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Biomedical subjects

J G Kellett

Publications and source records attributed to J G Kellett.

4 recordsLinked to original sources

Whither the rationale for thrombolytic agent administration? A retrospective review of traditional intuitive decision-making using a decision analysis model.

Of 50 consecutive patients admitted to Nenagh Hospital coronary care unit 50 per cent did not develop a myocardial infarction. Only 10 patients had definite evidence of infarction on admission. Of the 40 remaining patients, only 15 subsequently developed electrocardiographic and enzymatic confirmation of infarction. Streptokinase was administered to 5 patients who did not infarct, and was not given to 10 patients who did. These decisions to use or withhold thrombolytic therapy were retrospectively reviewed using a computer programme incorporating a decision analysis of the benefits and risks of thrombolysis. The programme examined four scenarios that used different estimates of the chance of death from infarction (pdiMI), and different safety profiles of thrombolytics. The scenario that assumed the worst safety profile and estimated pdiMI from patient age would have recommended thrombolytic treatment to the most with, and to the least without, acute infarction (i.e. 60 per cent of patients with an infarct and 8 per cent without an infarct would have been treated). Depending on the scenario assumed, the traditional intuitive method of decision-making gained from 0.08 and 0.25 quality adjusted life years (QALY's) for the average patient. Had decision analysis been used to guide these decisions these gains would have been enhanced by from 0.21 to 0.28 QALY's per patient, regardless of scenario used.

Decision Support Techniques

The effect of growth hormone treatment on somatomedin levels in growth hormone-deficient children.

Serum levels of immunoreactive somatomedin (IRSM) and insulin-like activity (ILAs) by receptor assay have been measured in 177 GH-deficient (GHD) children treated with 2 U GH three times weekly for 6-10 months. The overall mean (+/- SD) pretreatment IRSM and ILAs levels were 0.21 +/- 0.30 and 0.39 +/- 0.25 U/ml, respectively. Pretreatment IRSM and ILAs levels were in the normal range for chronological age and sex in 15.8% and 33% of these GHD children. Mean IRSM and ILAs levels increased after 1 month of therapy to 0.36 +/- 0.51 and 0.62 +/- 0.33 U/ml, respectively (P less than .0001). The increase in serum IRSM levels (from 0.2 to 2.0 U/ml) that normally occurs from 1-16 yr of age is also evident in untreated GHD children, albeit to a lesser extent. In addition, the mean increase in IRSM after GH was greater in older patients. However, individual responses varied greatly. An increase in IRSM or ILAs with an increase in height velocity (HV) was observed in the majority of children, but all other combinations occurred, including increased SM with decreased HV, decreased SM with increased HV, and decreased SM with decreased HV. In summary 1) age-dependent factors in GHD children importantly influence basal and treatment SM leels; 2) a basal SM level is not a very sensitive diagnostic test, since a significant proportion of GHD children have SM levels in the normal range; and, 3) SM levels in individual patients may not increase with GH therapy and, thus, cannot be used to predict a clinical response to GH therapy.

Adolescent

The characterization of growth factor activity in human brain.

The purification of fibroblast growth factor from bovine brain has been reported (Gospodarowicz, D., Bialecki, H., and Greenberg, G. (1978) J. Biol. Chem. 253, 3736-3743). Westall et al. (Westall, F. C., Lennon, V. A., and Gospodarowicz, D. (1978) Proc. Natl. Acad. Sci. U. S. A. 75, 4675-4678) showed that bovine brain fibroblast growth factor was composed of three fragments derived by limited proteolysis from myelin basic protein. In the present study using similar purification methods, we isolated a fraction enriched in growth factor activity from human brain. The mitogenic activity could not be resolved from myelin basic protein by chromatographic procedures but, upon isoelectric focusing, the mitogen and myelin basic protein were readily dissociated. At least two potent growth factors (pI values 7.2 to 7.4 and 8.1 to 8.6) were identified. Studies of a relatively crude basic extract of human brain suggested that the brain may contain a number of growth factors.

Brain Chemistry

A thrombolytic decision tree.

We constructed a decision analysis model based on data in the medical literature to estimate the possible outcomes of thrombolytic therapy in patients 50 to 80 years old with possible myocardial infarction. We used the model to test the most likely effects of treatment (determined by averaging the values in reports of large studies) and the worst effects reported so far. The program begins by asking the patient's age, the hours from the onset of pain, and the probability of acute myocardial infarction. It then provides an opportunity to perform sensitivity analyses by changing the values for these variables and for the probability of death in the absence of thrombolytic therapy, as well as for the probability of major stroke and hemorrhage. The counterintuitive findings observed with this program are that the benefits of thrombolytic therapy increase with age and that young patients derive surprisingly little benefit from it.

Age Factors