In Vitro Potentiation of Antibiotic Activities by a Catecholate Iron Chelator against Chloroquine-Resistant Plasmodium falciparum

FR160, a catechol iron chelator, and tetracyclines or norfloxacin exert in vitro additive or synergistic activity against a chloroquine-resistant Plasmodium falciparum clone. FR160 shows antagonistic effects in association with macrolides, ofloxacin, and rifampin.     

Iron chelators as antimalarial agents: in vitro activity of dicatecholate against Plasmodium falciparum

The present study was undertaken to explore the antimalarial effect of a series of dicatecholate iron chelators. They may be made more or less lipophilic by increasing or reducing the length of the R substituent on the nitrogen. In vitro activity against the W2 and 3D7 clones of Plasmodium falciparum, toxicity on Vero cells and toxicity on uninfected erythrocytes by measure of the released haemoglobin were assessed for each compound. These findings were compared with the ability of iron(III), iron(II) and ferritin to reverse the inhibitory effect of catecholates. This study shows that increased lipid solubility of catecholate iron chelators does not lead to improved antimalarial activity. However, their activity is well correlated with their interaction with iron and with their toxicity against Vero cells. This study demonstrates a potent antimalarial effect of FR160 (R = C9H19) on five different strains of P. falciparum in vitro. FR160 inhibited parasite growth with an IC50 between 0.8 and 1.5 micro M. The effects of FR160 on mammalian cells were minimal compared with those obtained with malaria parasites. FR160 acted on parasites at considerably higher rates than desferrioxamine, and at all stages of parasite growth. The drug was more effective at the late trophozoite and young schizont stages, although FR160 affected rings and schizonts as well. Ascorbic acid, a free radical scavenger, reduced the activities of FR160 and artesunate. FR160 might induce formation of free radicals, which could explain why FR160 antagonized the effects of artesunate and dihydroartemisinin.     

Gender Differences in the Clinical Characteristics and Atrioventricular Nodal Conduction Properties in Patients With Atrioventricular Nodal Reentrant Tachycardia

Gender Differences in Patients With AVNRT. Introduction: The detailed electrophysiological characteristics of the gender differences associated with atrioventricular nodal reentrant tachycardia (AVNRT) have not been clarified. This study investigated the gender‐related electrophysiological differences in a large series of patients undergoing radiofrequency catheter ablation. Methods and Results: A total of 2,088 consecutive AVNRT patients (men/women 869/1,219) who underwent catheter ablation were enrolled in this study. We evaluated the gender differences in their electrophysiological characteristics. Women had a significantly younger age of onset, higher incidence of multiple jumps, shorter AH interval, atrial effective refractory period (ERP), anterograde fast pathway ERP, anterograde slow pathway ERP, and retrograde slow pathway ERP, and longer ventricular ERP than men. The incidence of baseline ventriculoatrial dissociation was lower in women than in men. Women needed less isoproterenol/atropine to induce AVNRT. No gender differences in the radiation exposure time, procedure time, complication rate, acute success rate, or second procedure rate were noted. Both typical and atypical AVNRT were more predominant in women. In the patients with atypical AVNRT, there was no significant gender difference in incidence of baseline ventriculoatrial dissociation; however, the retrograde slow pathway ERP was significantly shorter in women than in men. Women of premenopausal age (≤50 years old) had a significantly higher incidence of anterograde multiple jumps and a retrograde jump phenomenon, and a shorter anterograde slow pathway ERP and retrograde slow pathway ERP than those of women over 50 years old. Conclusion: Gender differences in the anterograde and retrograde AV nodal electrophysiology were noted in the patients with AVNRT. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1114‐1119)     

Persistent erythema multiforme: a report of three cases

Three cases of persistent erythema multiforme, two of unknown aetiology and one precipitated by influenza are reported. Lesions were widespread, mostly atypical in appearance and regressed in response to immunosuppressants (systemic steroids and/or azathioprine) or, in one case, to dapsone. One patient developed erythroderma responding eventually to etretinate. Histology in all patients was consistent with the mixed, epidermodermal pattern of erythema multiforme. There were no significant laboratory abnormalities nor marked symptomatology apart from itching. The persistent form appears to belong to the spectrum of erythema multiforme being heterogeneous with respect to inducing stimuli, including viral antigens, neoplastic or inflammatory disease or unknown causes. Whenever it is possible, treatment should be adjusted depending on the causative agent.     

