Subjective adverse reactions to metronidazole in patients with amebiasis

Subjective adverse reactions to metronidazole were analyzed in 111 patients with amebiasis. Metronidazole was administered to 36 patients at a daily dose of 2250 mg and 75 patients at daily doses lower than 2250 mg. The reactions reported included nausea without vomiting in 11 (9.9%) patients, nausea with vomiting in 2 (1.8%), dysgeusia in 2 (1.8%), diarrhea in 1 (0.9%), headache in 1 (0.9%), numbness in 1 (0.9%), dizziness in 1 (0.9%), urticaria in 1 (0.9%), exanthema in 1 (0.9%), and discomfort in 1 (0.9%). Nausea was reported by 28% (10/36) of the patients receiving metronidazole at a daily dose of 2250 mg and 4% (3/75) of the patients receiving lower daily doses. The duration of the metronidazole administration in days was not associated with the appearance of nausea. No life-threatening adverse reactions were identified, and good clinical therapeutic effects were observed in 96% (107/111) of the patients. While metronidazole appears to be a safe anti-protozoal agent for patients with amebiasis, our results indicate that a daily metronidazole dose of 2250 mg is excessive for amebiasis, as it often induces nausea.     

Phase I evaluation of coumarin (1,2-benzopyrone) and cimetidine in patients with advanced malignancies.

Fifty-four patients with advanced malignancies were treated on this phase I trial of coumarin and cimetidine. The dose of coumarin was escalated, with three patients treated at each dose level, while the cimetidine dose was held constant at 300 mg four times daily. Patients received coumarin alone as a single daily oral dose for 14 days; on day 15, cimetidine was added and both drugs were continued until progression of disease. This trial was initiated with patients receiving coumarin at 400 mg daily and closed at 7 g daily with four of five patients on this dose experiencing nausea and vomiting. Treatment was generally well tolerated over a wide range of coumarin doses. Symptomatic side effects were few, mild, and usually self limited. Side effects included insomnia, nausea, vomiting, diarrhea, and dizziness. Two patients withdrew from therapy because of daily nausea and vomiting. Typically, nausea, vomiting, and dizziness occurred 2.5-3 hours after a dose of coumarin. In most patients, these side effects abated spontaneously with continuation of therapy. There was no significant hematologic or renal toxicity. Hepatotoxicity occurred in only one patient and was manifested by asymptomatic abnormal elevations of serum hepatic transaminases. This toxicity was reversible upon interruption of therapy. Objective tumor regressions were observed in six patients with renal cell carcinoma. Responses occurred at coumarin doses ranging from 600 mg to 5 g daily. Coumarin is a relatively nontoxic, oral, outpatient therapy that warrants further investigations for the treatment of human malignancies. Because of its low toxicity, there is potential for combining coumarin with chemotherapeutic and/or biological agents in an attempt to improve on efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Two year Cottbus reinfarction study with 30 mg aspirin per day.

All 701 heart infarction patients admitted to 15 hospitals in the district of Cottbus between 1981 and 1983 were randomly administered 30, 60 or 1000 mg aspirin daily according to the territorial affiliation of their local hospitals. The physical and drug therapy during the 2 years follow-up was highly standardized; deviations--as far as they occurred--were documented. Lower all-cause mortality was statistically demonstrated in patients over 60 and a lower fatal reinfarction rate in patients over 50 as well as in men. Deaths and fatal reinfarctions were significantly lower among patients with a history of angina pectoris, marked ST-depression, with an infarction location except for the posterior wall and among hypercholesterolemic patients. The preventive effect of 60 mg aspirin daily was less than that of 30 mg in comparison to the 1000 mg group. Side effects were seen in 4 and 8% (first and second year), respectively, of the patients administered 30 mg aspirin as opposed to 22 and 17% in patients allocated 1000 mg. We conclude that the optimum dose of aspirin for preventing reinfarctions could be as low as 30 mg daily.     

