Search PubMed⌕ Search

Biomedical subjects

D C Young

Publications and source records attributed to D C Young.

At least 55 records · Page 3Linked to original sources
PubMed1996

The role of diagnostic imaging in women with breast implants.

Women who have undergone augmentation mammoplasty with silicone gel implants may present for routine breast cancer screening or with palpable breast lumps. Conventional mammography supplemented by additional displaced or Eklund view is usually sufficient to detect most abnormalities. Ultrasonographic evaluation may be performed as an ancillary technique to characterize palpable lumps or nonpalpable lesions detected on mammography. In patients suspected of having implant rupture, conventional mammography and displaced views are performed. If clinical findings warrant, magnetic resonance imaging may be performed to detect intracapsular and extracapsular rupture and migration of silicone globules to the axilla, branchial plexus and adjacent structures.

Breast↗
PubMed1996

Intra-abdominal patterns of disease dissemination in colorectal cancer identified using radioimmunoguided surgery.

PURPOSE: Patterns of metastatic spread are difficult to determine with routine postoperative follow-up. This study was undertaken to evaluate two selected populations of colorectal cancer patients injected and screened with anti-tumor antibody. METHODS: Eighty-six evaluable patients with colorectal cancer underwent exploratory laparotomy with both traditional surgical exploration and radioimmunoguided surgery (RIGS) following injection of 125I-labeled CC49 monoclonal antibody. RIGS-positive tissue detectable with a handheld gamma-detecting probe was defined as tissue involved with the disease process. Comparisons were made between extent of disease using traditional exploration and extent using RIGS. RESULTS: In 41 patients with primary disease, traditional exploration detected 45 sites of disease (1.1 sites/patient) compared with 153 RIGS-positive sites (3.7 sites/patient). In 45 patients with recurrent disease, traditional exploration found 116 sites (2.6 sites/patient) vs. 184 RIGS-positive sites (4.1 sites/patient). Involvement by selected anatomic sites is shown below [Table: see text]. CONCLUSION: RIGS detected more tissue involved in disease process for all sites in both primary and recurrent disease except liver metastases. Areas with highest proportion of RIGS-positive tissue, the gastrohepatic ligament and celiac nodes, are rarely resected and are not pathologically examined. Positive RIGS localization of tumor antigen in these areas suggests more extensive dissemination of disease process.

Abdominal Neoplasms↗
PubMed1996

Radioimmunoguided surgery for colorectal cancer.

BACKGROUND: Operations for patients with colorectal cancer are based on traditions established by historical experience. Radioimmunoguided surgery (RIGS) provides new information that challenges these traditions. METHODS: Thirty-two patients with primary colorectal cancer underwent RIGS after being injected with anti-TAG-72 murine monoclonal antibody CC49 labeled with iodine-125. Sixteen of the patients had all gross tumor and RIGS-positive tissue removed (RIGS-negative group), and 16 had only traditional extirpation of the tumor because RIGS-positive tissue was too diffuse (RIGS-positive group). RESULTS: In the 16 patients having all RIGS-positive tissue removed, five had traditional regional en bloc resections and 11 had additional extraregional tissues resected. Identification of extraregional disease added two liver resections and 25 lymphadenectomies: 10 of the gastrohepatic ligament, five celia axis, six retroperitoneal, and four iliac. With a median follow-up of 37 months, survival in the RIGS-negative group is 100%. In 14 of 16 patients (87.5%) there is no evidence of disease. In the RIGS-positive group, follow-up shows 14 of 16 patients are dead and two are alive with disease (p < 0.0001). CONCLUSION: These results suggest that RIGS identifies patterns of disease dissemination different from those identified by traditional staging techniques. Removal of additional RIGS-positive tissues in nontraditional areas may improve survival.

Adult↗
PubMed1996

Intraperitoneal hyperthermic perfusion with mitomycin C for colorectal cancer with peritoneal metastases.

