Brijesh Sharma

Current status of Takayasu arteritis in India.

The clinical features of 106 patients of Takayasu arteritis (TA) seen over a period of 16 years are documented (65 females and 41 males). The mean age was 27.3 +/- 9.2 years. Hypertension was the commonest mode of presentation (51.3%) and was detected in 82 patients (77.4%) at the time of presentation. Vascular bruits were heard in 72 patients (67.9%) and 13 patients (12.3%) were in congestive heart failure. Aortography was performed in 95 patients. Based on the extent of involvement, Type I (branches of aortic arch) was seen in 7 (6.6%) patients, Type II (aortic arch, its branches and descending thoracic aorta) in 7 (6.6%) patients, Type III (descending thoracic aorta and abdominal aorta) in 4 (3.8%) patients, Type IV (abdominal aorta only) in 29 (27.3%) patients and Type V (aortic arch, descending thoracic aorta and abdominal aorta) in 59 (55.7%) patients. Therapeutic modalities included antihypertensive drug therapy in 81 patients, antitubercular drugs in 8 patients, steroids in 16 patients and cyclophosphamide in one patient. Response to steroids was satisfactory in 5 of these 16 patients while the lesions of vasculitis healed in the patient who was treated with cyclophosphamide. Surgical interventions included nephrectomy and autotransplantation of kidney in 3 patients each and revascularization in 4 patients and angioplasty in 4 patients. In the area of pathogenesis of this disease, a high activity of protein kinase C(PKC), an increased intracellular calcium and inositol 1,4,5 triphosphate in both unstimulated and stimulated T cells of TA was observed. These findings suggest an activation of PKC-calcium pathway in TA.

A follow-up study of balloon angioplasty and de-novo stenting in Takayasu arteritis

Percutaneous balloon angioplasty (PTBA) is a universally accepted mode of therapy for stenotic coronary and peripheral arterial lesions. To establish the role of PTBA and stent placement in patients with Takayasus arteritis (TA), these procedures were performed in 20 patients with TA. All patients received steroids, aspirin and ticlodipine (for stent placement) prior to procedure. Angioplasty was carried in patients with symptomatic stenotic vessel of more than 70% of normal diameter or a peak systolic gradient of more than 50 mm across stenotic aortic lesion. Stenting was performed for ostial lesion, long segment lesion or incomplete relief of stenosis and dissection following angioplasty. Carotid angioplasty and stenting was performed in five patients, aortic angioplasty in nine patients, aortic angioplasty and stenting in four patients, renal angioplasty in three patients, renal angioplasty and stenting in two patients and subclavian angioplasty in two patients, subclavian, angioplasty and stenting in three patients and coronary angioplasty and stent placement in one patient. The procedure was successful in all but one patient. On following up, two patients with carotid stent placement had restenosis. A saccular aneurysm developed at the lower end of stent in one patient with aortic stent placement. The PTBA with or without stent placement is a safe and effective method for relief of stenotic lesion in patients with TA.

Takayasu Arteritis in children and young Indians

Twenty four patients of Takayasu arteritis (TA) aged less than 18 years were studied over a period of 20 years (1978-98). There were 4 males and 20 females with a male:female ratio of 1:5. The mean age of presentation was 14 years and the disease had a mean onset of time 4+/-1.5 months prior to admission to the hospital. Hypertension was the commonest mode of presentation seen in 83% of patients. 16% patients had congestive heart failure. Left ventricular hypertrophy was present in 54% patients. Angiographic findings showed that abdominal aorta was the commonest segment of aorta that was involved (71% cases). Renal artery was involved in 75% cases. Treatment modalities included antihypertensive drugs in 19 patients, antitubercular drugs in 7 patients and steroids in 7 patients. Renal angioplasty was performed in 2 patients with excellent results. On follow up 2 patients died. The causes of mortality were renal failure and heart failure in one patient each. The clinical profile of young patients with TA is similar to that of adults with this disease.

