The 2010 outbreak of poliomyelitis in Tajikistan: epidemiology and lessons learnt.

A large outbreak of poliomyelitis, with 463 laboratory-confirmed and 47 polio-compatible cases, took place in 2010 in Tajikistan. Phylogenetic analysis of the viral VP1 gene suggested a single importation of wild poliovirus type 1 from India in late 2009, its further circulation in Tajikistan and expansion into neighbouring countries, namely Kazakhstan, Russia, Turkmenistan and Uzbekistan. Whole-genome sequencing of 14 isolates revealed recombination events with enterovirus C with cross-overs within the P2 region. Viruses with one class of recombinant genomes co-circulated with the parental virus, and representatives of both caused paralytic poliomyelitis. Serological analysis of 327 sera from acute flaccid paralysis cases as well as from patients with other diagnoses and from healthy people demonstrated inadequate immunity against polio in the years preceding the outbreak. Evidence was obtained suggesting that vaccination against poliomyelitis, in rare cases, may not prevent the disease. Factors contributing to the peculiarities of this outbreak are discussed. The outbreak emphasises the necessity of continued vaccination against polio and the need, at least in risk areas, of quality control of this vaccination through well planned serological surveillance.

Role of environmental poliovirus surveillance in global polio eradication and beyond.

Environmental poliovirus surveillance (ENV) means monitoring of poliovirus (PV) transmission in human populations by examining environmental specimens supposedly contaminated by human faeces. The rationale is based on the fact that PV-infected individuals, whether presenting with disease symptoms or not, shed large amounts of PV in the faeces for several weeks. As the morbidity:infection ratio of PV infection is very low, this fact contributes to the sensitivity of ENV which under optimal conditions can be better than that of the standard acute flaccid paralysis (AFP) surveillance. The World Health Organization has included ENV in the new Strategic Plan of the Global Polio Eradication Initiative for years 2010-2012 to be increasingly used in PV surveillance, supplementing AFP surveillance. In this paper we review the feasibility of using ENV to monitor wild PV and vaccine-derived PV circulation in human populations, based on global experiences in defined epidemiological situations.

FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians.

AIMS AND HYPOTHESIS: Variants of the FTO (fat mass and obesity associated) gene are associated with obesity and type 2 diabetes in white Europeans, but these associations are not consistent in Asians. A recent study in Asian Indian Sikhs showed an association with type 2 diabetes that did not seem to be mediated through BMI. We studied the association of FTO variants with type 2 diabetes and measures of obesity in South Asian Indians in Pune. METHODS: We genotyped, by sequencing, two single nucleotide polymorphisms, rs9939609 and rs7191344, in the FTO gene in 1,453 type 2 diabetes patients and 1,361 controls from Pune, Western India and a further 961 population-based individuals from Mysore, South India. RESULTS: We observed a strong association of the minor allele A at rs9939609 with type 2 diabetes (OR per allele 1.26; 95% CI 1.13-1.40; p = 3 x 10(-5)). The variant was also associated with BMI but this association appeared to be weaker (0.06 SDs; 95% CI 0.01-0.10) than the previously reported effect in Europeans (0.10 SDs; 95% CI 0.09-0.12; heterogeneity p = 0.06). Unlike in the Europeans, the association with type 2 diabetes remained significant after adjusting for BMI (OR per allele for type 2 diabetes 1.21; 95% CI 1.06-1.37; p = 4.0 x 10(-3)), and also for waist circumference and other anthropometric variables. CONCLUSIONS: Our study replicates the strong association of FTO variants with type 2 diabetes and similar to the study in North Indians Sikhs, shows that this association may not be entirely mediated through BMI. This could imply underlying differences between Indians and Europeans in the mechanisms linking body size with type 2 diabetes.

A test for constant fatality rate of an emerging epidemic: with applications to severe acute respiratory syndrome in Hong Kong and Beijing.

The etiology, pathogenesis, and prognosis for a newly emerging disease are generally unknown to clinicians. Effective interventions and treatments at the earliest possible times are warranted to suppress the fatality of the disease to a minimum, and inappropriate treatments should be abolished. In this situation, the ability to extract most information out of the data available is critical so that important decisions can be made. Ineffectiveness of the treatment can be reflected by a constant fatality over time while effective treatment normally leads to a decreasing fatality rate. A statistical test for constant fatality over time is proposed in this article. The proposed statistic is shown to converge to a Brownian motion asymptotically under the null hypothesis. With the special features of the Brownian motion, we are able to analyze the first passage time distribution based on a sequential tests approach. This allows the null hypothesis of constant fatality rate to be rejected at the earliest possible time when adequate statistical evidence accumulates. Simulation studies show that the performance of the proposed test is good and it is extremely sensitive in picking up decreasing fatality rate. The proposed test is applied to the severe acute respiratory syndrome data in Hong Kong and Beijing.

