In vitro and in vivo activity of meglumine antimoniate produced at Farmanguinhos-Fiocruz, Brazil, against Leishmania (Leishmania) amazonensis, L (L.) chagasi and L (Viannia) braziliensis

The leishmanicidal activity of four batches of meglumine antimoniate, produced in Farmanguinhos-Fiocruz, Brazil (TAMs), was assessed and compared to Glucantime(R)-Aventis Pharma Ltda. Using the amastigote-like in vitro model, the active concentrations of Sb v varied from 10microg/ml to 300 microg/ml for L. (L.) chagasi and from 50microg/ml to 300microg/ml for L. (L.) amazonensis, with no statistically significant differences among the four batches of TAMs and Glucantime(R). The inhibitory concentrations (IC50) determined by the amastigote-infected macrophage model for TAM01/03 and Glucantime(R) were, respectively: 26.3microg/ml and 127.6microg/ml for L. chagasi, 15.4microg /ml and 22.9microg/ml for L. amazonensis, and 12.1microg/ml and 24.2microg/ml for L. (V.) braziliensis. The activities of the four batches of TAMs were confirmed in an in vivo model by assessing, during eight weeks skin lesions caused by L. braziliensis in hamster that were treated with 20mg Sb v/Kg/day for 30 consecutive days. The meglumine antimoniate produced by Farmanguinhos was as effective as the reference drug, Glucantime(R)-Aventis, against three species of Leishmania that are of medical importance in Brazil.     

Effects on the murine mononuclear phagocyte system of chronic administration of liposomes containing cytotoxic drug or lipid A compared with empty liposomes

In experiments designed to examine the adverse effects of chronic liposome administration in vivo on the mononuclear phagocyte system (reticuloendothelial system), the presence of drug entrapped in the liposomes may increase the level of reticuloendothelial impairment. We have compared the effects on the mononuclear phagocyte system in mice of chronic administration of empty liposomes with the effects of liposomes containing the anti-leishmanial drug meglumine antimoniate. We have also examined the effect on the mononuclear phagocyte system of continued injections of liposomes containing lipid A, a component of bacterial lipopolysaccharide, which is responsible for macrophage activation. Ten intravenous injections of multilamellar liposomes composed of dipalmitoylphosphatidylcholine and cholesterol (1:0.75 M ratio) were given to ICR mice over a 25-day period. Two individual groups of mice received endotoxin-free liposomes in which meglumine antimoniate was either present or absent. One addition group received liposomes containing lipid A derived from Escherichia coli lipopolysaccharide. A control group received sterile saline injections. In each group, a depression of the phagocytic index, as measured by reduction of uptake of particulate carbon, was observed among some of the individual animals 24 h after the first injection. In many mice a marked splenomegaly was observed. A depressed phagocytic index and splenomegaly were most marked for mice receiving lipid A liposomes. However, there was a large individual variability among mice receiving these preparations and some mice in each group had normal spleen size and a nearly normal phagocytic index. Tissue distribution of liposomes containing [14C]dipalmitoylphosphatidylcholine as a phospholipid marker was examined in all groups in mice 24 h after the last injection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sensitivity of Leishmania braziliensis promastigotes to meglumine antimoniate (glucantime) is higher than that of other Leishmania species and correlates with response to therapy in American tegumentary leishmaniasis

The first line drugs for the treatment of leishmaniasis are antimonial derivatives. Poor clinical response may be credited to factors linked to the host, the drug, or the parasite. We determined the sensitivity of Leishmania sp. promastigotes and amastigotes by counting parasites exposed to increasing concentrations of meglumine antimoniate (Glucantime). Leishmania braziliensis promastigotes were significantly more sensitive than those belonging to other species. The sensitivity of L. braziliensis isolates from patients with unfavorable clinical outcome, such as therapeutic failure or relapse, was significantly lower than those from patients who had clinical cure. Poor clinical response to therapy (therapeutic failure or relapse) was also associated with inadequate antimonial therapy. We also found a significant and positive correlation between promastigotes and intracellular amastigotes with regard to their in vitro susceptibilities to meglumine antimoniate. Our data provide evidence for an association between the sensitivity of promastigotes to antimonials in vitro and clinical response to therapy in American tegumentary leishmaniasis. The high sensitivity of the local L. braziliensis to meglumine antimoniate in vitro provides an explanation for the good clinical response of cutaneous leishmaniasis in the municipality of Rio de Janeiro, Brazil, even when low-dose regimens are employed.     

