Biomedical subjects
Publications and source records attributed to S Shankar.
Myxomas are benign soft tissue neoplasms, which usually involve the heart, skin and subcutaneous tissues, and rarely the ocular adnexa. We present a rare case of orbital myxoma with magnetic resonance imaging (MRI) findings and a review of the literature.
Two radiolabeled analogues of 6-benzyloxy-9H-purin-2-ylamine (O(6)-benzylguanine; BG) potentially useful in the in vivo mapping of O(6)-alkylguanine-DNA alkyltransferase (AGT) were synthesized. Fluorine-18 labeling of the known 6-(4-fluoro-benzyloxy)-9H-purin-2-ylamine (FBG; 6) was accomplished by the condensation of 4-[(18)F]fluorobenzyl alcohol with 2-aminopurin-6-yltrimethylammonium chloride (4) or 2-amino-6-chloropurine in average decay-corrected radiochemical yields of 40 and 25%, respectively. Unlabeled 6-(3-iodo-benzyloxy)-9H-purin-2-ylamine (IBG; 7) was prepared from 4 and 3-iodobenzyl alcohol. Radioiodination of 9, prepared from 7 in two steps, and subsequent deprotection gave [(131)I]7 in about 70% overall radiochemical yield. The IC(50) values for the inactivation of AGT from CHO cells transfected with pCMV-AGT were 15 nM for IBG and 50 nM for FBG. The binding of [(18)F]6 and [(131)I]7 to purified AGT was specific and saturable with both exhibiting similar IC(50) values (5-6 microM).
With the goal of developing MIBG analogues with improved targeting properties especially for oncologic applications, several radioiodinated ring- and side-chain-substituted MIBG analogues were synthesized. Except for 3-[(131)I]iodo-4-nitrobenzylguanidine and N-hydroxy-3-[(131)I]iodobenzylguanidine, the radioiodinated analogues were prepared at no-carrier-added levels from their respective tin precursors. The radiochemical yields generally were in the range of 70-90% except for 3-amino-5-[(131)I]iodobenzylguanidine for which a radiochemical yield of about 40% was obtained. While the silicon precursor N(1),N(2)-bis(tert-butyloxycarbonyl)-N(1)-(4-nitro-3-trimethylsilylbenzyl)guanidine did not yield 3-[(131)I]iodo-4-nitrobenzylguanidine, its deprotected derivative, N(1)-(4-nitro-3-trimethylsilylbenzyl)guanidine was radioiodinated in a modest yield of 20% providing 3-[(131)I]iodo-4-nitrobenzylguanidine. Exchange radioiodination of 3-iodo-4-nitrobenzylguanidine gave 3-[(131)I]iodo-4-nitrobenzylguanidine in 80% radiochemical yield. No-carrier-added [(131)I]NHIBG was prepared from its silicon precursor N(1)-hydroxy-N(3)-(3-trimethylsilylbenzyl)guanidine in 85% radiochemical yield.
A number of ring- and side-chain-substituted m-iodobenzylguanidine analogues were evaluated for their lipophilicity, in vitro stability, uptake by SK-N-SH human neuroblastoma cells in vitro, and biodistribution in normal mice. As expected, the lipophilicity of m-iodobenzylguanidine increased when a halogen was introduced onto the ring and decreased with the addition of polar hydroxyl, amino, and nitro substitutents. Most of the derivatives showed reasonable stability up to 24 h in PBS at 37 degrees C. While N(1)-hydroxy-N(3)-3-[(131)I]iodobenzylguanidine and 3,4-dihydroxy-5-[(131)I]iodobenzylguanidine generated a more nonpolar product in addition to the free iodide, 3-[(131)I]iodo-4-nitrobenzylguanidine decomposed to a product more polar than the parent compound. The specific uptake of 4-chloro-3-[(131)I]iodobenzylguanidine, 3-[(131)I]iodo-4-nitrobenzylguanidine, and N(1)-hydroxy-N(3)-3-[(131)I]iodobenzylguanidine by SK-N-SH human neuroblastoma cells in vitro, relative to that of m-[(125)I]iodobenzylguanidine, was 117 +/- 10%, 50 +/- 4%, and 12 +/- 2%, respectively. The specific uptake of the known m-iodobenzylguanidine analogues 4-hydroxy-3-[(131)I]iodobenzylguanidine and 4-amino-3-[(131)I]iodobenzylguanidine was 80 +/- 4% and 66 +/- 4%, respectively. None of the other m-iodobenzylguanidine derivatives showed any significant specific uptake by SK-N-SH cells. Heart uptake of 4-chloro-3-[(131)I]iodobenzylguanidine in normal mice was higher than that of m-[(125)I]iodobenzylguanidine at later time points (11 +/- 1% ID/g versus 3 +/- 1% ID/g at 24 h; p < 0.05) while uptake of 3-[(131)I]iodo-4-nitrobenzylguanidine and of N(1)-hydroxy-N(3)-3-[(131)I]iodobenzylguanidine in the heart was lower than that of m-iodobenzylguanidine at all time points. In accordance with the in vitro results, none of the other novel m-iodobenzylguanidine derivatives showed any significant myocardial or adrenal uptake in vivo.