Beneficial effects of Lagenaria siceraria (Mol.) Standley fruit epicarp in animal models.

Lagenaria siceraria (Mol.) Standley fruit (bottle gourd), a commonly used vegetable in India is described as cardiotonic and as a general tonic in Ayurveda. Keeping in view the presence of free radical scavenging activity in L. siceraria and involvement of free radicals in the development of various disorders, present studies were designed to evaluate the ethanolic extract of L. siceraria fruit against the disorders where free radicals play a major role in pathogenesis. The extract was found effective as hepatoprotective, antioxidant, antihyperglycemic, immunomodulatory, antihyperlipidemic and cardiotonic agent. The results showed that the radical scavenging capacity of L. siceraria fruit may be responsible for various biological activities studied.

Emergent balloon mitral valvotomy in patients presenting with cardiac arrest, cardiogenic shock or refractory pulmonary edema.

OBJECTIVES: The present study was performed to determine the outcome of emergent balloon mitral valvotomy (BMV) in patients with cardiac arrest, pulmonary edema or cardiogenic shock. BACKGROUND: In India, many patients with mitral stenosis present in critical condition. They have high mortality despite surgical relief. The role of BMV in such patients is ill-defined. METHODS: Of 558 patients undergoing BMV between January 1993 and December 1994, 40 presented with cardiogenic shock, cardiac arrest or pulmonary edema refractory to medical treatment and underwent emergent BMV (group I). Elective BMV was performed in the remaining 518 patients (group II). RESULTS: Age ([mean +/- SD] 40 +/- 13 vs. 31 +/- 9 years, p < 0.05), incidence of atrial fibrillation (35% vs. 11%, p < 0.05), pulmonary artery systolic pressure (PAsP) (64 +/- 14 vs. 51 +/- 12 mm Hg, p < 0.001) and mitral valve (MV) score (7.4 +/- 1.2 vs. 6.4 +/- 1, p < 0.001) were higher and MV area lower (0.74 +/- 0.17 vs. 0.86 +/- 0.14 cm2, p < 0.001) in group I patients. After emergent BMV in group I, mitral regurgitation occurred in 15%, and the mortality rate was 35%. Stepwise logistic regression analysis identified MV score > or =8 (p = 0.008), PAsP > or =65 mm Hg (p = 0.023) and cardiac output < or =3.151 liters/min (p = 0.001) as significant predictors of a fatal outcome. Follow-up of 1 to 16 months (median 8) was available in 20 of 26 survivors in group I, of whom 15 were asymptomatic. The gain in MV area and the decrease in transmitral gradient and PAsP obtained immediately after BMV persisted during the follow-up period. CONCLUSIONS: Emergent BMV is feasible in critically ill patients. In-hospital survivors have excellent clinical and hemodynamic status at intermediate follow-up.

Characteristics of gestational diabetic mothers and their babies in an Indian diabetes clinic.

AIMS AND OBJECTIVES: To compare clinical and metabolic features of mothers with gestational diabetes (GDM) and their offspring with those in non-diabetic pregnancies at the King Edward Memorial Hospital, Pune, India. MATERIALS AND METHODS: Antenatal information was obtained from hospital records. GDM was diagnosed by 75 g OGTT (Oral Glucose Tolerance Test) in clinically high-risk women. Anthropometric measurements of mother and the babies were recorded within 24h of delivery and a maternal blood sample collected for hematological and biochemical measurements. RESULTS: Between the period Jan 1998 to December 2003,265 women with gestational diabetes were treated in our Unit. Forty nine percent had first-degree relatives with diabetes. Compared to non-diabetic mothers (n=215) GDM mothers were older (29.0 vs. 26.0y, p<0.001), more obese (body mass index- BMI 26.0 vs. 22.0 kg/m2, p<0.001), centrally obese (Waist hip ratio-WHR 0.89 vs 0.86, p<0.001), adipose (sum of 4 skinfolds 98.4 vs. 61.4 mm, p<0.001) and had higher blood pressure (127/80 vs. 122/70 mmHg, p<0.001). GDM mothers had higher concentrations of plasma triglycerides (195.0 vs. 153.0 mg/dl, p<0.01); blood hemoglobin (11.7 vs 10.9 g/dl, p<0.001) and higher platelet count but lower concentration of HDL cholesterol and albumin. Sixty percent GDM mothers and 34% of non-diabetic mothers were delivered by caesarean-section, 23% of GDM mothers delivered pre term (<37 wk). Despite the smaller gestation, babies of GDM mothers were heavier (BW 2950.0 vs. 2824.0g, p<0.001, adjusted for gender), longer (48.9 vs. 48.0 cm, p<0.01) and more adipose (sum of 2 skinfolds 10.5 vs. 8.5 mm). Only 5% of babies born to GDM mothers weighed > 4000 g but 30% were >90th centile of birth weight of babies born to non-diabetic mothers. Babies of GDM mothers suffered higher neonatal morbidity. CONCLUSIONS: GDM mothers in urban India are more obese and more adipose than non-diabetic mothers, frequently have a family history of diabetes and show metabolic features of insulin resistance syndrome, suggesting high cardiovascular risk. Neonates of GDM mothers are heavier, longer and more adipose than those born to non-diabetic mothers, and suffer higher neonatal morbidity.

