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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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Dyslipidemias are the most important coronary artery disease (CAD) risk factor. Proper management of dyslipidemia is crucial to control the epidemic of premature CAD in India. Cardiological Society of India strived to develop consensus-based guidelines for better lipid management for CAD prevention and treatment. The executive summary provides a bird's eye-view of the 'CSI: Clinical Practice Guidelines for Dyslipidemia Management' published in this issue of the Indian Heart Journal. The summary is focused on the busy clinician and encourages evidence-based management of patients and high-risk individuals. The summary has serialized various aspects of lipid management including epidemiology and categorization of CAD risk. The focus is on management of specific dyslipidemias relevant to India-raised low density lipoprotein (LDL) cholesterol, non-high density lipoprotein cholesterol (non-HDL-C), apolipoproteins, triglycerides and lipoprotein(a). Drug therapies for lipid lowering (statins, non-statin drugs and other pharmaceutical agents) and lifestyle management (dietary interventions, physical activity and yoga) are summarized. Management of dyslipidemias in oft-neglected patient phenotypes-the elderly, young and children, and patients with comorbidities-stroke, peripheral arterial disease, kidney failure, posttransplant, HIV (Human immunodeficiency virus), Covid-19 and familial hypercholesterolemia is also presented. This consensus statement is based on major international guidelines (mainly European) and expert opinion of lipid management leaders from India with focus on the dictum: earlier the better, lower the better, longer the better and together the better. These consensus guidelines cannot replace the individual clinician judgement who remains the sole arbiter in management of the patient., (Copyright © 2023 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Background: In this study, we carried out an investigation of Kyasanur Forest Disease (KFD) suspected human cases reported in Karnataka state, India from December 2018 to June 2019., Methods: The clinical samples of KFD suspected cases ( n  = 1955) from 14 districts of Karnataka were tested for KFD using real-time RT-PCR and IgM ELISA. Further, the KFD-negative samples were tested for IgM antibodies against dengue and chikungunya viruses. Monkey samples ( n  = 276) and tick pools ( n  = 11582) were also screened using real-time RT-PCR. KFD-positive samples were further analysed using next-generation sequencing along with clinico-epidemiological analysis., Results: Of all, 173 (8.8%) cases tested positive for KFD either by real-time RT-PCR ( n  = 124), IgM ELISA ( n  = 53) or both tests ( n  = 4) from seven districts. Among KFD-negative cases, IgM antibody positivity was observed for dengue (2.6%), chikungunya (5.8%), dengue and chikungunya coinfection (3.7%). KFD cases peaked in January 2019 with fever, conjunctivitis, and myalgia as the predominant symptoms and a mortality of 4.6%. Among confirmed cases, 41% received a single dose and 20% received two doses of the KFD vaccine. Of the seven districts with KFDV positivity, Shivamogga and Hassan districts reported KFD viral RNA positivity in humans, monkeys, and ticks. Sequencing analysis of 2019 cases demonstrated a difference of less than 1.5% amino acid compared to prototype KFDV., Conclusion: Although the KFD has been endemic in many districts of Karnataka state, our study confirms the presence of KFDV for the first time in two new districts, i.e. Hassan and Mysore. A comparative analysis of KFDV infection among the KFD-vaccinated and non-vaccinated populations demonstrated an insignificant difference.

