Characterization of "Yaa Chud" Medicine on the Thailand-Myanmar border: selecting for drug-resistant malaria and threatening public health

Multidrug-resistant Plasmodium falciparum malaria is a severe public health problem on the Thailand-Myanmar border. Many villagers buy packets of 4-5 mixed medicines ("yaa chud") from shops without medical assessment as their first-line malaria treatment. In 2000-2001 a local researcher purchased 50 yaa chud from 44 shops around Mae Sot, Thailand and Myawaddy, Myanmar (Burma), for his wife who was said to be pregnant with fever and drowsiness. The tablets/capsules were provisionally identified by appearance and active ingredients determined in a subset by using mass and atomic spectrometry. The most frequently detected active ingredients were acetaminophen (22%), chlorpheniramine (13.4%), chloroquine (12.6%), tetracycline/doxycycline (11.4%), and quinine (5.1%). Only seven bags contained potentially curative medicine for malaria. A total of 82% of the bags contained medicines contraindicated in pregnancy. Inappropriate, ineffective antimalarial drugs on the Thailand-Myanmar border are likely to increase malaria morbidity, mortality and health costs and engender the emergence and spread of antimalarial drug resistance.     

Both heterozygous and homozygous alpha+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya

Although the alpha+ thalassemias almost certainly confer protection against death from malaria, this has not been formally documented. We have conducted a study involving 655 case patients with rigorously defined severe malaria and 648 controls, frequency matched on area of residence and ethnic group. The prevalence of both heterozygous and homozygous alpha+ thalassemia was reduced in both case patients with severe malaria (adjusted odds ratios [ORs], 0.73 and 0.57; 95% confidence intervals [95% CIs], 0.57-0.94 and 0.40-0.81; P = .013 and P = .002, respectively, compared with controls) and among the subgroup of children who died after admission with severe malaria (OR, 0.60 and 0.37; 95% CI, 0.37-1.00 and 0.16-0.87; P = .05 and P = .02, respectively, compared with surviving case patients). The lowest ORs were seen for the forms of malaria associated with the highest mortality-coma and severe anemia complicated by deep, acidotic breathing. Our study supports the conclusion that both heterozygotes and homozygotes enjoy a selective advantage against death from Plasmodium falciparum malaria.     

The effects of dobutamine on cardiac sympathetic activity in patients with congestive heart failure

OBJECTIVES: The goal of this work was to study the effects of short-term infusion of dobutamine on efferent cardiac sympathetic activity. BACKGROUND: Increased efferent cardiac sympathetic activity is associated with poor outcomes in the setting of congestive heart failure (CHF). Dobutamine is commonly used in the therapy of decompensated CHF. Dobutamine, through its effects on excitatory beta-receptors, may increase cardiac sympathetic activity. METHODS: Seven patients with normal left ventricular (LV) function and 13 patients with CHF were studied. A radiotracer technique was used to measure cardiac norepinephrine spillover (CANESP) before and during an intravenous infusion of dobutamine titrated to increase the rate of rise in LV peak positive pressure (+dP/dt) by 40%. RESULTS: Systemic arterial pulse pressure increased significantly in response to dobutamine in the normal LV function group (74 +/- 3 mm Hg to 85 +/- 3 mm Hg, p = 0.005) but remained unchanged in the CHF group. Dobutamine caused a significant decrease in LV end-diastolic pressure in the CHF group (14 +/- 2 mm Hg to 11 +/- 2 mm Hg, p = 0.02), an effect not observed in the normal LV group. In the normal LV function group, CANESP did not change in response to dobutamine (75 +/- 22 pmol/min vs. 72 +/- 22 pmol/min, p = NS). In contrast, dobutamine infusion was associated with a significant reduction in CANESP in patients with CHF (199 +/- 43 pmol/min to 128 +/- 30 pmol/min, p < 0.0009). CONCLUSIONS: Dobutamine infusion caused a significant sympatholytic response in patients with CHF. This sympathetic withdrawal response is probably related to reduction of LV filling pressures and/or activation of ventricular mechanoreceptors with dobutamine infusion.     

Improving the Gastrointestinal Tolerability of Aspirin in Older People

Interventions to reduce mortality and disability in older people are vital. Aspirin is cheap and effective and known to prevent cardiovascular and cerebrovascular disease, many cancers, and Alzheimer dementia. The widespread use of aspirin in older people is limited by its gastrointestinal side effects. Understanding age-related changes in gastrointestinal physiology that could put older people at risk of the side effects of aspirin may direct strategies to improve tolerance and hence lead to greater numbers of older people being able to take this effective intervention.     

