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Biomedical subjects

G H Hinkle

Publications and source records attributed to G H Hinkle.

At least 37 records · Page 2Linked to original sources
PubMed1988

Neutralization of thrombin by antithrombin III in the presence of cultured human fibroblasts.

Recent evidence suggests that heparan sulfate on endothelial cell surfaces acts as a catalyst for the neutralization of thrombin by antithrombin III (AT III). Fibroblasts also produce heparan sulfate which is present on the cell surface and secreted into the extracellular matrix. We evaluated the ability of cultured human fibroblasts to catalyze the interaction between thrombin and AT III and found that heparan sulfate produced by post-confluent fibroblasts was anticoagulantly active. Furthermore, after initial binding of thrombin to cells, thrombin-heparan sulfate appeared in the fluid phase above the cells; this thrombin could be rapidly neutralized by AT III independent of the further presence of cells. These results indicate that fibroblasts do produce an anticoagulantly active species of heparan sulfate and that the normal interaction between AT III and thrombin may be driven by initial release of heparan sulfate from the cell surface by thrombin followed by AT III interaction with the soluble thrombin-heparan sulfate complex.

Antithrombin III↗
PubMed1988

Limits of sensitivity for the radioimmunodetection of colon cancer by means of a hand held gamma probe.

This study was undertaken to define the limits for the radioimmunodetection of minimal deposits of colorectal cancer cells using a hand held gamma probe. 125I labeled monoclonal antibody 17-1A and its F(ab')2 fragments were reacted in vitro with cells of the human colorectal cancer line SW 1116. The limits of sensitivity of the probe were determined by injecting doubling dilutions of 125I-antibody coated SW 1116 cells ranging from 10(7) to 3.9 x 10(4) subserosally at 2 cm intervals into 60 cm segments of freshly obtained autopsy or surgical specimens of human colon. A linear relationship was observed between the number of cells injected and the number of counts obtained with either the probe or well counter. As few as 6.25 x 10(5) 125I-antibody coated cells (less than 1 mm3) were detected under experimentally defined conditions by an earlier version of the probe, and 3.9 x 10(4) coated cells (much less than 1 mm3) could be detected by the currently available model. Although the count rates were less than 5% of those obtained by well counter, nevertheless, these were 10-25 times greater than background and allowed the detection of tumor cell deposits that otherwise would not have been discernible by either palpation or external scintigraphy. These findings, in conjunction with ongoing clinical studies, suggest that the hand held gamma probe may increase the usefulness of monoclonal antibodies for the radioimmunodetection of cancer.

Antibodies, Monoclonal↗
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↗
PubMed1987

Radioimmunoguided surgery using the monoclonal antibody B72.3 in colorectal tumors.

The authors have developed a hand-held gamma-detecting probe (GDP) for intraoperative use that improves the sensitivity of external radioimmunodetection. Radiolabeled monoclonal antibody (MAb) B72.3 was injected in six patients with primary colorectal cancer and 31 patients with recurrent colorectal cancer an average of 16 days preoperatively. The GDP localized the MAb B72.3 in 83 percent of sites. The technique, known as a radioimmunoguided surgery (RIGS) system did not alter the surgical procedure in patients with primary colorectal cancer but did alter the approach in 26 percent (8/31) of patients with recurrent colorectal cancer. Two patients avoided unnecessary liver resections and two underwent extraabdominal approaches to document their disease. The RIGS system may influence the short-term morbidity and mortality of surgery for colorectal cancer. Larger series and longer follow-up are needed to determine whether the RIGS system confers a survival advantage to the patient with colorectal cancer.

Antibodies, Monoclonal↗
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↗
PubMed1987

Radioimmunodetection of implanted tumors with gamma probe.

Tumor uptake of 125I- and 131I-radiolabeled anti-CEA antibodies was compared in female Swiss nude mice, each bearing a CEA-producing human colon adenocarcinoma xenografted in one flank. Counts from the tumor and contralateral flank were recorded with a manipulatable, cadmium-telluride crystal gamma detector at 24, 48, and 72 hours following injection. The animals were killed, and the tumors and other organs were removed, weighed, and then assessed in an automatic gamma counter. The cadmium-telluride counter was more efficient at counting 125I-labeled antibodies than 131I antibodies. The tumor to contralateral flank ratios improved with the use of a monoclonal anti-CEA and polyclonal anti-CEA in combination compared with the single antibodies. The investigation of the external counting characteristics of the portable gamma detector demonstrated the potential of the adjunctive use of intraoperative detection with external radioimmunoscintigraphy for detection and localization of gastrointestinal tumors.

Adenocarcinoma↗
PubMed1986

Intraoperative probe-directed immunodetection using a monoclonal antibody.

