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Biomedical subjects

C W Young

Publications and source records attributed to C W Young.

At least 19 recordsLinked to original sources
PubMed1979

Vindesine. A review of phase-II trials.

Vindesine is a new vinca alkaloid with broad-spectrum antineoplastic activity in experimental tumor models. Phase-I studies have shown that a weekly dosage regimen of 3--4 mg/m2 IV produces manageable toxicity, with leukopenia and peripheral neuropathy being dose-limiting. Two hundred seventy-five patients have been enlisted in Phase-II trials at the Memorial Sloan-Kettering Cancer Center. Major objective responses (complete and partial remissions) were seen in bronchogenic carcinomas, melanoma, testicular carcinoma, esophageal carcinoma, acute lymphocytic leukemia, malignant lymphoma (Hodgkin's and non-Hodgkin's) and Wilms' tumor. Patients with hematologic and germ cell neoplasms were treated on a daily administration schedule (1.0--1.3 mg/m2 IV for 5--7 days). Vindesine was well tolerated, with less than 5% of patients having a WBC nadir of less than 1000 cells/mm3 and with a platelet-sparing effect noted. Dose-related peripheral neuropathy occurred frequently and was generally mild to moderate in degree. Vindesine appears to be an active agent whose role will be further defined by completion of ongoing trials.

Blood Cell Count↗
PubMed1979

Feedback-controlled dextrose infusion during surgical management of insulinomas.

Through the use of a feedback-controlled dextrose infusion system, we obtained continuous monitoring of the blood glucose level in a patient undergoing surgery for multiple pancreatic beta-cell tumors. In addition, this device infused dextrose at variable rates to maintain a predetermined euglycemic level of 90 mg/dl. Before locating the source of excessive insulin production, the maximum dextrose infusion rate of 400 mg/min was required; but after extirpation of multiple insulinomas, the dextrose-infusion rate declined whereas the blood glucose level rose above the preselected level. These results emphasize the usefulness of a monitoring and infusion system not only in protecting the patient from the hazard of hypoglycemia under anesthesia but also as an aid in determining whether all insulin-secreting tumors have been removed.

Adenoma, Islet Cell↗
PubMed1979

Health care requirements of dairy cattle. I. Response to milk yield selection.

To measure direct response to single trait selection for milk yield and correlated response in health problems, two homologous base populations were formed by pairing 66 Holstein females by sire. Base populations and descendants were managed identically except for selection by milk yield. One base and lineage were mated with sires with highest predicted difference milk (selection group); other base and lineage were mated with average sires in 1964 (control group). Milk yield, supplemental labor, and veterinary and semen expense were recorded specific to each cow. Over 9 yr, 130 selection and 163 control cows were observed. Selection cows yielded more milk but with increase in labor and expense for health care. Estimates of labor for the selection group were greater for mammary, locomotion, and digestion categories and for expense in mammary, respiration, first insemination, and later insemination categories. Labor and expense for reproduction did not differ for genetic groups. Differences between groups in annual estimated labor and expense totaled $27.00. Extra income over feed cost more than compensated for greater health care and semen cost; however, the magnitude of the latter indicates a need for them to be considered when economically evaluating breeding programs where major emphasis is on milk yield.

Animals↗
PubMed1979

Phase I trial of chlorozotocin.

Chlorozotocin was given to 37 patients with advanced malignant tumors in a daily X 5 schedule at 6-week intervals. Total iv doses for each course ranged from 75 to 200 mg/m2. Myelosuppression was dose-limiting, with a platelet count depression regularly observed at doses of greater or equal to 150 mg/m2; leukopenia occurred only at the highest dose level. Nausea and vomiting were mild and uncommon. No hyperglycemia or adverse drug-related effects on renal or hepatic function were observed. No major antitumor activity occurred; however, three patients with renal cell carcinoma and one patient each with lung cancer, ovarian carcinoma, and Hodgkin's disease had minor objective decreases in tumor size. A dose range of 150--200 mg/m2 iv for each 5-day course is recommended for phase II studies.

Adolescent↗
PubMed1979

Phase II evaluation of vindesine in patients with non-small cell carcinoma of the lung.

Fifty-two patients with non-small cell carcinoma of the lung were treated iv with doses of vindesine at 3--4 mg/m2/week iv. Partial responses occurred in all histologic types in ten of 46 adequately treated patients, for an overall response rate of 22%. Patients not previously treated with chemotherapy had a higher response rate than those who had received prior chemotherapy (33% versus 12%). Reversible peripheral neuropathy occurred in all patients, and was generally of a mild to moderate degree. Mild leukopenia was seen frequently, with a median wbc nadir of 2900/mm3. As reported with the older vinca alkaloids, platelet-sparing with occasional episodes of thrombocytosis occurred with vindesine. It is concluded that vindesine is an active agent in non-small cell carcinoma of the lung and that further studies in previously untreated patients are indicated.