Relationship of systolic BP to obstructive sleep apnea in patients with heart failure

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is an independent risk factor for hypertension in the general population. Hypertension is, in turn, an important risk factor for the development and progression of congestive heart failure (CHF). Our objective was to determine whether OSA would be associated with elevated daytime BP in medically treated patients with CHF. DESIGN: Cross-sectional study. SETTING: Tertiary care, university-affiliated sleep disorders and heart failure clinics. PATIENTS: Three hundred one consecutive patients with CHF. MEASUREMENTS AND RESULTS: We measured daytime BP and performed overnight sleep studies to assess for the presence of OSA. Among these patients, OSA was present in 121 patients (40%) and their systolic BP was significantly higher than in patients without OSA. Patients with OSA were 2.89 times (95% confidence interval, 1.25 to 6.73) more likely to have systolic hypertension (ie, BP > or = 140 mm Hg) than those without OSA after controlling for other risk factors, including obesity. The degree of systolic BP elevation was directly related to the frequency of obstructive apneas and hypopneas. CONCLUSIONS: In medically treated patients with CHF, daytime systolic BP and the prevalence of systolic hypertension are significantly increased in patients with OSA, compared to those without OSA, independent of other potentially confounding factors. OSA may therefore have contributed to the presence of systolic hypertension in some of these patients.     

Genetic and chromosomal alterations in Kenyan Wilms Tumor

Wilms tumor (WT) is the most common childhood kidney cancer worldwide and poses a cancer health disparity to black children of sub‐Saharan African ancestry. Although overall survival from WT at 5 years exceeds 90% in developed countries, this pediatric cancer is alarmingly lethal in sub‐Saharan Africa and specifically in Kenya (36% survival at 2 years). Although multiple barriers to adequate WT therapy contribute to this dismal outcome, we hypothesized that a uniquely aggressive and treatment‐resistant biology compromises survival further. To explore the biologic composition of Kenyan WT (KWT), we completed a next generation sequencing analysis targeting 10 WT‐associated genes and evaluated whole‐genome copy number variation. The study cohort was comprised of 44 KWT patients and their specimens. Fourteen children are confirmed dead at 2 years and 11 remain lost to follow‐up despite multiple tracing attempts. TP53 was mutated most commonly in 11 KWT specimens (25%), CTNNB1 in 10 (23%), MYCN in 8 (18%), AMER1 in 5 (11%), WT1 and TOP2A in 4 (9%), and IGF2 in 3 (7%). Loss of heterozygosity (LOH) at 17p, which covers TP53, was detected in 18% of specimens examined. Copy number gain at 1q, a poor prognostic indicator of WT biology in developed countries, was detected in 32% of KWT analyzed, and 89% of these children are deceased. Similarly, LOH at 11q was detected in 32% of KWT, and 80% of these patients are deceased. From this genomic analysis, KWT biology appears uniquely aggressive and treatment‐resistant. © 2015 The Authors. Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc.     

WONCA研究论文摘要汇编——基层抑郁症风险患者的连续性服务

背景目前已开展了对重性精神病患者进提供连续性服务的研究。目的探讨基层对有抑郁症风险患者提供连续性服务的水平,并与对心力衰竭患者的服务水平进行对比。方法采用抑郁症风险患者与心力衰竭患者对比的探索性研究。采用患者问卷评估服务的持续性,包含如下内容:(1)联系的服务提供者数(个人连续性);(2)诊所内服务提供者之间的合作(团队连续性)(6个项目,分数1~5分);(3)诊所外全科医师与服务提供者之间的合作(跨界连续性)(4个项目,分数1~5分)。结果大多数抑郁症风险患者在过去1年中寻遍整个服务提供界联系了几个服务提供者,曾遇到过高水平团队连续性服务及低水平跨界连续性服务。在诊所中可接触到的不同服务提供者要明显多于心力衰竭患者服务提供者(P<0.01)。抑郁症风险患者的服务提供者之间的合作更好一些,每项平均得分4.3分,心力衰竭患者得分为4.0分(P=0.03)。然而,跨界连续性服务方面正好相反:抑郁症风险患者每项平均得分3.5分,心力衰竭患者得分为4.0分(P=0.01)。结论抑郁症风险患者与心力衰竭患者之间的探索性对比显示:体验服务连续性方面的差距不大。对此还应行进一步分析。     

Traumatic Lingual Hematoma Resulting in Bilateral Temporal Mandibular Joint Dislocations

Background

Lingual hematoma (LH) is a relatively uncommon entity seen after both medical and traumatic etiologies. Regardless of the cause, the feared complication is acute airway obstruction.