Experience with the treatment of patients with hypertrophic cardiomyopathy with obsidan and isoptin

Forty-five patients with hypertrophic cardiomyopathy were examined clinically and echocardiographically. The results of their treatment with obsidan and isoptin in relation to various types of central hemodynamic disorders are presented. The data have been obtained making it possible to treat patients differentially with regard to the form of the disease. The treatment of this category of patients requires the echocardiographic monitoring of the parameters of the central hemodynamics and myocardial contractility.     

Women with gout: efficacy and safety of urate-lowering with febuxostat and allopurinol

Objective

To compare the characteristics of female versus male gout patients and assess urate‐lowering efficacy and safety of febuxostat or allopurinol treatment in women with gout.

Methods

This was a retrospective analysis of 4,101 hyperuricemic (serum urate [sUA] level ≥8.0 mg/dl) gout subjects enrolled in 3 phase III comparative trials and randomized to receive placebo, febuxostat (40 mg, 80 mg, 120 mg, or 240 mg daily), or allopurinol (100 mg, 200 mg, or 300 mg daily, based on renal function). Baseline demographics and characteristics were summarized and compared between female and male subjects. Urate‐lowering efficacy, which was defined as the proportion of subjects with sUA levels <6.0 mg/dl at final visit, was assessed for all subjects and, among women, according to baseline renal function.

Results

Female gout subjects (n = 226) were older with significantly higher rates of obesity and metabolic and cardiovascular comorbidities than their male counterparts. The percentage of female subjects with sUA levels <6.0 mg/dl at final visit was 0% in the placebo group, 54.3%, 85.1%, 81.0%, and 100.0% in the febuxostat 40 mg, 80 mg, 120 mg, and 240 mg groups, respectively, and 45.9% in the allopurinol group. Similar patterns of urate‐lowering efficacy rates were observed when stratified by renal function. Among all the female subjects, febuxostat 80 mg was significantly more efficacious than allopurinol (P < 0.001). Rates of adverse events (AEs) were low. The most frequently reported AEs were upper respiratory tract infections, musculoskeletal/connective tissue disorders, and diarrhea.

Conclusion

These data suggest that febuxostat 80 mg may be more efficacious than commonly prescribed doses of allopurinol in female gout subjects with high rates of comorbidities.     

Treatment of metastatic renal cancer with ifosfamide and mesnum with and without irradiation

Ifosfamide (50-60 mg/kg of body weight, Days 1-5) and mesnum (10-12 mg/kg of body weight, Days 1-5) were given to 15 patients with measurable metastatic renal cancer. This treatment was repeated on Day 29. In addition, six of these 15 patients received irradiation to some of the metastatic areas. There was one partial remission among 11 evaluable patients after two ifosfamide courses. The partial remission was seen in a metastatic area treated with low-dose irradiation prior to the first ifosfamide course. Two cases of early death and two cases of toxic death (urotoxicity) were observed. The main hematologic complication was moderate to severe leukopenia. Previously reported high response rates to ifosfamide treatment of renal cancer could not be confirmed.     

Risk of thrombosis with lenalidomide and its prevention with aspirin

Lenalidomide, an analog of thalidomide, is an effective new treatment for multiple myeloma. Both compounds are associated with an increased risk of venous thromboembolism, particularly when used in combination with high-dose dexamethasone. As new trials with lenalidomide are being planned and performed, investigators are placing high importance on reducing the risk of thrombosis by incorporating an antithrombotic agent into the therapeutic regimen. Low-molecular-weight heparin, warfarin, and aspirin have all been suggested as candidate drugs for thromboprophylaxis, but none of these agents have been evaluated in randomized clinical trials. A body of opinion has evolved that aspirin is very effective in preventing venous thrombosis in myeloma patients treated with lenalidomide. If correct, this view has important implications, because aspirin is inexpensive and is safer and more convenient than anticoagulants. On the other hand, aspirin is less effective than anticoagulants for preventing venous thrombosis in other high-risk groups, and therefore might not be the most appropriate choice for preventing of venous thrombosis in myeloma patients. This commentary examines the strength of the evidence supporting the effectiveness of aspirin in preventing venous thrombosis in multiple myeloma patients treated with lenalidomide. It is concluded that the evidence that aspirin is efficacious in preventing venous thrombosis in myeloma patients is based on "before/after" and retrospective studies, with potential for bias and confounders. There is, therefore, a critical need to incorporate a randomized comparison of aspirin with an anticoagulant in future trials evaluating lenalidomide in multiple myeloma.     

