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Biomedical subjects

S Bakshi

Publications and source records attributed to S Bakshi.

At least 19 recordsLinked to original sources

In situ breast carcinoma after treatment during adolescence for thyroid cancer with radioiodine.

We reviewed the courses of patients treated during childhood or adolescence for thyroid cancer to estimate the frequency of, and to identify possible risk factors for, the occurrence of second malignant tumors in this population. We identified all patients treated for thyroid cancer in a cohort of 1,406 pediatric cancer patients who were diagnosed prior to 20 years of age during the period January 1, 1960 through December 31, 1988 and who were treated at Roswell Park Cancer Institute. Twelve patients were treated for thyroid cancer, of whom nine were women. In situ breast carcinoma was diagnosed 25 and 26 years after diagnosis of thyroid cancer in two of four women treated with radioiodine. No new cancers were diagnosed in the five women treated with thyroidectomy only. Two of four women treated for thyroid cancer during adolescence with radioiodine, which is concentrated in the breast as well as other organs, developed in situ breast carcinoma. Review of a large cohort of adolescent female thyroid cancer patients treated with radioiodine is necessary to provide an accurate estimate of their risk of developing breast cancer. These patients must remain under medical surveillance throughout their lifetimes to facilitate prompt diagnosis of and early intervention for new conditions, such as the occurrence of breast cancer.

Adolescent

Magnetic resonance spectroscopy in childhood AIDS encephalopathy.

Twenty-five children with acquired immunodeficiency syndrome (AIDS) underwent cranial magnetic resonance imaging and proton magnetic resonance spectroscopy. Patients were divided into 2 groups based on clinical parameters: encephalopathy and nonencephalopathy. N-acetyl aspartate/creatine ratios were compared between the 2 groups and to control data. Spectra were obtained for 2 volumes of interest: the basal ganglia region and the white matter. The mean basal ganglia region ratio for the AIDS encephalopathy patients (n = 8) was 1.12 and the ratio for the AIDS nonencephalopathy patients (n = 17) was 1.48. The ratio for the 9 controls was 1.57. The encephalopathy group had a significantly lower ratio than both the control (P < .001) and the AIDS nonencephalopathy group (P < .002). The mean white matter ratio for the encephalopathy group (n = 8) was 1.47 and for the AIDS nonencephalopathy group (n = 13) was 1.82 with a control (n = 6) ratio of 1.82. The encephalopathy patients had a lower white matter ratio than the nonencephalopathy (P < .05) patients but the ratio was not different than controls (P < .11). It is concluded that N-acetyl aspartate/creatine ratios are reduced in childhood AIDS encephalopathy and proton magnetic resonance spectroscopy may be helpful in defining brain human immunodeficiency virus-1 infection. However, further longitudinal studies are necessary to determine the sensitivity and specificity of this technique.

AIDS Dementia Complex

Improved specificity of in vitro anti-HIV antibody production: implications for diagnosis and timing of transmission in infants born to HIV-seropositive mothers.

In vitro anti-HIV antibody production (IVAP), initially introduced as a method for diagnosis of human immunodeficiency virus type 1 (HIV-1) infection in infants, has been limited in its application because of poor specificity and sensitivity early in life. The aims of this study were to improve the specificity of the IVAP assay and to evaluate its sensitivity in conjunction with assays of HIV culture, polymerase chain reaction (PCR), and p24 antigen. To prevent false-positive reactions resulting from maternal serum-derived cytophilic anti-HIV IgG, additional preculture and washing steps for peripheral blood mononuclear cells (PBMCs) were introduced that resulted in dramatic improvement in specificity of IVAP. The sensitivity of the revised IVAP at age < 3 months in 20 infected infants was, however, only 25%; of 15 infected infants initially negative in IVAP, 13 became positive at a mean estimated age of 4.4 +/- 1.8 months. When correlated with virological assays, a failure to respond in IVAP at age < 1 month was often associated with negative virological identification, whereas a positive IVAP response at age < 3 months was always associated with positive results in all virological assays. Moreover, conversion from negative IVAP to positive responses occurred subsequent to, and not concurrently with, a positive virological identification of infected infants. The revised IVAP methodology renders this assay potentially useful as an additional tool not only for the diagnosis of HIV infection, but for estimating timing of maternal-infant HIV transmission as well.

