Effect of Renal Impairment on the Pharmacokinetics and Tolerability of Tiagabine

Summary: Purpose: We wished to determine the effect of renal impairment on the pharmacokinetics and tolerability of the new antiepileptic drug tiagabine (TGB).
Methods: We assessed TGB pharmacokinetics and tolerability in 25 subjects with various degrees of renal function (based on creatinine clearance, n = 4–6 per group) from healthy (group I) to requiring hemodialysis (group V) in a single and multiple dose (every 12h), one-period (groups I-IV) or a single dose, two-period (group V) study (4-mg oral doses of TGB · HCl). Blood samples were collected after the first dose (both periods for group V) and after the last dose on day 5 (groups I-IV). TGB plasma concentrations and plasma protein binding were determined by high-performance liquid chromatography (HPLC) and ultrafiltration, respectively.
Results: TGB was well tolerated by all study subjects. The pharmacokinetics of TGB were similar in all subjects; no pharmacokinetic parameter (based on either total or unbound concentrations) was statistically correlated with creatinine clearance. For total TGB in plasma, single-dose mean values of the maximum plasma concentration, clearance, and half-life (t1/2) ranged from 52 to 108 ng/ml, from 7.14 to 11.02 I/h, and from 6.4 to 8.4 h, respectively.
Conclusions: TGB pharmacokinetics and tolerability were independent of renal function; therefore, dosage adjustment is unnecessary for epilepsy patients with renal impairment.     

Maternal satisfaction following post-shelter family reunification

The purpose of this study was to examine the correlates of post-shelter maternal family satisfaction in a group of youth who were reunified with their families following a shelter stay. Findings indicated that higher ratings of family satisfaction were related to greater maternal problem solving skill and less family conflict.     

Practice Functions Necessary for the Delivery of Pharmaceutical Care

Pharmaceutical care is a concept outlining the responsibilities of individual pharmacists to individual patients. Although widely accepted on a philosophical basis, there is a lack of comprehensive information about the functions and responsibilities pharmacists undertake when providing pharmaceutical care. Pharmacy educators and practitioners at the faculty of pharmacy, University of Toronto, developed and informally tested a process that details the practice functions required of pharmacists when providing pharmaceutical care as originally defined.     

Long-latency auditory-evoked potentials: Role of polysensory association cortex in the cat

The objective of this study has been to define the role of polysensory association cortex in the generation of "wave NA" and of "wave C," long-latency auditory-evoked potentials recorded from the vertex of conscious cats as, respectively, a marked negative potential of latency 30-48 msec followed by a broad positive wave of latency 50-75 msec. Wave C may represent the feline analogue of the longer latency human auditory-evoked potential wave P2, insofar as both waveforms are very large amplitude, long duration positivities characterized by long recovery cycles. Based on previous studies of wave C and the generators of other middle-latency evoked potentials, we hypothesized that both wave NA and wave C might reflect, at least in part, the cortical culmination of a nonlemniscal line auditory association system arising in reticulothalamic projections to intralaminar and associated ventral thalamic regions. Relays from these thalamic areas are known to project to polysensory association cortex, including pericruciate gyrus, anterolateral gyrus, and medial suprasylvian gyrus. Therefore we implemented a series of lesion experiments to characterize the role of each of these cortical areas in the production of wave NA and wave C. Our results indicate that all three polysensory association areas contribute significantly to both waves NA and C, although the largest effects followed ablation of the pericruciate area alone. Thus, the generator substrates of waves NA and C appear to involve a long-recovery cycle system which functionally incorporates activation of association cortex.     

Correlation of manual dexterity and comprehension with oral hygiene and periodontal status in mentally handicapped adults

Although there is relatively little information concerning the oral health of handicapped adults there is increasing evidence to suggest that their oral condition, particularly periodontal health, is poor. The present investigation involved assessment of 382 handicapped patients attending four different Adult Training Centres in Birmingham. The caries status, oral hygiene, and periodontal conditions were evaluated and the Community Periodontal Index of Treatment Need (CPITN) was calculated. In order to assess the manual dexterity and the comprehension of the trainees a standard test was devised. This consisted of timing each participant in carrying out simple instructions to pick up and position certain common objects. The results indicated high levels of plaque, calculus, and bleeding with a mean CPITN of 7.43. The mean time taken for the manual dexterity and comprehension test was 23.9 seconds with a range from 10 to 80 seconds, S.E.+/- 1.33. This compares with results from 34 "normal" adults of a mean time of 8.2 seconds +/- 1.8 with a range of 6 to 12 seconds. There was no significant correlation between the Manual Dexterity and Comprehension scores and the periodontal indices in the handicapped adults.     

