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Biomedical subjects

I Harrison

Publications and source records attributed to I Harrison.

At least 19 recordsLinked to original sources

Pathology and the OSCE: insights from pilot study.

Undergraduate medical education in Manchester in undergoing wholesale revision, with the introduction of problem-based learning (PBL) in each successive year of the curriculum, as the cohort of students who joined the faculty in 1994 advances through the course. This cohort has now entered year 3, which primarily hospital-based. In preparation for this, we have explored the development of an OSCE, not only to assess core interpersonal skills such as history taking, clinical examination, and the ability to explain things to patients, but also to integrate the examination of important skills relating to investigational sciences. These include the correct choice of laboratory tests, accurate interpretation of data, and appropriate selection of clinical responses to test results.

Attitude of Health Personnel

A study of the degradation of phenoxyacid herbicides at different sites in a limestone aquifer.

The biodegradation of three phenoxyalkanoic acid herbicides, viz. MCPA, dichlorprop and mecoprop, under aerobic and anaerobic conditions was investigated using microcosm techniques. The field studies were conducted in a limestone aquifer that had suffered contamination from leaking landfill sites in which phenoxyalkanoic acid herbicides (mostly mecoprop) had undergone disposal. The results from in situ field and laboratory microcosms indicated that under microbially active aerobic conditions the biotransformation of all three herbicides was rapid and that lag phases were short. Under fully aerobic conditions the concentration of each of the three herbicides was reduced from 2,000 micrograms/l to below the detection limit (approx. 10 micrograms/l) of the HPLC system, used for their analysis, within 14 days. However, under microbially active anaerobic conditions no degradation of the herbicides could be discerned over the 100-200 day duration of the experiments. This finding has significant implications for the disposal of phenoxyalkanoic acid herbicides particularly in situations where any resulting leachate may find its way into underlying water resources.

2,4-Dichlorophenoxyacetic Acid

Audit of 6 years' experience of breast fine needle aspiration (FNA) cytology using the cytospin method; improvement through multidisciplinary clinical audit.

A breast FNA cytology service for palpable breast lumps was commenced in 1989 using the cytospin method. Over the following 6 years 2314 aspirates were received. The results were audited in detail in 1990, 1991/1992 and 1994. Multidisciplinary clinical audit meetings followed each audit cycle. Practice change was agreed after each audit. Each audit cycle was followed by demonstrable improvement in the complete sensitivity of the technique, being respectively 79%, 88% and 96%. The cytospin method is a viable alternative to the conventional smear method.

Biopsy, Needle

Distribution of selenium in human blood plasma and serum.

A method has been developed which separates the three major selenium-containing proteins found in human blood serum and plasma: selenoprotein-P, glutathione peroxidase and albumin. They were separated from plasma or serum by affinity chromatography and the Se content determined directly by ETAAS. Selenoprotein-P is retained on a heparin-Sepharose column, and subsequently eluted with an excess of heparin, while glutathione peroxidase is separated by a blue-Sepharose column. The amount of Se associated with albumin was assumed to be the Se remaining in the rest of the sample. The detection limit of the ETAAS method, when applied to the separated fractions, was 0.8 microgram l-1 (2 ng absolute) and the accuracy of the determination was confirmed by comparison with spectrofluorimetry. The distribution of Se in the serum or plasma of 21 healthy people was determined, showing that 53 +/- 6% of the total present is associated with selenoprotein-P, 39 +/- 6% as glutathione peroxidase and 9 +/- 4% as albumin.

Adult

Improved molecular fluorescence method for the determination of selenium in biological samples.

A procedure for the determination of selenium in whole blood and urine has been improved by optimization of the digestion and derivatization procedures. An overnight pre-digestion step with 4 + 1 concentrated nitric-perchloric acids reduced the time of mineralization at 170 degrees C from 4 h to 30-45 min. Conversion of all the selenium to selenite (SeIV) was optimized by addition of 1 ml of concentrated hydrochloric acid, with heating to 100 degrees C for 30 min. The rate of formation of the 2,3-diaminonaphthalene (DAN) complex of selenium was improved by heating to 70-100 degrees C for a minimum of 30 min. Co-addition of hexane during derivatization simplified the extraction procedure. The modified method was applied successfully to the analysis of Seronorm quality control whole blood and urine (83 and 24 micrograms l-1 Se, respectively). Samples from 12 healthy adults, gave results in expected ranges (mean concentrations of 75 +/- 8 micrograms l-1 in blood and 25 +/- 8 micrograms l-1 in urine). The structure of the Se-DAN complex was investigated using elemental analysis, FTIR spectrometry, 1H and 13C NMR spectroscopy, and FAB MS. The information obtained indicates that the selenodiazo group does not contain an Se-O bond or protonated nitrogens, as proposed in other studies.