Antibody Specificity

Immunoscintigraphy using 111InCyt103 prior to second look laparotomy in ovarian cancer. A pilot study.

A prospective pilot study was performed in order to determine the efficacy of 111InCyt103 (ONCOScintr CR/OV) in the detection of the presence and location, or absence of disease among patients with epithelial ovarian cancer who demonstrated no clinical or biochemical (Ca 125: < 35 mu/ml) evidence of disease at the end of first-line therapy. Among 15 patients who underwent second-look laparotomy, the overall accuracy of the test was 60%. The test demonstrated a sensitivity of 62.5% and a specificity of 57.1%. The predictive value of a positive test was 62.5% and of a negative test was 57.1%. The correct location of disease was predicted in 57% of patients with macroscopically appreciable tumors. ONCOScintr CR/OV offers little appreciable advantage over current modalities in discriminating between the presence or absence of disease among patients with epithelial ovarian cancer who demonstrate no clinical evidence of disease at the end of first-line therapy.

Adult

99mTc-IMMU-4 monoclonal antibody scan in colorectal cancer. A prospective study.

A blinded prospective study of 34 patients with colorectal adenocarcinoma using the Fab' fragment of the anticarcinoembryonic antigen monoclonal antibody type IMMU-4 labeled with technetium 99m was conducted to compare, on a lesion-by-lesion basis, the findings of radioimmunoscintigraphy, preoperative computed tomography, and exploratory celiotomy. Of 115 lesions detected at surgery, 113 were adenocarcinoma. Radioimmunoscintigraphy detected 59 lesions and computed tomography detected 62; both studies combined detected 72. Twenty-nine (54%) lesions missed by radioimmunoscintigraphy and 24 (45%) missed by computed tomography were 1 cm or smaller. When both studies were combined, the sensitivities were 90%, 24%, and 42%, and the specificities were 52%, 86%, and 61% for hepatic, extrahepatic intra-abdominal, and pelvic lesions, respectively. In 10 patients, additional information obtained with the radioimmunoscintigram could have altered the treatment of these patients. In this study, radioimmunodetection scan was complementary to computed tomographic scan in the examination of patients with colorectal carcinoma.

Adenocarcinoma

Varicella does not appear to be a cofactor for human immunodeficiency virus infection in children.

We performed a retrospective analysis of longitudinal clinical and immunologic data obtained from 22 children in the early stages of infection with human immunodeficiency virus (HIV) when they developed varicella. We studied the course of HIV infection to determine whether clinical deterioration occurred after chickenpox. We examined the following indices: growth and development; neurologic status; helper T lymphocyte counts; blood values of core (p24) antigen of HIV; changes in the stage of HIV infection; and need for administration of zidovudine. We studied children for a mean of 2.8 years and for as long as 9.8 years after onset of varicella. There was little evidence that chickenpox affected HIV infection. Three (14%) children developed clinical zoster, 2 of whom (9%) had evidence of chronic infection with varicella-zoster virus. One additional child (5%) had 2 episodes of chickenpox. These observations suggest that children with early HIV infection could be considered for immunization with live attenuated varicella vaccine, which would be predicted to decrease their morbidity from varicella-zoster virus.

CD4-Positive T-Lymphocytes

Biodistribution, pharmacokinetic, and imaging studies with 186Re-labeled NR-LU-10 whole antibody in LS174T colonic tumor-bearing mice.