Fractional administration of adriblastin and modified route of ara-C administration for the treatment of acute leukaemia

Two groups of AML patients (n1 = 63, n2 = 20) and two groups of ALL patients (n1 = 33, n2 = 15) were treated using polychemotherapy protocols which in each leukaemia subtype differed mainly in adriblastin administration being either in bolus form (30 mg/m2/day i.v.) or fractional form at the beginning 20 mg i.v., then 6 mg/m2 every 6 h. The fractional method of administration was elaborated on experimental data indicating the superiority of continuous infusion of anthracyclines. In AML additional ara-C was given in continuous infusion only on 1 to 3 days, on 4 to 8 days duplicated dose was administered subcutaneously (i.e. 100 mg/m2 every 12 h). In patients given fractional doses of adriblastin and in AML also ara-C in the modified way the statistical analysis revealed a higher CR (ALL - 67%/93%, AML - 46%/60%) and CR + PR rates, a lower rate of infections as the cause of death in the AML group, lower rates of nausea and vomiting as well a lower increase of infections in the course of the induction treatment in the AML group. Another advantage was a lower total dose of adriblastin for remission induction treatment as well as an elevated cumulative dose which allows anthracyclines to be longer used. The efficacy of the modified ara-C administration confirms our earlier observation.     

NXX-066 in patients with Alzheimer's disease: a bridging study

Reduced cholinergic transmission is a key neurotransmitter dysfunction in Alzheimer's Disease (AD). NXX-066, a physostigmine analog and acetylcholinesterase (AChE) inhibitor, has demonstrated activity in animal models of memory function, and was well tolerated in healthy subjects up to a single dose of 64 mg and multiple doses of 60 mg QD for seven days. Since AChE inhibitors are often tolerated differently in AD patients than in healthy volunteers, a randomized, placebo-controlled, double-blind, single-center, inpatient bridging study was conducted to determine the maximum tolerated dose (MTD) of NXX-066 in the target patient population. Seven consecutive panels of eight AD patients each (6 active, 2 placebo) received fixed oral doses of NXX-066 (20, 30, 40, 50, 60, 70, or 80 mg BID) for seven days. Initiation of each subsequent panel (dose group) was contingent upon the tolerability of lower dose levels. The MTD was determined to be 70 mg BID when four of six patients receiving 80 mg BID were prematurely discontinued from the study due to nausea and/or vomiting, accompanied in some patients by mild to moderate dizziness, headache, asthenia, and gastric symptoms. Wide variability in plasma levels of NXX-066 was observed in all dose panels. AChE inhibition in whole blood correlated with both maximum plasma concentration and dose; however, AChE inhibition was not predictive of adverse events. In this study, AD patients tolerated larger daily doses of NXX-066 on a BID regimen than healthy normal subjects had tolerated with QD dosing. Further studies are warranted to examine whether differing tolerability between patients and healthy subjects or the reduced dosing interval explains these findings.     

Chronic treatment of Paget's disease of bone with synthetic human calcitonin.

Twelve patients with Paget''s disease of bone were treated with synthetic human calcitonin for seven to 26 months (mean 15.3 months). This group included six patients who had previous therapy. Eleven of the 12 patients experienced relief of the symptoms associated with Paget''s disease. The initial therapy of synthetic human calcitonin 0.5-1.0 mg subcutaneously was administered daily until the alkaline phosphatase had declined to a plateau response; the dose was then decreased to thrice weekly. The major biochemical findings were a 47 percent fall in serum alkaline phosphatase and a comparable decline in 24-hour urinary hydroxyproline. Two subjects discontinued therapy because of side effects; persistent nausea and vomiting in one and a cutaneous allergic reaction in the other. Other side effects were minor. Preliminary results suggest that some patients will maintain the same biochemical response on the reduced dose but that this is not predictable by pre-treatment data. We conclude that synthetic human calcitonin is a safe and effective treatment for Paget''s disease of bone. Preliminary results suggest that the dose and frequency of administration of this agent must be individualized.     