Adenocarcinoma↗
PubMed1979

Phase I evaluation of tetrahydrouridine combined with cytosine arabinoside.

In conventional clinical use, cytosine arabinoside (ara-C) is rapidly deaminated by pyrimidine nucleoside deaminase to the nontoxic compound uracil arabinoside. Tetrahydrouridine (THU) effectively inhibits this enzymatic degradation but is by itself nontoxic. This study demonstrates that concomitant administration of THU markedly increases the myelosuppressive potency of ara-C. When 25 or 50 mg/kg of THU iv and 0.1--0.2 mg/kg of ara-C iv are given daily x 5 days, they produce moderate-to-severe leukopenia and mild-to-moderate thrombocytopenia. A dose of 25 mg/kg of THU with 0.1 mg/kg of ara-C iv daily x 5 days appears appropriate for phase II studies; it produces myelosuppression equivalent to that produced by 3 mg/kg/day x 5 days of ara-C alone. No toxicity occurred with this combination that would not have been expected from ara-C given alone in an equitoxic dose. Although THU and ara-C produced a reduction in peripheral blood and bone marrow blast cells in eight of nine patients with acute leukemia, bone marrow remission did not occur in any of these heavily pretreated patients.

Bone Marrow↗
PubMed1978

Corneal endothelial dystrophy. A study of 64 families.

A prospective study was undertaken during an 18-month period with 64 families who had endothelial dystrophy. Two hundred twenty-eight relatives were examined. Of those older than the age of 40, 38% were affected. Women were affected more severely and 2.5 times more frequently than men. The disease showed a strong familial tendency: there was one family in which three generations were affected and 16 families in which two generations were affected. There were four families that had members with edema in two generations. There was no association between edema in a parent and edema in a child. The proportion of relatives affected and the severity of involvement increased with age. Fifty-three probands and 18 relatives had endothelial dystrophy with edema (Fuchs' dystrophy). Of these 71, one had glaucoma.

Adolescent↗
PubMed1978

Studies on acid lipase, and E 600-resistant acid esterase activities in human tissue homogenates.

Detailed comparison of acid lipase and acid esterase activities of human spleen, liver and kidney homogenates has been carried out by means of the following substrates: 14C-tripalmitin, alpha-naphthyl acetate, alpha-naphthyl butyrate, alpha-naphthyl laurate, p-nitro-phenyl acetate, butyrate and laurate. In addition, homogenates of the three tissues were subjected to isoelectric focusing in polyacrylamide gels and histochemical staining with the above mentioned naphthyl substrates in the presence and absence of the organophosphate esterase inhibitor diethyl-p-nitrophenyl phosphate (E 600). These studies provide extensive support for the proposal that E 600-resistant acid naphthyl butyryl and lauryl esterase activities in human tissues derive largely from the enzyme acid lipase. The studies suggest that the most specific chromogenic substrate for this enzyme at a biochemical and histochemical level is alpha-napthyl laurate in the presence of E600 (3 X 10(-6) M).

Carboxylic Ester Hydrolases↗
PubMed1978

Phase I trial of vindesine in patients with advanced cancer.

A phase I evaluation of vindesine was carried out in 69 adult patient with advanced malignancies. Two escalating dose schedules were explored: (a) a single dose every 7--14 days, and (b) daily injections X 5--10 days as tolerated. The main toxic effects were myelosuppression, alopecia, paresthesia, asthenia, myalgia, and hyporeflexia. Antitumor activity was seen during this phase I study in patients with leukemia, lymphoma, and testicular neoplasms. Disease oriented phase II trials of 3--4 mg/m2 every 7--14 days or 1.3--2.0 mg/m2/day X 5--7 days every 3 weeks would be appropriate.

Adult↗
PubMed1977

Combination chemotherapy of MOPP-resistant Hodgkin's disease with adriamycin, bleomycin, dacarbazine and vinblastine (ABDV).

Twenty-four patients with advanced Hodgkin's disease, resistant to the MOPP regimen, were treated with a combination of Adriamycin, bleomycin, dacarbazine and vinblastine (ABDV). Fifteen (63%) achieved objective remission, 14 partial remissions and one complete remission. The median duration of remission in this group of patients was 6.5 months; four of the 15 patients are still in remission (8+, 8+, 9+, 10+ months). Objective remission occurred rapidly within 1.5 months. Regression was evident in disease within nodes, lung, liver and bone. Toxic manifestations caused by ABDV were well tolerated and reversible. In one patient death was directly attributed to drug toxicity. This combination has produced a better rate and duration of remission than that reported with single agent chemotherapy in MOPP-resistant patients with Hodgkin's disease. In our hands, ABDV did not equal the recent results reported with Bleomycin-CCNU-Velban in a seemingly similar group of patients.

Adult↗
PubMed1977

HLA and MLC typing in patients with Hodgkin's disease.

