Maternal death review in selected countries of South East Asia Region.

Understanding the underlying factors that led to maternal deaths through a maternal death review (MDR) throws light on the causes, characteristics and circumstances of the death. We reviewed and report on the implementation of MDR in India, Indonesia, Myanmar, Nepal and Sri Lanka, capturing the experiences of MDR initiatives, follow-up actions and lessons learnet. Overall, while the findings from MDRs have been used to design or change policies and strategies for improvement of services provided, there are still challenges in scaling up these initiatives, particularly in the larger countries.

A case report of disabling bone pain after long-term kidney transplantation.

A 77-year-old man, who received a renal transplant 13 years before for IgA glomerulonephritis, was referred after he developed bilateral mid-tibial aching pain that did not improve with simple analgesia. He had recently been changed from low-dose cyclosporine to tacrolimus, but the pain did not improve when this was reversed. He had a history of focal prostatic adenocarcinoma, cryptococcal lung infection, osteoporosis treated with alendronate for 2 years and multiple squamous cell carcinomas, including one requiring left neck dissection and radiotherapy. Upon physical examination, he had gouty tophi and marked bilateral tibial tenderness but had no other clinical findings. Laboratory investigations included an elevated intact parathyroid hormone value of 7.9 pmol/L (1.6 to 6.9), bone specific alkaline phosphatase of 22 µg/L (3.7 to 20.9), urinary deoxypyridinoline/creatinine ratio of 7.2 nmol/mmol (2.5 to 5.4) and C-reactive protein. Chest X-ray and tibial X-rays were normal, but there was marrow oedema and a prominent periosteal reaction on magnetic resonance imaging. A radionuclide bone scan showed increased symmetrical, linear uptake in both tibiae and the left femur, and uptake was also noted in both clinically asymptomatic humeri. Tibial bone biopsy disclosed small deposits of poorly differentiated metastatic cancer and a follow-up chest CT revealed a lung lesion. It was concluded that the bone pain and periostitis was caused by primary lung cancer with metastatic disease to bone, and an associated hypertrophic osteoarthropathy.

The burden of invasive pneumococcal disease in children with underlying risk factors in North America and Europe.

BACKGROUND: Characterisation of risk groups who may benefit from pneumococcal vaccination is essential for the generation of recommendations and policy. METHODS: We reviewed the literature to provide information on the incidence and risk of invasive pneumococcal disease (IPD) in at-risk children in Europe and North America. The PubMed database was searched using predefined search terms and inclusion/exclusion criteria for papers reporting European or North American data on the incidence or risk of IPD in children with underlying medical conditions. RESULTS: Eighteen references were identified, 11 from North America and 7 from Europe, with heterogeneous study methods, periods and populations. The highest incidence was seen in US children positive for human immunodeficiency virus infection, peaking at 4167 per 100,000 patient-years in 2000. Studies investigating changes in incidence over time reported decreases in the incidence of IPD between the late 1990s and early 2000s. The highest risk of IPD was observed in children with haematological cancers or immunosuppression. Overall, data on IPD in at-risk children were limited, lacking incidence data for a wide range of predisposing conditions. There was, however, a clear decrease in the incidence of IPD in at-risk children after the introduction of 7-valent pneumococcal conjugate vaccine into immunisation programmes, as previously demonstrated in the general population. CONCLUSION: Despite the heterogeneity of the studies identified, the available data show a substantial incidence of IPD in at-risk children, particularly those who are immunocompromised. Further research is needed to determine the true risk of IPD in at-risk children, particularly in the post-PCV period, and to understand the benefits of vaccination and optimal vaccination schedules.

Test performance characteristics of quantitative nucleic acid testing for polyomaviruses in kidney and kidney-pancreas transplant recipients.

