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R Mason

Publications and source records attributed to R Mason.

At least 19 recordsLinked to original sources
PubMed1995

Agmatine recognizes alpha 2-adrenoceptor binding sites but neither activates nor inhibits alpha 2-adrenoceptors.

It has been suggested that agmatine (decarboxylated arginine) is an endogenous clonidine-displacing substance (CDS) which recognizes alpha 2-adrenoceptor and non-adrenoceptor, imidazoline binding sites. We have examined the effect of agmatine at alpha 2-adrenoceptor binding sites and pre- and postjunctional alpha 2-adrenoceptors. Agmatine produced a concentration-dependent inhibition of 1 nmol/l 3H-clonidine binding to both rat (pKi-5.10 +/- 0.05) and bovine (pKi-4.77 +/- 0.38) cerebral cortex membranes. However, agmatine (0.1-100 microM) failed to activate pre-junctional alpha 2-adrenoceptors regulating transmitter release in the guinea-pig isolated ileum and rat isolated vas deferens, nor did it activate postjunctional alpha 2-adrenoceptors of the porcine isolated palmar lateral vein which mediate contraction or inhibition of forskolin-stimulated cyclic AMP formation. High concentrations of agmatine (10-30-fold the pKi at alpha 2-adrenoceptor binding sites) failed to influence alpha 2-adrenoceptor activation by either clonidine or UK-14304 (5-bromo-6-[2-imidazolin-2-ylamino]-quinoxaline bitartrate) in any of the peripheral preparations examined. Moreover, even in a preparation where an interaction with alpha 2-adrenoceptor binding sites on cell membranes can be demonstrated, the rat cerebral cortex, agmatine failed to inhibit forskolin-stimulated cyclic AMP in the intact tissue or affect the inhibition produced by the selective alpha 2-adrenoceptor agonist UK-14304. Agmatine was also devoid of agonist activity in two preparations, the rat isolated thoracic aorta and the rat isolated gastric fundus, in which CDS has been reported to produce non-adrenoceptor effects. Thus, we have confirmed that agmatine recognizes alpha 2-adrenoceptor binding sites and, therefore, is a CDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1995

Plastic-covered metallic endoprostheses in the management of oesophageal perforation in patients with oesophageal carcinoma.

OBJECTIVE: To evaluate the role of plastic-covered self-expanding metallic endoprostheses in patients with oesophageal perforation occurring during endoscopically guided dilatation prior to laser treatment for malignant obstruction. SUBJECTS AND METHODS: Six patients with oesophageal perforation following laser treatment for malignant obstruction were treated. Four patients received the polyurethane-covered Wallstent endoprosthesis (Schneider SA, Bulach, Switzerland) and two patients the barbed polyethylene-covered Gianturco stent (William Cook, Europe). RESULTS: All patients had successful stent placement under intravenous sedation and fluoroscopic guidance with immediate relief of dysphagia and sealing of the perforation. Following the procedure all patients could eat either a normal diet or soft food and five patients were discharged within 3-4 days. None of the serious sequelae usually associated with oesophageal perforation were observed. Two patients required second overlapping stents to be inserted within 1 week because of minor migration of the initial endoprostheses. In one patient two stents were necessary because the carcinoma extended over 17 cm. Five patients died after stent insertion (mean survival time = 49 days, range 16-80; median survival time = 37 days, range 16-80) due to a general deterioration in their condition, although all could swallow normally until death. The remaining patient was well and tolerating a light diet at 1 month. CONCLUSION: This technique is quick, safe and cost-effective and is now our preferred method of managing malignant oesophageal obstruction associated with perforation.

Aged↗
PubMed1995

Expression of pulmonary surfactant protein D in rat gastric mucosa.

Gastric mucosa is protected from an acidic lumenal environment by an extracellular layer composed in part of phospholipids that are similar in composition to the phospholipids of lung surfactant. The function and metabolic processing of lung surfactant is regulated, in part, by surfactant specific proteins. We speculated that the gastric extracellular acid barrier might be regulated by such proteins. We demonstrate by RNA blot analysis, RT-PCR, and immunostaining and protein blot the synthesis of surfactant protein D (SP-D) in mucus-secreting cells of the gastric mucosa. SP-D protein and mRNA were not detected in the duodenum and the remainder of the gastrointestinal tract. We speculate that SP-D may participate in the regulation of secretion or assembly of the gastric acid barrier. Alternatively, SP-D may participate in gastric mucosal host defense.

