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Biomedical subjects

E W Martin

Publications and source records attributed to E W Martin.

At least 91 records · Page 5Linked to original sources
PubMed1988

Intraoperative radioimmunolocalization of colorectal carcinoma with a hand-held gamma probe and MAb B72.3: comparison of in vivo gamma probe counts with in vitro MAb radiolocalization.

A new intraoperative approach to tumor localization using radiolabelled monoclonal antibody (MAb) B72.3 involves the use of a hand-held gamma-detecting probe (GDP) by the surgeon and, subsequently, the pathologist. We report here the use of 125I-labelled MAb B72.3 IgG and a GDP to localize primary and metastatic colorectal cancer in 31 patients. The patients were administered radiolabelled MAb i.v., and all underwent surgical exploration 5 to 35 days post-injection. In vivo localization of the MAb was evaluated using a GDP, with tumor and normal tissue counts being obtained. In each case, the subsequent tumor and normal tissue that were resected were analyzed in vitro for MAb localization; this was evaluated by calculating the radiolocalization index, i.e., the ratio of the injected dose per gram localized to tumor versus that of normal tissue. When the GDP was used intraoperatively, MAb B72.3 localized tumors in 68% (21/31) of the patients; the arbitrary criterion of tumor-to-normal tissue ratios higher than or equal to 2.0:1 in vivo being taken as positive. Resected tumor radiolocalization indices ranged from 0.5 to 543, and 71% (22/31) of the patients studied had tumors with radiolocalization indices higher than or equal to 3. Of 50 carcinoma biopsies, 34 that were probe-positive were antigen-positive when B72.3 was used in immunoperoxidase assays, while 4 carcinoma biopsies that were probe-negative were also antigen-negative. Twelve of 50 biopsies were probe-negative and antigen-positive, but many of these lesions only contained a few antigen-positive cells; none of the 50 was probe-positive and antigen-negative. Tumors of all histologic grades localized injected MAb and, in general, higher in vivo probe ratios and radiolocalization indices were obtained from patients who underwent surgery 20 to 35 days following injection of the MAb. MAb B72.3 localized tumor in all sites to which colon carcinoma commonly metastasizes, including mesenteric and peri-aortic lymph nodes, liver, lung, and peri-rectal soft tissue. There was a strong statistical correlation (p = 0.001) between detecting MAb B72.3 localization to tumors using the GDP intraoperatively and subsequent in vitro analysis of cpm/g for tumor versus normal tissues. These studies thus further validate the use of 125I-labelled MAb B72.3 IgG and of a hand-held gamma probe for the intraoperative detection of carcinomatous lesions.

Adult↗
PubMed1988

Use of polar solvents in chemoprevention of 1,2-dimethylhydrazine-induced colon cancer.

To examine the effect of the polar solvents on 1,2-dimethylhydrazine (DMH)-induced colon cancer, 100 male Sprague-Dawley rats were randomly allocated to a control and three treatment groups. Treated animals received N-methylformamide (NMF), dimethylsulfoxide (DMSO), or methylsulfonylmethane (MSM) added to drinking water 1 week before carcinogen injections commenced and for the duration of the experiment. Primary tumors were detected by serial laparotomy under ether anesthesia performed at 2-month intervals and commencing after carcinogen injections had been completed. The average time to tumor onset was significantly delayed in rats receiving NMF and MSM (P = 0.0141 and 0.0398 respectively, Mantel-Haenszel test). In addition, fewer poorly differentiated tumors were noted in treatment groups. No weight loss or toxicity was observed. These findings demonstrate that the polar solvents significantly reduce the latent period to tumor onset in DMH-induced colon cancer and indicate the need to further investigate such compounds as chemopreventive agents.

1,2-Dimethylhydrazine↗
PubMed1988

Multiple reoperations in recurrent colorectal carcinoma. An analysis of morbidity, mortality, and survival.