Systemic manifestations of Takayasu arteritis: The expanding spectrum

Takayasu arteritis (TA) is a chronic inflammatory and obliterative disease of large vessels particularly the aorta and its major branches. Recently, the disease has been shown to involve the parenchyma of various organs. Specific glomerular lesions reported in patients with TA are mesangial proliferative, membrano-proliferative, crescentic glomerulonephritis and amyloidosis. Dermatological manifestations of this disease are erythema nodosum, facial lupus rash and erythema induratum. Dilated cardiomyopathy, myocarditis and pericarditis have been reported in TA. Rarely, interstitial lung disease, pneumonic consolidation, idiopathic ulcerative colitis, rheumatoid arthritis and polymyositis have been described in association with TA. In this report, five patients of TA with primary parenchymatous involvement of kidneys, skin, heart and gastrointestinal tract have been described. An association of primary parenchymatous organ involvement and TA suggests an autosensitization to an unidentified antigen in the pathogenesis of TA.

Immunogenetic analysis of Takayasu arteritis in Indian patients

The distribution of HLA-A, B, C and DR antigens was determined in a cohort of 104 unrelated Indian patients with Takayasu arteritis (TA) belonging to the North Indian states of Punjab, Haryana, Uttar Pradesh and Delhi. The data was compared with healthy controls belonging to the same ethnic group. In addition, polymorphism in the MHC class I chain related A (MIC A) gene was studied in a group of 25 TA patients and 40 healthy controls. The data revealed a strong association of the disease with HLA-B5 (chi2=22.5, P<1 x 10(-6), RR=3.08) as well as its two common serological subtypes, B51 (chi2=20.5) and B52 (chi2=18.5). No particular association was observed with any of the five alleles of the MIC A gene, nor any linkage disequilibrium could be established with these alleles and those of HLA-B locus in this population. The observation suggest that HLA linked genes are definitely involved in the development of Takayasu arteritis and that the disease in Indian subjects is associated with HLA-B5 and its two serological subtypes, B51 as well as B52.

Molecular characterization and in vitro antifungal susceptibility of 80 clinical isolates of mucormycetes in Delhi, India.

Mucormycosis is a highly aggressive disease which is usually fatal in immunocompromised patients. The species of mucormycetes show significant differences in susceptibility to amphotericin B, azoles and terbinafine. The precise species level identification for this fungal group could be achieved by internal transcribed‐spacer (ITS) region sequencing. Herein, we present the largest series of antifungal susceptibility data of molecularly characterised isolates of mucormycetes reported so far from India. Eighty isolates originating from 71 patients comprised 50 (62.5%) from pulmonary cases, 15 (19%) from rhino‐orbital‐cerebral, 13 (16.2%) from cutaneous and 2 (2.5%) from disseminated mucormycosis. ITS and D1/D2 regions sequencing of the isolates identified, Rhizopus arrhizus var. delemar (n = 25), R. arrhizus var. arrhizus (n = 15), R. microsporus (n = 17), R. stolonifer (n = 3), Syncephalastrum racemosum (n = 11), Apophysomyces elegans (n = 2), A. variabilis (n = 2), Lichtheimia ramosa (n = 3) and Mucor circinelloides f. lusitanicus (n = 2). Amplified fragment length polymorphism analysis was done to genotype Rhizopus isolates and revealed 5 clusters of R. arrhizus, which were well separated from R. microsporus. Amphotericin B was the most potent antifungal followed by posaconazole, itraconazole and isavuconazole. Etest and CLSI MICs of amphotericin B showed 87% agreement. Overall, the commonest underlying condition was uncontrolled diabetes mellitus. Records of 54 patients revealed fatalities in 28 cases.