Objectives: The presentation and outcomes of acute decompensated heart failure (ADHF) during COVID times (June 2020 to Dec 2020) were compared with the historical control during the same period in 2019., Methods: Data of 4806 consecutive patients of acute HF admitted in 22 centres in the country were collected during this period. The admission patterns, aetiology, outcomes, prescription of guideline-directed medical therapy (GDMT) and interventions were analysed in this retrospective study., Results: Admissions for acute heart failure during the pandemic period in 2020 decreased by 20% compared to the corresponding six-month period in 2019, with numbers dropping from 2675 to 2131. However, no difference in the epidemiology was seen. The mean age of presentation in 2019 was 61.75 (±13.7) years, and 59.97 (±14.6) years in 2020. There was a significant decrease in the mean age of presentation (p = 0.001). Also. the proportion of male patients decreased significantly from 68.67% to 65.84% (p = 0.037). The in-hospital mortality for acute heart failure did not differ significantly between 2019 and 2020 (4.19% and 4.,97%) respectively (p = 0.19). The proportion of patients with HFrEF did not change in 2020 compared to 2019 (76.82% vs 75.74%, respectively). The average duration of hospital stay was 6.5 days., Conclusion: The outcomes of ADHF patients admitted during the Covid pandemic did not differ significantly. The length of hospital stay remained the same. The study highlighted the sub-optimal use of GDMT, though slightly improving over the last few years., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ALL PARTICIPATING CENTRE CO INVESTIGATORS reports financial support was provided by Cardiological Society of India., (Copyright © 2023 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Objective: To find out differences in the presentation, management and outcomes of COVID-19 infected STEMI patients compared to age and sex-matched non-infected STEMI patients treated during the same period., Methods: This was a retrospective multicentre observational registry in which we collected data of COVID-19 positive STEMI patients from selected tertiary care hospitals across India. For every COVID-19 positive STEMI patient, two age and sex-matched COVID-19 negative STEMI patients were enrolled as control. The primary endpoint was a composite of in-hospital mortality, re-infarction, heart failure, and stroke., Results: 410 COVID-19 positive STEMI cases were compared with 799 COVID-19 negative STEMI cases. The composite of death/reinfarction/stroke/heart failure was significantly higher among the COVID-19 positive STEMI patients compared with COVID-19 negative STEMI cases (27.1% vs 20.7% p value = 0.01); though mortality rate did not differ significantly (8.0% vs 5.8% p value = 0.13). Significantly lower proportion of COVID-19 positive STEMI patients received reperfusion treatment and primary PCI (60.7% vs 71.1% p value=< 0.001 and 15.4% vs 23.4% p value = 0.001 respectively). Rate of systematic early PCI (pharmaco-invasive treatment) was significantly lower in the COVID-19 positive group compared with COVID-19 negative group. There was no difference in the prevalence of high thrombus burden (14.5% and 12.0% p value = 0.55 among COVID-19 positive and negative patients respectively) CONCLUSIONS: In this large registry of STEMI patients, we did not find significant excess in in-hospital mortality among COVID-19 co-infected patients compared with non-infected patients despite lower rate of primary PCI and reperfusion treatment, though composite of in-hospital mortality, re-infarction, stroke and heart failure was higher., (Copyright © 2023 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Background: A wide range of insect-specific viruses (ISVs) have been reported worldwide. There are no studies from India that have reported ISVs. The current study describes the identification of Phasi Charoen-like virus (PCLV) from Aedes aegypti mosquito-pools from six districts of Karnataka state, India. Materials and Methods: During the Chikungunya virus (CHIKV) outbreak in the Bangalore Urban district in 2019, using conventional PCR, it was found that both human and mosquito samples were positive for CHIKV. For retrieve the complete genome sequence, mosquito samples were subjected to next generation sequencing (NGS) analysis and PCLV was also found. During 2019, as part of a vector-borne disease surveillance, we received 50 mosquito pool samples from 6 districts of the state, all of them were subjected to NGS to identify PCLV. Results: The A. aegypti mosquito-pools samples were subjected to the NGS platform that led to identification of an ISV, PCLV. PCLV was identified in 26 A. aegypti mosquito-pools collected from 6 districts. We also found mixed infection of PCLV with the Dengue virus (DENV; genotypes 1 and 3) and CHIKV from five pools. The nucleotide identity for the L gene of Indian PCLV sequences ranged between 97.1% and 98.3% in comparison with the Thailand sequences. Conclusions: To the best of our knowledge, this is the first report of PCLV dual infection with DENV and CHIKV in India. The present study confirms the presence of PCLV in A. aegypti mosquitoes from Karnataka state. The study adds India in the global geographical distribution of PCLV.