Treatment of strongyloidiasis with mebendazole and its combination with thiabendazole

Although Strongyloides stercoralis (S. stercoralis) infection rate in Okinawa Prefecture was less than 2% by the traditional method, it has been proven to be 6.2% by the new technique--agar plate method. Thiabendazole has strong activity to eradicate the organism, but it is well known that the rate of severe side effects is extremely high. Therefore, we attempted to evaluate the new treatment for the infection by mebendazole and its combination with thiabendazole. The reason for use of the drug is based on the reports of successful treatment of S. stercoralis infection in humans with the mild and infrequent side effects produced by the drug. Thirty three patients were orally given mebendazole 100 mg twice daily for 28 days. Twenty six patients were given thiabendazole 500 mg thrice daily for 5 days and after that, mebendazole 100 mg twice daily for 9 days. This combination therapy was repeated twice. The following results were obtained: 1) Out of a total of 59 patients, the cure rate was 83.3% (20/24) in single use of mebendazole and 100.0% (22/22) in the combination therapy. 2) Constipation (9.1%) and headache (9.1%) were of relatively high incidence in the mebendazole group, but they were mild. Nausea (19.2%) and headache (15.4%) were observed in the combination therapy group and the drug was discontinued in 2 patients. 3) The incidence of the elevation of S-GOT, S-GPT was noted in 71.4% (20/28) for the mebendazole group and 52.2% (12/23) for combination therapy group. All 13 patients of the mebendazole group were negative in lymphocyte stimulation test for mebendazole.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of amodiaquine alone and combined with sulfadoxine-pyrimethamine and of sulfadoxine pyrimethamine combined with artesunate

The safety and the efficacy of amodiaquine (AQ) alone, AQ plus sulfadoxine-pyrimethamine (SP) (AQ plus SP), and artesunate (ART) plus SP (ART plus SP), three possible alternatives to chloroquine (CQ), were investigated in 379 Rwandan children 6-59 months old with uncomplicated Plasmodium falciparum malaria who visited one urban/peri-urban health center and two rural health centers. The three treatment regimens were well tolerated and no serious adverse effects were observed. Children treated with AQ plus SP had less clinical failures than those treated with ART plus SP (odds ratio [OR] = 0.25, 95% confidence interval [CI] = 0.06-0.81, P = 0.01) or AQ alone (OR = 0.33, 95% CI = 0.07-1.10, P = 0.08). Even after new infections were excluded, AQ plus SP was still significantly more efficacious than ART plus SP (P = 0.05). At day 14, the mean packed cell volume was significantly higher in the AQ plus SP group compared with the ART plus SP group (P = 0.02) and with the AQ alone group (P = 0.01). In Rwanda, AQ plus SP has been chosen to replace CQ as a first-line treatment. However, this is considered an interim measure and new combinations, possibly co-formulated, should be identified and tested.     

十二指肠乳头旁憩室与胆胰疾病的关系及对内镜诊疗的影响

目的 探讨十二指肠乳头旁憩室（JPDD）与胆胰疾病发生的关联性及JPDD对ERCP诊疗的影响。方法 2012年1月至2017年1月,中国医科大学附属盛京医院普通外科1 230例行ERCP诊疗病例纳入回顾性分析,首先按是否存在JPDD分成JPDD组（n=360）和非JPDD组（n=870）,然后再将JPDD组病例按是否为憩室内乳头分成憩室内乳头组（n=41）和非憩室内乳头组（n=319）,JPDD组与非JPDD组间、憩室内乳头组与非憩室内乳头组间胆胰疾病发生率、ERCP插管成功率、取石成功率、术后并发症发生率等数据比较采用χ2检验或Fisher确切概率法,P＜0.05为差异具有统计学意义。结果 胆总管结石、原发性胆总管结石、复发性胆总管结石发生率JPDD组分别为87.78%（316/360）、31.11%（112/360）、6.67%（24/360）,非JPDD组分别为75.52%（657/870）、19.08%（166/870）、4.02%（35/870）,2组间比较差异均有统计学意义（χ2=23.158,P＜0.001;χ2=21.068,P＜0.001;χ2=3.897,P=0.048）;ERCP插管、一次性取石成功率,术后出血、胰腺炎、高淀粉酶血症发生率,2组间比较差异均无统计学意义（P均＞0.05）。复发性胆总管结石发生率憩室内乳头组为14.63%（6/41）,非憩室内乳头组为5.64%（18/319）,2组间比较差异有统计学意义（χ2=4.721,P=0.030）;胆总管结石、原发性胆总管结石发生率,ERCP插管、一次性取石成功率,术后出血、胰腺炎、高淀粉酶血症发生率,2组间比较差异均无统计学意义（P均＞0.05）。结论 JPDD与原发性胆总管结石的发生相关,JPDD患者ERCP治疗后更易复发胆总管结石,且憩室内乳头患者更为明显。     

Correlation of Serum and Cryoglobulin IgM with Activity,and Serum IgG with Remission

