Community perspective and healthcare assessment in malaria endemic states of India: a cross-sectional study protocol.

INTRODUCTION: India's contribution to the malaria burden was highest in South-East Asia Region in 2021, accounting for 79% of the estimated malaria cases and 83% of malaria-related deaths. Intensified Malaria Control Programme supported by Global Funds to Fight against AIDS, Tuberculosis and Malaria has deployed crucial interventions to reduce the overall burden of malaria in India. Evaluation of utilisation of malaria elimination interventions by the community and assessment of the healthcare system is underway in eleven high malaria endemic states in India. Health system preparedness for malaria elimination, logistics, and supply chain management of diagnostic kits and anti-malarial drugs in addition to the knowledge, attitude and practice of the healthcare workers is also being assessed. METHODS AND ANALYSIS: The study is being undertaken in 11 malaria endemic states with a variable annual parasite incidence of malaria. In total, 47 districts (administrative unit of malaria control operations) covering 37 976 households are to be interviewed and assessed. We present here the protocol following which the study is being undertaken at the behest and approval of Ministry of Health and Family Welfare in India. ETHICS AND DISSEMINATION: No patients were involved in the study. Study findings will be shared with Institutional ethics board of National Institute for Malaria Research New Delhi (NIMR) in a timely, comprehensive, accurate, unbiased, unambiguous and transparent manner and to the National Vector-borne Disease (Malaria) Control Programme officers and the Community public who participated. Important findings will be communicated through community outreach meetings which are existing in the Health system. Results will be informed to study participants via local fieldwork supervised by District Malaria Officers. Also findings will be published in reputed journals based on Indian Council of Medical Research (ICMR) publication policy.The ICMR-NIMR ethics committee approved the study via letter No. NIMR/ECM/2023/Feb/14 dated 24 April 2023 for version 5. All standard ethical practices will be followed.

Endovascular Embolization of Intrapulmonary Sequestration.

Traditionally, management of lung sequestrations has been surgical. This is one of the few reports where a percutaneous management has resulted in resolution of symptoms and offers a novel approach for management.

Sheath-Induced Sterile Abscesses.

Sterile inflammatory reactions at vascular access sites have rarely been reported in the literature. Simple conservative treatment, as in this case, can lead to resolution of even extensive sterile abscesses.

Coronary Artery Air Embolism.

Coronary artery air embolism can be fatal if not proficiently managed. Vasospasm is said to be protective in that it breaks the larger air bubbles, as occurred in the present case.

Non-polio Enteroviruses in Karnataka, India: Virological surveillance of acute flaccid paralysis cases (July 1997-2013).

BACKGROUND AND OBJECTIVES: Since 1997 National Institute of Virology, Bangalore Unit involved in WHO's Acute flaccid paralysis paediatric cases surveillance programme to isolate and detect polioviruses. Stool samples yielded not only polioviruses but also Non-Polio enteroviruses. This report is an overview of non-polio Enterovirus (NPEV) epidemiology in Karnataka state, India for the period of 16-years and 6 months from July 1997-2013. METHODS: A total of 19,410 clinical samples were processed for virus isolation as a part of acute flaccid paralysis (AFP) surveillance for Global Polio Eradication Programme in India at National Polio Laboratory, at Bengaluru. NPEV detection was performed by virus isolation on cell culture according to World Health Organisation recommended protocols. RESULTS: A total of 4152 NPEV isolates were obtained. The NPEV isolation rate varied from year to year but with a total NPEV rate of 21.39%. CONCLUSION: A seasonal variation was noted with high transmission period between April and October with peaks in June-July. The male to female ratio was 1:1.2. The isolation of NPEV decreased significantly with the increase in age. Epidemiology of NPEVs from AFP cases in Karnataka is described.

Mumps disease outbreak in Davangere district of Karnataka, India.

BACKGROUND: Mumps is a vaccine-preventable disease that usually occurs as a parotitis, but it can also lead to several life- threatening complications, including pancreatitis, meningitis and encephalitis. OBJECTIVE: To determine and diagnosis of mumps disease, which is communicable disease usually affects childrens. Although it is seen worldwide, but outbreaks not common in India. MATERIALS AND METHODS: Thirty one suspected mumps cases, who presented to the unimmunized population of Chikkahallivana village in Davangere district of Karnataka, India in January 2014, with clinical evidence of fever, cervical lymphadenitis and ear pain, manifest with self-limited uni-or bilateral parotitis. A total of 31 cases consisting of 31 blood and 31 throat swabs were tested for diagnosis of mumps disease. RESULTS: Of the 31 suspected cases, laboratory results showed 18 positive for mumps IgM antibodies and 7 cases showed presence of mumps virus RNA by RT-PCR using MV specific nested primers. From 31 cases, 5 were positive with both the methods. CONCLUSION: We confirmed the cases by serological as well as a sensitive RT-nested PCR-based method and sequencing results for the molecular identification of mumps infection. Sequencing results of the SH gene identified outbreak strain as genotype C, which was consistent with other outbreaks in India.

