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Biomedical subjects

J D Miller

Publications and source records attributed to J D Miller.

At least 163 records · Page 9Linked to original sources
PubMed1993

Depot leuprolide acetate versus danazol in the treatment of women with symptomatic endometriosis: a multicenter, double-blind randomized clinical trial. II. Assessment of safety. The Lupron Endometriosis Study Group.

OBJECTIVES: This is the first multicenter, double-blind randomized clinical trial that compares a depot gonadotropin-releasing hormone agonist with danazol in the treatment of endometriosis. Efficacy results have been previously reported; this report focuses on safety data. STUDY DESIGN: A total of 270 patients from 22 centers were randomly selected to receive either leuprolide acetate depot (3.75 mg injected monthly) or danazol (800 mg administered orally daily). Safety outcomes included adverse effects, clinical laboratory changes, and bone mineral density changes. RESULTS: Most patients receiving either drug reported side effects, most of which were related to the hypoestrogenism of leuprolide (e.g., vasodilatation) and relative hyperandrogenism of danazol (e.g., weight gain). Similarly small numbers of patients dropped out of the two treatment groups because of the side effects encountered. Leuprolide depot caused a greater decrease in bone density; preliminary data suggest a return to baseline on cessation of the drug. Danazol was associated with alteration of serum lipids, specifically a significant decrease in high-density lipoprotein. CONCLUSIONS: Although side effects were commonly reported in both groups, the drugs were similarly safe in terms of the absence of serious complications and the results of cessation of therapy. Side effects were largely reversible on discontinuation of medication. More longitudinal data are necessary before the possibility of long-term risks can be excluded, especially as they pertain to bone mineral density and lipids.

Adolescent↗
PubMed1993

A novel adenylyl cyclase-activating serotonin receptor (5-HT7) implicated in the regulation of mammalian circadian rhythms.

We report the cloning and characterization of a novel serotonin receptor, designated as 5-HT7, which is coupled to the stimulation of adenylyl cyclase. 5-HT7 mRNA is expressed discretely throughout the CNS, predominantly in the thalamus and hypothalamus. 5-HT7 has a unique pharmacological profile that redefines agonist and antagonist classification of ligands previously thought to be "selective." The circadian phase of spontaneous neuronal activity of the rat suprachiasmatic nucleus of the hypothalamus advances in response to serotonin ligands with a pharmacological profile consistent exclusively with that of 5-HT7. These findings suggest a physiological role in the regulation of circadian rhythms for one subtype of serotonin receptor, 5-HT7, and provide a pharmacological test to evaluate its role in other neuronal systems.

Adenylyl Cyclases↗
PubMed1993

Effect of cataract wound incision size on acute changes in corneal topography.

A randomized prospective trial compared keratometric and visual outcomes for 196 patients receiving 3.2 mm, 5.0 mm, or 6.0 mm incisions for cataract removal and intraocular lens implantation. There were no statistically significant differences among the groups preoperatively or at one to two days or three to six months postoperatively in mean keratometric cylinder, no differences postoperatively in surgically induced cylinder, and no differences in best-corrected visual acuity. Significantly more (P < .01) 3.2 mm cases (75%) had uncorrected visual acuity of 20/40 or better at one to two days postoperatively than 5.0 mm (50%) or 6.0 mm cases (47%). Computer-assisted corneal topographic images were available for the last 56 patients enrolled. Patients receiving 3.2 mm incisions had significantly less wound-related flattening than other patients (P < .05) and tended to have fewer surgically induced changes in corneal shape overall. Changes identified by corneal topography were inconsistent with keratometrically assessed cylinder in 14 patients.

Acute Disease↗
PubMed1993

Head injury.

Explore the source record for details and available documents.

Brain Diseases↗
PubMed1993

On the nature of the circadian clock in mammals.

The evidence for the essential role of the suprachiasmatic nucleus (SCN) for the generation and maintenance of circadian rhythms in mammals is briefly reviewed. The pharmacology of the phase-response curve is considered and a new circadian measure, the phase-dose-response surface (PDRS), is introduced. The role of neurotransmission, ion fluxes, and non-neuronal cellular elements in the generation and maintenance of circadian rhythmicity is considered. Cell culture of the SCN is proposed as a tool for the functional analysis of clock mechanism. The critical contribution of coupling and synchronization of clock elements is reviewed in the context of the explicit predictions generated by a strong coupling model of the circadian clock. Finally, the nature of the circadian output signal is analyzed from a phylogenetic viewpoint.