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.

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.

Accordion effect or concertina effect - also known as "crumpled coronary" - is an uncommon occurrence during coronary angioplasty. It usually has no major clinical sequelae and should be differentiated from spasm, dissection, and thrombosis, which require special management.

Background and Objectives: Idiopathic pulmonary arterial hypertension (IPAH) is rare disorder of unknown aetiology associated with poor survival. Disease severity assessment by various prognostic factors play important role in management of these patients. The aim of our study was to assess various factors and their natural history and course of disease in Indian population., Material and Methods: We followed 27 patients of IPAH after complete work up of exclusion of other causes of pulmonary hypertension and analysed various demographic, echocardiographic and haemodynamic parameters and their correlation with mortality., Results: A total of 27 patients (14 new and 13 previously diagnosed) were followed for mean duration of 18 months. At time of data analysis, 11 patients were alive and 16 patients died with overall mortality rate of 59.25%. Among various factors, presence of pericardial effusion (p=0.005), pulmonary artery acceleration time (PAAT) (p = 0.005), tricuspid Annular Plane Systolic Excursion (TAPSE) (p = 0.0004), heart rate (p=0.031), mean blood pressure (p =0.017), right atrial pressure (p=0.045), mean pulmonary artery pressure (PAP) (p=0.039) and six minute walk distance (p= 0.0002) were significantly associated with mortality. On multivariate cox proportional hazard analysis, PAAT (p =0.034), TAPSE (p=0.003) and six minute walk distance (p=0.002) remained significant predictors of mortality., Conclusion: Idiopathic pulmonary arterial hypertension is associated with poor prognosis and survival despite advancements of disease specific therapies. Higher mortality in our study is due to delayed presentation and diagnosis. Also lack of availability of prostacyclins and lung transplantation in advanced stages of disease contribute to higher mortality in Indian setup. Non-invasive echocardiographic factors and six minute walk distance are important prognostic factors that help in disease severity stratification to identify patients in need of intensive medical management., (© Journal of the Association of Physicians of India 2011.)

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 (NPEV) are one of the known causative agents of Acute Flaccid Paralysis (AFP). In the present study, we identified, sequenced and characterized the complete genome of sixty-five Coxsackievirus-A10, an NPEV. These were isolated from stool specimens of AFP cases from Bihar, Karnataka, Kerala, and Uttar Pradesh (UP) states of India. Evolutionary analysis of complete genome (7420 nucleotides) and VP1 gene (894 nucleotides) demonstrates that there are four different intra-typic strains circulating in India which were dissimilar to Chinese strains. First intratypic strain circulating in UP, Bihar, and Karnataka; second in UP and Karnataka; third in UP and Bihar and; fourth was restricted only to Kerala state. The divergence of Kerala strain with respect to all other circulating strain of UP, Bihar and Karnataka states in India is 24%, 24.9%, and 24.4% respectively. Recombinations were observed between few of these strains which might be one of the factors of the observed intra-typic diversity. ARTICLE SUMMARY LINE: We report the identification, characterization and phylogenetic analysis of sixty-five Non-Polio Enterovirus (NPEV) isolates, performed during the year 2009-17, causing acute flaccid paralysis in pediatric cases with their divergences and recombinations from four states of India., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Competing Interests: There are no conflicts of interest.