Intestinal ganglioneuromatosis diagnosed in adult patients

AIM: Intestinal ganglioneuromatosis is essentially described in children and rarely in adults. The purpose of this study was to evaluate the clinical pathological patterns of intestinal ganglioneuromatosis diagnosed in adult patients. MATERIALS AND METHODS: Ten patients were included in this study (6 men, 4 woman; mean age=55.4 years). The diagnosis was established from ileocolorectal biopsies (n=5) or from a surgical specimen (n=5). An immunohistochemical study was performed with antibodies directed against S100 protein, synaptophysin, PGP9.5, neurofilament, tau protein, c-Kit and c-Ret. Clinical symptoms, endoscopic data and outcome were retrospectively reviewed. RESULTS: The diagnosis of intestinal ganglioneuromatosis was established solely on the basis of the microscopic examination in all 10 cases. Three patients presented with acute occlusion. The endoscopic examination showed unusual spasticity of the colon or colectasia in 5 cases, raspberry-like polyps in 2 cases and finger-like polyps in 3 cases. Ganglioneuromatosis was characterized by diffuse Schwann cell hyperplasia expressing S100 protein in close contact to nerve fibers expressing neurofilament, tau protein, synaptophysin, PGP9.5 and to ganglion cells expressing c-Ret. There was no hyperplasia of interstitial cells of Cajal. Intestinal ganglioneuromatosis was localized in the mucosa in 9 cases and extended through the entire intestinal wall in 1 case. The finger-like polyps corresponded to ganglioneuromatosis, while the raspberry-like polyps corresponded to adenomas. Two patients had von Recklinghausen's disease, 1 had multiple endocrine neoplasia type 2B and 1 had Cowden's disease. Intestinal ganglioneuromatosis was associated with nonfamilial adenomatous polyposis in 2 patients and colonic adenocarcinoma in 1 patient. The patients with finger-like polyps had no associated disease. CONCLUSION: Intestinal ganglioneuromatosis in adults is distinctive from that in children. In adults, intestinal ganglioneuromatosis is always a microscopic diagnosis although finger-like polyps observed at colonoscopy may be suggestive. Gastroenterologists must be aware of the higher risk of occlusion and intestinal neoplasia.     

兔腰椎间盘内显微注射方法的相关问题及其解剖学特点

目的：测量兔腰椎间盘解剖学数据，并探讨兔腰椎间盘内显微注射方法中的相关问题。方法：实验于2004-10在中山大学附属第二医院完成。实验动物选择三四月龄的新西兰大白兔10只，麻醉后空气栓塞法处死，取出腰椎间盘观察其解剖结构。并测量椎间盘纤维环前后径长度，测量前部纤维环前后径长度，测量椎间盘前正中点到髓核中心点的长度。取同样10只白兔，麻醉后，右侧卧位，沿左侧12肋末向下至髂嵴做纵切口，切开胸腰筋膜后层，在骶棘肌和腰方肌的外缘与胸腰筋膜前层间钝性分离。推开腰椎间盘前方筋膜和前纵韧带，以椎体前方的纵性骨棘为标志从腰椎间盘前方中心点处垂直进针，以微量注射器注入25μL黑色墨水作为标记。体会显露椎体和椎间盘的入路和手术方式，观察侧方手术入路能否良好显露腰椎间盘，能否较好的完成椎间盘内注射。观察椎间盘内注射的入针点，进针长度，进针角度，注射剂量，注入结果。小心取出注射入墨水的兔脊柱（包含L1～L7范围），共计70个，迅速置入-20℃低温冷冻，2h后取出，微解冻后以尖刀从中间水平切开椎间盘，观察墨水注入髓核的情况。结果：20只动物实验过程中无死亡，全部进入结果分析。①解剖学观察：兔髂嵴短，平髂嵴最高点连线在俯卧位时经过L6棘突，可做为手术操作的体表标志。椎间盘为三明治结构，上下为软骨终板，与上下方椎体相连；由外向内依次为外层纤维环、内层纤维环、移行区、髓核。②手术入路：顺利显露出L3～L6椎间盘，显露操作时间平均为15min，共计70个椎间盘。⑧椎间盘内注射方法：选择在嵴状突起于椎间盘水平中线的交点即为进针点，保持进针深度3mm，注射最大液体量25μL。注射效果理想者64个，其中L3～L6椎间盘共计40个，注射效果良好者39个，成功率97．2％。结论：通过对兔腰椎间盘的部分解剖学数据，椎间盘纤维注射的注射方式、手术入路的选择，进针点、进针长度、进针角度的确定、注射液体量的观察及实践，证明以本方法进行腰椎间盘内微量注射操作规范，可取得理想效果。     

Factors predicting blood pressure normalization in hypertensive patients treated with a fixed-dose combination of bisoprolol 2.5 mg/hydrochlorothiazide/6.25 mg

It is not clear which duration of treatment is needed to achieve complete efficacy with fixed low dose antihypertensive therapy. The aim of this study was to compare blood pressure control rate in patients treated with bisoprolol 2.5 mg/HCTZ 6.25 mg, not controlled after 4 weeks, but treated at the same dosage for one more month to patients not controlled after 4 weeks, and uptitrated to bisoprolol 5 mg/HCTZ 6.25 mg for one month. The 641 patients who entered the study had a mean age of 58 +/- 12 with SBP/DBP at baseline of 165 +/- 12/96 +/- 7 mmHg. After 4 weeks, 252 (39%) where normalized (< 140/90) with SBP/DBP reductions of -27/-15 mmHg. In uncontrolled patients, 19% of those randomized to B 2.5 mg/H 6.25 mg and 33% of those treated with B 5 mg/H 6.25 mg where normalized at the end of the study (p < 0.001). Multivariate analysis indicates determinants of blood pressure normalisation after 4 weeks with B2.5 mg/HCTZ 6.25 mg as female gender, initial BP < 175/105 mmHg, previously untreated hypertension, age < 50 years. In conclusion, when the initial therapy with bisoprolol 2.5 mg/HCTZ 6.25 mg is not sufficient to control blood pressure, continuation with the same dosage 4 weeks longer increases the rate of blood pressure control. However, up-titration to bisoprolol 5 mg/6.25 mg is more efficacious to increase the number of patients with a final blood pressure < 140/90 mmHg.