Clinical exome sequencing unravels the diverse spectrum of genetic heterogeneity and genotype-phenotype correlations in hypertrophic cardiomyopathy.

BACKGROUND: Catalogues of pathogenic genetic mutations in hypertrophic cardiomyopathy (HCM) are disproportionately small when compared to that of the size of the population with South Asian ancestry and their collective increased risk of heart disease. METHODS: We conducted clinical exome sequencing of 200 HCM patients to identified cardiomyopathy-associated genetic mutations. The clinical and echocardiographic characteristics of genotype-positive and genotype-negative patients were compared, and the likelihood of detecting a positive genetic test result was evaluated. Allelic burden analysis was done to compare the minor allele frequencies (MAF) of the pathogenic or likely pathogenic (P/LP) variants and variants of uncertain significance (VUSs) identified in the cohort against various population genomics databases. RESULTS: The genetic yield was 40% for P/LP variants, with MYBPC3 and MYH7 as the predominant sarcomere genes. Younger age-at-diagnosis, family history of HCM, asymmetric hypertrophic (ASH) pattern, the ratio of the interventricular septum to posterior wall thickness (IVS/PW ratio), left atrial (LA) dimensions, severe mitral regurgitation grade (MR grade), late gadolinium enhancement (LGE) detected fibrosis and absence of hypertension were associated with an increased likelihood of HCM-associated variants. Patients who experienced ventricular tachycardia and premature cardiovascular death were significantly likely to carry MYBPC3 or loss-of-function variants. LA and interventricular septal (IVS) dimensions were associated with MYH7 variants. The rare variant burden for P/LP variants and VUSs was significantly enriched in HCM cases compared to population controls. CONCLUSION: Our study provides a comprehensive evaluation of HCM-associated genetic mutations from an Indian population. The identified genotype-phenotype associations could improve the yield of targeted genetic testing in HCM.

Linear lesions in dermatology: a clinicoaetiopathological study.

BACKGROUND: Linear lesions are fairly common in our daily practice. However, the appearance of these lesions can vary, thus complicating the diagnosis. AIMS: To study the various clinical presentations, the demographic profile of patients and the clinicopathological correlations of dermatoses presenting with a linear distribution. METHODS: We conducted an institution-based, cross-sectional, descriptive study of 281 consecutive patients with linear lesions attending dermatology clinics. MedCalc software (V11.6) was used for statistical analysis. RESULTS: Patients were divided into eight groups: lesions along the lines of Blaschko (n = 136), lesions along blood vessels (n = 3), lesions along lymphatics (n = 3), Koebner phenomenon (n = 24), autoinoculation (n = 24), external factors (n = 45), infestations (n = 2) and 'other' (n = 44). The mean age at presentation was 24.50 ± 18.82 years and the male/female ratio was 1.32 : 1. The commonest symptom was itching/burning (56.94% of patients), while the commonest site was the arm (44.48%); followed by the leg (30.60%), trunk and abdomen (22.42%), head and neck (19.20%), and genitalia (0.35%). Apart from the common cases, there was a wide gamut of rare conditions (e.g. angiokeratoma circumscriptum naeviforme, porokeratotic eccrine ostial and dermal duct naevus, Blaschko-linear syringocystadenoma papilliferum, progressive cribriform and zosteriform hyperpigmentation, unilateral naevoid acanthosis nigricans, fixed drug eruption, discoid lupus erythematosus). CONCLUSION: Linear lesions act as diagnostic clues to many dermatological conditions, therefore, the importance of meticulous examination in clinical dermatology cannot be overemphasized.

Catheter-related blood stream infections: prevalence, risk factors and antimicrobial resistance pattern.

BACKGROUND: Intravascular devices have significant potential for producing iatrogenic diseases resulting in catheter-related blood stream infections (CRBSIs). A study was undertaken to find the prevalence of CRBSI among patients in acute wards and to analyze the associated risk factors, causative pathogens with their antibiotic susceptibility (ABST) patterns. METHODS: Randomly ten days per month were chosen, for a period of two years. All the acute wards patients who were on indwelling blood catheters were identified. Those fulfilling the CRBSI criteria were further worked up for confirmation of diagnosis by differential time to positivity. The catheter tip was cultured by Maki's semiquantitative method. ABST of the isolates obtained was performed by Kirby-Bauer disk diffusion method. RESULTS: The prevalence of CRBSI was found to be 39.25% with the most common organism isolate being Serratia marcescens (23.81%). The immunocompromised status of the patients and catheterisation time were significant risk factors. Methicillin resistance was found to be 33.33% in coagulase-negative staphylococci. The resistance to vancomycin among the Entercoccus faecium isolates was found to be 33.33%. Among the gram negatives, resistance to aminoglycosides, fluoroquinolones and third-generation cephalosporins was high. CONCLUSION: The study highlights the importance of regular surveillance programs, an efficient infection control program, strict adherence to antiseptic measures and use of a rational antibiotic policy for the early diagnosis and better management of CRBSI.

