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Biomedical subjects

D Hamilton

Publications and source records attributed to D Hamilton.

At least 19 recordsLinked to original sources

Central serotonin receptors and delayed gastric emptying in non-ulcer dyspepsia.

OBJECTIVE: To determine whether central serotonin receptors are involved in the pathophysiology of non-ulcer dyspepsia. DESIGN: Between subjects study of solid phase gastric emptying and prolactin response to buspirone challenge. SUBJECTS: 12 patients fulfilling criteria for non-ulcer dyspepsia and 12 age and sex matched controls. MAIN OUTCOME MEASURES: Solid phase gastric emptying measured by scintigraphic assessment of the movement of a standard meal labelled with technetium-99m and indium-111; responsiveness of central serotonin 1A receptors measured by the prolactin release following challenge with oral buspirone 60 mg. RESULTS: Solid phase gastric emptying was significantly delayed in the patients with non-ulcer dyspepsia (t 1/2 = 90.6 (SD 14.5) minutes in patients and 54.6 (10.7) minutes in controls; 95% confidence interval 24.7 to 46.7 minutes, p < 0.001). Prolactin release was significantly greater in patients compared with controls (1272.7 (1039.9) mU/l v 292.9 (136.1) mU/l; 352.1 to 1607.5 mU/l, p < 0.01). Gastric emptying and prolactin release were significantly correlated (r = 0.59, p = 0.04) in the patients but not in the controls (r = 0.23). CONCLUSION: Central serotonin 1A receptors may have a role in the pathophysiology of non-ulcer dyspepsia of the dysmotility subtype.

Adult

Random mutagenesis of Schizosaccharomyces pombe SRP RNA: lethal and conditional lesions cluster in presumptive protein binding sites.

Signal recognition particle (SRP), a ribonucleoprotein composed of six polypeptides and one RNA subunit, serves as an adaptor between the cytoplasmic protein synthetic machinery and the translocation apparatus of the endoplasmic reticulum. To begin constructing a functional map of the 7SL RNA component of SRP, we extensively mutagenized the Schizosaccharomyces pombe SRP7 gene. Phenotypes are reported for fifty-two mutant alleles derived from random point mutagenesis, seven alleles created by site-directed mutagenesis to introduce restriction sites into the SRP7 gene, nine alleles designed to pinpoint conditional lesions, and three alleles with extra nucleotides inserted at position 84. Our data indicate that virtually all single nucleotide changes as well as many multiple substitutions in this highly structured RNA are phenotypically silent. Six lethal alleles and eleven which result in sensitivity to the combination of high temperature and elevated osmotic strength were identified. These mutations cluster in conserved regions which, in the mammalian RNA, are protected from nucleolytic agents by SRP proteins. The effects of mutations in the presumptive binding site for a fission yeast SRP 9/14 homolog indicate that both the identity of a conserved residue and the secondary structure within which it is embedded are functionally important. The phenotypes of mutations in Domain IV suggest particular residues as base-specific contacts for the fission yeast SRP54 protein. A single allele which confers temperature-sensitivity in the absence of osmotic perturbants was identified in this study; the growth properties of the mutant strain suggest that the encoded RNA is somewhat defective even at the permissive temperature, and is most likely unable to correctly assemble with SRP proteins at the nonpermissive temperature.

Alleles

Imaging of medullary carcinoma of the thyroid using 111In-labelled anti-CEA monoclonal antibody fragments.

The distribution of 111In-labelled anti-carcinoembryonic antigen (CEA) monoclonal antibody fragments [F(Ab')2] was studied in five patients either with known inoperable medullary carcinoma of the thyroid (MCT) or evidence of recurrence/metastases based on elevated calcitonin (hCT) levels. All five cases had elevated serum CEA levels and positive immunohistochemical stains for both hCT and CEA prior to scintigraphy. In two patients with identified inoperable disease both planar and SPECT scans were positive. In the remaining three patients, where the recurrence/metastatic sites were unknown, SPECT images were positive in two. Of these, only one had positive planar images. These results indicate that 111In-labelled anti-CEA F(ab')2 scintigraphy, especially in conjunction with SPECT, is useful for the diagnostic evaluation of patients with MCT. The limiting factor of this technique is the high level of non-specific uptake, particularly in the liver, but improvements in the specificity of newer anti-CEA antibodies and the ability to label these with 99Tcm is addressing this problem.

