Hand-foot syndrome in patients treated with capecitabine-containing combination chemotherapy

Clinical characteristics and risk factors of hand-foot syndrome were investigated in patients who received capecitabine-containing chemotherapy. Toxicity data were analyzed from 179 patients in 4 prospective clinical trials testing docetaxel/capecitabine/cisplatin in stomach cancer, capecitabine/cisplatin in biliary or stomach cancer, and vinorelbine/capecitabine in breast cancer. Hand-foot syndrome was reported in 116/179 (64.8%) of patients, with grade 3 hand-foot syndrome in 8/179 (4.5%). Hand-foot syndrome first developed within the first 3 chemotherapy cycles in 100/116 (86.2%) patients, with the median onset for all 3 treatment regimens occurring during cycle 2. Because severe reactions were rare, hand-foot syndrome was not a major factor influencing treatment schedule. Risk factor analyses showed that combined use of docetaxel and preceding chemotherapy-related stomatitis were significant risk factors for the development of hand-foot syndrome. Our results suggest that a combined treatment agent and a patient's susceptibility to chemotherapy-related toxicity may increase the risk of capecitabine-induced hand-foot syndrome.     

Cancer-free survival of psoriasis patients treated with methotrexate and cyclosporine combination

Context: Combination of methotrexate and cyclosporine was used and reported to be effective for recalcitrant psoriasis patients. Also each agent is accused for development of malignancies.

Objective: To evaluate the cancer-free survival of psoriasis patients who received methotrexate and cyclosporine treatment at the same time.

Methods: Psoriasis patients who had been treated with combination of cyclosporine and methotrexate between March 2000 and April 2005 were questioned in 2011. A diagnosis of new cancer during follow-up period was asked and also each patient was evaluated by a questionnaire.

Results: Seventeen psoriasis patients were not treated due to a diagnosis of new cancer during the follow-up period. Also none of them complained of possible symptoms of skin or lymphoproliferative malignancies. The median follow-up time was 76 months.

Conclusion: Psoriasis patients who had been treated with methotrexate and cyclosporine combination did not report a detected malignant disease.     

Oxazepam pharmacokinetics in patients with epilepsy treated long-term with phenytoin alone or in combination with phenobarbitone

The pharmacokinetics and serum protein binding of oxazepam, a drug mainly eliminated by a single step glucuronidation reaction, were studied in nine epileptic patients treated long-term with phenytoin or phenytoin with phenobarbitone, and in nine healthy control subjects. Oxazepam elimination half-life was shorter and apparent oral clearance higher in treated patients than in age and sex matched control subjects. Serum bilirubin concentration was lower in treated patients. There was no significant correlation between serum bilirubin concentrations and oxazepam elimination. Serum alpha 1-acid glycoprotein concentration was higher in the treated patients than in the control group. Oxazepam was more than 93% bound to serum proteins, but the extent of binding was not significantly different between the two groups. These results show that oxazepam glucuronyl transferase activity is increased by treatment with phenytoin alone or in combination with phenobarbitone in epileptic patients.     

Canadian survey to determine the rate of drug resistance to isoniazid, PAS and streptomycin in newly detected untreated tuberculosis patients and retreatment cases.

In 1975, a survey was carried out in Canada to determine the primary and acquired drug resistance of M. tuberculosis isolates to isoniazid (INH), para-aminosalicylic acid (PAS) and streptomycin. The results of this investigation were compared with those of the primary drug resistant study of Armstrong, undertaken in 1963-64. It revealed that primary drug resistance has increased from 4.9% to 6.3%. The increase is mainly due to immigrants having arrived in this country during the last 12 years. In these newcomers the primary resistance rate was 11.5%. Moreover, 57.8% of the immigrants examined in the survey were of Asian origin, with a drug resistance rate of 11.7%, while 15.6% had arrived from South Europe with a resistant ratio of 16.7%. In retreatment cases, the national average of drug resistance was 26.4%. Among the Canadian provinces, the highest drug resistance rate in retreatment patients (40%) was found in Quebec. While in primary resistance Streptomycin exhibited the highest incidence, in retreatment cases isoniazid resistance proved to be more frequent. In natives, the rates and patterns of primary and acquired resistance were very similar to those observed in other Canadian born patients.     