Protocol for the Arterial Revascularisation Trial (ART). A randomised trial to compare survival following bilateral versus single internal mammary grafting in coronary revascularisation [ISRCTN46552265]

Background

Cutaneous Leishmaniasis is a worldwide disease, endemic in 88 countries, that has shown an increasing incidence over the last two decades. So far, pentavalent antimony compounds have been considered the treatment of choice, with a percentage of cure of about 85%. However, the high efficacy of these drugs is counteracted by their many disadvantages and adverse events. Previous studies have shown nitric oxide to be a potential alternative treatment when administered topically with no serious adverse events. However, due to the unstable nitric oxide release, the topical donors needed to be applied frequently, making the adherence to the treatment difficult. The electrospinning technique has allowed the production of a multilayer transdermal patch that produces a continuous and stable nitric oxide release. The main objective of this study is to evaluate this novel nitric oxide topical donor for the treatment of cutaneous leishmaniasis.

Methods and design

A double-blind, randomized, double-masked, placebo-controlled clinical trial, including 620 patients from endemic areas for Leishmaniasis in Colombia was designed to investigate whether this patch is as effective as meglumine antimoniate for the treatment of cutaneous leishmaniasis but with less adverse events. Subjects with ulcers characteristic of cutaneous leishmaniasis will be medically evaluated and laboratory tests and parasitological confirmation performed. After checking the inclusion/exclusion criteria, the patients will be randomly assigned to one of two groups. During 20 days Group 1 will receive simultaneously meglumine antimoniate and placebo of nitric oxide patches while Group 2 will receive placebo of meglumine antimoniate and active nitric oxide patches. During the treatment visits, the medications will be daily administered and the presence of adverse events assessed. During the follow-up, the research group will visit the patients at days 21, 45, 90 and 180. The healing process of the ulcer, the health of the participants, recidivisms and/or reinfection will also be assessed. The evolution of the ulcers will be photographically registered. In case that the effectiveness of the patches is demonstrated, a novel and safe therapeutic alternative for one of the most important public health problems in many countries will be available to patients.     

Role of residual Sb(III) in meglumine antimoniate cytotoxicity and MRP1-mediated resistance

Despite the clinical use of pentavalent antimonials for more than half a century, their metabolism in mammals and mechanisms of action and toxicity remain poorly understood. It has been proposed that the more active and toxic trivalent antimony form Sb(III) plays a critical role in their antileishmanial activity and toxicity. The aim of this work was to investigate the role of residual Sb(III) both in the antileishmanial/antitumoral activities of the pentavalent meglumine antimoniate and in the MRP1 (multidrug resistance-associated protein 1)-mediated resistance to this drug. Samples of meglumine antimoniate differing in their amount of residual Sb(III) (meglumine antimoniate synthesized either from SbCl₅ or from KSb(OH)₆ as well as commercially-available meglumine antimoniate) were evaluated in vitro and in vivo on Leishmania amazonensis infections, as well as for their cytotoxicity to normal and MRP1-overexpressing GLC4 cell lines. Although in vitro the two most effective drugs contained the highest levels of Sb(III), no correlation was found in vivo between the antileishmanial activity of meglumine antimoniate and its residual Sb(III) content, suggesting that residual Sb(III) contributes only marginally to the drug antileishmanial activity. On the other hand, the GLC4 cells growth inhibition data strongly suggests a marked contribution of residual Sb(III). Additionally, the potassium salt of antimoniate (non-complexed form of Sb(V)) was found to be more cytotoxic than meglumine antimoniate. Although MRP1-overexpressing GLC4 cells showed a marked resistance to trivalent antimonials, cross-resistance to meglumine antimoniate was observed only for the products that contained relatively high levels of Sb(III) (at least 0.03% by weight), suggesting that MRP1 mediates resistance to Sb(III) but not to Sb(V). In conclusion, our data strongly suggest that residual Sb(III) in pentavalent antimonial drugs does not contribute significantly to their antileishmanial activity, but is responsible for their cytotoxic activity against mammalian cells and the MRP1-mediated resistance to these drugs.     

