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Biomedical subjects

Thomas H Miller

Publications and source records attributed to Thomas H Miller.

6 recordsLinked to original sources

Sequence of pituitary-adrenal cortical hormone responses to low-dose physostigmine administration in young adult women and men.

We previously demonstrated greater HPA axis activation in adult men compared to adult women following low-dose administration of the anticholinesterase inhibitor, physostigmine (PHYSO). Because blood sampling was done infrequently following PHYSO, the rise times of AVP, ACTH1-39, and cortisol could not be determined. In the present study, we determined the sequence of hormone increases by frequent blood sampling following PHYSO. Twelve adult women and 12 adult men underwent three test sessions 5-7 days apart: PHYSO, saline control, and repeat PHYSO. As in the earlier study, PHYSO produced no side effects in half the subjects and mild side effects in the other half, with no significant female-male differences. None of the hormone responses was significantly correlated with the presence or absence of side effects. In both women and men, the AVP increase preceded the ACTH1-39 increase, which in turn preceded the cortisol increase. The AVP and ACTH AUCs were significantly positively correlated in both women and men, supporting AVP as an acute stimulus to ACTH secretion. Also as in the earlier study, the AVP response to PHYSO was more than twice as great in men as in women, but the difference was not statistically significant. We therefore analyzed the results of both studies combined (N=26 women and 26 men). The men had a significantly greater AVP response and a trend toward a greater ACTH1-39 response compared to the women. These findings further support the concept of sexual diergism (functional sex difference) in the influence of CNS cholinergic systems on HPA hormone secretion.

Adrenocorticotropic Hormone↗

Adrenal cortical responses to low- and high-dose ACTH(1-24) administration in major depressives vs. matched controls.

Increased hypothalamo-pituitary-adrenocortical (HPA) axis activity occurs in 30-50% of patients with major depression. This includes normal-to-increased adrenal cortical hormone (cortisol) secretion in spite of reduced corticotropin (ACTH) stimulation. A possible explanation is increased adrenal responsiveness to ACTH. Supporting this possibility is the finding of increased adrenal volume, which reverts to normal with successful treatment. Eight female and six male patients with major depression, and eight female and six male individually matched controls, underwent two test sessions 5-7 days apart. On the first day, a low ACTH(1-24) dose (0.014 microg/kg i.v.), equivalent to 1 microg in a 70-kg individual, was given. On the second day, a supramaximal stimulating dose (250 microg i.v.) was given. Serial blood samples were analyzed for immunoreactive (IR-)ACTH, ACTH(1-39), and cortisol. There were no significant sex or patient-control differences in IR-ACTH areas under the curve (AUCs) following low-dose ACTH(1-24), and the correlation between patient and matched control AUCs was +0.71, indicating good correspondence in the amount of circulating ACTH(1-24) available for adrenal stimulation. There were no significant sex or patient-control differences in cortisol response and no significant interaction between dose and subject group, indicating that patients did not differ from controls in their cortisol responses to either low- or high-dose ACTH(1-24). These findings do not indicate increased adrenal cortical responsiveness in patients with major depression. Neurochemical/neurohormonal and neural stimulatory factors other than ACTH might be responsible for the increased adrenal gland size and cortisol secretion, in spite of reduced pituitary ACTH secretion, that has been reported in this illness.

Adrenal Glands↗

Characteristics associated with discharge to home following prolonged mechanical ventilation: a signal detection analysis.

The objective of study was to identify characteristics associated with being home at 6 months in 80 patients on prolonged mechanical ventilation (PMV) (> or =7 days). At 6 months, 47.5% were home, 13.8% institutionalized, and 38.8% deceased and classified "not home." Using signal detection methodology (SDM), four mutually exclusive groups at high and low probability of being home were identified. The best outcome (94.4% home) was achieved by patients with an admission Charlson Comorbidity Score < or =3 and an Acute Physiology Score (APS) < or =21 and the worst outcome (23.4% home) by patients with an admission Charlson Comorbidity Score >3 and Health Assessment Questionnaire score >2.7. SDM provided an effective means of identifying subgroups likely to be discharged home using available information.

Activities of Daily Living↗

Growth hormone responses to low-dose physostigmine in elderly vs. young women and men.

