Simultaneous quantitation of plasma doxorubicin and prochlorperazine content by high-performance liquid chromatography

A high-performance liquid chromatographic method has been developed and tested for simultaneous extraction, elution and determination of doxorubicin and prochlorperazine content in human plasma samples. The procedure consists of extraction through a conditioned C18 solid-phase extraction cartridge, elution from a Spherisorb C8 reversed-phase column by an isocratic mobile phase (60% acetonitrile, 15% methanol and 25% buffer) followed by detection with electrochemical and fluorescence detectors. Recovery of doxorubicin and prochlorperazine from pooled human plasma samples (n=3) containing 100 ng/ml of the two drugs was 77.8+/-3.5% and 89.1+/-6.0%, respectively. The lower limits of quantitation for doxorubicin and prochlorperazine in plasma samples were 6.25 ng/ml and 10 ng/ml, respectively. A linear calibration curve was obtained for up to 2 microg/ml of doxorubicin and prochlorperazine. This combination method may be of particular value in clinical studies where phenothiazines such as prochlorperazine are used to enhance retention of doxorubicin in drug resistant tumor cells.     

Efficacy and tolerability of oral ondansetron versus prochlorperazine in the prevention of emesis associated with cyclophosphamide-based chemotherapy and maintenance of health-related quality of life

This study compared the efficacy and tolerability of oral ondansetron (8 mg twice daily [BID] for up to 3 days) with those of phenothiazine prochlorperazine (10 mg BID for up to 3 days) in 133 cancer patients receiving cyclophosphamide-based chemotherapy. In addition, the study evaluated the impact of these treatments on patients' health-related quality of life, measured with both the Functional Living Index--Cancer and the Functional Living Index--Emesis questionnaires. The first dose of study drug was administered 30 minutes before initiation of chemotherapy. Patients received a rescue antiemetic at their request or if the investigator deemed it necessary. There was a statistically significant difference in the number of patients with no emetic episodes over the 3-day study period: 60% in the ondansetron group compared with 21% in the prochlorperazine group. Twenty-five percent of ondansetron-treated patients compared with 68% of prochlorperazine-treated patients experienced three or more emetic episodes, rescue medication use, or withdrawal from the study due to adverse events or lack of efficacy of the study drug. Among patients with at least one emetic episode, the mean time to emesis was significantly longer (13 hours and 37 minutes) in the ondansetron group compared with the prochlorperazine group (9 hours and 30 minutes). Nausea and appetite scores did not differ significantly between groups. The score on the vomiting subscale of the Functional Living Index--Emesis was significantly more favorable in the ondansetron group compared with the prochlorperazine group, indicating better maintenance of health-related quality of life in ondansetron-treated patients. Both treatments were well tolerated. The most common potentially drug-related adverse event was headache, which occurred in significantly more (16%) ondansetron-treated patients compared with prochlorperazine-treated patients (3%). The results of this study demonstrate that oral ondansetron 8 mg BID for up to 3 days is more effective than prochlorperazine 10 mg BID for up to 3 days in the prevention of emesis associated with moderately emetogenic chemotherapy.     

Efficacy of ondansetron and prochlorperazine for the prevention of postoperative nausea and vomiting after total hip replacement or total knee replacement procedures: a randomized, double-blind, comparative trial

BACKGROUND: Limited data are available on the efficacy of ondansetron hydrochloride compared with prochlorperazine maleate for the treatment of postoperative nausea and vomiting (PONV). OBJECTIVE: To evaluate the comparative efficacy of ondansetron and prochlorperazine for the prophylaxis of PONV in patients undergoing total hip replacement or total knee replacement procedures. METHODS: A randomized, double-blind, comparative trial was conducted at a tertiary care, university hospital. Seventy-eight patients undergoing elective total hip or total knee replacement procedures received a single dose of ondansetron hydrochloride (n = 37), 4 mg intravenously, or prochlorperazine maleate (n = 41), 10 mg intramuscularly, at the end of the surgical procedure. Rescue therapy was administered every 4 hours as needed during the initial 48 hours. Primary outcome measures were the incidences and severity of PONV. Secondary outcome measures included the number of rescue antiemetic doses required, number of physical therapy cancellations because of PONV, length of hospital stay, and cost of antiemetic agents administered. RESULTS: The incidence of nausea was significantly greater in the ondansetron group compared with the prochlorperazine group (81% vs 56%; odds ratio, 3.4; 95% confidence interval, 1.2-9.4) as was the severity of nausea (P = .04). Multivariate analysis identified administration of ondansetron, history of PONV, obesity, and female sex as risk factors for a nausea event. The incidence of vomiting tended to be greater in the ondansetron group (49% vs 32%; odds ratio, 2.0; 95% confidence interval, 0.8-5.0). The need for rescue antiemetic therapy was also greater in the ondansetron group (46% vs 27%; odds ratio, 2.3; 95% confidence interval, 0.9-6.0). The mean antiemetic drug cost per patient was significantly greater for the ondansetron group ($47.56 vs $2.47; P<.001). However, the proportion of patients who were unable to participate in physical therapy because of PONV and the median length of hospital stay were similar in both groups. CONCLUSION: Prochlorperazine is associated with superior efficacy and significant cost savings compared with ondansetron for the prevention of PONV in patients undergoing total hip and total knee replacement procedures.     