Leishmania infantum: stage-specific activity of pentavalent antimony related with the assay conditions

The determination of the intrinsic sensitivity of Leishmania strains to pentavalent antimonials in clinical trials, before treatment is begun, is essential in order to avoid failures and to allow alternative drugs to be chosen. A comparative study of SbV activity on promastigotes, axenic amastigote-like cells, and intracellular amastigotes of Leishmania infantum, when administered in the form of meglumine antimoniate and free, in hydrochloric solution, was performed. Results indicate that the conditions under which the promastigotes were cultured affect the IC(50) obtained, although results were homogeneous when the products were assayed on axenic-like and intracellular amastigotes. The IC(50) obtained for SbV in the form of meglumine antimoniate or in hydrochloric solution on promastigotes cultured in Schneider's medium depends on the growth rate of the culture and therefore could be regulated by modifying the fetal calf serum concentration in the medium. The pH of the culture medium strongly affected the activity of meglumine antimoniate but not that of the SbV hydrochloric solution on promastigotes cultured in Schneider's medium. This influence of pH was observed to a much lesser extent when promastigotes were cultured on M199 or RPMI media. In homogeneous culture conditions, which included the regulation of the promastigote growth rate through the heat-inactivated fetal calf serum concentration in the medium and the dilution of the meglumine antimoniate with Schneider's medium at pH 6.5, the activity of SbV, free or in the form of meglumine antimoniate, was the same in promastigotes, intracellular amastigotes, and axenic amastigote-like cells.     

布比卡因局部阻滞治疗输尿管结石所致肾绞痛60 例的临床观察

目的:比较药物治疗与布比卡因局部阻滞治疗输尿管上段结石所致的肾绞痛的临床疗效。方法:选择输尿管结石患者共120例。随机分成药物治疗组(M组)与局部阻滞组(B组)各60例,其中药物治疗组采用杜冷丁加阿托品治疗,局部阻滞组采用布比卡因行痛区局部阻滞,两组年龄、性别均无统计学差异,比较两组患者治疗的总有效率、不良反应、镇痛起效时间、缓解时间等疗效指标。结果:局部阻滞组治疗的总有效率大于药物治疗组,不良反应也比药物治疗组少。疼痛起效时间及缓解时间,局部阻滞组均明显短于药物治疗组。结论:布比卡因局部阻滞治疗输尿管上段结石所致的肾绞痛临床疗效明显优于以杜冷丁加阿托品为代表的药物治疗。     

The Absence of CYP3A5*3 Is a Protective Factor to Anticonvulsants Hypersensitivity Reactions: A Case-Control Study in Brazilian Subjects

Although aromatic anticonvulsants are usually well tolerated, they can cause cutaneous adverse drug reactions in up to 10% of patients. The clinical manifestations of the antiepileptics-induced hypersensitivity reactions (AHR) vary from mild skin rashes to severe cutaneous drug adverse reactions which are related to high mortality and significant morbidity. Genetic polymorphisms in cytochrome P450 genes are associated with altered enzymatic activity and may contribute to the risk of AHR. Here we present a case-control study in which we genotyped SNPs of CYP2C19, 2C9 and 3A5 of 55 individuals with varying severities of AHR, 83 tolerant, and 366 healthy control subjects from São Paulo, Brazil. Clinical characterization was based on standardized scoring systems and drug patch test. All in vivo investigation followed the ENDA (European Network of Drug Allergy) recommendations. Genotype was determined by real time PCR using peripheral blood DNA as a template. Of all 504 subjects, 65% were females, 45% self-identified as Afro-American, 38% as Caucasian and 17% as having non-African mixed ascendancy. Amongst 55 subjects with AHR, 44 had severe cutaneous drug adverse reactions. Of the 46 drug patch tests performed, 29 (63%) were positive. We found a strong association between the absence of CYP3A5*3 and tolerant subjects when compared to AHR (p = 0.0002, OR = 5.28 [CI95% 2.09–14.84]). None of our groups presented positive association with CYP2C19 and 2C9 polymorphisms, however, both SNPs contributed to separation of cases and tolerants in a Classification and Regression Tree. Our findings indicate that drug metabolism genes can contribute in the tolerability of antiepileptics. CYP3A5*3 is the most prevalent CYP3A5 allele associated with reduced enzymatic function. The current study provides evidence that normal CYP3A5 activity might be a protective factor to aromatic antiepileptics-induced hypersensitivity reactions in Brazilian subjects.     

