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Biomedical subjects

S Stevens

Publications and source records attributed to S Stevens.

At least 73 records · Page 4Linked to original sources

Kinetics of technetium-99m-Sestamibi and thallium-201 in a transient ischemic myocardium animal model: insight into the 'redistribution' phenomenon.

This study was designed to determine the redistribution potential for technetium-99m (99mTc)-hexakis-2-methoxy isobutyl isonitrile (99mTc-Sestamibi) as compared to thallium-201 (201Tl) in a transiently ischemic swine heart model. The left anterior descending coronary artery (LAD) was totally occluded for 10 min. One minute prior to the release of the LAD, 99mTc-Sestamibi, 201Tl and a set of 95Nb-radiolabeled microspheres (15 microns) were injected. A second set of 51Cr-radiolabeled microspheres was injected prior to sacrifice in order to document reflow. Animals were sacrificed at different times post-LAD release (ranging from 1 min to 4 h). The left ventricle was sectioned into 0.2- to 0.5-gram pieces for the gamma spectroscopic counting of the 99mTc-Sestamibi, 201Tl and radiolabeled microspheres. Linear regression analysis of radiotracer localization versus microsphere-determined regional myocardial blood flow (rMBF) demonstrates an initial slight filling in of 99mTc-Sestamibi into transiently ischemic zones, with subsequent stable kinetics up to 4 h (i.e., it does not further redistribute). In comparison, the ischemic to normal ratios for 201Tl activity increase progressively in a time-dependent manner. These differences between 99mTc-Sestamibi and 201Tl might be explained on the basis of their blood clearance kinetics and/or their net clearance from normal and ischemic zones of the heart. It is concluded that 99mTc-Sestamibi is a stable and reliable indicator for rMBF over time, and that the lack of normalization of 99mTc-Sestamibi into transient ischemic zones will necessitate two separate injections for differentiation between ischemia and persistent defects.

Animals↗

High-dose, short-duration cisplatin/doxorubicin combination chemotherapy for advanced ovarian epithelial cancer.

Sixty-one patients with epithelial ovarian cancer were treated with intensive high-dose, short-course chemotherapy that consisted of cisplatin (120 mg/m2) and doxorubicin (70 mg/m2) every 3 weeks for four cycles. Patients in complete clinical remission were offered second-look laparotomy (SLL). Patients with minimal or no residual disease at SLL were randomized to either cyclophosphamide (1000 mg/m2 every 21 days for six cycles) or whole-abdominal radiation therapy. All patients completed therapy with a median leukocyte nadir 1.3/microliter and platelet nadir of 90/microliters. Forty-five patients (74%) had a complete clinical response. Results of twenty-two of 36 second-look procedures (64%) showed no evidence of disease (NED). After SLL, 19 patients received six courses of cyclophosphamide and 16 patients received whole-abdominal radiation. Nine patient who refused SLL and one patient with negative SLL findings refused additional treatment. The median survival time for all patients was 51.3 months. High-dose intensive chemotherapy regimens have high response rates, but survival needs to be compared with traditional low-dose regimens. Although high-dose cisplatin and doxorubicin were myelosuppressive, the resulting complications were manageable. There was no significant difference between the mean survival times of patients receiving Cytoxan, abdominal radiation, or no treatment as second-line therapy.

Adult↗

Initial clinical study of indium-111-labeled clone 110 anticarcinoembryonic antigen antibody in patients with colorectal cancer.

A murine monoclonal antibody directed against carcinoembryonic antigen (CEA) was labeled with indium-111 (111In) by means of a benzylisothiocyanate derivative of diethylenetriamine penta-acetic acid (DTPA) and used for clinical radioimmunodetection studies. Twenty-one patients having a history of surgically resected colorectal cancer and rising serum CEA levels suggestive of tumor recurrence were studied. Patients were infused over 20 minutes with 5, 10, or 20 mg of the monoclonal antibody labeled with 5 mCi of 111In. The mean radiochemical purity was greater than 96%. No toxicity was seen. The stability of the radiolabel on antibody in patient serum was demonstrated by high-performance liquid chromatography (HPLC), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with autoradiography, and immunoprecipitation for up to 96 hours after infusion. Tumor sites were identified in 20 of 21 patients. Sites of antibody accumulation in 20 patients were confirmed as tumor either by resection at laparotomy (16 patients) or fine-needle biopsy (four patients). Nine patients who had the identified lesion resected or irradiated showed return of the serum CEA antigen level to normal or near normal values. In the absence of high levels of circulating CEA (greater than 500 ng/mL), the disappearance of radioactivity from patient serum demonstrated first order elimination kinetics, with a mean half-life of 38 hours. The serum half-life was not affected by the dose of antibody administered or by serum CEA titers below 500 ng/mL. Despite a mean liver uptake of 18% injected dose (ID) 24 hours after administration, hepatic metastases were easily visualized as areas of increased uptake of radioactivity. Radioimmunodetection of recurrent colorectal cancer, not detected by computed tomographic (CT) scans, appears achievable with this agent. This may allow successful clinical intervention in selected patients.