Adult

A nursing challenge: adult-onset Tay-Sachs disease.

Adult-onset GM2 gangliosidosis (AOG), also labelled Adult-Onset Tay-Sachs disease, is a slowly progressing disease caused by a gradual accumulation of the GM2 ganglioside in neurons due to defective hexosaminidase A. Recent research findings and clinical experiences suggest that AOG may be more widespread than previously believed. Moreover, the diagnosis of AOG is often delayed because patients present with psychotic symptoms that mimic dementia, schizophrenia, mania, and depression. Because AOG patients typically respond poorly to psychiatric drug therapy and the symptomatology is so diverse, nurses must design and implement nursing care that ensures safety, structure, and comfort.

Adult

Operating room scheduling. Choosing the best system.

The multiple criteria involved in the hospital OR scheduling problem cannot be ignored. Our goal is to identify the important criteria regarding this problem and determine the degree to which the scheduling approaches in use do or do not support these criteria. This contingency approach to selecting an OR scheduling system should enable hospital administrators to make policy decisions that will most effectively support stated and unstated organizational objectives.

Consumer Behavior

Head and neck cancer localization with indium labelled carcinoembryonic antigen: a pilot project.

Antibodies reacting with cancer cells are playing an increasing role in cancer detection. Most antibodies under study are directed at onco-fetal proteins, principally carcino-embryonic antigen (CEA). In terms of imaging, most work has concentrated on the abdominal and pelvic regions. Although the majority of primary head and neck cancers are amiable to clinical identification, detection of regional metastases and recurrences following radiotherapy can be difficult. Antibody to CEA was radiolabelled with Indium-111 and used to identify proven head and neck tumors by external imaging. In seven patients with squamous cell tumors, five of five primary sites and two of three secondary sites were imaged satisfactory. Comparison with conventional scanning showed good correlation. There were no false positive scans, no consistent relationship between serum or tissue CEA levels and the success of imaging was evident. The success of this pilot study should encourage the search for more tumor-specific antigens, and further studies of external scintigraphic techniques in the localization of head and neck cancers.

Aged

Cell wall structures which may be important for successful immunization with Salmonella-Shigella hybrid vaccines.

Three separate lots of S. typhi/S. sonnei hybrid (Ty/Shig) live oral vaccine strain 5076-1C were tested for efficacy in human volunteers challenged with virulent S. sonnei. Two lots (2 and 5) protected volunteers, a third lot (8) did not. The three lots were evaluated by immunological tests and electron microscopy. Lots 2 and 5, which protected, contained bacteria that reacted with anti-flagellar serum and had observable attached flagella and pili. Lot 8, which failed to protect, did not react with anti-flagellar serum, and had no observable pili. There was no correlation between vaccine efficacy and the reaction of IgG in patient's sera in western blot analysis. Surface structures on the Ty-Shig hybrid may be important for generating a protective immune response.

Animals

Clozapine: a new antipsychotic drug.

Clozapine is a new antipsychotic drug that displays antipsychotic efficacy of the classic neuroleptics without the associated extrapyramidal side effects. This article briefly reviews the action and use of clozapine in order to help nurse clinicians become familiar with the drug usage. Clozapine is presently in use only in clinical trials, but is expected to be marketed by Sandoz Pharmaceutical Corporation (Hanover, NJ) in 1990.

Clozapine

Acute myocardial infarction. A feasibility study using record-linkage of routinely collected health information to create a two-year patient profile. Manitoba, 1984-85 and 1985-86.

