The efficacy of halofantrine in the treatment of acute malaria in nonimmune travelers.

A multicenter prospective trial was performed to investigate the efficacy and the tolerability of halofantrine in nonimmune patients with malaria imported from areas with drug-resistant falciparum parasites (mainly Africa). Forty-five of the 74 subjects were treated with a one-day regimen (3 x 500 mg) of halofantrine, and the other 29 received the same regimen with an additional treatment on day 7. In the second group, a 100% efficacy rate was demonstrated, but in the group receiving the one-day regimen, four recrudescences were observed in patients with falciparum malaria. Only five mild adverse reactions were seen, which disappeared spontaneously after the end of the treatment. We conclude that halofantrine is highly effective in curing malaria in nonimmune subjects. The treatment scheme for such persons should include an additional treatment on day 7 for nonimmune individuals. This drug was well tolerated in our patients, indicating that halofantrine will be useful in the treatment of multidrug-resistant malaria in nonimmune persons.     

Liver-derived cytotoxic T cells in hepatitis A virus infection

An autologous in vitro model was developed to analyze the immunologic cause of liver tissue injury during hepatitis A virus (HAV) infection. Human T lymphocytes infiltrating the livers of two patients with acute HAV infection were isolated from liver biopsy cores, cloned, and expanded in vitro. Procedures using a cell culture system with HAV-infected autologous skin fibroblasts demonstrated that 42% and 53% of the liver-infiltrating CD8+ clones were HAV-specific and that they kill HAV-infected skin fibroblasts in a human leukocyte antigen-restricted manner. Data show virus-specific killing by liver-infiltrating T lymphocytes in man and support the hypothesis that liver cell injury in acute HAV infection is mediated by HAV-specific CD8+ T lymphocytes and is not caused by a cytopathic effect of the virus itself.     

Comparative analysis of Bayer wide-range C-reactive protein (wr-CRP) and the Dade-Behring high sensitivity C-reactive protein (hs-CRP) in patients with inflammatory bowel disease

OBJECTIVE: The recently introduced Bayer wide‐range C‐reactive protein (wr‐CRP) assay might be relevant for the real‐time low‐cost and online determination of inflammatory bowel disease (IBD) activity. Our aim was to examine whether wr‐CRP can substitute for the Dade Behring high sensitivity C‐reactive protein (hs‐CRP) assay in IBD patients. METHODS: A total of 71 patients with IBD, of whom 48 had Crohn's disease CD and 23 had ulcerative colitis (UC) with various intensities of disease activity participated in the study. The CRP of patients who were under treatment at the Department of Gastroenterology and Liver Diseases were measured using both wr‐CRP and the hs‐CRP. RESULTS: A significant (r = 0.995; P < 0.001) correlation was noted between the hs‐CRP and wr‐CRP measurements for the whole sample as well as for the two diseases, CD (r = 0.994; P < 0.001) and UC (r = 0.997; P < 0.001), which were analyzed separately. CONCLUSION: The Bayer wr‐CRP assay might be a useful low‐cost and real‐time inflammation‐sensitive biomarker in patients with IBD.     

L-Cysteine Increases Glucose Uptake in Mouse Soleus Muscle and SH-SY5Y Cells

Previous investigation demonstrated the potential of L-cysteine (L-Cys) at high concentrations to cause hypoglycemia in mice totally deprived of insulin. For further elucidation of the glucose-lowering mechanism, glucose uptake and quantity of glucose transporters (GLUTs 3 and 4) in mouse soleus muscle and C2C12 muscle cells, as well as in human SH-SY5Y neuroblastoma cells, were investigated. A marked enhancement of glucose uptake was demonstrated, peaking at 5.0 mM L-Cys in soleus muscle (P < 0.05) and SH-SY5Y cells (P < 0.001), respectively. In contrast, glucose uptake was not affected in the C2C12 muscle cells. Kinetic analysis of the SH-SY5Y glucose uptake showed a 2.5-fold increase in maximum transport velocity compared with controls (P < 0.001). In addition, both GLUT3 and GLUT4 levels were increased following exposure to L-Cys. Our findings point to a possible hypoglycemic effect of L-Cys.     

Autoimmune smoke and fire—coexisting rheumatoid arthritis and chronic obstructive pulmonary disease: a cross-sectional analysis

To assess the association between RA and chronic obstructive pulmonary disease (COPD) in a population-based case-control study. A cross-sectional analysis performed utilizing the database of Clalit Health Services, the largest healthcare provider organization in Israel. Patients over the age of 20 years who were diagnosed with RA (‘cases’) and who were treated with any anti-rheumatic drug were compared with a sample of age- and gender-matched enrollees (‘controls’) without regard for the prevalence of COPD. Data on health-related lifestyles and other comorbidities were collected. χ², t tests, and logistic regression models were used to compare the study groups. The study included 9,039 RA cases and 15,070 controls. The proportion of COPD was significantly higher in patients with RA as compared to the control group (8.6 vs. 4.4 %, p < 0.0001, odds ratio (OR) 2.06, 95 % confidence interval (CI) 1.85–2.29). A multivariate logistic regression model demonstrated that RA was significantly associated with COPD, after controlling for confounders, including age, sex, socioeconomic status, smoking, and obesity (adjusted OR 1.98, 95 % CI 1.77–2.21, p < 0.0001). In this large data-based study, RA was found to be associated with COPD.     