Adult↗

Pharmacokinetics in patients of an anti-carcinoembryonic antigen antibody radiolabeled with indium-111 using a novel diethylenetriamine pentaacetic acid chelator.

The pharmacokinetics of the C110 anti-carcinoembryonic antigen antibody radiolabeled with 111In via a novel benzylisothiocyanate derivative of diethylenetriamine pentaacetic acid have been determined in 12 patients. The chelator was attached to the protein via a thiourea bond and in such a way that all 5 carboxymethyl arms were presumably able to participate in chelation. Patients with known or suspected colorectal carcinoma received between 5 and 20 mg of the IgG antibody labeled with 5 mCi of 111In. Individual organ radioactivity levels were quantitated, and serum and urine samples were analyzed, principally by size exclusion high-performance liquid chromatography (HPLC). Total urinary excretion averaged 0.18% of the injected dose/h with large patient to patient variation. At early times postadministration (less than 8 h) the predominant radiolabeled species in urine was free diethylenetriamine pentaacetic acid most probably administered as a small radiocontaminant in the injectate. Thereafter, radioactivity in urine was primarily present as a low molecular weight catabolic product. Analysis of serum by size exclusion HPLC occasionally showed 3 radioactivity peaks, 2 of which are due to circulating immune complexes and labeled antibody. The third peak is of low molecular weight and is due to one or more products of antibody catabolism. Transchelation of 111In to circulating transferrin was observed but at modest levels. Quantitation of organ radioactivity showed that 18 +/- 4 (SD)% of the injected dose was in the liver at 1 day postadministration and 1.4 +/- 1.1 and 1.2 +/- 0.9% was in the spleen and in both kidneys, respectively, at this time. The mean half-life for clearance of total injected radioactivity was fitted to a single exponential and was found to be 34 h (SD, 14 h; N = 13) and that for antibody alone, assessed by size exclusion HPLC analysis of serum samples, was calculated to be 22 h (SD, 8 h; N = 10). Neither of these values nor organ radioactivity levels were affected by antibody-loading dose.

Adult↗

Just a matter of time.

As Midwestern foodservice directors & dietitians recently discovered when an earthquake alert was sounded in their area, it's never too early to review & update emergency plans. Herein is a compendium of tips that can be used by any foodservice professional working in an area at risk of disaster, whether it be earthquake, tornado, hurricane, blackout or flood.

Disaster Planning↗

Tissue- and species-specific expression of inhibitory guanine nucleotide-binding proteins. Cloning of a full-length complementary DNA from canine heart.

Three different isoforms of the inhibitory guanine nucleotide-binding protein alpha-subunit (Gi alpha) have been cloned. However, little information on the cardiac-specific expression of these isoforms is available. The deduced amino acid sequence of a full-length Gi alpha 2 complementary DNA from a canine ventricular library displays several unique residues compared with those from other species. In contrast to previously described complementary DNA clones for Gi alpha 2, this complementary DNA has a complete 3'-untranslated region with the expected consensus sequence for polyadenylation. Gi alpha 2 is the predominant isoform in the heart, and its message level of 14.7 +/- 4.9 pg/10 micrograms total ventricular RNA is about fourfold lower than that of the stimulatory guanine nucleotide-binding protein.

Amino Acid Sequence↗

Women residents: expanding their role to increase treatment effectiveness in substance abuse programs.

It has long been noted that chemically dependent women have special needs that differ from the needs of chemically dependent men. A therapeutic community model, which has been found effective, suggests several changes in traditional treatment approaches. After intervention with our female-based therapeutic model, several positive changes occurred. Extremely disproportionate populations of males and females began to even out, with female residents' length of stay increasing dramatically. Length of stay for male residents also increased by a significant amount. Success of treatment, as measured by the number of drug-free ex-residents, also increased significantly for male and female populations.

Adult↗

Children's solution strategies and mental rotation: evidence for a developmental shift.

We examined children's ability to anticipate the appearance of transformed multicomponents using visual stimuli with variations of a mental rotation task. We hypothesized that (a) performance would depend on the presence, location, and spatial relationship of specific stimulus features, and that (b) younger children would use a single component to make their predictions, whereas older children would be more likely to use multiple components. In Study 1, 40 first-, and fifth-grade subjects were presented with 32 rotation problems consisting of varied stimulus characteristics; subjects selected the correct option from a field where foils were indicative of the strategy used. Analyses of variance and log linear analyses revealed the hypothesized stimulus effect differentially associated with the children's ages. In Study 2, sixty 5-, 7-, and 9-year olds confronted 64 mental rotation problems with multicomponent stimuli and a construction task. Results and implications confirmed those of Study 1.

