Biomedical subjects

P Richards

Publications and source records attributed to P Richards.

At least 91 records · Page 5Linked to original sources

PubMed1985

Focal epilepsy with mesial temporal sclerosis after acute meningitis.

Following acute meningitis associated with severe convulsions in childhood, two patients had chronic, drug-resistant, temporal lobe epilepsy. This disorder was preceded by an entirely natural development, in one case extending for nine years and in the other case for eight years. Each patient was treated with right anterior temporal lobectomy. Classic mesial temporal sclerosis (Ammon's horn sclerosis) was found in both patients. Relief of the epilepsy was associated with remission of the concomitant social and psychiatric handicaps. At least ten years of follow-up are required in the evaluation of the treatment of early brain infections. Chronic focal epilepsy after childhood meningitis with febrile convulsions merits neurosurgical consideration.

Acute Disease↗

PubMed1985

The development and in-vivo behavior of tin containing radiopharmaceuticals--I. Chemistry, preparation, and biodistribution in small animals.

Tin is an essential ingredient of most technetium-99m radiopharmaceutical preparations but its in-vivo distribution and long-term fate are not well understood. Tin-117m (t1/2 14d; gamma 159 keV, 86%) is an ideal tracer for studying biological behavior of tin compounds as well as for developing clinically-useful radiopharmaceuticals. This work describes the preparation and in-vivo distribution in mice of a number of tin-117m labeled compounds with commonly used ligands. High bone uptake of most compounds studied as well as the unexpectedly high bone uptake of Sn4+-DTPA indicates a high bone affinity of tin bound to chemically diverse ligands. Various compounds show subtle but significant differences in blood clearance, excretion, and soft-tissue uptake. Differences among Sn2+ and Sn4+ compounds with the same ligand are particularly noteworthy. For stannic chelates, higher bone uptake, faster blood clearance, and reduced soft-tissue concentration were observed. It appears that tin compounds bind to bone predominantly through the tin atom and that the differences in biodistribution depend on factors such as the net charge on the complex, the oxidation state of tin, and hydrolytic and kinetic stabilities of the complexes. The results indicate that the favorable half-life and decay characteristics of tin-117m in various stannic compounds, especially stannic-DTPA, make it potentially useful as an agent for skeletal scintigraphy and radiotherapy of bone tumors.

Animals↗

PubMed1985

The development and in-vivo behavior of tin containing radiopharmaceuticals--II. Autoradiographic and scintigraphic studies in normal animals and in animal models of bone disease.

Various 117mSn (2+ and 4+) compounds in well defined oxidation states were studied in normal mice using whole body autoradiography (WBARG), tissue distribution and scintigraphy in animal models of vitamin A induced bone disease, fracture, infected fracture and ischemic muscle lesions. The 117mSn4+-DTPA showed high affinity to normal bone with low soft tissue concentration. Increased deposition of this compound in fractures and ischemic lesions in muscle was also demonstrated. In hypervitaminosis A, reduced bone uptake of 117mSn4+-DTPA was shown to occur. Nude mice bearing osteogenic sarcoma of human origin showed uptake in spiculated pattern. The similar distribution of 117mSn4+-DTPA which does not contain phosphate or phosphonate groups, and the 99mTc(Sn) skeletal imaging compounds may indicate that tin is important in binding to bone. 117mSn4+-DTPA may not be ideal for routine imaging except when long term follow up is required. It should however be considered for therapy of bone tumors because of the long physical half-life of 117mSn (t1/2 = 14.03 days), abundance of short-range conversion and Auger electrons and its preferential deposition in cortical bone as indicated by our results.

Animals↗

PubMed1985

Effect of respiratory motion on pulmonary activity determinations by positron tomography in dogs.

The effect of respiratory motion on pulmonary activity determinations by positron emission tomography (PET) was studied in dogs with experimentally created pulmonary emboli (PE). The location of the PE was evaluated by planar 99mTc lung imaging to determine the appropriate sites for transaxial PET scans. PET scans of the lung then were obtained after i.v. injection of 68Ga-labeled microspheres. PET scans were acquired during slow (15 breaths/min) and fast (30 breaths/min) breathing with the same minute ventilation and then postmortem. Lung perfusion patterns were documented by i.v. injection of India ink before sacrifice. Cross sections of the excised lungs were made at the same levels as the PET scans, and eight sections containing 14 perfusion defects were analyzed. The scans obtained during slow breathing consistently showed edge blurring and demonstrated defects less well than scans obtained during fast breathing or postmortem. The normal-to-defect activity ratios during fast breathing and on the postmortem studies were similar and approximately 17% higher (P less than .01) than in scans obtained in the same animals during slow breathing. The results demonstrate the need for motion correction during quantitative analysis of regional lung activity by positron tomography, and suggest that high-frequency respiration at small tidal volumes may be one means for obtaining this correction.