Drug sensitivity pattern of various Staphylococcus species isolated at a tertiary care hospital.

BACKGROUND: Staphylococcus aureus and other Staphylococcus species are important pathogenic organisms and are responsible for various hospital infections. These are the predominant organisms found in pus and blood culture isolates. Infections arising due to these bacterial isolates are difficult to treat because of developing multidrug resistance. METHODS: Over a 1-year period at a tertiary care hospital laboratory, 524 Staphylococci species were isolated from pus, blood and urine samples and species-level identification was done. RESULTS: S. aureus formed the predominant species (70.8%) followed by coagulase-negative Staphylococcus (CoNS) (29.20%). S. aureus (91%) was the main isolate from pus samples; however, CoNS was isolated in equally higher proportion in blood culture (63.58%). Among the CoNS, Staphylococcus hemolyticus was the main isolate (9.3%). ß-Lactamase production, alteration of PBP and MLSB resistance were seen in variable degrees in different species. CONCLUSION: CoNS group of Staphylococci is becoming an important cause of infection at tertiary care centres. The increased multidrug resistance among various Staphylococcus species is a cause of great concern and requires adequate measures to prevent the spread of these microorganisms in the hospital and the community.

Density functional theory study of the effect of helium clusters on tritium-containing palladium lattices.

Density functional theory (DFT) calculations have been employed to calculate the energetics, structures and migration behaviour of helium in palladium tritides. Increasing the tritium concentration in palladium leads to a decrease in the formation energies of helium clusters, indicating that He clusters can form in the lattices. The calculated results show less lattice expansion in Pd defect-containing lattices compared to the perfect lattice owing to smaller lattice distortions. The lowest energy migration path for helium diffusion is along octahedral-tetrahedral-octahedral sites but the energy barrier increases with increasing tritium concentration. Repulsive interactions occur between Pd d and He s orbitals, suggesting that displacement of the metal atoms in the lattice leads to growth of pressure inside the lattices. This process may change the microstructural properties leading to the degradation of the material.

Transvaginal sonography versus hysteroscopy in evaluation of abnormal uterine bleeding.

BACKGROUND: Abnormal uterine bleeding (AUB) accounts for 33% of female patients referred to gynaecologists. Common causes of AUB include endometrial polyps, endometrial hyperplasia, submucous fibroids and anovulation. Accurate diagnosis of the cause of AUB can reduce the frequency of hysterectomy. This study was aimed at assessing the usefulness of TVS in comparison with hysteroscopy in AUB evaluation. METHODS: 100 female patients with AUB were enrolled in the study. Each patient was subjected to TVS where uterine cavity was studied in detail and hysteroscopy under anaesthesia using saline as distension medium. Sensitivity, specificity and predictive value of TVS as compared to hysteroscopy were calculated. Subgroup analysis within each group was also performed. RESULTS: Menorrhagia was the commonest presenting symptom in the study population (n = 58) followed by metrorrhagia, menometrorrhagia and continuous bleeding >21 days. 74 female patients had normal size uterus. In 57 patients, the uterine cavity was normal on TVS. Thickened endometrium, endometrial polyp and submucous fibroids were seen in 19, 16 and 6 patients respectively. Hysteroscopy showed normal cavity in 59 female patients and polypoidal endometrium, polyps or submucous fibroids in 41. TVS was found to have high sensitivity and specificity (95.23 and 94.82 respectively) and high positive and negative predictive value. Strength of agreement between TVS and hysteroscopy was high (kappa value 0.898). CONCLUSION: TVS is recommended as first line investigation in AUB. If TVS shows normal cavity, further evaluation can be omitted and patient started directly on medical treatment for her symptoms.

A rare case of gangrenous appendicitis by eggs of Taenia species.

Cysticercosis and Taeniasis continue to be a major public health burden in the developing countries like India. Humans are the only definitive hosts infected by ingestion of eggs of Taenia species. Appendicular Taeniasis is rare with few isolated case reports during the past 30 years. Here, we report the case of a 38-year-old female patient from Nepal who presented with acute pain abdomen, was operated and diagnosed as suffering from gangrenous appendicitis caused by eggs of Taenia species.

Adolescent lumbar disc disease: findings and outcome.

