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Biomedical subjects

S Bhatia

Publications and source records attributed to S Bhatia.

At least 55 records · Page 3Linked to original sources

Gamma-interferon bioassay for detection of bovine tuberculosis in cattle: kinetics of production and dose response in whole blood culture.

Stimulation with Mycobacterium bovis PPD sensitised lymphocytes (whole blood or peripheral blood lymphocytes) results in release of gamma-interferon that can be detected by simple bioassay. The optimum concentration of bovine PPD was 20 micrograms ml and the optimum incubation period was 24 hr for maximum production of gamma-interferon in whole blood culture (128 units/ml) and peripheral blood culture (64 units/ml).

Animals↗

Modulation of T cell cytokine profiles and peptide-MHC complex availability in vivo by delivery to scavenger receptors via antigen maleylation.

We have previously shown that conversion of proteins to scavenger receptor (SR) ligands by maleylation increases their immunogenicity. We now show that maleyl-Ag-immune spleen cells make relatively more IFN-gamma and less IL-4 or IL-10 than native Ag-immune cells. This is also reflected in the IgG1:IgG2a ratios in Abs generated in vivo. SR engagement on macrophages does not alter their surface levels of the adhesive/costimulatory molecules CD11a/CD18, CD11b/CD18, CD24, CD54, or CD40, nor does it enhance their ability to support anti-CD3-driven proliferation of naive T cells in vitro. Costimulatory molecules implicated in differential Th1/Th2 commitment--CD80, CD86, and IL-12--are not inducible by SR ligation. In addition to macrophages and dendritic cells, B cells also show receptor-mediated uptake and enhanced presentation of maleyl-Ags. Using a monoclonal T cell line to detect peptide-MHC complexes expressed on spleen cells in Ag-injected mice, we find that higher levels of these complexes are generated in vivo from maleyl-proteins and they persist longer than those generated from the native protein. Together, these data suggest that in certain situations, the levels of cognate ligand available and/or the time course of their availability may play a major role in determining the cytokine profiles of the responding T cells in addition to the costimulatory signals implicated so far.

Animals↗

Family history of cancer and autoimmune disease and risk of leukemia in infancy: a report from the Children's Cancer Group (United States and Canada).

OBJECTIVES: As there are some suggestions that a family history of cancer or autoimmune disease might be associated with an increased risk of leukemia in children, we explored this possibility using data from a matched case-control study conducted by the Children's Cancer Group. METHODS: We compared the family history of cancer and autoimmune diseases of 302 infant leukemia cases (diagnosed within the first 18 months of life) with that of 668 individually matched controls in the United States and Canada. RESULTS: Although not significant, cancer history in parents was found to be associated with an elevated risk of infant leukemia (odds ratio [OR] = 1.4, 95 percent confidence interval [CI] = 0.6-3.6), predominantly acute myeloid leukemia (AML) (OR = 2.2, CI = 0.6-9.0). Cancer history among second-degree relatives was also related to a nonsignificantly elevated risk of AML. Family history of autoimmune diseases, on the other hand, was generally not found to be related to the risk of infant leukemia. CONCLUSION: This study provided no strong evidence that family history of cancer or autoimmune disease is a major risk factor for infant leukemia.

Autoimmune Diseases↗

Bone mineral density in patients undergoing bone marrow transplantation for myeloid malignancies.

Bone mineral density (BMD) was measured in 23 patients who had undergone bone marrow transplantation (BMT) at the University of Minnesota for myeloid leukemia. The median age at BMT was 22 years (range 3-53) and the median age at assessment of BMD was 27 years (range 4-56). Total body BMD was measured a median of 2 years (range 1-10) after BMT using Dual Photon X-ray Absorptiometry (DEXA). BMD was measured in g/cm2, with results expressed as percent of normal values and as Z (standard deviation) scores. Patients were categorized into two groups (pediatric and adult) according to age at BMT (< or = 18 years vs > 18 years). Total body BMD of patients in the pediatric age group was significantly decreased (median Z-score -0.5) compared to the adult population (median Z-score 0.0, P = 0.03). No association was observed between BMD and time elapsed since BMT, type of conditioning regimen, gonadal function, steroid intake or graft-versus-host disease. Investigation of decreased BMD in children with AML following BMT is needed to determine the metabolic basis, long-term implications, appropriate preventive measures and potential interventions.

