Pharmacokinetics of dolasetron after oral and intravenous administration of dolasetron mesylate in healthy volunteers and patients with hepatic dysfunction

In previous studies, dolasetron was shown to have both renal and hepatic elimination mechanisms. This study was conducted to determine the impact of varying degrees of hepatic dysfunction on the pharmacokinetics and safety of dolasetron and its reduced metabolites. Seventeen adults were studied: six healthy volunteers (group I), seven patients with mild hepatic impairment (Child-Pugh class A; group II), and four patients with moderate to severe hepatic impairment (Child-Pugh class B or C1; group III). Single 150-mg doses of dolasetron mesylate were administered intravenously and orally, with a 7-day washout period separating treatments. After intravenous administration, no differences were observed between healthy volunteers and patients with hepatic impairment in maximum plasma concentration (Cmax), areas under the plasma concentration-time curve (AUC), or elimination half-life (t1/2) of intact dolasetron. No significant differences were found in Cmax, AUC, or apparent clearance (C(lapp)) of hydrodolasetron, the primary metabolite of dolasetron. The mean t1/2 increased from 6.87 hours in group I to 11.69 hours in group III. After oral administration, C(lapp) of hydrodolasetron decreased by 42%, and Cmax increased by 18% in patients with moderate to severe hepatic impairment. There were less changes in patients with mildly hepatic impairment. Total percentage of dose excreted as metabolites was similar for healthy volunteers and patients with hepatic impairment, although urinary metabolite profiles differed slightly. Dolasetron was well tolerated and there were no apparent differences in adverse effects between groups or treatments. Because hepatic impairment did not influence Cl(app) of hydrodolasetron after intravenous administration, and the range of plasma concentrations of hydrodolasetron after oral administration was not different from those observed in healthy volunteers, dosage adjustments are not recommended for patients with hepatic disease and normal renal function.     

Selection of serum deproteinization methods

Dentists are often called upon to perform painful procedures on children. This may present a management problem for the practitioner who is unfamiliar with accepted behavioural management techniques or prescribing analgesics for paediatric patients. This article will review techniques that may be used to guide a child patient's behaviour through painful procedures as well as addressing the need for post-operative analgesics in the paediatric population.     

Health status of the over 60 years of age population and its relationship with sociodemographic factors (ANCO Project)

OBJECTIVE: To describe the health status of a population over 60 years and to study their relationship with several socio-demographic variables. DESIGN: A cross-sectional study, population based. SETTINGS: A community. PARTICIPANTS: A randomized sample of 1,103 non institutionalized people over 60 years living in the city of Cordoba (Spain). MEASUREMENTS AND MAIN RESULTS: By mean of a personal interview at home we used the OARS-MFAQ-VE questionnaire. Low self-rated health was associated with the age, to be female sex, a low cultural background, and a low income. Only 5.2% of the study people do not suffered any illness and 56% state that their health problems are major problems for doing their current activities. 4.9% declared to have some degree of physical incapacity. 3.7% of elderly population has an important cognitive deficit. CONCLUSIONS: The majority of elderly people has good health. Age is related with a poor health. Women have more health problems than men.     

Cryptococcosis in tree shrews (Tupaia tana and Tupaia minor) and elephant shrews (Macroscelides proboscides)