BACKGROUND: Lumbar disc herniation is mainly a disease of elderly people as degenerative changes progress with age. RESULTS AND DISCUSSION: Present retrospective analysis was performed on 742 patients of lumbar disc disease operated over 11 years. Of 742 cases aged 20 years or less, 25 has been evaluated to see the clinical features, radiological features, operative findings, and outcome of lumbar disc surgery. The incidence of lumbar disc herniation in pediatric and adolescent populations was 3.5% (aged 20 years or less). All patients presented with low back pain with or without radiculopathy (n = 25). Diagnosis was easily made on magnetic resonance imaging. Gross degenerative changes in disc and end plates were uncommon (16%) in this population. The trauma may not be a predisposing factor in most of them. In 88% (n = 22) of the cases, only 1 level was affected; the commonest was L4-5 (n = 13). Disc herniation was centrolateral in 72% (n = 18) and central in 28% (n = 7). Disc was mostly soft, hydrated, and rubbery in 92% (n = 23). Disc herniation were subligamentous in 80% (n = 20) and extruded in 4% (n = 1). Sixteen percent (n = 4) of the patients had disc bulge with intact annulus. CONCLUSIONS: Operative intervention in the form of simple discectomy offers good result in 92% (n = 23) cases irrespective of approach and method. Longer follow-up is mandatory because the chances of recurrence or another level involvement cannot be denied.

Reduction of mechanical heart valve thrombosis through a clinical audit.

BACKGROUND AND AIM OF THE STUDY: Patients with mechanical heart valves implanted at four cardiothoracic centers were followed up in a hospital in Eastern India. Despite successful surgery and regular hospital visits, long-term survival was compromised by anticoagulation-related complications. METHODS: Systematic analysis revealed under-anticoagulation in most patients. Thrombosis risk in 80 patients on regular follow up from 1989 to 1997 was 8.68 per 100 patient years (pt-yr). The incidence of both thrombotic and bleeding complications was reported as less than two per 100 pt-yr, when prothrombin time was consistently in the range of INR 2.5 to 3.9. In targeting this low event rate, impediments to optimum anticoagulation in the local set-up were identified. International Normalized Ratio (INR) was introduced to report prothrombin time (PT). Patients and doctors were educated about drug and diet interactions with oral anticoagulants (OAC) and the early features of valve thrombosis. Treatment protocols were evolved. The impact of the remedial measures was studied in 81 patients (64 old, 17 new) over a total of 254 pt-yr of follow up, from 1998 to 2001. RESULTS: Thrombosis risk was reduced from 8.68 to 5.12 per 100 pt-yr, while non-fatal bleeding events increased from 0.28 to 1.96 per 100 pt-yr. Due to early recognition of occlusive prosthetic valve thrombosis and institution of fibrinolytic therapy, fatal events were reduced from 3.8 per 100 pt-yr to none for four consecutive years (statistically significant at 99% CI). CONCLUSION: The clinical audit proved to be a valuable tool for understanding the problems in health care delivery, and bringing about improvement.

Renal artery involvement in patients of coronary artery disease undergoing coronary angiography--a prospective study.

METHODS: We prospectively studied the angiographic incidence of renal artery stenosis in 1000 consecutive patients who underwent coronary angiography for clinically suspected coronary artery disease since December, 1998. Selective renal arteriography was performed in all the patients (mean age 57 years, 74.6% males) after coronary angiography. RESULTS: Systemic arterial hypertension was present in 52%, 29.1% were smokers, 21% had diabetes and 31.2% had hypercholesterolemia. Significant coronary artery diseases was found in 849 (84.9%) patients. Of the total patient cohort, 103 (10.3%) patients had renal artery disease; 78 (7.8%) had insignificant stenosis (> 50%) and significant renal artery stenosis (< 50%) was identified in 25 (2.5%) patients. Three had bilateral renal artery stenosis. Comparisons were made between renal artery stenosis and risk factor profile. There was no statistically significant association between renal artery stenosis and parameters like diabetes mellitus, hypertension, smoking, lipid levels and serum creatinine. CONCLUSION: In our study, the absolute number of cases with significant renal artery stenosis is small, so no statistical analysis could be performed to demonstrate the relationship of presence of renal artery stenosis with severity of CAD. However patients with severe coronary artery disease or having multiple risk factor showed a trend towards increased prevalence of renal artery stenosis, hence renal angiography should be done for this subset of patients.

Coronary stenting without pre-dilatation: an observational study.

