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K A Harrison

Publications and source records attributed to K A Harrison.

At least 37 records · Page 2Linked to original sources
PubMed1996

On the safety of 5-[125I]iodo-2'-deoxyuridine--Preclinical evaluation in swine.

To increase tumor incorporation and minimize hepatic degradation of radio-IUdR, compartmental administration routes are being considered as an alternative to intravenous (i.v.) injections. Although there are significant data on the biodistribution and some reports on radiotoxicity of i.v.-administered 125IUdR, similar results for other routes of delivery are not available. We have undertaken a series of experiments intended to examine radiation effects of 125IUdR after intravesical (3 swine; eight 3 mCi doses at 4-day intervals), intracarotid (3 swine; two 10 mCi doses at 2-week intervals), and intra-aortic (5 swine, single dose of 10 mCi) administration in a swine model. Liver, renal functions, and complete blood counts were monitored throughout the duration of the experiment. Pharmacokinetics, systemic distribution of radioactivity and metabolites were measured. The normal tissue 125IUdR uptake and histology were determined after necropsy. No adverse systemic effects were identified. Clinical observations, laboratory data, and necropsy results were within normal range.

Administration, Intravesical↗
PubMed1996

Radiolabeled iododeoxyuridine: safety evaluation.

UNLABELLED: The emphasis of radiolabeled iododeoxyuridine (*IUdR) research at our institution to date has been to assess its safety as a potential therapeutic agent. Toward this goal, we have performed preclinical and clinical studies, using various routes of administration, to detect adverse changes in normal tissues in both humans and animals. As IUdR is rapidly dehalogenated by the liver, the intravenous route is unlikely to be successful in therapeutic efforts. We have therefore focused our attention on more "protected" routes: intra-arterial and intravesicular administration. METHODS: Studies were performed in farm pigs after multiple administrations of [125I]IUdR into the aorta, carotid artery and bladder. IUdR and metabolites were measured in venous blood samples at appropriate time intervals after administration, after which histologic examination of tissues was performed. Studies in human have been performed after intra-arterial administration of [123I]IUdR in patients with liver metastases and intravesicular administration in patients with bladder carcinoma, initially using [123I]IUdR and currently using both [123I]IUdR and [125I]IUdR. Blood samples for pharmacokinetics and metabolite analysis and tissue for autoradiography (when feasible) have been obtained. RESULTS: To date, no evidence of adverse effects on normal tissue or alteration of hematologic or metabolic indices have been seen in pigs or humans. When instilled in the bladder, there is little leakage of IUdR in the circulation. CONCLUSION: When [125I]IUdR is used as a therapeutic agent, we anticipate little or no effect on normal tissues.

Administration, Intravesical↗
PubMed1995

Isoleukotrienes are biologically active free radical products of lipid peroxidation.

The free radical oxidation of arachidonic acid esterified to glycerophospholipids is known to generate complex metabolites, termed isoprostanes, that share structural features of prostaglandins derived from prostaglandin H2 synthase. Furthermore, certain isoprostanes have been found to exert biological activity through endogenous receptors on cell surfaces. Using mass spectrometry and ancillary techniques, the free radical oxidation of 1-hexadecanoyl-2-arachidonoyl-glycerophosphocholine was studied in the search for products of arachidonic acid isomeric to the leukotrienes that are derived from 5-lipoxygenase-catalyzed metabolism of arachidonic acid. Several conjugated triene metabolites were chromatographically separated from known 5-lipoxygenase products and structures characterized as 5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid esterified to the glycerophosphocholine backbone. We have termed these products as B4-isoleukotrienes. Following saponification some, but not all, B4-isoleukotrienes were found to exert biological activity in elevating intracellular calcium in Indo-1-loaded human polymorphonuclear leukocytes. This activity could be blocked by a leukotriene B4 receptor antagonist. An EC50 of approximately 30 nM was determined for one unique B4-isoleukotriene with a relative retention index of 2.54. We have shown that free radical processes can lead to the formation of biologically active isoleukotrienes in glycerophosphocholine liposomes, and we propose that B4-isoleukotrienes may also be formed in membrane glycerophospholipids as a result of lipid peroxidation during tissue injury. Such B4-isoleukotrienes could then mediate events of tissue damage through activation of leukotriene B4 receptors on target cells.

Arachidonic Acid↗
PubMed1995

SPECT imaging of fluorine-18.

