Therapy with macrolides in patients with cystic fibrosis

Cystic fibrosis affects 1/2500 individuals and is the most common lethal autosomal recessive disease in people of northern European descent. It is characterized by chronic infections with mucoid Pseudomonas aeruginosa and progressive deterioration of respiratory function. Much research has focused on the inflammatory component of the disease. Macrolide antibiotics are postulated to suppress inflammatory mediators and interfere with biofilm formation produced by P. aeruginosa. In vitro studies show promising results, and a limited number of human studies reported improvements in respiratory function with the drugs. Macrolide antibiotics are generally safe and well tolerated and may prove to be effective in patients with cystic fibrosis.     

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.     

Satisfaction with information and its relationship with adherence in patients with chronic pain

□ Due to the nature of chronic pain it would be expected that patients are highly adherent to their pain medication. However, results from this study have shown that 23 per cent of patients often or always avoid using their pain medication, 13.4 per cent often or always alter dosages, and 10.3 per cent often or always stop taking their medication for a while. This suggests intentional non‐adherence to pain medication □ Less than 50 per cent of respondents were satisfied with information provided on side effects, what to do if side effects occur, and possible interactions with other medication □ Patients' satisfaction with information about their medication was related to self‐reported adherence; greater satisfaction was associated with higher self‐reported adherence     

Tenoxicam compared with diclofenac in patients with ankylosing spondylitis

A randomized study was performed on 24 patients with ankylosing spondylitis to compare the efficacy and tolerability of 20 mg tenoxicam daily with 50 mg diclofenac twice daily. There were 6 withdrawals from the group taking tenoxicam and 4 from the diclofenac group. Depression in 1 patient taking tenoxicam was the only significant adverse event. Both drugs were otherwise well tolerated. Tenoxicam and diclofenac were rated as good or excellent by 27% and 55% of patients, respectively. Global assessment, pain and duration of morning stiffness were improved with both drugs but this improvement was not statistically significant and there was no statistically significant difference between the two groups. This study confirms that tenoxicam is effective and well tolerated but larger numbers would be required to detect a small difference between groups.     

Controlled-release naproxen compared with isoxicam in patients with osteoarthritis

The therapeutic efficacy and tolerability of a new controlled-release 1000 mg tablet of naproxen (naproxen CR) were compared with 200 mg isoxicam in 100 out-patients with osteoarthritis. Medications were administered once daily for 4 weeks in a controlled, randomized, double-blind, parallel trial. Patients were assessed for duration of stiffness, global pain, pain in the worst affected joint, night pain, pain on full passive movement, and pain on selected activity. No statistically significant differences were found between naproxen CR and isoxicam for any of the efficacy variables. Only 3 patients (2 with naproxen CR, 1 with isoxicam) reported adverse events, all mild to moderate; no patient withdrew from the study. At the conclusion of the study, patients and physician evaluated therapeutic response independently; both drugs provided steady improvement as judged by patients and physician. Both physician and patients evaluated naproxen CR as very good or good for 36 (72%) patients, and isoxicam as good or very good for 35 (73%) patients. Naproxen CR and isoxicam proved equally effective and well-tolerated for the treatment of osteoarthritis in this study.     

Genomic profiling associated with recurrence in patients with rectal cancer treated with chemoradiation

PURPOSE: Stage II and III adenocarcinoma of the rectum has an overall 5-year survival rate of approximately 50%, and tumor recurrence remains a major problem despite an improvement in local control through chemotherapy and radiation. The efficacy of chemoradiation therapy may be significantly compromised as a result of interindividual variations in clinical response and host toxicity. Therefore, it is imperative to identify those patients who will benefit from chemoradiation therapy and those who will develop recurrent disease. In this study, we tested whether a specific pattern of 21 polymorphisms in 18 genes involved in the critical pathways of cancer progression (i.e., drug metabolism, tumor microenvironment, cell cycle regulation, and DNA repair) will predict the risk of tumor recurrence in rectal cancer patients treated with chemoradiation. PATIENTS AND METHODS: A total of 90 patients with Stage II or III rectal cancer treated with chemoradiation were genotyped using polymerase chain reaction (PCR)-based techniques for 21 polymorphisms. RESULTS: A polymorphism in interleukin (IL)-8 was individually associated with risk of recurrence. Classification and regression tree analysis of all polymorphisms and clinical variables developed a risk tree including the following variables: node status, IL-8, intracellular adhesion molecule-1, transforming growth factor-beta, and fibroblast growth factor receptor 4. CONCLUSION: Genomic profiling may help to identify patients who are at high risk for developing tumor recurrence, and those who are more likely to benefit from chemoradiation therapy. A larger prospective study is needed to validate these preliminary data using germline polymorphisms on tumor recurrences in rectal cancer patients treated with chemoradiation.     