Improved therapy of experimental leishmaniasis by use of a liposome-encapsulated antimonial drug

The anti-leishmanial antimonial drug meglumine antimoniate (Glucantime ®) was incorporated into liposomes, and was tested for effects against experimental leishmanial infection in hamsters. When the hamsters had been infected for a short period before treatment (3 days), treatment doses of 416 mg/kg of free meglumine antimoniate, or 4 mg/kg of liposome-encapsulated drug, each gave 99.8% suppression of parasites. After 10 or 17 days of infection prior to treatment liposome-encapsulated compound was more than 300 times as effective as the antimonial drug alone. Use of liposomes containing appropriate drugs is proposed as a markedly superior means to treat certain chronic intracellular parasitic infections.     

布拉酵母菌联合三联疗法根除幽门螺杆菌疗效研究

目的探讨布拉酵母菌（S．Boulardii）散剂联合标准三联疗法根除幽门螺杆菌（Helicobacterpylori,H．pylori）的有效性和安全性。方法将210例初次接受根除治疗的Hpylori阳性患者随机分为2组,A组：口服埃索美拉唑＋阿莫西林＋呋喃唑酮,每日2次,疗程10d;B组：与A相同的三联10d疗法,加s．Boulardii散剂口服500mg／次,2次／d,共用药14d。观察患者不良反应发生情况及对药物耐受情况,停药4周后检测H．pylori根除率。结果A、B组Hpylori根除率按方案（PP）分析分别为70．7％、86．3％,按意向性（ITT）分析分别为66．7％、83．8％,B组PP和ITT根除率均高于A组,差异有统计学意义（P〈0．05）;B组不良反应发生率低于A组（8．8％vs 28．3％,P〈0．05）;在药物耐受程度方面,B组明显优于A组（P〈0．05）。结论S．Boulardii散剂联合标准三联疗法作为初次根除Hpylori治疗时可提高根除率,降低不良反应,增加药物耐受程度。     

Leishmania infantum infection rates in Phlebotomus perniciosus fed on naturally infected dogs under antimonial treatment

Dogs naturally infected with Leishmania infantum Nicolle were treated with three courses of meglumine antimoniate. Changes were observed in the dogs' clinical signs, antibody titres and in infection rates of Phlebotomus perniciosus Newstead fed on the dogs. A large reduction in the sandfly infection rate was observed for 4-5 months after the first treatment. The use of antimonial drugs is advocated for the control of canine leishmaniasis and to reduce risks of L.infantum transmission.     

Clinical, epidemiological and molecular features of the HIV-1 subtype C and recombinant forms that are circulating in the city of São Paulo, Brazil

