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Biomedical subjects

J Shuster

Publications and source records attributed to J Shuster.

At least 109 records · Page 6Linked to original sources

Economic impact of kidney stones in white male adults.

A large survey of patients hospitalized for kidney stones in the Carolinas and the Rocky Mountain states yielded information that can be translated into conservative estimates of cost of this disease. Hospital costs were estimated by considering number of surgeries, the approximate cost of various types of surgery, number of days hospitalized, and room rates. Work force costs were estimated from information on work days lost and income categories. Estimated recurrence rates for this disease are used to approximate the total cost, due to stones, for the next year for a current stone case. Each incident of stone disease costs, on the average, approximately $2,000, exclusive of recurrences. Hospital stays average four to five days. The average annual cost of recurrence for a current stone case is conservatively estimated to be in the $300 to $400 range. A conservative projection of these costs to the entire national population of white males in the age range of eighteen to sixty years yields an annual cost due to kidney stones approaching $315,000,000.

Adolescent↗

Clinical uses of monoclonal antibodies.

Immunization of animals for the purpose of generating antisera for clinical and experimental use results in the production of antibodies with multiple specificities directed at the parent antigen. Furthermore, if the immunogen contains contaminants of a highly immunogenic nature, large amounts of irrelevant antibody will be generated and which must subsequently be absorbed. The unpredictable nature of heteroantisera can be overcome by adopting the monoclonal antibody technique which allows one to produce standardized antibody with well defined and selected specificity toward a given epitope on a macromolecule. Cross-reactions are not eliminated by monoclonal antibodies.

Animals↗

Targeting of liposomes: monoclonal antibodies coupled to phospholipid vesicles provide selective transfer of trapped reagents into cultured cells.

Monoclonal antibodies were incorporated in small unilamellar vesicles by means of ultrasonic irradiation. In order to increase the incorporation efficiency, the immunoglobulins were previously treated at low pH (pH 2), following recent suggestions on the existence of a lipid soluble conformational isomer for serum IgG. The lipid to protein ratios obtained were comparable to the values obtained by other authors using covalent coupling of the antibody to the lipid matrix. Liposome-incorporated monoclonal antibodies directed towards carcinoembryonic antigen (CEA) provided increased transfer of the fluorescent dye carboxyfluorescein from liposomes into cultured human colon carcinoma cells. Another independent experiment was performed on the drug-resistant CHO cell line B30, using a monoclonal antibody to a cell surface marker of drug resistance. Selective liposome mediate drug killing was observed following incubation of the cells with liposomes containing the antitumor agent drug, daunorubicin.

Animals↗

Immunologic dysfunction in patients with classic hemophilia receiving lyophilized factor VIII concentrates and cryoprecipitate.

The occurrence of the acquired immune deficiency syndrome (AIDS) in patients with hemophilia has suggested that an infectious agent transmitted through the frequent use of pooled blood products could be responsible. To determine if the amount or type of factor VIII preparation alters the risk of acquiring immune defects, three groups of asymptomatic heterosexual men were studied: 34 with severe classic hemophilia who were receiving lyophilized factor VIII concentrate, 10 with either mild classic hemophilia or moderately severe von Willebrand's disease who were receiving cryoprecipitate and 22 normal men who served as controls. Anergy was noted in 68%, 57% and 5% respectively of the three groups. In comparison with the control group, the group treated with lyophilized factor VIII concentrate had a significantly decreased mean ratio of helper to suppressor T lymphocytes, poor responses of the lymphocytes to mitogens, high unstimulated background activity of these cells and significantly elevated serum IgG levels. Although some of the patients with classic hemophilia who were treated with cryoprecipitate were also anergic, they did not manifest these in-vitro abnormalities. The data indicate that a majority of apparently immunocompetent individuals with classic hemophilia show in-vivo and in-vitro evidence of impaired cellular immunity and may be at risk for the development of opportunistic infections and neoplasms.

