Prevalence and associated risk factors of drug-resistant tuberculosis in Thailand: results from the fifth national anti-tuberculosis drug resistance survey.

OBJECTIVE: To assess the prevalence and risk factors of drug-resistant tuberculosis (TB), the fifth national anti-TB drug resistance survey was conducted in Thailand. METHODS: A cross-sectional study was conducted by stratified cluster sampling with probability proportional to size of TB cases from public health facilities in 100 clusters throughout Thailand from August 2017 to August 2018. Susceptibility testing of TB isolates to first- and second-line anti-TB drugs was performed on Löwenstein-Jensen medium using the indirect proportion method. Multiple imputation was done for handling missing data using Stata 16. The proportion of TB cases with drug resistance was determined. The odds ratio was used to evaluate risk factors associated with drug-resistant TB. RESULTS: Among 1501 new TB and 69 previously treated TB cases, 14.0% [95% confidence interval (CI): 12.1-16.1] and 33.4% (95% CI: 23.6-44.8), respectively, had resistance to any anti-TB drug. Multidrug-resistant TB accounted for 0.8% (95% CI: 0.5-1.4) of new TB cases and 13.0% (95% CI: 6.5-24.4) of previously treated TB cases. Drug-resistant TB was associated with prior TB treatment [odds ratio (OR), 2.9; 95% CI: 1.6-5.0], age at 45-54 years (OR, 1.6; 95% CI: 1.0-2.4), male (OR, 1.5; 95% CI: 1.0-2.1) and human immunodeficiency virus (HIV) infection (OR, 1.6; 95% CI: 1.0-2.4). CONCLUSIONS: The burden of drug-resistant TB remains high in Thailand. Intensified prevention and control measures should be implemented to reduce the risks of drug-resistant TB in high-risk groups previously treated, especially individuals of late middle age, males and those with coinfection of TB and HIV.

Complementary Indicators for Diagnosis of Hepatic Vein Stenosis After Pediatric Living-donor Liver Transplantation.

INTRODUCTION: Although hepatic vein stenosis after liver transplantation is a rare complication, the complication rate of 1% to 6% is higher in pediatric living-donor liver transplantation than that in other liver transplantation cases. Diagnosis is very important because this complication can cause hepatic congestion that develops to liver cirrhosis, graft loss, and patient loss. However, this is unlikely in cases where there are no ascites or hypoalbuminemia. OBJECTIVES: Eleven of 167 patients who had undergone pediatric living-donor liver transplantation were identified in the outpatient clinic at Jichi Medical University as having suffered from hepatic vein stenosis, and were enrolled in the study. METHODS: We conducted a retrospective study in which we reviewed historical patient records to investigate the parameters for diagnosis and examine treatment methods and outcomes. RESULTS: The 11 patients were treated with 16 episodes of balloon dilatation. Three among these received retransplantation and another 2 cases required the placement of a metallic stent at the stenosis. Histological examination revealed severe fibrosis in four of nine patients who had a liver biopsy, with mild fibrosis revealed in the other five grafts. Furthermore, hepatomegaly and splenomegaly diagnosed by computed tomography, elevated levels of hyarulonic acid, and/or a decrease in calcineurin inhibitor clearance were found to be pathognomonic at diagnosis, and tended to improve after treatment. CONCLUSIONS: Diagnosis of hepatic vein stenosis after liver transplantation can be difficult, so careful observation is crucial to avoid the risk of acute liver dysfunction. Comprehensive assessment using volumetry of the liver and spleen and monitoring of hyarulonic acid levels and/or calcineurin inhibitor clearance, in addition to some form of imaging examination, is important for diagnosis and evaluation of the effectiveness of therapy.

High prevalence of vitamin D deficiency in patients with xeroderma pigmetosum-A under strict sun protection.