Activity of diclofenac used alone and in combination with streptomycin against Mycobacterium tuberculosis in mice

The non-steroidal anti-inflammatory drug diclofenac (DCL) shows noteworthy in vitro and in vivo antimycobacterial activity. The aim of this study was to ascertain whether DCL used in combination with the first-line antitubercular antibiotic streptomycin (STM) synergistically augments its efficacy in vitro as well as in a murine tuberculosis infection model. In vitro minimum inhibitory concentrations (MICs) and synergistic activities of the drugs with respect to standard strains and clinical isolates of Mycobacterium tuberculosis were determined. Swiss albino male mice were intravenously infected with 2.3x10(7) M. tuberculosis H37Rv. Mice were treated with DCL or STM alone as well as in combination for 4 weeks to determine the survival rate, spleen weight and colony-forming unit (CFU) counts in the lungs and spleen. DCL was bactericidal at 40 microg/mL (4xMIC) against M. tuberculosis H37Rv and was synergistic with STM in vitro (fractional inhibitory concentration index 0.37). A dose of 10 microg/g/day DCL or 150 microg/g/day STM for 4 weeks, administered from 1 day post infection, significantly (P<0.05) lowered bacterial counts and reduced mean spleen weight of mice compared with untreated animals. Simultaneous administration of both agents further decreased CFU counts (P<0.05) in the lungs and spleen compared with mice receiving STM alone. Thus, the ability of extended antibiotic therapy may be improved with the help of this synergistic drug pair in murine tuberculosis, and further investigations may throw light on new directions to combat multidrug-resistant tuberculosis infections in humans.     

Population pharmacokinetics of intravenous and intramuscular streptomycin in patients with tuberculosis

STUDY OBJECTIVES: To determine population pharmacokinetic parameters of streptomycin after administration of multiple intramuscular and intravenous doses. DESIGN: Prospective, unblinded clinical study. SETTING: Two medical centers in Denver, Colorado. PATIENTS: Thirty patients with tuberculosis. INTERVENTION: Patients received multiple doses of streptomycin as part of their tuberculosis treatment. They received concurrent drugs based on in vitro susceptibility data. MEASUREMENTS AND MAIN RESULTS: Serum samples were collected over a 10-hour period and assayed by validated high-performance liquid chromatography Concentration-time data were analyzed using population methods. Streptomycin concentrations increased linearly with increasing intravenous doses. The intramuscular doses did not produce as linear a relationship, presumably because of variability in rates of and, potentially, completeness of absorption. Streptomycin elimination decreased with declining renal function. Higher, intermittent doses were well tolerated and appeared to maximize the peak concentration:minimal inhibitory concentration ratio. CONCLUSION: Overall, pharmacokinetic parameters of streptomycin were comparable with those previously published for streptomycin and other aminoglycosides. Higher, intermittent doses maximize pharmacodynamic parameter estimates and might have advantages for treatment of tuberculosis.     

苯磺酸左旋氨氯地平联合氢氯噻嗪治疗高血压40例疗效观察

目的探讨苯磺酸左旋氨氯地平联合氢氯噻嗪治疗高血压的疗效。方法将2011年1月～2012年1月本院收治的80例高血压患者随机分为治疗组和对照组,每组40例,治疗组给予苯磺酸左旋氨氯地平＋氢氯噻嗪治疗,对照组仅给予苯磺酸左旋氨氯地平,两组疗程均为12周,疗程结束后比较两组疗效。结果治疗组总有效率为92.5%,对照组总有效率为77.5%,治疗组总有效率显著高于对照组,P〈0.05;对照组出现不良反应4例,不良反应发生率为10.0%,治疗组仅出现头痛1例,不良反应发生率为2.5%,两组不良反应发生率比较差异有统计学意义,P〈0.05。结论苯磺酸左旋氨氯地平联合氢氯噻嗪治疗高血压效果好,且副作用少,是治疗的理想方案。     

阿司匹林与卡托普利合用对麻醉犬血液动力学的影响

目的观察阿司匹林(Asp),卡托普利(Cap)单用和合用对麻醉开胸犬血液动力学的作用。方法张力指数(TTI)、左室做功指数(LVWI)、平均动脉压(MAP)、总外周血管阻力(TPVR)、股动脉血流量(FBF)、左室内压(LVSP)、 dp/dtmax、左室舒张末期压(LVEDP)、心率(HR)均同步记录于多导生理记录仪及电磁流量计上。结果Asp5、10mg·kg-1iv对血液动力学各项指标均无明显影响,Cap0.5mg·kg-1iv对LVSP、 dp/dtmax、LVEDP、HR无明显影响 ,CI稍增加 ,但可使TTI、LVWI、TPVR显著下降 ,Asp与Cap 合用与Cap 单用结果相似。结论Asp不影响Cap对心血管功能的改善     

Evaluation of compliance and health care utilization in patients treated with single pill vs. free combination antihypertensives

Abstract

Objectives:

To compare compliance/persistence, health care resource utilization, and costs associated with single-pill combination (SPC) vs. free-combination (FC) therapies among adult hypertension patients at the national and state level. Combination therapies with angiotensin receptor blocker (ARB)?+?calcium channel blocker, ARB?+?hydrochlorothiazide, and angiotensin-converting enzyme inhibitor?+?hydrochlorothiazide were evaluated.     