The population genomics of begomoviruses: global scale population structure and gene flow.

BACKGROUND: The rapidly growing availability of diverse full genome sequences from across the world is increasing the feasibility of studying the large-scale population processes that underly observable pattern of virus diversity. In particular, characterizing the genetic structure of virus populations could potentially reveal much about how factors such as geographical distributions, host ranges and gene flow between populations combine to produce the discontinuous patterns of genetic diversity that we perceive as distinct virus species. Among the richest and most diverse full genome datasets that are available is that for the dicotyledonous plant infecting genus, Begomovirus, in the Family Geminiviridae. The begomoviruses all share the same whitefly vector, are highly recombinogenic and are distributed throughout tropical and subtropical regions where they seriously threaten the food security of the world's poorest people. RESULTS: We focus here on using a model-based population genetic approach to identify the genetically distinct sub-populations within the global begomovirus meta-population. We demonstrate the existence of at least seven major sub-populations that can further be sub-divided into as many as thirty four significantly differentiated and genetically cohesive minor sub-populations. Using the population structure framework revealed in the present study, we further explored the extent of gene flow and recombination between genetic populations. CONCLUSIONS: Although geographical barriers are apparently the most significant underlying cause of the seven major population sub-divisions, within the framework of these sub-divisions, we explore patterns of gene flow to reveal that both host range differences and genetic barriers to recombination have probably been major contributors to the minor population sub-divisions that we have identified. We believe that the global Begomovirus population structure revealed here could facilitate population genetics studies into how central parameters of population genetics namely selection, recombination, mutation, gene flow, and genetic drift shape the global begomovirus diversity.

Pseudoaneurysm following lateral wall myocardial infarction.

Pseudoaneursym (PA) formation of left ventricle (LV) following acute myocardial infarction (AMI) is uncommon and is usually believed to be associated with a grave prognosis. We describe a case of 55 year old male patient presented with AMI and heart failure with a systolic murmur later diagnosed to have PA of the lateral wall of LV on echocardiography (transthoracic and transesophageal, TTE andTEE). Cardiac MRI and coronary angiogram (CAG) were performed. CAG showed 60% lesion at origin of major obtuse marginal artery (OM1). The patientwas advised surgical treatment, but he refused and took discharge against medical advice on 27th dayof admission on stable condition.

Pharmacokinetically guided dose escalation of carboplatin in epithelial ovarian cancer: effect on drug-plasma AUC and peripheral blood drug-DNA adduct levels.

BACKGROUND: Platinum based drugs are active agents in epithelial ovarian cancer and increased platinum drug dose intensity is thought to lead to improved survival, because of the largely untested assumption that increased dose intensity results in an increased interaction of the platinum drug with its target, DNA. In a previously reported phase I trial (Lind et al., J Clin Oncol 1996; 14: 800-5), carboplatin dose intensity was increased by the use of G-CSF to support the bone marrow and using pharmacokinetically-guided carboplatin dosing. The objectives of this study were to validate the carboplatin dosing formula during high dose intensity therapy and evaluate the relationship between systemic carboplatin exposure and Pt-DNA adduct levels in peripheral blood leucocytes. PATIENTS AND METHODS: A total of 17 patients were studied over four levels of dose intensification. The carboplatin dose was calculated using the 'Calvert formula'. Levels of drug-target interaction in peripheral blood leukocytes were measured using an immunoassay based on a monoclonal antibody that recognises DNA-platinum adducts. Pharmacokinetic measurements were carried out using a previously validated single sample method. RESULTS: The area under the curve of concentration of unbound carboplatin in plasma versus time (AUC) for target AUC values of 5, 7 and 9 mg/ml x min were: 5.6 +/- 1.0, 7.3 +/- 0.7 and 9.8 +/- 0.5 mg/ml x min (mean +/- S.D.). There was a good correlation between target and achieved dose intensities (r2 = 0.899) and the slope of the linear regression line was 0.95 (+/- 0.09 SD) not significantly different to 1.0 (P > 0.6). The levels of immunoreactive DNA adducts were not detectable at a target AUC of 5 mg/ml x min but increased progressively at the higher AUC levels. Accumulation of adducts between courses was not detected. CONCLUSIONS: Pharmacokinetically-based carboplatin dosing during high intensity therapy accurately predicted the dose required to achieve a target AUC and resulted in consistent patient exposure to active drug. During the dose escalation study, peripheral blood leucocyte DNA platinum-DNA adduct levels were positively related to drug dose and drug AUC.

Dilated cardiomyopathy in non-specific aortoarteritis.