Treatment with ketoconazole in diabetic patients with vaginal candidiasis

Thirty-two diabetic patients with vaginal candidiasis were treated orally with 400 mg ketoconazole once daily for five days. At the end of the treatment period symptoms had disappeared and cultures for Candida were negative in 18 patients; a total of 28 reported improved symptoms. One month later 15 patients were still negative for Candida and 24 showed improved symptoms. The remaining 8 repeated the course of treatment; 6 became negative while 2 cases remained refractory to treatment. It was concluded that these encouraging results and low relapse rates indicate ketoconazole as a drug of first choice for candidiasis in patients with predisposing conditions such as diabetes.     

Experience with pneumocystis carinii pneumonia in patients with AIDS

We have reviewed admission data, some diagnostic tests, treatment and outcome of 31 male homosexual patients infected with the human immunodeficiency virus with 37 consecutive episodes of presumptive Pneumocystis carinii pneumonia treated at the infectious disease unit, Auckland Hospital, between 1985 and 30 June 1988. The median age was 39 years. Eight episodes were proven Pneumocystis carinii pneumonia, 18 satisfied Centres for Disease Control criteria for presumptive Pneumocystis carinii pneumonia and 11 lacked one Centres for Disease Control criterion. Patients began intravenous or oral cotrimoxazole in 32 episodes, initially 20 mg/k/d of trimethoprim component, but since early 1988 10 mg/k/d. In nine episodes treatment was changed to intravenous pentamidine because of side effects or failure to respond while five received pentamidine as their only drug. Cotrimoxazole caused side effects in 20 of 32 episodes (rash in 11) and pentamidine in 10 of 14 (renal impairment in nine). Two patients died (ie, a 5% mortality for all 37 episodes or 8% for 26 proven and Centres for Disease Control presumptive episodes). Median hospital stay for survivors was 11 days. Fourteen other patients have subsequently died a median eight months after the initial episode. Pneumocystis carinii pneumonia is an important infection in patients infected with the human immunodeficiency virus.     

Clinical experience with nisoldipine in patients with atrio-ventricular blocks

The effect of the 1,4-dihydropyridine calcium antagonist nisoldipine (Bay k 5552) on the atrio-ventricular (AV) conduction was studied in 9 patients with AV blocks. The impuls propagation through the AV node (A-H time) and the bundle of His (H-V time) was determined before, 1-3 min and 10-15 min after the intravenous injection of nisoldipine (1.5 micrograms/kg body weight). Except for one patient, A-H and H-V times almost remained unaffected by the calcium antagonist. In this patient with an AV block II, Mobitz type I, A-H time transiently increased from 290 to 410 ms. Nisoldipine did not aggravate an AV block I or II to an AV block II or III, respectively. Furthermore, ventricular heart rates did not change significantly. It is concluded that, in general, nisoldipine does not impair the impulse propagation of the AV node in patients with AV blocks although a transient increase of the A-H time may occur.     

川崎病的静脉注射免疫球蛋白治疗

川崎病(Kawasaki disease,KD)的病因目前尚未完全明了,尽管许多证据表明其发病可能与感染有关,但是尚未被证实.     

原发胃癌恶性表型与患者自发淋巴细胞微核形成的关系

目的 探讨淋巴细胞微核形成与胃癌恶性度的关系.方法 术前取外周血采用体内微核实验方法检测130例胃癌患者(胃癌组)、13例良性胃肠病变(良性病变组)及59例正常人(对照组)淋巴细胞微核率(MNF).结果 胃癌组淋巴细胞MNF为(1.93±0.93)‰,明显高于良性病变组的(0.62士0.49)‰和对照组的(0.51±0.45)‰(P＜0.01);MNF随着胃癌组分化度降低及淋巴结转移率的增加而逐渐上升(P＜0.01).结论 淋巴细胞微核形成与胃癌恶性度密切相关,为胃癌患者的术前恶性度的判断和高危人群筛查提供了一个有用的生物学标志物.     

Compliance with national guidelines in patients with diabetes in a family practice clinic

STUDY OBJECTIVE: To assess whether clinicians are treating patients with both type 2 diabetes and hyperlipidemia according to national goals for blood pressure, low-density lipoprotein cholesterol (LDL), and glucose levels. DESIGN: Retrospective chart review. SETTING: University-based family medicine teaching practice. PATIENTS: One hundred twenty-four patients with both type 2 diabetes and hyperlipidemia. MEASUREMENTS AND MAIN RESULTS: Sixty-nine patients (58%) met the National Cholesterol Education Program Adult Treatment Panel II's goals for LDL (< 130 mg/dl for primary prevention and < 100 mg/dl for secondary prevention). Only 47 patients (38%) were in compliance with national standards for both systolic and diastolic blood pressures. The mean hemoglobin A1c (A1C) level was 8.6%; 27 patients (21.8%) had A1C levels below 7%. CONCLUSION: A high percentage of patients in our family practice clinic met their goals for reducing lipid levels, but more aggressive therapy is necessary to attain glucose and blood pressure goals. Data from this study emphasize the need for understanding which factors influence clinicians' treatment decisions.     

