Pharmacokinetics and safety of bromotetrandrine (BrTet, W198) after single-dose intravenous administration in healthy Chinese volunteers

Objective: To investigate the safety and pharmacokinetics of bromotetrandrine (BrTet, W198), a novel inhibitor of P‐glycoprotein (P‐gp), after single‐dose i.v. infusion in healthy Chinese volunteers. Methods: We conducted a randomized, dose‐escalating, phase I clinical study for that purpose. Thirty healthy subjects received BrTet at the doses of 10, 20 or 30 mg/m² by i.v. infusion. Plasma and urine concentrations of bromotetrandrine were determined by using a liquid chromatography–tandem mass spectrometric (LC/MS/MS) method. AUC was calculated by the trapezoidal rule extrapolation method. C_max, T_max, t_1/2α, t_1/2β, Cl and V_d were compiled from the plasma concentration–time data. Results: Bromotetrandrine was generally well tolerated at all doses. No serious or severe adverse events were found in the study. The pharmacokinetic parameters of BrTet after single i.v. infusion doses of BrTet 10, 20 and 30 mg/m² were as follows: T_max were 1·5 h in three groups, C_max were 24·79, 39·59 and 64·31 μg/L, t_1/2α were 0·37, 0·29 and 0·30 h, t_1/2β were 62·88, 56·45 and 52·20 h. AUC_0–194h were 345·83, 688·15 and 1096·28 μg h/L, Cl were 23·68, 25·69 and 25·66 L h/m², V_d were 157·73,156·96 and 140·73 L/m². In urine, the total eliminate rate of originate compound was 0·61 ± 0·19%. Conclusions: This study suggested that bromotetrandrine was well tolerated in healthy volunteers within the dose range evaluated. The pharmacokinetics parameters of bromotetrandrine indicated that the compound was rapidly distributed and accumulated in the tissues, and slowly cleared from plasma, which supported the use of BrTet for a once or twice dosing per chemotherapy cycle.     

Who can give ‘spiritual care’? The management of spiritually sensitive interactions between nurses and patients

kevern p. (2012) Journal of Nursing Management  20, 981–989
Who can give ‘spiritual care’? The management of spiritually sensitive interactions between nurses and patients Aims This article considers the purpose of contemporary ‘spiritual care’ in order to help managers make informed decisions about its appropriate delivery in a clinical context. Background Although there are national policies in place concerning spiritual care, surveys indicate that nurses are reluctant to engage with the spiritual needs of patients. Evaluation A consideration of the character of spiritual care indicates the need to take account of the context of contemporary Western society. A model drawn from the social psychology of religion is used to analyse the different types of nurse–patient interaction available in the provision of spiritual care. Key Issues Although religious and spiritual commitments can vary widely, they are subject to the same pressures in a secular and pluralist social context. This enables some general guidelines to be developed. Conclusions Effective spiritual care requires a consideration of both the patient’s and the nurse’s implicit and explicit religious commitments. Implications for nursing management Nurse managers need to take account of the personal commitments of nurses when directing them to offer spiritual care. This article offers a diagnostic tool for deploying nurses in an appropriate way.     

Pityriasis alba: a study of pathogenic factors

BACKGROUND: The aetiology of pityriasis alba (PA), a common dermatosis in childhood, is still controversial. The objective of this study was to assess the possible aetiopathogenic factors of this disease in infants. METHODS: Forty-four patients with PA and 31 healthy children were examined and compared. Personal hygiene habits, sun exposure, presence of Staphylococcus aureus in nasal fossae and presence of major or minor signs of atopy were assessed during anamnesis and physical examination. Susceptibility to ultraviolet (UV) B radiation was measured by the onset of a contact hypersensitivity reaction to diphenylcyclopropenone in individuals sensitized in previously irradiated areas. RESULTS: The prevalence of PA was higher in individuals with darker skin, in high phototype categories, as well as in males. The number of daily baths and sun exposure between 10.00 h and 15.00 h were significantly higher in the PA group when compared with controls (P = 0.03 and P = 0.0015, respectively). The presence of atopy signs was more common in pityriasis patients (P = 0.002). Susceptibility to UVB radiation was 29.6% in the PA group vs. 29.0% in the control group; nevertheless, important differences were found after stratification in order to control possible confounding factors. The presence of S. aureus in the nostrils was equal in both groups. CONCLUSIONS: Our results confirm that PA, in our population, is more prevalent in males and in individuals in higher phototype categories. In those with inadequate personal hygiene and sun exposure habits the disease is more accentuated, demonstrating that the xerosis presenting in individuals with atopic diathesis is an important element in the development of the disease. S. aureus is not an important aetiopathogenic factor in PA. Susceptibility to UVB becomes important when related to the patient's phototype.     