BACKGROUND: Intraperitoneal (i.p.) metastases pose a special problem for surgical treatment because of their multiplicity and microscopic size. This study was designed to examine the feasibility and safety of i.p. hyperthermic perfusion (IPHP) with mitomycin C (MMC) for treating recurrent colorectal cancer. METHODS: Fifteen patients with metastatic colon cancer were treated. All patients underwent cytoreductive procedures leaving only residual i.p. metastases < 1 cm in diameter. All patients had received prior systemic chemotherapy, but their disease had progressed. Intraperitoneal chemotherapy was administered through three large catheters (28 French) using a closed system of two pumps, a heat exchanger, and two filters. After the patient's abdominal temperature reached 41 degrees C, 45-60 mg of MMC was circulated intraperitoneally for 1 h. RESULTS: The majority of patients had various anastomoses: small bowel (n = 11), large bowel (n = 5), and urologic (n = 5). No anastomotic complications occurred in any of the patients. One patient experienced severe systemic MMC toxicity, which caused cytopenia and respiratory depression. In all patients the carcinoembryonic antigen (CEA) level decreased after surgery and IPHP. Median follow-up was 10 months, and recurrence was defined as an elevation in CEA level. Disease recurred in three patients within 5 months, and disease recurred in seven other patients over the next 3 months; one patient remains clinically free of disease after 8 months. CONCLUSION: Our data suggest that IPHP is a safe palliative method of treatment for patients with peritoneal carcinomatosis. The median patient response duration of 6 months may warrant consideration of a repeat IPHP procedure at that time.

Antibiotics, Antineoplastic↗
PubMed1996

Vaginal misoprostol for induction of labor: a randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness and safety of the vaginal application of misoprostol for induction of labor at term, with the interval duration from labor induction to vaginal birth as the primary outcome measure. METHODS: Two hundred twenty-two women with indications for induction of labor at term were randomized to receive either misoprostol 50 micrograms per vagina every 4 hours as needed or our standard approach (physician-chosen combinations of intracervical or vaginal dinoprostone every 6 hours, artificial rupture of membranes, and oxytocin infusion). RESULTS: Mean (+/-standard deviation) time to vaginal delivery was 753 +/- 588 minutes for misoprostol versus 941 +/- 506 minutes for the physician-chosen combination (P = .018). Oxytocin infusion was used less frequently (relative risk [RR] 0.48, 95% confidence interval [CI] 0.31-0.74). There was no significant difference in cesarean rate or maternal morbidity. Neonatal outcomes, including cord-blood acid-base analysis, were not significantly different. The estimated cost per patient in Canadian dollars for prostaglandins was $0.22 with misoprostol and $70.00 with standard therapy. CONCLUSION: Vaginal misoprostol is a cost-effective alternative to current labor-induction protocols. We found no evidence of harm to mother or newborn in substantive outcomes.

Administration, Intravaginal↗
PubMed1996

An algorithm for predicting nonorgan confined prostate cancer using the results obtained from sextant core biopsies with prostate specific antigen level.

PURPOSE: We determined the enhanced ability to predict nonorgan confined prostate cancer using several histopathological and quantitative nuclear imaging parameters combined with serum prostate specific antigen (PSA). MATERIALS AND METHODS: Several independent pathological and quantitative image analysis variables obtained from sextant biopsy specimens, as well as preoperative PSA were used. The study population included 210 patients with pathologically staged disease (192 with PSA). All variables were examined by univariate and multivariate logistic regression analyses to assess ability to predict disease organ confinement status. RESULTS: Univariate logistic regression analysis demonstrated that, in decreasing order, quantitative nuclear grade, preoperative PSA, total percent tumor involvement, number of positive sextant cores, preoperative Gleason score and involvement of more than 5% of a base and/or apex biopsy were significant (p < or = 0.006) for prediction of disease organ confinement status. Backward stepwise logistic regression was applied to these univariately significant variables, including deoxyribonucleic acid ploidy, to calculate a multivariate model for prediction of disease organ confinement status. This algorithm had a sensitivity of 85.7%, specificity 71.3%, positive predictive value 72.9%, negative predictive value 84.7% and area under the receiver operating characteristic curve 85.9%. CONCLUSIONS: Information from pathological study of sextant prostate biopsies, preoperative PSA blood test and a new image analysis variable termed quantitative nuclear grade can be combined to create a multivariate algorithm that can predict more accurately nonorgan confined prostate cancer compared to previously reported methods.