Manitoba's hospital separations and physician medical files were linked for the fiscal years 1984-85 and 1985-86. The result was a study file consisting of records for 5,293 males and 3,143 females, who, during this period, suffered an Acute Myocardial Infarction (AMI), commonly called a heart attack. Merging the two types of files created a comprehensive data base for these AMI victims. The Manitoba age-sex standardized AMI rate was 38.0 per 10,000 population. Age-specific rates were higher for males than for females for all age groups. Hospitalized cases accounted for 7,201 individuals or 85.4% of AMI victims. Age-sex standardized rates of hospitalization per 10,000 population ranged from 27.1 in the Central region to 36.0 in the Westman region. The Manitoba age-specific rates of hospitalization for males in the 35-54 and 55-64 age groups were about three times the female rates for the same age groups. One quarter of AMI hospitalized victims died in hospital. The Manitoba age-specific death rates for males in the 35-54, 55-64 and 65-74 age groups were double the rates for females in the same age groups. Of the 8,436 AMI victims under study, 86.4% had at least one other concurrent medical condition such as angina, other forms of ischemic heart disease, diabetes, or hypertension. Of AMI victims, 93.8% underwent at least one of the following procedures: coronary artery bypass surgery, angiogram, electrocardiogram, cardiac catheterization, arteriography, or blood cholesterol testing. A higher percentage of procedures was performed on males than on females.

Acute Disease

Glutathione peroxidase and selenium deficiency in patients receiving home parenteral nutrition: time course for development of deficiency and repletion of enzyme activity in plasma and blood cells.

The time course for the depletion of red blood cell (RBC) and plasma glutathione peroxidase (GSHPx) activity in five patients receiving home parenteral nutrition was documented. During the development of the RBC GSHPx deficiency, enzymatic activity and protein content decreased. Plasma and RBC selenium content were similarly decreased as was cellular metabolism of exogenous hydrogen peroxide. When the replacement of Se (selenious acid) began, there was a rapid increase (within 6 h) in plasma GSHPx activity. Platelet and granulocyte (PMN) GSHPx activity, which were low when Se replacement began, became normal within a time consistent with the kinetics of platelet and PMN production. RBC GSHPx did not become normal for 3-4 mo. This is consistent with the time course for RBC production. It appears that the repletion of blood cell GSHPx requires the formation of these cells in the presence of Se.

Adult

What 'makes' a good doctor?

The relation between gender, personality, school scores, grades at medical school and eventual achievement as a medical practitioner 8 years after qualifying has been explored by path analysis in a cohort of medical students. Factor analysis of data derived from a questionnaire identified a significant factor accounting for 75% of the common variance of the professional achievement scores. Standardized path coefficients were computed to indicate the relative importance of the causal factors to postgraduate achievement. Gender played an important role at many levels. For example it was apparent that many of our women graduates were seriously disadvantaged in their professional careers. Of the school subjects, chemistry was a surprising long-term predictor of postgraduate achievement. Academic achievement during medical school training, particularly in the final year, was a significant predictor, while personality attributes made their contribution to one or other aspect of achievement at earlier stages in training but made little additional direct contribution to postgraduate performance.

Achievement

The bends.

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Adult

114Inm oxine-labelled lymphocytes--therapeutic applications.

It has shown that, after intravenous administration of autologous lymphocytes labelled with the beta-emitting radionuclide 114Inm, the cells initially migrate normally before succumbing to the toxic effects of the radiation. The radioactive material is then released from the cell and taken up by neighbouring radioresistant macrophages, thereby localizing a field of radiation to the site of lymphocyte death. Using this technique, lymphocytopoenia has been produced in rats. We have measured the whole-body distribution and excretion of radioactivity in patients who received escalating activities of 114Inm-labelled lymphocytes. All patients had active non-Hodgkin's lymphoma involving the spleen and liver which proved resistant to combination chemotherapy and conventional radiotherapy. Following intravenous administration, the labelled cells cleared rapidly from the vasculature with only 15% remaining in the peripheral blood at 30 min. The radioactivity continued to fall over the next 5 days to approximately 3% and was maintained at approximately 2% for up to 90 days. There was an almost immediate uptake of radioactivity by the spleen and liver which reached approximately 85% of the injected dose by 48 h. The localization of radioactivity stabilized by 48 h and thereafter the whole-body content fell by approximately 0.8% per day. Up to 5% of the administered radioactivity accumulated in the bone marrow. The activities administered were too low to produce a therapeutic response and no toxicity was experienced by the patients. A therapeutic study at higher activities is now underway.

Humans