Improvement in quality of life with omalizumab in patients with severe allergic asthma

ABSTRACT

Background: Patients with severe persistent asthma experience daily symptoms and frequent serious exacerbations that contribute to a significant impairment of health-related quality of life (QoL).

Methods: A pooled analysis was completed of six controlled clinical trials that evaluated the effect of add-on omalizumab on asthma-related QoL in patients with severe persistent allergic (IgE-mediated) asthma. Asthma-related QoL was assessed at baseline and treatment endpoint using the well-validated Juniper Asthma Quality of Life Questionnaire (AQLQ). Change from baseline in AQLQ total score was compared between treatments using analysis of covariance methods. The percentage of patients who achieved a clinically meaningful (≥ 0.5-point) improvement in AQLQ total score was compared using the Mantel–Haenszel Chi-square test.

Results: The pooled patient population comprised 2548 patients (omalizumab, n = 1342; control, n = 1206), of whom 96% had severe persistent asthma according to the GINA 2002 classification. Omalizumab produced significantly greater improvements in AQLQ total score vs the control group (mean increases of 1.01 and 0.61 points, respectively; p < 0.001). In addition, significantly more omalizumab-treated patients achieved a clinically meaningful improvement in AQLQ total score than patients in the control group (66.3% vs 52.4%; p < 0.001).

Conclusions: Add-on therapy with omalizumab improves QoL to a significant and clinically meaningful level in patients with severe persistent allergic asthma.     

拉氧头孢联合罗红霉素治疗支气管扩张症继发肺部感染疗效观察

目的观察拉氧头孢联合罗红霉素治疗支气管扩张症继发肺部感染的疗效和不良反应。方法选取38例支气管扩张症继发肺部感染的患者,对比拉氧头孢联合罗红霉素治疗前后的临床情况、炎症指标、肺通气功能参数、细菌学评价,分析其疗效和观察不良反应。结果在全部38例病人中,痊愈18例,显效8例,进步6例,无效6例,总有效率84.2%（32/38）,细菌清除率为82.4%,没有发现严重不良反应。结论拉氧头孢联合罗红霉素可以作为支气管扩张症继发肺部感染的治疗方案之一。     

尼妥珠单抗联合化疗治疗30例晚期非小细胞肺癌的临床观察

目的:回顾性分析尼妥珠单抗联合化疗治疗晚期非小细胞肺癌的临床疗效和安全性。方法:纳入中国医学科学院肿瘤医院2011年1月至2014年12月30例经病理组织学或细胞学确诊的晚期非小细胞肺癌患者,其中腺癌19例、鳞状细胞癌8例、未知型3例。所有患者均接受尼妥珠单抗联合化疗的治疗,其中19例采用含铂类方案,11例采用非含铂类方案。尼妥珠单抗给药剂量为200 mg,静脉给药,每周1次。尼妥珠单抗联合化疗作为一线方案患者5例,二线方案9例,三线及以上方案16例。每治疗2个周期后按照实体瘤疗效评价标准(RECIST)1.1进行疗效评价;采用NCI-CTCAE3.0标准评价不良反应。结果:30例患者均完成了至少一次疗效评价,其中无完全缓解(CR),部分缓解(PR)5例,疾病稳定(SD)12例,病情进展(PD)13例;客观缓解率(ORR)为16.7%(5/30),疾病控制率(DCR)为56.7%(17/30),中位无进展生存时间(PFS)为89 d(74~104 d),中位总生存时间(OS)为307d(197~417 d)。进一步分析显示,腺癌患者中位OS显著长于鳞癌患者(327 d vs 185 d,P=0.008)。药物安全性评价结果显示尼妥珠单抗联合化疗的安全性良好。结论:尼妥珠单抗联合化疗治疗非小细胞肺癌疗效确切,不良反应较轻,值得临床进一步研究。     

重症胰腺炎血小板计数的动态变化与预后的关系

目的探讨血小板计数变化对重症急性胰腺炎(SAP)并发腹膜后出血、多脏器功能衰竭及死亡率的的影响。方法将该院2009年10月～2011年8月收治的73例SAP患者,按血小板计数的动态变化,分成血小板降低组(100×109.L-1)和血小板正常组(≥100×109.L-1)。分析两组血小板计数动态变化对胰腺炎并发腹膜后出血、多脏器功能衰竭及死亡率的影响。结果血小板计数降低组47例,占64.4%;血小板计数正常组26例,占35.6%。两组在并发腹膜后出血、多脏器功能衰竭发生率及死亡率上均有统计学意义(P0.05)。结论血小板计数动态变化对提示重症胰腺炎的预后有一定的临床指导意义。