Animals↗
PubMed1995

Combined bile acid therapy is more effective on biliary lipids and dissolution rates than monotherapy after gallstone lithotripsy.

BACKGROUND: Accurate sampling of gallbladder bile for biliary analysis is essential for determining any potential difference between combined bile acid therapy and monotherapy in gallstone patients. METHODS: In 104 gallstone patients undergoing extracorporeal shock wave lithotripsy with following bile acid therapy [either chenodeoxycholic acid (500 mg/day) and ursodeoxycholic acid (500 mg/day), group I (n = 53), or ursodeoxycholic acid alone (1000 mg/day), group II (n = 51)], bile samples, obtained by direct fine needle puncture of the gallbladder, were investigated for biliary lipids, total biliary protein concentration, and nucleation time before and after 12 months of bile acid therapy. RESULTS: Initially, a negative correlation was found between nucleation time and number of gallstones and between total biliary protein concentration and nucleation time (r = -0.52 and r = -0.49 in group I vs r = -0.56 and r = -0.51 in group II, p < 0.01 in each group). The correlation between total biliary protein concentration and nucleation time was also found after 12 months of bile acid treatment (r = -0.54 in group I vs r = -0.47 in group II, p < 0.01 in each group). In group I, the decrease in cholesterol saturation index, biliary cholesterol, cholic acid, deoxycholic acid, and total protein concentration was more pronounced than in group II (p < 0.01). The same effect was found concerning the prolongation of nucleation time (p < 0.01). Furthermore, dissolution rates were higher in group I compared with group II (80.4 vs 69.0%, p < 0.01). CONCLUSION: In gallstone patients, combined therapy with urso- and chenodeoxycholic acid is superior to either ursodeoxycholic acid alone or biliary parameters in bile samples obtained by direct fine needle puncture of the gallbladder.

Bile↗
PubMed1994

Identification of futility in intensive care.

Rising costs of intensive care and the ability to prolong the life of critically ill patients creates a need to recognise early those patients who will die despite treatment. We used changes in a modified APACHE II score (organ failure score) to make daily predictions of individual outcome in 3600 patients. 137 patients were predicted to die and of these, 131 (95.6%) died within 90 days of discharge from hospital (sensitivity 23.4%, specificity 99.8%); a false-positive diagnosis rate of 4.4%. 2 of the 6 survivors have subsequently died but 4 are alive with good quality of life. Patients predicted to die stayed 1492 days in intensive care and incurred 16.7% of total intensive care expenditure and 46.4% of the cost of all patients that died. Median survival after a prediction to die was 2 days, accounting for 62% of intensive care patient days in this patient group, giving an effective intensive care cost per survivor of UK 129,651 pounds. If used prospectively, this algorithm has the potential to indicate the futility of continued intensive care but at the cost of 1 in 20 patients who would survive if intensive care were continued.

APACHE↗
PubMed1994

Tau-mutant hamster SCN clock neurones express a 20 h firing rate rhythm in vitro.

In vitro neurophysiological studies have demonstrated a circadian rhythm with a period of 24 h in spontaneous neuronal discharge frequency within the rodent suprachiasmatic nucleus (SCN) circadian clock. This report examines the 'circadian' firing rate rhythm in the SCN of the homozygous Tau-mutant Syrian hamster which expresses a short period behavioural rhythm. The spontaneous SCN neuronal firing rate patterns are similar to those observed in wild types. The Tau SCN firing rate rhythm displays a peak in neuronal activity occurring 5-6 h before the predicted onset of wheel-running activity, with a peak-to-peak period of 20 h. This period of the rhythm of spontaneous neuronal discharge within the Tau-mutant SCN parallels the behavioural free-running period of 20 h.

Action Potentials↗
PubMed1994

The effects of BTS 54,505, a metabolite of sibutramine, on monoamine and excitatory amino acid-evoked responses in the rat dorsolateral geniculate nucleus in vivo.

