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Biomedical subjects

G Hinkle

Publications and source records attributed to G Hinkle.

50 records · Page 3Linked to original sources
PubMed1989

The impact of radioimmunoguided surgery (RIGS) on surgical decision-making in colorectal cancer.

Radioimmunoguided surgery (RIGS system) was performed in ten patients with rectal or low sigmoid colon carcinoma with the use of a hand-held gamma detector (Neoprobe 1000) intraoperatively and externally after injection of radiolabeled (125I) monoclonal antibody to detect pelvic and metastatic tumor. Fifteen procedures, including six exploratory laparotomies, four transperineal explorations, two transsacral explorations, one transvaginal biopsy, one brachytherapy, and one transanal polypectomy, were performed. Two patients had previous low anterior resection, seven abdominoperineal resection, and one a rectal polypectomy. Five patients had previous pelvic radiation therapy. Reoperation was indicated by elevated CEA levels in seven patients (70 percent), persistent pelvic pain in six (60 percent), and a suspicious radiologic study in seven (70 percent). RIGS system localized tumors verified by histopatholoy in all ten patients (100 percent); one patient with a positive CT scan and probe findings lacked histopathologic confirmation on frozen section, but had a tumor confirmed on permanent histology. Five major abdominal operations were avoided; in five patients major modifications were made in the surgical procedure based on probe findings. Six received chemotherapy or radiation therapy based on findings of the RIGS system. In six patients with negative or equivocal CT scans, the RIGS system localized histopathologically confirmed tumor. Major abdominal procedures can be avoided, the surgical approach modified, and other modes of therapy instituted earlier with the use of the RIGS system.

Aged↗
PubMed1989

Localization by hand-held gamma probe of tumor labeled with antibody "cocktail".

Five groups (n = 4) of congenitally athymic female nude mice bearing subcutaneous implants of CX-1 and/or SW-1116 tumor in the hind limbs received iodine-125 radio-labeled monoclonal antibodies (MoAbs) B72.3 (two groups), 17-1A (two groups), and cocktail (one group) (iodogen method, 50 microCi/10 micrograms/mouse). Daily probe counts were made in duplicate with a hand-held detector over each tumor site and the front leg (background) for 21 days. Animals were sacrificed and appropriate well counts were obtained. All the single MoAb preparations localized well in both tumor cell lines. Uptake of monoclonal antibody 17-1A was similar in the two tumor cell lines, with counts initially high and slowly decreasing over the 21-day period. Tumor/background ratios continued to increase over time, indicating that both tumor lines have similar antigenic expression for the monoclonal antibody 17-1A. This was not the case for monoclonal antibody B72.3, which showed a preferential uptake by the CX-1 tumor, with higher initial counts and prolonged binding of the antibody, giving rise to higher tumor/background ratios. The mixture of monoclonal antibodies B72.3 and 17-1A markedly improved the uptake by the CX-1 tumor cell line but not that by the SW-1116 cell line, where the effect was negative when compared to the uptake of the single MoAb preparations. The use of a monoclonal antibody mixture can enhance targeting of some tumor sites. Due to the heterogeneity of tumor cell lines, even within the same animal, different mixtures of monoclonal antibodies are needed to increase the targeting of tumor.

Adenocarcinoma↗
PubMed1989

Staging of carcinoma of the breast using a hand-held gamma detecting probe and monoclonal antibody B72.3.

Radioimmunoguided Surgery (RIGS) uses a hand-held gamma detecting probe to identify radiolabeled monoclonal antibodies (Mab). Fourteen patients with carcinoma of the breast proved at biopsy received Mab B72.3 (5 millicuries of 125I per 1 milligram, Iodo-Gen method) intravenously six to 26 days before exploration. Probe counts were measured intraoperatively in mammary tissue and axillary lymph nodes. In the mammary tissue, the RIGS system identified tumor that was histologically confirmed in seven of eight patients and confirmed the absence in four of six patients. Probe counts were suspicious for tumor that was not proved histologically in two of 14 patients. Unsuspected tumor was identified in three of 14 patients. In axillary tissue, probe counts identified one of two tumors that were confirmed histologically and verified the absence of tumor in eight of 12 patients. Probe counts in axillary tissue were suspicious for tumor that could not be documented histologically in four of 14 patients. RIGS appears to be able to identify residual, subclinical and multicentric carcinoma of the breast and accurately delineate the pattern of antigenic drainage of tumor into adjacent lymph nodes.

