Extended spectrum beta lactamase producing organisms causing urinary tract infections in Sri Lanka and their antibiotic susceptibility pattern -A hospital based cross sectional study.

BACKGROUND: Extended Spectrum Beta- Lactamase producing organisms causing urinary tract infections (ESBL-UTI) are increasing in incidence and pose a major burden to health care. While ESBL producing Klebsiella species seem to account for most nosocomial outbreaks, ESBL-producing E. coli have been isolated from both hospitalized and non-hospitalized patients. Although 95-100% ESBL organisms are still considered sensitive to meropenem, rapid emergence of carbapenem resistance has been documented in many countries. The objective of this study was to evaluate urinary tract infections caused by ESBL producers and the antibiotic susceptibility patterns in Sri Lanka. METHODS: Patients with confirmed ESBL-UTI admitted to Professorial Medical Unit, Colombo North Teaching Hospital from January - June 2015 were recruited to the study. Their urine culture and antibiotic susceptibility reports were evaluated after obtaining informed written consent. RESULTS: Of 61 culture positive ESBL-UTIs, E. coli caused 53 (86.8%), followed by Klebsiella in 8 (13.1%).30 (49.1%) had a history of hospitalization within the past three months and included 6/8(75%) of Klebsiella UTI and 24/53(45.2%) of E.coli UTI. Antibiotic susceptibility of ESBL organisms were; Meropenem 58 (95%), Imipenem 45 (73.7%), Amikacin 37 (60.6%) and Nitrofurantoin 28(45.9%). In 3(4.9%), E.coli were resistant to Meropenem. These three patients had received multiple antibiotics including meropenem in the recent past for recurrent UTI. CONCLUSIONS: We observed a higher percentage of E. coli over Klebsiella as ESBL producing organisms suggesting most ESBL-UTIs to be community acquired, Carbapenems seem to remain as the first line therapy for majority of ESBL-UTIs in the local setting. However 4.9% prevalence of meropenem resistance is alarming compared to other countries. Although prior antibiotic utilization and hospitalization may contribute to emergence of ESBL producing Klebsiella and E.coli in Sri Lanka, high prevalence of community acquired ESBL-E. coli needs further investigations to identify potential causes . Being a third world country with a free health care system, observed alarming rate of carbapenem resistance is likely to add a significant burden to health budget. We feel that treatment of infections in general needs a careful approach adhering to recommended antibiotic guidelines in order to prevent emergence of multi drug resistant organisms.

Thyrotoxic crisis presenting with jaundice.

BACKGROUND: Thyrotoxic crisis is a medical emergency requiring early diagnosis and urgent management, which can be challenging due to its diverse clinical presentations. While common presentations include fever, sweating, palpitations, tremors and confusion, presence of jaundice is rare. CASE PRESENTATION: We report a 35-year-old male who presented with jaundice due to cholestasis along with other features of thyrotoxic crisis due to Graves' disease. He had a good clinical recovery with resolution of cholestasis following treatment for thyrotoxic crisis. CONCLUSION: Jaundice can be a rare manifestation of thyrotoxic crisis, and should be considered in the differential diagnosis when other clinical features of thyrotoxic crisis are present. However secondary causes of jaundice should be looked into and excluded.

Trends and determinants of childhood stunting and underweight in Sri Lanka.