Screening for polyoma BK virus (BK) using nucleic testing (NAT) is recommended for kidney and kidney-pancreas transplant recipients, but the performance characteristics of quantitative BK NAT at different thresholds of plasma BK viral loads are unclear. We aim to evaluate the diagnostic accuracy of quantitative BK NAT as an add-on test to qualitative polyoma NAT for the diagnosis of BK virus-associated nephropathy (BKVAN) in kidney and kidney transplant recipients. We calculated the test sensitivity, specificity, and predictive values at the different thresholds of plasma BK viral load for BKVAN. At the recommended threshold of >1 × 10(3) serum BK copies/mL serum for test positivity, the sensitivity for BKVAN was 92.9% (95% confidence intervals [CI]: 66.1-99.8) and specificity 79.1% (95%: CI 67.4-88.1), with corresponding positive and negative predictive values of 42.0% (95% CI: 24.8-57.7%) and 98.6% (95% CI: 98.3-99.9%), respectively. The overall area under curve for the quantitative BK NAT was 0.92 (95% CI: 0.85-0.97). Quantitative BK NAT displays properties of high sensitivity and specificity that are fit for purpose as an add-on test to qualitative polyomavirus NAT for kidney and kidney-pancreas transplant recipients at risk of BKVAN.

A monounsaturated fatty acid-rich pecan-enriched diet favorably alters the serum lipid profile of healthy men and women.

Frequent consumption of nuts is associated with decreased risk of cardiovascular disease. We investigated the effect of pecans rich in monounsaturated fat as an alternative to the Step 1 diet in modifying serum lipids and lipoproteins in men and women with normal to moderately high serum cholesterol. In a single-blind, randomized, controlled, crossover feeding study, we assigned 23 subjects (mean age: 38 y; 9 women, 14 men) to follow two diets, each for 4 wk: a Step I diet and a pecan-enriched diet (accomplished by proportionately reducing all food items in a Step I diet by one fifth for a 20% isoenergetic replacement with pecans). The percentage of energy from fat in the two diets was 28.3 and 39.6%, respectively. Both diets improved the lipid profile; however, the pecan-enriched diet decreased both serum total and LDL cholesterol by 0.32 mmol/L (6.7 and 10.4%, respectively) and triglyceride by 0.14 mmol/L (11.1%) beyond the Step I diet, while increasing HDL cholesterol by 0.06 mmol/L (2.5 mg/dL). Serum apolipoprotein B and lipoprotein(a) decreased by 11.6 and 11.1%, respectively, and apolipoprotein A1 increased by 2.2% when subjects consumed the pecan compared with the Step I diet. These differences were all significant (P < 0.05). A 20% isoenergetic replacement of a Step I diet with pecans favorably altered the serum lipid profile beyond the Step I diet, without increasing body weight. Nuts such as pecans that are rich in monounsaturated fat may therefore be recommended as part of prescribed cholesterol-lowering diet of patients or habitual diet of healthy individuals.

Small intestinal mucosal pattern of Myanmar children.

BACKGROUND: Little is known about the small intestinal mucosal pattern of Myanmar children. METHODS: Duodenal, jejunal and ileal mucosal specimens obtained from children within 6 h of death were examined under a dissecting microscope with the objective of determining villus pattern in relation to site within the small intestine and then correlated with age. RESULTS: Abnormalities in the small intestinal mucosa were detected at a very young age. In children under 1 year of age, the changes are more marked proximally and become less marked distally, perhaps reflecting exposure to the causative agent(s) in early life. Presumably these agents are ingested orally and inactivated progressively. The pattern in older children reflects more severe changes in the ileum. CONCLUSIONS: It is postulated that frequent intestinal infections or small bowel bacterial contamination could lead to damage of the intestinal mucosa.

Glycoxidation and lipid peroxidation of low-density lipoprotein can synergistically enhance atherogenesis.

