Evolving management of insulinoma: Experience at a tertiary care centre.

BACKGROUND & OBJECTIVES: Since our previous study in 2006, several new modalities for localization of cause of endogenous hyperinsulinemic hypoglycaemia such as multiphasic computed tomography (CT), multiphasic magnetic resonance imaging (MRI), endoscopic ultrasound (EUS), intraoperative ultrasound, and intra-arterial calcium infusion with arterial stimulation venous sampling (ASVS) have become available. Therefore, to evaluate the relative usefulness of various imaging modalities to guide future management in terms of diagnosis and patient care, we analyzed presentation and management of patients of endogenous hyperinsulinemic hypoglycaemia. METHODS: In this retrospective study, medical records of patients admitted with endogenous hyperinsulinemic hypoglycaemia were retrieved. Data pertaining to clinical features, diagnosis, imaging, surgery and patient outcome were extracted. The localization of insulinoma by preoperative imaging techniques was compared with the findings at surgery to assess the accuracy of localization. RESULTS: Fasting hypoglycaemia was present in all, and post-prandial hypoglycaemia (plasma glucose ≤50 mg/dl within four hours of meal) in 25.8 per cent. Mean duration of symptoms before reaching a diagnosis of hyperinsulinemic hypoglycaemia was 3.9 years. Mean duration of provocative fast was 21.8 h (range 6-48 h). Among the currently used imaging modalities, the sensitivity of localizing tumour was 79.3 per cent for multiphasic CT, 85 per cent for multiphasic MRI and 95 per cent for EUS. EUS detected tumour missed by both CT and MRI. All, except one of the operated patients, were cured by surgery. INTERPRETATION & CONCLUSIONS: Our results suggest that patients with insulinoma have a varied presentation. Multiphasic contrast-enhanced MRI/CT scan, EUS and ASVS may be complimentary in pre-operative localization.

Postprandial endothelial dysfunction and CIMT after oral fat challenge in patients with type 2 diabetes mellitus with and without macrovascular disease - A preliminary study.

BACKGROUND: Very few studies have reported on association of postprandial lipids and endothelial dysfunction among patients with diabetes. Whether endothelial dysfunction particularly postprandial FMD is worse in patients with T2DM with macrovascular disease compared to those without and whether this difference is related to postprandial hypertriglyceridemia (PPHTg) is unclear. Therefore, present study was aimed to assess the relationship between PPHTg and endothelial function in patients with T2DM with and without macrovascular disease. METHOD: Endothelial dysfunction by FMD and CIMT were compared in patients with T2DM with and without macrovascular disease (n = 13 each group) and 13 age, sex and BMI matched healthy individuals after an oral fat challenge. RESULTS: There was significant postprandial deterioration of FMD 4-hr after fat challenge in patients with diabetes (P < 0.001) as well as healthy individuals (P = 0.004). Patients with diabetes with macrovascular disease had significantly lower fasting (5.7 ± 6.1% vs. 22.7 ± 10.0% and vs. 24.7 ± 5.3%) as well as postprandial (4-hr) (3.1 ± 5.0% vs. 15.3 ± 8.1% and vs. 15.4 ± 5.7%) FMD compared to other two groups. Fasting, postprandial as well as change in FMD and CIMT in patients with diabetes correlated significantly with fasting as well as postprandial triglycerides with stronger correlation in those with macrovascular disease. CONCLUSION: Study found significant endothelial dysfunction by FMD that shows substantial further deterioration postprandially following high fat meal in patients with diabetes with macrovascular disease compared to patients with diabetes without macrovascular disease and healthy individuals. Study also indicates that PPHTg is a contributor to endothelial dysfunction. However, more studies are required to corroborate these findings.

Anaemia in patients with type 2 diabetes mellitus without nephropathy is related to iron deficiency.

BACKGROUND AND AIMS: Iron deficiency anaemia, although well reported in diabetic nephropathy, has not been well studied in type 2 diabetes patients in the absence of nephropathy. We studied the prevalence of anaemia and iron deficiency in type 2 diabetes patients without nephropathy. MATERIAL AND METHODS: A total of 89 patients were selected for this study. 24 h urine protein less than 500 mg was used as the criteria to rule out diabetic nephropathy. Complete hemogram, iron profile and high sensitivity C reactive protein (hs CRP) levels were performed in each patient.Functional iron deficiency (FID) was defined as serum ferritin more than 100 µg/l with serum transferrin less than 20% and total iron deficiency state was defined as serum ferritin less than 100 µg/l. RESULTS: Fifteen patients (16.8%)had anaemia out of which 13 had total iron deficiency and one each had functional iron deficiency and normal iron status respectively. Assessment of the iron status overall showed that 49 patients had TID (55.05%), 16 had FID (17.9%)and 24 (27.05%) had normal iron status. The hs-CRP was significantly higher in those with iron deficiency. CONCLUSIONS: The present study found a high prevalence of iron deficiency anaemia in type 2 diabetic patients even in the absence of nephropathy. Most of the diabetic subjects also displayed an iron deficiency state the cause of which needs further investigation.