INTRODUCTION: Child undernutrition is a major risk factor for child mortality and adult ill-health. Despite substantial progress in most health indicators, undernutrition remains high in Sri Lanka, with recent trends being unclear, owing to methodological differences in national surveys. METHODS: This study uses data from the 1987, 1993, 2000 and 2006-07 Demographic and Health Surveys (DHS) and the 2009 Nutrition and Food Security Survey (NFSS) to investigate trends and determinants of child undernutrition in Sri Lanka. The prevalence rates of stunting, underweight and wasting were re-estimated using the 2006 WHO growth standards to ensure consistency. Multivariate regression analysis was then undertaken to analyse the determinants of height-forage in children aged 9-23 months, and 24-59 months, and the relative impact of key factors was assessed using prediction models. RESULTS: Stunting and wasting substantially improved from 1987 to 2000, but rates stagnated from 2000 to 2006/07. Whilst economic inequalities in under nutrition were greater than in most other countries, the multivariate analysis found that maternal height, household wealth, length of breast-feeding and altitude are significant determinants of stunting, but differences in child feeding practices and other factors were not. Of these, maternal height and household wealth had the most influence. CONCLUSION: The results are consistent with the finding that food insecurity is the main driver of undernutrition, but more research is required to validate this. The strong relationship of child height with maternal height suggests that epigenetic factors, proxied by short maternal height, constrain the applicability of the WHO growth standards in Sri Lanka.

Trends, inequalities and determinants of low birth weight in Sri Lanka.

INTRODUCTION: This study analyses the DHS 1993, 2000 and 2006-07 and NFSS 2009 survey data to investigate trends, inequalities and determinants of low birth weight (LBW) in Sri Lanka. METHODS: We re-evaluated recent trends in LBW incidence, adjusting for changes in the coverage of DHS surveys to ensure comparability, and used multivariate logistic regression to investigate determinants. We quantified the degree of economic inequality using wealth and concentration indices, and assessed the contribution of determinants to inequality by decomposition. RESULTS: There was a continuing, but slowing decline in LBW incidence, reaching 17% during 2001/02-2006/07, whilst very low birth weight incidence declined from 0.9% to 0.6%. Concentration indices reveal persistent, large economic inequalities in LBW incidence. Maternal body mass index (BMI), height and education, altitude and Indian Tamil ethnicity were the major determinants of LBW, with supply of 'Thriposha' having no significant impact. Accounting for maternal BMI and height largely eliminates the impact of economic status, and reduces the impact of ethnicity. Decomposition analysis reveals the major contributors to the inequalities are maternal BMI (21%), height (12%) and education (14%), ethnicity (9%) and altitude (7%). CONCLUSIONS: The results imply that food insecurity mediates the association of LBW with poverty, and is the major amenable risk factor. The impact of maternal height and Indian Tamil ethnicity suggests that epigenetic mechanisms play a role, and that reductions in LBW incidence will take considerable time. There is a need to substantially improve the effectiveness of interventions to reduce LBW in coming generations.

Sphygmomanometers in use in general practice: an overlooked aspect of quality in patient care.

OBJECTIVES: To assess the condition, accuracy and safety of mercury and anaeroid sphygmomanometers in use in general practice and to pilot a scheme for sphygmomanometer maintenance within the district. DESIGN: Instruments were checked on site according to set protocols which related to established guidelines and standards and data were entered into a specially designed database. Mercury sphygmomanometers were removed to the laboratory for servicing. Practices received written feedback on the condition of each instrument checked, repairs undertaken and advice, where necessary, for further work required. Participant views on the scheme were sought. MATERIALS AND METHODS: A total of 472 instruments (75.4% mercury) located in 86 general practices (87.8% of practices participated) in a health district in the West Midlands. Instruments were checked against 28 (mercury) and 25 (anaeroid) quality standards and (for mercury instruments) against British Hypertension Society guidelines. RESULTS: 69.1% of mercury and 95.7% of anaeroid instruments checked, had no service records. Of the remainder, only 29 mercury (8.1%) and one anaeroid (0.9%) had a record of a check or service within the previous 12 months. None of the instruments met all of the relevant quality standards and 14 (3.9%) mercury and seven (6.1%) anaeroid instruments met less than half. A large proportion of mercury sphygmomanometers tested had defects likely to affect recommended measurement technique. Only two-thirds were accurate at all pressure levels tested. Only 38.8% of anaeroid instruments were accurate at all test pressure levels. CONCLUSIONS: The level of defects noted could have an impact on diagnosis and monitoring of hypertension.

First isolation of Legionella pneumophila in Sri Lanka.