1. The effects of BTS 54,505, the primary amine metabolite of the non-tricylic putative antidepressant sibutramine, on the responses evoked by visual stimulation and ionophoretic application of noradrenaline (NA), 5-hydroxytryptamine (5-HT) and excitatory amino acids (EAAs) in the rat dorsolateral geniculate nucleus (dLGN) have been investigated. 2. Ionophoretic application of 5-HT to dLGN neurones attenuated visually-evoked (n = 46), NMDA-evoked (n = 21) and AMPA-evoked responses (n = 21), while ionophoretic application of NA potentiated visually-evoked activity in these cells (n = 27). 3. Simultaneous application of BTS 54,505 with 5-HT (over 120 s) resulted in a prolongation of the recovery time (i.e. the period required by a neurone to recover by 50%, RT50) from the 5-HT-mediated suppression of discharge activity (approximately 275% increase in RT50). BTS 54,505 also prolonged the recovery time from a NA-mediated potentiation of firing (approximately 450% increase in RT50). These effects on recovery time are attributed to the inhibition of uptake of both 5-HT and NA by BTS 54,505. The amplitude of the response to 5-HT or NA was unaffected by co-ejection of BTS 54,505. 4. Ionophoretic application of N-methyl-D-aspartate (NMDA) produced a current-dependent increase in neuronal firing, as did application of the non-NMDA receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). A simultaneous 120 s application of BTS 54,505 inhibited the NMDA response in all cells studied (mean ED50 = 16 +/- 5 nA) but had no effect on AMPA-evoked activity in the majority of the same cells (n = 15/21).5. Short 10 s applications of BTS 54 505, at ejecting currents (>30 nA) that attenuated NMDA-evoked activity in all cells studied, had no effect on either response amplitude or recovery time from ionophoretic application of 5-HT, suggesting that inhibition of NMDA-evoked activity by BTS 54 505 was not mediated by 5-HT uptake blockade.6. These results suggest that BTS 54 505 inhibits NMDA-evoked activity, and the observation that this effect is unlikely to be due to raised levels of endogenous 5-HT following monoamine uptake blockade indicate that BTS 54 505 may interact directly with the NMDA receptor ionophore complex.

Animals↗
PubMed1994

The relation between biliary lipids, nucleation time, and number of gallbladder stones after percutaneous gallbladder puncture.

BACKGROUND: Biliary lipids and nucleation time are increasingly of importance in the understanding of the cholesterol nucleation process in gallstone patients. METHODS: Biliary lipids, total lipid concentration (TLC), cholesterol saturation index (CSI) and nucleation time (NT) were studied in 221 bile samples from patients with solitary (n = 120) and multiple (n = 101) gallbladder stones. RESULTS: Biliary cholesterol concentration and CSI did not differ between patients with solitary or multiple stones; however, it was positively correlated with the CSI (r = 0.93; p < 0.01). We found a negative correlation between CSI and TLC (r = -0.77 for solitary stones and r = -0.79 for multiple stones; p < 0.01). Furthermore, levels of total bile acids and phospholipids were similar in cases with solitary and multiple gallbladder stones. TLC did not correlate with single or multiple stones, whereas NT was determined to be negatively correlated with the number of gallstones (r = -0.39; p < 0.01). Patients with solitary stones had a significantly (p < 0.01) longer NT than those with multiple gallbladder stones (7.5 +/- 4.2 days versus 2.3 +/- 1.5 days). CONCLUSIONS: Our findings suggest that there exists a nucleation-promoting activity, which seems to be more pronounced in patients with multiple gallbladder stones than in those with solitary stones, indicating a major risk factor for the higher recurrence rate seen in these patients.

Adult↗
PubMed1994

Thymic epithelial defects and predisposition to autoimmune disease in BB rats.