Antibodies, Monoclonal↗
PubMed1989

Radioimmunoguided surgery in recurrent colorectal cancer: the role of carcinoembryonic antigen, computerized tomography, and physical examination.

From January 1986 to December 1987, 32 patients with recurrent colorectal cancer had second-look radioimmunoguided surgery (RIGS system). All patients had pathologic confirmation of recurrence. The RIGS system identified 81% of recurrences, and in six patients recurrent tumor was identified only by RIGS. All patients had physical examination, carcinoembryonic antigen (CEA) assay, and computerized tomography of the abdomen and pelvis. Detection of recurrence was based on symptoms in six, elevated CEA value in 25, and physical examination in one. The CEA was elevated preoperatively in 30 patients; two false-negative results occurred in symptomatic patients who had pelvic recurrence. The median CEA value in those with liver recurrence was 30 ng/ml (range 5.2 to 298) and for pelvic recurrence 13 ng/ml (range 1.9 to 31) (P less than .05). The overall sensitivity of CT was 41% (abdomen other than liver 37%, liver 56%, and pelvis 22%). The combination of elevated CEA, symptoms, and physical findings identified 100% of recurrences. We conclude that a rising CEA remains the most accurate indicator of recurrence. CT should not be done routinely to detect recurrent colorectal cancer unless CEA is elevated or the patient is symptomatic. In our study the intraoperative use of the RIGS system aided the surgeon in identifying occult tumors.

Adolescent↗
PubMed1988

Pharmacokinetic studies of DISIDA disposition. I. Animal studies.

The whole blood pharmacokinetics of intravenously administered 99mTc-disofenin (DISIDA) have been studied in dogs. Serial blood sampling permitted calculation of whole blood disposition rates, which principally represent liver clearance. There were striking differences in these rates between 6 normals and 7 animals in whom liver damage was induced by chronic bile duct ligation (256 vs 58 ml/min, P less than 0.001). Blood levels of radioactivity fell in a biexponential fashion characterized by rapid and slow disposition phases, whose half times were 2.4 and 58 min in normal animals. On 3 occasions, plasma was obtained from 1 animal by exsanguination 35 min after the administration of DISIDA and rapidly transfused into a 2nd animal. The whole blood pharmacokinetics of the second (recipient) animal showed a predominance of the slow disposition phase and a small rapid phase. The hepatic extraction ratio of blood radioactivity was measured in 3 dogs and was high (75%-90%) early after injection of DISIDA, but fell rapidly to remain around 10%. These experiments suggest the presence of two different species in the radiopharmaceutical studied, each being removed from the blood stream by the liver, but at different rates. The contribution of renal clearance to overall whole blood pharmacokinetics was negligible, since three nephrectomized dogs displayed similar pharmacokinetics to normals. Whole blood DISIDA pharmacokinetics are more complex than previously thought but appear to be capable of providing an accurate measure of liver function.

Animals↗
PubMed1988

Pharmacokinetic studies of DISIDA disposition. II. Clinical studies.