BACKGROUND/OBJECTIVES: Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by defective repair of ultraviolet (UV) irradiation-induced DNA damage and high risk of skin cancer. Thus, these patients require strict photoprotection. Considering the importance of UV-mediated cutaneous vitamin D production, such rigorous photoprotection would cause vitamin D deficiency. Then, we have studied the vitamin D status in patients with XP-A, a group requiring the most strict photoprotection. SUBJECTS/METHODS: Twenty-one patients with XP-A (aged 6-25) were evaluated for their vitamin D intake, serum levels of 25-hydroxy-vitamin D (25OHD) and parathyroid hormone (PTH). Vitamin D intake was assessed by a 2-day food weighing method. RESULTS: Median dietary intake of vitamin D was 4.1 µg/day, and the median concentrations of serum 25OHD and PTH were 7.7 and 49.9 pg/ml, respectively. In 76% of the patients, serum 25OHD level was lower than 10 ng/ml, indicating vitamin D deficiency. Vitamin D intake and serum 25OHD level were significantly lower in patients under enteral nutrition (EN) than those with oral intake (OI). Multivariate analyses revealed that EN was a significant predictor of decreased serum 25OHD level (ß coefficient=-0.59, P=0.03). CONCLUSIONS: Vitamin D deficiency is highly prevalent in XP-A patients, and supplementation should be considered to avoid unfavorable skeletal consequences in these patients. In addition, determination of dietary vitamin D requirement has been a difficult work issue in the decision of dietary reference intakes (DRIs) because of its cutaneous production. Data from XP patients would yield useful information for the determination of DRIs for vitamin D.

Iron overload after pediatric liver transplantation: a case report.

Iron is an essential nutrient for living cells; however, an excessive accumulation of iron leads to organ damage and directly affects systemic immunity. Iron overload is clinically classified as hereditary or secondary. Most of secondary iron overload is caused by frequent blood transfusions because there is no active mechanism to excrete iron from the body. As recommended in various guidelines, chelation therapy is effective for reducing iron burden and improving organ function. There have been few reports on iron overload through blood transfusion during the perioperative period of liver transplantation. This report presents a case of iron overload due to repeated transfusions after pediatric liver transplantation managed by chelation therapy. The patient, an 11-month-old female with biliary atresia, underwent living donor liver transplantation. She revealed refractory anemia and required frequent blood transfusion. Both serum ferritin and transferrin saturation tended to increase after repeated transfusions, leading to secondary iron overload. Iron chelation therapy was started to prevent progression to organ failure and infection due to iron overload, and yielded a favorable outcome. It is crucial to consider the possibility of secondary iron overload and to achieve early detection and treatment to avoid progression to irreversible organ damage.

Evaluation of collaborative tuberculosis and human immunodeficiency virus activities in Phnom Penh, Cambodia.

SETTING: Phnom Penh, Cambodia. OBJECTIVES: 1) To monitor the number of tuberculosis (TB) patients undergoing human immunodeficiency (HIV) testing during TB treatment and trends of referral of TB-HIV patients to HIV services following the appointment of TB-HIV coordinators in TB wards, and 2) to investigate factors that influence undesirable TB treatment outcomes. DESIGN: Retrospective descriptive study based on a review of patient records and interviews with programme staff. RESULTS: Eighty-six per cent of newly registered TB patients underwent HIV testing. Most of the TB-HIV patients were referred to HIV services. Using logistic regression analysis, the risk of an undesirable treatment outcome in extra-pulmonary TB was significantly lower than in smear-positive pulmonary TB. Interviews revealed that patients in poor clinical condition at the start of TB treatment or who faced social problems, such as homelessness or foreign nationality, were at considerable risk for undesirable TB treatment outcomes. CONCLUSION: The appointment of TB-HIV coordinators to TB wards resulted in better HIV testing uptake and referral to HIV care and treatment services. To save TB-HIV patients' lives, it is important to continue this kind of study over a longer term to monitor these activities and to identify high-risk patients.

High prevalence of pollinosis symptoms among the farmers cultivating Japanese pears.

In a district of Japanese pear cultivators, a questionnaire survey and an IgE antibody survey were conducted on the pollinosis. A high prevalence of 36.3 percent of the farmers complained of pollinosis symptoms. By the IgE antibody survey, the symptoms were found to be related to the airborne pollens in the orchard.

Allergenic pollens and spores in the working environment of Japanese pear farmers.