Background: The aims of the study were to assess the right ventricular (RV) functions in patients with idiopathic pulmonary arterial hypertension (IPAH) with RV longitudinal strain (RVLS) in addition to conventional parameters, as well as its correlation with severity and prognosis in IPAH., Methods: Twenty-two IPAH patients were followed up for 1 year. ANOVA and Gabriel's pairwise comparison tests were used for comparison of RVLS with respect to WHO functional class status. Patients were divided into non-survival (group 1) and survival (group 2), and clinical and echocardiographic parameters of RV function were compared at baseline and at 6 months with t -test & Mann-Whitney test., Results: At baseline, with respect to WHO functional class, mean RVLS showed no significant interclass difference (P = 0.0781). Among the other conventional echocardiographic parameters, RV E/A showed significant difference at baseline (P = 0.004), but not at 6 months (P = 0.366); whereas tricuspid annular plane systolic excursion (TAPSE) which had no significant difference initially (P = 0.174) revealed a significance level at 6 months (P = 0.029) between the two groups. Fractional area change (FAC), RV index of myocardial performance (RIMP), and right atrial (RA) area displayed significant difference neither at baseline nor at 6 months. RVLS exhibited significant difference neither at baseline (P = 0.912) nor at 6 months (P = 0.181). None of the echocardiographic parameters including RVLS showed a significant average change with change in severity of PAH both at 6 and 12 months., Conclusion: RVLS was not proved to be a useful parameter for early detection of RV dysfunction and prognosis in patients with IPAH in comparison with the conventional echocardiographic parameters.

Comparing photoconductivity measurements, using p-n diodes formed along individual single-walled carbon nanotubes (SWNT), with modeling results, allows determination of the quantum efficiency, optical capture cross section, and oscillator strength of the first (E11) and second (E22) excitonic transitions of SWNTs. This is in the infrared region of the spectrum, where little experimental work on SWNT optical absorption has been reported to date. We estimate quantum efficiency (η) ~1-5% and provide a correlation of η, capture cross section, and oscillator strength for E11 and E22 with nanotube diameter. This study uses the spectral weight of the exciton resonances as the determining parameter in optical measurements.

Inhibitors based on a benzo-fused spirocyclic oxazepine scaffold were discovered for stearoyl-coenzyme A (CoA) desaturase 1 (SCD1) and subsequently optimized to potent compounds with favorable pharmacokinetic profiles and in vivo efficacy in reducing the desaturation index in a mouse model. Initial optimization revealed potency preferences for the oxazepine core and benzylic positions, while substituents on the piperidine portions were more tolerant and allowed for tuning of potency and PK properties. After preparation and testing of a range of functional groups on the piperidine nitrogen, three classes of analogs were identified with single digit nanomolar potency: glycine amides, heterocycle-linked amides, and thiazoles. Responding to concerns about target localization and potential mechanism-based side effects, an initial effort was also made to improve liver concentration in an available rat PK model. An advanced compound 17m with a 5-carboxy-2-thiazole substructure appended to the spirocyclic piperidine scaffold was developed which satisfied the in vitro and in vivo requirements for more detailed studies., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

E-readers provide an opportunity for hospital librarians to reach out to staff and patients with new approaches to library lending. Librarians in four Veterans Health Administration medical centers are using e-readers to enlarge their scope of service in unique ways. The libraries of VA hospitals in Minneapolis, Des Moines, Tampa, and Philadelphia have developed several ways to reach out to new library users.

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.

Torsades de pointes (TdP) or polymorphic ventricular tachycardia owing to drug-induced QT prolongation is a common cause of withdrawal of marketed drugs and has caused increasing concern in the recent past. Carbimazole, the common antithyroid drug, is not a very well-known offender to cause QT prolongation and TdP. Only a few cases of carbimazole-induced TdP have been reported so far. We report a 53-year-old woman who was on tab. carbimazole (10 mg) twice daily for one month and who presented with respiratory distress, palpitation and syncope attack. Her surface electrocardiogram (ECG) was showing the evidence of TdP and subsequently hypokalemia was also detected. She received conservative management including potassium supplementation. However, QT prolongation persisted even after normalization of serum potassium level. Carbimazole was withdrawn and the patient was discharged as she remained stable and symptom free. This study highlights a possible association between carbimazole and TdP.