Hypertension and insulin resistance in a native unindustrialised rural population of India

A cross-sectional survey of 2964 individuals aged 16-70 years from a rural area of North India was carried out to test the hypothesis that a rural unindustrialised hypertensive population of North India has central obesity and hyperinsulinemia. Oral glucose tolerance test was carried out on 68 newly detected hypertensives, 82 age- and sex-matched community controls and 58 genetically related members of hypertensives (family controls). Fasting blood samples were examined for plasma glucose, serum insulin and lipids. Postglucose-load blood samples were examined for plasma glucose and serum insulin. Three blood pressure readings were recorded using Random Zero Sphygmomanometer. Anthropometric measurements (waist-hip ratio, subscapular and triceps skinfold thickness) of all three groups of individuals (hypertensives, community controls and family controls) were also recorded. The hypertensives had significantly higher fasting and postglucose-load serum insulin levels (P<0.05), body mass index (21.3 vs. 19 kg/m2: P<0.05), waist-hip ratio (0.89 vs. 0.85: P<0.001), subscapular (18.5 mm vs. 12.7 mm: P<0.001) and triceps fold thickness (17.6 mm vs. 12.9 mm: P<0.05) than community controls. The family controls had significantly higher systolic blood pressure than community controls (P<0.05). The lipids were not significantly different in all the three groups. Multiple logistic regression showed that both fasting and postglucose-load serum insulin were significantly associated with hypertension independent of waist-hip ratio and body mass index. The results of the present study suggest that hyperinsulinemia is related to hypertension in a rural unindustrialised population of North India.

Direct role of HLA-B5 in influencing susceptibility to Takayasu Aortoarteritis

To investigate genetic factors involved in the pathogenesis of Takayasu arteritis (TA), North Indian patients belonging to the states of Punjab, Haryana, Uttar Pradesh and Delhi were examined for HLA-class I and class II antigens and the data compared with healthy controls from the same ethnic group. Additionally, DNA typing was performed using polymerase chain reaction/sequence specific oligonucleotide probe (PCR-SSOP) technique to evaluate the distribution of molecular alleles in the healthy Indian population as compared to orientals and Western caucasoids. The frequency of HLA-B5 was significantly increased in patients as compared to controls (chi 2 = 32.5, corrected P value, Pc = 3 x 10(-6), relative risk = 4.3). Serological splitting of B5 into B51 and B52 did not reveal an association with any of the two subtypes. Weak association was also noticed with DR8 in the patient group (chi 2 = 8.2, Pc = 0.05). Distribution of the molecular subtypes of various HLA-B and DR alleles indicated that although the Indian population is essentially caucasoid, it comprises of an admixture of both caucasoid as well as oriental alleles/haplotypes. The observations clearly suggest that (a) HLA-linked genes are involved in the development of Takayasu arteritis, and (b) rather than a subtype of B5, the whole molecule or its closely linked gene(s) influence susceptibility to TA.

Reaction cross-sections for light nuclei on 12C using relativistic mean field formalism

The reaction cross-sections are calculated for various Li, Be and B+12C systems, also involving the exotic halo nuclei, by using both the spherical and deformed relativistic mean field (RMF) densities in the finite range Glauber model with Coulomb effects included. For reactions at higher energies (>500 MeV/nucleon), both the spherical and deformed RMF densities give similar results for all the isotopic chains of exotic nuclei studied here. On the other hand, for reactions between stable nuclei, though the two RMF densities (spherical and deformed) result in simply an overall normalization for the excitation functions, it gives an improved comparison with experimental data, at high and low energies for spherical and deformed densities, respectively. A similar normalization is obtained for other densities, which means to stress that, though densities are different, they do not change much with the excitation energy. Finally, some details of the characteristic properies of exotic light nuclei are shown to contain the deformation effects of the halo nuclei.

Sweet's syndrome in association with myelodysplastic syndrome

No toxicity was encountered during the three courses of GM-CSF treatment, except a low grade fever with a maximum of 38 O C which responded to paracetamol. The patient died 1 month after the last course, from intracerebral bleeding and systemic fungal infection caused by bone marrow aplasia. Bone marrow recovery after a toxic insult appears to depend on available progenitor cells and growth factors. Interestingly, deficiency of growth factors seems to limit bone marrow recovery after regulardose chemotherapy since infusion of exogenous CSFs shortens the duration of aplasia after various chemotherapy regimens and autologous bone marrow transplantation ( 2 , 5 ) . Until now, no exhaustion of bone marrow reserve has been described even after repeated cycles of chemotherapy followed by