Comparison of Three Methods for Diagnosis of Cutaneous Leishmaniasis

Background

Leishmaniasis is one of the infectious parasitic diseases of highest incidence in the world. Cutaneous Leishmaniasis (CL) has long been reported in Shiraz, Southern Iran. There is a need to find a sensitive and specific method for treatment and control of the disease.

Methods

We have compared the sensitivity of the conventional methods microscopy and cultivation of lesion scrapes against PCR amplification of parasite kinetoplast DNA from these samples. The samples (n=219) were obtained from the patients clinically suspected of CL. The smears were stained with Giemsa for microscopy and cultured in Novy-Nicolle-McNeal (NNN) blood agar for promastigote growth. For PCR, the dry smears were scraped off the slides and DNA was extracted.

Results

The positive rates from 219 specimens were 76.71%, 50.68%, and 93.61% for microscopy, cultivation, and PCR, respectively. The highest correlation was found between PCR and microscopy method (P=0.014). In PCR assay, 95.61%, 3.9%, and 0.49% of the samples were identified as Leishmania major, L. tropica, and dermatropic L. infantum, respectively.

Conclusion

The PCR method appears to be the most sensitive for the diagnosis of CL and is valuable for identifying the other species of Leishmania with confusing dermatropic signs.     

Acute cytomegalovirus infection in liver transplant recipients: An independent risk for venous thromboembolism

Acute cytomegalovirus (CMV) infection is a commonly encountered complication in the post liver transplant setting. We present a case of a 71-year-old male with acute CMV infection, initially presenting with a gastrointestinal bleed due to acute CMV gastritis and later on complicated by acute venous thromboembolism occurring as an unprovoked event in the post liver transplant period. Traditional risk factors for venous thromboembolism have been well described in the medical literature. Sporadic cases of thromboembolism due to CMV infection in the immune compromised patients have been described, especially in the post kidney transplant patients. Liver transplant recipients are equally prone to CMV infection particularly in the first year after successful transplantation. Venous thromboembolism in this special population is particularly challenging due to the fact that these patients may have persistent thrombocytopenia and anticoagulation may be a challenge for the treating physician. Since liver transplantation is severely and universally limited by the availability of donor organs, we feel that this case report will provide valuable knowledge in the day to day management of these patients, whose clinical needs are complex and require a multidisciplinary approach in their care and management. Evidence and pathophysiology linking both the conditions is presented along with a brief discussion on the management, common scenarios encountered and potential impact in this special group of patients.     

A phase II study to evaluate the efficacy and toxicity of oxaliplatin in combination with gemcitabine in carcinoma of unknown primary

Background

Preclinical and clinical data suggest synergy for gemcitabine and oxaliplatin. These agents were tested in several known cancers that also comprise the common carcinoma of unknown primary (CUP) subtypes; namely, lung and pancreaticobiliary profiles.

Methods

The study enrolled 29 patients of whom 28 patients were eligible for treatment. Gemcitabine was given at 1,000 mg/m² as a fixed dose rate infusion and oxaliplatin was infused at 100 mg/m² every 2 weeks with restaging performed after 3 cycles at 6 weeks.

Results

The study reported one complete response (CR) (4%), 6 patients with a partial response (PR) (25%), and 13 with stable disease (SD) (54%); and 4 patients had progressive disease (PD) (17%) on restaging. Median overall survival (OS) and progression-free survival were 12.8 months (95% confidence interval [CI] 8.5–18.5) and 3.1 months (95% CI 1.7–6), respectively. The 1-year OS was 54%. The most common grade 3 toxicities were nausea (22%), vomiting (15%), and fatigue (11%). There were no grade 4 toxicities. This study was closed early as we moved from an empiric therapy platform to a more individualized approach.

Conclusions

Gemcitabine and oxaliplatin is a well-tolerated regimen in CUP with similar outcomes to previously documented CUP studies. In selected good performance status patients this combination may serve as a first-line doublet chemotherapy option for CUP patients (clinicaltrials.gov ID:NCT00353145).     