Acquired Immunodeficiency Syndrome↗

Interaction between prognostic factors and treatment.

In randomized trials, the better therapy may depend on values of a prognostic factor. This article presents methodology for subdividing a target population into three subsets: one region of superiority of each treatment, and one region of uncertainty. The basis of such a subdivision is treatment by prognostic factor interaction. The importance of this analysis in group trial sequences is discussed briefly.

Clinical Trials as Topic↗

High-dose methotrexate as part of remission maintenance therapy for childhood acute lymphocytic leukemia: a Pediatric Oncology Group pilot study.

Seventeen children with acute lymphocytic leukemia (ALL) in remission were treated with parenteral high-dose methotrexate (HDM) pulses every eight weeks during standard 6-mercaptopurine and methotrexate (MTX) oral maintenance therapy. MTX (1,000 mg/m2) was infused over one hour followed by one hour of intravenous hydration for the purpose of achieving plasma and cerebrospinal fluid (CSF) levels greater than 10(-6) M for a period of 24 hours. Leucovorin (15 mg/m2) was administered orally six, 12, and 18 hours after completion of the HDM. Plasma and CSF concentrations of MTX were evaluated serially in the first 48 hours. During the first 24 hours, the plasma MTX level was maintained at greater than 10(-6) M. The patients receiving intrathecal MTX at a dose of 15 mg/m2 had an adequate, sustained MTX level in the CSF, but when no intrathecal MTX was administered, the CSF levels were less than 10(-6) M. For that reason, intrathecal MTX in a low dose (6 mg/m2) was injected intrathecally one hour after the HDM infusion, allowing the MTX level in CSF to approximate 10(-6) M over the 24 hours. The toxicity of this therapy was minimal. Due to the facts that the plasma and CSF MTX levels could be sustained above the desired concentrations and this regimen could be given in the outpatient clinic, this program has been incorporated into an ongoing study in an effort to prolong complete remissions.

Adolescent↗

Maternal plasma HbF levels in pregnancy.

Serial maternal serum hemoglobin F (HbF) levels were measured by radioimmunoassay in 23 normal pregnancies. The maternal HbF fraction remains within the normal range during the first trimester (mean + 2 S.D. = 0.15 + 0.13). After 15 weeks gestation, maternal HbF levels rise in some, but not all, pregnancies. In about 30% of the cases the HbF fraction remains within the range seen in adult men and non-pregnant women. Irregular rises in HbF were found in other pregnancies studied serially. The maternal HbF fraction may be an indicator of transplacental hemorrhage.

Female↗

Auto-immunity in patients with end-stage renal disease maintained on hemodialysis and continuous ambulatory peritoneal dialysis.

Auto-immunity as assessed by rheumatoid factor, anti-DNA, antinuclear, smooth muscle and mitochondrial circulating antibodies was evaluated in 2 groups of 25 patients with end-stage renal disease (ESRD) being maintained either on hemodialysis or on continuous ambulatory peritoneal dialysis (CAPD). In the group of hemodialysis patients, 56% showed at least one serological abnormality on pre-dialysis samples: anti-DNA (8%), antinuclear (8%), smooth muscle (40%) and mitochondrial (4%) antibodies; on post-dialysis samples, 64% of the patients demonstrated abnormalities due to a rise in the incidence of anti-DNA antibodies from 8-24%. In the group of CAPD patients, 44% showed at least one serological abnormality: rheumatoid factor (4%), anti-DNA (16%), antinuclear (24%) and smooth muscle (4%) antibodies. These serological changes were generally scattered randomly within both groups. In the hemodialysis group, 2 abnormalities were present in 1 patient pre-dialysis and in 3 post-dialysis. One CAPD patient had 2 abnormalities. No correlation of these findings with age, sex, duration of dialysis and nature of renal disease could be found. The results are discussed in the context of possible abnormal antigenic stimulation in ESRD patients maintained on either form of dialysis.