Voices of fear and anxiety and sadness and depression: The effects of speech rate and loudness on fear and anxiety and sadness and depression.

Two studies investigated the role of expressive vocal behavior (specifically, speech rate and loudness) in fear and anxiety and in sadness and depression. In the 1st study, participants spoke about personally experienced fear and anxiety-arousing and neutral events using 3 different voice styles: fast and loud, normal, and slow and soft. In the 2nd study, participants spoke about personally experienced sad or depressing and neutral events using the same 3 voice styles. In both studies, the participants' highest levels of subjective affective and cardiovascular (CV) arousal occurred when they spoke about the emotional events in a mood-congruent voice style: fast and loud in the case of fear and anxiety, and slow and soft in the case of sadness or depression. Mood-incongruent voice styles canceled the heightened levels of CV arousal normally associated with these negative emotions. The voice-style manipulation had no significant effect on the participants' levels of CV arousal during the neutral discussions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Synthesis and analysis of mixed chlorinated-fluorinated dibenzo-p-dioxins and dibenzofurans and assessment of formation and occurrence of the fluorinated and chlorinated-fluorinated dibenzo-p-dioxins and dibenzofurans

Despite the use of multimodal therapy, higher-grade glioma is still uniformly fatal in the adult population. There is a considerable difference between the length of survival in each given patient, even within the same tumor type and malignancy grade group, suggesting that there are factors that might differentially influence outcome. To identify such factors, 107 patients with anaplastic or malignant glioma were retrospectively investigated. Clinical parameters and paraclinical data on the p53, mdm2, and EGFR genes at the DNA or protein level were evaluated by univariate analysis and Cox proportional hazards regression modeling. Kaplan-Meier survival estimation demonstrated that immunohistochemical positivity for mdm2 protein in patients with anaplastic astrocytoma or with glioblastoma multiforme was associated with a shorter survival time (p = 0.02). P53 gene mutations and immunopositivity for the epidermal growth factor receptor (EGFR) protein were not significantly related to poor prognosis. The Cox proportional hazards model revealed immunohistochemical positivity for p53, mdm2, or for both of them, the presence of postoperative irradiation, and the extent of surgical resection of tumor to be variables significantly associated with prolonged survival. EGFR overexpression, age over 60 years, and Karnofsky performance score below 40 points did not significantly shorten survival time. In conclusion, the present study identified immunohistochemically detected mdm2-protein overexpression as a statistically significant negative prognostic parameter in patients bearing anaplastic or malignant glioma. Association analysis of variables revealed a possible correlation between mdm2 and p53, which is also consistent with the biological interaction mode of both proteins in vivo.     

Sexuality and aging--usual and successful

BACKGROUND: As aging research increasingly reflects an effort to dissociate true time-driven changes from those that can be improved, sexuality in later life remains largely unexplored. Several problems are evident. There is a lack of normative data, a lack of a conceptual framework relating to the biology, psychology, and sociology of sex, and an attitudinal resistance that obscures the entire topic. METHODS: We conducted a three-part instructional series on major topics involved with sexuality and aging. We surveyed our group of attendees (n 158, average age 68 for males, 65 for females) before and after the series. RESULTS: A remarkably robust sex life was evidenced by both the men and the women, even until advanced old age. Yet, a substantially decreased involvement was reported from 10 years earlier. Despite current activities, people of both sexes wished they were participating even more than they currently were. Impotency was identified as the major negative feature for the men; relationship problems were for the women. A questionnaire 6 months after the series reported improved sexual attitudes, but no change in sexual activities from the earlier survey. CONCLUSION: Sexuality is a major quality-of-life issue which persists into old age. Our study showed that the usual sexual practices reported by our group were not considered by them to be ideal. The intervention of this instructional series provided improved sexual attitudes but not performance. Additional studies are encouraged.     