We report an association between thymic epithelial defects and predisposition to autoimmunity. Diabetes-prone (DP) BB rats develop spontaneous hyperglycemia and are deficient in T cell subsets expressing the RT6 alloantigen. Diabetes resistant (DR) BB rats become diabetic if depleted of RT6+ T cells. The inciting immune system defects are unknown. We made the following observations: 1) Regions of thymic cortex and medulla devoid of thymic epithelium exist in DP-BB, DR-BB, and Lewis rats, all of which are susceptible to autoimmune disorders. Such defects were absent in eight normal rat strains. 2) Thymic epithelial defects are absent at birth, but present in BB rats at 4 weeks of age. 3) The genetic predisposition to thymic epithelial defects is an autosomal dominant trait. 4) The observation of thymic defects in (DP x WF)F1 rats led to the prediction that such animals, which never develop spontaneous autoimmunity, might be susceptible to its induction. Following depletion of RT6+ T cells we observed diabetes in 91%, and thyroiditis in 43%, of treated F1 animals (n = 23). Pancreatic insulitis was uniformly present. Because thymic epithelium participates in the positive and negative selection of developing thymocytes, we propose that thymic epithelial defects may play an important role in the predisposition of BB rats to autoimmunity.

Aging↗
PubMed1994

Erythropoietin in pregnancies complicated by pyelonephritis.

OBJECTIVE: To determine whether antepartum pyelonephritis causes an acute or delayed alteration in erythropoietin production. METHODS: Serum erythropoietin concentrations were determined prospectively using an enzyme-linked immunosorbent technique in 36 pregnant women admitted to Parkland Hospital with pyelonephritis. Healthy nonanemic pregnant women served as controls. RESULTS: Serum erythropoietin levels in women with antepartum pyelonephritis were not different from those measured in normal pregnant women. Specifically, there were no differences in erythropoietin levels in women who had anemia at admission (n = 6; 13.8 mU/mL), hemolysis (15.4 versus 12.9 mU/mL), or renal insufficiency (14.5 versus 12.9 mU/mL) secondary to renal infection as compared to controls. CONCLUSION: We conclude that antepartum pyelonephritis does not alter erythropoietin production either acutely or within several days of infection. Because erythropoietin production was not decreased, we suggest that hemolysis is the major factor contributing to anemia associated with renal infection.

Adult↗
PubMed1994

The effect of ursodeoxycholic acid on nucleation time in patients with solitary or multiple gallbladder stones.

OBJECTIVE: The objective of this study was to determine the effect of ursodeoxycholic acid (UDCA), 1000 mg/day, on nucleation time and cholesterol saturation index (CSI) in human gallbladder bile. METHODS AND RESULTS: In 48 patients with cholesterol gallbladder stones undergoing extracorporeal shockwave lithotripsy, bile samples exhibited a significant longer median nucleation time in the case of solitary stones (7.9 +/- 5.1 days) than in patients with multiple stones (1.7 +/- 1.0 days; p < 0.0001). Stone number and nucleation time were correlated inversely (r = -0.79). UDCA led to a significant prolongation of nucleation time (solitary stones 17.9 +/- 5.8 days, multiple stones 18.0 +/- 5.7 days; p < 0.01) with a concomitant disappearance of cholesterol liquid crystals and cholesterol monohydrate crystals in gallbladder bile. Initially, there was no difference in the CSI between patients with solitary stones or multiple gallbladder stones (1.4 +/- 0.3 vs. 1.4 +/- 0.4, respectively). UDCA caused a significant decrease in CSI by 64.3% (p < 0.01). CONCLUSIONS: We conclude that UDCA prolongs the nucleation time by decreasing the cholesterol saturation index, as well as by diminishing cholesterol liquid crystals and cholesterol monohydrate crystals in gallbladder bile from patients with cholesterol gallstones. Second, recurrent stones essentially occur in patients with multiple cholesterol gallstones, reflected by a concomitant short nucleation time.

Bile↗
PubMed1993

Depression, demoralization and control over psychotic illness: a comparison of depressed and non-depressed patients with a chronic psychosis.

This paper explores the hypothesis that depression in chronic schizophrenia is in part a psychological response to an apparently uncontrollable life-event, namely the illness and its long-term disabilities. It is suggested that depression is linked to patients' perception of controllability of their illness and absorption of cultural stereotypes of mental illness. Clinically and operationally diagnosed schizophrenic and manic-depressive patients receiving long-term maintenance treatment were studied. The cross-sectional prevalence of depression in schizophrenics was 29% and 11% for patients with bipolar affective illness. The hypothesis was supported. Multivariate analyses revealed that patients' perception of controllability of their illness powerfully discriminated depressed from non-depressed psychotic patients. Although those patients who accepted their diagnosis reported a lower perceived control over illness and an external locus of control, label acceptance was not associated with lowered depression, self-esteem or unemployment. The cross-sectional nature of the study makes the direction of causality and the role of intrinsic illness variables difficult to ascertain; however, the results set the scene for prospective and intervention studies and the various possibilities are discussed.