ABSTRACT: BACKGROUND: The city of Sao Paulo has the highest AIDS case rate, with nearly 60% in Brazil. Despite,several studies involving molecular epidemiology, lack of data regarding a large cohort studyhas not been published from this city.ObjectivesThis study aimed to describe the HIV-1 subtypes, recombinant forms and drug resistancemutations, according to subtype, with emphasis on subtype C and BC recombinants in thecity of S?o Paulo, Brazil.Study designRNA was extracted from the plasma samples of 302 HIV-1-seropositive subjects, of which211 were drug-naive and 82 were exposed to ART. HIV-1 partial pol region sequences wereused in phylogenetic analyses for subtyping and identification of drug resistance mutations.The envelope gene of subtype C and BC samples was also sequenced. RESULTS: From partial pol gene analyses, 239 samples (79.1%) were assigned as subtype B, 23 (7.6%)were F1, 16 (5.3%) were subtype C and 24 (8%) were mosaics (3 CRF28/CRF29-like). Thesubtype C and BC recombinants were mainly identified in drug-na?ve patients (72.7%) andthe heterosexual risk exposure category (86.3%), whereas for subtype B, these values were69.9% and 57.3%, respectively (p = 0.97 and p = 0.015, respectively). An increasing trend ofsubtype C and BC recombinants was observed (p < 0.01). CONCLUSION: The HIV-1 subtype C and CRFs seem to have emerged over the last few years in the city ofS?o Paulo, principally among the heterosexual population. These findings may have animpact on preventive measures and vaccine development in Brazil.     

替考拉宁在感染的血液病患者中血药浓度的监测与应用价值分析

目的:探讨替考拉宁在感染的血液病患者中血药浓度的监测与应用价值。方法:回顾分析2017年12月-2019年12月来我院治疗的42例革兰氏阳性球菌引起感染的血液病患者临床资料,按照临床替考拉宁的给药剂量分A组和B组,每组21例。利用高效液相色谱法(HPLC)检测患者第5天用药前30 min的血药浓度,利用酶联免疫荧光法检测患者降钙素原(PCT)水平。比较两组血药浓度,临床疗效及PCT水平的差异,并记录不良反应。结果:B组患者血药浓度(15.12±4.68)mg/L高于A组的(11.76±5.31)mg/L,且B组患者PCT水平(0.86±1.21)ng/mL低于A组的(2.23±1.63)ng/mL,差异均有统计学意义(P<0.05)。B组患者临床有效率为95.24%(20/21),A组临床有效率为71.43%(15/21),两组临床有效率比较差异有统计学意义(P<0.05)。A组发生不良反应发生率为23.81%(5/21),B组不良反应发生率为19.05%(4/21),两组患者不良反应发生率比较差异无统计学意义(P>0.05)。有效组患者血药浓度(17.21±6.64)mg/L高于无效组的(10.14±5.48)mg/L;且有效组患者PCT水平(0.65±1.31)ng/mL低于无效组的(2.63±1.87)ng/mL,差异均有统计学意义(P<0.05)。结论:对感染的血液病患者,提高替考拉宁初始负荷剂量可以达到较高的有效血药浓度,临床疗效更好,且不良反应未见增加。对感染的血液病患者进行血药浓度监测,能够一定程度上反映出临床治疗效果,具有临床参考价值。     

Seroepidemiological studies of HIV-1 infection in large Brazilian cities

The prevalence of HIV-1 antibodies in selected groups of individuals from Rio de Janeiro, S?o Paulo and Santos was determined retrospectively. These groups and respective prevalences were: hemophiliac patients from Rio de Janeiro (1983-1984) 98.0%; polytransfused hemodialysis patients from S?o Paulo (1985-1986) 3.0% and (1987) 7.7%; intravenous drug addicts from S?o Paulo and Rio de Janeiro (1986-1987) 15.9%; male prisoners from S?o Paulo (1988) 12.5%, and pregnant women from Santos (1988-1989) 3.6%. These data stress the magnitude of AIDS in Brazil.     