Adiposity and hyperinsulinemia in Indians are present at birth.

We studied body size and cord blood leptin and insulin concentrations in newborn urban Indian (Pune, India) and white Caucasian (London, UK) babies to test the hypothesis that the adiposity and hyperinsulinemia of Indians are present at birth. Indian babies (n = 157) were lighter in weight compared with white Caucasian babies [n = 67; median weight, 2805 g vs. 3475 g, respectively; P < 0.001, adjusted for gestational age and sex; -1.52 SD score; confidence interval (CI), -1.66, -1.42] and had smaller abdominal (-2.39 SD score; CI, -2.52, -2.09), midarm (-1.47 SD score; CI, -1.58, -1.34), and head (-1.23 SD score; CI, -1.42, -1.13) circumferences. However, their skinfolds were relatively preserved: subscapular (central) skinfold (-0.32 SD score; CI, -0.43, -0.20) was better preserved than triceps (peripheral) skinfold (-0.86 SD score; CI, -0.97, -0.75). Cord plasma leptin (median, 6.2 ng/ml Pune and 6.4 ng/ml London) and insulin (median, 34.7 pmol/liter Pune and 20.8 pmol/liter London) concentrations were comparable in the two populations but were higher in Indians when adjusted for birth weight, confirming relative adiposity and hyperinsulinemia of Indian babies. Indian mothers were smaller in all respects, compared with white Caucasian mothers, except subscapular skinfold, which was similar in the two populations. Our results support the intrauterine origin of adiposity, central adiposity, and hyperinsulinemia in Indians. Further research should concentrate on elucidating genetic and environmental influences on fetal growth and body composition. Prevention of insulin resistance syndrome in Indians will need to address regulation of fetal growth in addition to prevention of obesity in later life.

Electrolyte shifts between brain and plasma in hypoglycemic coma.

Hypoglycemia of sufficient severity to cause cessation of EEG activity (coma) is accompanied by energy failure and by loss of ion homeostasis, the latter encompassing a marked rise in extracellular fluid (ECF) K+ concentration and a fall in ECF Ca2+ concentration. Presumably, ECF Na+ concentration decreases as well. In the present study, the extent that the altered ECF-plasma gradients give rise to net ion fluxes between plasma and tissue is explored. Accordingly, whole tissue contents of Ca2+, Mg2+, K+, and Na+ were measured. The experiments were carried out in anaesthetized and artificially ventilated rats given insulin i.p.; cerebral cortical tissue was sampled at the stage of slow-wave EEG activity, after 10, 30, and 60 min of coma (defined as isoelectric EEG), as well as after 1.5, 6, and 24 h of recovery. In the precomatose animals (with a slow-wave EEG pattern), no changes in electrolyte contents were observed. During coma, tissue Na+ content increased progressively and the K+ content fell (each by 20 mumol g-1 during 60 min). During recovery, these alterations were reversed within the first 6 h. The Mg2+ content remained unchanged. In spite of the appreciable plasma to ECF Ca2+ gradient, no significant calcium accumulation was observed. It is concluded significant calcium accumulation was observed. It is concluded that hypoglycemia leads to irreversible neuronal necrosis in the absence of gross accumulation of calcium in the tissue.

Regional differences in arachidonic acid release in rat hippocampal CA1 and CA3 regions during cerebral ischemia.

