Purslane supplementation has anti-oxidative, anti-inflammatory, skeletal muscle-relaxant activities. However, it is unknown if the ingestion of purslane will affect the...     

[11C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain

The PET tracer [¹¹C]5-hydroxytryptophan ([¹¹C]5-HTP), which is converted to [¹¹C]5-hydroxytryptamine ([¹¹C]5-HT) by aromatic amino acid decarboxylase (AADC), is thought to measure 5-HT synthesis rates. But can we measure these synthesis rates by kinetic modeling of [¹¹C]5-HTP in rat? Male rats were scanned with [¹¹C]5-HTP (60 minutes) after different treatments. Scans included arterial blood sampling and metabolite analysis. 5-HT synthesis rates were calculated by a two-tissue compartment model (2TCM) with irreversible tracer trapping or Patlak analysis. Carbidopa (inhibitor peripheral AADC) dose-dependently increased [¹¹C]5-HTP brain uptake, but did not influence 2TCM parameters. Therefore, 10 mg/kg carbidopa was applied in all subsequent study groups. These groups included treatment with NSD 1015 (general AADC inhibitor) or p-chlorophenylalanine (PCPA, inhibitor of tryptophan hydroxylase, TPH). In addition, the effect of a low-tryptophan (Trp) diet was investigated. NSD 1015 or Trp depletion did not affect any model parameters, but PCPA reduced [¹¹C]5-HTP uptake, and the k₃. This was unexpected as NSD 1015 directly inhibits the enzyme converting [¹¹C]5-HTP to [¹¹C]5-HT, suggesting that trapping of radioactivity does not distinguish between parent tracer and its metabolites. As different results have been acquired in monkeys and humans, [¹¹C]5-HTP-PET may be suitable for measuring 5-HT synthesis in primates, but not in rodents.     

Brucellar spondylitis: review of 35 cases and literature survey.

Thirty-five patients aged 14-74 years (average, 54 years) who had brucellar spondylitis were treated between January 1991 and December 1997. The time from onset of symptoms to diagnosis of spondylitis ranged from 1 week to 8 months (median, 9 weeks). Back or neck pain (100% of patients), fever (66%), and constitutional symptoms (57%) were the most common symptoms. Cultures of blood specimens from 26 patients (74%) were positive for Brucella melitensis. The duration of antimicrobial therapy (median, 120 days; range, 45-535 days) varied according to clinical response and the presence of epidural and paravertebral masses. One of the 35 patients underwent surgical treatment of a spinal epidural abscess. Therapy failed for 9 patients (26%; 95% confidence interval [CI], 12%-43%), and 5 (14%; 95% CI, 5%-30%) had a relapse. There were no deaths or severe sequelae in this study. Brucellar spondylitis causes considerable suffering and absenteeism from work, but long-term clinical responses are favorable.