HLA typing for 27 A and B locus antigens was performed in 137 Caucasian patients with Hodgkin's disease. A and B locus antigen frequencies were compared for the entire group of patients, for 51 patients studied in a prospective manner and for 62 patients surviving with Hodgkin's disease for more than 5 years. MLC typing (HLA-D) was performed in 51 unselected Caucasian patients using 6 differend HLA-D homozygous test cells which define 3 HLA-D specificity groups (DW2, DW3, and DW4). HLA-AW33 was found in 0.0% of patients and in 5.9% of random Caucasian blood donors at the Sloan--Kettering Institute (X2 equals 7.04, p less than 0.01). HLA-A1 was found to be increased to 35.8% in the entire patient group (N = 137) as compared to 25.4% in 855 random North American Caucasians (X2 = 5.97, p less than 0.02). There was no significant deviation of any A or B locus antigen in relation to sex, histology, age of patient, or duration of survival (newly diagnosed vs 5-year survivors). No significant deviation for either of the 3 common HLA-D determinants (DW2, DW3, or DW4) was observed.

Adult↗
PubMed1977

Interactions between "fever" proteins and normal serum proteins in febrile cancer patients.

When analyzed by cationic discontinuous electrophoresis in urea-containing polyacrylamide gels, plasma or serum from febrile individuals contains trace quanitites of five protein bands that are not recognizable in the blood of normal individuals. These proteins appear and disappear in parallel in sequential samples. Cerebrospinal fluid from febrile and nonfebrile individuals contains a protein band that is electrophoretically identical with only one of these proteins. Since the trace proteins migrate, in urea-containing polyacrylamide gel electrophoresis, as if they has molecular size of less than or equal to30,000 daltons, their absence from cerebrospinal fluid implies the existence, in vivo, of interactions between them and other serum proteins. Under nondissociating conditions, four of the bands appear to circulate in physical interaction with one another. In molecular sieve chromatography at neutral pH in lipid-free sera, the trace proteins have an approximate molecular size of 165,000 daltons; in lipemic sera they have a molecular weight of larger than or equal to200,000 daltons. Their behavior in gel filtration and in ion-exchange chromatography excludes extensive interaction with any of the following: immunoglobulin M, immunoglobulin G, alpha2-macroglobulin, haptoglobin, and albumin. Interactions between these and other serum proteins are reduced by high concentrations of urea and by low PH. The mechanisms responsible for the observed protein-protein associations would appear to include electrostatic attraction, hydrogen bonding, and weak hydrophobic interaction.

Blood Proteins↗
PubMed1977

Depressed in vitro lymphocyte responses to PHA in patients with Hodgkin disease in continuous long remissions.

Twenty consecutive patients with Hodgkin disease in continuous complete remission and off treatment for at least 5 yr (range 5-25 yr, median 9 yr) were studied with a battery of immunologic parameters. Skin test reactivity to four common antigens, sensitization to 2,4-dinitrochlorobenzene, absolute lymphocyte count, relative percentage of T cells (as measured by spontaneous rosette formation with sheep erythrocytes) and B cells (as measured by immunofluorescence with polyvalent antiserum), and absolute number of T and B cells were normal when compared with controls. However, the mean value of lymphocyte response in vitro to the mitogen phytohemagglutinin for the study population was significantly decreased (p less than 0.001) when compared with the controls. This abnormality in response to mitogen could not be correlated with age, sex, stage, symptoms, histologic subclassification, or previous treatment. The data suggest the existence of a persisting cell-mediated immune defect in the circulating lymphocytes in patients with long-standing Hodgkin disease that might otherwise be considered "cured."

Antigens↗
PubMed1976

Eight-drug combination chemotherapy (MOPP and ABDV) and local radiotherapy for advanced Hodgkin's Disease.

Thirty-seven patients with advanced Hodgkin's disease have been treated for greater than or equal to 3 months with a protocol consisting of alternate monthly courses of MOPP (mechlorethamine, Oncovin [vincristine], procarbazine, and prednisone) and ABDV (adriamycin, bleomycin, DTIC, and vinblastine) with local radiotherapy (RT) to areas of originally bulky disease. This therapy produced CR in 19 of 19 previously untreated patients (100%), eight of nine previously treated with RT (89%), and six of nine previously treated with RT and MOPP (67%). The remaining patients are all PRs tending toward CR status. The median time to CR was 3.0 months. The median time in remission to date for the previously untreated patients is 8+ months (2+-14+). After an induction period of eight cycles of chemotherapy patients are maintained on alternate-month treatment continuing the alternating sequence. During this phase three patients have experienced reappearance of disease (one recurrence, one possible second primary lymphoma, and one recurrence in a patient whose original diagnosis is in doubt). The regimen has been well tolerated. All patients were treated as outpatients. Alopecia and neurotoxicity were mild and myelosuppression was moderate. Clinically significant cardiopulmonary toxicity has been limited to mild radiation pneumonitis in one patient and bleomycin pneumonitis which cleared during prednisone in a second patient.

Adolescent↗