Clinical pharmacology of oral and intravenous 4-demethoxydaunorubicin

Summary The clinical pharmacology of 4-demethoxydaunorubicin (4-DMDNR) was studied in 28 patients with advanced breast cancer, using a sensitive reverse-phase HPLC technique. All patients had normal renal and hepatic function. The serum levels of 4-DMDNR after a single i.v. bolus injection followed a triple exponential decay curve (T1/2=9.6 min, T1/2=3.2 h and T1/2=34.7 h) and conformed to a three-compartment model. Comparison of the area under the curve (AUC) and urinary excretion for the oral and i.v routes suggests an oral bioavailability of approximately 24%. In patients treated with a schedule of weekly oral administration for periods of up to 12 months there was no significant alteration in either AUC or elimination half-life for the parent drug or its principal metabolite 13-OH4DMDNR. Moreover, there was no evidence of accumulation of the metabolite although measurable amounts were present 7 days after administration of 4-DMDNR.This work was supported by the Cancer Research Campaign and Farmitalia Carlo Erba Ltd     

Efficacy of misoprostol (twice daily dosage) in acute healing of duodenal ulcer

This study was undertaken to evaluate the efficacy of misoprostol taken twice daily for the healing of duodenal ulcer. Three hundred thirty patients with endoscopically proven duodenal ulcer participated in a multicenter, double-blind, controlled trial comparing placebo with misoprostol 200 μg and 400 μg twice daily for up to four weeks. Patient characteristics were similar in all three treatment groups. Ulcers were between 0.3 cm and 2.0 cm in length. Healing was determined by endoscopy at two weeks; if ulcers were not healed, endoscopy was repeated at four weeks. All patients were given Al(OH)₃ antacid (up to 54 meq a day) to be used as needed for pain. Healing rates at four weeks for a total of 280 evaluable patients in the three treatment groups were as follows: misoprostol 400 μg bid, 65.4%; misoprostol 200 μg bid, 52.9%; and placebo, 42.2%. Misoprostol 400 μg bid was superior to placebo (P=0.002) in healing ulcers. However, the healing rate for misoprostol 200 μg bid did not differ significantly from placebo. The percentage of nonsmokers who healed at four weeks was higher than that of smokers in both misoprostoltreatment groups, although the difference was not analyzed for statistical significance. There were no differences in antacid consumption or pain relief among the three experimental groups during the study. Diarrhea was the most common side effect but was mild and self-limiting, occurring in 8.9%, 5.9%, and 1.8% of the misoprostol 400 μg, 200 μg, and placebo groups, respectively. These results indicate that misoprostol 400 μg, 200 μg, and for four weeks is effective and safe for the treatment of duodenal ulcers.     

Raising the ambient potassium ion concentration enhances carbachol stimulated phosphoinositide hydrolysis in rat brain hippocampal and cerebral cortical miniprisms

Summary The influence of the ambient potassium ion concentration ([K⁺]_ upon agonist stimulated hydrolysis of phosphoinositides (PI) has been studied in isolated miniprisms of rat hippocampus and cerebral cortex. When the external [K⁺] was raised from 6 to 18 mmol/l, there was little or no increase in the hydrolysis of PI in the absence of agonist, however, carbachol (100 mol/l) stimulated hydrolysis was greatly enhanced in both brain regions studied. Thus, carbachol stimulated the hydrolysis of PI to 146% and 386% of control levels at potassium concentrations of 5.8 and 18.2 mmol/l, respectively, in the rat hippocampus. A similar enhancement of muscarine (100 mol/l) stimulation was observed in cortical miniprisms with 18 mmol/l [K⁺]. A further enhancement was seen at higher ambient [K⁺], although basal hydrolysis of PI was then also increased. The carbachol-stimulated hydrolysis of PI found at both 6 and raised [K⁺] was prevented by atropine (1 and 10 mol/l) and tetraethylammonium (20 mmol/l), but not by 10 mmol/l Mg²⁺. Pirenzepine (50 nmol/l) also reduced this response. The ions Cs⁺ and Rb⁺ (but not Li⁺ or Tris⁺) produced a similar enhancement of the carbachol stimulation to that found with K⁺. At a buffer [K⁺] of 6 mmol/l, noradrenaline (100 mol/l) produced a 2-fold increase in the hydrolysis of PI whereas 5-hydroxytryptamine (100 mol/l) and histamine (500 mol/l) had little or no effect. However, histamine and 5-hydroxytryptamine did stimulate the hydrolysis of PI when [K⁺] was increased. Miniprism ATP content was not changed by a rise in [K⁺] to 18 mmol/l. The significance of these results is discussed in terms of the postsynaptic cellular events following cholinergic stimulation.     

Distinct groups of smokers in primary care based on mental health diagnosis

Journal of Public Health - To determine whether statistically distinct classes of smokers exist according to mental health (MH) diagnoses within primary care and to evaluate whether class...     

Establishing the minimal clinically important difference of the EQ-5D-3L in older adults with a history of falls

Quality of Life Research - Establish the minimal clinically important difference (MCID) of a health-related quality of life (HRQoL) measure—the EuroQol EQ-5 Dimensions-3 Level...     

Correction to: Patterns of School Victimization and Problem Behaviors: Longitudinal Associations with Socioeconomic Well-Being and Criminal Justice Involvement

Child & Youth Care Forum -     

Describing the Use of a Mindfulness-Based App for Sleep and Mental Well-Being,Across Age,in Children

Child & Youth Care Forum - In the United States, 68% of children do not get the recommended nine hours of sleep, which can lead to many negative health outcomes (e.g., mental health)....     

Racial Identity Clusters and Their Relation to Postpartum Maternal Functioning in Black Women

Maternal and Child Health Journal - Racial identity, which is the degree that individuals define themselves regarding their racial group membership, may influence the mental well-being of Black...     

The Impact of Culturally-Centered Care on Peripartum Experiences of Autonomy and Respect in Community Birth Centers: A Comparative Study

Maternal and Child Health Journal - National studies report that birth center care is associated with reduced racial and ethnic disparities and reduced experiences of mistreatment. In the US, there...     

Musculoskeletal injury survivors’ resiliency: A systematic review

BackgroundMusculoskeletal traumas are on the rise in the United States; however, limited studies are available to help trauma providers assess and treat concerns beyond the physical impact. Little is understood about the psychological, social, and spiritual factors that protect patients from adverse effects after a physical trauma or their experiences with each factor afterward.ObjectiveThis systematic review was conducted to investigate and review advancements in research related to risk and resiliency factors experienced by survivors of traumatic musculoskeletal injuries. The use of biopsychosocial-spiritual (BPS–S) framework and resiliency theory guided the analysis.MethodsResearchers reviewed 1003 articles, but only seven met the search criteria. Due to the complexity and uniqueness of traumatic brain injuries, studies on that target population were excluded.ResultsOf the seven articles reviewed, three identified psychological protective factors that protect against negative health outcomes; three identified negative psychological, social, or spiritual outcomes; and none investigated social or spiritual health.ConclusionsThere are significant gaps in the literature surrounding risk and resiliency factors related to the BPS-S health of musculoskeletal injury survivors.