UNLABELLED: The objective of this work was to determine the potential clinical usefulness of SPECT to image 511-keV annihilation photons. METHODS: A triple-headed gamma camera equipped with ultra-high-energy collimators was used to image 18F. Sensitivity measurements were carried out and the FWHM and FWTM were determined in air and for a unit-density scattering medium. Additionally, tomographic phantom studies were acquired to evaluate image quality. RESULTS: The sensitivities of the three cameras were, for all practical purposes, identical. At a source-to-collimator distance of 100 mm, the FWHM and FWTM were 13 and 29 mm, respectively. A tomographic phantom study demonstrated that spheres with a diameter of 20 mm were well resolved when filled with 18F activity and placed inside a water-filled phantom. CONCLUSION: The triple-headed SPECT camera in this investigation is a practical means of acquiring tomographic 18F images. The reconstructed slices were of sufficient quality to be of value in some clinical studies.

Fluorine Radioisotopes↗
PubMed1995

Diagnostic use of radiolabeled antibodies for cancer.

Antibodies against a variety of tumor-associated antigens have been studied, as well as a number of modifications to the antibodies themselves, including Fab' fragments and chimeric, humanized, and human antibodies. The appropriate use of radioimmunoconjugates in the evaluation of cancer patients has not yet been clearly defined. Only a few studies have assessed their use, primarily through the intravenous route, in initial disease staging. To date, immunolymphoscintigraphy has not proven promising in the staging of cancers. More emphasis has been given to the use of IV radioimmunoconjugates to detect residual and recurrent disease, with generally favorable results. In addition, radioimmunoguided surgery, using small, handheld probes to detect foci of antibody accumulation, appears to be a valuable tool. As better production techniques become available and large clinical trials provide more clearly defined indications for radioimmunoconjugate use, these agents should enter the arena for routine diagnostic use.

Antibodies, Monoclonal↗
PubMed1994

A novel human homeobox gene distantly related to proboscipedia is expressed in lymphoid and pancreatic tissues.

A novel human homeobox gene, HB9, was isolated from a cDNA library prepared from in vitro stimulated human tonsil B lymphocytes and from a human genomic library. The HB9 gene is composed of 3 exons spread over 6 kilobases of DNA. An open reading frame of 1206 nucleotides is in frame with a diverged homeodomain. The predicted HB9 protein has a molecular mass of 41 kilodaltons and is enriched for alanine, glycine, and leucine. The HB9 homeodomain is most similar to that of the Drosophila melanogaster homeobox gene proboscipedia. Northern blot analysis of poly(A) RNA purified from the human B cell line RPMI 8226 and from activated T cells revealed a major mRNA transcript of 2.2 kilobases. Similar analysis of poly(A) RNA from a variety of adult tissues demonstrated HB9 transcripts in pancreas, small intestine, and colon. Reverse transcriptase-polymerase chain reaction was used to examine HB9 RNA transcripts in hematopoietic cell lines. HB9 RNA transcripts were most prevalent in several human B cell lines and K562 cells. In addition, transcripts were detected in RNA prepared from tonsil B cells and in situ hybridization studies localized them in the germinal center region of adult tonsil. These findings suggest the involvement of HB9 in regulating gene transcription in lymphoid and pancreatic tissues.

Adult↗
PubMed1994

Induction of high grade astrocytoma (HGA) by protons: molecular mechanisms and RBE considerations.

Protons of a specific energy, 55 MeV, have been found to induce primary high grade astrocytomas (HGA) in the Rhesus monkey (Macaca mulatta). Brain tumors of this type were not induced by protons of other energies (32-2,300 MeV). Induction of HGA has been identified in human patients who have had radiation therapy to the head. We believe that the induction of HGA in the monkey is a consequence of dose distribution, not some unique "toxic" property of protons. Comparison of the human experience with the monkey data indicates the RBE for induction of brain tumors to be about one. It is unlikely that protons cause an unusual change in oncogenic expression, as compared to conventional electromagnetic radiation.

Animals↗
PubMed1994

Delayed gastric emptying of both the liquid and solid components of a meal in chronic liver disease.

