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Biomedical subjects

D C Young

Publications and source records attributed to D C Young.

At least 73 records · Page 4Linked to original sources
PubMed1995

Radioimmunoguided surgery in primary colorectal carcinoma: an intraoperative prognostic tool and adjuvant to traditional staging.

BACKGROUND: The prognostic value of traditional staging classification for colorectal cancer has changed little since Dukes created the first staging scheme. Some patients with known metastatic disease are long-term survivors, while other patients with local disease die early. New intraoperative cancer detection technology, the radioimmunoguided surgery (RIGS) system, is being studied as a tool to aid in prediction of patient outcome. PATIENTS AND METHODS: Thirty-one patients with primary colorectal cancer were injected with the monoclonal antibody CC49, which was radiolabeled with iodine 125 (125I). A hand-held gamma-detecting probe was used at surgery to detect the radiolabeled antibody. Patients were classified as to the presence or absence of 125I-CC49-positive residual tissue at the close of surgery. Patient survival was analyzed. RESULTS: Follow-up ranged from 30 to 54 months. Survival of 11 stage I or II patients was longer than in 20 stage III or IV patients (P = 0.019). All 14 patients cleared of RIGS-positive tissue were alive at last follow-up, while 15 of 17 RIGS-positive patients died of their disease (P < 0.0001). CONCLUSIONS: The RIGS system used during surgery provides the surgeon with immediate prognostic information on patients with colorectal cancer and supplements traditional pathologic staging.

Adult↗
PubMed1995

Radioimmunoguided Surgery system improves survival for patients with recurrent colorectal cancer.

BACKGROUND: Advanced colorectal cancer is fatal. No systemic therapies have resulted in increased patient survival. METHODS: One hundred thirty-one patients with recurrent colorectal cancer enrolled in two prospective nonrandomized studies using Radioimmunoguided Surgery (RIGS) system from May 1986 to April 1992 have been analyzed. Eighty-six patients were injected with the anti-tumor-associated glycoprotein (TAG) antibody B72.3, and 45 patients were injected with the second-generation anti-TAG monoclonal antibody CC49. Both monoclonal antibodies were radiolabeled with iodine 125. Both traditional and RIGS explorations were used to determine resectability. Follow-up was a minimum of 28 months. RESULTS: Forty-nine (37.4%) of the 131 patients underwent a curative resection. Twenty-seven of the patients (55%) are alive 2 to 8 years after operation. The cancers of the remaining 82 patients were unresectable, and only two patients (2%) are alive. In this unresectable group alternative intraoperative therapeutic methods (intraoperative radiation therapy, intraperitoneal hyperthermic perfusion, hepatic lines, and brachytherapy) were tried in 11 patients with two survivors. There were no survivors in 18 patients whose cancers were found to be traditionally resectable but unresectable with RIGS or in the 53 patients whose cancers were clearly unresectable by traditional exploration. Patients selected for curative resection had significantly increased survival (p < 0.0001). CONCLUSIONS: As an intraoperative tool RIGS significantly improves the selection of patients for curative resection.

Adenocarcinoma↗
PubMed1995

Phase I trial of escalating doses of interleukin-1 beta in combination with a fixed dose of interleukin-2.

PURPOSE: Interleukin-1 (IL-1) and IL-2 have synergistic antitumor and myelostimulatory activities. We investigated the clinical and biologic effects of IL-1/IL-2 therapy. PATIENTS AND METHODS: Twenty patients with metastatic cancer, divided into five cohorts, were treated with escalating doses of IL-1 beta (0.005 to 0.2 micrograms/kg/d) administered as a 30-minute intravenous (IV) infusion on days 1 to 4, combined with a fixed dose of IL-2 (0.1 mg/m2/d) administered by continuous IV infusion on days 1 to 4. The 4-day cycles were repeated weekly for up to 8 weeks in the absence of toxicity and/or progressive disease. RESULTS: Patients tolerated up to 0.2 microgram/kg/d of IL-1 beta in combination with IL-2 without severe adverse effects. Peripheral-blood CD4-to-CD8 ratios and lymphokine-activated killer (LAK) activity were higher at the lower doses (0.005 to 0.05 microgram/kg/d) of IL-1 beta and higher than that of a cohort of patients treated with IL-2 alone. WBC counts, primarily neutrophils, increased significantly with higher doses of IL-1 beta (0.1 to 0.2 microgram/kg/d). Platelet counts were not significantly altered. Increases in serum IL-6, interferon gamma (IFN-gamma), and soluble IL-2 receptor levels were observed, but did not vary with IL-1 beta dose. Tumor regressions were observed in patients with colorectal cancer, melanoma, and renal cell carcinoma. CONCLUSION: IL-1 beta cancer be administered in combination with IL-2 with acceptable toxicity. Our results suggest that the addition of even low-dose IL-1 beta to IL-2 may be associated with potentially beneficial biologic activity; higher doses of IL-1 beta (0.1 to 0.2 microgram/kg/d) may add potentially beneficial hematologic activity.