Fifty-eight patients in an existing prospective study were evaluated to determine if multiple reoperations for recurrent colorectal carcinoma extended survival. All patients had at least three major operative procedures. The median survival from first, second, third, fourth, and fifth recurrence was 29.9, 17.3, 16, 12.3, and 7.2 months, respectively. The median postoperative hospital stay was 11 days, with a range of 1 to 96 days. The major complication rate was 17%. Twenty-one patients are still alive 19 to 140 months from diagnosis (mean, 50.3 months), 9 to 125 months from the first recurrence (mean, 31.1 months), and 5 to 109 months (mean, 22 months) from the second recurrence. Eleven patients have no evidence of disease. Reoperation for recurrent colorectal carcinoma can be done with acceptable morbidity and mortality and an increase in survival.

Adult↗
PubMed1988

Radioimmunoguided surgery using monoclonal antibody.

The potential proficiency of radioimmunoguided surgery in the intraoperative detection of tumors was assessed using labeled monoclonal antibody B72.3 in 66 patients with tissue-proved tumor. Monoclonal antibody B72.3 was injected 5 to 42 days preoperatively, and the hand-held gamma-detecting probe was used intraoperatively to detect the presence of tumor. Intraoperative probe counts of less than 20 every 2 seconds, or tumor-to-adjacent normal tissue ratios less than 2:1 were considered negative (system failure). Positive probe counts were detected in 5 of 6 patients with primary colon cancer (83 percent), in 31 of 39 patients with recurrent colon cancer (79 percent), in 4 of 5 patients with gastric cancer (80 percent), in 3 of 8 patients with breast cancer (37.5 percent), and in 4 of 8 patients with ovarian cancer (50 percent) undergoing second-look procedures. Additional patients in each group were scored as borderline positive. Overall, radioimmunoguided surgery using B72.3 identified tumors in 47 patients (71.2 percent), bordered on positive in 6 patients (9.1 percent), and failed to identify tumor in 13 patients (19.7 percent). Improved selection of patients for antigen-positive tumors, the use of higher affinity second-generation antibodies, alternate routes of antibody administration, alternate radionuclides, and more sophisticatedly bioengineered antibodies and antibody combinations should all lead to improvements in radioimmunoguided surgery.

Antibodies, Monoclonal↗
PubMed1988

Reoperation directed by carcinoembryonic antigen level: the importance of a thorough preoperative evaluation.

Many asymptomatic patients suspected to have recurrent colorectal cancer based on an elevated carcinoembryonic antigen level will be spared unnecessary operation if strict attention is paid to their preoperative evaluation. Liver and renal function should be assessed. Unresectable extraabdominal and intraabdominal recurrence or metastases should be excluded. Patients being evaluated for recurrence after curative resection of a rectosigmoid cancer should undergo a bone scan. Having satisfactorily ensured normal results for these investigations, the surgeon should then proceed to search for an intraabdominal source of tumor recurrence.

Carcinoembryonic Antigen↗
PubMed1987

Variation in recognition of recurrent colonic cancer by different CEA assays.

Forty-six patients were followed with serial CEA determinations by two CEA assays after curative resection of a primary or recurrent colonic cancer. Thirteen have had a histologically proven recurrence, of which only six (46 percent) were predicted by both assays, while seven (54 percent) were predicted by one assay only. The assays appear complementary in indicating tumor recurrence, and preliminary findings suggest that it may be beneficial to follow patients with more than one CEA assay after resection of a primary or recurrent colonic cancer.

Aged↗
PubMed1987

The distribution and turnover of 35S methionine as influenced by diet in the dark-eyed Junco (Junco hyemalis).

1. Dark-eyed Juncos (Junco hyemalis) were maintained on one of three semi-synthetic diets, differing only in their sulphur amino acid content. 2. 35S-methionine was administered intraperitoneally after 3 days on their respective diets and the animals were killed 24 or 96 hr post-injection. 3. Faecal loss of 35S-methionine was significantly lower in the low methionine/high cysteine (HC) group after 24 hr when compared with other two dietary groups (4.69 vs 5.53 and 5.47%) indicating a whole-body conservation of the limiting amino acid. 4. Incorporation of 35S-methionine in hepatic and intestinal tissues was also greater in the HC group, even as the animals were losing body weight.