Adult↗

CNS prophylaxis in acute lymphoblastic leukemia: comparison of two methods a Southwest Oncology Group study.

Children with acute lymphoblastic leukemia were randomized to one of two treatment options for CNS prophylaxis. All patients received intrathecal therapy over a one-year period with methotrexate, hydrocortisone and cytosine arabinoside. One-half of the patients also received 2400 rad cranial radiation over 2 1/2 weeks. There was no significant difference in CNS relapse rate, length of hematologic remission or survival between the two groups. No further CNS relapses have been observed for the last four years. CNS relapse was associated with subsequent disease recurrence in the 67% of patients.

Adolescent↗

Water hardness and urinary stone disease.

On the macrogeographic scale, a strong negative association exists in the United States between water hardness and urinary stone disease. This investigation studies the association on the microgeographical scale, where it is possible to control for confounding environmental factors. The study was conducted on 2,295 patients from 2 regions: the Carolinas which had soft water and high stone incidence, and the Rockies which had hard water and low stone incidence. Home tap water samples from urinary stone patient hospitalizations were compared with that of controls, concurrent inguinal hernia patient hospitalization. After adjusting for environmental factors, no significant difference (p = 0.59) between the 2 groups was obtained in tap water calcium, magnesium, and sodium concentrations. An incidental but potentially important finding was that those consuming water from a private well had an estimated relative risk of 1.5 (p less than 0.01) compared to those using public water. While no cause-effect relationship is suggested, stone-formers might consider avoiding private well water. On the other hand, water hardness should be a minor concern with respect to stone formation.

Calcium↗

alpha-Fetoprotein and cystic fibrosis.

Because of unconfirmed reports that the serum level of alpha-fetoprotein (AFP) is high in children with cystic fibrosis and intermediate in their siblings and parents, this level was measured in 25 children with cystic fibrosis, 26 of their siblings, 42 of their parents and 31 age-matched children without cystic fibrosis who were attending outpatient clinics of the Montreal Children's Hospital. Liver function tests were performed at the same time since patients with liver disease may have unusually high serum AFP levels and patients with cystic fibrosis often have liver involvement. AFP was not detected in any of the serum samples, and the results of the liver function tests were normal in all but 1 individual, a control subject. In simultaneous assays of serum from children with ataxia telangiectasia, however, high AFP levels were detected in 15 of 16 samples. Thus, measurement of the serum AFP level is of no value in detecting carriers of the cystic fibrosis gene.

Adolescent↗

Monoclonal antibodies to human lung tumor antigens demonstrated by immunofluorescence and immunoprecipitation.

Various studies have demonstrated the usefulness of monoclonal antibodies in recognizing discrete tumor antigenic determinants. The present study describes the tissue reactivity of monoclonal antibodies prepared against a squamous cell carcinoma of the lung. Antigens were purified from the tumor extract by anti-beta 2 microglobulin affinity chromatography. These beta 2-associated antigens demonstrated tumor specificity by the leukocyte adherence inhibition assay. Antibody-secreting hybridomas were generated by fusion of mouse myeloma cells with mouse spleen cells immunized with purified tumor antigens. Hybridomas were selected by a solid-phase tumor membrane-binding immunoassay. The target specificity of the secreted monoclonal antibodies was ascertained by radioimmunoprecipitation analysis and indirect immunofluorescence on various human tumor and normal tissue sections. Monoclonal antibody-secreting hybridomas 48.4.8 and 48.4.2 secreted immunoglobulin that selectively immunoprecipitated polypeptide fragments from human lung tumor membrane antigens. Hybridoma 9.2.2 secreted antibody that was strongly positive by indirect immunofluorescence on all tested lung squamous cell carcinomas. Adjacent or intervening normal lung tissue did not display significant immunofluorescence. Adenocarcinomas of the lung were negative or focally positive when focal squamous cell differentiation was present. Oat cell carcinomas were negative. The secreted antibody did not significantly stain three extrapulmonary tumors or a variety of normal tissues.

Animals↗