Aims and Objectives: To investigate the potential role of a simple insulin resistance index i.e. Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) in identifying insulin resistance in patients admitted with an acute coronary syndrome without diabetes mellitus and its effect on short term outcome on cardiovascular morbidity and mortality., Methods: Seventy non-diabetic patients with impaired fasting glucose admitted with a diagnosis of acute myocardial infarction and followed prospectively for a median of six months for outcomes. Admission fasting glucose and insulin concentrations were measured and from these values an Insulin Resistance index was calculated., Results: During hospital course a high incidence of heart failure (11/;29 vs5/;41; p<0.05) and mortality (4/29 vs 1/41; p=0.152) was seen in patients with Index > 2 as compared to patients with Index <2, but mortality data failed to show any statistical significance because of small sample size. At six months patients with Index >2 had high incidence of heart failure (9/25 vs 4/40; p<0.020), reinfarct (2/25 vs. 0; p=0.141), repeated admissions (7/25 vs 3/40; p=0.092) and mortality (1/25 vs 1/40; p=0.181). Six out of twenty-five (p<0.001) patients with Index > 2 required antidiabetic treatment to achieve glycemic control., Conclusions: A simple index of insulin resistance (Homeostatic Model Assessment-Insulin Resistance) measured on patients admitted with myocardial infarction provides an important predictive measure of poor outcome and is superior to admission glucose measurement. It may be useful in identifying patients admitted with myocardial infarction who could benefit from alternative early invasive strategies.

Anginal symptoms are less predictive of abnormal coronary anatomy in women. The diagnostic accuracy of exercise treadmill test for obstructive coronary artery disease is less in young and middle aged women. High sensitive C-reactive protein has shown a strong and consistent relationship to the risk of incident cardiovascular events. Carotid intima media thickness is a non-invasive marker of atherosclerosis burden and also predicts prognosis in patients with coronary artery disease. We investigated whether incorporation of high sensitive C-reactive protein and carotid intima media thickness along with exercise stress results improved the predictive accuracy in perimenopausal non-diabetic women subset. Fifty perimenopausal non-diabetic patients (age 45 +/- 7 years) presenting with typical angina were subjected to treadmill test (Bruce protocol). Also carotid artery images at both sides of neck were acquired by B-mode ultrasound and carotid intima media thickness were measured. High sensitive C-reactive protein was measured. Of 50 patients, 22 had a positive exercise stress result. Coronary angiography done in all 50 patients revealed coronary artery disease in 10 patients with positive exercise stress result and in 4 patients with negative exercise stress result. Treadmill exercise stress test had a sensitivity of 71.4%, specificity of 66.7% and a negative predictive accuracy of 85.7% in this study group. High sensitive C-reactive protein in patients with documented coronary artery disease was not significantly different from those without coronary artery disease (4.8 +/- 0.9 mg/l versus 3.9 +/- 1.7 mg/l, p=NS). Also carotid intima media thickness was not significantly different between either of the groups with coronary artery disease positivity and negativity respectively (left: 1.25 +/- 0.55 versus 1.20 +/- 0.51 mm, p=NS; right:1.18 +/- 0.54 versus 1.15 +/- 0.41 mm, p=NS). High sensitive C-reactive protein and carotid intima media thickness were not helpful in further adding to the predictability of coronary artery disease in perimenopausal patients with typical angina as assessed by treadmill exercise stress test.

Monkey studies were conducted for the preclinical safety assessment of SCH 412499, an adenovirus encoding p21, administered by subconjunctival injection prior to trabeculectomy for postoperative maintenance of the surgical opening. Biodistribution of SCH 412499 was minimal and there was no systemic toxicity. Findings included swollen, partially closed or shut eye(s) and transient congestion in the conjunctiva. A mononuclear cell infiltrate was present in the conjunctiva, choroid and other ocular tissues, but completely or partially resolved over time. Electroretinograms and visual evoked potentials revealed no adverse findings. Thus, the findings are not expected to preclude the clinical investigation of SCH 412499.