Termination of second trimester pregnancy with laminaria and intramuscular 16 phenoxy-ω-17,18,19,20 tetranor PGE2 methylsuldonylamide (sulprostone) — A randomised study

16 phenoxy-ω-17,18,19,20 tetranor PGE₂ methylsulfonylamide (Sulprostone) was used for termination of second trimester pregnancy in four groups of 30 patients. The drug was administered in intramuscular doses of either 0.5 mg four hourly or 1.0 mg 8 hourly. In two groups of 30 patients a medium size sterile laminaria was inserted into the cervical canal eight hours before the start of prostaglandin treatment. In the group treated with 1.0 mg sulprostone eight hourly, 96.7% of those with laminaria and 86.7% without laminaria aborted in respective mean times of 11.2 hrs and 17.5 hrs. All 30 patients (100%) in the laminaria group treated with 0.5 mg sulprostone four hourly aborted within 30 hours in a mean time of 10.4 hours compared with 26 patients (86.7%) in a mean time of 16.7 hours in the group without laminaria.One patient receiving 0.5 mg sulprostone four hourly (no laminaria) sustained a cervical tear requiring repair. The incidence of nausea, vomiting, diarrhoea, cold and shivering was low and similar in the four groups.     

Comparison of the effectiveness of metoclopramide and dexamethasone in the prevention of cytostatic-induced vomiting

Efficiency of anti-emetic properties of metoclopramide and dexamethasone was compared. Both drugs were administered to 22 patients with newly diagnosed untreated previously Hodgkin's disease during ABVD therapy. Number of vomiting episodes, nausea intensity and everyday patients' activity on the day of cytostatics administration were evaluated. Metoclopramide prevented vomiting in 55% of patients while dexamethasone in 65%. This difference was statistically insignificant. Patients' everyday activity was statistically significantly more frequently normal in patients receiving dexamethasone in comparison with placebo and decreased in patients receiving metoclopramide. Therefore, patients preferred dexamethasone.     

舒芬太尼复合吗啡硬膜外术后镇痛的最佳剂量配伍

目的：观察腹式子宫全切术后硬膜外镇痛应用舒芬太尼复合吗啡时两种药物不同剂量的镇痛效果和不良反应,以寻找其最佳剂量配伍。方法：选择90例美国麻醉医师协会（ASA）标准Ⅰ-Ⅱ级、年龄20-60岁拟行腹式子宫全切术的病人,均实施腰硬联合麻醉。随机分成3组,每组30例：Ⅰ组：舒芬太尼10μg＋吗啡2 mg＋氟哌利多1 mg＋1%罗哌卡因20 mg;Ⅱ组：舒芬太尼15μg＋吗啡1.5 mg＋氟哌利多1 mg＋1%罗哌卡因20 mg;Ⅲ组：舒芬太尼20μg＋吗啡1 mg＋氟哌利多1 mg＋1%罗哌卡因20mg。术中监测生命体征,记录术后24小时内的镇痛效果、不良反应及辅助镇痛药物的使用情况。镇痛效果评价采用视觉模拟评分（visual analogue scale,VAS）标准。结果：2组各个时间点VAS评分均明显低于1组（P〈0.05）,在术后6 h,8 h,12 h,18 h,24 h与3组有统计学差异（P〈0.05）,3组在2 h,4 h,6 h的VAS评分低于1组（P〈0.05）;2组恶心评分与3组相比明显较低（P〈0.05）,其他不良反应三组间没有统计学差异;各组患者在术后24h内辅助镇痛药物使用情况比较无统计学差异（P〉0.05）。结论：舒芬太尼15μg复合吗啡1.5 mg用于腹式子宫全切术后硬膜外镇痛效果优于其他常用剂量配伍,镇痛效果平稳确切且不良反应少,具有临床应用价值。     