Adjuvants, Immunologic↗
PubMed1995

Preoperative identification of patients at risk for delirium after major head and neck cancer surgery.

This study was performed to determine preoperative criteria for identifying patients at risk for delirium after major head and neck cancer surgery. The authors prospectively evaluated 138 consecutive patients undergoing head and neck cancer surgery lasting more than 2 hours at the Arthur G. James Cancer Hospital and Research Institute, Ohio State University, Columbus, from July 1993 through May 1994. Postoperative delirium developed in 24 of 138 patients (17%; 95% confidence interval 11% to 24%). The strongest univariate predictors of delirium were living alone (P = .005), the American Society of Anesthesiologists class (P = .003), and the preoperative white blood cell count (P < .0001). A predictive model for delirium using five criteria--age of 70 or more years, alcohol abuse, poor cognitive status, poor functional status, and markedly abnormal serum sodium, potassium, or glucose level--stratified the patients into three cohorts with an increasing risk of postoperative delirium (i.e., 9%, 19%, and 25%).

Aged↗
PubMed1994

Localization of tumor-reactive lymph node lymphocytes in vivo using radiolabeled monoclonal antibody.

BACKGROUND: Lymph node lymphocytes vary in their responsiveness to tumor. A technique has been developed that uses radiolabeled monoclonal antibody (MoAb) against the tumor-associated mucin, TAG-72, and a gamma-detecting probe by which lymph nodes containing microscopic tumor and/or shed TAG-72 can be identified in vivo. The immunologic characteristics of these lymph nodes were examined. METHODS: Patients with colon cancer received 125I-labeled MoAb CC49 by intravenous injection preoperatively. During laparotomy lymph nodes that appeared normal on inspection and palpation but which contained radiolabeled MoAb were identified using a hand-held gamma-detecting probe. These lymph nodes and other lymph node and tumor specimens were resected for analysis. RESULTS: Lymph nodes identified by the probe were found by immunohistochemical studies to contain microscopic tumor and/or shed antigen associated with germinal centers. They were characterized by greater CD4+:CD8+ ratios, rates of expansion, and cytolytic activity compared with lymphocytes from lymph nodes with macroscopic tumor, noninvolved lymph nodes, and tumors. All lymph node lymphocytes identified by the probe demonstrated significant proliferative responses to autologous tumor and, in contrast to lymphocytes from noninvolved lymph nodes, significant proliferative responses to allogeneic TAG-72+ tumor cells and to soluble TAG-72+ mucin. CONCLUSIONS: By locating lymph nodes with microscopic tumor and/or shed antigen, the use of radiolabeled MoAb in vivo can be used to reproducibly identify tumor-reactive lymph node lymphocytes. This technique may be useful in identifying cells for use in adoptive immunotherapy programs and in studying the regulation of immune responses in vivo.

Antibodies, Monoclonal↗
PubMed1994

High doses of oral contraceptives do not alter endometrial alpha 1 and alpha v beta 3 integrins in the late implantation window.

