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Biomedical subjects

R Mason

Publications and source records attributed to R Mason.

At least 19 recordsLinked to original sources
PubMed1992

A neurophysiological study of a lithium-sensitive phosphoinositide system in the hamster suprachiasmatic (SCN) biological clock in vitro.

Lithium lengthens the period of free-running circadian rhythms in many species. In mammals the hypothalamic suprachiasmatic nucleus (SCN) has been identified as a biological clock which generates circadian rhythms. The effect of lithium-induced depletion of the intracellular pool of inositol, leading to decreased intracellular second messengers IP3 and DAG, was examined neurophysiologically. Extracellular recordings were obtained from spontaneously discharging SCN neurones maintained in vitro. Superfusion of slices with lithium-containing (0.1-30 mM) aCSF, but not rubidium-containing aCSF, suppressed neuronal firing in a dose-dependent manner. Lithium-induced suppressed firing was reversed by myo-inositol, but not by epi-inositol. These studies provide evidence for basal phosphoinositide turnover in neurones and implicate a lithium-sensitive phosphoinositide system in the maintenance of the spontaneous discharge activity of SCN neurones.

Animals↗
PubMed1992

Poor palliation of colorectal malignancy with the neodymium yttrium-aluminium-garnet laser.

The neodymium yttrium-aluminium-garnet (NdYAG) laser was used to palliate the symptoms of 38 patients with rectal carcinoma unsuitable for radical surgery. All patients with small tumours (n = 6) reported resolution of their symptoms. In contrast, those with large tumours frequently showed little improvement (n = 18) and alternative surgical management was necessary in 12 patients. The overall early mortality rate (less than 1 month after first treatment) was 21 per cent. The NdYAG laser offers good palliation and may even cure small colorectal tumours in patients who are unsuitable for surgery. For large circumferential tumours, those associated with obstruction and those close to or involving the anal sphincters, however, the results are poor and better symptom control may be achieved by other means.

Aged↗
PubMed1992

Evidence for direct vasoconstrictor activity of melatonin in "pressurized" segments of isolated caudal artery from juvenile rats.

Responses of isolated, 60 mmHg 'pressurized' segments of the distal caudal artery of adult and juvenile Wistar rats to melatonin and the selective alpha 2-adrenoceptor agonist 5-bromo-6-[2-imidazolin-2-ylamino]-quinoxaline bitartrate (UK-14304) were examined using the Halpern pressure myograph. Melatonin showed no direct vasoconstrictor activity in vessels from adult rats, whereas UK-14304 produced moderate vasoconstriction (pD2-7.43 +/- 0.09). In the presence of phenylephrine-induced tone, melatonin produced a variable but small constrictor response (less than 10 microns reduction in diameter) in some vessels; the response to 1 mumol/l UK-14304 was less than in the absence of tone. In vessels isolated from juvenile rats, melatonin caused concentration-dependent vasoconstriction with a maximum response about 70% of the maximum response elicited by UK-14304. Vessels from juvenile rats were more sensitive to melatonin (pD2-9.40 +/- 0.07) than they were to UK-14304 (pD2-8.12 +/- 0.14). In the presence of phenylephrine-induced tone, the vasoconstrictor responses to both melatonin and IK-14304 were markedly less; the sensitivity to melatonin was not different from that seen in the absence of tone. These findings indicate that 'pressurized' segments of the isolated distal caudal artery may provide a simple and convenient, functional model of melatonin receptors. The findings also appear to implicate melatonin in thermoregulatory processes in juvenile rats.

Aging↗
PubMed1992

A simple and rapid method for improving recording characteristics using multibarrelled micropipettes.

A method for the simple and rapid fabrication of multibarrelled micropipettes with improved signal-to-noise characteristics is described. The process of silicone coating the exterior of the multibarrel assembly was found to improve recording characteristics greatly and to reduce recording noise during the passage of ionophoretic current. This simple process of fabrication and silicone coating is completed within 15-20 min and is technically undemanding.

Action Potentials↗
PubMed1992

Comparative hemodynamic effects of Org 7797, flecainide, and propafenone in anesthetized pigs with developing myocardial infarcts.