Adolescent↗

Consumption of 'country liquor' and its relation to alcoholic liver disease in Mumbai.

The amount of alcohol intake required for the development of liver disease has been determined in Western populations; corresponding figures in Indians, many of whom consume locally brewed liquors, are not known. We studied 328 patients from a public hospital in Mumbai who admitted to regular alcohol consumption, to determine the pattern of alcohol consumption and its relation to liver disease. Liver disease was more common in those who consumed illicitly-brewed as compared to licit liquor. Daily drinking, volume of consumption > 200 ml per day, and duration of drinking > 14 years were each significantly more common in those with liver disease. A cumulative intake of > 2000 ml. years, calculated as the product of volume (ml per day) and duration (years), was a reliable cut-off level for association with liver disease (sensitivity 65%, specificity 77%) and cirrhosis (sensitivity 70%, specificity 59%). The content of alcohol in these liquors, estimated in 23 samples, ranged from 23-36.1 g/100 ml, being lower in the illicit liquors. Thus, in Mumbai, alcoholic liver disease occurs more commonly with consumption of illicit liquor (despite its lower alcohol content); liver involvement appears earlier and with lower consumption levels than in the West.

Adult↗

Randomized double-blind trial of metronidazole versus secnidazole in amebic liver abscess.

OBJECTIVE: To compare the efficacy of secnidazole with metronidazole in the treatment of amebic liver abscess. METHODS: Thirty two patients with uncomplicated liver abscesses were studied in a randomized, double-blind trial. Fifteen received metronidazole (400 mg t.i.d. for 7 days) and 17 secnidazole (500 mg t.i.d. for 5 days). All abscesses were aspirated on day 1 and laboratory tests and ultrasonographic examination were done on days 1 and 10. RESULTS: One patient in the metronidazole group developed intraperitoneal rupture. The other 31 patients had 40 abscesses (19 in metronidazole group, 21 in secnidazole group). Complete resolution of signs occurred by day 10 in 10 patients on metronidazole and 12 on secnidazole, and in all others by day 28. On day 10 ultrasonography in the metronidazole group showed complete disappearance of abscess in one patient, decrease in 8 and increase in 5 (versus 2, 12 and 3, respectively in the secnidazole group). After 6 months, four asymptomatic patients (two from each group) had small abscess cavities on ultrasonography; there were no recurrences. CONCLUSIONS: Secnidazole is as effective in the treatment of amebic liver abscess as metronidazole; it is equally well tolerated.

Adult↗

Autopsy study of patients dying of bleeding diathesis.

Ten thousand & thirty seven autopsies performed from the year 1982 to 1992 were studied retrospectively, to find out the number of deaths due to bleeding diathesis. Eighty-seven (0.87%) patients died due to bleeding diathesis, out of which haemolytic uraemic syndrome (HUS) was seen in 9 cases (10.34%), disseminated intravascular coagulation (DIC) in 67 cases (77.01%) & 11 cases were grouped as miscellaneous. Martius scarlet blue stain was carried out to demonstrate fibrin & depending on the number of thrombi in the glomerulus & blood vessels, the lesions were graded as mild, moderate or severe. Kidney was the most common organ involved in all groups of bleeding diathesis. In DIC kidney & lung involvement was almost equal.

Autopsy↗

Stability of association of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine with liposomes is composition dependent.