OBJECTIVE: To assess the effects of an emergency contraceptive agent on the distribution of integrin heterodimers during that part of the implantation window. DESIGN: Prospective, case-controlled study in a university-based Population Program. In the first ovulatory control cycle after the detection of LH surge, patients had endometrial sampling 11 days after the surge. In the next cycle the procedure was repeated 2 days after the administration of a postcoital contraceptive agent on day 9 after LH surge (100 g ethinyl E2 and 2 mg norgestrel). MAIN OUTCOME MEASURES: The effects of postcoital contraceptives on the expression of integrin heterodimers (alpha 1 and alpha v beta 3 subunits) reported to be unique to secretory phase was determined. RESULTS: All six specimens were consistent histologically with days 24 and 25 of the menstrual cycle by light microscopy. Using immunohistochemistry, strong membrane staining of endometrial glandular cells and superficial epithelium for both alpha 1 subunit and vitronectin (alpha v beta 3) receptor was observed in treatment and controls. No diminution of intensity or distribution was observed relative to pretreatment controls. CONCLUSIONS: There is no apparent change in the level of these two integrins in the human endometrium when high-dose oral contraceptives are given in the later stages of the implantation window. This suggests that the high doses of steroids used in emergency contraceptives may exert their effect through more complex mechanisms than endometrial cell surface changes.

Contraceptives, Oral↗
PubMed1994

Correlation of human bladder tumor histoculture proliferation and sensitivity to mitomycin C with tumor pathobiology.

This study examined the in vitro proliferation and mitomycin C (MMC) sensitivity of patient bladder tumors as a function of the tumor pathobiology. Surgical specimens of transitional cell carcinoma of the bladder were maintained as histocultures on collagen gels. The thymidine labeling index (LI) was determined by autoradiography and the labeling for proliferating cell nuclear antigen (PCNA) by immunohistochemistry. There was a linear correlation between the thymidine LI and the PCNA LI, but the PCNA LI were quantitatively lower than the thymidine LI. The mean thymidine LI were 30.9, 32.4 and 51.5% for the grade I, II and III tumors, 33.6 and 56.3% for the superficial (Tis, Ta and T1) and invasive (T2-T4) tumors, and 28.9 and 50.9% for the diploid and aneuploid tumors. Analysis of variance indicates that these differences were statistically significant. These data indicate that the proliferation of tumor histocultures paralleled the tumor aggressiveness in vivo. The tumor sensitivity to MMC, measured by the inhibition of the thymidine LI of tumor cells, was studied in 31 tumors. At a 2 hour exposure, as is currently used in intravesical therapy, the MMC concentrations required for 50% inhibition of thymidine LI (IC50) showed a 120-fold intertumor variation (0.102 to 12.4 micrograms./ml.). The sensitivity to MMC inversely correlated with tumor aggressiveness. The IC50 increased with tumor LI (p < 0.05). The mean IC50 were 2.61 and 5.79 micrograms./ml. for superficial and invasive tumors (p < 0.05), 1.06, 3.05 and 4.49 micrograms./ml. for grade I, II and III tumors (p < 0.05), and 2.53 and 4.31 micrograms./ml. for diploid and aneuploid tumors (p = 0.14). These data indicate a large difference in sensitivity of human bladder tumors to MMC, with greater sensitivity for well-differentiated superficial tumors and lesser sensitivity for undifferentiated, invasive tumors.

Autoradiography↗
PubMed1994

The assessment of obstruction in the newborn with unilateral hydronephrosis by measuring the size of the opposite kidney.

We measured the size of the normal kidney opposite a unilateral hydronephrotic kidney in infants to determine if compensatory changes occurred and could be used as a diagnostic test for defining or excluding obstruction. Comparison of subgroups of neonates with unilateral hydronephrosis or multicystic renal dysplasia to normal controls demonstrated that compensatory changes do occur in the normal kidney. Normal kidneys opposite obstructed hydronephrotic kidneys requiring surgery became larger than normal for age. Normal kidneys opposite nonobstructed poorly functioning hydronephrotic kidneys whose function rapidly improved were smaller than normal for age. These changes in renal growth by the normal newborn kidney reflect renal counterbalance, which is exaggerated in this age group and which may be used to corroborate rapid changes in renal function caused by the presence or absence of obstruction. By plotting serial measurements of normal renal length on a renal growth chart, the diagnosis of obstruction in newborn hydronephrosis can be facilitated and the clinical management of the patient improved.

Humans↗
PubMed1994

Emergency contraception alters progesterone-associated endometrial protein in serum and uterine luminal fluid.