OBJECTIVE: The purpose of this study was to clarify the role of glycoxidation and lipid peroxidation of low-density lipoprotein (LDL) in atherogenesis. METHODS AND RESULTS: We examined the formation of N(epsilon)-(carboxymethyl) lysine (CML), a glycoxidation product, and malondialdehyde (MDA), a lipid peroxidation product, in vitro and their co-localization in human atherosclerotic lesions. Immunochemical analysis revealed that CML was formed in a time-dependent manner by human LDL incubated with copper ions and glucose, i.e. an in vitro model of glycoxidation of LDL. When LDL was exposed to copper ions alone, a small amount of CML was formed, however this was significantly less in oxidized LDL than glycoxidative LDL. In contrast, MDA formation was observed in both oxidation and glycoxidation of LDL, but not in glycation of LDL. Hexitol-lysine (HL), an Amadori product, was formed by both glycation and glycoxidation of LDL, but not by oxidation of LDL. Immunohistochemical analysis showed that CML and MDA accumulated mainly in macrophage/foam cells, while pyrraline, a non-oxidative product of glycation, and apolipoprotein B were localized in the extracellular matrix in atherosclerotic lesions. Atheromas were positive for CML and MDA, but negative for pyrraline. Macrophage/foam cells in atherosclerotic lesions exhibited co-localization of macrophage scavenger receptor-A with CML and MDA, but not with pyrraline. CONCLUSION: Our results suggest that glycoxidation and lipid peroxidation of LDL synergistically promote the development of atherosclerotic lesions through interaction with macrophage scavenger receptor-A.

Urinary 1-methylhistidine is a marker of meat consumption in Black and in White California Seventh-day Adventists.

Meat consumption predicts risk of several chronic diseases. The authors validate the accuracy of meat consumption reported by food frequency questionnaires and the mean of eight 24-hour recalls, using urinary methylhistidine excretion, in 55 Black and 71 White Adventist subjects in Los Angeles and San Diego, California, in 1994-1997. 1-Methylhistidine excretion predicts vegetarian status in Black (p = 0.02) and in White (p = 0.005) subjects. Spearman's correlation coefficients between 1-methylhistidine and estimated meat consumption were usually between 0.4 and 0.6 for both food frequency questionnaires and 24-hour recall data. This is despite the chance collection of dietary recalls and urines from omnivores on meatless days.

High prevalence of hepatitis C in patients with thalassemia and patients with liver diseases in Myanmar (Burma).

We conducted Myanmar-Japan cooperation studies on hepatitis B and hepatitis C virus markers in patients with thalassemias and those with liver diseases. Among the 102 patients with liver diseases, 92% had a history of hepatitis B virus infection (antibody to hepatitis B core antigen positive), 35% were hepatitis B surface antigen positive, 39% were positive for anti-HCV. Among 28 patients with hepatocellular carcinoma, 46% had hepatitis B surface antigen, 21.4% had antibody to hepatitis C virus, and 7% were positive for both hepatitis B surface antigen and anti hepatitis C virus. The history of HCV infection among blood recipients at the Haematology Department of the Yangon General Hospital and at the Yangon Children's Hospital was found to be 55.5% and 46.7%, respectively, which is comparable to the history of hepatitis B infection (66.7% and 46.7%, respectively). This preliminary survey also encountered 2 cases positive for anti-HCV among 34 voluntary blood donors. This survey is the first one to report that hepatitis C is at the epidemic stage in Myanmar. As there is no effective treatment for hepatitis C in this country, a screening program for blood used in transfusion should be started immediately.

Gain in functions of mutant Cu,Zn-superoxide dismutases as a causative factor in familial amyotrophic lateral sclerosis: less reactive oxidant formation but high spontaneous aggregation and precipitation.

Eight mutant Cu,Zn-superoxide dismutases (SODs) related to familial amyotrophic lateral sclerosis (FALS) were produced in a baculovirus/insect cell expression system and their molecular properties in terms of hydroxyl radical formation and aggregation were compared with the wild-type enzyme. Treatment of the enzymes with Chelex 100 resin decreased Cu contents as well as SOD activities in all mutant Cu,Zn-SODs, indicating that the affinities of the enzymes for copper ion were decreased. Contrary to previous reports, all the mutant Cu,Zn-SODs exhibited less reactive oxidant producing ability in the presence of hydrogen peroxide than the wild-type enzyme. Both SOD activities and their reactive oxidant forming correlated well with the copper ion content of the molecules. In addition, the proteins spontaneously aggregated and were precipitated by simple centrifugation at 12,000g for 20 min in keeping their enzyme activities. Since hyaline inclusions found in FALS patients with SOD1 mutations contained components which were reactive to anti-Cu,Zn-SOD antibody, a primary reaction caused by mutant SOD1 may be attributed to their propensity to form aggregates. Aggregated but still active mutant SOD1 would be expected to mediate the formation of reactive oxygen species and nitrosylation in a more condensed state.