OBJECTIVES: To determine the presence of legionellae and species composition of the genus Legionella in Sri Lankan hotel cooling towers, and to determine the previous exposure of hotel workers to Legionella pneumophila. DESIGN: Collection of water samples from 16 cooling towers of air conditioning plants from 7 representative hotels, and blood samples from hotel workers. SETTING: Department of Bacteriology, Medical Research Institute, Colombo 8. RESULTS: Water samples from 4 (57.4%) hotels selected were positive for legionellae. Five (38.4%) selected cooling towers yielded legionellae with viable counts ranging from 1 to 5 colony forming units (CFU)/ml. 93.7% of the isolates were Legionella pneumophila. Only one hotel worker had significant antibody levels denoting past infection to Legionella pneumophila. CONCLUSION: Legionella does occur in the Sri Lankan hotel environment and Legionella pneumophila appears to be the most common species.

Tissue tropism of avian reoviruses is genetically determined.

Two genome segments, M2 and S1, were preferentially selected in reassortants isolated in Vero cells. Analysis with monoclonal antibodies (MAbs) against RAM-1 strain showed that the 39-kDa protein encoded by the genome segment S1 contained epitopes involved in neutralisation of virus infectivity for both Vero and chicken kidney (CK) cells. The 39-kDa protein appeared to have two major epitopes that are attachment sites for cell receptors, one interacting only with CK cell receptors and the other with both CK and Vero cell receptors but principally Vero cell receptors. These results suggest that the strain RAM-1 may have developed an epitope for Vero cell receptors owing to mutation in the S1 genome segment, but still retained the epitope responsible for infection of CK cells.

Association between the sigma C protein of avian reovirus and virus-induced fusion of cells.

Monoclonal antibodies (MAbs) against a 39 kDa (sigma C) protein of the avian reovirus RAM-1 strain inhibited virus-induced fusion of cells and the protein was expressed on the surface of infected cells. The fusion-inhibiting activity of the three MAbs reacting with the sigma C protein suggest two putative epitopes were involved: one epitope recognised by antibody 6H1 and involved in fusion of both Vero and CK cells and a second epitope recognised by antibody 1G1 involved in fusion of Vero cells but not CK cells. The activity of the MAb 6E2 was intermediate, suggesting it may have been located in an intermediate position between the two putative epitopes and inhibited fusion by steric hindrance.

Immune response to avian reovirus in chickens and protection against experimental infection.

OBJECTIVES: To assess the efficacy of the vaccination procedure and the effect of the transfer of maternal antibodies to progeny chickens on reovirus pathogenicity. DESIGN: To vaccinate chickens and challenge progeny chickens with high doses of homologous and heterologous viruses. PROCEDURE: High doses of reovirus strains RAM-1, 1091 and 724 were used to induce tenosynovitis lesions. High doses were produced by concentration of viruses grown in cell culture. Then similar doses of viruses were used to challenge immunised chickens progeny. RESULT: Vaccination of breeding hens with the RAM-1 strain of avian reovirus, which resulted in the passive transfer of neutralising antibody to progeny chickens, completely prevented the development of tenosynovitis in 80% of progeny chickens infected with the homologous virus. Even though multiple injections of hens resulted in broadening of the normal type-specificity of the neutralising antibody response against heterologous serotypes of avian reovirus, only marginal protection against strains of two heterologous serotypes of avian reovirus was obtained. CONCLUSIONS: A model for assessing the efficacy of vaccination against avian reovirus strains on clinical sign such as tenosynovitis was developed that overcome the normal low virulence of Australian strains of avian reovirus. Breeding hens can be immunised with Australian strain of avian reovirus with passive transfer of antibody via the yolk to the progeny chickens. Although the neutralising antibody response to three injections of inactivated virus decreased the specificity of the neutralising antibody response against antigenically heterologous strains of avian reovirus, the protective immunity appeared to retain type-specificity.

Uncoupling of GABA(A) and benzodiazepine receptor binding activity in the hippocampal formation of schizophrenic brain.

