Analyses of cytochrome b mutations in Plasmodium falciparum isolates in Thai-Myanmar border

BACKGROUND: The combination of atovaquone and proguanil (Malarone) has been established as a drug of choice to prevent and treat multi-drug resistant Plasmodium (P.) falciparum malaria in travelers. However, several cases of resistance against Malarone have been reported in some parts of Africa, and many of the cases are believed to be associated with mutations at the codon 268 of cytochrome b gene in mitochondria of P. falciparum. The aim of the study was to estimate the effectiveness of Malarone in treatment and prophylaxis for the travelers to Thai-Myanmar border where multi-drug resistant malaria is highly endemic. METHODS: Seventy P. falciparum samples obtained from patients from Thai-Myanmar border were sequenced to detect mutations around the codon 268. The same samples were also sequenced to detect P. falciparum chloroquine resistance transporter mutation (PfCRT K76T). RESULTS: All the 70 samples showed no mutations at the codon 268 of cytochrome b gene. Whereas, 50 samples, whose pfcrt genes were sequenced successfully, had an identical genotype for K76T mutation. CONCLUSION: In Asian countries, even in the multi-drug resistant areas in the great Mekong region, no case of Malarone resistance has been reported clinically or genetically thus far. In this study, all the P. falciparum parasites tested successfully were shown to be chloroquine resistant but atovaquone susceptible genetically. The more the usefulness of Malarone increases for both treatment and prophylaxis, the wider the drug-resistance against Malarone may spread in the region. Although the total number of samples examined is not large, it is concluded from these findings that Malarone should be recommended for prophylaxis of malaria for travelers to the Mekong region.     

Ki-ras mutations in codon 12 and p53 mutations (biomarkers) and cytology in bile in patients with hepatobiliary-pancreatic carcinoma

BACKGROUND/AIMS: The differentiation between benign and malignant jaundice is sometimes difficult even with modern diagnostic modalities. With recent advances in molecular biology, Ki-ras point mutation in codon 12 and p53 mutation have been reported as novel biomarkers of hepatobiliary and pancreatic carcinoma. The purpose of this study was to compare exfoliative bile cytology and biomarkers of the bile in patients with hepatobiliary and pancreatic diseases. METHODOLOGY: Cytologic examination and novel biomarkers, point mutations of codon 12 of Ki-ras and p53 mutations, were examined in the biliary tract bile aspirated through percutaneous transhepatic biliary drainage (PTBD) tube in 30 Japanese patients with benign and malignant hepatobiliary and pancreatic diseases. RESULTS: Sensitivity of the exfoliative bile cytology for malignant conditions was 31% and specificity 100%, while sensitivity of molecular markers of the bile was 25% and specificity 93%. When the cytologic examination and genetic study were in conjunction, sensitivity increased to 50% and specificity remained 93%. CONCLUSIONS: These findings suggest that genetic examinations of the bile, when used in conjunction with cytology, may improve the diagnostic yield for suspected malignant tumors of the hepatobiliary and pancreatic system.     

Revision total hip replacement using a cementless interlocking distal femoral stem with allograft-cemented composite and the application of intramedullary and onlay cortical strut allografts: two case reports

It is often difficult to perform repeated revision total hip replacement (re-THR) after prosthesis loosening stemming from infection, mechanical loosening, and osteolysis. Reasons for this include the size of the bone defect and poor quality of the remaining bone. We have previously performed revision surgery using a cementless interlocking distal femoral stem with segmental cortical allograft-cemented composite for reconstruction in the presence of circumferential bone loss of the proximal femur according to Gustilo classification type IV [1]. However, in the case where the distal femur had a stovepipe canal due to osteoporosis, osteolysis, and infection, it was difficult to achieve stable fixation to the distal femoral cortical bone using a cementless interlocking distal femoral stem. Therefore, a cortical strut allograft is inserted into the femoral bone canal on the medial side, followed by the insertion of an interlocking stem. A further cortical strut allograft is inserted on the lateral side of the distal femur. In addition, the distal onlay allograft should pass over the allograft–host bone junction. The two allografts are finally secured with interlocking screws. The bone allografting to augment femoral bone deficiency was performed using mainly cadaveric bone allografts obtained from our bone bank [2, 3]. In this report, we describe two cases of re-THR involving the use of intramedullary and onlay cortical strut allografts with a cementless interlocking distal femoral long stem to achieve favorable fixation stability. The two patients were asked if the data from the case could be submitted for publication, and both gave their consent     

Phylogenetic relationship of Plasmodium falciparum populations in the Philippines

Malaria is one of the major infectious diseases in the Philippines. It is being targeted for control through sustained early diagnosis, treatment and mosquito control. It is in this light that understanding the genetic background of the parasite population is important not only for basic biology of the organism but also for epidemiology and control of the disease. In the present study, molecular phylogenetic relationships of the 3 Plasmodium falciparum populations in the Philippines with the other populations in the world were inferred based on polymorphisms of 9 highly polymorphic microsatellite DNA loci in the parasite genome. A total of 92 P. falciparum isolates collected from 3 provinces (Kalinga, Palawan and Davao del Norte) in the Philippines, and 8 from other populations (3 African, 2 South American, 2 Papua New Guinean, and 1 Thai) that were previously reported, were used for the analysis. The phylogenetic tree showed that the 3 Philippine populations were genetically divergent from each other as compared to the other populations. The branching pattern of the tree suggests that the 3 Philippine populations were relatively close to the Thai population, rather than the Papua New Guinean populations, indicating that the ancestor of the 3 Philippines populations were introduced from Indochina peninsula, and not from countries located south of the Philippines such as Papua New Guinea or Indonesia.