Adult

Dose dependence of the oxygen enhancement ratio (OER) in radiation inactivation of Chinese hamster V79-171 cells.

The dose dependence of the oxygen enhancement ratio (OER) has been examined through multiple measurements of the response of Chinese hamster V79-171 cells to low and high doses of radiation under aerobic and hypoxic conditions. In this series of experiments the cells were maintained at 37 degrees C throughout the gassing and irradiation periods, to simulate normal physiological conditions. Flow cytometry and cell sorting techniques were used to facilitate accurate measurement of cell survival throughout the dose range, but particularly at low dose. The OER was found to decrease significantly at low dose, qualitatively confirming earlier reports from this laboratory, though the decrease was somewhat smaller in the present series. This difference may be a temperature effect since in the earlier experiments irradiation was at 0 degree C. This report shows that the OER decreases from a value of 2.87 +/- 0.16 (standard deviation of mean) at S = 0.01 to 2.36 +/- 0.19 at S = 0.80. Both alpha and beta are altered by the presence of oxygen. The OER is presented as a function of dose in nitrogen.

Aerobiosis

The radiation response of asynchronous cells at low dose: evidence of substructure.

Flow cytometry and cell sorting techniques have been used together with repeated measurement in an attempt to define better the radiation survival response of asynchronously dividing Chinese hamster V79-171 cells under aerobic and hypoxic conditions. Although the first two decades of cell inactivation have been examined, particular attention has been given to the low-dose range of a few grays, as used in individual radiation therapy treatments. A single linear-quadratic dose-response function was consistently unable to fit both the low-dose and high-dose data satisfactorily, suggesting a two-component response. Separate fitting of the low-dose and high-dose portions of the response yielded alpha and beta values which differed significantly (P = 0.001 to 0.002). The data are consistent with the hypothesis that the observed substructure simply reflects the presence of subpopulations of sensitive (G1-, G2-phase) and resistant (late S-phase) cells, which are resolved in these measurements. These results may have significance for certain situations in radiation therapy and in biophysical modeling of the radiation response.

Aerobiosis

The pony as an animal model for vascular implants.

This study evaluated the pony as a potentially suitable model for vascular implant research. Healthy, conditioned ponies were randomly assigned to one of three groups: group I, carotid artery autografts (n = 6); group II, e-PTFE carotid interpositional grafts (n = 5); and group III, e-PTFE carotid interpositional grafts plus aspirin (10 mg/kg) and dipyridamole (3.5 mg/kg) drug administration. It was found that autografts remained patent longest (mean = 396.2 days; grafts were still patent at time of writing) followed by group III grafts (157.5 days), with group II grafts remaining patent for the shortest duration (61.1 days), (p less than 0.01). Patency was determined using two-dimensional real-time ultrasonography with Doppler velocimetry and/or arteriography. It was demonstrated that the pony's response to antithrombotic drugs was consistent and comparable to that in other animal models, both with respect to platelet function and affect on patency rate. The combination of the ease of surgical manipulation, drug administration, and platelet function testing, the comparable size of the pony and its heart and blood vessels to that of an adult human, the long life span of ponies, and the patency results of this study have demonstrated that the pony is a valuable animal model for vascular research.

Animals

Surgical management of multiple lung metastases of different origin.

A case of synchronous carcinoma of the colon and the kidney with solitary metastatic nodules to each lung from each cancer is presented. The time interval between the original surgery and the first metastasis was 3 months and between the first and second metastases, 7 months. The patient underwent wedge resection of both metastases. Eight years after surgery he remains free of tumor.

Adenocarcinoma

Radiosensitization of hypoxic cells at low doses.

