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Biomedical subjects

J Thornton

Publications and source records attributed to J Thornton.

At least 109 records · Page 6Linked to original sources

Developing a drug usage evaluation program.

One of the goals of the University of Illinois Hospital and Clinic's Pharmacy and Therapeutic Agent Review Program is to monitor and evaluate prescribing practices for drugs used in their facilities and to comply with Joint Commission standards with regard to conducting drug usage evaluations (DUE). Presented below is an overview of each step taken in the DUE process at the University of Illinois. The process described here can be adopted by other institutions that wish to improve their own DUE program.

Chicago↗

Inhibition of protein synthesis does not block myocardial protection afforded by preconditioning.

It is currently unknown how preconditioning the heart with brief periods of ischemia makes it resistant to infarction from a subsequent ischemic insult. The protein synthesis inhibitors, cycloheximide and actinomycin D, were used to determine whether preconditioning involves synthesis of a protective protein. Ischemia was produced by occlusion of a branch of the left coronary artery in open-chest anesthetized rabbits. All groups were subjected to 30 min of ischemia followed by 3 h of reperfusion. The first two groups served as noninhibited controls. Group 1 was subjected to ischemia with no preconditioning. Group 2 was preconditioned with two 5-min ischemic periods each followed by 10 min of reperfusion, before the 30-min ischemic period. Groups 3 and 4 were the same as groups 1 and 2, respectively, except that cycloheximide was administered before coronary occlusion. Groups 5 and 6 were also the same as groups 1 and 2 except that actinomycin D was administered before coronary occlusion. After 3 h of reperfusion all hearts were removed and the size of the ischemic zone and infarct were determined. The percent of the ischemic zone infarcted was small and similar in all preconditioned groups (3.3 +/- 1.1% for group 2, 7.4 +/- 3.3% for group 4, and 0.5 +/- 0.7% for group 6). All nonpreconditioned groups had large infarcts with no differences between groups (39.0 +/- 8.5% for group 1, 31.6 +/- 6.3% for group 3, 30.8 +/- 5.9% for group 5). Because neither cycloheximide nor actinomycin D could block protection afforded by preconditioning, it seems unlikely that synthesis of a protective protein is the mechanism of protection.

Animals↗

A description of a successful computerized adverse drug reaction tracking program.

The University of Illinois Hospital Drug Information Center recently began using a database software program (File Express, Version 4.0, Redmond, WA) for storing and retrieval of reported adverse drug reactions (ADRs). Important features of the software program include the capability of easily generating reports, rapid sorting of data, large storage capability, minimal startup cost, and a user friendly menu system. The number of reported ADRs increased from 24 in 1987 to 124 in 1988 due, in part, to increased educational efforts, revision of the ADR reporting form, and cooperation from the medical records department in identifying reported ADRs during chart review. Overall, pharmacists were found to report most of the ADRs. Retrospective analysis of the ADR reports may help identify trends in ADRs based on the drug and route of administration. A decrease in the incidence of some ADRs and, thus, improved patient care, may result as the information obtained from the computer-based ADR reporting system is shared among healthcare professionals.

Drug Information Services↗

Open-trial maintenance pharmacotherapy in late-life depression: survival analysis.

We report preliminary findings from an ongoing, open trial of maintenance nortriptyline pharmacotherapy in 27 elderly depressed patients (median trial length: 18 months). While patients were on maintenance nortriptyline (mean dose: 50 mg/day) with steady-state plasma levels in the range of 50-150 ng/ml, 58% of Q-6 monthly ratings on the Hamilton Rating Scale for Depression have been 10 or lower, Folstein Mini-Mental State ratings have remained above 27, and a minimal level of side effects with no increase over time has been observed. Four of 27 patients (14.8%) have suffered recurrences and have required rehospitalization at 6, 9, 10, and 13 months. Survival analysis showed an 85% survival rate (without recurrence) at 12 months and 81.5% at 18 months. Mean survival time without recurrence is 21.3 months to date. Although our pilot experience with maintenance nortriptyline in late-life depression appears more favorable than outcomes reported in earlier naturalistic studies (where no attempt was made to keep patients in systematic maintenance therapy), the need for controlled studies of maintenance therapies in late-life depression is nonetheless underscored by the current data and other naturalistic data from the United Kingdom.

Aged↗

Muscular adaptation of horses during intensive training and detraining.