Dental students' knowledge and compliance in cross infection control procedures at a UK dental hospital

OBJECTIVES: To assess the knowledge and clinical practice of dental students in infection control procedures at a UK dental hospital.
DESIGN: A questionnaire concerning various aspects of infection control was completed by all clinical dental students under examination conditions. Their actual clinical practice was later observed and certain aspects recorded.
SETTING: A UK dental hospital.
SUBJECTS: One hundred and eleven dental students from three clinical years completed the questionnaire. Clinical practice for all 3 years was observed in a total of 280 treatment events.
METHODS: The questionnaire was marked by two of the authors and observations recorded by another author. MAIN OUTCOME MEASURES: Degree of compliance with recognised policy for infection control.
RESULTS: Knowledge of infection control procedures was variable particularly concerning duties usually undertaken by the dental nurse. The suggested high compliance with masks and eye protection was not always apparent in clinical practice, although virtually all students washed their hands prior to donning gloves, which were worn by all students.
CONCLUSION: There can be marked differences between what students say they would do and what they actually do in clinical practice. The topic of infection control requires a pro-active approach throughout the course, since results for the final year were not significantly different from the other clinical yearS. Ways of improving compliance are discussed.     

Anterior Cruciate Ligament Reconstruction with Bone Patellar Tendon Bone Graft through a Mini Arthrotomy

Instability after rupture of anterior cruciate ligament (ACL) may lead to recurrent episodes of giving way, an increased risk of meniscal injury and premature degenerative changes. A total of 25 cases with ACL injuries were evaluated after reconstruction with bone patellar tendon bone graft through a mini-arthrotomy. All patients were male. Maximum number of patients were between 25-30 years of age (40%). The most common modality of injury was contact sports (44%). Most common complaint was instability of knee (100%). Average Lysholm score increased from pre-operative of 47 (27-75) to post-operative of 87 (68-95). Two patients (8%) had retropatellar pain. Moderate to severe graft site tenderness was present in 4 (21%). After an average follow up of one year three months, the results were comparable with the results of arthroscopic reconstruction.Key Words: Anterior cruciate ligament reconstruction, Mini arthrotomy     

普罗布考和抗氧化维生素不影响体外实验条件下内皮细胞的白细胞粘附

为探讨预防动脉粥样硬化的药物普罗布考,维生素C和维生素E是否抑制内皮细胞表面粘附分子表达和白细胞一内皮细胞的粘附,以及这种抑制是否通过影响核因子－kB的活性来实现的,在液体流动小室中进行细胞粘附实验。用ELISA方法测定内皮细胞粘附分子E－选择素的表达;用电泳迁移率分析测定内皮细胞核因子－kB的活性,经肿瘤坏死因子α刺激的内皮细胞核因子－B活性增加,粘附分子E－选择素的表达上调（是基础水平的3．5倍）,其表面HL60细胞的粘附增加（是基础水平的4－26倍）,而抗氧化剂PDTC使所有这些变化都受到抑制。PDTC浓度为18umol/L时对粘附分子E－选择素的表达呈最大半抑制;PDTC浓度为52umol/L时对内皮细胞表面HL60细胞的粘附呈最大半抑制,普罗布考,维生素C和维生素E对肿瘤坏死因子α诱导的粘附分子表达和HL60细胞与内皮细胞的粘附没有作用,对核因子－kB的活性没有影响,临床上常用的这三种抗氧化剂并未影响作为动脉粥样硬化始动机制之一的E－选择素介导的白细胞－内皮细胞粘附水平。     

Phase 2 trial of talactoferrin in previously treated patients with metastatic renal cell carcinoma

BACKGROUND: Talactoferrin (TLF), a recombinant form of human lactoferrin (hLF), is an immunomodulatory iron-binding glycoprotein first identified in breast milk. Its immunomodulatory functions include activation of natural killer (NK) and lymphokine-activated killer cells and enhancement of polymorphonuclear cells and macrophage cytotoxicity. Studies in animal models have shown promising anticancer activity, and clinical antitumor activity has been observed in nonsmall cell lung cancer and other tumor types. The purpose of the current study was to evaluate the activity and safety of TLF in patients with refractory metastatic renal cell carcinoma (RCC). METHODS: Forty-four adult patients with progressive advanced or metastatic RCC who had failed prior systemic therapy received oral talactoferrin at a dose of 1.5 g twice daily on a 12-week-on 2-week-off schedule. Patients were evaluated for progression-free survival at 14 weeks, overall response rate, and progression-free and overall survival. RESULTS: TLF was well tolerated. No significant hematologic, hepatic, or renal toxicities were reported. The study met its predefined target with a 14-week progression-free survival rate of 59%. The response rate was 4.5%. The mMedian progression-free survival was 6.4 months and the median overall survival was 21.1 months. CONCLUSIONS: TLF is a well-tolerated new agent that has demonstrated preliminary signs of clinical activity. Given the lack of toxicity, the lack of rapid disease progression in this cohort, and the preclinical data on immune activation, a randomized study assessing its effects on disease progression in patients with metastatic RCC is rational.     