Biodistribution, pharmacokinetic, and radioimaging studies were performed with 186Re-labeled NR-LU-10 whole antibody in athymic nude mice bearing the LS174T tumor growing either s.c. or in an experimental hepatic metastasis model. NR-LU-10 is an IgG2b murine monoclonal antibody (MAb) that reacts with virtually all human tumors of epithelial origin. NR-BC-1, a IgG2b murine MAb that reacts with normal human B-cell and B malignancies, was used as an isotype-matched control. These MAbs were radiolabeled with 186Re (3.7-day physical half-life; 1.07-MeV beta particle and 137-keV gamma, 9% abundance) by a preformed chelate approach by using the triamide thiolate ligand system. 186Re-labeled NR-LU-10 (50 microCi) was injected into nude mice bearing LS174T tumors growing s.c. Biodistribution studies revealed that the LS174T tumor retained the highest concentration of 186Re-labeled NR-LU-10 (5.3% injected dose/g) at day 6. The tumor:blood ratio ranged from 0.1:1 to 10.8:1 by day 6, the last day of analysis. In contrast the tumor:blood ratio of 186Re-labeled NR-BC-1, the isotype-matched MAb control, was 1:1 on day 6. Pharmacokinetic analysis indicated that the t1/2 beta of NR-LU-10 for blood and other tissues ranged from 21 to 25 h, while the t1/2 beta for the LS174T tumor averaged 52 h. The area under the curve for tumor compared to blood was 2.8- to 5.7-fold higher than the area under the curve for all other tissues and organs. The mean residence time for NR-LU-10 in blood and all other organs ranged from 23 to 26 h, while the mean residence time for NR-LU-10 in the LS174T tumor was 72 h. Scintigraphic images revealed selective uptake of the 186Re-labeled NR-LU-10, but not of the 186Re-labeled NR-BC-1, at the LS174T tumor site. Studies in an experimental model of hepatic metastasis revealed a similar selective pattern of 186Re-labeled NR-LU-10 accumulation. Scintigraphic images of the LS174T tumor growing within the athymic nude mouse liver were obtained. The biodistribution, pharmacokinetic, and scintigraphic image results suggest that 186Re-labeled NR-LU-10 shows promise as a therapeutic agent for gastrointestinal cancer.

Adenocarcinoma

Steroid response to adrenocorticotropin stimulation in children with human immunodeficiency virus infection.

To evaluate whether frank or subtle disorders of adrenal steroidogenesis exist in human immunodeficiency virus (HIV)-infected children, the adrenal steroid response to an iv bolus of ACTH-(1-24) (0.25 mg Cortrosyn) was determined. Ten children (six males and four females, aged 7 months to 7.5 yr) were studied. Five underwent repeat testing 3-5 months after initial assessment. Nine patients were classified as P2 or symptomatic according to the Center for Disease Control criteria for HIV infection in children. Eight had failure to thrive, six had opportunistic infections and neurological deficits, and two were receiving ketoconazole at the time of ACTH testing. Only one patient had a neonatally acquired transfusion-related HIV infection. Three of the children died 2-5 months after ACTH testing. All patients had normal or slightly elevated baseline and stimulated cortisol levels compared to the control population. The mean post-ACTH cortisol level was significantly higher than the mean post-ACTH level in the control population. No patient demonstrated an impaired aldosterone response to ACTH. The basal and ACTH-stimulated dehydroepiandrosterone levels were normal. Although individual deoxycorticosterone and corticosterone levels were variable, the mean stimulated deoxycorticosterone and corticosterone levels in the patients were suggestive of a selective defect of the 17-desoxy pathway in the adrenal fasciculata. No changes were noted in the patients' cortisol, dehydroepiandrosterone, and aldosterone responses on repeat ACTH testing. In HIV-infected children we have demonstrated that cortisol and aldosterone synthesis is intact. Thus, the chronic debilitation observed cannot be explained on the basis of adrenal insufficiency. However, a selective deficiency of 17-desoxysteroid hormone production from the adrenal fasciculata may be present.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Function Tests

Five and ten year estimated survival and disease-free rates after intraperitoneal chromic phosphate; stage I ovarian adenocarcinoma.

