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Biomedical subjects

C J Martin

Publications and source records attributed to C J Martin.

At least 109 records · Page 6Linked to original sources

Response of canine lower esophageal sphincter to gastric distension.

The aim of this study was to localize the region of the stomach responsible for triggering distension-induced transient lower esophageal sphincter relaxation (TLESR). The canine stomach was partitioned into subsegments by a row of buttressed sutures. This separated either the fundus from the lesser curve or the proximal stomach from the antrum. After 1 mo each region was progressively distended while gastroesophageal pressures were monitored. At the time of the first TLESR, gastric wall tension was estimated from the bag pressure and volume. Distension of the intact stomach, lesser curve, or proximal stomach in 12 dogs produced a progressive increase in lower esophageal sphincter (LES) pressure, which was interrupted at low gastric wall tension (29, 35, and 40 mmHg.cm, respectively) by a superimposed TLESR. Background LES pressure fell progressively with distension of the antrum but was unchanged by distension of the fundus alone. Both the fundus and antrum had significantly higher thresholds for triggering TLESR (96 and 105 mmHg.cm). In another two dogs truncal vagotomy performed at the time of gastric partitioning prevented both the change in background LES pressure, and the triggering of TLESR, associated with proximal gastric and antral distension. We conclude that the subcardiac region of the stomach is primarily responsible for triggering TLESR induced by distension and that the effect on background LES pressure depends on the region distended.

Animals↗

Damp housing, mould growth, and symptomatic health state.

OBJECTIVE: To examine the relation between damp and mould growth and symptomatic ill health. DESIGN: Cross-sectional study of random sample of households containing children; separate and independent assessments of housing conditions (by surveyor) and health (structured interview by trained researcher). SETTING: Subjects' homes (in selected areas of public housing in Glasgow, Edinburgh, and London). SUBJECTS: Adult respondents (94% women) and 1169 children living in 597 households. END POINTS: Specific health symptoms and general evaluation of health among respondents and children over two weeks before interview; and score on general health questionnaire (only respondents). MEASUREMENTS AND MAIN RESULTS: Damp was found in 184 (30.8%) dwellings and actual mould growth in 274 (45.9%). Adult respondents living in damp and mouldy dwellings were likely to report more symptoms overall, including nausea and vomiting, blocked nose, breathlessness, backache, fainting, and bad nerves, than respondents in dry dwellings. Children living in damp and mouldy dwellings had a greater prevalence of respiratory symptoms (wheeze, sore throat, runny nose) and headaches and fever compared with those living in dry dwellings. The mean number of symptoms was higher in damp and mouldy houses and positively associated with increasing severity of dampness and mould (dose response relation). All these differences persisted after controlling for possible confounding factors such as household income, cigarette smoking, unemployment, and overcrowding. Other possible sources of bias that might invalidate the assumption of a causal link between housing conditions and ill health--namely, investigator bias, respondent bias, and selection bias--were also considered and ruled out. CONCLUSION: Damp and mouldy living conditions have an adverse effect on symptomatic health, particularly among children.

Adolescent↗

Phytic acid-enhanced metal ion exchange reactions: the effect on carboxypeptidase A.