OBJECTIVES: To evaluate gastric emptying in patients with chronic liver disease and portal hypertension. METHODS: We measured gastric emptying of both the liquid and solid components of a meal in 10 consecutive patients with chronic liver disease and portal hypertension, but free of ascites, and 14 age- and sex-matched healthy controls. In the patients with liver disease, relationships between emptying and liver function were examined. To measure gastric emptying, subjects consumed a test meal that consisted of scrambled eggs labeled with 99mTc-sulfur colloid and 4 oz of water labeled with 111In-diethylene triamine pentacetic acid (DTPA). RESULTS: Patients with liver disease and portal hypertension demonstrated delayed emptying of both the liquid (t1/2, min, mean +/- SE, patients vs. CONTROLS: 69.4 +/- 19.4 vs. 31.4 +/- 1.8, p < 0.01) and solid (post-lag phase solid emptying: 141 +/- 32.9 vs. 69.8 +/- 4.6, p < 0.006) components of the meal. We could not identify any correlation between gastric emptying and tests of liver function. CONCLUSIONS: Gastric emptying is delayed in patients with liver disease and portal hypertension; this abnormal gastric motor function may contribute to the pathophysiology of foregut complaints in this patient population.

Adult↗
PubMed1993

Behavior analysis and intervention during hospitalization for brain trauma rehabilitation.

Continued problematic behavior in children and adolescents after brain trauma is a major barrier to medical care, rehabilitation, and eventual independent living. The present study demonstrates the application of already well-developed behavior analysis techniques to the early posttrauma expression of behavior problems during hospital recovery. To satisfy concerns regarding both cost and individualized treatment, interventions were carried out primarily by regular hospital staff (nurses and therapists), medical record data were used to document gains, and time series, within subject designs were used to show experimental control. Four patients (three male and one female) ranging in age from 10 to 16 years, received intervention based on behavior analysis techniques, which reduced disruption and increased cooperation with therapy and medical care. Behavior analysis techniques will be relevant to future rehabilitation research to the extent that the posttrauma patient's behavior is effected by environmental consequences as demonstrated here.

Adolescent↗
PubMed1993

Plasma D-dimer: a useful tool for evaluating suspected pulmonary embolus.

Although ventilation-perfusion lung scanning is widely used in evaluating patients with suspected pulmonary embolus, additional rapid screening tests are needed to supplement scintigraphy in patients in whom the scan is indeterminate or the scan results are discordant with clinical suspicion. D-dimer is a fibrin degradation product which should be elevated in the presence of intravascular coagulation. We prospectively studied patients referred for lung scanning by obtaining a plasma D-dimer latex agglutination assay at the time of the scan. Of 64 patients who had pulmonary angiography to confirm the diagnosis, 16 were positive for pulmonary embolus and only one had a normal D-dimer. The D-dimer was normal in 27 of 48 patients without embolus and elevated in 21. Although an elevated D-dimer level is a nonspecific finding, we conclude that a normal D-dimer is a good negative predictor for pulmonary embolus, with a negative predictive value of 0.97.

Enzyme-Linked Immunosorbent Assay↗
PubMed1991

Response patterns of children with learning disabilities: is impulsivity a stable response style?

A correlational analysis was conducted to assess the relationship among various assessment instruments, including Kagan, Rosman, Day, Albert, and Phillips's (1964) Matching Familiar Figures Test (MFFT), and actual classroom performance vis-à-vis impulsive responding. Subjects were 22 children (16 male, 6 female), ages 5 to 11 years, enrolled in an academic remediation program. The results do not support a relationship between impulsivity, as measured by the MFFT, and academic progress in a classroom setting. Implications for task-specific measures of impulsivity and remediation are discussed.

Achievement↗
PubMed1988

Statistical interactions in studies of physician utilization. Promise and pitfalls.

It has been suggested that use of interactive statistical models would greatly increase the proportion of variance accounted for by studies of physician utilization. The purpose of this paper is to evaluate and describe the benefits and pitfalls of using interactive statistical models of physician utilization. The paper presents Monte Carlo simulation data and real world data to determine how much more of the variance in physician utilization can be accounted for by interactive regression models. Results indicate that adding interaction terms is unlikely to produce large increases in variance accounted for. The usefulness of interactive models is particularly low when there is substantial measurement error in the predictor variables. Other advantages and disadvantages of interactive models are discussed, including 1) improved understanding, 2) inflation of alpha, 3) sensitivity to transformations and scale of measurement, and 4) confounding of interaction effects with nonlinear effects.

Computer Simulation↗