We have measured the radiosensitization produced in hypoxic V79 cells in vitro by SR 2508, Ro-03-8799, and oxygen at conventional doses (0-30 Gy) as well as at low doses (0-4 Gy). Two techniques have been used: (a) FACS (Fluorescence Activated Cell Sorter) plating followed by the conventional colony formation assay and (b) microscopic scoring of surviving and non-surviving cells using the DMIPS (Dynamic Microscope Image Processing Scanner) system. The results show that the enhancement ratios (ER) for both drugs and for oxygen are dose dependent, decreasing somewhat at doses less than 4 Gy. The low dose sensitization measured at S = 0.8 for SR 2508, Ro-03-8799 and O2 was found to be approximately 73%, 61% and 75% of the high dose sensitization for these three agents, respectively. These values are not significantly different. Both the alpha- and beta-components of cell kill appeared to be sensitized by all three agents. The enhancement ratios obtained by the two different techniques are in general agreement, though some qualitative differences have been observed.

Animals

Reserpine toxicosis in a horse.

A single injection of reserpine in an adult horse was believed to induce toxicosis for several days. Clinical signs included erratic, colic-like behavior followed by depression, bradycardia, miosis, ptosis, and paraphimosis. Diarrhea was not observed and may have been due to the effect of xylazine given with the reserpine. The horse was supported with IV fluids and intensive nursing care. Gradual improvement was noted 72 hours after the horse received the drug. Qualitative analysis via high-performance liquid chromatography was positive for reserpine. Methamphetamine is the recommended antidote but was not used in this case.

Animals

Radiosensitization by diamide at low radiation doses.

In vitro studies in this laboratory indicated that at low radiation doses (0-3 Gy), sensitization by misonidazole diminishes. We have suggested that this results from a failure of misonidazole to enhance effectively the single-hit or alpha component of cell inactivation. Our low dose assay uses a partially automated microscopic analysis procedure which scores both surviving and killed cells. If enough cells are scored, this assay provides much better accuracy at low doses than the conventional assay. Recently, we have applied our low dose assay to a study of sensitization by diamide. This was done, in part, as a test of our assay system, since many investigators have shown that diamide substantially reduces the shoulder of the hypoxic cell survival curve. At high doses (D = 6.5 to 10 Gy, S = 0.1 to 0.01) we obtained for 150 microM diamide an enhancement ratio (ER) of 2.6 for hypoxic cells and 1.1 for aerobic cells. At low doses, 0-2.5 Gy, diamide still sensitized hypoxic cells well; with 150 microM diamide, the ER at 1 Gy (S = 0.8) was 2.0, about equal to the oxygen enhancement ratio (OER) at this dose. The fact that diamide shows good sensitization at low doses with our assay adds to the credibility of the assay and reduces the likelihood that our observations with misonidazole are an artifact of our system.

Anaerobiosis

Treatment of hygromata in horses.

A surgical technique of open drainage, using penrose drains and pressure bandages, was used for the treatment of hygromata in four horses. In 3 cases with hygroma of the carpus, one with a secondary infection, there was complete resolution of the condition whereas in the one case with hygroma of the elbow resolution was more protracted because of difficulties in bandaging. The cosmetic and functional results after operation were most satisfactory.

Animals

Spironolactone and canrenoate-K: relative potency at steady state.

Relative dose ratios of the mineralocorticoid antagonists spironolactone (100 mg and 200 mg daily) and canrenoate-K (200 mg daily) at steady state were defined in six healthy subjects with fludrecortisone as the mineralocorticoid agonist. The urine log 10 Na/K responses during spironolactone treatments were consistent with the law of mass action. The potency of canrenoate-K was 0.68 (95% C.L. 0.53 to 0.89) that of spironolactone on a weight basis. Approximately 72% of the renal antimineralocorticoid activity of spironolactone could attributed to the metabolite canrenone. The results at steady state are contrasted with those of a previously study comparing single doses of spironolactone and canrenoate-K.

Administration, Oral

Spironolactone and potassium canrenoate in normal man.

The pharmacological activity of single doses of the two aldosterone antagonists, potassium canrenoate and spironolactone, was examined in two studies in healthy volunteers. Both drugs were active in reversing urinary electrolyte changes induced by fludrocortisone in periods 2 to 16 hr after treatment. Potassium canrenoate was significantly less potent that spironolactone on a weight or molar basis, with best estimates of the relative potency potassium canrenoate: spironolactone of approximately 0.3:1. On a weight basis the two drugs yielded plasma levels of the metabolite canrenone which were approximately equivalent. The results indicate that canrenone is not the principal pharmacologically active metabolite of spironolactone. Our study suggests that a major part of the renal antimineralocorticoid activity of spironolactone may be attributable to minor sulfur-containing metabolites or their precursors having a high renal clearance that affords access to their site of activity via the renal tubular fluid.

Canrenoic Acid