Bottom-up or top-down: unit cost estimation of tuberculosis diagnostic tests in India.

SETTING: Of 18 sites that participated in an implementation study of the Xpert® MTB/RIF assay in India, we selected five microscopy centres and two reference laboratories. OBJECTIVE: To obtain unit costs of diagnostic tests for tuberculosis (TB) and drug-resistant TB. DESIGN: Laboratories were purposely selected to capture regional variations and different laboratory types. Both bottom-up and the top-down methods were used to estimate unit costs. RESULTS: At the microscopy centres, mean bottom-up unit costs were respectively US$0.83 (range US$0.60-US$1.10) and US$12.29 (US$11.61-US$12.89) for sputum smear microscopy and Xpert. At the reference laboratories, mean unit costs were US$1.69 for the decontamination procedure, US$9.83 for a solid culture, US$11.06 for a liquid culture, US$29.88 for a drug susceptibility test, and US$18.18 for a line-probe assay. Top-down mean unit cost estimates were higher for all tests, and for sputum smear microscopy and Xpert these increased to respectively US$1.51 and US$13.58. The difference between bottom-up and top-down estimates was greatest for tests performed at the reference laboratories. CONCLUSION: These unit costs for TB diagnostics can be used to estimate resource requirements and cost-effectiveness in India, taking into account geographical location, laboratory type and capacity utilisation.

Market assessment of tuberculosis diagnostics in India in 2013.

BACKGROUND: India represents a significant potential market for new tests. We assessed India's market for tuberculosis (TB) diagnostics in 2013. METHODS: Test volumes and unit costs were assessed for tuberculin tests, interferon-gamma release assays, sputum smear microscopy, serology, culture, speciation testing, nucleic-acid amplification tests (i.e., in-house polymerase chain reaction, Xpert(®) MTB/RIF, line-probe assays) and drug susceptibility testing. Data from the public sector were collected from the Revised National TB Control Programme reports. Private sector data were collected through a survey of private laboratories and practitioners. Data were also collected from manufacturers. RESULTS: In 2013, India's public sector performed 19.2 million tests, with a market value of US$22.9 million. The private sector performed 13.6 million tests, with a market value of US$60.4 million when prices charged to the patient were applied. The overall market was US$70.8 million when unit costs from the ingredient approach were used for the 32.8 million TB tests performed in the entire country. Smear microscopy was the most common test performed, accounting for 25% of the overall market value. CONCLUSION: India's estimated market value for TB diagnostics in 2013 was US$70.8 million. These data should be of relevance to test developers, donors and implementers.

Risk of seizures and neurocysticercosis in household family contacts of children with single enhancing lesions.

A small, single enhancing lesion (SEL) is often noted upon computed tomography (CT) in children and young adults with recent focal or generalized seizures. A high frequency of seizures has been reported in family members of persons with SEL. We studied the prevalence of seizures and cysticercus electro-immuno-transfer blot (EITB) based seropositivity among family members, specifically household family contacts of pediatric subjects with a SEL. An attempt was also made to determine the etiology of seizures in household family contacts using magnetic resonance imaging (MRI). Information regarding seizure semiology, personal and food habits and detailed family pedigrees was obtained from 20 consecutive pediatric subjects with a SEL and 51 of their household family contacts. EITB sero-assays and stool examinations were performed on all participating subjects. MRIs were done on all EITB positive household family contacts. A family history of seizures was obtained in six index children (30%) (five household first-degree relatives and two distant relatives). Seventeen index children (85%) and 14 family contacts (27%) were EITB positive. A tendency towards clustering of EITB positive cases within individual families was observed. Stool examinations did not reveal Taenia species ova in any of EITB positive subjects. Neuroimaging studies revealed abnormalities consistent with active or inactive neurocysticercosis in all five household family contacts with history of seizures. Four of these five subjects were EITB positive and one was EITB negative. We concluded that children with SEL and seizures may have a family history of seizures. There is a high seropositivity rate in household family contacts of pediatric subjects with solitary cysticercus granulomas (SCGs). EITB based seropositivity in household family contacts with seizures, strongly predicts a cysticercal etiology for seizures. It may be worthwhile to screen household family contacts of children with SEL for taeniasis-cysticercosis.

Does inhaled nitric oxide improve survival in operated congenital disease with severe pulmonary hypertension?