Changes in the levels of arachidonic acid during ischemia in selectively vulnerable areas of the hippocampus were studied in the rat brain. Since neurons in the CA1 region are more vulnerable to ischemia than neurons in the adjacent CA3 region, the release of arachidonic acid in these two regions was measured during decapitation ischemia of 4- to 12-min duration. The concentration of free arachidonic acid increased with the duration of ischemia in both regions. However, the level was significantly higher in CA1 than in CA3 after 8 and 12 min of ischemia. This difference in arachidonic acid accumulation may reflect differences between the regions in agonist-dependent phospholipid breakdown as well as calcium-dependent phospholipase activity. The importance for the development of neuronal necrosis is discussed.

Calcium accumulation and neuronal damage in the rat hippocampus following cerebral ischemia.

The present study was undertaken to correlate calcium accumulation with the development of neuronal necrosis following transient ischemia. After 10 min of forebrain ischemia in the rat--a period that leads to reproducible damage of CA1 pyramidal cells--determination of calcium concentration and evaluation of morphological signs of cell body necrosis in the dorsal hippocampus were performed at various recirculation times. Tissue calcium concentration was not different from control at the end of ischemic period and did not change after 3, 6, 12, or 24 h of recirculation. However, after 48 h, calcium content increased significantly, with a further increase being seen after 72 h. At early recovery periods, only scattered necrotic neurons were observed. After 48 h, only 2 of 12 hemispheres showed more than 25 necrotic cells per section. More conspicuous neuronal death was observed after 72 h. The results thus demonstrate that net accumulation of calcium in regio superior of the hippocampus precedes marked necrosis of CA1 pyramidal cells. The results suggest that one primary event in the delayed death of these cells is membrane dysfunction with increased calcium cycling.

Hospitalizations for traumatic injuries among children in Maryland: trends in incidence and severity: 1979 through 1988.

Trends in incidence and severity of hospitalized injury among children aged 0 through 13 years in the state of Maryland from 1979 through 1988 (n = 35,746) were examined using routinely reported hospital discharge data. Hospital discharge rates declined over the study period from 509 per 100,000 population in 1979 to 320 in 1988. There was a decline in incidence trends for both races. However, the decrease in the nonwhite population was smaller than in whites. Analysis of incidence rates for specific Injury Severity Score groups revealed a declining trend in all Injury Severity Score groups, although the mildest group (Injury Severity Score 1 through 4) had the most notable decline of 44% compared with an average decline of 20% in the other severity groups. These data suggest a change in admission practices of mildly injured children as a major cause for the observed overall decline in hospitalization rates. The smaller decrease in the hospitalization rates of non-white children compared with white children requires further study to determine the cause.

Direct extension of bronchogenic carcinoma through pulmonary veins into the left atrium mimicking left atrial myxoma.

Direct extention of bronchogenic carcinoma via pulmonary veins into the left atrium is rare. We describe two such cases, one which presented as a left atrial mass with pulmonary edema, and another which was detected at autopsy.

Primary undifferentiated sarcoma of the pericardium.

A 60-year-old woman was found to have a pericardial mass on two-dimensional echocardiography and computerized tomography. At autopsy, there was a large tumor arising from the epicardial surface of the left ventricle. The tumor encircled the great arteries and invaded the wall of the pulmonary artery. Microscopic examination showed features of an undifferentiated sarcoma.

Subvalvular left ventricular aneurysms.

Subvalvular left ventricular aneurysms can be subaortic or submitral with variable etiology. This is a retrospective study of 19 subvalvular aneurysms seen in 16 cases. There were 12 isolated subaortic aneurysms, 3 isolated submitral aneurysms, and in 1 case with multiple subaortic and submitral aneurysms. Subaortic aneurysms were associated with infective endocarditis, while there seems to be a strong association between submitral aneurysms and tuberculosis. Five cases of subvalvular aneurysm has associated aneurysm sinus of Valsalva-this association suggests a congenital weakness in the attachment of aortic and mitral annuli to the underlying myocardium. Cardio Pathol 2000;9:267-271

Cardiac valve prostheses at autopsy: an analysis of 337 cases with clinicopathologic correlation.

We evaluated the pathologic findings at autopsy in 337 patients who had undergone cardiac valve replacement over 10 years (1982 to 1991). Rheumatic heart disease was the most common indication for valve replacement (84% of cases). Among the 255 patients with short-term survival (<1 month), in 162 cases (63.5%), the cause of death was related to surgery and/or underlying cardiovascular conditions. Host-prosthetic valve interactions contributed to mortality in 14.9% cases. However, in longtime survivors (82 patients), a significant number (86.5%) showed evidence of prosthesis-related complications, such as infective endocarditis, thrombosis, anticoagulant-related hemorrhage, and bioprosthetic valve degeneration.

Pathology of the diffuse variant of supravalvar aortic stenosis.