Adaptation, Psychological↗
PubMed1993

Evidence for functional dissociation of dependence and tolerance in guinea-pig isolated ileal segments following 20 hour exposure to morphine in vitro.

1. In the present study we have examined the relationship between tolerance and dependence in isolated ileal segments from the guinea-pig under three different conditions: fresh preparations not previously exposed to morphine (fresh/morphine naive); preparations stored overnight at 4 degrees C in modified Krebs-Henseleit saline (overnight-stored/morphine-naive); preparations stored overnight at 4 degrees C in Krebs-Henseleit saline containing 10 microM morphine and extensively washed with modified Krebs-Henseleit saline to remove residual morphine (overnight-stored/morphine-exposed). 2. Morphine produced a concentration-dependent inhibition of the response of ileal segment to 0.1 Hz, 1 ms and 10 V transmural field stimulation in fresh/morphine-naive, overnight-stored/morphine-naive and overnight-stored/morphine-exposed preparations. The maximum effect observed was similar in all three preparations-approximately 80% inhibition. Although, morphine was significantly more potent in the fresh/morphine-naive preparations (pD2 6.72 +/- 0.05, n = 8) than either the overnight-stored/morphine-native (pD2 6.42 +/- 0.11, n = 8) or the overnight-stored/morphine-exposed (pD2 6.44 +/- 0.14, n = 8), there was no significant difference between the overnight exposure to ileal segments to 10 microM morphine at 4 degrees C failed to induce tolerance to morphine. 3. The mu opiate receptor antagonist, naloxone (10 microM), produced contractions in both fresh/morphine-naive and overnight-stored/morphine-naive ileal segments following acute exposure to 10 microM morphine. Naloxone (10 microM) also produced contractions in 2/9 fresh/morphine-naive, 1/9 overnight-stored/morphine-naive and 7/9 overnight-stored/morphine-exposed preparations in the absence of morphine. The greater incidence of naloxone-induced contractions in overnight-stored/morphine-exposed preparations,suggests that dependence in this model is the product of adaptive changes that outlive the presence of morphine.4. The selective alpha2-adrenoceptor agonists, clonidine (0.3 microM) and 5-bromo-6-[2-imidazolin-2-ylamino]-quinoxaline bitartrate (UK-14304, 1 microM), inhibited naloxone-induced contractions in overnight-stored/morphine-exposed preparations of ileal segments (n = 4 preparations for each agonist), suggesting that the response is due to transmitter release from the myenteric plexus.5. The findings in the present study indicate that tolerance and dependence to morphine in ileal segments of the guinea-pig can be functionally dissociated by overnight exposure to morphine at 4 degrees C.The development of tolerance to morphine, unlike dependence, appears to be a temperature-dependent process. This also raises the possibility that naloxone possesses intrinsic negative agonism at morphine sensitive receptors, which is manifested as a functional response only after adaptive changes in the myenteric plexus following exposure to morphine.

Animals↗
PubMed1993

Neurophysiological analysis of circadian rhythm entrainment.

We review recent studies in our laboratory that have investigated the neural mechanisms underlying photic entrainment of the mammalian circadian system. The results from studies of extracellular single-unit recordings and of photic induction of Fos-like immunoreactivity (Fos-lir) indicate that excitatory amino acid (EAA) transmission, and particularly activation of the N-methyl-D-aspartate (NMDA) receptor subtype, is important for conveying photic information to suprachiasmatic nucleus (SCN) cells. We have also found that a subregion of the SCN still shows Fos-lir after blockade of EAA receptors, and we have evidence suggesting that these cells are innervated by a distinct subdivision of the retinal projection to the SCN. In addition, we have found that photic responses of cells in the intergeniculate leaflet (which projects to the SCN) and of SCN cells are modulated by serotonin (5-HT) via a receptor that resembles the 5-HT1A subtype.

Animals↗
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↗