昂丹司琼联合泮托拉唑对宫颈癌同步放化疗所致恶心呕吐的临床疗效

摘要 目的：研究昂丹司琼联合泮托拉唑对宫颈癌同步放化疗所致恶心呕吐的临床疗效。方法：选择2018年1月～2020年1月我院收治的79例宫颈癌患者,均采取同步化疗,将其随机分为两组。对照组在当天化疗前30 min和随后的6 d连续静脉注射昂丹司琼,每次8 mg,1次/d;同时给予地塞米松磷酸钠注射液10 mg,1次/d。观察组在昂丹司琼的基础上静脉注射泮托拉唑,每次40 mg,1次/d,给药的时间与昂丹司琼相同。比较两组宫颈癌患者恶心呕吐的完全缓解率、癌因性疲乏评分和不良反应的发生情况。结果：两组化疗第1、2 d恶心呕吐的完全缓解率比较差异无明显统计学意义(P>0.05),观察组化疗第3、4、5、6 d恶心呕吐的完全缓解率分别为76.92 %、79.49 %、87.18 %、87.18 %,均明显高于对照组(P<0.05);观察组的癌因性疲乏评分为(45.39±7.29)分,明显低于对照组的(67.24±8.36)分(P<0.05);两组的乏力嗜睡、便秘、椎体外系反应、失眠/不安、腹泻、轻度头痛的发生率比较无明显统计学差异(P>0.05)。结论：昂丹司琼联合泮托拉唑对宫颈癌同步放化疗所致恶心呕吐的疗效显著优于单用昂丹司琼治疗,并能明显减轻癌因性疲乏,且安全性高。     

Labour induction using buccal prostaglandin E2

Prostaglandins may remain in the circulation for some two hours after oral therapy and any resultant hypertonus may be difficult to treat in these circumstances. Buccal administration based on the concept that tablets could be discarded should this occur, has been evaluated in 30 patients. Effective uterine stimulation occured in 90% of subjects receiving a dose of 1mg hourly. No hypertonus occured but two patients had a prolonged contraction on a single occasion during labour. The fact that the tablets dissolve rapidly and in addition produce an unpleasant taste with a high incidence of nausea and vomiting, indicates buccal prostaglandins do not have advantages over alternative methods of oxytocic administration.     

两性霉素B治疗侵袭性肺部真菌感染的临床分析

目的 分析两性霉素B治疗ICU内侵袭性真菌感染的疗效与不良反应.方法 回顾性分析98例合并侵袭性肺部真菌感染的重症患者接受两性霉素B微泵静脉给药的临床资料.结果 两性霉素B的临床有效率77.55％,真菌清除率75.51％.不良反应包括寒战发热（9.18％）、皮疹（4.08％）、静脉炎（1.02％）、恶心呕吐（6.12％）、低钾血症（16.32％）、肝损害（1.02％）和肾损害（4.08％）.结论 国产两性霉素B对于重症患者侵袭性真菌感染疗效确定,采用持续微泵静脉给药不良反应发生率低.     

Results of ciprofloxacin therapy in urinary and respiratory tract infections

Ciprofloxacin was administered to 218 patients with various urinary and respiratory tracts infections, including 142 patients with urinary tract infections and 76 patients with respiratory tract infections. Bacteriological tests and routine laboratory tests were performed thrice (before, during and after therapy) in all patients. Ciprofloxacin was administered orally in daily dose of 500 mg for 10 days. Daily dose was increased to 1000 mg in 23 patients with severe respiratory tract infections. Satisfactory results (recovery or regression of the symptoms of exacerbated chronic disease) were achieved in 185 patients (84.9%) and no effect in 10 patients (4.6%). Significant improvement or transient improvement were noted in 23 patients (10.5%).     