Animals↗

PubMed1985

Microsurgery for stroke.

Stroke remains a major problem in the Western world but microneurosurgical procedures are applicable only to a minority of victims, namely those with intracranial carotid occlusion and those with aneurysms or arteriovenous malformations. The operating microscope has made the technical approach to these feasible. However, questions remain as to the validity of the extracranial-intracranial bypass in carotid occlusion and the timing of aneurysm surgery. These questions tend to overshadow the technical advances following on from use of the operating microscope.

Cerebral Revascularization↗

PubMed1985

Immunoreactivity and biodistribution of indium-111-labeled monoclonal antibody to a human high molecular weight-melanoma associated antigen.

The anti-human, high molecular weight-melanoma associated antigen (HMW-MAA) MoAb 225.28S was chelated with 111In and then tested for its in vitro reactivity with cultured human melanoma cells and for its biodistribution in human melanoma bearing nude mice. In vitro studies showed that the radiolabeled antibody reacted specifically with cultured melanoma cells. However, binding of DTPA to the monoclonal antibody reduced its titer with cultured melanoma cells from 1:1024 to 1:512. Further labeling of the DTPA-antibody conjugate with 111In caused an additional reduction of its titer to 1:128. Injection of the radiolabeled monoclonal antibody into nude mice resulted in the accumulation of significantly (p less than 0.001) higher radioactivity in melanoma tissue than in nude mice injected with either [111In] chloride or 111In-labeled antibody to human acid phosphatase. The specificity of the distribution of the radiolabeled antibody in nude mice also was indicated by its poor localization in lesions other than melanoma (e.g., human prostate carcinoma and chronic abscess). The localization of antibody in liver and kidney was also high, although lower than that achieved in tumor. These results indicate that 111In-labeled monoclonal antibodies to human tumor associated antigens may be useful for localizing malignant lesions. However, there is a need to improve labeling and/or purification of antibody in order to decrease renal and hepatic activity.

Animals↗

PubMed1984

Audit of admission to medical school: III--applicants' perceptions and proposals for change.

Applicants to St Mary's Hospital Medical School were asked to comment freely on the process of selection. They were particularly concerned about the role of interviews, excessive emphasis on academic achievement, the problem of rank-ordering choices on the UCCA form, and possible biases in selection. These concerns and the results of our survey suggest that candidates should not be asked to rank their choices in order of preference, that UCCA applications for medicine should be subject to an early closing date, that as many applicants as possible should be interviewed, that applicants should be encouraged to apply after taking A levels, that educational opportunity should be taken into account in assessing A level grades, and that mature students should be encouraged, not least by providing mandatory awards for a second degree in medicine.

Attitude↗

PubMed1984

Audit of admission to medical school: II--Shortlisting and interviews.

Analysis of shortlisting of applicants for interview at St Mary's Hospital Medical School showed that factor analysis could reduce the selection criteria to three independent scales--"academic ability," "interests," and "community service"--all of which contributed to the interview decision. Early applicants scored more highly on all three factors but were still at a greater advantage in selection for interview than would have been predicted. The dean's judgment of priority for interview from the UCCA form was found to predict a candidate's chance of acceptance at other medical schools besides St Mary's. Analysis of interviewing showed high correlations among interviewers in their assessments, although there was evidence of influence by the chairmen. Factor analysis showed three major factors--academic suitability, non-academic suitability, and health--of which non academic suitability was the major determinant of interview success. Non academic suitability was related to personality (high extraversion and low psychoticism) and to the choices made on the UCCA form. The system of admission interviews enabled greater emphasis to be put on broader interests and achievements than if selection had been on the basis of UCCA application form alone.

Education, Medical, Undergraduate↗

PubMed1984

Audit of admission to medical school: I--Acceptances and rejects.