BACKGROUND: The present study aimed to assess the impact of inhaled nitric oxide on survival following correction of congenital heart defects with residual pulmonary arterial hypertension. METHODS AND RESULTS: Inhaled nitric oxide was utilized for the management of residual pulmonary hypertension in 24 children following surgical correction of their underlying heart defects. Their ages ranged from 15 days to 14 months (median 5 months). Pulmonary artery hypertension was diagnosed either by direct pulmonary artery pressure monitoring or by echocardiography. Inhaled nitric oxide was used electively in 22 patients when the ratio of the mean pulmonary arterial pressure and mean systemic arterial pressure exceeded 0.5. In the remaining 2 patients, nitric oxide was used only to manage a pulmonary hypertensive crisis. Inhaled nitric oxide was also used a second time in 2 patients who developed delayed pulmonary hypertensive crisis. Twenty-two patients showed an initial response to therapy and the pulmonary artery pressures dropped significantly. Of the patients on direct pulmonary artery pressure monitoring, a pulmonary artery to systemic artery pressure ratio below 0.3 on prolonged therapy was associated with a survival ratio of 4/6 (including 1 neurological death and one reoperation); that between 0.3 and 0.5 with a survival ratio of 3/4. Three out of four patients with sustained echocardiographic and clinical response also survived and were discharged from the hospital. All the patients who showed a lack of response to (n=2), tolerance to (n=1), or dependence on (n=6) the use of inhaled nitric oxide died. In addition, all 5 patients who had a pulmonary hypertensive crisis died, 3 in spite of successful resuscitation with nitric oxide. Thus, excluding one neurological death and one re-operation, only 9 (41%) out of 22 patients survived. CONCLUSIONS: Though inhaled nitric oxide is effective in lowering pulmonary pressure, it does not appear to improve the survival rate following repair of congenital heart disease in those with associated severe pulmonary hypertension. A randomized trial between the use and non-use of inhaled nitric oxide is warranted to determine its exact role in influencing survival in patients with residual pulmonary hypertension following surgical repair.

Elucidation mechanism of organic acids production from organic matter (grass) using digested and partially digested cattle feed.

The process of anaerobic digestion is highly influenced by the environmental and operational factors like organic acids concentration and the reactor volume occupied by the feed material. The optimum level of organic acids is commonly assumed to be in the range between 2,500 and 3,500 mg/l for the anaerobic digestion process. It was observed that the production of total organic acids during hydrolysis of grass using cattle dung slurry (CDS) as the inoculum reached up to 4,850 mg/l in 6 days, while on the other hand it reached 5,700 mg/l within 4 days when rumen content was used as inoculum. The organic acids production continued to the 30th day in the case of rumen content, while in the case of CDS it stopped within 10 days because of pH drop. As compared to CDS the anaerobic digestion of grass with rumen content showed better degradation and biogas production with nearly 80% of methane and up to 80 and 95% reduction in chemical oxygen demand and organic acids respectively.

Population dynamics of rumen microbes using modern techniques in rumen enhanced solid incubation.

The microbial ecology of the rumen is very complex. Different species of bacteria, protozoa, and fungi are involved in digestion of plant material in ruminants. In spite of complicated interrelationships among the various groups of microorganisms in the rumen ecosystem, Bacteria and Archaea are believed to play a major role because of their numerical predominance and metabolic diversity. In this work we are presenting the results for microbial population dynamics of rumen microbes during two-stage anaerobic digestion of grass. The reactors were inoculated with fresh rumen content. Fluorescent in situ hybridization, confocal laser scanning microscopy and epifluorescence microscopy were employed for microbial investigation. It was observed that Bacteria dominated in the hydrolytic reactor (1st stage) whereas Archaea were predominant in the methanogenic reactor (2nd stage). The stability of the methanogenic reactor was result of the dominance of Methanosaeta species (mainly the filamentous type).

Membrane separation to improve degradation of road side grass by rumen enhanced solid incubation.

Membrane separation proved to be an excellent means to maintain high residence time of microorganisms in an anaerobic hydrolysis reactor, and relatively low concentration of hydrolysis products. The microbial biocommunity typical for the rumen environment could be maintained, and the reactor efficiency of the reactor improved. Less than 4 days were reqired to reach almost complete hydrolysis of the grass fed into the reactor. To avoid blocking of the membrane unit, a backwash system is necessary. The membranes needed to be backwashed every 20 min with 4 bar gas-pressure for 10 s. After this treatment the initial permeability was regained. The plant was operated with a flux of 12 ml h(-1) cm(-2) on average. The transmembrane pressure was in the range of 0.8-0.9 bar. 90% of the dissolved fatty acids permeated through the membrane.

Parental attitudes towards epilepsy.

Parents of 352 children with history of epilepsy were interviewed by a pretested, open ended questionnaire to ascertain the nature of first aid care during an epileptic fit, complications arising out of this care, and parents' perceptions regarding causes of epilepsy. The commonest form of care provided was to force liquids by mouth (50.6%), followed by pressure over body to restrain convulsive movements (13.0%) or to put some object to force the teeth open (11.9%). The various causes of epilepsy according to the parents were: due to an evil spirit (26.7%0, heritable causes (13.9%), physical or mental weakness (6.6%) and brain damage (5.9%). The need of imparting knowledge and clear understanding about epilepsy among parents is emphasized.