OBJECTIVES: Atherosclerosis has emerged as an important late complication of systemic lupus erythematosus (SLE). Asian Indians, as an ethnic group, are known to be metabolically predisposed to development of early atherosclerosis. No data on this aspect of SLE are available from Asia. This study was undertaken to find the frequency of atherosclerosis in Indian lupus patients and the factors affecting such an occurrence. METHODS: Carotid artery intimo-medial thickness (IMT) and plaque were used as markers of atherosclerosis. High-resolution B-mode ultrasonography was used to compare carotid IMT and plaque in 50 patients with SLE and 50 age- and sex-matched healthy controls. RESULTS: Patients with lupus (age 31.6+/-10.05, median 30.5 years; disease duration 52.3+/-36.7, median 46 months) exhibited a significantly greater IMT than controls (0.417+/-0.07 vs. 0.362+/-00.07 mm; p = 0.003). Carotid plaques were seen in seven (14%) cases. None of the control population had plaques (p = 0.006). On bivariate analysis, the IMT was significantly affected by age, systolic blood pressure (SBP), disease duration and menopausal status. On multivariate analysis, the only factor significantly affecting IMT was SBP. The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) score was the sole factor found to significantly affect the occurrence of plaque. CONCLUSIONS: Asian Indian lupus patients in our study, despite being relatively young and with shorter disease duration, exhibited premature atherosclerosis in the form of significantly thicker intimo-media and plaque. The factors found to affect accelerated atherosclerosis in our cohort were age, SBP, disease duration, postmenopausal status and the SLICC/ACR score.
This study assessed cancer knowledge, beliefs, and awareness of signs, symptoms, and early detection methods in immigrant Salvadorean women in the Washington, D.C. metropolitan area (DCMA). A face-to-face survey sampled 843 females aged 20 and above. Descriptive statistics were used to compute frequency of response for sociodemographic characteristics, beliefs, and awareness of signs, symptoms, and early detection methods. The sample's mean age was 34.5 years; 10% had no schooling, and 7.4% had more than a high school education. Sixty-six percent of the women worked full- or part-time; 16% had an annual income of $20,000 or more; and 26% reported having medical insurance. Thirty percent of the sample lacked knowledge of the etiology and spread of cancer. The statement, "Bumps on your body can cause cancer" was endorsed by 61.6%. Beliefs that "destiny cannot be changed" or "just about anything can cause cancer" were prevalent among 18.5%. "Cancer is a punishment from God" was believed by 10.9%. A general physical examination was the most frequent (82%) early detection method mentioned. The Pap test was identified by 24.2%, and mammography by 14%; 5.6% mentioned breast self examination. Similar to other Hispanics, immigrant Salvadorean women in DCMA demonstrated a lack of knowledge of cancer's signs and symptoms, and early detection methods of and beliefs about cancer. Educational programs designed specifically for immigrant Salvadorean women to increase their knowledge of cancer and prevention methods are essential.
BACKGROUND AND PURPOSE: An increased incidence of intestinal helminthic infections has been observed in patients with viral encephalitis in endemic areas. Both Japanese B encephalitis (JE) and neurocysticercosis (NCC) share some common socio-demographic and ecologic factors, and pigs act as the intermediate carrier for both. Our purpose was to show the coexistence of JE and NCC in brain on MR images and highlight the possible role of NCC as an amplifier of JE. METHODS: MR images from 10 cases of coexistent JE and NCC were studied retrospectively. T1-weighted axial and sagittal, proton T2-weighted axial and coronal, and T2-weighted fluid-attenuated inversion recovery axial and coronal sections of the brain were evaluated. NCC was diagnosed on the basis of neuroimaging. Diagnostic serologic testing for JE was conducted using paired blood and CSF samples. RESULTS: The JE changes were bilateral and asymmetrical and were more severe on the side harboring the solitary cyst or the side bearing the greater number of cysts or lodging the degenerating cyst. In each of nine of 10 cases, at least one degenerating cyst was found on the side of predominant JE pathologic abnormality. CONCLUSION: The study suggests that the co-occurrence of JE and NCC is not just a chance coincidence. NCC apparently predisposes a person to JE infection and is a positive modulator of the encephalitic process. The study shows a spectrum of MR imaging findings of coexistent JE and NCC.
Rheumatoid arthritis (RA) is the commonest inflammatory joint disease with considerable morbidity and mortality. Conventional disease-modifying antirheumatic drugs like methotrexate form the cornerstone of therapy. However, they have several limitations in terms of slow onset of action, adverse effects and modest remission and retention rates. Several cytokines are involved in the pathogenesis of RA. Biological agents that specifically inhibit the effects of tumour necrosis factor-a (TNF-a) or Interleukin-1 (IL-1) represent a major advancement in the treatment of RA. By targeting molecules that are directly involved in the pathogenesis of RA, these therapies are proving to be efficacious, highly specific and better tolerated than standard therapies. The use of these agents needs to be monitored carefully for possible side-effects, including the development of infections. Additional anti-cytokine agents for the treatment of RA are under further development.
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