A prospective study of the process of application, selection, and admission to medical school was performed. St Mary's Hospital Medical School received 1478 UCCA applications for admission in October 1981: 94 (6.4%) applicants entered St Mary's in October 1981, 436 (29.5%) entered other medical schools, 176 (11.9%) read a subject other than medicine, and 772 (52.2%) did not enter university. The study included 12.6% of all applicants and 12.9% of all entrants to British medical schools in October 1981. Educational qualifications, demographic variables, type of schooling, family background, and the manner of application were examined in relation to overall selection. A level achievement was the major determinant of acceptance. O level achievement, early application, and medical parents had significant but smaller independent effects on the chance of acceptance. Social class, age, sex, and school type did not predict acceptance when corrected for academic and other factors. Few differences in personality, career preference, cultural interests or attitudes were found between those accepted and those rejected.

Educational Measurement↗

PubMed1984

University cuts, medicine, and the public interest.

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Cost Control↗

PubMed1984

Long-term outcome in children with temporal lobe seizures. V: Indications and contra-indications for neurosurgery.

One hundred unselected children with temporal lobe epilepsy were followed up between 1948 and 1982. The series was a personal one. None was lost to observation. For 42 patients, contra-indications for surgery had emerged before the end of their schooldays. 29 cases were considered for surgery. 16 were rejected on technical grounds, and none of these made an epileptic, social, psychiatric or personality recovery. 13 patients were operated on, none of whom continued to have habitual epilepsy: all their biographies were remarkably improved, though several years postoperative care sometimes was needed. The authors conclude that surgery plays a major rôle in the treatment of temporal lobe epilepsy of childhood, and those who would benefit usually can be recognised before leaving school.

Adolescent↗

PubMed1984

Developmental aspects of focal epilepsies of childhood treated by neurosurgery.

Data on 50 patients treated surgically for intractable focal epilepsy were analysed. There were 10 hemispherectomies, 32 temporal lobectomies and eight operations to other areas of the brain. The median age at operation was 14 years. 29 patients were found to have mesial temporal sclerosis or sclerotic hemispheres and 17 had alien tissue and one sclerosis with heterotopia. No lesion was found in three cases. The nature of the first seizure was found to relate significantly to pathology. 30 patients had suffered an early convulsion. Between the convulsive insult and the onset of focal epilepsy there was a silent interval, the duration of which was biased by sex and side of lesion. The remaining 20 patients, of whom a highly significant number had alien tissue, had not had an early convulsion before the onset of focal epilepsy. The importance of accurate clinical histories is stressed. Clinical considerations alone predicted the pathology and laterality of the lesion in more than half the series. Regular EEG recordings and repeat scanning were found to be important investigations. Major disorders of behaviour had occurred in 44 patients. As adults, the series were free of severe psychiatric symptoms, but many required years of careful rehabilitation. 31 children had been excluded from normal schools before operation. Postoperatively, many patients continued their education in normal schools. Some required basic remedial teaching, others successfully undertook higher education and training. 49 patients benefited over-all from neurosurgical treatment. 34 had no more habitual epilepsy at all. Full global gains often took at least five years to achieve.

Adolescent↗

PubMed1984

Practical prospects for the therapeutic use of essential amino acid analogues.

Interest in essential amino acid analogues developed as a means of diverting ammonia nitrogen into protein synthesis in patients with chronic renal failure, urea cycle enzyme defects and hepatic failure. Long-term practical therapeutic value has so far only been proved in children with urea cycle defects. Recent work confirms that the alpha-keto acid of leucine in particular alters protein turnover and may prove of wide practical application to improve nitrogen balance in post-operative patients and others with severe illness.

Amino Acids, Essential↗

PubMed1984

A comparison of the cyclic anhydride and mixed anhydride methods for 111In-DTPA chelation to monoclonal antibodies.

The cyclic anhydride (CA) and the mixed anhydride (MA) of DTPA were synthesized and used to chelate 111In to an antimelanoma monoclonal antibody. The CA and MA methods showed mean labeling efficiencies of 25.7 and 20.5%, respectively (p = NS). The binding efficiency of labeled antibody to human melanoma cells in tissue culture also was similar (means = 52 and 50%, respectively, p = NS), as was tumor uptake in nude mice at 96 hrs post-injection (16%-CA vs 12%-MA). The method required less complicated chemical syntheses, much less preparation time, and the product was stable over a much longer period. The results suggest that the CA method is preferable for bifunctional chelate labeling of monoclonal antibodies with 111In-DTPA.

Animals↗

PubMed1983