Multiple-dose pharmacokinetics of efavirenz with and without the use of rifampicin in HIV-positive patients

Rifampicin (RIF) decreases serum concentrations of several antiretroviral drugs. We carried out a prospective, comparative study to define efavirenz (EFV) pharmacokinetics in 16 cases and 13 controls. Cases were HIV and tuberculosis (TB) co-infected adults assuming RIF 600 mg once daily and EFV 800 mg once daily. Patients on EFV at standard 600 mg dose without RIF were taken as controls. EFV levels in plasma were assayed by high-performance liquid chromatography (HLPC) predose (C(trough)) and at 1, 2, 3, 4, 5, 6, 8, 10, 11, 12, 13, 14, 16, 18, 22 and 24 hours post-dose, and pharmacokinetic parameters were determined by non-compartmental methods. Among cases, 81% were males, mean age was 37 years, 50% were Caucasians, mean weight was 64 kg, mean CD4 cell counts and log HIV RNA copies were 160/microl and 5.2 /microl, respectively. Cases had a significantly higher Cl/F/kg if compared with controls (0.269 +/- 0.12 versus 0.167 + 0.05 L/h/kg, p<0.01). Otherwise, dose-dependent pharmacokinetic parameters of EFV were similar between cases and controls. Interindividual variability was consistently higher among TB cases compared to controls for all considered parameters. All cases completed combined treatment and no increased EFV toxicity was observed. These results suggest that a dose of 800 mg of EFV in association with rifampicin may be appropriate for patients of weight > 60 kg in Europe. Therapeutic drug monitoring may be beneficial for patients on combination therapy with RIF.     

Evaluation of Mental Health First Aid training with members of the Vietnamese community in Melbourne, Australia

Background  

The aim of this project was to investigate in members of the Vietnamese community in Melbourne the impact of Mental Health First Aid (MHFA) training on attitudes to people with mental illness and on knowledge about mental disorders. Our hypotheses were that at the end of the training participants would have increased knowledge of mental disorders and their treatments, and decreased negative attitudes towards people with mental disorders.     

The clinical significance of body composition and anthropometric evaluation in athletes

Body composition and anthropometric assessment provide the sports physician with useful information on the health state of the athlete and with some necessary elements to plan specific training loads in the most appropriate way. In practice, the chemical composition of an athlete’s body (especially those who carry out 1–2 daily workouts) is always in a physiologic condition that we can define as “dynamic” (concentration of electrolytes, hydration state and relationship between intra-and extra-cellular water, stages of growth of muscle mass and/or reduction of fat mass, etc.), with the exception of few times of year, such as the short resting break before resuming training. As a consequence, a real “baseline” (or “stationary”) physiological state, allowing to detect the parameters of body composition under the same conditions several times during the year, is only rarely achieved. In this paper, we wanted to review the most interesting parameters and methods for the evaluation of athletes’ body composition, and underline their potential applications, possible advantages, theoretical and practical limitations.     

An economic evaluation of home-care assistance for AIDS patients: a pilot study in a town in northern Italy.

OBJECTIVE: To evaluate the costs and cost-effectiveness of home-care assistance (HCA) as an alternative to hospital-based care only for patients with AIDS (PWA). DESIGN: A 6-month prospective study. Use of resources by a control group of PWA receiving ordinary hospital-based care (OC group) was compared with that by a random group of PWA who, in addition to hospital care, were also receiving home care (HC group). SETTING: Home- and hospital-based care for PWA in Vicenza, Italy. PATIENTS: HC group selection was based on eligibility criteria for severity of illness, home location and economic and family support. Ten of the PWA satisfying all eligibility criteria were randomly allocated to the HC group. The control group consisted of 32 PWA lacking one or more of the eligibility criteria. INTERVENTION: HCA involved the provision of palliative care for PWA by a multidisciplinary team of caregivers. Hospital-based services covered inpatient and outpatient services. MAIN OUTCOME MEASURE: The health benefits for HC and OC groups using a quantitative quality of life measure (the Quality of Well-Being Scale). RESULTS: Overall health-care cost savings of 6-7%, relative to the OC group, were predicted for the HC group. Costs per well week were estimated at US$482 for the HC group and US$791 for the OC group. CONCLUSION: Home-care assistance appears to be a cost-effective strategy for the treatment and care of PWA if strict eligibility criteria are adhered to.     