On the basis of the known interaction of phytic acid to form soluble or insoluble complexes with cations, the effect of this naturally occurring polydentate ligand on carboxypeptidase A, a zinc-containing metalloenzyme, and its Co(II)-substituted derivative, has been studied. Under conditions of rigorous exclusion of adventitious metal ions, phytate showed no inhibitory effect. However, the addition of Cu(II) ions to form soluble phytate-Cu(II) complexes at pH 7.2 and 25 degrees C caused more than a 95% decrease in activity. The Cd(II) ion was nearly as effective but other ions showed only a small or no effect. In the absence of phytate, incubation of the enzyme with Cu(II) or Cd(II) at the same concentration produced only about a 25% reduction in activity. The decrease in activity followed first-order kinetics, and the rate constant was the same (1.2 x 10(-4) sec-1) as seen upon incubation with EDTA. However, in contrast to that observed upon incubation of the enzyme with phytate and Cu(II), exposure to EDTA produced a complete loss in activity which could be regained by addition of Zn(II) to the assay solution. In the former case, not only was there residual activity left after incubation at pH 7.2 for 24 hrs at 25 degrees C, but the initial activity could not be regained under similar assay treatment. An increase in either the Cu(II) or phytate concentration while the other was kept constant, yielded saturation curves with maximal effect at 3 x 10(-5) M for Cu(II) and at 5 x 10(-5) M for phytate (enzyme at ca. 10(-6) M). At these ratios, all of the cupric ions are completely bound to phytate as determined by ion-selective potentiometry. A preparative scale reaction of phytate and Cu(II) with carboxypeptidase A (kcat 8460 min-1; K'M 0.23 mM with CBZ-glycyl-glycyl-L-phenylalanine as substrate at pH 7.5, 25 degrees C) gave a product isolated in 95% yield but with lower activity (kcat 198 min-1; K'M 0.25 mM). A Cu(II)-carboxypeptidase preparation had similar kinetic parameters (kcat 207 min-1; K'M 0.34 mM). This near identity of constants suggested that a metal exchange reaction had occurred, i.e., incubation of Zn(II)-carboxypeptidase with a phytate-Cu(II) complex resulted in not only the removal of the zinc ion from the active site but also the sequential and rapid incorporation of a cupric ion into the apoenzyme so formed.(ABSTRACT TRUNCATED AT 400 WORDS)

Cadmium↗

Burn wound evaporation--an evaluation of air diffusion resistances governing heat transfer in a clean air unit.

Heat losses from burned patients need to be reduced to avoid placing unnecessary demands on body metabolism. In order to allow more accurate assessments of heat loss, heat transfer has been studied in a clean air unit used for intensive care of burned patients. Evaporation rates have been measured from a phantom representing a recumbent human torso with burn wounds simulated by moist lint strips mounted on the surface. Heat transfer is determined by a complex interaction of free and forced convection, with evaporation rate being greatest on the side of the abdomen in free convection and towards the top in the forced case. Air diffusion resistances have been derived to describe evaporative heat transfer from different parts of a body. Equations have been fitted to data obtained under a wide range of conditions, and will be used to evaluate heat losses from burned patients in order to improve treatment conditions.

Air↗

Cesium-137, 134Cs and 110mAg in lambs grazing pasture in NE Scotland contaminated by Chernobyl fallout.

The decline in Cs radioisotope levels has been studied in tissues from lambs grazing lowland pasture. The lambs were slaughtered 18 and 115 d after contamination with Chernobyl fallout. During this time the Cs activity decreased to 13% of the initial amount in animals that had continued to graze contaminated pasture and to 3.5% in animals consuming uncontaminated feed. The 137Cs concentration in grass from the field grazed by the lambs decreased with a half-time of 22 d over the period 11-100 d after contamination. The amounts of Cs radionuclides removed from the pasture by the grazing animals amounted to only 0.01% of the total, the rest remaining in the soil, with over 40% in the upper 10 mm. Small amounts of 110mAg, found in grass, declined with a half-time of 8.9 d, and the radionuclide was found to accumulate in liver tissue.

Accidents↗

Inositol hexaphosphate and its Cu(II) coordinate complex as inhibitors of intestinal alkaline phosphatase.