The hemodynamic effects of a new Ic antiarrhythmic agent (Org 7797) were compared with those of flecainide and propafenone in anesthetized pigs with developing myocardial infarcts. One hour after acute coronary artery occlusion, the only significant hemodynamic effect of an intravenous (i.v.) dose of Org 7797 (0.5 mg/kg) known to prevent ischemia-induced ventricular fibrillation (VF) in dogs was a decrease in heart rate (HR) (of 3%) while cardiac output (CO), stroke volume (SV), and left ventricular (LV) dP/dtP-1 were unchanged. At four times this dose, the only sustained and significant responses to Org 7797 were decreased CO and bradycardia, whereas decreases in arterial and LV pressures (BP and LVP) and LVdP/dtP-1 were transient. In contrast, a therapeutic dose of flecainide (2 mg/kg) induced sustained reductions in CO, SV, LVdP/dtP-1, and LVP whereas a similar (therapeutic) dose of propafenone decreased LVP, reduced CO partly as a result of bradycardia and decreased LVdP/dtP-1 but not sufficiently to decrease SV. Two electrical deaths occurred in each of the propafenone (n = 6) and flecainide (n = 7) groups, but arrhythmic deaths did not occur in Org 7797- or saline-treated animals. We conclude that Org 7797 in therapeutic doses, unlike propafenone and especially flecainide, is not cardiodepressant in animals whose cardiac function is already compromised. In addition, there was no evidence of proarrhythmogenicity at the doses of Org 7797 used.

Animals↗
PubMed1992

Role of the antrum in the gastric emptying of a non-nutrient liquid in the rat.

Forty male Wistar rats underwent liquid gastric emptying analysis with a non-nutrient liquid--99mTC-tin colloid in physiologic saline. Twenty then had two-thirds resection of the glandular stomach with Billroth-II-type reconstruction. Twenty served as controls: 10 unoperated and 10 with a laparotomy alone. Emptying was studied weekly for 4 weeks, then monthly for 4 months. Emptying was unchanged in unoperated controls. Laparotomy alone caused delayed emptying for 2 months (p less than 0.05). After Billroth-II resection emptying was delayed for 4 months (p less than 0.01). This delay included both the early and late phases of gastric emptying. We conclude that a laparotomy alone delays gastric emptying. The addition of an antrectomy causes a greater emptying delay, which persists for longer than that due to laparotomy alone. Thus, in a situation in which the small bowel and gastric feedback mechanisms are inoperative, the antrum is seen to play an important role in the gastric emptying of liquids. This supports the concept in man that antral contractions are important in ensuring the normal active emptying of liquids from the stomach.

Animals↗
PubMed1992

Exit-site/tunnel infection and catheter outcome in peritoneal dialysis patients.

STUDY OBJECTIVE: To study exit-site/tunnel infections and catheter outcomes in peritoneal dialysis patients. DESIGN: The study was designed to investigate exit-site (ESI)/tunnel infections (TI) and catheter losses in all chronic PD catheters inserted in ESRD patients from 9/88 to 9/91. SETTING: Tertiary-referral university hospital. PATIENTS AND METHODS: Seventy-three patients (40 males, 33 females) underwent 78 double-cuff coiled swan-neck catheter implantations surgically. The curettage of exit site was performed weekly for tunnel infection refractory to medical management. The subcutaneous cuff was excised in persistent ESI/TI. RESULTS: Fifty-nine episodes of ESI/TI in 34 patients were observed over 946 patient-months. Thirty-nine patients experienced no ESI/TI, 27 patients had one and seven had two or more episodes of ESI/TI. Four patients had five episodes of peritonitis associated with ESI/TI. Eight recurrent episodes of ESI/TI with S. aureus in 8 patients were treated successfully with Rifampin. Seven subcutaneous cuffs were excised successfully in 7 patients with tunnel infection, five with S. aureus and two with Pseudomonas aeruginosa. No catheter was removed due to ESI/TI or ESI/TI associated peritonitis. CONCLUSIONS: Aggressive exit site care including repeated curettage, excision of the subcutaneous cuff and appropriate antibiotics reduced significantly catheter losses related to ESI/TI.

Bacterial Infections↗
PubMed1992

Metabolic studies in kidney stone disease.

