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Biomedical subjects

D Healy

Publications and source records attributed to D Healy.

At least 109 records · Page 6Linked to original sources

Esophageal carcinoma. Improved quality of survival with resection.

Twenty years ago the experience with carcinoma of the esophagus at Vanderbilt University and affiliated hospitals was reported in 263 patients. Overall 5-year survival was 2 per cent. Esophagectomy was possible in 89 patients (34%) and was associated with a 32 per cent mortality. This study updates the authors' experience with squamous cell carcinoma of the esophagus in 311 patients seen from 1966 to 1985. Overall 5-year survival has increased to 6 per cent. Esophageal resection was accomplished in 104 patients (33%), with a 10 per cent operative mortality and 41 per cent complication rate. Multi-variant analysis disclosed that smoking, alcohol use, sex, race, and site of tumor did not influence survival. Actuarial survival rates following esophageal resection were 51 per cent at 1 year, 21 per cent at 2 years, and 13 per cent at 5 years. These survival rates were not influenced by adjuvant radiotherapy. Radiation therapy was used for attempted cure in 83 patients. Actuarial survival rates following curative doses of radiation were 29 per cent at 1 year, 15 per cent at 2 years, and 4 per cent at 5 years. These survival rates were significantly (P less than 0.001) lower than survival rates following esophagectomy. The quality of life following treatment was good or fair in 83 per cent of patients undergoing esophagectomy and good or fair in 64 per cent of patients receiving "curative" doses of radiation. The results of this review demonstrate that esophageal resection using the Lewis operation or transhiatal esophagectomy can be done with an acceptable operative mortality, results in prolonged survival, and improves the quality of life.

Adult↗

The structure of psychopharmacological revolutions.

Thomas Kuhn's model of the structure of scientific procedure is outlined and applied to salient aspects of recent psychopharmacological research into the bioneural substrates of the affective disorders. It is argued that the amine hypotheses of these disorders are irrefutable in practice although not in principle and that their survival despite a lack of convincing supporting evidence and dis-proof of their initial premises suggests that they serve a paradigmatic function and that the core of this paradigm is psychological in nature rather than neurobiological. An attempt is made to show how an awareness of such functions may help explain otherwise puzzling features of the literature on the psychopharmacology of the affective disorders. Such an awareness may also help to indicate the steps necessary to replace the amine hypotheses or the likely future prospects for these hypotheses.

Antidepressive Agents↗

Variations in platelet 5-hydroxytryptamine in control and depressed populations.

Platelet 5-hydroxytryptamine uptake was measured in a group of 28 endogenously depressed patients at three points during the day, before, during and after treatment and in 20 controls at the same three times. Uptake rates varied in control subjects in a manner consistent with the presence of a circadian rhythm in uptake. This variation was absent in depressed subjects. Normal variation was restored in those patients showing a clinical response, irrespective of the effects of treatment on the affinity of the uptake system. This restoration was not found in nonresponders or acutely after treatment was commenced. These findings suggest that depression is associated with a disruption of circadian rhythms, that abnormalities of platelet 5-hydroxytryptamine uptake are secondary to such a disruption and that antidepressants may act to correct this disruption.

Adult↗

Cross-over trial of superovulation protocols from two major in vitro fertilization centers.

A study was undertaken as a controlled comparison of two different superovulation induction protocols currently in use in major Australian in vitro fertilization (IVF) clinics. Thirty patients each from the Monash University and the Royal Women's Hospital (RWH) IVF programs were stimulated for ovulation induction by the other program. Once timing for oocyte retrieval was scheduled, all care reverted to the program from which the patient first came. Results given as pregnancies per patient commencing stimulation were: RWH patients on Monash protocol, 27%; RWH control patients, 15%; Monash patients on RWH protocol, 7%; Monash control patients, 13%. In the year preceding the trial pregnancy rates were 16.9% at Monash and 10.6% at RWH. Stimulation protocols were also compared with respect to each of administration, cost, and patient stress. The results of this cross-over trial demonstrated major differences between the two ovulation induction protocols studied, although it was not possible to conclude that differences in pregnancy rate were due to stimulation alone.

Adult↗

11-Dehydrothromboxane B2: a quantitative index of thromboxane A2 formation in the human circulation.