Myo-Inositol hexaphosphate (phytic acid), a naturally occurring plant constituent capable of forming coordinate complexes with polyvalent cations, reversibly inhibits the hydrolysis of p-nitrophenyl phosphate by alkaline phosphatase. Kinetics of the inhibition is of the strictly competitive type with Ki equal to 260 microM at pH 8.0 and 25 degrees. A similar result is also obtained in the presence of an inositol hexaphosphate-cupric ion coordinate complex. This inhibition of substrate hydrolysis by either inositol hexaphosphate or its Cu(II) complex is to be differentiated from the effect of the latter on alkaline phosphatase in the absence of substrate. In this case total inhibition of the enzyme is obtained in a time-dependent process which apparently involves a metal ion exchange reaction, i.e., substitution of the enzyme's zinc atoms for copper atoms. The effect of inositol hexaphosphate on alkaline phosphatase contrasts with that of inorganic phosphate which gives inhibition kinetics of the partially competitive type with Ki (for its effect on KM) 17.1 microM; a value close to that of KM for the substrate (15.2 microM). At a low phosphate concentration relative to that of inositol hexaphosphate in the assay solution the observed inhibition was partially additive. At a higher phosphate to inositol hexaphosphate ratio, the inhibition was essentially a phosphate effect. This provides additional support for the conclusion that Inositol hexaphosphate and, by extension, an inositol hexaphosphate-Cu(II) complex inhibits alkaline phosphatase by interaction at the active sites in competition with the substrate.

Alkaline Phosphatase↗

The 20 alpha-hydroxysteroid dehydrogenase of Streptomyces hydrogenans.

In addition to the well-known 3 alpha,20 beta-hydroxysteroid dehydrogenase ('cortisone reductase'), Streptomyces hydrogenans produces a relatively stable, NAD-dependent 20 alpha-hydroxysteroid dehydrogenase of molecular mass approximately 48 kDa. This enzyme catalyzes the transfer of hydrogen from the 4-pro-S position of NADH.

20-Hydroxysteroid Dehydrogenases↗

Heat of complex formation of A1(III) and Cd(II) with phytic acid. IX.

The interactions of Cd(II) and A1(III) with phytic acid to form both soluble and insoluble complexes have been studied by calorimetry. The reactions were examined at metal ion: phytate mol ratios ranging from 1-6 in the case of Cd(II) and 1 and 4 in the instance of Al(III). The heats of reactions were endothermic within these mol ratios. The enthalpies of soluble complex formation of Cd(II) are compared to those of other divalent metal cations that were studied under similar conditions. Based on the enthalpies, it is suggested that the order of combining affinity of these metal cations for phytic acid is Cu(II) greater than or equal to Zn(II) greater than or less than Cd(II) greater than Mn(II) greater than Mg(II) greater than Co(II) greater than Ni(II) The heats of precipitations (which includes binding, solvation changes, etc.) to form the insoluble Cd(II)- and Al(III)-phytate complexes were determined. The reactions were endothermic and had enthalpies of 20.2 and 28.7 kcal mol-1, respectively. From measurements of the Cd(II) and Al(III) concentrations, it was calculated that 5.4 mol Cd(II) and 4 mol Al(III) bind per mol of precipitated phytate. Al(III) only formed soluble complexes with phytic acid at mol ratios of metal cation:phytate of 1. This reaction was markedly slower, at least as judged by the thermal decay curves, and had an enthalpy considerably larger in magnitude (6-17-fold) than those of all of the divalent cation-phytate reactions thus far investigated in this manner.

Aluminum↗

Effect of general anaesthesia on transient lower oesophageal sphincter relaxations in the dog.

This report investigates the hypothesis that gastro-oesophageal flow is modulated by central nervous activity. The hypothesis was examined using the canine model in which gastro-oesophageal flow was stimulated by gastric insufflation of air at 80 ml/min and central nervous depression was produced with the anaesthetic agents thiopentone, nitrous oxide and halothane. Duplicate paired studies were performed in four dogs, either unsedated or anaesthetized. Gastro-oesophageal flow was assessed manometrically by a sleeve catheter assembly and by pH electrode. Gastric compliance was assessed by inflation of a thin-walled, plastic bag. Transient lower oesophageal sphincter relaxation, the dominant mechanism of retrograde trans-sphincter flow in unsedated animals, was abolished by general anaesthesia. Retrograde flow of gas across the lower oesophageal sphincter in anaesthetized animals eventually occurred, but only after massive gastric distension and elevation of gastric pressure to lower oesophageal sphincter pressure. The effects observed could not be explained by a direct action of anaesthetic on the lower oesophageal sphincter or on the gastric wall. It is proposed that general anaesthesia results in blockade of the neural pathway responsible for transient lower oesophageal sphincter relaxation by withdrawal of facilitative higher centre activity. The findings have implications for the use of sedation in experimental studies on factors which control gastro-oesophageal reflux, and clinical application to the risk of tracheal aspiration during general anaesthesia.