Five horses were studied during a five-week regime of controlled intensive daily training on a high-speed treadmill followed by five weeks of detraining. Muscle biopsies were taken weekly from both the right and left gluteus muscle and from the sternocephalicus muscle before, and at the end of, the training and detraining periods. Histochemical and biochemical analyses of the sternocephalicus muscle showed no metabolic adaptation with either training or detraining. No significant differences were observed in any of the analysed parameters in the gluteus muscle between contralateral sites. Glycogen levels decreased by 10 to 15 per cent after one to two weeks of training, remained low during the training period and increased to pretraining levels after one week's cessation of training. Citrate synthase activity increased rapidly and was 27 per cent higher after one week and 42 per cent higher after five weeks of training. Lactate dehydrogenase activity decreased by 15 per cent during this period. The changes seen in these enzyme levels persisted during the detraining period. No alterations were seen in fibre type composition but type IIA fibre areas decreased by 19 per cent after five weeks training and capillary density increased by 17 per cent. It is concluded that a period of intensive training will rapidly increase the oxidative capacity and the capillary density in an actively working muscle, and that these metabolic adaptations are well maintained during a subsequent period of detraining.

Animals↗

Tardive dyskinesia: a five year follow-up.

A group of chronic schizophrenic patients receiving prolonged treatment with neuroleptics was assessed in 1978 at an outpatient clinic to determine the prevalence of Tardive Dyskinesia. Those with TD were reassessed after two and five years with regard to change in TD severity. The Smith scale was used every time and, on the last assessment, the AIMS scale and videotaped interviews were added. Because of the high attrition rate, results, though interesting, cannot be generalized.

Adult↗

Pharmacy-laboratory interactions: a unique method to control antibiotic costs.

Because a large percentage of hospital antibiotic use is regarded as inappropriate, hospital pharmacists must investigate ways of decreasing such usage. A unique approach was evaluated for its impact on cost-effective antibiotic therapy. By functioning as a team, the pharmacy and laboratory departments implemented the following steps: cost-code index on antimicrobial susceptibility and organism identification reports; suppression of cost-ineffective antibiotics within the same pharmacologic group from the antimicrobial susceptibility reports; design of minimum inhibitory concentration panels to conform to the hospital formulary; daily delivery of the antimicrobial susceptibility reports to the pharmacy. Of the 1078 documented therapeutic interventions by the clinical pharmacist, 100 were randomly selected for review, 62% of which involved direct interaction with the laboratory. Estimated cost savings due to these interactions were $8214; annual savings were $88,554. The results of this study show the importance of pharmacy departments forming and maintaining lines of communication with the hospital laboratory department.

Anti-Bacterial Agents↗

Cervical screening in the workplace.

In an attempt to improve cervical cytology screening uptake in women aged over 40, a mobile screening unit was used to make screening easily available to women at work. This service was organized jointly between the District Health Authority, the Women's National Cancer Control Campaign and the South West Thames Regional Cancer Organization, and was offered to all companies employing at least 25 women. Thirty-nine out of 82 companies accepted the offer. Among those companies which were able to supply a register of their employees aged over 40, 91 per cent of eligible women attended the mobile clinic. The clinic doctors followed District guidelines in not taking smears from women who had been screened and found negative within the previous three years, or who had had a hysterectomy for an unrelated reason. Of the 1038 women who attended the clinic, cervical smears were taken from 568 (55 per cent). Fifteen women were found to have cervical neoplasia, of whom nine had either never been screened before or had last been screened more than five years previously; a further two women (one of whom was found to have early invasive cancer) had previously had an abnormal smear for which the recommended follow-up had not been done. It was not possible to quantify the benefits of other tests (clinical breast examination, blood pressure, urinalysis and gynaecological examination) included in the screening clinic, but they were popular with the women attending. Provided that the health authority is involved in the planning and organization of workplace screening, it can be a valuable adjunct to improving screening coverage, particularly for women aged over 40.

Adolescent↗

A randomized, double-blind, placebo-controlled investigation of the safety of intravenous immune globulin administration to preterm neonates.