Aged↗
PubMed1996

Baseline hemoglobin as a predictor of risk of transfusion and response to Epoetin alfa in orthopedic surgery patients.

A multicenter, double-blind, placebo-controlled, parallel-group study was undertaken to determine whether Epoetin alfa can reduce perioperative transfusion requirements. Twenty-six medical centers enrolled 316 patients who were scheduled for major orthopedic surgery and were expected to require > or = 2 units of blood. Patients were stratified according to baseline hemoglobin levels and randomly assigned to receive either Epoetin alfa (300 IU/kg or 100 IU/kg) or placebo for 15 consecutive days starting 10 days prior to, on the day of, and for 4 days after surgery. Epoetin alfa (300 IU/kg) resulted in significantly less exposure to allogeneic blood transfusion compared with placebo (16%) versus 45%) in patients whose baseline hemoglobin level was > 10 to < or = 13 g/dL (P = 0.024). Mean number of units transfused per patient was also lower among those treated with Epoetin alfa (overall, P = 0.027). Epoetin alfa was safe and well tolerated in this population.

Aged↗
PubMed1995

Screening of cyclic peptide phage libraries identifies ligands that bind streptavidin with high affinities.

The screening of combinatorial peptide libraries has emerged as an important tool in the discovery of novel substrates or ligands for enzyme and receptor targets. For example, screening linear peptide libraries using streptavidin as a model receptor system has previously identified many low-affinity peptide ligands, all of which contain the common motif His-Pro-Gln (HPQ). We reasoned that constraining the conformational freedom of linear peptides by cyclization in a library would yield peptide ligands of increased affinity. Three different cyclic peptide libraries were constructed in an M13 phage display system as N-terminal pIII protein fusions. The random peptide sequences were flanked by two cysteine residues, which allows efficient disulfide bond formation and cyclization during phage assembly. These cyclic peptide libraries were screened with streptavidin as the model receptor system. Many sequences, all of which contained the motif His-Pro-Gln (HPQ), were discovered, and in the preceding paper, the structures of complexes of streptavidin-bound cyclic and linear peptides are described (Katz, 1995). Analysis of binding kinetics and affinities demonstrated that the conformationally constrained cyclic peptides bound streptavidin with affinities up to 3 orders of magnitude higher than linear peptides identified in previous library screens. These results demonstrate the potential of screening conformationally constrained peptide libraries for high-affinity novel receptor ligands or enzyme substrates.

Amino Acid Sequence↗
PubMed1995

Keto/enol epoxy steroids as HIV-1 Tat inhibitors: structure-activity relationships and pharmacophore localization.

Inhibition of the HIV-1 nuclear regulatory protein tat could potentially yield particularly useful drugs because it functions as an activator of transcription. It has no known cellular counterpart, and deletions in the tat gene destroy the ability of HIV-1 to replicate. We recently reported that a structurally unique class of tat inhibitors, 3-keto/enol 4,5-alpha-epoxy steroids bearing electron-withdrawing substituents at position 2, specifically inhibit tat-induced gene expression in virus free transfected SW480 cells. In this paper, we report on additional SAR (structure-activity relationships) for the steroid series and the localization of the pharmacophore to the A-ring functionality. There is a weak enantioselective preference for the natural steroid stereochemistry and hints of additional SAR in the electron-withdrawing group. Compound 34a is of particular interest in that it inhibits HIV replication in H9 cells at a concentration equivalent to its inhibitory level in the primary tat assay.

Cell Line↗
PubMed1995

Cyclic variations of 3-quinolinecarboxamides and effects on antiherpetic activity.

Supported by the antiherpetic properties of 3-quinolinecarboxamides and the importance of the planar intramolecular H-bonded beta-keto amide pharmacophore, a series of novel conformationally rigid analogues that contain a heterocyclic bridge between the 3- and 4-positions of the quinoline ring have been evaluated. Two isoxazolo-fused derivatives 17 and 23 displayed good in vitro antiherpetic potency that was similar to that of 1, the 3-quinolinecarboxamide that served as the comparison structure for this study. The pyrazolo, pyrrolo, and pyrimido derivatives showed considerably less or no activity. In vitro activity did not translate to in vivo efficacy. For 17, the lack of in vivo activity is likely a consequence of insufficient plasma drug levels (both Cmax and duration) in mice relative to the MIC versus HSV-2.