In human plasma, 11-dehydrothromboxane (TX) B2 is a major long lived metabolite (t1/2 45 min) formed from infused TXB2, the hydration product of biologically active TXA2. Plasma concentrations of TXB2 itself are readily confounded by ex vivo platelet activation and, theoretically, an enzymatic derivative of this compound, not subject to formation in whole blood, would more accurately reflect TXA2 formation in vivo. To address this hypothesis, we developed a sensitive assay for both 11-dehydro-TXB2 and TXB2, using capillary gas chromatography/negative-ion chemical ionization mass spectrometry. We established that whole blood possesses a minor capacity to form 11-dehydro-TXB2, attributable to nonenzymatic formation in erythrocytes. However, the nonenzymatic formation of 11-dehydro-TXB2 was not a practical limitation to its use as an index of TX biosynthesis. Blood was drawn from healthy volunteers (i) via an indwelling catheter at the time of insertion and at 30, 60, 90, 180, and 240 min thereafter and (ii) via separate venipunctures at 0 time and at 90 and 240 min thereafter. Plasma TXB2 drawn via the catheter at baseline (66 +/- 63 pg/ml) was substantially greater than the maximal estimate of endogenous TXB2 (1-2 pg/ml) in plasma [Patrono, C., Ciabattoni, G., Pugliese, F., Perruci, A., Blair, I. A. & FitzGerald, G. A. (1986) J. Clin. Invest. 77, 590-594] and increased in magnitude and variance over time (339 +/- 247 pg/ml at 240 min). By contrast, 11-dehydro-TXB2 did not change significantly in the sequential catheter samples or in the samples drawn by separate venipuncture. Basal plasma concentrations in volunteers were depressed by pretreatment with 325 mg of aspirin. Furthermore, the range of concentrations in patients with severe atherosclerosis in whom urinary 2,3-dinor-TXB2 was increased was significantly higher (5-50 pg/ml, P less than 0.01) than in healthy subjects (0.9-1.8 pg/ml). Concentrations of 11-dehydro-TXB2 were increased in patients who had recently suffered a pulmonary embolism to a greater extent than either the 11-dehydro-13,14-dihydro-15-keto-TXB2 or the 2,3-dinor-TXB2 metabolites in plasma. These results indicate that plasma TXB2 is readily confounded by platelet activation ex vivo. Measurement of enzymatic metabolites of TXB2 minimizes this problem. The 11-dehydro metabolite is the most appropriate analytic target to detect phasic release of TXA2 in the human circulation, such as might occur in human syndromes of platelet activation.

Aspirin↗

Increases in platelet 5HT uptake rates following treatment with "uptake inhibiting" drugs.

A kinetic analysis of 5HT uptake into platelets and its inhibition by antidepressants is the most commonly used method of assessing the effects of antidepressants on 5HT uptake in humans. This study suggests that there is a naturally occurring variation in the uptake rates for 5HT into platelets, consistent with the presence of a circadian rhythm in uptake. There appears to be a derangement of this variation in depressed patients, which is reversed by effective treatment. Antidepressants may have effects both at the 5HT transport site and on the overall degree of variation. In view of this variation and its disruption in depression, it is suggested that measurement of the effects of "uptake inhibiting" drugs in depressed patients may yield different results to those obtained from controls. This difference is most apparent when uptake is measured at several time points. Furthermore, results from in vitro and ex vivo assays may yield distinctly different findings.

Adult↗

Peripheral adrenoceptors and serotonin receptors in depression. Changes associated with response to treatment with trazodone or amitriptyline.

Changes in platelet and lymphocyte adrenoceptor densities, platelet serotonin uptake and aggregatory response to serotonin were assessed in a group of moderately depressed patients before and during treatment with either trazodone or amitriptyline. Platelet serotonin receptor activity and uptake were lower before the start of treatment in all patients than in those patients responding to treatment. The densities of alpha 2- and beta-adrenoceptors tended to be higher in the patients before treatment and returned to control values after effective therapy. There were no major differences in the biochemical changes between the patients treated with trazodone or amitriptyline. When the biochemical data was correlated with the clinical history of the patients, it was found that only endogenously depressed patients, and not those with non-endogenous depression, had a significantly reduced platelet serotonin uptake rate. In addition, female depressives had a slightly lower platelet 5-HT aggregatory response than males irrespective to the type of depression.

Adolescent↗

Biochemical correlates of antidepressant response. Results of a trazodone versus amitriptyline trial.