阿片类药物滴定法治疗癌痛的疗效及不良反应分析

目的:探讨阿片类药物滴定法治疗癌痛的疗效及不良反应分析,为临床治疗提供依据。方法:采用回顾性分析选择2012年1月~2015年12月我院收治的肿瘤患者共110例,采用数字评定量表(NRS)和面部表情疼痛分级量表(FRS)进行疼痛评价,采用滴定法从小剂量开始给药,并记录患者的疼痛状况和不良反应发生状况。结果:患者总用药时间为28~170 d,平均用药时间(45.7±19.4)d,中位时间为48d。阿片类药物使用剂量(换算成吗啡剂量计算)40~500 mg,中位剂量74 mg。110例患者中有101例(91.82%)达到中度以上缓解。发生不良反应63(57.27%)例,消化道副反应为最常见的不良反应,主要有便秘48例(43.64%)例和恶心呕吐25例(22.73%)、其次依次为嗜睡15例(13.64%)、头晕9例(8.18%)、排尿困难5例(4.55%)、皮肤瘙痒3例(2.73%)和呼吸抑制2例(1.82%)。结论:阿片类药物能够有效缓解癌症患者的中重度癌痛,其主要不良反应是便秘和恶心呕吐。应合理、安全的使用阿片类药物,从小剂量开始,规范剂量滴定。     

Caffeine potentiates the enhancement by choline of striatal acetylcholine release.

We investigated the effect of peripherally administered caffeine (50 mg/kg), choline (30, 60, or 120 mg/kg) or combinations of both drugs on the spontaneous release of acetylcholine (ACh) from the corpus striatum of anesthetized rats using in vivo microdialysis. Caffeine alone or choline in the 30 or 60 mg/kg dose failed to increase ACh in microdialysis samples; the 120 mg/kg choline dose significantly enhanced ACh during the 80 min following drug administration. Coadministration of caffeine with choline significantly increased ACh release after each of the choline doses tested. Peak microdialysate levels with the 120 mg/kg dose were increased 112% when caffeine was additionally administered, as compared with 54% without caffeine. These results indicate that choline administration can enhance spontaneous ACh release from neurons, and that caffeine, a drug known to block adenosine receptors on these neurons, can amplify the choline effect.     

Pyrantel Embonate in Treatment of Hookworm Infestation

The efficacy of pyrantel embonate (1,4,5,6-tetrahydro-1-methyl-2-(trans-2-(2-thienyl)-vinyl)-pyrimidine embonic acid salt; Combantrin) was evaluated in 60 cases of hookworm infestation. They were divided into six groups of 10 cases. Pyrantel embonate was administered orally, in dosage schedules (randomized) of 100, 75, 50, 20, 15, and 10 mg/kg of body weight. The stool examination for hookworm ova and coproculture were positive in each case. The predominant species was Ancylostoma duodenale (in 58 patients). After treatment with pyrantel embonate the stool examination for hookworm ova and coproculture were negative on the 10th and 15th days in each group. The blood levels of the drug were significantly higher in patients receiving 100 and 75 mg/kg body weight. In groups A and B one patient experienced nausea and vomiting on the day of administration of drug. There were no abnormal changes in liver function tests or blood urea levels in any of the groups. Hence the optimum single dose of the drug effective against hookworm infestation is 10 mg/kg body weight, and further studies are required to evaluate the minimum effective dose of pyrantel embonate.     

Effectiveness of trimetazidine in patients with hypertension and the symptoms of coronary disease]

The investigations were aimed at the objective evaluating of trimetazidine efficacy in the treatment of 30 patients with arterial hypertension and ischemic heart disease carried out in non-invasive manner. It was found that trimetazidine complies with several requirements for the effective drug administered to the patients with hypertension associated with ischemic heart disease as it: (a) reduces peripheral resistance and exerts favourable effect on the walls tonus of larger arteries; (b) lowers specifically post-exercise arterial pressure and improves resting arterial pressure; (c) reduces demand for oxygen; (d) is safe, and well tolerated by 83% of the treated patients in daily dose of 60 mg.     