To assess monoclonal antibody (MAb) 17-1A and its F(ab')2 fragment in intraoperative radioimmunodetection and to evaluate further the clinical usefulness of a hand-held gamma-detecting probe (GDP), we injected radiolabeled monoclonal antibody 17-1A three to six days preoperatively or its F(ab')2 fragment two to three days preoperatively into 18 patients with colorectal cancer. Intraoperative GDP counts with tumor-tissue ratios of 1.5:1 or greater were obtained from 15 (75%) of 20 tumor sites, with ratios averaging 2.3:1 for fragments and 3.4:1 for whole antibody. The GDP counts contributed to intraoperative decision making in three patients, either by localization of tumor not identified by inspection or palpation or by mapping margins of resection with histologic confirmation of a local/regional recurrence. These preliminary data demonstrate that probe-directed, intraoperative radioimmunodetection can assist the surgeon in detecting subclinical tumor deposits and thus better evaluate the extent of primary or recurrent colorectal cancers intraoperatively.

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

Nonvisualization of sterile surgical incisions with indium-111 labeled leukocytes.

The localization of In-111 labeled leukocytes (WBCs) in recent surgical incisions was studied in 18 patients. In-111 WBC images correlated well with culture results and clinical findings. No accumulation of In-111 WBCs was detected at the site of noninfected incisions in nine patients. In-111 WBCs did accumulate at incision sites in nine patients with infected surgical incisions. These results indicate that In-111 WBC study can accurately distinguish between normal healing and infection of recent surgical incisions.

Adult↗
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

Absence of hepatic uptake of Tc-99m sulfur colloid in an infant with Coxsackie B2 viral infection.

After the intravenous administration of Tc-99m sulfur colloid, there was found homogeneous lung, renal, and splenic uptake with absence of uptake by the liver and bone marrow of a nine-day-old female infant. More than 20 other doses were dispensed from the same Tc-99m sulfur colloid preparation with the expected biodistribution. A necropsy done two days later showed diffuse hepatic hemorrhagic necrosis without evidence of intravascular fibrin deposition in the lungs or kidneys. The underlying cause of the infant's disease was a Coxsackie B2 viral infection, based upon positive postmortem viral cultures of kidney and liver tissues and characteristic histopathologic lesions of the central nervous system and viscera. The altered biodistribution presumably reflected marked impairment of Kupffer cell function and an apparent increase in pulmonary macrophages.

Coxsackievirus Infections↗
PubMed1982

Effects of concurrent drug therapy on technetium Tc-99m gluceptate biodistribution.

Drug interactions with technetium Tc-99m gluceptate resulting in altered biodistribution were studied using chart review and animal tests. Charts of nine patients who had abnormal gallbladder uptake of technetium Tc-99m gluceptate during a two-year period were reviewed to obtain data such as concurrent drug therapy, primary diagnosis, and laboratory values. Adult New Zealand white rabbits were then used for testing the biodistribution of technetium Tc-99m gluceptate when administered concurrently with possibly interacting drugs identified in the chart review--penicillamine, penicillin G potassium, penicillin V potassium, acetaminophen, and trimethoprim-sulfamethoxazole. Chart review revealed no conclusive patterns of altered biodistribution associated with other factors. The data did suggest the possibility that the five drugs listed above might cause increased hepatobiliary clearance of the radiopharmaceutical. Animal tests showed that i.v. penicillamine caused substantial distribution of radioactivity into the gallbladder and small bowel. Minimally increased gallbladder radioactivity occurred when oral acetaminophen and trimethoprim-sulfamethoxazole were administered concurrently. Oral and i.v. penicillins did not increase gallbladder activity. Penicillamine may cause substantial alteration of the biodistribution of technetium Tc-99m gluceptate.

Acetaminophen↗
PubMed1981

Kit preparation of radioiodinated o-iodohippuran.

The purpose of this study ws to evaluate a kit preparation for radioiodinated o-iodohippuran (I). All ingredients, excluding the radionuclide, were packaged in a ready-to-use kit for easy, quick formulation. Electrophoresis was utilized to evaluate the radiochemical purity of the labeled product and indicated that the radiolabeling technique provided a product with greater than 95% radiochemical purity. Biodistribution studies in rats and rabbits provided an indication of the tissue distribution and localization of the radiopharmaceutical. Computer-generated renogram curves plotted from gamma-camera images of rabbits showed the equivalency of the 131I-labeled I and 123I-labeled I to the commercially available radiopharmaceutical.

Animals↗
PubMed1981

Thymic gallium-67 localization in pediatric patients on chemotherapy: concise communication.

Localization of Ga-67 in the thymus has been reported to occur in children. In our control group of 87 patients, 15% of children under 5 yr and 11% of children over 5 yr demonstrated thymic localization. In contrast, in our study group of seven children with acute lymphocytic leukemia or malignant lymphoma, lymphocytic diffuse, treated on a modified non-Hodgkin's lymphoma protocol, Sloan-Kettering LSA2-L2, thymic localization occurred during treatment in five of the seven. We conclude that increased thymic gallium localization in children under chemotherapy for a known malignancy may reflect increased activity of thymic medullary epithelial cells and regeneration of thymic lymphocytes during recovery form involution induced by certain chemotherapeutic agents.

Adolescent↗