From 1975 to 1982, 25 evaluable patients with FIGO Stage I ovarian cancer were treated with intraperitoneal chromic phosphate (32P). All patients underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy with (28%) or without (72%) omentectomy, with no other surgical staging procedures prior to referral. Patients were restaged by laparoscopy (inspection of diaphragms, abdomen, and pelvis), biopsy of suspicious lesions, and peritoneal cytologic washings prior to intraperitoneal chromic phosphate therapy. For the 25 patients, the estimated 5- and 10-year recurrence-free rates and the 5- and 10-year survival rates are 84% and 75%, respectively. Excellent 10-year recurrence-free rates were achieved for Stages IA and IC, nonruptured cysts, and Grade I and II tumors. In contrast, very low 10-year survival rates were achieved for patients with Stage IB, ruptured cysts, or Grade III tumors.

Adenocarcinoma

Doxorubicin hydrochloride (Adriamycin) cardiotoxicity evaluated by sequential radionuclide angiocardiography.

A prospective study was carried out to evaluate the role of radionuclide angiocardiography (CEF) in accessing subclinical cardiotoxicity secondary to Adriamycin (doxorubicin) therapy in 73 women with gynecologic malignancies. Based on the findings of this study, the authors conclude that all patients should have an initial CEF before Adriamycin therapy. In patients with an initial CEF of greater than or equal to 55, frequent determinations are not necessary unless there is a significant decrease from the initial CEF. Patients with low normal initial CEF or significant difference between the initial CEF and minimum CEF should have CEF studies performed at more frequent intervals. Patients who develop below normal CEF should have Adriamycin withheld and CEF should be repeated at more frequent intervals. If the CEF returns to normal Adriamycin therapy can be reinstated. Patients requiring continuation of Adriamycin past 550 mg/m2, can safely do so as long as the CEF values remain normal.

Adult

CT abnormalities and altered methotrexate clearance in children with CNS leukemia.

Seventeen children with CNS leukemia treated with chemotherapy and 5 children treated with both cranial radiation (CRT) and chemotherapy were evaluated. Eighty-eight percent of patients treated with chemotherapy alone had CT abnormalities, and all treated with CRT and chemotherapy had abnormal CT. The severity of CT abnormality paralleled intraventricular methotrexate levels and clinical signs of leukoencephalopathy. Children who receive chemotherapy for CNS leukemia, even without cranial irradiation, are more likely to have leukoencephalopathy than children without CNS leukemia. Moreover, patients with CNS leukemia may have abnormalities of CSF clearance of intraventricularly administered drugs.

Central Nervous System Diseases

Heart size and function after radiation therapy to the mediastinum in patients with Hodgkin's disease.

Changes in the transverse heart diameter and cardiothoracic ratio were determined by comparing the pretreatment and last follow-up posteroanterior chest x-rays of 96 patients with stage I-III Hodgkin's disease who had received radiation therapy (RT) to the mediastinum, with the same parameters observed in 20 similar patients whose mediastinum was not irradiated. A significantly higher proportion of patients who had received RT to the mediastinum had a decrease in transverse heart diameter and cardiothoracic ratio. Among patients presenting with a large mediastinal mass, these changes were more pronounced as compared to the other groups; however, this difference was not of statistical significance. First-pass left ventricular ejection fraction (LVEF) performed with 99mTc pertechnetate (obtained in 55 of these patients 30-120 months after RT to the mediastinum) was compared with the LVEF of 20 normal controls. The control group had a significantly higher LVEF than the group of patients who had received RT to the mediastinum. No correlation was observed between changes in these parameters and the use of adjuvant, salvage, or no chemotherapy after mediastinal RT. None of these patients presented congestive heart failure or constrictive pericarditis, but our findings indicate a subclinical cardiomyopathy in more than one-half of the patients who received RT to the mediastinum, suggesting that the incidence of heart damage after mediastinal RT might be higher than expected. Prospective studies are necessary to elucidate the incidence and implications of this potentially serious complication.