Phylogenetic analysis of human G9P[8] rotavirus strains circulating in Jiangsu,China between 2010 and 2016

Rotavirus A (RVA) is the leading cause of acute viral gastroenteritis in children under 5 years of age worldwide. G9P[8] is a common RVA genotype that has been persistently prevalent in Jiangsu, China. To determine the genetic diversity of G9P[8] RVAs, 7 representative G9P[8] strains collected from Suzhou Children’s Hospital between 2010 and 2016 (named JS2010‐JS2016) were analyzed through whole‐genome sequencing. All evaluated strains showed the Wa‐like constellation G9‐P[8]‐I1‐R1‐C1‐M1‐A1‐N1‐T1‐E1‐H1. Furthermore, phylogenetic analysis revealed that the VP7 genes of all strains clustered into lineage G9‐III and G9‐VI. With the exception of strain JS2012 (P[8]‐4), the VP4 sequences of all strains belonged to the P[8]‐3 lineage. Sequencing further revealed that amino acid substitutions were present in the antigenic regions of the VP7 and VP4 genes of all strains. Moreover, there were multiple substitutions in antigenic sites I and II of the nonstructural protein 4 (NSP4) genes, whereas the other NSP genes were relatively conserved. In conclusion, our phylogenetic analysis of these 7 G9P[8] strains suggests that RVA varied across regions and time. Therefore, our findings suggest that continued surveillance is necessary to explore the molecular evolutionary characteristics of RVA for better prevention and treatment of acute viral gastroenteritis.     

Defective opsonization in multiple myeloma

The mechanisms responsible for the unusual susceptibility of multiple myeloma (MM) patients to infections are incompletely defined. Since MM is associated with decreased production of normal serum proteins, we investigated the possibility that the production of opsonins might also be impaired. The neutrophil chemiluminescence assay of opsonization was used to evaluate the ability of serum from patients with MM to opsonize zymosan. It was found that sera from 18 MM patients exerted only 50% +/- 2.5% (mean +/- SEM) of the opsonic activity found in 18 control sera (p less than 0.001). In mixture experiments, untreated normal serum completely restored the opsonic activity of MM serum, suggesting a deficiency of opsonic factors rather than an inhibitor. In other mixture experiments, heat-inactivated normal serum only partially corrected the opsonic defect in MM serum. Serum from three patients had low C3 levels, and treatment of particles with these resulted in a greater opsonic defect than the patient population as a whole (p less than 0.02). No correlation between the opsonic defect and infections was established over an 18-mo period. These data suggest that MM serum lacks both heat-stable and heat-labile opsonic activity, the direct clinical significance of which remains to be clarified. However, these studies support the concept that defective host resistance in MM may be multifactoral, combining opsonic abnormalities with other defects previously described.     

Synergistic cytotoxic effect of azidothymidine and recombinant interferon alpha on normal human bone marrow progenitor cells

Azidothymidine (AZT) and interferon alpha (IFN-alpha) are among the drugs showing strong in vitro activity against the human immunodeficiency virus type-1 (HIV-1). Each drug, however, has significant toxicity against normal marrow progenitor cells that frequently proves dose-limiting in patients. In this study, AZT and recombinant IFN-alpha 2a (rIFN-alpha 2a) were tested as single agents and in combination against normal myeloid (CFU-GM) and erythroid (BFU- E) colony forming cells in a standard methylcellulose culture assay. The data were analyzed using a quantitative computerized analysis based on the median-effect principle and the isobologram equation as described by Chou and Talalay (Adv Enz Regul 22:27, 1984). The ED90 for BFU-E and CFU-GM inhibition was then compared with previously measured in vivo plasma levels of each drug and the ED90 for the anti-HIV-1 effect in vitro. We demonstrate that (a) the drugs are strongly synergistic in inhibiting marrow progenitor cell growth and that this synergism occurs at drug levels that are within the range of measured plasma levels in phase I clinical trials, (b) BFU-E are more sensitive than CFU-GM to the inhibiting effects of AZT, rIFN-alpha 2a or both drugs in combination, (c) the drug concentrations in combination that synergistically inhibit bone marrow progenitors are much higher than those required to inhibit HIV-1 replication in vitro, and (d) the anti- HIV-1 effect for the combination of AZT and rIFN-alpha 2a was clearly superior to the effect of AZT or rIFN-alpha 2a alone as indicated by the combination index and the dose-reduction index. These data suggest that substantially lower doses of AZT and rIFN-alpha than those currently being tested in clinical trials might not only maintain a strong synergistic anti-HIV-1 effect but might also avoid significant hematologic toxicity.