Low rates of homogenization of the DBC-150 satellite DNA family restricted to a single pair of microchromosomes in species from the Drosophila buzzatii cluster

A satellite DNA family, termed DBC-150, comprises slightly GC-rich repeat units of approximately 150 bp that were isolated (by DNA digestions or PCR) from the genome of all seven Drosophila species from the buzzatii cluster (repleta group). The presence of subrepeats suggests that part of the extant DBC-150 monomer originated by the duplication of small sequence motifs. The DBC-150 family is compared to the previously described pBuM satDNA family, an abundant component of the genome of five species of the cluster. The two families are different in several aspects, including primary structure, A + T content, intraspecific and interspecific variability and rates of homogenization (or nucleotide spread). The data indicate a lower rate of homogenization (and absence of complete concerted evolution) of the DBC-150 compared to the pBuM family. FISH on metaphase chromosomes revealed that the DBC-150 family is located exclusively in the microchromosomes. To our knowledge this is the first record of a complex Drosophila satDNA restricted to a single pair of microchromosomes. The observed low rates of homogenization of the DBC-150 family might be related to a presumed reduction or suppression of meiotic recombination in the microchromosomes.     

"Focus groups can be fun": the use of activity-oriented questions in focus group discussions

Interest in focus group discussions has grown recently, and so has the recognition of them as a valuable method for qualitative data collection. Despite increasing popularity, they are not an easy option, and moderators must find appropriate ways to approach participants to achieve good-quality data. A path to reach this aim is the inclusion in the focus group agenda of some "exercises" (or activity-oriented questions) that are enjoyable and productive supplements to questions. Exercises provide a different way of gathering information and are beneficial, for instance, for more reflective participants. They can help focus the group's attention on the core study topic and also make subsequent comparative analysis more straightforward. They can also be helpful with young people and to discuss sensitive topics. The author describes and provides suggestions for use and examples of several exercises, illustrating their application in a research project investigating the cultural meaning of youth suicide in university students in Italy, India, and Australia.     

Monosomy of chromosome 17 in breast cancer during interpretation of HER2 gene amplification

Monosomy of chromosome 17 may affect the assessment of HER2 amplification. Notably, the prevalence ranges from 1% up to 49% due to lack of consensus in recognition. We sought to investigate the impact of monosomy of chromosome 17 to interpretation of HER2 gene status. 201 breast carcinoma were reviewed for HER2 gene amplification and chromosome 17 status. FISH analysis was performed by using double probes (LSI/CEP). Absolute gene copy number was also scored per each probe. HER2 FISH test was repeated on serial tissue sections, ranging in thickness from 3 to 20 µm. Ratio was scored and subsequently corrected by monosomy after gold control test using the aCGH method to overcome false interpretation due to artefactual nuclear truncation. HER2 immunotests was performed on all cases. 26/201 cases were amplified (13%). Single signals per CEP17 were revealed in 7/201 (3.5%) cases. Five out of 7 cases appeared monosomic with aCGH (overall, 5/201, 2.5%) and evidenced single signals in >60% of nuclei after second-look on FISH when matching both techniques. Among 5, one case showed amplification with a pattern 7/1 (HER2/CEP17>2) of copies (3+ at immunotest); three cases revealed single signals per both probes (LSI/CEP=1) and one case revealed a 3:1 ratio; all last 4 cases showed 0/1+ immunoscore. We concluded that: 1) monosomy of chromosome 17 may be observed in 2.5% of breast carcinoma; 2) monosomy of chromosome 17 due to biological reasons rather than nuclear truncation was observed when using the cut-off of 60% of nuclei harboring single signals; 3) the skewing of the ratio due to single centromeric 17 probe may lead to false positive evaluation; 4) breast carcinomas showing a 3:1 ratio (HER2/CEP17) usually show negative 0/1+ immunoscore and <6 gene copy number at FISH.     