OBJECTIVE: To evaluate the effect of high-dose oral contraceptives on serum and uterine luminal fluid progesterone-associated endometrial protein in the luteal phase. METHODS: Five ovulatory women participated in the study. In a control cycle, serum and uterine lavage samples were collected on luteal day 11. In the next cycle, on luteal day 9, the participants were given two 50-micrograms ethinyl estradiol-norgestrel tablets, repeated 12 hours later. Serum and uterine lavage samples were collected 48 hours (luteal day 11) after the last dose and analyzed by two-dimensional polyacrylamide gel electrophoresis and radioimmunoassays of the serum. RESULTS: Progesterone-associated endometrial protein levels were lower in sera from treated compared with control cycles. Analysis of serum levels of this protein by two-dimensional polyacrylamide gel electrophoresis did not reveal bands corresponding to the known size and charge characteristics (27 kd and pI of 4.9) in either control or treatment samples. On the other hand, in uterine lavage samples, a complete suppression of the 27-kd, pI-4.9 species was evident after treatment. CONCLUSION: High-dose ethinyl estradiol-norgestrel emergency contraception effectively suppresses progesterone-associated endometrial protein in the midluteal uterus, potentially altering the endometrial environment unfavorably and affecting the survival of the early embryo.

Contraceptives, Oral, Hormonal↗
PubMed1993

Selective inactivation of eukaryotic beta-galactosidase in assays for inhibitors of HIV-1 TAT using bacterial beta-galactosidase as a reporter enzyme.

Bacterial beta-galactosidase is one of several reporter enzymes used in studying the transcriptional activity of eukaryotic promoters. Although it is one of the easiest and least expensive enzymes to assay, its use has been limited because of its low sensitivity, which is due in part to endogenous levels of beta-galactosidase in many eukaryotic cells. In this study, we compared the pH and salt requirements, as well as the heat stability, of bacterial and eukaryotic beta-galactosidase in order to identify conditions which would inhibit the beta-galactosidase enzyme endogenous to eukaryotic cells without adversely affecting the activity of either purified bacterial beta-galactosidase or reporter beta-galactosidase produced after transfection of expression vectors into eukaryotic cells. Heat treatment at 50 degrees C for 1 h inactivated the beta-galactosidase activity endogenous to several eukaryotic cell lines by as much as 40-fold without adversely affecting the activity of bacterial beta-galactosidase. This treatment increased the sensitivity of this reporter enzyme and allowed the development of a rapid and quantifiable screening assay for HIV-1 tat inhibitors.

Animals↗
PubMed1993

Treatment of Diamond-Blackfan anemia with recombinant human interleukin-3.

This report describes the response of eighteen Diamond-Blackfan anemia (DBA) patients to recombinant human interleukin-3 (rhIL-3). rhIL-3 was administered subcutaneously once daily on an escalating dose schedule (0.5 to 10 micrograms/kg/d). The rhIL-3 dose was escalated every 21 days until erythroid response was attained, grade III or IV nonhematologic toxicity was observed, or the maximum rhIL-3 dose was reached. Four patients experienced clinically significant erythroid responses. Two of the responders were steroid-dependent and transfusion-independent, while two were steroid-independent and transfusion-dependent. Baseline clinical or laboratory parameters, in particular in vitro bone marrow erythroid progenitor assays, were not useful in predicting rhIL-3 response. rhIL-3 administered at 5 to 10 micrograms/kg/d was associated with an increase in total white blood cell count, secondary to increases in neutrophils, eosinophils, and lymphocytes. Patients experienced a dose-dependent elevation in absolute eosinophils across the entire dose range. Two of the responding patients remain on maintenance rhIL-3, without diminution of effect at 244 and 370 + days. rhIL-3 was discontinued in the other two responders, because of the development of deep venous thrombi.

Adolescent↗
PubMed1993

3-Quinolinecarboxamides. A series of novel orally-active antiherpetic agents.

A series of novel 3-quinolinecarboxamides that are structurally similar to the quinolone class of antibacterial agents possess excellent antiherpetic properties. By modifying the quinoline ring at the 1-, 2-, 3-, and 7-positions, analogues were identified that have up to 5-fold increased HSV-2 plaque-reduction potency relative to acyclovir. In a single-dose mouse model of infection, one of the most potent derivatives in vitro, 1-(4-fluorophenyl)-1,4-dihydro-4-oxo-7-(4-pyridinyl)-3-quinolinecarbo xamide (97), displayed comparable oral antiherpetic efficacy to acyclovir at 1/16 the dose; in a multiple-dose regimen, however, 97 was 2-fold less potent. In mice dosed orally with 97, sustained plasma drug levels were evident that may account for the high efficacy observed. The molecular mechanism of action of these agents is not known; however, based on in vitro studies with acyclovir resistant mutants, it is likely that the mechanism differs from that of acyclovir. In vitro plaque-reduction potency was not generally predictive of oral efficacy in mice. An X-ray crystal structure of 97 corroborated the assignment of structure and provided useful insights as to the effect of conformation on plaque-reduction potency.