Occupational allergies such as pollinosis are reported in several agricultural works in Japan. Many pollens and spores were observed in Japanese pear orchard during the artificial pollination season. By the study on daily symptoms in an allergic farmer, we confirmed that the pollinosis symptoms were most common and most severe during the artificial pollination. These results suggest that the exposure to allergenic pollens and spores induces allergic symptoms. Thus, caution should be paid for the avoidance of the exposure to these allergenic pollens and spores to prevent the allergy.

Nationwide survey on the prevalence of anti-tuberculosis drug resistance in the Republic of Yemen, 2004.

OBJECTIVES: To determine the prevalence of resistance to the four major anti-tuberculosis drugs, isoniazid, rifampicin, streptomycin and ethambutol, in Yemen. METHODS: Cluster sampling with probability proportionate to size was applied. Susceptibility to four major anti-tuberculosis drugs was examined. The proportion method using Löwenstein-Jensen medium or Ogawa medium was carried out. RESULTS: A total of 790 primary culture isolates from tuberculosis (TB) cases enrolled at the National Tuberculosis Institute, Yemen, were examined. In the confirmation culture at the supranational reference laboratory, 227 of them failed to grow on the secondary culture or were proved to be mycobacteria other than Mycobacterium tuberculosis and were excluded from further analysis. Among 563 cultures, 510 were obtained from new cases and 53 from previously treated cases. The prevalence of resistance to any four drugs was 9.8% (95%CI 7.0-12.5) among new cases and 17.4% (95%CI 12.0-33.5) among previously treated cases. The prevalence of multidrug-resistant TB was 3.0% (95%CI 1.5-4.5) among new cases and 9.4% (95%CI 0.2-18.7) among previously treated cases. CONCLUSION: The first nationwide prevalence survey on resistance to the four major anti-tuberculosis drugs in Yemen showed a relatively low prevalence of drug-resistant cases, but a high prevalence of multidrug resistance among new cases.

The national tuberculosis drug resistance survey in Cambodia, 2000-2001.

SETTING: Cambodia has a high incidence of tuberculosis (TB). Hospital-based DOTS was predominant throughout the country from 1994 to 2002. OBJECTIVES: To determine the prevalence of resistance to four major anti-tuberculosis drugs, isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and streptomycin (SM), among new cases as a baseline before a new National Tuberculosis Programme strategy with decentralised ambulatory DOTS was widely implemented. DESIGN: A cluster sampling of TB diagnostic centres with probability proportional to the number of new cases in a diagnostic centre in 1999 was used. Intake of cases took place from October 2000 to April 2001. RESULTS: From 734 isolates collected, drug susceptibility test results were obtained for 638 new cases. The prevalence of resistance to any of four drugs was 10.1% (95%CI 7.7-13). Resistance to INH was 6.1% (95%CI 4.3-8.4) and resistance to RMP 0.6% (95%CI 0.2-1.6). No multidrug-resistant (MDR) case was found among the new cases (95%CI 0.0-0.6). Three of 96 previously treated cases had MDR (3.1%, 95%CI 1.0-9.0). CONCLUSION: The first survey indicates that the current prevalence of MDR is low. It is necessary to track resistance trends when restructuring a DOTS-based programme.

Improvement of scopolamine-induced memory impairment by Z-ajoene in the water maze in mice.

Z-ajoene, a major compound containing sulfur in oil-macerated garlic products, exhibited inhibitory effects against scopolamine-induced memory impairment in mice using the Morris water maze test. The effects of Z-ajoene were observed dose-dependently (0.25-25 mg/kg). At the highest dosage, the memory performance of mice was improved compared to normal mice. The acetylcholinesterase (AChE) activity in the brain was reduced by administration of Z-ajoene dose-dependently. However, alliin and diallyl disulfide, organosulfur compounds from garlic, did not improve memory performance nor AChE inhibitory effect. These results suggest that Z-ajoene may act on the cholinergic system and on memory impairment caused by excess activity of AChE.

Low M(r) protein tyrosine phosphatase inhibits growth and migration of vascular smooth muscle cells induced by platelet-derived growth factor.