Evolution of gastric electrical features and gastric emptying in children with Duchenne and Becker muscular dystrophy

OBJECTIVES: Although muscular dystrophy (MD) affects primarily striated muscles, smooth muscle cells of the gastrointestinal tract may also be involved. We recorded gastric electrical activity and gastric emptying time (GET) in children with MD at initial presentation and at 3-yr follow-up in order to detect gastric motor abnormalities and study their evolution along the clinical course. METHODS: Twenty children with MD (median age: 4.6 yr; range age: 3-7 yr) were investigated by means of ultrasonography, for measuring GET, and by electrogastrography (EGG); 70 children served as controls. RESULTS: Ten patients had Duchenne muscular dystrophy (DMD) and 10 Becker muscular dystrophy (BMD). GET was significantly more delayed in MD patients (DMD, median: 195 min; range 150-260 min; BMD, median: 197 min; range: 150-250 min) than in controls (median: 150 min; 110-180 min; p < 0.05); it markedly worsened at the follow-up in DMD (median: 270 min; range 170-310 min; p < 0.001 vs controls) but not in BMD patients (median: 205 min; 155-275 min; p < 0.05 vs DMD). Baseline EGG showed a significantly lower prevalence of normal rhythm and significantly higher prevalence of dysrhythmias in both groups of patients as compared to controls (% of normal rhythm: DMD 66.7 +/- 8.2, BMB 67.2 +/- 11.5, controls 85.3 +/- 7.2, p < 0.001; % of tachygastria: DMD 28.4 +/- 8.0, BMB 29.8 +/- 12.3, controls 10.6 +/- 5.1, p < 0.001; % of dominant frequency instability coefficient: DMD 36.1 +/- 6.0, BMB 33.2 +/- 2.9, controls 17.9 +/- 7.1, p < 0.001); furthermore, no difference in fed-to-fasting ratio of the dominant EGG power was found between the two groups and controls (DMD 2.84 +/- 1.27, BMB 2.82 +/- 0.98, controls 3.04 +/- 0.85, ns). However, at the follow-up no significant change in the prevalence of normal rhythm and dysrhythmias occurred in both groups (ns vs baseline values), whereas only DMD patients showed a marked reduction in fed-to-fasting power ratio (0.78 +/- 0.59; p < 0.001 vs controls and BMD; p < 0.05 vs baseline), which correlated with the progressive neuromuscular weakness occurring in DMD subjects (r, 0.75; p < 0.001). CONCLUSIONS: In children with MD, there is an early abnormality in gastric motility that is due to deranged regulatory mechanisms, whereas contractile activity of smooth muscle cells seems to be preserved. At the follow-up, DMD patients exhibited a progressive failure in neuromuscular function, which was accompanied by a gastric motility derangement with worsening in GET and in EGG features suggesting an altered function of gastric smooth muscle cells.     

Human CD4+ T cell clone longevity in tissue culture: lack of influence of donor age or cell origin.

CD4+ human T cell clones were derived from activated peripheral blood lymphocytes of healthy young adults to establish cloning efficiencies (CE) and clonal longevities. These results were compared with those obtained using cells from the very elderly, also in excellent health. CE and both maximal and average longevities under appropriate culture conditions were very similar in the two groups. Moreover, CE of CD34+ hematopoietic progenitor cells and longevities of clones derived from them were also similar. Finally, CE and longevities of clones derived from a patient with chronic myelogenous leukaemia were found to be comparable as well. Hence, T cells with absolutely no antigenic exposure in vivo prior to cloning (i.e. CD34-derived) and those potentially exposed to chronic antigenic stimulation (CML-derived) and those from young or old donors all had similar cloning and propagation properties in vitro. These results imply that the longevity of T cells in culture is more likely to be dictated by cloning conditions than any intrinsic differences between the cells studied.