BACKGROUND: Growth hormone (GH) secretion is a sensitive measure of CNS cholinergic neurotransmission, and GH decreases considerably with age. Cholinesterase inhibitors, which increase acetylcholine concentrations, have been used in elderly subjects to investigate the neuroendocrine effects of aging and Alzheimer's disease. However, there have been only a few studies of a potential sex difference in GH responses to cholinesterase inhibitors in elderly subjects, with mixed results. OBJECTIVE: We therefore administered low-dose physostigmine (PHYSO), a cholinesterase inhibitor, to normal, non-hormone-replaced, elderly women and men, to ascertain a potential sex difference in GH response. We hypothesized: (1) elderly women and men would have similar hormone responses, because of relatively low circulating estrogen in the women, and (2) the elderly women would have significantly lower baseline GH and GH responses to cholinergic challenge than the young women we studied previously. METHODS: Normal elderly women and men > or =65 years of age meeting stringent inclusion and exclusion criteria were studied on three test days, 4-7 days apart, by serial blood sampling for several hours for baseline GH, followed by administration of low-dose PHYSO (first and third days) or saline (second day) at 18:00 h. Frequent blood sampling was continued for several hours. Plasma GH and hypothalamo-pituitary-adrenal cortical hormones were measured in each sample. RESULTS: PHYSO administration produced no side effects in about half the elderly subjects and mild side effects in the other half, with no significant female-male differences and no significant relationship between the presence or absence of side effects and GH response. PHYSO significantly increased GH compared to saline, to a similar degree in the elderly women and men. The elderly women had a significantly greater GH response to PHYSO than did the young women, whereas GH responses were similar in the elderly and young men. CONCLUSIONS: These results indicate similar GH responses to low-dose PHYSO in elderly women compared to elderly men, and a significantly greater GH response in elderly women compared to young women. A likely mechanism is increased sensitivity of central cholinergic systems that inhibit somatostatin and/or enhance GHRH release from the hypothalamus.

Adolescent↗

Comparison of 2 models for managing tracheotomized patients in a subacute medical intensive care unit.

OBJECTIVE: To compare 2 models for managing patients admitted to a subacute medical intensive care unit (MICU) who required prolonged mechanical ventilation (> or = 7 d). METHODS: The subjects were 192 consecutive patients (mean +/- SD age 61.5 +/- 16.1 y, 52% male, 86% white) managed during alternating 7-month blocks of time by an attending physician in collaboration with an acute care nurse practitioner (ACNP) (n = 98 patients) or by an attending physician in collaboration with critical care/pulmonary fellows (n = 94 patients). The total observation time was 28 months (14 mo per team). RESULTS: At unit entry, there were no significant differences in age, sex, race, comorbidity, Acute Physiology and Chronic Health Evaluation III score, or time of tracheostomy between the patients managed by the 2 teams. Patients managed by the ACNP team were more likely to have required mechanical ventilation due to an acute pulmonary problem (p = 0.005). At subacute MICU discharge, the groups were not significantly different in regard to subacute MICU length of stay, days on mechanical ventilation, or discharge weaning status (p > 0.05). The number of readmissions to the MICU was similar for the ACNP team (n = 7) and fellows team (n = 8), as were readmissions to the subacute MICU < or = 72 h after discharge (ACNP = 2, fellows = 1). Each team had 2 deaths without treatment limitation. CONCLUSION: As hypothesized, management of patients who required prolonged mechanical ventilation with tracheostomy had equivalent outcomes with the ACNP team or the fellows team.

Aged↗

Evaluation of syncope.

Though relatively common, syncope is a complex presenting symptom defined by a transient loss of consciousness, usually accompanied by falling, and with spontaneous recovery. Syncope must be carefully differentiated from other conditions that may cause a loss of consciousness or falling. Syncope can be classified into four categories: reflex mediated, cardiac, orthostatic, and cerebrovascular. A cardiac cause of syncope is associated with significantly higher rates of morbidity and mortality than other causes. The evaluation of syncope begins with a careful history, physical examination, and electrocardiography. Additional testing should be based on the initial clinical evaluation. Older patients and those with underlying organic heart disease or abnormal electrocardiograms generally will need additional cardiac evaluation, which may include prolonged electrocardiographic monitoring, echocardiography, and exercise stress testing. When structural heart disease is excluded, tests for neurogenic reflex-mediated syncope, such as head-up tilt-table testing and carotid sinus massage, should be performed. The use of tests such as head computed tomography, magnetic resonance imaging, carotid and transcranial ultrasonography, and electroencephalography to detect cerebrovascular causes of syncope should be reserved for those few patients with syncope whose history suggests a neurologic event or who have focal neurologic signs or symptoms.

Algorithms↗