Vascular smooth muscle cell (VSMC) migration and growth are positively regulated by protein tyrosine phosphorylation. Therefore, a dephosphorylation process controlled by protein tyrosine phosphatases (PTPs) must also be critical. The present study identified six cytoplasmic PTPs expressed in VSMCs: low M(r) protein tyrosine phosphatase (LMW-PTP), SHP-2, PTP36, PTP2, PTP1B, and FAP1. We further examined the functions of LMW-PTP in VSMCs using the adenovirus-mediated gene transfer of recombinant LMW-PTP. PDGF-induced activation of p38, but not of ERK MAP kinase, was blocked by LMW-PTP. LMW-PTP as well as the p38 inhibitor SB203580 inhibited DNA synthesis and cell migration upon PDGF stimulation. LMW-PTP dephosphorylated activated PDGF receptors in NIH3T3 cells, but not in VSMCs. Thus, LMW-PTP negatively regulates PDGF functions by inhibiting the p38 pathway in VSMCs although its substrate is unclear. These findings strongly demonstrate that PTPs are important as negative regulators for VSMC growth and migration, processes that are closely related to the progression of atherosclerosis.

Gender difference in delays to diagnosis and health care seeking behaviour in a rural area of Nepal.

SETTING: Directly observed treatment for tuberculosis using a short-course regimen (DOTS) was introduced in a rural area of Nepal. All new patients assigned to DOTS from mid-December 1997 to mid-June 1999 were eligible for the study. OBJECTIVE: To examine delays in tuberculosis (TB) diagnosis and compare health care seeking behaviour between men and women. DESIGN: A cross-sectional analysis of patient interviews. RESULTS: Women were found to have a significantly longer total delay before diagnosis of tuberculosis (median 2.3 months for men, 3.3 months for women). When they visited traditional healers first, women had a significantly longer delay than men from the first visit to health care providers to diagnosis (median 1.5 months for men, 3.0 months for women). More women (35%) visited traditional healers before diagnosis than men (18%), and were more likely to receive more complicated charms from traditional healers. Men tended to visit the government medical establishment first if they knew that free TB treatment was available, but women did not. CONCLUSION: Women were more likely to visit and to believe in traditional healers; this might lead to the longer delays experienced before TB diagnosis.

Protective effect of ajoene on acetaminophen-induced hepatic injury in mice.

Ajoene, a garlic-derived sulfur-containing compound, exhibited a hepatoprotective effect against acetaminophen-induced liver injury in mice. A pretreatment with ajoene suppressed the rise in serum glutamic-pyruvic transaminase activity and the reduction in the hepatic reduced glutathione level. These effects of ajoene were observed dose-dependently (20-100 mg/kg). The pretreatment by ajoene also suppressed the decrease in hepatic protein thiol content resulting from acetaminophen administration.

Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia.

Abetalipoproteinemia (ABL) is an inherited disease characterized by the virtual absence of apolipoprotein B (apoB)-containing lipoproteins from plasma. Only limited numbers of families have been screened for mutations in the microsomal triglyceride transfer protein (MTP) gene. To clarify the genetic basis of clinical diversity of ABL, mutations of the MTP gene have been screened in 4 unrelated patients with ABL. Three novel mutations have been identified: a frameshift mutation caused by a single adenine deletion at position 1389 of the cDNA, and a missense mutation, Asn780Tyr, each in homozygous forms; and a splice site mutation, 2218-2A-->G, in a compound heterozygous form. The frameshift and splice site mutations are predicted to encode truncated forms of MTP. When transiently expressed in Cos-1 cells, the Asn780Tyr mutant MTP bound protein disulfide isomerase (PDI) but displayed negligible MTP activity. It is of interest that the patient having the Asn780Tyr mutation, a 27-year-old male, has none of the manifestations characteristic of classic ABL even though his plasma apoB and vitamin E were virtually undetectable. These results indicated that defects of the MTP gene are the proximal cause of ABL.

Contribution of angiogenesis to the progression of colon cancer: possible inhibitory effect of angiogenesis inhibitor TNP-470 on tumor growth and hepatic metastasis.