Follow-Up Studies

Intraperitoneal chromic phosphate in peritoneoscopically confirmed stage I ovarian adenocarcinoma.

From December 15, 1975 to June 16, 1980, 20 evaluable patients with International Federation of Gynaecology and Obstetrics Stage I invasive adenocarcinoma of the ovary were entered into a prospective study, including pretherapy restaging peritoneoscopy followed by treatment with intraperitoneal chromic phosphate if there was no evidence of residual macroscopic tumor. During a follow-up of 1 1/2 to 6 years (median, 3 years and 1 month), the survival rate without evidence of recurrent ovarian carcinoma was 95%. Moreover, there was a total absence of complications with the use of the sequential steps of pretherapy peritoneoscopy, a normal preinjection peritoneogram, injection of chromic phosphate in large volumes of solution, frequent change of position of the patient after injection, and abdominal scans after injection. This method appears to be safe and is associated with a significantly high survival rate.

Adenocarcinoma

The use of subcutaneous cerebrospinal fluid reservoirs for the prevention and treatment of meningeal relapse of acute lymphoblastic leukemia.

Subcutaneous cerebrospinal fluid reservoirs (Ommaya) were placed in 27 children and adolescents with acute lymphoblastic leukemia. Eleven of the reservoirs were used for administration of preventive central nervous system therapy and the remaining 16 reservoirs were used in the management of overt meningeal leukemia. Seven of the 11 patients treated prophylactically had recurrence of leukemia. The first site of recurrence was the central nervous system in three (42%) cases. Four of the 16 patients with reservoirs placed for the treatment of overt meningeal leukemia have not had recurrent disease. Of the 12 patients who relapsed, the site of first recurrence was the central nervous system in five cases. The incidence of major complications was 26%.

Adolescent

Carcinoma of the thyroid gland.

Thyroid cancer is not a common cancer and consists of a variety of tumors with different biological characteristics. Diagnosis and therapeutic approaches differ considerably, depending on which subgroup the tumor belongs to. Differentiated carcinomas, which constitute the bulk of thyroid carcinoma, often retain the features of the thyroid gland, which can be taken advantage of in their management. The prognosis of these patients is usually excellent. Undifferentiated carcinoma, in contrast, is an aggressive tumor and usually is fatal within a year from the diagnosis. Therefore, an aggressive therapeutic approach is required. Transformation of differentiated carcinoma to undifferentiated carcinoma does occur, although infrequently. The importance of proper management of patients with differentiated carcinoma is obvious. Medullary carcinoma, which originates from the parafollicular cells, has various interesting biological characteristics and is a medium-grade malignancy.

Adenocarcinoma

Chemotherapy of nonirradiated malignant gliomas. Phase II: study of the combination of methyl-CCNU, vincristine, and procarbazine.

Twenty-eight adult patients with nonirradiated malignant gliomas of the brain were administered a combination of methyl-CCNU (130 mg/m2, p.o., day 1), vincristine (2 mg/m2, i.v., day 1) and procarbazine (100 mg/m2, p.o., days 2 to 15) (MVP), scheduled to be given at successive 6 week intervals. Nineteen (67.9%) were not responsive to MVP and 9 (32.1%) were. Of 16 who had previous partial resection of their tumors, 8 (50%) responded to MVP and 8 (50%) did not. Of 12 who had previous biopsy, only 1 (8.3%) responded. Overall 1-year survival rate for the 28 patients was 28.6%. Major side effects of MVP were leukopenia, thrombocytopenia, pulmonary emboli, and thrombophlebitis, detected mainly during the first 20 to 24 weeks of treatment.

Adult