A recent postmortem study has reported that there is a widespread upregulation of GABA(A) receptor binding activity throughout most subregions of the hippocampal formation of schizophrenic brain. The current study has been undertaken to determine whether the benzodiazepine (BZ) receptor, which is a component of the GABA(A) receptor complex, may also be upregulated in schizophrenics. Using a low-resolution film autoradiographic technique to localize [3H]flunitrazepam binding, the subregional and laminar distribution of specific BZ receptor binding was found to parallel that of the GABA(A) site, except in the area dentata where BZ binding was approximately 73% higher in the outer molecular layer. When BZ receptor binding was compared in the same normal control (n = 15) and schizophrenic (n = 8) cases in which the GABA(A) receptor was analyzed, there were very few differences noted between the two groups, except for small, though significant, increases in the stratum oriens of CA3 (30%), the subiculum (20-30%) and the presubiculum (15-20%) of the patient group. These latter increases overlapped with the subregions and laminae in schizophrenics showing the most marked increases of GABA(A) receptor binding. Using a high-resolution technique to evaluate specific BZ receptor binding on different neuronal subtypes, no difference was observed on either pyramidal or nonpyramidal neurons of sector CA3 where GABA(A) receptor activity had been found to be significantly increased on the latter neuronal subtype. The potential confounding effects of age, postmortem interval and exposure to either benzodiazepine or neuroleptic drugs do not account for the lack of marked differences in BZ receptor binding in the schizophrenic group. Taken together, the results of this study are consistent with the possibility that defective GABAergic integration in schizophrenia may be associated with an uncoupling in the regulation of the GABA(A) and BZ receptors.

Differences in the subregional and cellular distribution of GABAA receptor binding in the hippocampal formation of schizophrenic brain.

Recent postmortem studies have reported a marked upregulation of GABAA receptor binding activity in the anterior cingulate and prefrontal cortices of schizophrenic subjects. Because the hippocampal formation is a key corticolimbic region that has also been implicated by both postmortem and brain imaging studies in the pathophysiology of this disorder, the current report has sought to determine whether alterations of GABAA receptor binding might also be detected in this region from 15 normal controls and 8 schizophrenic subjects. Using a low resolution autoradiographic approach, the results show a significant increase of specific GABAA receptor binding activity in the area dentata (granule cell layer), CA4, CA3 (str. oriens, str. pyramidale), subiculum, and presubiculum of the schizophrenic group. The magnitude of the increase was greatest in CA3 and lowest in the CA1 sector. When high resolution analyses were performed on emulsion-coverslip preparations, a modest increase of binding (43%, P = 0.05) was observed on pyramidal, but not non-pyramidal neurons in sector CA1. Rather unexpectedly, GABAA binding in sector CA3 was not significantly different on pyramidal cells, but was almost three-fold higher (P = 0.015) on non-pyramidal neurons of the schizophrenic group. There was no relationship of age or the postmortem interval to the parameters showing significant changes in the schizophrenic group. Moreover, patients both with and without neuroleptic exposure showed upregulation of GABAA receptor binding activity. Taking together the rather modest increase of binding activity in CA1 and the more marked upregulation in CA3, as well as the differential changes on pyramidal neurons of CA1 vs. non-pyramidal neurons in CA3, the findings reported here are consistent with the possibility that a disturbance of brain development could have occurred either perinatally or perhaps even well into the postnatal period, and have given rise to discreet subregional and cellular alterations of disinhibitory GABAergic modulation in sector CA3 of schizophrenics. Overall, the data reported here provide further evidence that alterations of GABAergic activity may occur in the hippocampal formation of schizophrenic patients.

Type-specific antigenicity of avian reoviruses.