Acyclovir↗
PubMed1993

Identifying high-risk patients before head and neck oncologic surgery.

Patients from the Comprehensive Cancer Center of the Arthur G. James Cancer Hospital and Research Institute, Ohio State University, Columbus, who were undergoing major head and neck oncologic surgery were prospectively studied to determine predictors of postoperative medical complications and wound infection. Of 119 patients studied, 28 (24%) had at least one postoperative medical complication. The strongest predictors of medical complication were poor functional capacity as assessed by the Specific Activity Scale questionnaire and alcohol abuse. Thirteen patients (11%) developed wound infections. The strongest predictors of wound infection were an elevated preoperative platelet count and prolonged surgery. Wound infection was the strongest correlate of prolonged hospital stay. These findings suggest that the Specific Activity Scale questionnaire identifies patients at risk for medical complication, that alcohol abuse should be managed aggressively, and that thrombocytosis identifies patients at risk for wound infection.

Adult↗
PubMed1993

Successful treatment of Diamond-Blackfan anemia with interleukin 3.

This report describes the response of 18 Diamond-Blackfan anemia (DBA) patients to recombinant human interleukin 3 (rhIL-3). rhIL-3 was administered s.c. once daily on an escalating dose schedule (0.5-10 micrograms/kg/day). The rhIL-3 dose was escalated every 21 days until erythroid response was attained, grade III or IV nonhematologic toxicity was observed, or the maximal rhIL-3 dose was reached. Four patients experienced clinically significant erythroid responses. Two of the responders were steroid-dependent and transfusion-independent, while two were steroid-independent and transfusion-dependent. Baseline clinical or laboratory parameters, in particular in vitro bone marrow erythroid progenitor assays, were not useful in predicting rhIL-3 response. Two of the responding patients remain on maintenance rhIL-3 without diminution of effect at 490 and 855+ days. rhIL-3 was discontinued in the other two responders because of the development of deep venous thrombi.

Animals↗
PubMed1993

Cortical blindness and seizures possibly related to cisplatin, vinblastine, and bleomycin treatment of ovarian dysgerminoma.

Ovarian dysgerminoma is the most common ovarian malignancy in young women. Conservative treatment is indicated in the reproductive-age woman who wishes to preserve childbearing capacity. This case report describes a patient with ovarian dysgerminoma who underwent chemotherapy with a cisplatin-vinblastine-bleomycin regimen that resulted in serious toxic complications--including cortical blindness and seizures--that were transient in nature. Although current chemotherapy regimens have dramatically improved the overall survival of women with germ-cell tumors, there are toxic complications such as those demonstrated in this report, and toxicity must be balanced against presumed benefit.

Adult↗
PubMed1993

GnRH agonist exposure during the first trimester of pregnancy.

OBJECTIVE: To evaluate pregnancy outcome in infertility patients with unrecognized exposure to a GnRH agonist in the first trimester. METHODS: Five women were given GnRH agonist before controlled ovarian hyperstimulation for in vitro fertilization cycles. The medication was administered in a dose of 0.5 mg/day, with drug exposure beginning on cycle day 21. The duration of exposure in all patients was 14-21 days. Thus, all five women received the medication at 3-6 weeks' estimated gestational age by menstrual dating. Pregnancy tests were not performed before the first injection of the GnRH agonist. RESULTS: Three of the five pregnancies progressed to term without complication, and normal healthy infants were delivered. Missed abortion occurred in one pregnancy, and another ended in induced abortion at 13 weeks because of trisomy 18. CONCLUSIONS: This experience suggests that despite manipulation of the hypothalamic-pituitary-ovarian axis by administration of GnRH agonist in the first trimester of pregnancy, normal pregnancies can result. Pregnancies in these patients should not be terminated because of drug exposure alone.

Abortion, Missed↗