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Biomedical subjects

J M Gray

Publications and source records attributed to J M Gray.

At least 19 recordsLinked to original sources

Antiestrogen binding sites in brain and pituitary of ovariectomized rats.

In addition to interacting with estrogen binding sites in a number of tissues, antiestrogens have recently been shown to interact with a separate, estrogen-non-compatible, antiestrogen-specific binding site (AEBS). In order to better understand possible mechanisms by which the antiestrogens may effect behavioral and physiological changes, we have examined AEBS in several areas of the brain and pituitary in adult, ovariectomized rats. Single point binding assays with 2 nM [3H]tamoxifen (TAM) in the presence of saturating amounts (1 microM) E and +/- 1 microM TAM indicated the existence of specific binding to AEBS throughout the brain and pituitary. In most areas of the brain (cortex, cerebellum, amygdala, area postrema/nucleus of the solitary tract region) as well as pituitary. Scatchard analyses revealed the presence of a single AEBS with a dissociation constant (Kd = 1-4 x 10(-9) M) similar to that previously reported for other tissues. However, in both hypothalamus and preoptic area, an additional, higher affinity site (Kd = 6-9 x 10(-11) M) was found. Competitive inhibition studies revealed that there was little competition by the potent estrogen agonist, diethylstilbesterol, for AEBS binding. Antiestrogens competed in the following order: tamoxifen greater than or equal to nafoxidine much greater than keoxifene. Additional competitive inhibition studies were run using neurotransmitter antagonists. The phenothiazines, chlorpromazine and fluphenazine, bind to both D1 and D2 dopamine receptors and effectively compete with [3H]TAM for binding at the AEBS. Other pharmacological substances, including specific antagonists of the D2 sites, as well as antagonists of the norepinephrine, opiate, histamine, GABA and acetylcholine systems, were ineffective competitors for [3H]TAM binding.

Animals

Lithotripsy as an outpatient service.

A lithotripsy outpatient service was introduced in Hamilton in April 1989 and between then and July 1990 452 patients with renal calculi were treated. The patients came from throughout New Zealand. A three month follow up showed that with stones less than 20 mm in diameter there was total clearance of residual fragments of less than 2 mm in 70% of patients. With stones of diameter greater than 20 mm the clearance rate was 50%. Posttreatment complications needing medical assistance occurred in 7% (31 patients). In 21 patients the stone either could not be found or did not disintegrate.

Ambulatory Care

The Assessment Unit of the Epilepsy Centre, Quarriers Homes.

The work of the Assessment Unit in the Epilepsy Centre, Quarriers Homes, Scotland is described. One hundred and thirty patients with severe epilepsy were admitted over a three year period for investigation of seizures and rationalisation of therapy. The degree of psychomotor impairment due to epilepsy itself, or to anti-epileptic drugs was estimated. Cognitive functioning and levels of ability with interpersonal relationships were measured and plans were drawn up for rehabilitation. A plea is made for NHS funding to support the provision of this service for people with epilepsy.

Anticonvulsants

Derotational analysis of Cotrel-Dubousset instrumentation in idiopathic scoliosis.

Ten patients with idiopathic scoliosis were treated with posterior spinal fusion and Cotrel-Dubousset instrumentation. Computed tomographic scans and intraoperative photographs were used to evaluate the derotational effect of the Cotrel-Dubousset instrumentation. The frontal deformity was corrected from an average of 51 degrees to 15 degrees and the kyphosis from 9.5 degrees to 18 degrees. The amount of preoperative vertebral rotation was variable, however, and insignificant postoperative changes were documented in the majority of cases.

Adolescent

Software support for Huntingtons disease research.

Huntingtons disease (HD) is a hereditary disorder involving the central nervous system. Its effects are devastating, to the affected person as well as his family. The Department of Medical and Molecular Genetics at Indiana University (IU) plays an integral part in Huntingtons research by providing computerized repositories of HD family information for researchers and families. The National Huntingtons Disease Research Roster, founded in 1979 at IU, and the Huntingtons Disease in Venezuela Project database contain information that has proven to be invaluable in the worldwide field of HD research. This paper addresses the types of information stored in each database, the pedigree database program (MEGADATS) used to manage the data, and significant findings that have resulted from access to the data.