Patients with kidney stones (n = 59) and healthy controls (n = 31) collected a 24-hour urine sample and later underwent a 6-hour 'fast and load' test in which an oral calcium load was taken after 2 hours. In the 24-hour urine sample, mean calcium excretion was higher in patients than controls, while mean urate, oxalate and citrate levels were similar. The patients had higher levels of fasting plasma calcium, serum calcitriol and fasting urinary calcium, and lower levels of plasma phosphate than did the controls. Following the calcium load, plasma and urinary calcium increased similarly in both groups. Serum parathyroid hormone (PTH) levels were similar in both groups and decreased similarly following the calcium load. Multiple linear regression, relating the presence or absence of stone formation to all variables, found the only variables significantly related to stone formation to be plasma levels of calcium (p less than 0.001) and phosphate (p = 0.001) and fasting urinary urea (p less than 0.001), and 24-hour urinary calcium excretion (p less than 0.05). Urinary oxalate and citrate were not related to stone formation. The data do not support the hypothesis that primary stimulation by calcitriol produces a normal fasting plasma calcium level, with an exaggerated increase after an oral calcium load. The findings instead suggest an abnormality of parathyroid cell 'set point', such that PTH secretion continues until the plasma calcium level is a little higher and the phosphate a little lower than in controls.

Adult↗
PubMed1991

Geniculo-hypothalamic tract lesions block chlordiazepoxide-induced phase advances in Syrian hamsters.

Administration of the benzodiazepine triazolam at the appropriate time in the circadian cycle has been shown to induce phase shifts in hamster circadian rhythms. These phase shifts can be blocked by geniculo-hypothalamic tract (GHT) ablation or by restraint of activity. The present study examined the effects of the benzodiazepine chlordiazepoxide on running-wheel activity rhythms of hamsters. The phase-advancing effect of intraperitoneal injections of chlordiazepoxide administered at circadian time 6 (CT 6) was dose-dependent. Average shifts ranged from 6 min at a dose of 0.05 mg/kg to 135 min at a dose of 200 mg/kg. Four of twenty hamsters did not show a phase shift to any dose tested. Phase advance shifts to chlordiazepoxide (CT 6; 100 mg/kg) were blocked by GHT lesions. Chlordiazepoxide injections at doses which induced phase shifts were often followed by sedation. These results indicate that chlordiazepoxide is similar to triazolam, in that its ability to induce phase shifts at circadian time 6 is blocked by GHT lesions.

Animals↗
PubMed1991

The effects of GABA and benzodiazepines on neurones in the suprachiasmatic nucleus (SCN) of Syrian hamsters.

Administration of benzodiazepines at appropriate times in the circadian cycle induce phase-shifts in circadian locomotor activity. The possibility that benzodiazepine-induced shifts are mediated at the level of the suprachiasmatic nuclei (SCN), identified as the circadian pacemaker in mammals, was examined electrophysiologically. Extracellular recordings were made from Syrian hamster (Mesocricetus auratus) hypothalamic SCN neurones in vitro to assess (1) the effects of gamma-aminobutyric acid (GABA) on SCN neuronal activity and (2) the effects of benzodiazepines (chlordiazepoxide and flurazepam) on GABA-evoked responses. Of 93 SCN cells tested, 86 were suppressed by iontophoresed GABA (20 mM) in a current(dose)-dependent manner, while 6 were unaffected; suppression was found during both the projected light and dark phases of the circadian cycle. Application of bicuculline methiodide alone elevated mean discharge activity, while GABA-evoked suppressions were blocked by bicuculline (n = 9/11 cells). Iontophoresis of chlordiazepoxide or flurazepam (20 mM; 1-10 nA) alone produced a current(dose)-dependent prolonged suppression of cell firing which was antagonised by bicuculline. These results indicate that benzodiazepine/GABA-evoked responses are at least partially mediated by GABAA receptors within the SCN and suggest that SCN may be a possible locus for the action of benzodiazepines in their induction of phase-shifts in circadian function.

Animals↗
PubMed1991

The effects of continuous light exposure on Syrian hamster suprachiasmatic (SCN) neuronal discharge activity in vitro.

The circadian variation in neuronal discharge activity recorded in vitro from the Syrian hamster suprachiasmatic nucleus (SCN), identified as a circadian clock, was used as an index of SCN circadian function. SCN neurones (n = 89) following in vitro commissural section of the paired SCN showed a similar peak in spontaneous discharge activity during the projected light phase (between CT 06.00 and 08.00 h) as the commissural intact LD 12:12 preparations (n = 230 neurones). Long-term exposure to continuous lighting (LL) may induce either arrhythmicity or splitting of locomotor behaviour. Circadian variation in SCN discharge activity was absent in hamsters (44 cells, 6 animals) showing LL-induced arrhythmicity. In 4 hamsters exhibiting split free-running behaviour two peaks in SCN discharge activity (n = 32 cells) were observed. Fifteen LL free-running animals showed no evidence of splitting or arrhythmicity and subsequent SCN recordings revealed only a single peak in SCN discharge activity. These LL-induced changes in overt circadian behaviour appeared paralleled by changes in neuronal discharge activity of the SCN circadian clock and support the view that the paired SCN act as a mutually coupled circadian oscillator.