Saturation recovery-prepared magnetic resonance angiography for assessment of left atrial and esophageal anatomy

Objectives:Magnetic resonance angiography (MRA) has been established as an important imaging method in cardiac ablation procedures. In pulmonary vein (PV) isolation procedures, MRA has the potential to minimize the risk of severe complications, such as atrio-esophageal fistula, by providing detailed information on esophageal position relatively to cardiac structures. However, traditional non-gated, first-pass (FP) MRA approaches have several limitations, such as long breath-holds, non-uniform signal intensity throughout the left atrium (LA), and poor esophageal visualization. The aim of this observational study was to validate a respiratory-navigated, ECG-gated (EC), saturation recovery-prepared MRA technique for simultaneous imaging of LA, LA appendage, PVs, esophagus, and adjacent anatomical structures.Methods:Before PVI, 106 consecutive patients with a history of AF underwent either conventional FP-MRA (n = 53 patients) or our new EC-MRA (n = 53 patients). Five quality scores (QS) of LA and esophagus visibility were assessed by two experienced readers. The non-parametric Mann–Whitney U-test was used to compare QS between FP-MRA and EC-MRA groups, and linear regression was applied to assess clinical contributors to image quality.Results:EC-MRA demonstrated significantly better image quality than FP-MRA in every quality category. Esophageal visibility using the new MRA technique was markedly better than with the conventional FP-MRA technique (median 3.5 [IQR 1] vs median 1.0, p < 0.001). In contrast to FP-MRA, overall image quality of EC-MRA was not influenced by heart rate.Conclusion:Our ECG-gated, respiratory-navigated, saturation recovery-prepared MRA technique provides significantly better image quality and esophageal visibility than the established non-gated, breath-holding FP-MRA. Image quality of EC-MRA technique has the additional advantage of being unaffected by heart rate.Advances in knowledge:Detailed information of cardiac anatomy has the potential to minimize the risk of severe complications and improve success rates in invasive electrophysiological studies. Our novel ECG-gated, respiratory-navigated, saturation recovery-prepared MRA technique provides significantly better image quality of LA and esophageal structures than the traditional first-pass algorithm. This new MRA technique is robust to arrhythmia (tachycardic, irregular heart rates) frequently observed in AF patients.     

Lymphatic Dissemination in Cutaneous Leishmaniasis Following Local Treatment

Cutaneous leishmaniasis (CL) is diverse in its clinical presentation but usually demonstrates an erythematous, infiltrated, ulcerated, and crusted papule or nodule in exposed areas of the body. Rare clinical features have been reported including lymphatic dissemination, usually with subcutaneous nodules along lymphatic channels. Herein, we present six patients suffering from Old World CL with lymphatic dissemination characterized by sporotrichoid subcutaneous nodules along the lymphatic channels draining the primary lesion. Patients'' history, clinical and laboratory findings were collected and summarized. Lymphatic dissemination of CL in our patients manifested as subcutaneous nodules without epidermal involvement within the axis of lymphatic drainage toward the regional lymph node, at times accompanied by regional lymphadenopathy. In all patients, the lymphatic dissemination was not present at initial diagnosis of CL, appearing only after local (topical or intralesional) treatment was initiated. In three patients, the subcutaneous nodules resolved without systemic treatment. Lymphatic dissemination of Old World CL is not uncommon and may possibly be triggered by local treatment. It should be recognized by dermatologists, especially those working in endemic areas. Systemic treatment may be not necessary since spontaneous resolution may occur.Old World cutaneous leishmaniasis (CL) is diverse in its clinical presentation and outcome. The disease spectrum is governed by an interplay between the parasite and the immuno-inflammatory response of the host. The typical clinical presentation of CL is an erythematous, infiltrated, ulcerated, and crusted papule or nodule on any region of the body, with frequent involvement of exposed areas, especially the face and limbs. Lesions heal slowly over a period of months.¹ Although CL often resolves spontaneously, it can result in severe disfiguration. Treatment is usually initiated to hasten healing and prevent scarring.²Old World CL is endemic in Israel and was attributed in the past almost exclusively to Leishmania (Leishmania) major, confined to rural areas of the Negev Desert in southern Israel. Over the last decade, CL due to Leishmania tropica has been increasingly reported in the Judean Desert in central Israel, as well as in northern Israel. Leishmania tropica is often more resistant to treatment and heals more slowly than L. major infections.³Lymphatic dissemination of CL is uncommon but has been reported, usually with dermal or subcutaneous nodules along lymphatic vessels draining the region of the primary lesion.^4–7 Herein, we present six cases of CL with subcutaneous sporotrichoid dissemination after local treatment of the primary lesion, probably caused by lymphatic spread of the parasites. The sporotrichoid dissemination was characterized by deep subcutaneous nodules without any sign of epidermal involvement.The demographic, clinical, and laboratory data of the patients are summarized in 8 performed on tissue obtained from primary lesions (patients 4 and 5) or from subcutaneous nodules (patient 6) confirmed L. tropica infection. Regional lymphadenopathy was noted in two patients (patients 2 and 3). In patients 3 and 6, a biopsy from the subcutaneous nodules established the presence of a deep granulomatous process with Leishmania bodies. After the occurrence of subcutaneous nodules, three patients were treated with intravenous sodium stibogluconate (patient 1, 3, and 4), or with sodium stibogluconate injected directly into the primary cutaneous lesion alone (patient 6) or into both the cutaneous lesion and the subcutaneous nodule (patient 5). The patients experienced total resolution of the primary lesions, the subcutaneous nodules, as well as regional lymphadenopathy. On the parents'' request, intralesional injections of pentostam were terminated after a single treatment in patient 2. The primary lesion eventually healed with a scar and the subcutaneous nodules spontaneously regressed within a few weeks.

Table 1

Demographic, clinical, and laboratory findings