Out of 195 cases of Takayasu's arteritis who presented in our institute between January 1988 and December 1997, 12 (5.58%) had dilated cardiomyopathy. Age of these patients ranged from 10 to 30 years (17.25 +/- 5.30 years) and male-female ratio was 1:11. All the cases had cardiovascular system features (dyspnoea, oedema, palpitation, angina, etc. but without hypertension), three had central nervous system features (headache, vomiting, convulsion etc.) and all had general systemic features like weight loss, malaise, fever, arthralgia etc. Electrocardiography, chest X-ray and echocardiographic findings were consistent with dilated cardiomyopathy. Haemodynamic findings showed raised left ventricular end-diastolic pressure and pulmonary capillary wedge pressure in all; raised pulmonary artery pressure, pulmonary vascular resistance, right ventricular pressure and right atrial pressure in 6, 6, 4 and 2 cases, respectively; reduced left ventricular peak systolic pressure in 10 cases but central aortic pressure and systemic vascular resistance in all the cases were within normal limits. Angiography showed type I, II and III involvement in 7 (majority), 3 and 2 cases, respectively. Coronary and pulmonary angiography were normal and left ventricular angiography showed poor left ventricular systolic function in all the cases. Histopathological study (on 3 autopsy cases) showed non-specific inflammation of myocardium with lymphocyte/mononuclear cell infiltration and normal coronary vessels. So, dilated cardiomyopathy in Takayasu's arteritis is not rare, though not much reported, and can influence the prognosis of aortoarteritis cases.

Vacuolation in renal tubular epithelium of Cd-1 mice: an incidental finding.

Prominent cytoplasmic vacuoles were observed in renal tubular epithelial cells of the outer medulla in several kidneys from test article-dosed mice (Crl:CD-1 (ICR)BR VAF/PLUS) during routine light microscopic (LM) examination. Because the vacuolar change was detected infrequently and was not found in any control mice from that study, it was not clear whether the vacuolation represented a drug-induced change. To address this question, kidney sections from mice from multiple unrelated studies were examined by LM for similar vacuolar changes. Vacuolation was seen by LM in 2.3% of the control and 2.8% of the test article-dosed mice. Transmission electron microscopy (TEM) was also performed on kidneys with prominent light microscopic vacuoles in 5 control mice and 2 test article-dosed mice to further characterize the vacuoles. Ultrastructurally, the vacuoles contained fibrillar and finely stipled granular material or membranous whorls. Kidneys from control mice lacking light microscopic evidence of vacuolation had smaller vacuoles containing similar material when examined by TEM. Because vacuoles were present in both control mice and test article-dosed mice, it was concluded that the vacuoles were incidental and unrelated to compound administration. These studies also demonstrated that vacuoles can be expected to be observed by LM examination in 2-3% of Crl:CD-1 (ICR)BR VAF/PLUS, mice.

Coronary artery lesions in Takayasu's arteritis--clinical and angiographic study.

Two hundred and twenty five patients of Takayasu's arteritis were studied over 13 years. Male:Female ratio was 1:7. Mean age of the study population was 19 +/- 4 years. Of these 225 patients, 75 patients had symptoms and/or signs of cardiac involvement and these patients were subjected to coronary angiography. Significant coronary artery occlusion (i.e. more than 50% narrowing of luminal diameter) was present in 9 patients. Incidence of coronary artery lesions in Takayasu's arteritis is 12% in this study. The proximal segments of coronary arteries were involved while the distal segments were spared. Out of 34 patients with angina pectoris, only 3 patients had significant coronary arterial narrowing.

Safety evaluation of recombinant human interleukin-4. I. Preclinical studies.

Recombinant human IL-4 (rhuIL-4) has been evaluated in a series of preclinical studies. These studies have demonstrated that rhuIL-4 is a very potent cytokine with a wide range of pharmacologic and toxicologic effects. Target systems/organs included the cardiovascular system, liver, spleen, and bone marrow. The incidence and severity of effects correlated strongly with both the dose level and the duration of rhuIL-4 administration. The major dose-limiting toxicities identified included death, cardiac inflammation and necrosis, hepatitis, and hepatic necrosis and occurred at sc doses > or = 25 micrograms/kg/day, while a sc dose of 5 micrograms/kg/day was the highest tested that did not result in major dose-limiting toxicity. Clinical trials in humans have demonstrated that sc administration of Escherichia coli-derived rhuIL-4 is safe and well tolerated at doses up to and including 5 micrograms/kg/day and up to 10 micrograms/kg when administered 3 times/week.

Hypertension in the young in eastern India.

Three hundred and forty-one young hypertensives in the age group of 18-30 years were evaluated over a 7-year period. Essential hypertension constituted the single largest group (35.8%). Renal pathology was the most common cause of secondary hypertension (26.4%). Congenital coarctation of the aorta and endocrine causes accounted for 14.1 percent and 3.2 percent cases of secondary hypertension, respectively. A strikingly high incidence of nonspecific aortoarteritis (20.1%) was a distinguishing feature amongst secondary causes. Aortoarteritis was the commonest cause of renal artery stenosis. Renal angioplasty was performed in 11 patients with refractory hypertension. Forty percent of the patients achieved post-angioplasty control of blood pressure without drugs; in 25 percent, the blood pressure became easier to control. Restenosis was detected in 4 cases over 18-24 months of follow-up.