Spondylolysis and spondylolisthesis and sports

Spondylolysis and spondylolisthesis occur predominantly in the lower lumbar spine. Besides congenital defects such as predisposition of spondylolysis the correlation between competitive sports activities and an increased incidence of spondylolysis is proved. In early stages, complete healing can be achieved by conservative treatment (abstinence from sports activities for 3 months, orthesis). Persistence of pain, neurologic symptoms and progression of vertebral slipping are indications for operative treatment (reconstruction of the isthmus, dorso-ventral spondylodesis). The exercise tolerance depends on the extent of instability, progression of vertebral slipping and clinical symptoms. The limits of exercise tolerance vary among the individual athletes and require the decision of the physician. Backstroke swimming, abdominal and back muscle strengthening exercises, and types of sport involving smooth movements are advisable. Sports education in school is possible without restriction in patients with stable spondylolysis and in those with spondylolisthesis without unfavourable concomitant factors.     

Larks and owls and health, wealth, and wisdom

OBJECTIVE: To test the validity of Benjamin Franklin's maxim "early to bed and early to rise makes a man healthy, wealthy, and wise." DESIGN: Cross sectional analysis of sleeping patterns in a nationally representative group of elderly people, and longitudinal investigation of mortality. SETTING: Eight areas in Britain (five in England, two in Scotland, and one in Wales). SUBJECTS: 1229 men and women aged 65 and over who in 1973-4 had taken part in a survey funded by the Department of Health and Social Security and for whom data on sleeping patterns, health, socioeconomic circumstances, and cognitive function had been recorded. MAIN OUTCOME MEASURES: Self reported income, access to a car, standard of accommodation, performance on a test of cognitive function, state of health and mortality during 23 years of follow up. RESULTS: 356 people (29%) were defined as larks (to bed before 11 pm and up before 8 am) and 318 (26%) were defined as owls (to bed at or after 11 pm and up at or after 8 am). There was no indication that larks were richer than those with other sleeping patterns. On the contrary, owls had the largest mean income and were more likely to have access to a car. There was also no evidence that larks were superior to those with other sleeping patterns with regard to their cognitive performance or their state of health. Both larks and owls had a slightly reduced risk of death compared with the rest of the study sample, but this was accounted for by the fact that they spent less time in bed at night. In the study sample as a whole, longer periods of time in bed were associated with increased mortality. After adjustment for age, sex, the presence of illness, and other risk factors, people who spent 12 or more hours in bed had a relative risk of death of 1.7 (1.2 to 2.5) compared with those who were in bed for 9 hours. The lowest risk occurred in people who spent 8 hours in bed (adjusted relative risk 0.8; 0.7 to 1.0). CONCLUSION: These findings do not support Franklin's claim. A "late to bed and late to rise" lifestyle does not seem to lead to socioeconomic, cognitive, or health disadvantage, but a longer time spent in bed may be associated with increased mortality.     

Craniometaphyseal and craniodiaphyseal dysplasia, head and neck manifestations and management

Mechanical allodynia (MA) following hand injury is a well-documented clinical problem. The purpose of this pilot study was to examine the relationship between hand MA and the upper limb tension test (ULTT). The ULTT mechanically stresses the neural structures from the C5/6/7 neural foramina to the median nerve distally. This study examined 29 subjects with unilateral hand MA before and after a 2-week neural self-mobilization programme. There was a significant difference between the subjects' affected and unaffected sides when tested using the ULTT, both in reproduction of symptoms and in reduced range of motion of the ULTT. Following the self-mobilization program, there was an improvement in the range of the ULTT, and subjects reported a reduction in their symptoms. Complete recovery was not obtained in all cases. The results of this study suggest that the ULTT is a useful tool both in assessment and treatment of subjects with hand MA.     