Changes in the uptake of 3H-serotonin into platelets, serotonin receptor activity on platelets, and plasma free and bound tryptophan concentrations were determined in a group of 54 moderately to severely depressed patients (mean Hamilton Rating Scale 17) before and during treatment with either trazodone or amitriptyline. No difference was found between the free and bound tryptophan concentrations of the depressed patients or their controls nor was any change detected during drug treatment. Platelet serotonin receptor activity and uptake were significantly lower in the depressed patients than in the controls and in those patients which subsequently responded to drug treatment. There was no apparent correlation between the ability of trazodone to inhibit the uptake of serotonin into the platelets and the antidepressant response; all patients responding to drug treatment showed an enhanced serotonin uptake. There is evidence from this study that changes in serotonin receptor function and uptake into platelets may correlate with the clinical status of depressed patients.

Amitriptyline↗

Expression of the prolactin gene in human decidua-chorion.

Messenger RNA (mRNA) purified from human decidua-chorion hybridizes with a 32P-cDNA probe for human prolactin. In contrast, mRNA from human trophoblast and amnion does not hybridize to prolactin cDNA. The migration position on agarose gels of prolactin-specific mRNA from human decidua-chorion is similar to that for mRNA from ovine pituitary, suggesting a similar sized mRNA coding for prolactin in these different tissues and species. These data demonstrate unambiguously that the prolactin gene is expressed in human decidua-chorion, confirming previous immunochemical reports of prolactin production by this tissue in culture.

Amnion↗

Studies of the functional significance of angiotensin II receptors in the rat olfactory bulb: evidence for alterations in normal fluid intake.

The effects of continuous infusion of angiotensin II (ANG II, 1 microgram hr-1) into the olfactory bulb (O.B.) were studied on rats with chronically indwelling intracerebral cannulae. Chronic infusion (ALZA minipump system) of ANG II into the O.B. elicited a moderate dipsogenesis as compared to saline infused animals. The increased drinking occurred only during the dark phase (6 pm - 6 am) and appeared to be associated with food intake, which also occurred during this time. Removal of the food or disconnection of the minipump reduced water consumption to comparable levels in both groups. Acute injection of ANG II (250 ng) into the O.B. failed to elicit drinking. Since the olfactory bulb has a high concentration of ANG II receptors, these experiments suggest that ANG II may interact with the O.B. to facilitate the drinking associated with food intake.

Angiotensin II↗

Serum prolactin levels and the value of bromocriptine in the treatment of anovulatory infertility.

Basal serum levels of prolactin were measured in 37 infertile anovulatory patients who had failed to conceive on therapy with clomiphene citrate. Twenty of these patients, 16 of whom had galactorrhoea, had elevated basal serum prolactin values which were suppressed to normal or subnormal values during therapy with bromocriptine, the most commonly effective dose being 2.5 mg twice daily. Ovulation, as assessed by urinary oestrogen and pregnanediol measurements, was induced in 17 of these patients with pregnancy in 14. Ovarian responses short of defined criteria for ovulation were induced initially in eight patients, but these progressed to full ovulatory responses in five patients, either on the same or increased doses of bromocriptine. In all the patients who ovaulated, the prolactin levels had been reduced below the mean value for normal women (10.6 ng-ml). The three patients who failed to ovulate all had values higher than this at a dose of bromocriptine reaching 5.0 mg thrice daily. There seemed to be no value in increasing the dose of bromocriptine once ovulation had been achieved. Of the 17 patients with normal basal prolactin values, only one had an unequivocal response to bromocriptine with ovulation and conception, even though the prolactin values in the majority were suppressed to below normal.

Adult↗

A study of the effects of bromocriptine on serum prolactin, follicle stimulating hormone and luteinizing hormone and on ovarian responsiveness to exogenous gonadotrophins in anovulatory women.

Twelve anovulatory patients with normal serum prolactin values and six with elevated values were treated with bromocriptine and the effects on serum prolactin, FSH and LH levels were recorded. Ovulation resulted in one patient who had normal prolactin values and in all six who had raised values. No patient with normal basal prolactin values showed an increase in serum FSH during therapy with bromocriptine, whereas 5 of the 6 patients with elevated values showed significant increases. Similar results were obtained for LH. Although these differences were highly significant (P less than 0-005) the majority of the serum FSH and LH values remained within the normal ranges. Five patients with normal basal prolactin values and one with elevated values were also treated with human pituitary gonadotrophin (HPG). An increase in ovarian responsiveness to HPG during therapy with bromocriptine was recorded in the one patient with initially elevated prolactin values. It was concluded that bromocriptine acts by allowing FSH to rise above threshold requirements for follicular stimulation.

Adult↗