Nutritional rickets without vitamin D deficiency in Bangladesh.

To understand nutritional rickets in Bangladesh better, 14 rachitic and 13 'unaffected' children were evaluated. Seventy per cent of children with active rickets had no evidence of either vitamin D deficiency or familial rickets. Rickets in Bangladesh is probably related to calcium deficiency. Abnormalities in 'unaffected' children suggest that subclinical calcium insufficiency is common.

Ineffectiveness of breath methane excretion as a diagnostic test for lactose malabsorption.

BACKGROUND: In clinical and field conditions, breath gas analysis has been widely used in evaluating carbohydrate digestion. A field study was performed to determine the prevalence of lactose malabsorption in Myanmar children and to evaluate the possibility of using breath methane excretion to indicate lactose malabsorption in a field situation. METHODS: The study population consisted of 118 children aged 1 to 12 years. A hydrogen breath test after a lactose meal (2 g/kg, maximum 50 g) was used as a standard test. RESULTS: Lactose malabsorption was detected in 16.7% of children aged 1 to 2.9 years, with the prevalence increasing with age from 40.5% of those aged 3 to 5.9 years to 88.5% of those aged 6 to 8.9 years and reaching 91.7% in those aged 9 to 11.9 years. Lactose malabsorption was more prevalent when children were weaned before 4 months of age (87.2 vs. 41.1%; p < 0.01). Compared with lactose-tolerant children, those with lactose malabsorption had significantly higher concentrations of breath hydrogen excretion 60 minutes after the lactose test meal. Breath methane excretion was also significantly higher in samples at 120 minutes in children with lactose malabsorption. Breath methane excretion of greater than or equal to 2 parts per million at 180 minutes as a diagnostic test for lactose malabsorption had a sensitivity of 61.5% and a specificity of 84.6%. CONCLUSION: The breath methane test for lactose malabsorption has a lower sensitivity and specificity than the breath hydrogen test and therefore does not replace the lactose breath hydrogen test.

Glycoxidation in aortic collagen from STZ-induced diabetic rats and its relevance to vascular damage.

Glycoxidation reactions lead to the formation of permanent, irreversible chemical modifications and cross-links in protein, such as the glycoxidation products carboxymethyllysine (CML) and pentosidine. It has been implicated that CML as well as Amadori products play a role in the formation of superoxidative products, such as H2O2 and advanced glycosylation endproducts in trapping LDL. Therefore, a possible relationship between glycoxidation and lipoperoxidation might exist because oxidized lipoprotein, which has been directly linked to atheroma formation, could be produced by the superoxidative products released from the pathway of CML formation. Using a CML-specific monoclonal antibody (6D12) and a specific antiserum against hexitol-lysine (HL), an Amadori product, we studied the relationship between glycoxidation and lipoperoxidation by determining the aortic CML contents with ELISA and the fluorescence levels of lipoperoxidation side products, malondialdehyde (MDA) and hydroxynonenal (HNE) from STZ-induced diabetic rats and age-matched control rats. The immunohistochemical and ultrastructural changes relevant to glycoxidation and lipoperoxidation were also studied. The CML content measured by ELISA in DM rats was significantly higher than that in the control rats at 28 weeks (n = 11, P < 0.01). The levels of MDA-linked and HNE-linked fluorescence in the DM rats increased in a similar way and were significantly higher than the levels in control rats at 28 weeks (n = 11, both P < 0.01 at 28 weeks). The CML contents correlated with the fluorescence levels of both MDA-linked (n = 19, r = 0.638, P < 0.01) and HNE-linked fluorescence (n = 19, r = 0.629, P < 0.01) only in the DM rats, but not in the control rats. Our immunohistochemical study thus demonstrated that CML was initially formed in the aortic media of diabetic rats in the 16th week of diabetes, localized primarily in the extracellular matrix surrounding the aortic smooth muscle cells after HL occurred early in the 2nd week of diabetes. Consequently, a significant increase in the extracellular matrix and decrease in the area of the SMCs were observed in the aortic media in the DM rats by a morphometrical study. The in vivo results of this study provided the first evidence that CML correlated with fluorescence levels of MDA and HNE, and thus suggested the existence of a close relationship between glycoxidation and lipoperoxidation in vivo. This information is thus considered to shed some new light on the etiology of atherogenesis in diabetes.