Forty-eight patients with erythema chronicum migrans (ECM) were studied prospectively for 6 to 18 months. Twenty-six patients had no later symptoms, but 22 subsequently developed Lyme arthritis and 9 of them also experienced neurologic abnormalities. Eighty-seven percent of patients with active ECM followed by subsequent involvement had cryoglobulins containing IgM compared to only 13% of those with active ECM and no later symptoms. The former group also had significantly lower IgG, C3, and C4 levels. Sixty-seven percent of patients still had serum cryoglobulins when neurologic disease was most active, and 45% had them when joint symptoms were most severe, but only 11% continued to have small amounts in remission. The number of patients who continued to have serum cryoglobulins with recurrent attacks of arthritis decreased with time. In contrast, patients always had cryoglobulins in joint fluid, a finding Lyme arthritis shares with rheumatoid arthritis. The cryoprecipitates from 2 of 10 patients contained particles with internal structure, but their viral nature is problematic. All components of antisera obtained from goats and rabbits immunized with cryoglobulins were absorbed by normal human sera. The amount of IgM in cryoglobulins correlated directly with serum IgM, which generally rose during exacerbations and fell during remissions; serum IgG and IgA moved conversely. Thus, IgM was an important correlate of clinical disease activity and IgG of remission.     

Treatment of older persons with hypercholesterolemia with and without cardiovascular disease

Hypercholesterolemia is a risk factor for new coronary events in older men and women. Secondary prevention trials have demonstrated in persons with coronary artery disease (CAD) and hypercholesterolemia that statin drugs reduced in older persons all-cause mortality, cardiovascular mortality, coronary events, coronary revascularization, stroke, and intermittent claudication. Statins have also been shown to slow progression of coronary atherosclerotic plaques in persons with CAD, to reduce restenosis after coronary stent implantation, and to decrease myocardial ischemia in persons with CAD. Older men and women with CAD, prior atherothrombotic brain infarction, peripheral arterial disease, or extracranial carotid arterial disease and a serum low-density lipoprotein (LDL) cholesterol level higher than 125 mg/dl despite diet should be treated with statin drug therapy to lower the serum LDL cholesterol level below 100 mg/dl. Primary prevention trials have shown that statins were also effective in reducing cardiovascular events in older persons with hypercholesterolemia. On the basis of data from the Air Force/Texas Coronary Atherosclerosis Prevention Study, the physician should consider using statins in persons aged 65-80 years without cardiovascular disease with a serum LDL cholesterol level above 130 mg/dl and serum high-density lipoprotein cholesterol level below 50 mg/dl.     

Efficacy and safety of ezetimibe co-administered with simvastatin compared with atorvastatin in adults with hypercholesterolemia

This study compared the efficacy and safety of co-administered ezetimibe + simvastatin with atorvastatin monotherapy in adults with hypercholesterolemia. Seven hundred eighty-eight patients were randomized 1:1:1 to 3 treatment groups; each group was force-titrated over four 6-week treatment periods: (1) 10 mg of atorvastatin as the initial dose was titrated to 20, 40, and 80 mg; (2) co-administration of 10 mg of ezetimibe and 10 mg of simvastatin (10/10 mg) was titrated to 10/20, 10/40, and 10/80 mg of ezetimibe + simvastatin; and (3) co-administration of 10/20 mg of ezetimibe + simvastatin was titrated to 10/40 mg (for 2 treatment periods) and 10/80 mg of ezetimibe + simvastatin. Key efficacy measures included percent changes in low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) from baseline to the ends of (1) treatment periods 1 and 2 (for LDL cholesterol) comparing co-administration of 10/20 mg and 10/10 mg of ezetimibe + simvastatin with 10 mg of atorvastatin and (2) treatment period 4 (for LDL cholesterol and HDL cholesterol) comparing co-administration of 10/80 mg of ezetimibe + simvastatin with 80 mg of atorvastatin. Baseline LDL and HDL cholesterol levels were comparable between treatment groups. At the end of treatment period 1, the mean decrease of LDL cholesterol was significantly (p ≤0.001) greater for co-administration of 10/10 mg and 10/20 mg of ezetimibe + simvastatin than for 10 mg of atorvastatin. At the end of treatment period 4 and after comparing maximum doses, co-administration of 10/80 mg of ezetimibe + simvastatin was superior to 80 mg of atorvastatin in the percent LDL cholesterol decrease (−59.4% vs −52.5%, p <0.001) and HDL cholesterol increase (12.3% vs 6.5%; p <0.001). All treatments were well tolerated. Thus, a greater LDL cholesterol decrease and HDL cholesterol increase were attained by treating patients with co-administration of ezetimibe and simvastatin than with atorvastatin.