The contribution of angiogenesis to tumor growth and hepatic metastasis of colorectal cancer was investigated by means of immunohistochemical study and in vitro and in vivo experiments. Colorectal cancer specimens from 30 patients with hepatic metastasis and 39 patients without hepatic metastasis were studied by staining with antibodies against factor VIII-related antigen. Microvessel count in patients with liver metastasis was significantly higher than in those without liver metastasis (p<0.005). The effect of TNP-470 was evaluated with in vitro and in vivo experiments using human colon cancer cell line, LM and the highly hepatic metastasis cell line, LM-H5. The effect of TNP-470 on the proliferation of the cancer cells and human umbilical vein endothelial cells (HUVECs) was examined. TNP-470 inhibited more sensitively the proliferation of HUVECs than cancer cells in vitro. IC50 was approximately 3 pg/ml in HUVECs and approximately 2 microg/ml in cancer cells. The effect of TNP-470 on the growth of xenografts and liver metastases by LM-H5 in nude mice was examined. TNP-470 (30 mg/kg) was administered by subcutaneous injection every third day for 4 weeks. TNP-470 inhibited both the growth of xenograft and the hepatic metastasis. The number of metastatic foci in the liver was 78.2+/-30.1 in the control group and 20.6+/-16.5 in the treated group. These results suggest that TNP-470 is a potent agent to inhibit tumor growth and hepatic metastasis of colon cancer.

cDNA cloning of sesquiterpene cyclase and squalene synthase, and expression of the genes in potato tuber infected with Phytophthora infestans.

Sesquiterpene cyclase and squalene synthase are key branch point enzymes in isoprenoid pathway for the synthesis of sesquiterpenoid phytoalexins and sterols/steroid glycoalkaloids, respectively. cDNA clones encoding these enzymes were isolated from potato. A phylogenetic tree showed that the sesquiterpene cyclase is vetispiradiene synthase. Infection of Phytophthora infestans with potato tubers caused transient increases in the transcript level of vetispiradiene synthase in a compatible and an incompatible interactions. On the other hand, wound-induced expression of the squalene synthase was suppressed in favor of the expression of vetispiradiene synthase regardless of inoculated races.

Brief survey of leprosy situation in Congo: sero-epidemiologic profile in correlation with some emerging viral infections.

The Democratic Republic of Congo (DRC, former Zaire) in central Africa remains the foremost country for leprosy in Africa, with a total of 4877 registered cases, of which 4573 are new cases since 1997. These numbers are well above the regional average. About 94% of these patients are under multidrug therapy (MDT) coverage in the Congo, which ranks 8th in coverage rate among the surrounding nine nations. Available data on anatomo-clinical profile and bacillarity are provided, with reservations on the use of these data drwn due to relatively small sample sizes. The seroprofile of the disease was reviewed with regard to the association of other immunity impairing infections like HBV infection and the recently highly incident retroviral epidemics (HIV-1, HTLV-1, and HTLV-2). The leading role of non-governmental organizations is cited for improving leprosy patient conditions and also for future prospects, where the necessity of coordinated strategies with the government is emphasized. Recommendations for new trends and steps relevant to improving existing and future leprosy control strategies are put into perspective.

Effects of sleep deprivation: the phosphorus metabolism in the human brain measured by 31P-magnetic resonance spectroscopy.

Sleep deprivation (SD) has an antidepressant effect in some, but not all, patients with depression, although its biological mechanisms have not yet been characterized. We previously reported altered brain phosphorus metabolism measured by phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in patients with bipolar depression. We preliminarily examined effects of SD on phosphorus metabolism in the frontal lobes of 15 normal subjects using 31P-MRS. No significant differences of membrane phospholipid metabolism, high-energy phosphate metabolism and intracellular pH were found between before and after SD in these subjects. Further studies will be necessary to elucidate the physiological mechanism of SD for depressive patients.

A newly developed assay for melatonin using cells expressing human mel-1a receptor.

We have developed a radioreceptor binding assay (RRA) method for melatonin using membranes from Chinese hamster ovary cells that can stably express human mel-1a receptors. We measured melatonin levels in plasma samples collected every 4h for 24h using the RRA and radioimmunoassay (RIA) methods, simultaneously. There was a statistically significant correlation between the melatonin levels measured by the two methods, this newly developed method providing a sensitive bioassay. As it is possible to circumvent the cross-reactivity usually occurring in the RIA method, this method may be an important tool for detecting bioactive substances relative to the mel-1a receptor.