Phase 2 trial of oxaliplatin plus capecitabine (XELOX) as second-line therapy for patients with advanced pancreatic cancer

BACKGROUND.

To the authors' knowledge, there is no established second‐line chemotherapy for patients with pancreatic cancer who have received gemcitabine‐based therapy. A phase 2 trial was conducted to explore the efficacy of capecitabine and oxaliplatin (XELOX) in patients with advanced pancreatic cancer previously who were treated with gemcitabine.

METHODS.

Patients aged ≤65 years who had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 received oxaliplatin at a dose of 130 mg/m² given on Day 1 and capecitabine at a dose of 1000 mg/m² twice daily for 14 days. For patients aged >65 years or with an ECOG PS of 2, the oxaliplatin dose was 110 mg/m² on Day 1 and the capecitabine dose was 750 mg/m² twice daily for 14 days. The treatment was repeated every 3 weeks. Tumor measurements were performed every 9 weeks and the primary study objective was 6‐month overall survival.

RESULTS.

The study enrolled 41 patients. Of the 39 evaluable patients, 1 patient had a partial response and 10 patients demonstrated stable disease. The Kaplan‐Meier estimate of the overall median survival was 23 weeks (95% confidence interval [95% CI], 17.0‐31.0 weeks). Progression‐free survival was 9.9 weeks (95% CI, 9.6‐14.5 weeks). The 6‐month and 1‐year survival rates were 44% (95% CI, 31%‐62%) and 21% (95% CI, 11%‐38%), respectively. The most common grade 3‐4 nonhematologic toxicity was fatigue (toxicity was graded using the National Cancer Institute Common Toxicity Criteria [version 2.0]).

CONCLUSIONS.

The combination of capecitabine and oxaliplatin is active in gemcitabine‐pretreated patients with advanced pancreatic cancer, especially in patients with a good PS and those who have responded to first‐line chemotherapy. Cancer 2008. © 2008 American Cancer Society.     

Shear‐induced unfolding activates von Willebrand factor A2 domain for proteolysis

Summary. Background: To avoid pathological platelet aggregation by von Willebrand factor (VWF), VWF multimers are regulated in size and reactivity for adhesion by ADAMTS13‐mediated proteolysis in a shear flow dependent manner. Objective and methods: We examined whether tensile stress in VWF under shear flow activates the VWF A2 domain for cleavage by ADAMTS13 using molecular dynamics simulations. We generated a full length mutant VWF featuring a homologous disulfide bond in A2 (N1493C and C1670S), in an attempt to lock A2 against unfolding. Results: We indeed observed stepwise unfolding of A2 and exposure of its deeply buried ADAMTS13 cleavage site. Interestingly, disulfide bonds in the adjacent and highly homologous VWF A1 and A3 domains obstruct their mechanical unfolding. We find this mutant A2 (N1493C and C1670S) to feature ADAMTS13‐resistant behavior in vitro. Conclusions: Our results yield molecular‐detail evidence for the force‐sensing function of VWF A2, by revealing how tension in VWF due to shear flow selectively exposes the A2 proteolysis site to ADAMTS13 for cleavage while keeping the folded remainder of A2 intact and functional. We find the unconventional ‘knotted’ Rossmann fold of A2 to be the key to this mechanical response, tailored for regulating VWF size and activity. Based on our model we discuss the pathomechanism of some natural mutations in the VWF A2 domain that significantly increase the cleavage by ADAMTS13 without shearing or chemical denaturation, and provide with the cleavage‐activated A2 conformation a structural basis for the design of inhibitors for VWF type 2 diseases.