复方嗜酸乳杆菌片联合三联方案根除幽门螺杆菌的临床研究

目的探讨复方嗜酸乳杆菌片联合三联方案根除幽门螺杆菌(Helicobacter pylori,H.pylori)的疗效及不良反应。方法将143例H.pylori检测阳性的患者随机分为A1组(48例)、A2组(46例)和B组(49例)。B组给予三联方案(埃索美拉唑、阿莫西林、克拉霉素)根除H.pylori治疗,疗程10d。A1组、A2组分别在上述三联方案的基础上同时加用10d、20d的复方嗜酸乳杆菌片。治疗过程中观察并记录上述三组的不良反应发生情况,停药4周后查13 C呼气试验判别H.pylori根除是否成功。结果共133例患者完成治疗和随访,A1组、A2组、B组根除率按方案(PP)分析分别为65.9%、69.8%、63.0%,按意向性(ITT)分析分别为60.4%、65.2%、59.2%,无论按方案分析还是意向性分析三组根除率差异均无统计学意义(P0.05)。纳入三组的共143例患者均完成不良反应的随访,A1组、A2组、B组不良反应发生率分别为10.4%、8.7%、30.6%,三组相比差异有统计学意义(P0.05),其中A1组、A2组分别与B组相比差异有统计学意义(P0.05),A1组与A2组相比差异无统计学意义(P0.05)。结论三联方案加用10d、20d的复方嗜酸乳杆菌片未能提高H.pylori根除率,但可降低不良反应发生率。     

Coexistence of antibodies to tick-borne agents of babesiosis and Lyme borreliosis in patients from Cotia county,State of São Paulo,Brazil

This paper reports a case of coinfection caused by pathogens of Lyme disease and babesiosis in brothers. This was the first case of borreliosis in Brazil, acquired in Cotia County, State of S o Paulo, Brazil. Both children had tick bite history, presented erythema migrans, fever, arthralgia, mialgia, and developed positive serology (ELISA and Western-blotting) directed to Borrelia burgdorferi G 39/40 and Babesia bovis antigens, mainly of IgM class antibodies, suggestive of acute disease. Also, high frequencies of antibodies to B. bovis was observed in a group of 59 Brazilian patients with Lyme borreliosis (25.4%), when compared with that obtained in a normal control group (10.2%) (chi-square = 5.6; p < 0.05). Interestingly, both children presented the highest titers for IgM antibodies directed to both infective diseases, among all patients with Lyme borreliosis.     

Patients as a direct source of information on adverse drug reactions.

To determine whether patients should participate directly in detecting adverse reactions to drugs their ability to provide written reports of symptoms experienced during treatment with amoxycillin or trimethoprim-sulphamethoxazole was investigated. When compared with telephone interviews forms on which patients reported events were reliable (the observed agreement with the same statements posed during telephone calls was 85%, kappa = 0.56) and valid (sensitivity = 54%, specificity = 94%). Patients were also supplied with forms that invited them to report adverse reactions, and their perceptions were compared with those of a panel of experts, who were informed of all clinical events that had been reported during the detailed telephone interviews. Patients were more conservative than the experts in attributing clinical events to drug treatment. The extent of agreement varied and was notably poor for skin and bowel complaints (kappa = 0.13 in each case). The performance of event report forms and reaction report forms as instruments of detection was compared in a hypothetical situation in which the experts'' views represented the "truth" about adverse reactions to a new drug. Event reporting had a higher sensitivity than reaction reporting (42% v 24%) but a lower specificity (58% v 98%). National centres monitoring adverse drug reactions should probably resist pressure to accept reports of reactions directly from the public, but a system based on large scale reporting of events might be valuable in aiding the early detection of symptomatic reactions to new drugs.     

Visceral Leishmaniasis in Southwestern Iran: A Retrospective Clinico-Hematological Analysis of 380 Consecutive Hospitalized Cases (1999–2014)

