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Biomedical subjects

R Mason

Publications and source records attributed to R Mason.

At least 37 records · Page 2Linked to original sources

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

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

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

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

Assessment of splanchnic oxygenation by gastric tonometry in patients with acute circulatory failure.

OBJECTIVE: To investigate the importance of splanchnic ischemia in patients with acute circulatory failure by comparing gastric intramucosal pH as measured by tonometry with conventional methods of assessing adequacy of tissue oxygenation. DESIGN: Prospective cohort of patients with acute circulatory failure in first 24 hours after admission to the intensive care unit. SETTING: Two general intensive care units in London, England. PATIENTS: Consecutive sample of 83 patients of varying diagnostic categories that required pulmonary artery catheterization. MAIN OUTCOME MEASURES: Gastric intramucosal pH and hemodynamic, oxygen transport, and metabolic variables were measured on admission and at 12 hours and 24 hours after admission. Prediction of outcome (death or survival) by each measurement was assessed by sensitivity, specificity, and logistic regression analysis. RESULTS: Mean 24-hour Acute Physiology and Chronic Health Evaluation (APACHE II) score was 20.3. There were significant differences in mean gastric intramucosal pH between survivors and nonsurvivors on admission and at 24 hours, (7.40 vs 7.28, 7.40 vs 7.24, respectively; P < .001). Admission heart rate was higher (116 vs 101 beats per minute; P < .003) and mean arterial pressure lower (82 vs 97 mm Hg; P < .01) in nonsurvivors. There were no consistent differences in cardiac index, oxygen delivery, and oxygen uptake between survivors and nonsurvivors. Admission arterial pH was significantly lower (7.3 vs 7.36; P < .003), base excess more negative (-5.3 vs -1.9; P < .001), and lactate concentration higher (3.14 vs 1.91 mmol/L; P < .03) in nonsurvivors. Gastric intramucosal pH had a sensitivity of 88% for predicting death and a likelihood ratio of 2.32, higher than for any other variable. Only gastric intramucosal pH at 24 hours independently predicted outcome. CONCLUSIONS: Gastric intramucosal pH was the most reliable indicator of adequacy of tissue oxygenation in this group of patients. Inadequate regional blood flow as detected by a reduction in gastric intramucosal pH, but not by systemic measures, is an important contributor to morbidity and mortality in intensive care units.

Aged

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

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

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

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

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

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

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

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

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