OBJECTIVE: To determine the relation between metabolic and anthropometric parameters and circulating leptin concentrations in women with polycystic ovary syndrome (PCOS). DESIGN AND PATIENTS: Correlation of fasting serum leptin concentrations with anthropometric measures and multiple metabolic parameters including insulin and glucose responses to a 2-hour 75-g oral glucose tolerance test (OGTT) in 85 women with PCOS (17-36 years, body mass index (BMI) 29.9 +/- 0.9 kg/m2, mean +/- SD) and 18 control women (25-47 years, BMI 25 +/- 1.7 kg/m2). Diagnostic criteria for PCOS: characteristic ovarian morphology on ultrasound plus at least two of (1) elevated serum testosterone; (2) elevated serum androstenedione; and (3) reduced serum SHBG concentrations. MEASUREMENTS: Concentrations of androgens, lipids, PRL, gonadotrophins, and leptin were measured in the baseline fasting blood sample from an OGTT. Insulin and glucose were measured throughout OGTT. Serum leptin concentrations were measured by radioimmunoassay. RESULTS: Log leptin levels in the PCOS group correlated significantly with BMI (r = 0.85, P < 0.0001) and with 8 other parameters including waist/hip ratio (r = 0.51, P = 0.0005). By stepwise regression analysis, only BMI (P < 0.0001) and plasma high density lipoprotein concentration (P = 0.02) were independently correlated with log leptin levels, both positively. There was no effect of fat distribution, as measured by waist/ hip ratio, on leptin concentrations. Comparison of control subjects to a BMI-matched subgroup of 55 PCOS subjects revealed significantly higher circulating concentrations of LH, testosterone, DHEAS, progesterone and androstenedione, and higher glucose and insulin responses to OGTT in the PCOS group. Leptin levels were not different between the PCOS subgroup and control group (14.8 +/- 1.3 vs 12.1 +/- 2.3 micrograms/l, mean +/- SE, P = 0.26) and the relation of BMI to leptin levels determined by linear regression analysis also did not differ between the two groups. CONCLUSIONS: Our results indicate that circulating leptin concentrations in women with PCOS, a condition characterized by hyperandrogenaemia, increased LH concentrations and insulin resistance, are strongly related to BMI and not independently affected by circulating levels of insulin, gonadotrophins or sex hormones.     

Simple concepts for ion source improvement

We report on improvements in the overall intensity of a sputter ion source that evolved originally from an NEC MCSNICS. Beam output increases benefit both AMS measurements and nuclear physics experiments using low natural abundance beams. In particular, minor changes in source geometry suggested by a combination of electrostatic calculations and simple design principles have yielded increases in extracted negative ion intensity of nearly a factor of 4.     

Site-specific endonucleases RspLKI and RspLKII from Rhodococcus species LK2 are isoschizomers of SphI and BamHI

Two site-specific endonucleases, RspLKI and RspLKII, have been isolated and purified to functional homogeneity from the soil bacterium Rhodococcus species LK2. RspLKI recognizes the 5'-GCATG decreases C-3' DNA sequence and RspLKII recognizes the 5'-G decreases GATCC-3' sequence (arrows indicate DNA cleavage sites). The isolated enzymes are class II site specific endonucleases and are isoschizomers of endonucleases SphI and BamHI, respectively.     

Resection of the right middle lobe and lingula for mycobacterial infection

BACKGROUND: In a series of 229 patients infected with mycobacterial organisms, we noted a specific female phenotype that involves isolated infections of the middle lobe and lingula. METHODS: Thirteen patients were found to have infections of the middle lobe, lingula, or both. All of them were infected with Mycobacterium other then Mycobacterium tuberculosis, all were women, 12 of the 13 were slender, and most had variable combinations of skeletal abnormalities. All underwent resection of the middle lobe, lingula, or both. RESULTS: There were no operative deaths. Only 2 patients have had reactivation requiring additional antibiotic therapy. All patients have had a decreased number of pulmonary infections in the postoperative period. Anatomic findings at operation included a complete major fissure and at least a partially complete minor fissure with middle lobe resections or an elongated lingula. CONCLUSIONS: Mycobacterial infection of the middle lobe and lingula is primarily a disease of asthenic women and is often associated with skeletal abnormalities and complete fissures or an elongated lingula. We recommend that surgical intervention be performed early once the condition is identified.     

Incorporating social support into a community-wide smoking-cessation contest

Exposure to foreign particles sometimes causes inflammatory reactions through production of cytokines and chemoattractants by phagocytic cells. In this study, we focused on macrophage migration inhibitory factor (MIF) to evaluate its pathophysiological role in the phagocytic process. Immunohistochemical analysis of human pseudosynovial tissues retrieved at revision of total hip arthroplasty showed that infiltrating mononuclear and multinuclear cells were positively stained by both an anti-CD68 antibody and anti-human MIF antibody. For in vitro study, MIF was released from murine macrophage-like cells (RAW 264.7) in response to phagocytosis of fluorescent-latex beads in a particle dose-dependent manner. Northern blot analysis showed marked elevation of the MIF mRNA level in the phagocytic macrophage-like cells. Moreover, pretreatment of RAW 264.7 cells with rat recombinant MIF increased the extent of phagocytosis by 1.6-fold compared with the control. Taken together, these results suggest that MIF plays an important role by activating macrophages in autocrine and paracrine fashion to phagocytose foreign particles.