Animals↗
PubMed1995

The significance of intraoperative periportal lymph node metastasis identification in patients with colorectal carcinoma.

BACKGROUND: Nine patients who underwent Radioimmunoguided Surgery (RIGS) (Neoprobe Corporation, Dublin, OH) procedures for colorectal cancer were found to have disease recurrence in the periportal area. This led to a retrospective study to determine whether periportal lymph node involvement could have been predicted intraoperatively for these patients. METHODS: One hundred twenty-four patients underwent second-look RIGS for recurrent colon and rectal cancer from 1986 to 1992. The monoclonal antibody (MAb) B72.3 was administered as the carrier agent to 87 patients and the CC49 second-generation MAb was administered to 37 patients. Both MAbs were radiolabeled with Iodine-125. RESULTS: Periportal lymph nodes with RIGS-positive tissue were found in 47 (38%) patients, hematoxylin and eosin-positive lymph nodes were found in 13 of 47, and in further immunohistochemical studies performed for 31 of the remaining 34 patients, positive lymph nodes were found in 8, resulting in an incidence of 48% (21/44). A critical review of the nine patients' charts who later presented with a tumor mass in the periportal area demonstrated intraoperative gamma-detecting probe counts in ratios three to five times that of the normal adjacent tissues in the periportal area at the time of first exploration. Probe-directed biopsy was reported to be histologically negative for tumor in these patients, and, thus, the surgeon proceeded assuming the periportal area to be negative. A retrospective study of the periportal lymph nodes of these patients using cytokeratin immunohistochemical analysis identified tumor in five (56%). CONCLUSIONS: These findings suggest that the RIGS system may be a valuable method of intraoperative prediction and detection of periportal lymph node metastasis.

Antibodies, Monoclonal↗
PubMed1995

Analysis of topoisomerase I/DNA complexes in patients administered topotecan.

As part of a Phase II clinical trial of topotecan, DNA breakage in vivo was measured by detecting covalent topoisomerase/DNA intermediates in peripheral blood. The ICE (in vivo complex of enzyme) bioassay was used to assess topotecan activity in the peripheral blood of patients before, during, and after infusion therapy. The results can be summarized as: (a) ICE bioassay is a specific, antibody-based assay for topoisomerase I-mediated DNA damage. Topoisomerase I/DNA complex formation can be monitored unambiguously in the absence of topotecan to establish a basal level of endogenous enzyme action on DNA; (b) infusion of topotecan significantly stimulated formation of covalent enzyme/DNA complexes. Complexes were detected within 5 min postinfusion and increased over the course of a 30-min treatment; (c) after termination of infusion, complex formation decreased by 3-4-fold within 30 min, showing that cleavage complexes quickly reseal after drug withdrawal; and (d) formation of complexes varied widely between patients. The ICE bioassay can evaluate the effects of topoisomerase I inhibitors on target tissues; thus, it may valuable in predicting response to these drugs.

Antineoplastic Agents↗
PubMed1995

Decline of posttreatment tumor marker levels after therapy of nonsmall cell lung cancer. A useful outcome predictor.

BACKGROUND: The assessment of treatment efficacy in nonsmall cell lung cancer (NSCLC) is limited by the lack of a clear association between clinical response and survival. The prognostic usefulness of treatment-induced tumor-marker declines in NSCLC has not been established. The authors investigated the prognostic significance of treatment-induced declination in tumor marker levels of carcinoembryonic antigen, CA 19-9, and CA 125 in a group of patients with NSCLC treated with a brief course of cisplatin-based chemotherapy. METHODS: Eighty-three patients with NSCLC enrolled on 2 related treatment protocols had pretreatment tumor-marker determinations. Patients were restaged 10 to 12 weeks after study entry, and clinical and marker responses were determined. RESULTS: Thirty-eight patients (46%) had elevated pretreatment tumor markers, 36 (42%) of whom were evaluable for both clinical and marker responses. Pretreatment, the latter 36 individuals had measurable or evaluable disease, and at least one elevated tumor marker (greater than twice normal); posttreatment, they had follow-up measurements of both parameters. Of the 36 patients, 8 had normalization of tumor marker levels, 13 had 50-99% marker level declination, and 15 had less than 50% or no declination. In the same group of 36 patients, there were, 1 patient with complete clinical response, 11 with partial response, 19 with stable disease, and 5 with progressive disease. Marker responses occurred with equal frequency in clinical responders and nonresponders. There was no association between clinical response and survival, but there was a strong association between marker response and survival. CONCLUSIONS: In patients with nonsmall cell lung cancer with elevated pretreatment tumor marker levels, treatment-induced marker level declination can be a surrogate indicator for survival.