The whole blood pharmacokinetics of intravenously administered 99mTc-disofenin (DISIDA) has been studied in normal subjects and patients with documented liver disease. The apparent overall whole blood disposition rates of radioactivity were calculated from serial blood data, in order to evaluate liver clearance of DISIDA. The measurements obtained clearly discriminated 9 normal subjects from 7 patients with severe liver disease causing jaundice--1233 mls/min vs 384 mls/min (P less than 0.002). Nine subjects with liver disease of insufficient severity to cause jaundice also had clearly abnormal DISIDA disposition--642 ml/min (P less than 0.05 for difference to controls). The time activity curves from all subjects showed biexponential elimination of blood activity, with a rapid (T1/2 = 3.8 min) and a slow disposition phase (T1/2 = 75 min) in normals. These curves were fitted by computer to the timed rate of hepatic uptake, simultaneously obtained by gamma imaging over the liver. It was not possible to satisfactorily fit these using a model which assumed distribution of a single compound within two body compartments. However, another which assumed the administration of two radioactive agents satisfactorily fitted the two types of data. This conclusion is consistent with our animal experiments which indicate the existence of two compounds in injected DISIDA with contrasting high and low hepatic extraction efficiency (Fraser et al. 1988). A pharmacokinetic approach to DISIDA disposition can yield quantitative information which discriminates different degrees of liver dysfunction, but the mechanisms involved are more complicated than previously thought, so that further study should permit very precise quantification.

Adult↗
PubMed1988

Mychonastes desiccatus Brown sp. nova (Chlorococcales, Chlorophyta)--an intertidal alga forming achlorophyllous desiccation-resistant cysts.

An intertidal Chlorella-like alga Mychonastes desiccatus Brown sp. nova, capable of forming achlorophyllous desiccation-resistant cysts, has been grown in unialgal culture. This small alga was first isolated from a dried sample of a well-studied microbial mat. The mat, located at North Pond, Laguna Figueroa, San Quintin, Baja California, Mexico, is a vertically-stratified microbial community which forms laminated sediments. Morphology, pigment composition and G+C content are within the range typical for the genus Chlorella s. 1. Unlike other chlorellae, however, upon desiccation M. desiccatus forms an achlorophyllous, lipid-filled cyst (thick-walled resting stage) in which no plastid is evident. Rewetting leads to chloroplast differentiation, excystment and recovery of the fully green alga. During desiccation, sporopollenin is deposited within a thickening cell wall. Encystment cannot be induced by growth in the dark. The formation of desiccation-induced cysts allows the alga to survive frequent and intermittent periods of dryness. These chlorellae tolerate wide ranges of acidity and temperature; they both grow and form cysts in media in which sodium ions are replaced with potassium. Although the cysts tolerate crystalline salts, the cell grow optimally in concentrations corresponding from three-quarters to full-strength seawater.

Biopolymers↗
PubMed1981

Effect of cardiac drugs on imaging studies with thallous chloride Tl 201.

The effects of commonly used cardiac drugs on cardiac imaging with thallium-201-labeled thallous chloride were studied. This retrospective study included 62 men ranging in age from 37 to 70 years who had cardiac imaging attempted with thallium during an eight-month period. Seven drugs were being used by at least eight patients each--propranolol, nitroglycerin ointment, isosorbide dinitrate, digoxin, hydrochlorothiazide, potassium chloride, and quinidine. Myocardial-to-background (M/Bk) ratios were calculated for each patient. No drug consistently affected the M/Bk ratios. The lowest M/Bk ratio was found in patients receiving digoxin, but there was no significant difference between the M/Bk ratios for patients taking digoxin (1.38 +/- 0.16) and those not taking digoxin (1.45 +/- 0.10) (0.05 less than p less than 0.10, Student's t test). It is concluded that the drugs studied do not affect cardiac imaging with thallous chloride Tl 201.

Adult↗
PubMedDate not supplied

Decreased platelet adherence of polymer-coated tantalum stents.