The ether lipid, 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3), has anticancer activity, but it has serious side-effects, including hemolysis, which prevent its optimal use. We surmised if ET-18-OCH3 could be stably associated with liposomes, less free ET-18-OCH3 would be available for lytic interaction with red cells. Liposome composition variables investigated included acyl chain saturation, phospholipid head group and mole ratio of Chol and ET-18-OCH3. It was found that attenuation of hemolysis was strongly liposome composition dependent. Some ET-18-OCH3 liposome compositions were minimally hemolytic. For example, whereas the HI5 (drug concentration required to cause 5% human red cell lysis) was 5-6 microM for free ET-18-OCH3, it was approximately 250 microM for DOPC (dioleoylphosphatidylcholine):Chol (cholesterol):DOPE-GA (glutaric acid derivatized DOPE):ET-18-OCH3, (4:3:1:2) and 640 microM for DOPE (dioleyolphosphatidylethanolamine):Chol:DOPE-GA:ET-18-OCH3 (4:3:1:2) liposomes. Efflux of carboxyfluorescein (CF) from liposomes and Langmuir trough determinations of mean molecular area of lipids in monolayers (MMAM) were used as indicators of membrane packing and stability. Incorporation of ET-18-OCH3 in liposomes reduced the MMAM. Reduction in CF permeation was correlated with reduction in hemolysis. The most stable liposomes included components, such as cholesterol, DOPC and DOPE, which have complementary shapes to ET-18-OCH3.

Centrifugation, Density Gradient↗

Pleuropulmonary blastoma: a clinicopathologic study of 50 cases.

BACKGROUND: Pleuropulmonary blastoma (PPB) is a unique dysontogenetic neoplasm of childhood that appears as a pulmonary and/or pleural-based mass and is characterized histologically by a primitive, variably mixed blastematous and sarcomatous appearance. METHODS: Histologic material from all cases was reviewed and the tumors subclassified as type I (purely cystic), type II (cystic and solid), or type III (purely solid). Data regarding presenting symptoms, family history, operative findings, pathologic subtypes, therapeutic interventions, and outcome were correlated with survival by standard statistical methods. RESULTS: The series was comprised of 24 males and 26 females. Respiratory difficulty with or without fever was the most common clinical symptom reported. Cyst formation in the affected lung was identified radiographically in 19 children (38%) at or before the definitive pathologic diagnosis. The ages at presentation of the 7 type I, 24 type II, and 19 type III PPBs were significantly different: 10, 34, and 44 months, respectively (P < 0.001). Local recurrence developed in 1 of 7 type I PPBs (14%) and in 18 of 43 type II and III PPBs (46%); distant metastasis occurred in 13 patients, chiefly to the brain/spinal cord or bone, and was observed only in those with type II or type III PPB. Patients with pleural or mediastinal involvement fared significantly worse than those without such involvement. Five-year survival was 83% for type I and 42% for types II and III. Survival differences on the basis of pathologic subtype did not reach statistical significance. CONCLUSIONS: PPB is an aggressive, intrathoracic neoplasm of early childhood with an unfavorable outcome. Although survival differences among patients with different histologic subtypes of disease did not reach statistical significance, the apparently better outcome for patients with purely cystic type I tumors may be borne out in a large series. These observations support the premise that type I and III PPB are bridged morphologically by type II PPB with its combined cystic and solid features. The PPB should be regarded as the pulmonary dysontogenetic analogue to Wilms' tumor in the kidney, neuroblastoma in the adrenal gland, and hepatoblastoma in the liver. Molecular genetic investigations, especially in constitutional PPB, should be revealing. In view of the poor outcomes for patients with types II and III, new and aggressive therapies must be developed.

Adolescent↗

Langerhans cell histiocytosis: an exploratory epidemiologic study of 177 cases.