Sleep pattern and night awakening in healthy infants.

Sleep pattern and night-awakening were studied in 500 healthy infants by a semistructured interview method. A total of 92.2% infants shared bed with their mothers, 6.8% with grand parents and 1% with fathers. Paternal participation at bedtime was observed to be insignificant. Infants of non-working mothers and families with vegetarian habits slept significantly more as compared to the working mothers and families with non-vegetarian habits. Night-time awakening was reported in 96% of the infants. If a child is functioning well in other areas of life, parents can be assured that the problem is not of serious concern and unnecessary medication of infants should be avoided.

Extent of occurrence of the six vaccine preventable diseases in vaccinated/unvaccinated children.

Sixty two children who were diagnosed to be suffering from any of the six vaccine preventable diseases were studied to know their vaccination status prior to the occurrence of these diseases. A total of 33.9% of these children had developed these diseases inspite of full immunization. Nearly 75% of immunized children had received the vaccine from Government sources. The break-up diseases among the children studied was tetanus (35.5%), poliomyelitis and pulmonary tuberculosis (22.6% each), measles (11.3%), diphtheria (6.4%) and pertussis (1.6%). The vaccinated children who developed poliomyelitis belonged to a relatively higher age group. Seventy one per cent of measles cases developed bronchopneumonia as a complication. Seventy five per cent of the mortality in the children studied was due to tetanus neonatorum. Since one third of the children studied had developed diseases inspite of full immunization, it is inferred that closer monitoring of the Cold Chain System and intensive surveillance at peripheral levels are required.

Stool electrolytes in acute dehydrating gastroenteritis.

Stool electrolytes were studied in 100 cases of gastroenteritis. The duration of illness was 24-48 hours in 32% and 72-96 hours in 28% of the cases. On stool culture, 43% children had no growth, 23% had Enteropathogenic E. coli and 10% had cholera and rotavirus each. The stool sodium loss was more in cholera and shigella cases, diarrhea of shorter duration and in children between 24-30 months of age. Potassium loss in the stool was more in shiegella cases, diarrhea of short duration and in children between 30-36 months of age. In cases of gastroenteritis with severe malnutrition, stool sodium loss was less; stool potassium loss was not affected by the nutritional status. Total electrolytes lost in stools can be estimated by knowing purging rate and rehydration therapy can be planned accordingly.

Skinfolds in affluent Punjabi preschool children.

The skinfold thickness at three different sites (triceps, subscapular and suprailiac) were measured using Holtain Skin Fold Caliper in 941 children of 0-5 years of age. The sample consisted of children from affluent families of Ludhiana (Punjab) in order to include only the optimally growing children. The skinfold thickness at all the three sites showed a progressive rise in mean values upto the age of 1 year and thereafter the trend was downwards till the age of 5 years in both the sexes. The values were higher in girls in all age groups. The mean triceps skinfold thickness was the highest followed by subscapular and suprailiac thickness in both sexes in almost all age groups. There was no correlation between the body weight and skinfold thickness values (mean r value = 0.09). Triceps and suprailiac skinfold thickness were significantly lower than the corresponding British values in both the sexes in all age groups. However, the subscapular values were comparable with British values in the females of all age groups and also in males above three years of age. Larger multicentric studies are recommended to frame the norms for Indian children.

National estimate of HIV seroprevalence among tuberculosis patients in India.

The national estimate for human immunodeficiency virus (HIV) prevalence among tuberculosis (TB) patients in India has previously been estimated indirectly from global data. To derive an improved national estimate from local data, we correlated district-level HIV surveillance data from antenatal clinics and TB diagnostic centres, and applied this correlation to state-level HIV prevalence estimates for the antenatal population. We estimate that among the 1.96 million incident TB cases in 2007, 4.85% (95%CI 4.12-5.73) or 95 240 (95%CI 80 730-112 478) were HIV-infected. With these estimates from local data, the national programme can better plan TB-HIV collaborative activities and monitor efforts to detect HIV infection in this large population.

Distribution of HLA antigens in a sample of the North Indian Hindu population.

The Indian population can be divided broadly into Dravidians and the Aryans. In this report, we have attempted to analyze the HLA genetic profile of 400 native North Indian Hindus of Aryan descent. The gene frequencies of a majority of class I and II antigens show similarity to the Caucasoid population. An interesting finding was a complete lack of antigen B14 while B16 and B41 occurred with the least frequency. Haplotype A10, B8 with significant positive linkage disequilibrium as well as showing the highest incidence is characteristic of North Indians.