PURPOSE: To compare the acute thrombogenicity of polyurethane-coated stents with that of bare tantalum stents. MATERIALS AND METHODS: Thirty stents (15 coated with polyurethane) were balloon expanded in 8-mm x 80-cm sections of polytetrafluoroethylene grafts (six stents per graft). Under sterile conditions, 8- and 10-F vascular sheaths were placed percutaneously in the femoral artery and vein of a 100-lb (45-kg) swine. Platelets were labeled with indium-111 and reinjected for quantitative assay. The stented grafts were connected to the arterial and venous sheaths to create an ex vivo fistula. Each fistula was opened for 5, 10, 30, 60, or 120 minutes, exposing heparinized blood to fully expanded stents. The fistulas were closed, flushed with saline until clear, and fixed with formalin. Stents were explanted, placed in a radionuclide well counter, and scanned with electron microscopy. RESULTS: Quantitatively, there were considerably fewer platelets on coated versus uncoated stents. At 60 minutes, coated stents averaged 12.93 platelets per 1,000 microns 2 compared with 75.88 platelets per 1,000 microns 2 for bare metallic stents. At 120 minutes, there were 23.22 platelets/1,000 microns 2 versus 102.31 platelets/1,000 microns 2, respectively. Electron microscopy of coated stents demonstrated few scattered platelets at 5, 10, and 30 minutes. There was a uniform layer of platelets at 60 and 120 minutes. Uncoated stents demonstrated random areas of platelet clumping at 5, 10, and 30 minutes. At 60 and 120 minutes, uncoated stents showed extensive layering of platelets and fibrin. CONCLUSION: Polyurethane coating decreases platelet adhesion, relative to bare tantalum, at all time intervals tested.

Animals↗
PubMedDate not supplied

The evolution of the Vahlkampfiidae as deduced from 16S-like ribosomal RNA analysis.

The amoebae, a phenotypically diverse, paraphyletic group of protists, have been largely neglected by molecular phylogeneticists. To better understand the evolution of amoebae, we sequenced and analyzed the 16S-like ribosomal RNA genes of three vahlkampfiid amoebae: Paratetramitus jugosus, Tetramitus rostratus and Vahlkampfia lobospinosa. The Vahlkampfiidae lineage is monophyletic, branches early along the eukaryotic line of descent, and is not a close relative of the multicellular amoebae that also reversibly transform from amoebae to flagellates.

Animals↗
PubMedDate not supplied

Phylogeny of trichomonads inferred from small-subunit rRNA sequences.

Small subunit (16S-like) ribosomal RNA sequences were obtained from representatives of all four families constituting the order Trichomonadida. Comparative sequence analysis revealed that the Trichomonadida are a monophyletic lineage and a deep branch of the eukaryotic tree. Relative to the early divergent eukaryotic assemblages the branching pattern within the Trichomonadida is very shallow. This pattern suggests the Trichomonadida radiated recently, perhaps in conjunction with their animal hosts. From a morphological perspective the Devescovinidae and Calonymphidae are considered more derived than the Monocercomonadidae and Trichomonadidae. Molecular trees inferred by distance, parsimony and likelihood techniques consistently show the Devescovinidae and Calonymphidae are the earliest diverging lineages within the Trichomonadida, however bootstrap values do not strongly support a particular branching order. In an analysis of all known 16S-like ribosomal RNA sequences, the Trichomonadida share most recent common ancestry with unidentified protists from the hindgut of the termite Reticulitermes flavipes. The position of two putative free-living trichomonads in the tree is indicative of derivation from symbionts rather than direct descent from some free-living ancestral trichomonad.

Animals↗
PubMedDate not supplied

Radioimmunoguided breast surgery using radiolabeled antibody NR-LU-10 FAB: a pilot study.

AIM AND BACKGROUND: Radioimmunoguided surgery using radiolabeled NR-LU-10 Fab was evaluated as a method of intraoperative breast cancer detection. METHODS: Breast cancer patients were injected intravenously with 125I (74 MBq) labeled NR-LU-10 Fab (5 mg) and then underwent tumor excision 2, 4 or 7 days later, during which time the gamma detector probe was used to evaluate the primary tumor for evidence of radioactive uptake. RESULTS: Intraoperative probing revealed tumor localization in 7 of 10 patients (70%). Gamma probe counts of the excised tumor were elevated in all patients, although high counts in surrounding non-malignant tissue obscured the ability to detect the tumor in vivo in 3 patients. One patient with bilateral breast cancer was found to have a separate focus of occult tumor in each breast using the gamma detector probe. CONCLUSIONS: Radiolabeled NR-LU-10 Fab possesses favorable pharmokinetics and tumor-binding ability as a targeting agent. However, binding to non-malignant tissue limits its role in the intraoperative evaluation of tumor margins in breast cancer patients. Its role in other malignancies should be explored.

Adult↗