There is little information available regarding epidemiologic risk factors for Langerhans cell histiocytosis (LCH). An exploratory investigation was conducted using information obtained from parents of 177 cases of LCH diagnosed before 21 years of age (median 2 years). Utilizing data available from the Children's Cancer Group, LCH cases were compared to two matched control groups including 614 patients diagnosed with a variety of childhood cancers and 318 community controls. Questionnaire data included information on demographics, prenatal and perinatal factors, complications in the neonatal period, environmental exposures, family medical history, and childhood exposures. Factors found to be statistically significantly associated with an increased risk of LCH included: maternal urinary tract infection during the index pregnancy, feeding problems during infancy, and blood transfusions during infancy. Use of supplemental vitamins was associated with a significantly decreased risk of LCH. Results from this exploratory study provide a basis for speculation on potential etiologic risk factors for LCH. Future epidemiologic investigations of LCH need to consider the presenting disease characteristics in assessing possible etiologic factors.

Adolescent↗

Epidemiologic study of Langerhans cell histiocytosis in children.

OBJECTIVE: The etiology and pathogenesis of Langerhans cell histiocytosis (LCH) remain poorly understood. We conducted an exploratory epidemiologic study to investigate potential risk factors associated with LCH. STUDY DESIGN: We used a case-control study design to obtain data from parents of children with LCH (n = 459) who were members of the Histiocytosis Association of America and Canada. The two control groups consisted of 683 community control subjects and 3719 children with childhood cancers treated at participating Children's Cancer Group institutions. RESULTS: The median age at diagnosis of LCH was 1.8 years (range 0.1 to 14.6 years). Cases were categorized as multisystem LCH (MS-LCH) (n = 208) and single-system LCH (SS-LCH) (n = 198). Statistically significant associations included the following: infections in the neonatal period (MS-LCH, odds ratio (OR) = 2.2), solvent exposure (SS-LCH, OR = 54.9), childhood vaccinations (MS-LCH and SS-LCH, OR = 0.4), thyroid disease in the proband (MS-LCH and SS-LCH, OR = 21.6), and family history of thyroid disease (MS-LCH and SS-LCH, OR = 1.4). The association with thyroid disease in the proband was explained partially by the involvement of the pituitary, with the relative risk decreasing when patients with diabetes insipidus and thyroid involvement were excluded from analysis. CONCLUSIONS: This large hypothesis-generating study provides directions for future investigations in well-designed population-based or hospital-based epidemiologic studies.

Adolescent↗

Primary non-Hodgkin's lymphoma of the cranial vault.

We present a case of primary B-cell, large-cell, lymphoma of the skull vault in a 50-year-old HIV-positive male, who presented with a history of unilateral headache and a swelling on the scalp. Primary non-Hodgkin's lymphoma of the skull is rare, with only ten such cases in adults previously described. We suggest that this is the second reported case in an HIV-positive individual.

Antineoplastic Combined Chemotherapy Protocols↗

Hydrogel contact lens-corneal interactions: a new mechanism for deposit formation and corneal injury.

PURPOSE: In this study, we examined the interactions between hydrogel contact lenses and the cornea, and the role of these interactions in the pathogenesis of interfacial debris formation and the complications of contact lens use. METHODS: We used a corneal abrasion device to simulate the motion of contact lenses on the cornea and the ensuing abrasive interactions. We examined lens and corneal surfaces by Atomic Force Microscopy (AFM), Low Voltage Scanning Electron Microscopy (LVSEM), and optical microscopy (with vital staining of corneas) for unused hydrogel contact lenses, lenses tested in the corneal abrasion device, and worn contact lenses. Young's modulus of hydrogel contact lenses was also measured and compared with the modulus of the human cornea, as reported in the literature. RESULTS: We observed patterns of abrasive damage to the rabbit cornea in vitro caused by corneal interaction with hydrogel contact lenses. Comparison of AFM and SEM of unused lens surfaces with the surfaces of lenses tested in the abrasion device showed dramatic alterations of the contact lens surfaces. Damage to the lenses was also evident by AFM for lenses worn by volunteers. The modulus of hydrogel contact lenses was lower than the modulus of the human cornea. CONCLUSIONS: The surface morphology of hydrogel contact lenses is significantly altered during use. The Young's modulus of the cornea is higher than the modulus of hydrogel contact lenses. These observations suggest a new mechanism for contact lens complications; namely, damage to the contact lens by the cornea as an initial event that produces lens particles and deposits at the lens-cornea interface, followed by corneal abrasion and the onset of other complications.