Clinical, physiological, and histological features in a kindred with the T3271C melas mutation.

The majority of patients with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) have an A-->G mutation at nucleotide 3243 in mitochondrial transfer (t)RNA. To date there have only been 10 reported cases of MELAS syndrome in patients with a T-->C mutation at position 3271 of mitochondrial tRNA. Although many of the clinical features are similar between patients with these different mutations, it appears that the age at onset is later for the 3271 mutation. This report provides information from a North American kindred with the 3271 mutation (n = 6 proven; n = 2 probable; n = 3 possible) that adds clinical, physiological, histological, and molecular information to the pool of information on this rare disorder. Many of these features were similar to previous reports of both 3243 and 3271 patients. We conclude that the phenotypic expression of these different mutations are similar, but the age of onset for 3271 patients is later than for 3243 patients.

Envenoming by Chinese krait (Bungarus multicinctus) and banded krait (B. fasciatus) in Myanmar.

A retrospective study of 8 cases of envenoming by Chinese krait (Bungarus multicinctus) and one banded krait (B. fasciatus) in southern Myanmar is reported. Chinese krait bite produced minimal local reactions, except in one person bitten on the lip which resulted in local swelling. Onset of neurotoxic symptoms occurred 2.5-6 h after the bite, and the interval between bite and death ranged from 12-30 h. Three deaths were due to respiratory failure. Four mildly envenomed cases recovered spontaneously without assisted ventilation. One severely envenomed patient recovered after 8 d intensive respiratory care. Cobra (Naja kaouthia) antivenom had no value in reversing neurotoxic symptoms. Anticholinesterase injection given to one patient failed to improve neurotoxic symptoms. The bite of banded krait (B. fasciatus) resulted in neurotoxic envenoming within 2 h after the bite, with minimal local reactions. The victim died of respiratory failure 14 h after the bite.

Reducing sugars trigger oxidative modification and apoptosis in pancreatic beta-cells by provoking oxidative stress through the glycation reaction.

Several reducing sugars brought about apoptosis in isolated rat pancreatic islet cells and in the pancreatic beta-cell-derived cell line HIT. This apoptosis was characterized biochemically by inter-nucleosomal DNA cleavage and morphologically by nuclear shrinkage, chromatin condensation and apoptotic body formation. N-Acetyl-L-cysteine, an antioxidant, and aminoguanidine, an inhibitor of the glycation reaction, inhibited this apoptosis. We also showed directly that proteins in beta-cells were actually glycated by using an antibody which can specifically recognize proteins glycated by fructose, but not by glucose. Furthermore, fluorescence-activated cell sorting analysis using dichlorofluorescein diacetate showed that reducing sugars increased intracellular peroxide levels prior to the induction of apoptosis. Levels of carbonyl, an index of oxidative modification, and of malondialdehyde, a lipid peroxidation product, were also increased. Taken together, these results suggest that reducing sugars trigger oxidative modification and apoptosis in pancreatic beta-cells by provoking oxidative stress mainly through the glycation reaction, which may explain the deterioration of beta-cells under conditions of diabetes.

Glycation and inactivation of sorbitol dehydrogenase in normal and diabetic rats.