Intravenous immune globulin (750 mg/kg), or an equivalent volume of a placebo, was administered during the first week of life, in a randomized trial, to 20 preterm neonates weighing 710 to 1800 g. A variety of laboratory and clinical values were measured serially and analyzed for possible untoward effects. Serum IgG levels were also determined serially. No differences in heart rate, respiratory rate, urine output, blood glucose, serum osmolality, BUN, SGPT, pH, blood gasses, serum electrolytes, total or direct bilirubin, blood leukocyte concentration, absolute neutrophil count, or blood platelet concentration were observed between the intravenous immune globulin (IVIG) and placebo recipients before or following IVIG administration. The red blood cell concentration of IVIG recipients diminished transiently and only slightly (P less than .05). Serum IgG levels increased from 503 +/- 162 mg/dL (X +/- SD) to 1492 +/- 201 mg/dL 15 minutes after the IVIG administration (P less than .001). After 8 days, serum IgG levels were still elevated, at 675 +/- 297 mg/dL. All patients randomized to receive the placebo experienced a diminution in serum IgG over this 8-day period (P less than .01). All 20 patients survived and none in either group had a documented nosocomial infection. This study suggests that IVIG can safely be administered to preterm neonates, resulting in serum IgG levels comparable to those of term infants.

Blood Chemical Analysis↗

Molecular cloning of a phospholipid-cholesterol acyltransferase from Aeromonas hydrophila. Sequence homologies with lecithin-cholesterol acyltransferase and other lipases.

We have determined the nucleotide sequence of a gene encoding Aeromonas hydrophila phospholipid-cholesterol acyltransferase, an enzyme which shares many properties with mammalian lecithin:cholesterol acyltransferase. The derived amino acid sequence of the protein contains two regions which are homologous to the proposed active sites and binding sites of the plasma acyltransferase and to similar sequences in other interfacially acting lipolytic enzymes. The amino terminus is preceded by a typical 18 amino acid signal sequence. The protein, which is released into the culture supernatant by Aeromonas hydrophila, is confined to the periplasm of Escherichia coli.

Acyltransferases↗

Possible role of alpha-2-noradrenergic receptors in modulation of sexual behavior in female guinea pigs.

These studies examine whether alpha 1-noradrenergic receptor stimulation alone is sufficient to facilitate lordosis behavior in ovariectomized, estrogen-primed female guinea pigs and to what extent alpha 2-noradrenergic receptors are involved in this steroid-dependent behavior. Neither of the alpha 1-agonists, phenylephrine or methoxamine, significantly facilitated lordosis in ovariectomized females primed with 10 micrograms of estradiol benzoate for 1 or 3 days. Animals exhibiting estrogen plus clonidine-facilitated lordosis showed a decrease in the behavior when given one of two alpha 2-antagonists (yohimbine or idazoxan). Idazoxan also attenuated lordosis in animals given estrogen plus progesterone. These findings, in combination with previous findings (that specific alpha 1-antagonists block lordosis), suggest that alpha 2-receptors, in addition to alpha 1-receptors play a role in modulation of lordosis behavior.

Adrenergic alpha-Antagonists↗

Plasma prolactin and estradiol during sleep in impotent men and normal controls.

There are no investigations of sleep-related changes in circulating prolactin and estradiol in impotent men without known organic pathology. This study compares plasma levels of both hormones during sleep in 17 physically healthy patients with erectile impotence and 11 normal controls. Five men had never been able to achieve intercourse (primary impotent group) and 12 suffered from a lifelong history of intermittent erectile failure (secondary impotent group). The subjects, aged 23 to 36, were studied in a sleep laboratory from 3 to 6 nights with the last two devoted to sequential blood sampling every 20 min. Samples were pooled during consecutive 2-hr periods from 11 PM to 7 AM for hormonal assessment. There were no statistical differences in sleep measures among groups. Mean prolactin and estradiol values for all subjects were within the normal range. Both impotent groups showed a significant nocturnal increase in prolactin concentration and no time-related changes in plasma estradiol. There were no statistical differences in the plasma concentration of both hormones among groups or between study nights. The results suggest that severe and long-lasting erectile failure may occur in physically healthy individuals without associated abnormalities in circulating prolactin and estradiol.

Adult↗

Female-typical sexual behavior of rhesus and defeminization by androgens given prenatally.