Supravalvar aortic stenosis is a rare congenital heart anomaly, producing left ventricular outflow tract obstruction. Of the two anatomic variants that have been described, diffuse type is the rarest. We report five such cases in children between two months and nine years of age. None had features of Williams syndrome. The entire aorta was involved in three cases, with abdominal aortic coarctation in two cases. Stenosis was mainly due to involvement of the media, which showed smooth muscle hypertrophy, abnormal elastic fibers, and mild collagenization. Predominant intimal change was seen in one case. Pulmonary, coronary, arch, renal, and common iliac arteries were also involved.

Outpatient therapy of iatrogenic drug dependency following prolonged sedation in the pediatric intensive care unit.

The authors present their clinical experience with the oral administration of lorazepam, methadone, and pentobarbital to prevent or treat withdrawal symptoms following prolonged sedation in the PICU patient. The 3 patients presented required prolonged sedation for mechanical ventilation. Different agents were used for sedation in the 3 patients including intravenous fentanyl, midazolam, and pentobarbital. The switch to oral agents must take into consideration the differences in potency, half-life, and oral bioavailability between the agents. The authors discuss the appropriate conversion factors for opioids, benzodiazepines, and barbiturates. The switch to oral administration eliminated the need for intravenous access in the 3 patients and allowed for earlier discharge home. All 3 patients were discharged home on an oral, taper schedule. Such an approach may lead to earlier home discharge thereby improving the patient's quality of life as well as saving health care dollars.

Extracorporeal membrane oxygenation in children after repair of congenital cardiac lesions.

BACKGROUND: The purpose of this study was to review our experience in the early application of extracorporeal membrane oxygenation (ECMO) in patients requiring mechanical assistance after cardiac surgical procedures. METHODS: The hospital records of all children requiring ECMO after cardiac operation were retrospectively reviewed, and an analysis of variables affecting survival was performed. RESULTS: Fifty pediatric patients between May 1997 and October 2000 required ECMO for cardiopulmonary support after cardiac operation. Patients ranged in age from 1 day to 11 years (median age, 40 days). Forty-eight patients underwent repair of congenital cardiac lesions and 2 were included after receiving a heart transplant. Twenty-two children could not be weaned from cardiopulmonary bypass and were placed on ECMO in the operating room for circulatory support. Of the 28 children who required ECMO in the intensive care unit, 10 had ECMO instituted after cardiopulmonary arrest (mean cardiopulmonary resuscitation time 42 minutes; range, 5 to 110 minutes). In infants with single-ventricle physiology, survival to discharge was 61% (11 of 18 patients) as compared with 43% (14 of 32 patients) in those with biventricular physiology. Thirty of the 50 patients (60%) were successfully weaned from ECMO, of which 25 (83%) were discharged home. Overall survival to discharge in the entire cohort was 50%. Extracorporeal membrane oxygenation support greater than 72 hours was a grave prognostic indicator. Overall survival in this group was 36% (9 of 25 patients) compared with 56% (14 of 25 patients) in those with ECMO support less than 72 hours (p < 0.05). Univariate analysis revealed the presence of renal failure, extended periods of circulatory support, and a prolonged period of cardiopulmonary resuscitation as risk factors for mortality. The presence of shunt-dependent flow, operative procedure, and institution of ECMO in the intensive care unit did not alter survival. CONCLUSIONS: Extracorporeal membrane oxygenation provides effective support for postoperative cardiac and pulmonary failure refractory to medical management. Early institution of ECMO may decrease the incidence of cardiac arrest and end-organ damage, thus increasing survival in these critically ill patients.

Selective release of N-acetylaspartylglutamate from rat optic nerve terminals in vivo.

Glutamate (Glu) and aspartate (Asp) are considered to be the neurotransmitters of the optic pathway in submammalian species, but their roles in mammals is uncertain. Recently, N-acetylaspartylglutamate (NAAG) has been proposed as a neurotransmitter in mammalian optic pathway; however, the release of endogenous NAAG on stimulation of the optic pathway has not been demonstrated. Using an in vivo microdialysis technique, we now report that electrical stimulation of rat optic nerve markedly increased the extracellular concentration of NAAG but not Glu/Asp in superficial superior colliculus where retinal afferents terminate, whereas non-specific stimulation of neurotransmitter release by high potassium or veratridine increased both extracellular Glu/Asp and NAAG concentration in the perfusate. The release of NAAG was dependent on Ca2+ and the presence of optic terminals. We conclude that NAAG is a better candidate as a neurotransmitter of rat optic nerve terminals than Glu/Asp.