Sorbitol dehydrogenase (SDH) is involved in the polyol pathway, which plays an important role in the pathogenesis of diabetic complications. We have measured the tissue distributions of SDH mRNA, both the immunoreactive enzyme levels and the enzyme activity. SDH mRNA was especially abundant in liver, kidney and testis. Both the activity and enzyme content are high in liver and kidney but not in testis. The discrepancy between mRNA and immunoreactive enzyme levels and the activity of SDH observed in testis was also seen in livers of streptozotocin-induced diabetic rats. SDH was found to exist in both glycated and non-glycated forms, with larger amounts of the glycated protein in the diabetic liver. Moreover, after incubation of purified enzyme with glucose or fructose, its activity was markedly decreased. These results indicate that glycation causes a decrease in SDH activity in liver under diabetic conditions. The same post-transcriptional event might occur to decrease the activity of SDH in testis in normal animals.

The expanding clinical phenotype of the tRNA(Leu(UUR)) A-->G mutation at np 3243 of mitochondrial DNA: diabetic embryopathy associated with mitochondrial cytopathy.

We describe a family which demonstrates and expands the extreme clinical variability now known to be associated with the A-->G transition at nucleotide position 3243 of the mitochondrial DNA. The propositus presented at birth with clinical manifestations consistent with diabetic embryopathy including anal atresia, caudal dysgenesis, and multicystic dysplastic kidneys. His co-twin was normal at birth, but at 3 months of life, presented with intractable seizures later associated with developmental delay. The twins' mother developed diabetes mellitus type I at the age of 20 years and gastrointestinal problems at 22 years. Since age 19 years, the maternal aunt has had recurrent strokes, seizures, mental deterioration and deafness, later diagnosed as MELAS syndrome due to the tRNA(Leu(UUR)) A-->G mutation. A maternal uncle had diabetes mellitus type I, deafness, and normal intellect, and died at 35 years after recurrent strokes. This pedigree expands the known clinical phenotype associated with tRNA(Leu(UUR)) A-->G mutation and raises the possibility that, in some cases, diabetic embryopathy may be due to a mitochondrial cytopathy that affects both the mother's pancreas (and results in diabetes mellitus and the metabolic dysfunction associated with it) and the embryonic/fetal and placental tissues which make the embryo more vulnerable to this insult.

Leprosy in Myanmar, epidemiological and operational changes, 1958-92.

The registered caseload and prevalence of leprosy have declined in Myanmar from a peak of 86.2 per 10,000 population (95% CI 85.43-86.97) in 1973-77 to 26.82 (95% CI 18.46-35.18) in 1988-92. The new case detection rates have also declined from 7.41 per 10,000 (95% CI 6.3- 8.52) in 1968-72 to 1.96 (95% CI 1.43-2.52) in 1988-92. The increase in the multibacillary proportion of new cases from 11.85% (95% CI 11.84-11.86) in 1968-72 to 40.54% (95% CI 37.2-43.88) in 1988-92 and the decline in proportion of new cases under 14 years of age from 26.81% (95% CI 26.8-26.82) in 1968-72 to 11.22% (95% CI 10.92-11.52), coupled with the finding of declining detection rates among school children and in mass village surveys could mean that the incidence of leprosy may be declining.

Glycated Cu,Zn-superoxide dismutase in rat lenses: evidence for the presence of fragmentation in vivo.

Cu,Zn-superoxide dismutase (Cu,Zn-SOD) exists in tissues of rats as both glycated and non-glycated forms when separated by boronate acid column chromatography. Glycated Cu.Zn-SOD is most abundant in rat lenses compared to other tissues. In normal rats lens levels of glycated Cu.Zn-SOD showed a gradual increase with age, whereas in diabetic rats substantial increases were observed. Immunoblotting analyses, using anti-hexitol lysine IgG, indicated that glycated Cu.Zn-SOD contains Amadori products. Moreover, Cu.Zn-SOD in lenses was site-specifically fragmented probably because of glycation. This the first report of a fragmented protein, such as Cu,Zn-SOD, occurring in vivo.