Mosaic ring 12p and total anomalous pulmonary venous return

An infant born with total anomalous pulmonary venous return (TAPVR) was found to have an extra chromosome present as a small ring. Spectral karyotyping and FISH analysis identified the material as a duplication involving the short arm of chromosome 12. Previous cases describing a variety of cytogenetic abnormalities that have been associated with TAPVR are reviewed along with prior cases of duplication 12p with their associated findings. We believe ours is the first case to report the occurrence of mosaic ring 12p and its association with TAPVR.     

Sexual assault and other types of sexual harassment by workplace personnel: a comparison of antecedents and consequences

Although sexual assault by workplace personnel is widely viewed as a type of sexual harassment, little is known about whether these overlapping constructs may possess some unique characteristics. This article compares the theoretical antecedents and consequences of sexual assault by workplace personnel and other types of sexual harassment among 22,372 women employed in the U.S. military. Path analysis revealed that low sociocultural and organizational power are associated with an increased likelihood of both types of victimization. Organizational climate and job gender context are directly associated with sexual harassment but are only indirectly associated with sexual assault by workplace personnel. Both types of victimization are associated with a variety of negative outcomes, but the pattern of negative consequences differs.     

Degradation of rubella virus envelope components

Summary Tween-ether treatment of rubella virus, which has no effect on the antigenic and electrophoretic properties of the two envelope glycoproteins, destroys infectivity and enhances haemagglutinating activity. Trypsin treatment alters the electrophoretic pattern of the envelope glycoproteins so that the VPI peak is no longer evident and the VPII peak is reduced. At the same time, both the properties of haemagglutination and infectivity are inactivated but the capacity to combine with neutralizing antibody is retained, which suggests that VPII may be responsible for inducing the production of neutralizing antibody.With 6 Figures     

Thymic stromal cell specialization and the T-cell receptor repertoire

Ten years ago, we proposed a model for thymus function in which thymic epithelial cells are primarily responsible for imprinting major histocompatibility complex (MHC)-restricted specificity, and bone marrow-derived macrophages or dendritic cells are responsible for the induction of self-tolerance. Since then, transgenic and knockout models have allowed for a dissection of thymic stromal components in vivo, leading to a new understanding of their specialized functions. We have determined that with regard to class II-restricted CD4 T-cell development, two distinct subsets of thymic epithelium help shape the repertoire: Cortical epithelium appears solely responsible for positive selection, whereas a fucose-bearing subset of medullary epithelium is specialized for negative selection. This absolute separation of positive and negative selection into two distinct spatial and temporal compartments leads to a much simpler view of the process of repertoire selection. Finally, a novel view of the function of the thymic medulla is discussed.     

Education modifies the effect of apolipoprotein epsilon 4 on cognitive decline

OBJECTIVES: To assess the influence of education on the association between apolipoprotein E and cognitive change. DESIGN: Prospective cohort. PARTICIPANTS: HMO-based sample of 2168 non-demented community-dwelling elderly followed over 6 years. MEASUREMENTS: Generalized estimating equations were used with the difference between baseline and follow-up cognitive abilities screening instrument (CASI) as the outcome variable. RESULTS: At follow-up, 6% of the sample had a decline of 1.5 S.D. or greater on the CASI. Compared to individuals without an APOE4 allele, individuals with a single APOE4 allele did not have greater CASI decline. By contrast, individuals with two APOE4 alleles experienced greater decline in cognitive performance and the magnitude of that decline decreased as years of educational attainment increased. These relationships held after adjusting for age, gender, ethnicity, depression, diabetes, and history of vascular disease. CONCLUSION: Lower education was associated with steep 4-year cognitive decline for APOE4 homozygotes but not for APOE4 heterozygotes. Potentially modifiable host factors such as education could influence the association of high-risk genotypes and cognitive decline.