Adult↗
PubMed1995

Sextant prostate biopsies. A histopathologic correlation with radical prostatectomy specimens.

BACKGROUND: Among patients with clinically localized prostate cancer, preoperative prediction of tumor volume and pathologic stage has been unreliable. This study examines the application of transrectal ultrasound-guided sextant biopsies to predict the extent of disease. METHODS: One hundred and two patients with clinically resectable prostate cancer were evaluated by systematic sextant biopsies. Radical prostatectomy specimens were embedded totally as whole mounts, tumor areas were outlined, and volume was measured using a digital scanner. The number of positive sextant biopsies was compared with age, race, preoperative prostate specific antigen (PSA), PSA density, DNA ploidy, pathologic stage, capsular and seminal vesicle involvement, prostate and tumor volume, and Gleason score. Stepwise logistic regression was used to determine if pathologic stage or tumor size could be predicted by these parameters. RESULTS: The number of positive sextant biopsies correlated with traditional prognostic indicators. When patients with three or fewer positive biopsies were compared with those with four or more positive sextant biopsies, significant differences were identified relative to preoperative PSA (P < 0.001), tumor volume (P < 0.001), pathologic stage (P < 0.001), Gleason score (P < 0.001), seminal vesicle involvement (P < 0.001), and capsular penetration (P < 0.001). There were no significant differences based on age, race, DNA ploidy, and overall prostate volume. Logistic regression showed that patients with four or more positive sextant biopsies and high Gleason score had a greater likelihood of pT3 classification. Likewise, the probabilities of a tumor volume less than 0.5 ml could be predicted by the number of positive sextant biopsies and PSA alone. The number of positive sextant biopsies was the only factor that could predict a tumor volume greater than 4.0 ml. CONCLUSION: The number of positive sextant biopsies appears to be an important prognostic indicator of pathologic (pT) classification and tumor volume. This information is valuable in selecting the treatment strategy for patients with prostate cancer.

Age Factors↗
PubMed1995

The natural history of breast cancer with more than 10 positive nodes.

BACKGROUND: Experimental protocols are being used increasingly to treat breast cancer with > 10 positive nodes. An appreciation of the natural history of this disease is crucial for choosing the optimal therapeutic approach. PATIENTS AND METHODS: We retrospectively reviewed the records of 141 patients who had breast cancer with > 10 positive nodes and received definitive therapy at our institution in the years 1969 through 1991. Because therapy evolved during this period, we compared the results from 1969 through 1981 to those from 1982 through 1991. RESULTS: Ninety-one patients (65%) were > or = 50 years of age. Fifty-four (38%) were estrogen receptor (ER) positive, the remainder were ER negative or ER status unknown. Fifty-seven (40%) had 10 to 15 positive nodes, 63 (45%) had 16 to 25, and 21 (15%) had > 25. The ratio of positive nodes to total nodes was < 50% in 22 patients, 50% to 75% in 49, and > 75% in 70. One hundred thirty-four patients (95%) underwent modified or radical mastectomy. Forty (28%) received adjuvant chemotherapy, including 16 (11%) of 58 patients treated prior to 1981. Eleven patients (8%) were treated with adjuvant radiation therapy. The median survival for all patients was 52 months, with an actuarial survival of 29% at 10 years. Patients treated after 1981 had significantly improved survival. They lived a median of 68 months postoperatively, as compared to 41 months among patients treated earlier. CONCLUSIONS: This is a high-risk group of patients, yet there is a small subset who can obtain a long survival with standard treatment modalities.

Adult↗