Visceral Leishmaniasis (VL) is an endemic parasitic disease and remains as a major health concern in southwestern Iran. The current study describes clinico-hematological, epidemiological and therapeutic features of VL cases, admitted to university-affiliated hospitals, during 1999–2014 in Fars province, southwestern Iran. A total of 380 VL cases were recorded during a 16 years period, giving an average annual admission of 23.75 cases/year in which 217 (57.1%) were male and 163 (42.9%) were female. Mean age of the patients was 3.7 years. The majority of the cases (91.5%) were ≤ 5 years old. Bone-marrow aspiration detected Leishmania amastigotes only in 26.6% of cases. Fever (98.1%), abdominal protrusion (65.1%) and hepatosplenomegaly (63.7%) were the most common clinical presentations of the patients. Pancytopenia was noted in 43.1, anemia in 87.3 and thrombocytopenia in 64% of cases. Increase in the level of AST (aspartate aminotransferase), ALT (alanine aminotransferase), alkaline phosphatase, LDH (lactate dehydrogenase) and CRP (C-Reactive Proteins) were seen in 84.9, 53.6, 44.4, 72.5 and 83.1% of cases, respectively. Mortality was noted in 5.3% of cases. Deranged haemato-biochemical parameters including total and direct bilirubin, PLT (platelet) and pancytopenia were significantly contributed to mortality from VL. Moreover, clinical features such as severe splenomegaly as well as bacterial infections were meaningfully contributed to death from VL. The majority of patients (74.9%) were treated with meglumine antimoniate. Amphotericin B was administrated in 59 of cases, 11 of them were initially treated with meglumine antimoniate with a shift to amphotericin B, because of treatment failure. Findings of the current study demonstrated that VL is present in southwest of Iran with a fairly continual rate during the last 16 years period. Deranged haemato-biochemical parameters along with severe splenomegaly contributed to mortality from VL.     

金双歧联合四联疗法对幽门螺杆菌感染的治疗

目的观察金双歧联合四联疗法根除幽门螺杆菌(H.pylori)的临床疗效。方法选取福建省立金山医院南院2015年8月1日至2017年8月1日300例H.pylori感染患者,随机分为A组(50例,采用雷贝拉唑、枸橼酸铋钾、克拉霉素和阿莫西林治疗)、B组(50例,在A组基础上联用金双歧治疗)、C组(50例,采用雷贝拉唑、枸橼酸铋钾、阿莫西林和呋喃唑酮治疗)、D组(50例,在C组基础上联用金双歧治疗)、E组(50例,采用雷贝拉唑、枸橼酸铋钾、呋喃唑酮和四环素治疗)、F组(50例,在E组基础上联用金双歧治疗)。观察各组患者的临床疗效及不良反应。结果 A、B、C、D、E和F组患者的H.pylori根除率按PP分析分别为81.4%、95.7%、82.2%、95.8%、97.9%和97.9%,而各组患者H.pylori根除率按ITT分析分别为70.0%、88.0%、74.0%、92.0%、92.0%和94.0%,A组和B组,C组和D组H.pylori根除率的PP分析和ITT分析比较差异有统计学意义(P0.05);E组和F组根除率的PP分析和ITT分析比较差异无统计学意义(P0.05)。A、B、C、D、E和F组的总不良反应率分别为30.2%、10.9%、31.1%、10.4%、53.2%和22.9%,其中A组和B组,C组和D组,E组和F组总不良反应率差异均有统计学意义(P0.05)。结论金双歧联合四联疗法可提高H.pylori根除率,减少患者不良反应,可推荐用于H.pylori感染患者的根除治疗。     

Antimony Containing Drug and ECG Abnormalities in Children with Visceral Leishmaniasis

The objective of the paper was to evaluate the influence of antimony (5⁺) on electrocardiographic changes in children with visceral leishmaniasis. The study was based on weekly ECGs analysis of 87 children treated, from April 2001 to May 2006, with antimoniate N-methyl glucamine. Eligible subjects included children from 6 months to 12 years of age with weight of 6–34 kg. Forty-five children (52%) were males and forty-two (48%) were females. The cardiac response to antimony was significantly milder compared to the adult populations, so the usage of meglumine antimoniate is safer. Thus, during treatment sinus rhythm was maintained without ectopic beats. No changes were observed in the P wave and in PR interval. The QRS complex remained unaltered during the treatment, the amplitude being increased. The Sokolow`s indexes exceeded normal values in one child on the first week and in eight children on the fourth. The prolongation of QTc occurred in ten patients. The T wave flattening was observed in seven children on the first week. In total, ECG abnormalities were detected in 34.4% of treatment courses, while in adults they were reported in 53.8%. Antimony therapy needs ECG monitoring of the cardiac function in order to prevent complications.