Conventional coronary stenting is done after pre-dilatation of the lesion. The bleeding complications and incidence of subacute stent thrombosis have been reduced significantly by the use of antiplatelet agents and high pressure balloon inflation to ensure complete stent expansion. Elective stenting also can be done without pre-dilatation by "stent alone technique." This approach significantly reduces the procedural cost and ischaemia time, avoiding potential complications such as abrupt vessel closure because of extensive dissection after conventional angioplasty and prior to stent deployment. Eighty patients of stable angina pectoris suitable for coronary angioplasty underwent stenting without pre-dilatation. Out of the 100 stents used, 38 were hand-crimped and 62 were pre-mounted. The target vessels were left anterior descending artery in 56 percent, right coronary artery in 32 percent and left circumflex in 12 percent. The procedure was successful in 88 percent lesions. In 12 percent stenting could be done only after pre-dilatation. In all these, there was proximal tortuosity and calcification. The fluoroscopy time was 10.2 +/- 4.5 minutes. The average number of balloons used per lesion was 1.08. Stent embolisation occurred in only one patient. There were no major adverse cardiac events in any of the patients. Thus stenting without pre-dilatation is safe. Patients who are eligible for stenting without pre-dilatation are those with stable angina pectoris without fluoroscopically visible calcium or coronary artery tortuosity and with lesions of moderate complexity.

Coil embolization of a giant atherosclerotic coronary artery aneurysm.

The incidence of the coronary artery aneurysm varies from 1.5-5%. Atherosclerosis is the most common cause of coronary artery aneurysm in adults. A discrete, giant, saccular atherosclerotic coronary artery aneurysm in an artery without significant proximal stenosis is rare. We report the first such case of a giant atherosclerotic coronary artery aneurysm successfully treated with coil embolization.

Balloon mitral valvuloplasty with bifoil catheter: immediate and long-term follow-up results.

This report documents clinical and hemodynamic benefits of balloon mitral valvuloplasty (BMV) using a bifoil balloon catheter from a single center in 415 consecutive cases of rheumatic mitral stenosis (MS). The procedure was successful in 396 (95.2%) patients, with an increase in mitral valve area (MVA) from 0.82+/-0.35 cm2 to 2.21+/-0.24 cm2 (P < 0.001). There were 2 (0.48%) in-hospital deaths, and 6 (1.44%) patients developed acute mitral regurgitation. The procedural and fluroscopy time was reduced significantly from 52+/-11 and 38+/-6 min to 33+/-7 and 19+/-5 min, respectively, after modifications of technique in our last 326 cases. The bifoil balloon catheter technique is safe and effective, and provides excellent hemodynamic benefits which are sustained at long-term follow-up. This technique should be considered as an addition to the existing armamentarium of interventional cardiologists performing mitral balloon valvuloplasty.

A University of California State-supported AIDS research award program--a unique state and university partnership in AIDS research.

This article describes the State-supported University of California AIDS research award program and its major accomplishments. It shows how a partnership between a University and a State resulted in the formation of a successful, efficient, and cost-effective AIDS research award program. This program provides funds for rapid testing of investigator-initiated meritorious research ideas, new drugs, and treatment modalities. Funds were also utilized to establish three AIDS Clinical Research Centers, which evolved into regional consortia that coordinate trials of new drugs and other modalities. This program succeeded in involving investigators whose efforts have led to excellent medical care, advanced technologies, and new drugs for treating AIDS and AIDS-related diseases. The University remains committed to continuing support of all areas of AIDS research, emphasizing drug and vaccine development, pediatric AIDS, and AIDS prevention studies in groups at high risk for HIV infection.

Quantitative evaluation of peer review of program project and center applications in allergy and immunology.

We compared the review patterns of applications for program projects and centers in allergy and immunology, reviewed by the National Institute of Allergy and Infectious Diseases review committee, with those of individual research projects in immunology, reviewed by three Division of Research Grants study sections. A high concordance between these review groups was obtained with respect to the application approval rate, mean score, and distribution of applications in various priority score ranges. Furthermore, we observed a high degree of consensus among reviewers on the quality of many program project and center applications, especially those with priority scores between 100 and 200.

In vitro susceptibility of Escherichia coli of swine origin to carbadox and other antimicrobials.

Swine fecal Escherichia coli isolates were tested with the Microtiter broth dilution method for susceptibility to carbadox and 11 other antimicrobials. Of the 138 strains, 136 were resistant to sulfadiazine, 120 to tetracycline, 95 to streptomycin, and 63 to carbadox. Resistance to the remaining antimicrobials also was noted in various degrees, with the exception of amikacin, to which all strains were susceptible. Carbadox-resistant strains also were resistant to other antimicrobials. The multiple resistance pattern was most common to sulfadiazine and tetracycline or a combination of sulfadiazine, tetracycline, and streptomycin.