深云立交桥梁检测及加固改造

根据深云立交桥梁的检测结果，对该桥目前的整体状况、工作状态，及其使用情况做出综合评价，对桥的病害原因进行了分析，并提出合理的加固方案。     

关于摩尔浓度及其与硬度转换关系问题的讨论

众所周知，国际单位制物质的量采用摩尔(mol)表示，近几年出版的给排水专业书籍，为了与国际单位制接轨，逐渐将摩尔的使用频率不断提高，被给排水技术人员广泛应用的新版给排水设计手册，将表示物质浓度的单位“当量／升”或“毫克当量／升”．改为mol／l或mmol／l，虽然编者对其基本单元定义作了说明，但在实际运用上仍会出现误解，     

《儿子与情人》的语码转换与男女二元对立

劳伦斯小说《儿子与情人》一个鲜明的语言特色就是标准英语和当地方言频繁的语码转换。莫瑞尔用方言来对抗妻子,而妻子坚持用标准英语,偶尔也用方言来讽刺、挖苦丈夫。语码转换反映了劳伦斯男女二元对立的哲学思想。     

抗腐蚀高强耐磨涂料研发与应用

介绍了抗腐蚀高强度耐磨涂料的研制和开发，以及用作柳钢球团回转烘干机刮板保护涂层的应用效果。     

Intralesional and topical chemotherapy and immunotherapy

This article covers the principles and applications of radiation therapy in horses. The goal in treating tumors by irradiation is tumor control with minimum treatment complications. Various treatment techniques are available to achieve this goal. The prognosis depends on many factors such as the extent and location of the tumor, tumor type and tumor cell proliferation. Radiation therapy is a very effective treatment modality for equine tumors but logistical reasons limit its impact in equine oncology.     

Prohormone and proneuropeptide synthesis and secretion

Hormones and neuropeptides in eukaryotic cells, are synthesised as large precursor molecules in the rough endoplasmic reticulum (RER), from where they are translocated to the Golgi apparatus. The sorting of proteins destined for the regulated secretory pathway from those which will be released constitutively takes place in the trans-Golgi network (TGN). In both these pathways, vesicles need to be transported to the plasma membrane before their contents can be released by exocytosis. Hormones and neuropeptides need to be secreted from the cells in which are synthesised to exert their biological actions, although they can also play paracrine and autocrine actions. Prohormones and proneuropeptides must undergo post-translational modifications which occur in determined subcellular compartments within eukaryotic cells and are carried out in a strict succession of intracellular events, which give rise to biologically active products. The biosynthesis of prohormones/proneuropeptides is mediated by the action of endoproteolytic enzymes and other post-translational modifying enzymes within the secretory pathway. The major focus of this review will be the biosynthetic pathway, sorting and intracellular trafficking of prohormone and proneuropeptide precursors within the secretory pathway of eukaryotic cells.     

Screening and treatment of children and adolescents with hypercholesterolemias and dyslipidemias

Evidence was provided that atherogenesis develops for several decades before pathological changes are manifested. It may thus be stated, that the "incubation period" of atherosclerotic pathological consequences is very long but it is reduced markedly already from childhood and adolescence in subjects with an atherogenic lipoprotein phenotype. Atherogenic lipoprotein phenotype comprises subjects suffering from one or more, frequently from a combination of several of the following metabolic indicators: hypercholesterolaemia, elevated levels of LDL-cholesterol, apolipoprotein B, lipoprotein (a), reduced levels of HDL-cholesterol and apolipoprotein A-1. The atherogenic lipoprotein phenotype is in 95% conditioned by inborn metabolic errors, i.e. familial hyperlipoproteinaemia and dyslipoproteinaemia. In the population the following are encountered most frequently: combined familial hyperlipidaemia, familial hypertriacylglycerolaemia and familial hypercholesterolaemia. Active screening and treatment of children and adolescents from these affected families is of great importance in primary prevention of atherosclerotic complications in adult age.     

Comment on Mazza and Stevens and on Miller and Hester.

Supplements D. Mazza and D. Stevens's (1988) critique of W. R. Miller and R. K. Hester's (see record 1986-28253-001) review of alcoholism treatment. Of 6 studies cited in the review, 2 did not compare inpatient and outpatient treatment; 4 were conducted over 13 yrs earlier; methodological limitations of the studies preclude conclusions about outcomes; and the studies focused on late-stage, chronic populations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)