Animals↗
PubMed1987

Tumor-associated antigen expression of primary and metastatic colon carcinomas detected by monoclonal antibody 17-1A.

Murine monoclonal antibody (MAb) 17-1A has been used in radioimmunodetection and immunotherapy trials of intestinal adenocarcinoma in humans. Tumor heterogeneity of antigen expression has been recognized as a potential limiting factor in such studies. The authors report a study designed to evaluate the degree of heterogeneity of 17-1A antigen expression among primary and metastatic human colon carcinomas. All 141 specimens, including 74 primary or metastatic colonic adenocarcinomas, were evaluated with the use of an avidin-biotin complex immunoperoxidase technic on briefly fixed frozen tissue sections. All of these showed at least focal staining with MAb 17-1A. However, well- or moderately differentiated tumors generally showed diffuse cytoplasmic immunostaining, whereas poorly differentiated tumors showed minimal immunostaining with no detectable antigen in most areas. In 16 cases that had both primary and metastatic adenocarcinomas or multiple metastatic tumors, 17-1A antigen expression was similar among the tumor sites except for one case. This case showed variation in tumor differentiation and corresponding variation in 17-1A antigen expression. Of 36 additional malignant tumors that were not of colonic epithelial origin, adenocarcinomas of the stomach, duodenum, endometrium, ovary, and breast showed 17-1A antigen expression.

Adenocarcinoma↗
PubMed1987

Comparison of L-thyroxine and a saturated solution of potassium iodide in preventing damage to the thyroid following iodine-131-labeled antibody injection.

Following injection of radioiodinated antibodies in diagnostic amounts, there is variable uptake of radioiodine by the thyroid. Unless preventive steps are taken, radiation damage to the gland may occur. We have evaluated the role of L-thyroxine and a saturated solution of potassium iodide (SSKI) in preventing radiation damage to the thyroid glands of Sprague-Dawley adult male rats by measuring DNA strand breakage by the nucleoid sedimentation gradient method. Pretreatment with SSKI reduced DNA damage and also reduced 131I accumulation in the thyroid. Pretreatment with L-thyroxine also reduced DNA damage without significantly reducing 131I accumulation in the thyroid. The possible mechanisms of action of L-thyroxine and SSKI in preventing radiation damage to the thyroid are addressed.

Animals↗
PubMed1985

Neurologic complications of gastric partitioning.

Six patients who had gastric reduction for morbid obesity suffered severe complex neurologic disturbances that included confusion and inappropriate behavior. All were profoundly weak or paraplegic, and recovery was delayed and incomplete. Encephalopathy was documented by EEG and neurologic examination. The cause is uncertain. Acute catabolism of lipid may predispose to damage of the nervous system, but relative vitamin deficiency is a more obvious and treatable explanation.

Adult↗
PubMed1985

Intraoperative radioimmunodetection of colorectal tumor with a hand-held radiation detector.

A hand-held gamma detection probe was used intraoperatively to localize primary and recurrent colorectal tumors in 28 patients 48 to 72 hours after they received an intravenous injection of 2.2 mCi of iodine-131 labeled anticarcinoembryonic antigen polyclonal baboon antibody. Preoperative evaluation included determination of serum carcinoembryonic antigen, barium enema, colonoscopy, chest film, computerized axial tomography, liver, spleen, and bone scans, and endoscopy when indicated. Preoperative whole-body imaging correctly localized primary tumors in only 33 percent of the patients, whereas it correctly demonstrated tumor in 64 percent of those with recurrent disease. Intraoperative tumor-to-background ratios derived from the detector probe were elevated in all patients, averaging 3.97:1 in primary lesions and 4.18:1 in recurrent tumors. Postoperatively, carcinoembryonic antigen was localized in tissues with the avidin-biotin peroxidase staining technique to confirm intraoperative readings. Variations in stain uptake in a patient could be correlated with variations in radiation detector readings in the same patient. Results support our previous work in nude mice, demonstrating the improved sensitivity and specificity of the hand-held gamma detection device over whole-body imaging for intraoperative localization of immunoradiolabeled tumors.