Adult rhesus monkeys were observed in standardized tests for female-typical sexual and related social responses. In the first experiment reported, 7 castrated males and 5 spayed females were paired with each of 4 intact males on two occasions following intramuscular injection with estradiol benzoate (EB) (6 micrograms/kg X 14 days) and on two other occasions without such treatment. In tests without EB, males and females did not behave differently toward the intact male partners, and all responses were displayed at low frequencies. In tests with EB, females showed reliably higher frequencies than males of approaching, sitting close to, grooming, and soliciting, and they presented to a higher proportion of the male partner's sexual contacts. EB reliably increased the frequency of display of all of these same five responses in females but not in castrated males. The intact male partners displayed reliably fewer approaches, sexual contacts, mounts, intromissions, and ejaculations to castrated males than to spayed females regardless of estrogenization. In a second experiment 10 intact adult pseudohermaphroditic females and 6 intact control females were tested following EB injections with each of the same 4 intact males. Pseudohermaphrodites were experimentally produced by injecting pregnant females with either testosterone propionate (TP) or dihydrotestosterone propionate (DHTP). Pseudohermaphrodites, regardless of type of androgen used in their production, showed reliably fewer solicits than controls to male partners. Moreover, they displayed most of the other responses at lower average frequencies than controls. Frequencies of intromission and ejaculation by intact male partners were reliably lower with pseudohermaphrodites than with control females, but frequencies of approach, sexual contact, and mount were not reliably different. We conclude that in this testing and measurement situation male and female rhesus monkeys differ markedly in the degree of expression of female-typical sexual behaviors, and genotypic males are behaviorally less responsive to estrogens than females. Exposing genotypic females to androgens during fetal life decreases the expression of female-typical, estrogen-influenced responses, and the effect is most pronounced on those soliciting responses that subserve proceptivity.

Animals↗

The relationship of dietary fat to plasma lipid levels as studied by factor analysis of adipose tissue fatty acid composition in a free-living population of middle-aged American men.

We have used adipose tissue biopsies to assess the quality of fat in the diet and its influence on plasma lipid levels in 413 free-living normolipidemic male subjects. Factor analysis identified three factors which separated the fatty acids on the basis of their chemical structure. F1--monounsaturates--animal fats; F2--saturates--carbohydrates; F3--polyunsaturates--vegetable oils. An increase in F1 was associated with an increase in plasma triglycerides (TG), plasma total cholesterol (TC), and VLDL-C: an increase in F2 led to a decrease in VLDL-C. A rise in F3 was associated with lowered TG, VLDL-C, and HDL-C but increased LDL-C. However, the contribution of each of these factors to the variance in TG, TC, LDL-C, and HDL-C was small, namely: 5.48, 1.30, 2.57, and 2.02%, respectively. A special relationship between F3 and VLDL-C was found such that 16.22% of its variance could be attributed to F3. Our conclusion is that adipose tissue composition and, by implication, the type of dietary fat intake, explains only a small proportion (1-19%) of the variance in plasma lipids in normolipidemic subjects.

Adipose Tissue↗

Crown-rump length and serum human chorionic gonadotropin as predictors of gestational age.

The accuracy of fetal crown-rump length measurement and maternal serum human chorionic gonadotropin (hCG) concentration in the prediction of obstetric gestational age was analyzed in a study population of 77 patients for whom time of ovulation was reliably determined. Published nomograms relating maternal serum hCG concentration to gestational age were not found to be valid predictors of gestational age for the study population. Fetal crown-rump length measurement using the uncorrected regression equation of Robinson was found to give the most accurate prediction of gestational age.

Chorionic Gonadotropin↗

The role of dietary fat in human obesity.

Both the amount and quality of dietary fat have been implicated in the pathogenesis of obesity. Adipose tissue fatty and composition, which is known to reflect dietary intake, was sampled in 413 free-living, healthy American males appearing for a routine medical examination. The average age was 46.8 +/- 11.4 years (mean +/- s.d.) and body mass index (BMI)--weight/height--was 25.2 +/- 3.4. The BMI was correlated (P less than 0.01) with known risk factors for cardiovascular disease as follows: total cholesterol (TC) r = 0.18, triglycerides (TG) r = 0.32, low-density lipoprotein cholesterol (LDL-C) r = 0.18, high-density lipoprotein cholesterol (HDL-C) r = -0.24, systolic and diastolic blood pressure (BP) r = 0.30. Underlying patterns which might be related to diet were sought in the distribution of the seven major fatty acids in adipose tissue. Statistical analysis permitted delineation of three factors which were hypothetically related to animals fat intake (F1--monounsaturates), carbohydrate intake (F2--saturates) and vegetable oil intake (F3--polyunsaturates). F1 and F3 together accounted for 12 percent of the variance in BMI while F2 had no influence. Our conclusions are that the variance in BMI is related much more to non-dietary factors than to adipose tissue fatty acid composition and that the nature of dietary fat was not a major distinguishing factor in obesity in this population. There was also no evidence for a high dietary carbohydrate (low fat) intake in the obese.

Adipose Tissue↗