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.     

Laparoscopic renal-adrenal surgery in patients on oral anticoagulant therapy

PURPOSE: Patients requiring chronic anticoagulation are theoretically at increased risk for hemorrhage or thromboembolism perioperatively. Experience with laparoscopic renal/adrenal surgery in patients on chronic warfarin is limited. We assessed hemorrhagic/thromboembolic complications in this group of patients. MATERIALS AND METHODS: The records of 787 patients undergoing laparoscopic renal/adrenal surgery were retrospectively reviewed. A total of 25 patients on chronic oral anticoagulation with warfarin were identified. The indications for warfarin therapy as well as perioperative management were reviewed. Clinical parameters, including operative time, estimated blood loss, hemorrhagic/thromboembolic complications and transfusions, were documented and compared with those in patients not receiving chronic anticoagulation. RESULTS: Atrial fibrillation (56% of cases) and a prosthetic mitral valve (28%) were the most frequent indications for chronic anticoagulation. Bridging anticoagulation with unfractionated heparin was the most frequent management method (68% of cases). Patients with anticoagulation were older (p <0.001) and hospitalized longer (<0.001) than those without anticoagulation. Operative time, estimated blood loss and the conversion rate were not significantly different between the groups. However patients on chronic warfarin significantly more often required transfusion (24% vs 5.2%, p <0.005) and had more postoperative bleeding episodes (8% vs 0.9%, p <0.05) than patients not on chronic anticoagulation. No thromboembolic events occurred in the anticoagulated group, while 3 occurred in the nonanticoagulated group (p = 1). CONCLUSIONS: Laparoscopic renal/adrenal surgery in patients requiring chronic anticoagulation therapy can be performed safely. The risk of intraoperative bleeding is not increased, although the incidence of postoperative bleeding as well as transfusions is higher.     

Factors influencing vertebral bone density after renal transplantation

To improve our understanding of the mechanisms underlying osteoporosis following renal transplantation, we compared bone mineral density (BMD) in 158 transplant recipients and in 293 patients undergoing maintenance hemodialysis with age- and sex- matched normal controls. Observations in graft recipients were made up to several years following transplantation. Dual-energy X-ray absorptiometry was used to measure BMD. Correlations with clinical variables including serum concentration of parathyroid hormone (PTH) and steroid therapy were evaluated. Lumbar BMD was lower in transplant patients than in dialysis patients at all ages, and continued to decrease with increasing interval posttransplant until the second year after transplantation. Persistent hyperparathyroidism and daily prednisolone dosage were both associated with decreased BMD. Age and creatinine clearance were independent long-term predictors of BMD by multiple regression analysis. Treatment of renal graft recipients with calcium and vitamin D supplements or calcitonin may be indicated in the early months after transplantation.     

Metastatic primitive neuroectodermal tumor to the kidney

Primitive neuroectodermal tumors of the kidney are rare neoplasms that may mimic renal cell carcinoma, especially in the presence of locally advanced or metastatic disease. Although several cases have been identified as primary renal tumors, this is the first report of metastatic spread of a primitive neuroectodermal tumor to the kidney.     

A neuronal model of Alzheimer's disease: an insight into the mechanisms of oxidative stress-mediated mitochondrial injury

Alzheimer's disease (AD) is associated with beta-amyloid accumulation, oxidative stress and mitochondrial dysfunction. However, the effects of genetic mutation of AD on oxidative status and mitochondrial manganese superoxide dismutase (MnSOD) production during neuronal development are unclear. To investigate the consequences of genetic mutation of AD on oxidative damages and production of MnSOD during neuronal development, we used primary neurons from new born wild-type (WT/WT) and amyloid precursor protein (APP) (NLh/NLh) and presenilin 1 (PS1) (P264L) knock-in mice (APP/PS1) which incorporated humanized mutations in the genome. Increasing levels of oxidative damages, including protein carbonyl, 4-hydroxynonenal (4-HNE) and 3-nitrotyrosine (3-NT), were accompanied by a reduction in mitochondrial membrane potential in both developing and mature APP/PS1 neurons compared with WT/WT neurons suggesting mitochondrial dysfunction under oxidative stress. Interestingly, developing APP/PS1 neurons were significantly more resistant to beta-amyloid 1-42 treatment, whereas mature APP/PS1 neurons were more vulnerable than WT/WT neurons of the same age. Consistent with the protective function of MnSOD, developing APP/PS1 neurons have increased MnSOD protein and activity, indicating an adaptive response to oxidative stress in developing neurons. In contrast, mature APP/PS1 neurons exhibited lower MnSOD levels compared with mature WT/WT neurons indicating that mature APP/PS1 neurons lost the adaptive response. Moreover, mature APP/PS1 neurons had more co-localization of MnSOD with nitrotyrosine indicating a greater inhibition of MnSOD by nitrotyrosine. Overexpression of MnSOD or addition of MnTE-2-PyP(5+) (SOD mimetic) protected against beta-amyloid-induced neuronal death and improved mitochondrial respiratory function. Together, the results demonstrate that compensatory induction of MnSOD in response to an early increase in oxidative stress protects developing neurons against beta-amyloid toxicity. However, continuing development of neurons under oxidative damage conditions may suppress the expression of MnSOD and enhance cell death in mature neurons.