Animals↗
PubMed1993

When should patients with bacterial meningitis be referred to a neurosurgical unit?

The case records of 97 patients with proven bacterial meningitis who were referred to a regional neurosurgical unit between 1964 and 1991 were reviewed. Mortality declined from 34% in the first cohort referred between the years 1964-82 to 5% for 1983-91 (X2 = 11.78; p < 0.001). Fewer patients were admitted in coma, (X2 = 4.43; p < 0.05), or with focal neurological signs (X2 = 7.57; p < 0.01) in the second cohort. The rate of referral increased in the later period but the incidence of unsuspected brain abscess (16% and 15%) did not change. There was a strong correlation between coma on admission and death, (X2 = 17.3; p < 0.001) and with brain abscess and death (X2 = 6.73; p < 0.01). In conclusion patients with known or suspected bacterial meningitis coupled with a decreasing level of consciousness or focal neurological signs should be referred to a neurosurgical centre.

Adolescent↗
PubMed1993

Serotonin and the mammalian circadian system: I. In vitro phase shifts by serotonergic agonists and antagonists.

The primary mammalian circadian clock, located in the suprachiasmatic nuclei (SCN), receives a major input from the raphe nuclei. The role of this input is largely unknown, and is the focus of this research. The SCN clock survives in vitro, where it produces a 24-hr rhythm in spontaneous neuronal activity that is sustained for at least three cycles. The sensitivity of the SCN clock to drugs can therefore be tested in vitro by determining whether various compounds alter the phase of this rhythm. We have previously shown that the nonspecific serotonin (5-HT) agonist quipazine resets the SCN clock in vitro, inducing phase advances in the daytime and phase delays at night. These results suggest that the 5-HT-ergic input from the raphe nuclei can modulate the phase of the SCN circadian clock. In this study we began by using autoradiography to determine that the SCN contain abundant 5-HT1A and 5-HT1B receptors, very few 5-HT1C and 5-HT2 receptors, and no 5-HT3 receptors. Next we investigated the ability of 5-HT-ergic agonists and antagonists to reset the clock in vitro, in order to determine what type or types of 5-HT receptor(s) are functionally linked to the SCN clock. We began by providing further evidence of 5-HT-ergic effects in the SCN. We found that 5-HT mimicked the effects of quipazine, whereas the nonspecific 5-HT antagonist metergoline blocked these effects, in both the day and night. Next we found that the 5-HT1A agonist 8-OH-DPAT, and to a lesser extent the 5-HT1A-1B agonist RU 24969, mimicked the effects of quipazine during the subjective daytime, whereas the 5-HT1A antagonist NAN-190 blocked quipazine's effects. None of the other specific agonists or antagonists we tried induced similar effects. This suggests that quipazine acts on 5-HT1A receptors in the daytime to advance the SCN clock. None of the specific agents we tried were able either to mimic or to block the actions of 5-HT or quipazine at circadian time 15. Thus, we were unable to determine the type of 5-HT receptor involved in nighttime phase delays by quipazine or 5-HT. However, since the dose-response curves for quipazine during the day and night are virtually identical, we hypothesize that the nighttime 5-HT receptor is a 5-HT1-like receptor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Serotonin and the mammalian circadian system: II. Phase-shifting rat behavioral rhythms with serotonergic agonists.

The suprachiasmatic nuclei (SCN) receive primary afferents from the median and dorsal raphe, but the role of these projections in circadian timekeeping is poorly understood. Studies of the SCN in vitro suggest that quipazine, a general serotonin (5-HT) receptor agonist, can produce circadian time-dependent phase advances and phase delays in circadian rhythms of neuronal activity. The present study addresses whether quipazine and the selective 5-HT1A receptor agonist 8-OH-DPAT are similarly effective in vivo. Drinking and wheel-running patterns of male Wistar rats individually housed in constant darkness were monitored before and after subcutaneous administration of quipazine (5-10 mg/kg) at either circadian time (CT) 6 or CT 18, with and without running wheels available. Dose-dependent phase advances (20-180 min) were produced at CT 6. Significant phase shifts were not observed at CT 18. CT 6 quipazine-treated animals also showed a sustained and significant shortening of rhythm period (tau) following treatment (-0.28 hr; p < 0.002). tau shortening was inconsistently observed in CT 18 quipazine-treated rats. Neither quipazine-induced phase shifts nor tau effects were dependent on wheel-running activity per se. 8-OH-DPAT delivered via intracerebral ventricular treatment into the third ventricle (5 microliters at 100 microM in saline) produced slightly smaller phase advances (20-90 min) at CT 6, but did not produce phase delays at CT 18 or changes in tau. These findings support in vitro evidence that 5-HT-ergic agonists can phase-shift the circadian pacemaker.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Spontaneous growth hormone release in term infants: changes during the first four days of life.