Anesthesia, General↗

Housing conditions and ill health.

Lack of empirical evidence that living in damp houses has detrimental effects on health may partly be due to inadequate research. A preliminary study was therefore carried out of a random sample of council owned residences in a deprived area of Edinburgh, a respondent from consenting households being interviewed to obtain a profile of the physical and mental health of all adults and children. In addition, information was gathered about other factors that might be important, particularly smoking and selective bias in the allocation of tenants to houses. Independent measures of dampness were made by environmental health officers. No conclusive effects of damp on the health of adults were identified. Nevertheless, children living in damp houses, especially where fungal mould was present, had higher rates of respiratory symptoms, which were unrelated to smoking in the household, and higher rates of symptoms of infection and stress. Housing should remain an important public health issue, and the effects of damp warrant further investigation.

Disease↗

Studies on the mechanisms of action of activated charcoal on theophylline pharmacokinetics.

Oral administration of repeated doses of activated charcoal to volunteers and dogs significantly increased the systemic clearance of intravenously administered theophylline and decreased its elimination half-life. This effect is most likely to be due to theophylline entering the gut and being adsorbed onto the charcoal. The mechanism by which intravenously administered theophylline enters the gut has been examined. Its biliary excretion after intravenous administration to patients with T-tube biliary drainage accounted for 0.28% of the dose and a similarly small biliary excretion was found in dogs. In the latter total biliary diversion had no effect on the clearance or half-life of theophylline after intravenous administration. In two dogs the theophylline content of jejunal aspirate was comparable with that of simultaneously withdrawn venous plasma samples. These results suggest that the presence of charcoal in the gut represents a sink adsorbing theophylline entering the lumen by diffusion across the intestinal wall, and by this mechanism it increases clearance of the drug even after intravenous administration.

Animals↗

Effects of ageing on the alveolar pores of Kohn and on the cytoplasmic components of alveolar type II cells in monkey lungs.

The effects of ageing on the numbers of alveolar pores of Kohn and on the cytoplasmic components of alveolar type II cells were studied in monkey lungs by scanning and transmission electron microscopy. Lung tissue from 26 female and three male pigtail macaques whose ages ranged from 1 month to 31 years (life span is 35 years) was analysed. From the age of 1 month to 10 years there was a significant increase in the number of alveolar pores (r = 0.85, p less than 0. 001); however, between the ages of 14 years to 31 years there was no significant change. In seven animals ranging in age from 1 month to 4 years (mean 2.4 years) the number of pores was 5.8 +/- 3.9 (mean +/- S.D.), whereas in 10 animals aged 16 to 31 years (mean 20.3 years) the number of pores was 32.7 +/- 17.5 (mean +/- S.D.) per alveolar profile, a significant difference (p less than 0.002). In older animals (15-20 years) there was a significant decrease, both in the number of lamellar bodies per alveolar type II cell (p less than 0.01) and in the volume density of lamellar bodies to cytoplasmic volume (p less than 0.05) compared with young animals (1 month to 4.8 years). In older animals, there was also a significant increase in the volume density of a vacuole-like dilatation of the endoplasmic reticulum in alveolar type II cells (p less than 0.05) compared with young animals. These findings suggest impaired pulmonary surfactant production with aging. Both the increased number of alveolar pores and the postulated decrease of surfactant production could play a role in the pathogenesis of pulmonary emphysema.