应用双源CT诊断胸痛的卫生经济学分析

目的：对疑诊冠心病的低危胸痛患者的两种诊断程序进行卫生经济学评价。方法：采用前瞻性研究方法,根据是否采用双源CT诊断程序,将2007年7月～2009年12月本院心内科确诊的120例胸痛患者分为运动平板组和双源CT诊断程序组,分别接受运动平板或双源CT检查,计算其就诊费用、检查费用、住院时间、确诊时间等,运用经济学最小成本分析法进行评价。结果：两组平均检查费用、平均就诊费用差异无统计学意义,双源CT诊断程序组与运动平板组比较,平均住院时间长（P〈0.05）;但双源CT诊断程序组接受冠状动脉造影的患者总数显著少于运动平板组（P〈0.001）。结论：双源CT诊断程序与普通诊断程序对于胸痛的诊断具有相似的经济学效益,但显著减少了患者接受选择性冠状动脉造影的比例。     

提高肺结核患者肌注链霉素坚持使用率的研究

目的探讨提高肺结核患者肌注链霉素坚持使用率的途径。方法将92例需要肌肉注射链霉素的门诊肺结核患者随机分为研究组和对照组,两组患者分别选择不同的进针深度及进行不同的健康教育方式。结果研究组52例患者链霉素治疗2个月的过程中中断治疗6例,治疗中断率11．5％,有较强疼痛反应感8例,较强疼痛反应感率15．4％;对照组40例患者治疗2个月的过程中中断治疗15例,治疗中断率37．5％,有较强疼痛反应感16例,较强疼痛反应感率40．0％。对照组患者2个月治疗过程中中断治疗率和较强疼痛反应感率明显高于研究组,差异有统计学的意义（χ^2=8．65,P〈0．01;χ^2=7．10,P〈0．01）。结论根据患者臀部皮肤脂肪的厚度选择合适的进针深度,结合有效的健康教育贯穿在整个治疗过程中,可提高肺结核病患者肌注链霉素治疗的坚持使用率。     

Facilitation of shuttle-box avoidance behaviour in mice treated with nifedipine in combination with amphetamine

The dihydropyridine calcium channel antagonist nifedipine, tested in mice of CD-1, C57BL/6 and DBA/2 strains, at doses of 2.5, 5 and 10 mg/kg IP, had no significant effect on shuttle-box avoidance acquisition. Nifedipine also failed to affect performance retention in CD-1 mice subjected to a one-trial passive avoidance task (step-through). While ineffective alone, nifedipine strongly enhanced the shuttle-box avoidance facilitating action of amphetamine (1 and 2 mg/kg IP) in low performing CD-1 mice. The results indicate that although calcium channel blockers do not affect learning in avoidance paradigms in normal animals, they can interfere with the effects of other centrally acting drugs. Calcium antagonists might interfere with neuronal changes induced by amphetamine, but at present it is difficult to explain the strong avoidance facilitation produced by combinations of nifedipine and amphetamine. A possibility that the action of nifedipine on cerebral circulation is involved in the amphetamine-nifedipine interaction cannot be excluded.     

Delusional disorder, somatic type treated with aripiprazole--mirtazapine combination

Delusional disorder, somatic type (DDST) is a rare psychiatric disorder and the treatment is mostly based on observations, due to the lack of well-organized studies. Initially, antipsychotics and especially pimozide were considered to be the pharmacological approach of choice but, subsequently, tryciclic anti-depressants and selective serotonin re-uptake inhibitors (SSRIs) were also suggested to be effective, implicating the serotonergic system in the pathophysiology of the disorder. We present the case of a female with DDST, who responded to aripiprazole-mirtazapine combination, a finding that is in accordance with the initial approach of this disorder as a part of the schizophrenic spectrum, but also supports the hypothesis of serotonin dysfunction in DDST.