Healthy term infants have higher umbilical cord GH levels compared to older infants and children. In the sheep, GH concentrations rapidly fall within an hour of birth; the physiology of GH release after parturition in the human term infant is less well known. The purpose of this study was to investigate spontaneous 12-h GH release in male and female term infants of varying postnatal ages. We studied 14 infants (7 males and 7 females). Subjects were divided into those studied earlier following delivery (28.2 +/- 3.4 h of age, mean +/- SE) and into those studied at a later time (74.8 +/- 3.5 h, P < 0.0005). The age at study was defined as the age (hours) when blood sampling began. There were eight infants studied at an early age (four males and four females) and six studied at a later age (three males and three females). Subjects were comparable with respect to gestational age, birth weight, and length; all were biochemically euthyroid. One infant was large for gestational age although his head circumference was in the normal range. Blood (0.1 mL) was taken every 30 min over a 12-h period from an indwelling umbilical catheter; no stress occurred during the blood withdrawal. GH was determined by a double-antibody RIA using 0.01 mL plasma. GH pulse detection was undertaken using Cluster, a computerized pulse detection algorithm. Total insulin-like growth factor I (IGF-I) was measured following separation of the IGFs from the serum binding proteins. Spontaneous pulsatile GH release was observed in all infants studied. No differences in GH characteristics were found between male and female subgroups in the early or late study groups. In subsequent analysis, the data for the males and females are combined. The GH pulse frequency per 12 h was greater in the earlier studied group, 5.1 +/- 0.9 (mean +/- SE) vs. 2.5 +/- 0.7 in the later group (P < 0.05). The maximal pulse amplitude was 47.1 +/- 7.9 micrograms/L in the early and 27.1 +/- 4.1 in the later studied group (P < 0.06). The incremental pulse amplitude was 26.4 +/- 3.4 micrograms/L in the early and 12.8 +/- 2.7 in the later group (P = 0.01). The pulse width was greater in the later studied group (202.8 +/- 71.1 min vs. 84.1 +/- 21.6, P < 0.06).(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1993

Multimodality monitoring as a guide to treatment of intracranial hypertension after severe brain injury.

Transcranial doppler measurements of blood flow velocity in the middle cerebral artery were made during treatment of raised intracranial pressure (ICP) in 22 patients with severe brain injury. Twenty patients also had continuous measurement of arterial and jugular bulb venous oxygen saturation (SJO2). The transcranial Doppler parameters studied included both mean flow velocity and pulsatility index (PI). Successful treatment was defined as a reduction of ICP to less than 20 mm Hg with improvement or preservation of cerebral perfusion pressure (CPP) above 60 mm Hg. Successful therapy was associated with a significant rise in SJO2 and reduction of cerebral arteriovenous oxygen content difference (AVDO2) and PI only when the pretreatment CPP was less than 60 mm Hg. An increase in CPP beyond 70 mm Hg did not further improve cerebral oxygen delivery and PI, suggesting that autoregulation became a factor above this CPP threshold. Treatment failure during administration of hypnotic drugs resulted in a reduction in arterial pressure, CPP, SJO2, and mean velocity and in an increase in PI and AVDO2, despite a decrease in ICP. CPP is the most important parameter to monitor during ICP therapy. It should be maintained above 70 mm Hg in patients with severe brain injury.

Adolescent↗
PubMed1993

An experimental study of cerebrovascular resistance, pressure transmission, and craniospinal compliance.