Algorithms

81mKr equilibrium radionuclide ventriculography for the assessment of right heart function.

Right heart 81mKr equilibrium radionuclide ventriculography was used to derive right ventricular ejection fraction (RVEF) in 12 healthy male volunteers. Anatomical lung subtraction using 99mTc-MAA perfusion scintigraphy was compared with conventional background correction and the effect of imaging projection on the techniques of image analysis evaluated. Both intra and inter observer variability were reduced by anatomical lung subtraction when compared to conventional background correction. In the right anterior oblique (RAO) projection, background corrected RVEF was lower than lung subtracted RVEF - 0.544 +/- 0.05 and 0.612 +/- 0.08 (mean +/- SD) (P less than 0.02). Lung subtracted RVEF in the anterior projection was lower than that with background correction (P less than 0.05) and lower than lung subtracted RVEF in the RAO projection (P less than 0.001). We conclude that optimal separation of right heart structures is achieved in the RAO projection and that reproducibility of the analytical technique is improved by anatomical lung subtraction.

Adult

Corticosterone, foraging behavior, and metabolism in dark-eyed juncos, Junco hyemalis.

Male, dark-eyed juncos, Junco hyemalis, were held in captivity under conditions simulating winter temperature and photoperiod. Birds were administered corticosterone (B), metapyrone (MET), or control (empty) implants in silastic tubing. B implants resulted in higher plasma levels of B, especially on the first day following implantation. After 4 days, B-implanted birds had significant atrophy of the flight muscles and increased storage of fat in the furcular and abdominal adipose depots. Despite the increased fat deposition, no differences in adipose tissue lipoprotein lipase (LPL) activity or plasma levels of glycerol or free fatty acid were observed after 4 days of treatment. There were no differences in muscle LPL activity when enzyme activity was expressed per tissue. However, when enzyme activity was expressed per gram of tissue, muscle LPL was significantly greater in the B-treated birds. Therefore, despite the atrophy of muscle tissue, the LPL enzyme had been preserved. No differences were observed in either foraging behavior or food consumption, even in light of the dramatic changes in fat and muscle masses in B-treated birds. These data are discussed in light of the chronic effects of B which may be applicable to the advanced stage of stress in birds.

Adipose Tissue

Flexible cystoscopy as an adjunct to extracorporeal shockwave lithotripsy.

Ancillary procedures associated with extracorporeal shockwave lithotripsy (ESWL) include placement and subsequent removal of double pigtail ureteric stents. A simple new technique has been developed for the insertion of these stents. Using the flexible cystoscope, the procedure is performed on an out-patient basis under local anaesthesia. Placement of the stents was successful in 30/34 patients and removal was successful in 14/14 patients.

Adult

Non-verbal cues in the self-presentation of parkinsonian patients.

Parkinson's disease (PD) patients are seen as cold, withdrawn, unintelligent and moody, and appear to relate poorly to the interviewer (Pentland, Pitcairn, & Gray & Riddle, 1987). The cues responsible for this are shown to be related not only to the type of limb and body movements made, but also particularly to the facial expressions. The expressions seen are not only reduced in frequency but are also qualitatively different, particularly in the smiles which are seen to be 'false' smiles. The implications of this for a treatment regime are discussed in relation to the neurology of the disease. It would seem that non-verbal training methods may not produce the required effects because of the shift in neural pathway used from that which normally controls spontaneous expressive movements (via the basal ganglia) to that used in voluntary movements.

Affect

Impressions of parkinsonian patients from their recorded voices.