The type-specificity of the neutralizing activity in chicken antiserum to avian reoviruses was affected by the method of antiserum production. The neutralizing activity produced in response to virus infection had higher type-specificity than that produced by immunization with inactivated virus emulsified in adjuvant. By using reassortant viruses the induction of type-specific neutralizing activity was shown to be associated with the sigma C (sigmaC) virion protein. Antigenic classification of virus strains based on immunoprecipitation of the sigmaC protein by chicken antiserum was attempted and the results were similar to those obtained by reciprocal serum neutralization tests. One-way immunoprecipitation of the sigmaC protein by antisera to some heterologous viruses, similar to that reported in reciprocal neutralization tests, made it difficult to assign individual viruses to serogroups and showed that the type-specificity of the sigmaC protein was not absolute. The neutralization activity of monoclonal antibodies to the sigmaC protein of the RAM1 strain of avian reovirus suggested there were separate type- and group-specific antigenic domains on the sigmaC protein, and that the group-specific domains may be associated with the induction of antibody against heterologous viruses.

Avian reovirus proteins associated with neutralization of virus infectivity.

Monoclonal antibodies against two virion proteins of the RAM-1 strain of avian reovirus neutralized virus infectivity; antibody against a 124-kDa (lambda B) protein caused broadly specific neutralization and antibody against a 39-kDa (sigma C) protein caused neutralization of greater type-specificity. The neutralizing activity of the monoclonals also exhibited host cell specificity: antibodies against the lambda B protein inhibited virus infectivity in Vero cells and not chicken kidney cells; one monoclonal antibody against the sigma C protein neutralized virus in only chicken kidney cells, whereas two other monoclonals against the sigma C protein neutralized virus in both Vero and chicken kidney cells but had greater neutralizing activity in Vero cells.

The detection of mutagenic air pollutants from filter samples by the Salmonella/Mammalian S-9 mutagenicity test (Ames test) with S. typhimurium TA 98 (Part 1).

Particulate airborne pollutants, collected in 1977 at an urban point in Wanne-Eickel, G.F.R., were investigated for mutagenic activity in the Ames Salmonella/mammalian S-9 mutagenicity tet with S. typhimurium TA98. Two kinds of filters were used: Mikrosorbanfilters (polystyrene) and Membranfilters (cellulose nitrate). Sample preparations obtained following gel chromatography of solutions of the Mikrosorbanfilters showed only weak mutagenic activity. Soxhlet extracts of the Membranfilters gave positive dose-response relations (figs. 3-6), while splitting the initial extract into six fractions resulted in the bacterial reversion rates due to certain sub-fractions increasing over the reversion rates due to the unfractionated preparation (fig. 7). The highest activities were observed in the fractions of the polar compounds and of the polycyclic aromatic hydrocarbons. Some (30-50%) of the mutagenic activity was not enzymatically mediated. GC-MS analysis of the samples demonstrated the presence of an average content of around 11 microgram benzo(a)-pyrene/1000 m3 of air.

Spectral evidence of interaction of spice constituents with hepatic microsomal cytochrome P-450.

Spectral evidence has been obtained of the interaction of constituents of two commonly used spices, capsicum and cinnamon, with hepatic microsomal cytochrome P-450. It is proposed that influences of spice constituents on hepatic mixed-function oxidase activities may merit consideration during the investigation of some health-related problems characteristic of, or peculiar to, a given region or cultural group. An example considered relates to the evaluation of certain 'traditional medicines'.

Differential dependence on NADPH concentrations of two microsomal corticosteroid 21-hydroxylation reactions.

The dependency on NADPH concentrations of the bovine adrenal cortex microsomal 21-hydroxylation of progesterone and of 17-hydroxyprogesterone was investigated. The average Km for NADPH in the 21-hydroxylation of progesterone is 10.4 muM while that for the 21-hydroxylation of 17-hydroxyprogesterone is 0.6 muM. The optimal NADPH concentrations for these two hydroxylations are, in average, one order of magnitude apart. The different affinities of the two 21-hydroxylating activities with respect to NADPH may indicate the presence of independent 21-hydroxylation reactions for these two steroid substrates. This evidence is consistent with the observed genetic data in human congenital adrenal hyperplasia.