Attention↗

Radiation-induced increases in sensitivity of cataleptic behavior to haloperidol: possible involvement of prostaglandins.

The effects of radiation exposure on haloperidol-induced catalepsy were examined in order to determine whether elevated prostaglandins, through an action on dopaminergic autoreceptors, could be involved in the radiation-induced increase in the potency of this neuroleptic. Cataleptic behavior was examined in animals irradiated with various doses of gamma photons (1-150 Gy) and pretreated with a subthreshold dose of haloperidol (0.1 mg/kg). This approach was chosen to maximize any synergistic effects of radiation and haloperidol. After irradiation with doses less than or equal to 30 Gy, the combined treatment of haloperidol and radiation produced catalepsy, whereas neither treatment alone had an effect. This observed catalepsy could be blocked with prior administration of indomethacin, a prostaglandin synthesis inhibitor. Animals exposed to doses of radiation less than or equal to 50 Gy and no haloperidol, however, displayed apparent catalepsy. This effect was also antagonized by indomethacin. Prostaglandins can induce catalepsy and when administered in subthreshold doses along with subthreshold doses of haloperidol, catalepsy was observed. In order to assess a possible action of prostaglandins and radiation on dopaminergic activity, the functioning of striatal dopaminergic autoreceptors was examined by determining the effects of varying concentrations of haloperidol on the K+-evoked release of dopamine from striatal slices obtained from parallel groups of animals treated as above. Results indicated that sensitivity to haloperidol increased (higher K+-evoked dopamine release) in slices from irradiated or prostaglandin-treated animals and that this increase in sensitivity was blocked by indomethacin. Results from both experiments suggest that radiation-induced increases in endogenous neuronal mediators, such as prostaglandins, can induce catalepsy through an action on dopaminergic autoreceptors.

Animals↗

Electrodermal activity to auditory stimuli in autistic, retarded, and normal children.

Electrodermal activity to auditory stimuli was compared in 20 autistic children and their matched retarded and normal controls (N = 80). The autistic children were virtually indistinguishable in individual features of electrodermal activity from controls when both chronological and mental age comparisons were accounted for. When patterns of activity were considered globally, both autistic and retarded children could be distinguished from one another and from normal controls. However, in some respects autistic and same-aged normal children were alike--both showed sensitization to 70-dB tones and both had a higher incidence of children with larger left- than right-hand responses, interpreted as evidence of focused attention under left hemisphere control.

Acoustic Stimulation↗

Eimeria tenella: in vitro development in irradiated bovine kidney cells.

The initial infection and first-generation development of Eimeria tenella was quantified using a cloned MDBK (Madin-Darby Bovine Kidney) cell line, irradiated with gamma radiation prior to infection, as the host cell. Irradiated cell cultures were found to be more susceptible to infection and had a greater capacity to support parasite development than non-irradiated cultures. It was suggested that the larger proportion of cells in the G2 phase of the cell cycle, the larger individual cell size and the inhibition of cell division in the irradiated cultures were all factors contributing to the increased susceptibility to infection and capacity to support parasite growth and development. The application of this technique (host cell irradiation) to the cultivation of other intracellular, protozoan parasites is discussed.

Animals↗

Counterimmunoelectrophoresis for identification of equine urine.

Counterimmunoelectrophoresis was evaluated as a method to distinguish urine of human origin from that of equine origin. The procedure used anti-equine serum and anti-human serum antibodies that had been solid-phase absorbed to eliminate species cross-reactivity. Counterimmunoelectrophoresis reliably detected contamination of equine urine by human urine to a level of 10% with a minimum sensitivity to about 2% contamination. Compared with double diffusion, counterimmunoelectrophoresis was approximately 10 to 15 times more sensitive in the detection of urine proteins.

Animals↗

Increased leukocyte histamine release with elevated cyclic AMP-phosphodiesterase activity in atopic dermatitis.

Maximal leukocyte histamine release in response to concanavalin A was significantly higher in a group of 16 adult patients with moderate to severe atopic dermatitis when compared to 13 adult nonatopic, normal subjects. In a further four atopic dermatitis patients, histamine release was similar to that in the normal group suggesting the existence of "high-releaser" and "low-releaser" subsets within the atopic dermatitis group. Leukocyte cAMP phosphodiesterase activity was significantly higher in the high-releaser group than in the low-releaser and normal groups. High and low histamine release responses showed strong correlations with high and low phosphodiesterase activities. Pretreatment with the experimental cAMP phosphodiesterase inhibitor Ro-20-1724 in high releasers reduced the histamine release to normal levels. These findings suggest that increased histamine "releasability" in atopic dermatitis is related to abnormalities in cyclic nucleotide regulation. Basophil percentages within the leukocyte preparation and the histamine content per basophil were not significantly different between the atopics and normals. Histamine release did not correlate significantly with serum IgE levels.

3',5'-Cyclic-AMP Phosphodiesterases↗