Aging↗

Patterns of marital interaction associated with marital dissatisfaction and depression.

This research compared couples reporting high and low levels of marital interactions in which one spouse responds ineffectually to the rights-infringing behavior of the mate. The results of planned comparisons indicated that high frequencies of such interactions were associated with reports of marital dissatisfaction and depression in husbands and marital dissatisfaction in wives. When both spouses described their mates as transgressive and themselves as ineffectual responders to transgression, the dysfunction reported by both spouses was pronounced. Examination of partial correlation, coefficients indicated that each spouse's role in the interaction pattern contributed to its dysfunctional nature.

Depression↗

Abolition of gas reflux and transient lower esophageal sphincter relaxation by vagal blockade in the dog.

In the present study we have examined the hypothesis that transient lower esophageal sphincter relaxations are under vagal control. Fasting esophageal motor function was monitored with a manometric sleeve catheter passed via a cervical esophagostomy. Gastric insufflation with oxygen resulted in intermittent venting of gas into the esophagus during transient lower esophageal sphincter relaxations. Such venting of gas was associated with the occurrence of esophageal body common cavities and gas venting from the esophageal stoma, all of which increased with increasing rates of gastric insufflation. The optimal insufflation rate, 80 ml/min, produced stomal gas venting at a rate of 10.3 +/- 1.1/h (mean +/- SE). The time and pressure profiles of transient lower esophageal sphincter relaxations induced by gastric insufflation were similar to those relaxations seen with spontaneous postprandial gastroesophageal reflux and belching in dogs. Sphincteric relaxation started 10 s before the onset of common cavities. In all 4 dogs, cooling of cervical subcutaneous vagosympathetic loops abolished transient lower esophageal sphincter relaxations, common cavities, and stomal gas venting. Within 1-4 min of cessation of vagal cooling, all three markers of gastroesophageal gas venting returned. Atropine, 50 and 200 micrograms/kg i.v., did not block transient lower esophageal sphincter relaxations or gas reflux. Gastric gaseous distention is a potent and consistent trigger of transient lower esophageal sphincter relaxations in the dog. This effect can be used as a model for study of control mechanisms of transient sphincter relaxation-dependent gastroesophageal reflux. Our observations with this model indicate that transient lower esophageal sphincter relaxations are under vagosympathetic control, but that muscarinic mechanisms are not important mediators of this control.

Animals↗

Relationship of transient lower esophageal sphincter relaxation to postprandial gastroesophageal reflux and belching in dogs.

Methods have been developed for the recording of patterns of motor function associated with spontaneous gastroesophageal reflux and belching in trained, unsedated dogs. Pharyngeal, esophageal body, lower esophageal sphincter (LES), and gastric pressures were monitored in 3 dogs with a manometric assembly inserted through a cervical esophagostomy. Spontaneous changes in esophageal pH were recorded simultaneously with a glass electrode. Each dog was studied three times for 3 h starting directly after completion of a full-sized meal. Acid reflux was recorded on 40 occasions; on 35 of these occasions it was possible to analyze, in detail, motor events at the time of reflux. This analysis showed that the LES was completely relaxed at the time of reflux and that the relaxation occurred within the 15 s before the onset of esophageal acidification. In 77% of the reflux episodes LES relaxation occurred independently of swallowing or any other motor event. The remainder of the LES relaxations associated with reflux were secondary to a swallowing salvo or a single swallow that did not trigger an esophageal body peristaltic wave. Straining was associated with reflux during many episodes of LES relaxation, but did not induce reflux if there was measurable LES pressure. Belching was also related to complete LES relaxations with a pattern identical to that associated with acid reflux. In the dog, liquid and gas reflux occurred during transient LES relaxations that were very similar to those that allow reflux to occur in humans. The dog is a suitable model for investigation of the nature and control of reflux associated with transient LES relaxation.

Animals↗