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Biomedical subjects

R Mason

Publications and source records attributed to R Mason.

At least 91 records · Page 5Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Subcellular localization of calcium release in isolated rat myocardial cells.

Independent determinations of Ca2+ by two indicators showed that subcellular Ca2+ activity (intracellular free calcium concentration) was heterogeneous in rat myocardial cells. Arsenazo III (Az III), a membrane-impermeant absorbance indicator for Ca2+, was loaded into cardiac muscle via liposomes and calcium quantitated at two wavelengths through a focal point diaphragm in 5-100 microns 2 regions by a photometer. Fura-2, a high-affinity fluorescent calcium indicator, was loaded into cells as the ester form, and the light intensity was measured by digital-imaging microscopy using a photon-counting camera. Calcium activity at each picture element was quantitated by division of fluorescence excited by two ultraviolet wavelengths, and corrected for concentration differences in fura-2 by a third, Ca(2+)-insensitive wavelength. Both methods revealed hot spots of Ca2+ release and uptake that could be enlarged, added to, or altered. Addition of 1-10 nM norepinephrine caused up to a 500% increase in Ca2+ in localized regions, although whole cell average Ca2+ increased by only 0-80%, suggesting the importance of localized intracellular Ca2+ release for contraction.

Animals↗

Mesenteric blood flow in patients with diabetic neuropathy.

We examined flow velocities in the superior mesenteric artery and celiac artery in normal controls (group C, n = 11), diabetic patients (group D, n = 8), and diabetic patients with clinically evident autonomic neuropathy (group DN, n = 6) to further define the usefulness of duplex examination in the evaluation of the mesenteric circulation in normal and disease states. By use of a 3 MHz duplex scanner, peak systolic velocity, peak diastolic forward velocity, end-diastolic forward velocity, and peak diastolic reverse velocity were measured in centimeters per second before and after a standardized meal. The vessels' diameters in centimeters were also measured. After the meal peak diastolic reverse velocity disappeared in all patients. The average vessel diameter in the superior mesenteric artery (0.7 cm) and celiac artery (0.8 cm) did not change. Flow velocities in the celiac artery were not significantly altered by the meal. In the control group, peak systolic velocity in the superior mesenteric artery increased 38%, peak diastolic forward velocity rose 66%, and end-diastolic forward velocity increased by 70%. In the diabetic nonneuropathic group the changes were 15%, 98%, and 100%, respectively. These changes were statistically significant (p less than 0.01). On the other hand, the patients with diabetic autonomic neuropathy presenting a picture of gastroparesis did not exhibit the expected increases in postprandial velocities. Moreover, this alteration in blood flow velocity, although similar to that encountered in patients with intestinal angina, did not appear to be due to occlusive arterial disease on the basis of clinical examination and B-mode scanning.

Autonomic Nervous System Diseases↗

Neurophysiological responses to melatonin in the SCN of short-day sensitive and refractory hamsters.

The pineal hormone melatonin plays a central role in the regulation of seasonal reproductive cycles in mammals and several studies have implicated the suprachiasmatic nucleus (SCN) as a target on which melatonin acts. The Syrian hamster is a long-day breeder which exhibits gonadal regression when housed in short (less than 12.5 h) daily photoperiods or injected daily with melatonin in long photoperiods. In the present paper we address the question whether melatonin affects firing rates of SCN neurones and whether these effects change as the animals become refractory to short photoperiods. In long-day (LD14:10) hamsters SCN neurones were suppressed (31%), activated (15%) or unaffected (54%) by melatonin. In contrast, there was an increased proportion of melatonin insensitive cells (88%) in short-day (refractory) hamsters. Melatonin-responsive cells were found primarily during the late projected day and early projected night in both long-day and short-day animals. This reduced responsiveness of SCN neurones to melatonin in hamsters refractory to short-day exposure may represent part of the mechanism underlying the development of gonadal refractoriness and the onset of gonadal growth in anticipation of long spring photoperiods.

Animals↗

Analysis of below-knee suspension systems: effect on gait.

Seven different suspension systems for below-knee prostheses were tested on 20 adult, unilateral amputees. All subjects walked with a prosthesis. Gait was evaluated with regard to longitudinal and vertical accelerations of the body, forward velocity, axial (piston) movement of amputated limb in the socket, and knee movement. Harmonic analyses of variable waveforms provided the primary method to discriminate performances among the suspensions. The appropriateness of a given suspension system depended on both the length and the shape of the residual limb.

Adult↗

The aetiology of gastric stump carcinoma in the rat.

This study investigated the aetiology of gastric stump carcinoma in the rat. These carcinomas were induced by duodenogastric reflux without the need to administer carcinogens. Carcinoma was only detected when pancreatic exocrine secretions were present in the reflux. Malignant change was associated with dysplasia but not intestinal metaplasia or adenocystic proliferation of glands. The extent of resection increased tumour yield, but a truncal vagotomy did not. No difference was detected in intragastric pH, bacterial flora, or bile acid concentration between animals with and without carcinoma.

Adenoma↗

Prioritising waiting lists.

The 'top 22' patient conditions on the general surgical waiting list at Guy's Hospital were rated independently by five general surgeons. Each surgeon estimated the peri-operative mortality rates associated with each treatment; the proportion of patients who failed to benefit; the effect of successful treatment on life expectancy and on the patients' quality of life. the mean values were used to estimate the expected net benefits (in terms of quality-adjusted life-years) from treatment one year earlier than might otherwise have been the case. These benefits were then related to the operating times and length of stay associated with each treatment; this identified which treatments offered the greatest benefit per unit of each constrained resource. Of all conditions examined anal fissures where shown to be the least resource intensive in relation to the benefits generated, whilst varicose veins and epigastric hernias proved otherwise. For the full potential of this approach to be realised it needs to be repeated in other places and in other specialties. It nevertheless offers a more rational basis for interpreting waiting list data than presently exists and by using the short-cut methods is a relatively cheap way of generating much useful data.

Data Collection↗

Ulceration and osteomyelitis.

The pathophysiology, mortality, and morbidity of osteomyelitis and ulcers are discussed, including making the diagnoses. Treatments described include topical and surgical methods as well as hyperbaric oxygen therapy.

Foot Diseases↗