To successfully match the treatment to the cause for raised intracranial pressure (ICP) after a severe head injury, it is important to know the underlying mechanism at a given moment for the raised pressure. In particular, it is important to distinguish between active cerebral vasodilation, indicating functional autoregulation, and a passive vascular dilation as the cause for raised ICP. An experimental study was performed in feline models of diffusely raised ICP (n = 6), of active arterial vasodilation caused by arterial hypercarbia (n = 6), and of passive arterial dilation caused by pharmacologically induced arterial hypertension (n = 6) to determine if wave form analysis of ICP can distinguish active from passive arteriolar vasodilation. Pulsatile pressure transmission from the blood pressure pulse to the ICP pulse (cerebrovascular pressure transmission [CVPT]), cerebrovascular resistance, and craniospinal compliance were measured simultaneously at each level of raised ICP, arterial hypercarbia, and arterial hypertension. Arterial hypercarbia, caused by both 5 and 10% inspired CO2 increased low-frequency CVPT, which was followed by an increasingly negative phase shift between the blood pressure and ICP wave form (P < 0.05). Diffusely raised ICP caused by intraventricular infusion of mock cerebrospinal fluid caused increased low-frequency CVPT (P < 0.01) but resulted in no overall change in phase shift, although the sign of the phase shift remained negative. After arterial hypertension, caused by the infusion of angiotensin II, where there was loss of myogenic tone, an increased low-frequency CVPT was accompanied by a positive phase shift (P < 0.01). These data demonstrate it may be possible to distinguish active arteriolar vasodilation from a passive loss of autoregulatory vascular tone through simultaneous measurement of the low-frequency CVPT and phase shift. Analysis of the ICP wave form provides information relevant to the management of raised ICP.

Animals↗
PubMed1993

Congenital absence of a pedicle in a cervical vertebra: report of two cases.

Two cases of congenital absence of a cervical vertebral pedicle are reported. This condition includes hypoplasia of the ipsilateral posterior arch and may predispose to spinal cord injury. The radiographic and computed tomography (CT) findings are reviewed, and the importance of the ipsilateral oblique radiographic view and of CT in diagnosis is stressed.

Adolescent↗
PubMed1993

An evaluation of the role of omentopexy and of early perioperative corticosteroid administration in clinical lung transplantation. The University of Toronto and Washington University Lung Transplant Programs.

Early success in clinical lung transplantation was believed due in part to the technique of bronchial anastomosis, routine bronchial omentopexy, and avoidance of early postoperative corticosteroid therapy. A recent 16-month consecutive experience at the University of Toronto and Washington University with single or bilateral lung transplantation was compared to study the current short-term effect of these perioperative strategies. At the University of Toronto, of 37 patients undergoing lung transplantation, 30 (group I) had telescoped bronchial anastomoses, coverage of the bronchus with local tissue only (no omentopexy), and routine perioperative corticosteroid administration. At Washington University, of 50 patients having lung transplantation, 44 (group II) had end-to-end bronchial anastomoses wrapped in omentum and received no routine perioperative corticosteroid. In group I, septic lung disease was the most frequent indication (14 of 29 patients), whereas in group II obstructive lung disease was the most frequently encountered condition (24 of 44 patients). Sepsis accounted for three of five early deaths in group I (all due to resistant Pseudomonas cepacia infection in recipients who had cystic fibrosis) and for two of four perioperative deaths in group II (one Pseudomonas, and Candida). In group I, cytomegalovirus prophylaxis was administered to all patients except recipients negative for cytomegalovirus receiving grafts from donors also negative for cytomegalovirus. Cytomegalovirus infection requiring treatment was encountered in 5 of 30 patients in group I in comparison with 23 of 44 recipients in group II where only D+ and R- mismatches received prophylaxis. Routine omentopexy is not essential for successful lung transplantation. Early postoperative corticosteroids do not impair airway healing, but neither do these agents appear to protect against acute rejection episodes. While routine corticosteroids do not predispose the recipient to cytomegalovirus infection, their use may increase the likelihood of postoperative bacterial sepsis.

Adolescent↗
PubMed1992

Serotonergic phase shifts of the mammalian circadian clock: effects of tetrodotoxin and high Mg2+.

The mammalian circadian clock in the suprachiasmatic nuclei (SCN) can be phase-shifted in vitro by the serotonin agonist quipazine. Here we show that quipazine resets the SCN clock in the presence of tetrodotoxin or 10 mM Mg2+, treatments that block Na+ action potentials and Ca2+ channels, respectively. These results support the hypothesis that quipazine resets the clock by stimulating receptors located on clock elements rather than on cells afferent to the clock.

Animals↗
PubMed1992

Progress in the management of head injury.

Three 1-year surveys of head injury management spanning a 9-year period in a single regional centre are presented. There was a reduction in total numbers of head injury admissions after guidelines for admission and referral were implemented. More liberal use of computed tomography resulted in detection of a greater number of intracranial haematomas with the majority detected in non-comatose patients. The early mortality rate in severe head injury fell from 45 per cent to 34 per cent despite referral of large numbers of patients with multiple injuries and a substantial proportion (12 per cent) of patients aged more than 70 years in whom outcome did not improve. Total occupied bednights and bednights occupied per surviving patient with severe head injury fell over the period of study. Care for patients with significant head injury should be based on regional neurosurgical units associated with trauma services.

Aged↗