Animals↗

Examination of contact lens surfaces by Atomic Force Microscope (AFM).

PURPOSE: We evaluated the use of Atomic Force Microscopy (AFM) in examining the surfaces of unused and worn hydrogel contact lenses under natural, fully hydrated conditions. METHODS: Using the AFM contact mode, we examined hydrogel lenses (Acuvue, Surevue, NewVues, CSI Clarity, SeeQuence) that were hydrated. RESULTS: Surface morphologies characteristics of each lens type and wear history were readily observed. The surfaces of worn lenses showed evidence of abrasion and altered morphology. These changes varied with type of contact lens and conditions of use and by site on the lens. CONCLUSIONS: AFM is a very powerful tool for high resolution examination of hydrated contact lens surface structure. The method avoids artifacts due to dehydration and coating which can occur even with low voltage Scanning Electron Microscopy. Significant differences in contact lens surface morphology were observed before and after wear. These observations may be of importance in helping develop improved new lens polymers and ocular solutions.

Contact Lenses, Hydrophilic↗

Acute leukemia presenting as pericardial effusion--a case report.

We report a patient with acute lymphoblastic leukemia, who presented with pericardial effusion. There was no haematologic evidence of leukemia at the time of presentation. The pericardial effusion resolved with chemotherapy. Although a common finding at autopsy, clinically evident pericardial effusion is rare in leukemia. It is also extremely rare for pericardial effusion to be the presenting feature or to antedate haematologic evidence of leukemia. Physician awareness is important to make a correct diagnosis.

Adult↗

Malignant neoplasms following bone marrow transplantation.

We undertook an analysis of 2,150 recipients of bone marrow transplant (BMT) at the University of Minnesota to determine the incidence of post-BMT malignant neoplasms (MNs). Fifty-one patients developed 53 MNs, compared with 4.3 expected from general population rates (standardized incidence ratio [SIR], 11.6, 95% confidence interval [CI], 8.2-14.5). These included 22 occurrences of B-cell lymphoproliferative disorder (BLPD), 17 solid nonhematopoietic tumors, 10 myelodysplastic syndromes (MDS), 1 acute myelogenous leukemia (AML), 2 non-Hodgkin's lymphoma (NHL), and 1 Hodgkin's disease (HD). The estimated actuarial incidence of any post-BMT malignancy was 9.9% +/- 2.3% at 13 years posttransplant. The cumulative probability of BLPD plateaued at 1.6% +/- 0.3% by 4 years from transplant and factors independently associated with increased risk included in vitro T-cell depletion of marrow (relative risk (RR) = 11.9, P < .001), HLA mismatch (RR = 8.9, P < .001), use of antithymocyte globulin (ATG) for graft versus host disease (GVHD) prophylaxis (RR = 5.9, P < .001) or in the preparative regimen (RR = 3.1, P = .03) and primary immunodeficiency (RR = 2.5, P = .06). The cumulative probability of developing solid malignancy was 5.6% +/- 2.2% at 13 years from BMT. Malignant melanomas were the most common (SIR, 10.3, 95% CI 1.9 to 25.4). The actuarial incidence of MDS/AML plateaued at 2.1% +/- 0.8% at 9 years and was seen most often in older patients receiving autologous peripheral blood stem cells for HD or NHL. These data document that BMT recipients are at an increased risk of later malignancy, which may add significant morbidity and mortality to the transplant process. Methods for screening and identification of individuals at increased risk need to be addressed in future studies.

Adolescent↗