Pseudomonas vaccine: A phase I evaluation for cancer research

Summary A heptavalent lipopolysaccharide vaccine of Pseudomonas aeruginosa (Pseudogen) was administered at four dose levels (0.1, 0.25, 0.5, and 0.75 mg/m²) to patients with advanced metastatic cancer that had proved refractory to chemotherapy. The vaccine was administered subcutaneously twice weekly. Local toxicity was seen in erythema, edema, pain and tenderness at the site of injection, and painful regional lymphadenopathy; manifestations of systemic toxicity included fever, chills, myalgias, nausea, and vomiting. Toxicity showed a clear-cut dose dependence. The maximally tolerated dose by this route and schedule was 0.5 mg/m². A significant rise of antibody titers was observed at all four dose levels. Evaluation of the delayed cutaneous hypersensitivity response to recall antigens and to the pseudomonas vaccine, and quantification of peripheral blood T and B cell levels and of in vitro lymphocyte blastogenic responses to commonly used mitogens and pseudomonas vaccine failed to demonstrate significant change from pretreatment values. Clinical trials to evaluate the therapeutic efficacy of pseudomonas vaccine with or without chemotherapy can be undertaken safely with this route and schedule.     

Treatment of advanced breast cancer with 20 mg toremifene, a phase II study. Preliminary communication

Fourteen postmenopausal women with estrogen-receptor positive advanced breast cancer and no prior cytostatic treatment received 20 mg toremifene daily as a single dose after a loading dose (120----60----60 mg) for the first 3 days. All were evaluable and had undergone at least 6 weeks' treatment. Results were: no complete remissions (CR), 3 partial remissions (PR), 8 no change (NC) and 3 cases of progressive disease (PD). Three patients had mild side effects: nausea, insomnia, sweating and arm pain.     

The termination of first trimester pregnancy by extraovular “Prostaglandin-impact”

In 30 sedated volunteers first trimester pregnancy had been successfully terminated with Csapo's method of “Prostaglandin-Impact” (1). The patients were 24.1±0.4 years of age, 9.2±0.4 weeks pregnant, para 0.4±0.1. They all received an extraovular dose of 10 mg PG F2α, under intravenous sedation (100 mg pethidium hydrochloride, 50 mg DPP hydrochloride and 0.5 mg atropinum sulfate). Those 15 (out of 30) patients, whose clinical progress was slow received at 8 hours after the first PG Impact (PGI) a 2nd dose of 5 mg PG F2α, increasing the total average dose to 12.5± 0.5 mg.PGI invariably provoked a rapid and high level uterine contracture. At 4 hours after PGI plasma progesterone (P) already decreased by 20% and cyclic intrauterine pressure was in distinct evolution. At 8 hours after PGI, 15 of the 30 patients showed advanced clinical progress and 33% decrease in P levels. These women aborted in 10.2±1.1 hours, when their P levels decreased by 45% (P < 0.001). Abortion was complete in 13 and incomplete in 2 of the patients. The remaining 15 women, whose clinical progress was indistinct at 8 hours after PGI and whose P levels only decreased by 25% received a 2nd dose of 5 mg PG F2α. These women aborted after 18.5±1.5 hours, 9 completely and 6 incompletely, when their P levels decreased (as in the previous group) by 45% (P < 0.001).All the 30 patients aborted after a short IAT of 14.3±1.2 hours. Abortion was complete in 22 women, while 8 retained various amounts of placental tissue. The “Abortion Score” was high, 94.7±1.6. Only 13 patients had side effects, shortly after PGI, manifesting in vomiting and nausea, which were transient and mild. There were no complications during the study and followup. These findings confirm earlier results (1). When supplemented by extensive field trials, the technique of extraovular PGI might be broadly considered for the non-surgical termination of 1st trimester pregnancy.