The voices of patients suffering from Parkinson's disease change in various ways. This paper sets out to examine the effect of these changes on the impressions made on listeners, and to try to see what vocalic and prosodic features account for these impressions. Tape recordings from segments of interviews with 4 patients, and 4 control subjects with ischaemic heart disease, were played to 16 naive listeners. These listeners were asked to rate their impressions of these voices on 15 dimensions of personality. There were significant differences on most of the dimensions, despite the fact that there were no differences between the two groups on such scales as Beck's depression inventory and the mood adjective check list. The parkinsonian patients were seen to be cold, withdrawn and anxious, not to relate well to the interviewer and to be enjoying the interview less than the controls. These ratings are very similar to those previously reported for the same patients, using silent video recordings only. The voice recordings were analysed along various dimensions of prosody. The factors which were different between the groups included the frequency and type of pauses in speech and the range or variability of the fundamental frequency. The implications of this exploratory study for intervention are discussed.

Humans

Tracheobronchial and pulmonary histopathology following conventional and high-frequency jet ventilation.

The advent of high-frequency jet ventilation (HFJV) as an alternative method of respiratory support for newborns has been implicated as a causative agent of necrotizing tracheobronchitis (NTB). We conducted a controlled trial of prolonged HFJV and conventional mechanical ventilation (CMV) in adult cats to determine effects on airway injury related to mode of ventilation and placement of the jet injector (proximal vs distal trachea). Fifteen cats were randomly assigned to either high-frequency positive pressure ventilation, proximal injection jet ventilation, or distal injection jet ventilation. The animals were ventilated for more than 33 hours. Post mortem, the trachea and respiratory tree were removed en bloc and fixed in formalin. A pathologist, unaware of the mode of ventilation, examined tracheobronchial histology and assigned scores using a technique previously described. Lung parenchymal tissue was also assessed using a similar grading system. Statistical analysis (Kruskal-Wallis analysis of variance) demonstrated no significant differences between tracheobronchial or lung parenchymal histopathology regardless of the mode of ventilation. We conclude that (1) the adult cat serves as a useful model for evaluating histopathologic effects of prolonged ventilation, (2) the etiology and pathogenesis of airway injury appears to be multifactorial, and the mode of ventilation is only one of many contributing variables, and (3) previously demonstrated differences between CMV and HFJV may be related to a much shorter duration of ventilation.

Animals

Microcomputer-based rehabilitation for unilateral left visual neglect: a randomized controlled trial.

Microcomputers are widely used in cognitive rehabilitation of brain damage. Unilateral neglect is commonly a target of cognitive rehabilitation, both computer-based and non-computer-based. This study reports the results of a randomized controlled trial of computer-based rehabilitation with blind follow-up for six months. Thirty-six patients with unilateral neglect, as defined by the behavioral subtests of the Behavioural Inattention Test, were randomized into two groups. One group of 20 subjects received a mean of 15.5 (SD = 1.8) hours of computerized scanning and attentional training; the second group of 16 subjects received a mean of 11.4 (SD = 5.2) hours of recreational computing (selected to minimize scanning and timed attentional tasks). Blind follow-up at the end of training and six months after revealed no statistically or clinically significant results between groups. These findings argue against routine clinical use of this type of computerized training until further studies establish what type, frequency, and duration of training produces clinically significant changes in unilateral visual neglect if, indeed, computerized training can have an effect with this type of disorder.

Aged

Antihypertensive effectiveness of very low doses of hydrochlorothiazide: results of the PHICOG Trial.