Mononuclear cell infiltrate (MCI) in the uvea was observed in naïve, untreated (control group) cynomolgus monkeys in approximately 25% of drug safety evaluation studies. The total incidence of MCI in the choroid and the ciliary body was 29% of 342 males and 25% of 306 female monkeys. In the studies in which MCI was present in the ciliary body or choroid, the incidence was as high as 75%. There were no other ocular histopathologic findings in these monkeys. All monkeys were clinically healthy and the eyes were not remarkable when examined ophthalmoscopically.

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.

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.

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.

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.

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.

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.

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.

Implantation of a permanent pacemaker is an expensive proposition for the poor patients of our country. Many patients on permanent pacemaker die prematurely due to diseases or conditions not related to pacemaker function. The purpose of this study was to reuse these pacemakers after thorough cleansing and proper sterilisation in other suitable patients and compare the efficiency of the reused pacemakers with that of newly implanted ones. Between April 1979 and April 1992, 642 patients implanted with reused pacemakers were studied. The study population consisted of patients ranging in age from 15-85 years and included patients of both sexes (M:F = 4:1). The mean period of follow-up was 7.5 +/- 5.6 years. Removal and reimplantation of the pulse generators was carried out after obtaining the State Government's approval, informed consent of the donors, relatives and recipients. The functional status of the pulse generators was tested by a "pacing system analyser". The clinical indications for reuse were chronic complete heart block, symptomatic bifascicular heart block, sick sinus syndrome and chronic complete heart block with congestive heart failure, in decreasing order of frequency. In terms of morbidity and mortality, the efficacy of reused pacemakers was highly comparable with that of newly implanted ones. The infection rate in cases of reuse from dead patients was comparable to that in cases of new implantation. However, pacemakers reused in the same patient showed a high rate of infection. With the aid of newer generations of antimicrobials, infection when matched with efficacy and economy (of reuse) does not seem to be a major factor against pacemaker reuse.

Haemodynamic assessment was done by colour flow mapping and Doppler interrogation by both Transthoracic (TTE) and Transesophageal echocardiography (TEE) in 40 consecutive patients (mean age 36.6 +/- 12.35 years) with prosthetic valves. There were 30 cases of mitral (MVR) and 12 aortic (AVR) valve replacement. Major purpose of the study was to detect the sensitivity of TEE in detecting prosthetic valve malfunction particularly in comparison to TTE. Pannus was detected in 3 and 8 cases of MVR (p < 0.01) by TTE and TEE respectively; however, TEE was found to be of equal status in detecting pannus over AV (2 cases). Physiological regurgitation in MVR and AVR was detected in 13% and 25% by TTE and 20% and 33% by TEE respectively. Paravalvular leak was detected in 3 cases of MVR by TEE compared to only case by TTE. Though it is difficult to deduce any specific conclusion from this small number of patients, there is definite trend to higher sensitivity in detecting disorders with TEE specially for mitral prostheses.

Countries of the English-speaking Caribbean are in epidemiological transition. Following 30 years of socioeconomic change, obesity and chronic diseases have almost replaced malnutrition and infectious diseases as major health problems. Major risk factors for this modern epidemic are lifestyle-related. Project Lifestyle seeks to develop positive health lifestyles in schoolchildren gradually, sequentially, and systematically from grades 1-12 and throughout the school system on the island of Antigua. The four health habits addressed include weighing right, eating right, doing daily physical exercise, and having a positive self-concept. Since risk interventions with schoolchildren have produced positive results in several developed countries, this project developed an intervention methodology in the Caribbean context.

In a 3-month oral toxicity study of a pharmaceutical agent, intranuclear inclusions were seen in the secretory cells of the pars anterior of the pituitary gland of 22 of 40 cynomolgus monkeys, with similar incidences in control and dosed groups. All monkeys were clinically healthy. Electron microscopic examination revealed that the intranuclear inclusions were cytoplasmic invaginations.