Animals↗
PubMed1985

CEA-directed second-look surgery in the asymptomatic patient after primary resection of colorectal carcinoma.

Since 1971, serial carcinoembryonic antigen (CEA) levels have been measured to monitor patients after primary resection of colorectal cancer. Based solely on a rise in CEA level above the baseline established after primary resection, 146 patients were readmitted to the hospital. Chest films, liver-spleen scan, colonoscopy, bone scan, abdominal and pelvic CAT scan, and hepatic arteriograms were performed, and elevated CEA levels were confirmed before reexploration was undertaken. In the 146 patients, 139 (95%) had recurrences, and 81 (58%) of these were resectable for potential cure. Two of the first 22 patients re-explored between 1971 and 1975 are still living 11 and 14 years after second look; of 45 patients reoperated upon from 1976 through 1979 and followed for at least 5 years, 14 (31%) are still living. A rise in CEA above the baseline established after primary resection proved to be a sensitive indicator of recurrence and prompted reexploration before symptoms developed. Early alternative therapy was begun in patients with unresectable recurrences.

Carcinoembryonic Antigen↗
PubMed1984

A gamma-detecting probe for radioimmune detection of CEA-producing tumors. Successful experimental use and clinical case report.

The detection of tumors with radiolabeled antibodies against CEA is possible; however, current nuclear medicine scanning cameras rarely detect tumors smaller than 2 cm in diameter. One of the limitations to tumor detection is the inability to place a detecting camera near a deeply seated intra-abdominal tumor. A hand-held gamma-detecting probe, suitable for intraoperative use, was designed to locate radioactive tumors. Experimental work with CEA-producing colon tumor xenografts in nude mice suggests this probe is more sensitive than external scanners in detecting small tumors. A case report documents the clinical use of this new intraoperative probe.

Adenocarcinoma↗
PubMed1984

Portable gamma probe for radioimmune localization of experimental colon tumor xenografts.

Tumor radioimmune detection as presently practiced utilizes a gamma scintillation camera to image tumors. A major clinical limitation is the inability to detect tumors smaller than 2 cm. This limitation is due in part to the inverse square law which states: the number of detected radioactive counts is inversely proportional to the square of the distance separating a radioactive source from the detecting device. A hand-held gamma-detecting probe (GDP) suitable for intraoperative use has been developed. The GDP can be placed near radioactive tumors and take advantage of the inverse square law in a way not possible with external scanning cameras. The use of radiolabeled baboon carcinoembryonic antigen (CEA)-specific antisera produced increased tumor isotope localization in CEA-producing tumors compared to the injection of nonspecific antisera. Tumor isotope-antisera localization was not influenced by tumor volume or time since tumor implantation. The GDP probe counts demonstrated a high degree of correlation with gamma well tissue counts. The probe was able to detect preferential tumor localization in doses lower than could be detected with external scintillation cameras.

Adenocarcinoma↗
PubMed1983

Cholecystectomy in elderly patients.

Cholecystectomy was performed in 93 patients over the age of 70 years with an overall mortality of 7.5 percent. Complications occurred in 28 percent. Patients who underwent elective operations fared far better than those who required emergency surgery. Of the 50 patients who underwent elective cholecystectomy, there was 1 death (2 percent), and 10 patients (20 percent) experienced complications. In contrast, of the 43 patients who required emergency operation, 6 died (14 percent). Complications occurred in 14 (33 percent). Elective cholecystectomy in the elderly patient with symptomatic biliary tract disease is advocated before acute complications that necessitate emergency operation develop.

Age Factors↗