Animals↗
PubMed1991

Effects of idazoxan on dorsal raphe 5-hydroxytryptamine neuronal function.

The effects of the alpha 2-adrenoceptor antagonist idazoxan on 5-hydroxytryptamine (5-HT) neuronal firing and release have been investigated. Idazoxan, administered i.v. (10 micrograms/kg and 0.5 mg/kg) increased dorsal raphe nucleus (DRN)-5-HT neuronal firing rate in a dose-dependent fashion. At the higher dose, a voltammetric study revealed increases in extracellular 5-HT and 5-hydroxyindole acetic acid (5-HIAA) levels, there was no effect with the lower dose. Intra-raphe administration of idazoxan (1 ng) also elevated the firing rate of 5-HT neurones in the dorsal raphe, suggesting that idazoxan may produce the increase in firing by a direct effect in the DRN. However, microiontophoretic application of idazoxan did not increase the firing rate of 5-HT neurones in the DRN. Thus the increase in the firing rate of 5-HT neurones in the DRN observed with systemic and local administration of idazoxan is probably not due to a direct action of idazoxan on the 5-HT neurone. Possibly the idazoxan acted at alpha 2-adrenoceptors located on noradrenergic terminals thus stimulating noradrenaline release and consequently increased 5-HT activity. Chronic administration of idazoxan (0.8 mg/kg per h for 14 days), using osmotic mini-pumps, caused an elevation in basal firing rate and an attenuation of the inhibitory response of DRN 5-HT neurones to the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT) (10 micrograms/kg i.v.). This finding suggests that chronic infusion with idazoxan leads to desensitisation of the 5-HT1A somatodendritic autoreceptor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Trace element analysis in body fluids by glow discharge mass spectrometry: a study of lead mobilization by the drug cis-platin.

A method is described, using glow discharge mass spectrometry, to measure lead and platinum levels at the p.p.b. level in the urine of patients receiving cancer chemotherapy with the drug cis-platin. Using bismuth added as an internal standard, the method is found to compare very favourably with other quantitative techniques, and requires relatively little sample preparation. The data obtained support the idea that normally stored body lead is displaced by the platinum complexed in the drug, but only to a small extent.

Cisplatin↗
PubMed1991

Mechanisms of hemolysis and anemia associated with acute antepartum pyelonephritis.

Anemia develops in about a fourth of women whose pregnancy is complicated by pyelonephritis, although its exact mechanism has not been defined clearly. In this study of 18 women with antepartum pyelonephritis, although only a third had anemia (hematocrit less than 30 vol/dl), there was evidence for hemolysis in all 18. Specifically there was a mean decrease in hematocrit of 5 vol/dl from admission to discharge. With scanning electron microscopy, we compared erythrocyte morphologic aberrations that were found in women with renal infection with those of normally pregnant women, and the former had significantly increased proportions of echinocytes in particular, but schistocytes and spherocytes were increased also (total 10.3% vs 1.4%, p less than 0.0001). These changes, especially echinocytosis, have been induced in vitro by lipopolysaccharide, and they are known to lead to premature red blood cell destruction in vivo. We conclude that hemolysis with subsequent anemia in pregnant women with pyelonephritis is caused by lipopolysaccharide-induced red blood cell membrane damage.

Acute Disease↗
PubMed1991

Effect on gait using various prosthetic ankle-foot devices.

Five different commonly prescribed ankle-foot devices for below-knee prostheses were tested for effects on gait: SACH, SAFE, SEATTLE, SINGLE AXIS, and MULTIPLE AXIS. Subjective ratings by the amputees served to resolve which physical variables determined the preferred ankle-foot device. Ratings were related to age, body weight, length of residual limb, and ratio of stride frequency to stride length. Distinctions in performances were derived from analyses of anterior-posterior angular accelerations occurring in the prosthesis immediately following heel strike. The accelerations were characterized as a damped oscillatory waveform. These objective findings, when related to the subjective ratings, showed that the amputees preferred devices which developed the lesser shock and greater damping.

Acceleration↗