A large, multicenter, randomized, placebo-controlled, double-blind trial was carried out to determine the effects of the lowest dose of commercially available hydrochlorothiazide. Thus, Dyazide (which contains 25 mg of hydrochlorothiazide and 50 mg of triamterene in an approximately 50% bioavailable form), one capsule, was given daily to patients with either mild or moderate hypertension (supine diastolic blood pressure of 95 to 115 mmHg) for eight weeks. At the end of this eight-week period, supine diastolic blood pressure (SDBP) fell by 11.3 +/- 6.7 mmHg (mean +/- SD) in the Dyazide-treated compared to 4.6 +/- 6.9 mmHg in the placebo-treated group (P less than 0.001). In two thirds of the patients receiving active treatment the fall in SDBP was more than 10 mmHg, and in over half SDBP was completely normalized (ie, SDBP less than 90 mmHg). Supine systolic blood pressure fell by 14.7 +/- 12.3 mmHg in the Dyazide-treated group compared to 5.3 +/- 11.6 mmHg in the placebo-treated group (P less than 0.001). Approximately 80% of the antihypertensive effect occurred within two weeks and after four weeks there was no further significant reduction. Mildly (SDBP = 95 to 104 mmHg) and moderately (SDBP = 105 to 115 mmHg) hypertensive patients responded similarly to treatment. All studied subpopulations responded to treatment with a reduction of SDBP of at least an average of 10 mmHg; the best responders were blacks, women, the elderly (greater than 65 years old), and patients weighing less than 170 lbs. Side effects were mild and infrequent. In conclusion, by examining the effects of Dyazide (one capsule/day), this investigation demonstrated the effectiveness of low-dose hydrochlorothiazide in antihypertensive therapy and quantified it both in the general population and in clinically relevant subpopulations.

Adolescent

Factors associated with sexual dysfunction following transurethral resection of the prostate.

A retrospective analysis of 62 consecutive potent patients undergoing transurethral resection of the prostate is described. Each patient was interviewed a minimum of six months following surgery. Potency was retained in 89% of patients but 57% of these experienced a decrease from their preoperative level of function. Three factors were found to be significantly associated with a reduction in postoperative potency. These were systemic disease (p less than 0.001), small prostatic resections (p less than 0.001) and a reduced level of potency preoperatively (p less than 0.01). Of those men retaining a degree of potency, 90% achieved their first erection within two months of the procedure. The full extent of sexual dysfunction following transurethral resection of the prostate has not previously been appreciated, nor have the factors associated with this dysfunction.

Aged

Intracavernosal injection therapy for impotence: preliminary results.

Intracavernosal injection of vasoactive agents is a new technique for inducing penile erection. It has applications in the counselling, diagnosis and treatment of sexual dysfunction. Nineteen patients are reviewed representing our initial experience with this technique. Thirteen men (68%) achieved a full erection with this treatment and a further three (16%) had a partial response. The applications, method and complications are discussed.

Adult

Comparison of labetalol and prazosin in hypertensive patients using automated ambulatory monitoring.

The differential effects of prazosin and labetalol on blood pressure and heart rate in the clinic and during daily activity were measured in a double-blind study utilizing automatic ambulatory monitors. One hundred five patients with essential hypertension (sitting diastolic blood pressure equal to 101 mm Hg) were randomly assigned to receive prazosin (n = 52) or labetalol (n = 53). Sixty-eight percent of labetalol-treated patients and 50 percent of prazosin-treated patients achieved blood pressure control during clinic visits (sitting diastolic blood pressure less than 90 mm Hg) and were subsequently monitored for 12 hours of normal daily activities. Ambulatory monitoring revealed labetalol-treated patients to have significantly greater decreases in systolic and diastolic blood pressures during daily activity than prazosin-treated patients. Heart rate and rate-pressure product were significantly reduced in the labetalol group but not in the prazosin group. It is concluded that the potential benefits of dual adrenergic blockade, not readily apparent in the non-stressful clinic environment, become more evident during the course of daily activities.

Activities of Daily Living

Percutaneous ablation of canine prostate using transrectal ultrasound guidance. Absolute ethanol and Nd:YAG laser.

Percutaneous absolute ethanol injections and Nd:YAG laser ablations were performed bilaterally in canine prostates (N = 13) using transrectal ultrasound guidance. Seventy-one percent (10/14) of the ethanol injections produced an intraglandular focus of hemorrhagic necrosis. Associated morbidity of ethanol injections included necrosis of the external prostatic sphincter and mucosa of the urethra and bladder. Ninety-two percent (11/12) of the laser ablations produced intraglandular foci of thermal tissue damage, which had distinct margins of transition between necrotic and viable cells. The areas of ablation were well visualized by ultrasound and had minimal associated morbidity. The results of this study demonstrate the technical feasibility and low potential morbidity of transrectal ultrasound guided Nd:YAG laser ablations in the canine prostate.

Animals