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Biomedical subjects

C Bridges

Publications and source records attributed to C Bridges.

At least 19 recordsLinked to original sources

Structure of the defect perovskite Ce1/3NbO3: a redetermination by electron and neutron powder diffraction

The crystal structure of the defect perovskite Ce1/3NbO3, cerium niobium oxide, has been re-examined by neutron powder and electron diffraction. The results of a powder neutron Rietveld refinement indicate that the structure is monoclinic: space group P2/m with Z = 4, a = 5.5267 (3), b = 7.8824 (2), c = 5.5245 (3) A, beta = 90.294 (1)degrees, V= 240.67 (2) A3 at 298 K with chi2 = 2.570. Previous reports have described the Ce1/3NbO3 structure in a smaller (V/2) orthorhombic cell based solely upon X-ray powder diffraction data. The presence of weak reflections in the electron diffraction pattern provides conclusive evidence for a monoclinic superstructure of the orthorhombic cell. While these superlattice reflections are barely detectable with X-ray radiation, they are clearly visible in the neutron diffraction experiments. The superlattice reflections are shown to arise from a tilting of the NbO6 octahedra which results in the reduction of symmetry from orthorhombic to monoclinic. It is also found that the Ce3+ and Nb5+ cations are displaced from the centres of their respective polyhedra to accommodate the bond-valence requirements of the crystal structure. It is likely that distortions of this type are present in other Ln1/3NbO3 and Ln1/3TaO3 defect perovskites.

Journal Article↗

1988: use of a Bayesian statistical model for risk assessment in coronary artery surgery. Updated in 1995.

A computerized statistical model based on the theorem of Bayes was developed to predict mortality after coronary artery bypass grafting. From January, 1984, to April, 1987, at our hospital, 700 patients underwent isolated coronary artery bypass grafting. The presence or absence of 20 risk factors was determined for each patient. The first 300 patients formed the initial database of the Bayesian predictive model, and the remaining 400 patients were prospectively evaluated in four groups of 100 each. Each group was prospectively evaluated and then incorporated into the database to update the model. There was good agreement between predicted and observed results. Bayesian theory is particularly suited to this task because it (1) accommodates multiple risk factors, (2) is tailored to one's specific practice, (3) determines individual, rather than group, prognosis, and (4) can be updated with time to compensate for a changing patient population. These flexible attributes are especially valuable in light of recent changes in the coronary artery bypass graft patient profile.

Bayes Theorem↗

ACTIVE Na+-, Cl-- AND HCO3--DEPENDENT ACID EXTRUSION IN ATLANTIC COD RED BLOOD CELLS IN WINTER ACTIVATED BY HYPERCAPNIA

The relationship between intracellular pH (pHi) and extracellular pH (pHe) was investigated in red blood cells from the Atlantic cod (Gadus morhua) in carbon dioxide/bicarbonate-buffered salines. In summer animals (August/September), similar transmembrane distribution ratios of chloride ([Cl-]i/[Cl-]e=rCl-) and protons ([H+]e/[H+]i=rH+) suggested a passive Donnan distribution of these ions across the red blood cell membrane at pHe 6.7­8.4. In winter animals (February/March), a marked discrepancy occurred between rH+ and rCl- at low pHe values. The pronounced increase in rH+ resulted in significantly higher pHi values compared with those of red blood cells from summer animals and at pHe 6.7 pHi exceeded pHe by 0.3 units. The increases in rH+ values were completely abolished by cyanide and 2,4-dinitrophenol. The high disequilibrium rH+ values were sodium-, chloride- and bicarbonate-dependent. During hypercapnic acidosis, proton equivalents were extruded from the red blood cell. The resulting high rH+ values were accompanied by a reduced chloride shift into the red blood cell and a ouabain-insensitive net sodium influx. The net sodium influx into red blood cells from winter animals was significantly reduced in the presence of DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid). The results suggest the activation of a Na+-dependent Cl-/HCO3-exchanger at low pHe in the red blood cells of the Atlantic cod in winter.

Journal Article↗

CATECHOLAMINE-ACTIVATED SODIUM/PROTON EXCHANGE IN THE RED BLOOD CELLS OF THE MARINE TELEOST GADUS MORHUA

The effects of catecholamines on the pH and the cellular ion and water content were investigated in red blood cells from the Atlantic cod (Gadus morhua). Noradrenaline induced a rapid decrease in the extracellular pH (pHe) of red blood cells suspended in a CO2/bicarbonate or in a CO2/bicarbonate-free buffer system. The noradrenaline-induced changes in pHe were a saturable function of the external sodium ion concentration and were inhibited by amiloride but not by DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid, final concentration of both 10(-4) mol l-1). The catecholamine-induced extracellular acidification was accompanied by an intracellular alkalization and protons were moved from their electrochemical equilibrium. Proton extrusion was associated with an increase in the red blood cell sodium and chloride concentrations. In the presence of DIDS, the chloride movements were blocked and the net proton efflux under these conditions matched the net sodium influx. The results strongly suggested the activation of a sodium/proton exchanger by catecholamines in the red blood cells of the Atlantic cod. The red blood cell receptor affinity for adrenaline was three times higher than that for noradrenaline. Comparison with data in the literature for in vivo catecholamine concentrations indicated that adrenaline was more effective than noradrenaline in activating the red blood cell sodium/proton exchanger in the Atlantic cod in vivo.

Journal Article↗

Direct measurement of first-pass ileal clearance of a bile acid in humans.

The purpose of this study was to develop and validate a method of directly measuring ileal bile acid absorption efficiency during a single enterohepatic cycle (first-pass ileal clearance). This has become feasible for the first time because of the availability of the synthetic gamma-labeled bile acid 75Selena-homocholic acid-taurine (75SeHCAT). Together with the corresponding natural bile acid cholic acid-taurine (labeled with 14C), SeHCAT was infused distal to an occluding balloon situated beyond the ampulla of Vater in six healthy subjects. Completion of a single enterohepatic cycle was assessed by obtaining a plateau for 75SeHCAT activity proximal to the occluding balloon, which prevented further cycles. Unabsorbed 75SeHCAT was collected after total gut washout, which was administered distal to the occluding balloon. 75SeHCAT activity in the rectal effluent measured by gamma counter was compared with that of absorbed 75SeHCAT level measured by gamma camera and was used to calculate first-pass ileal clearance. This was very efficient (mean value, 96%) and showed very little variation in the six subjects studied (range, 95%-97%). A parallel time-activity course in hepatic bile for 14C and 75Se during a single enterohepatic cycle, together with a ratio of unity for 14C/75Se in samples obtained at different time intervals, suggests that 75SeHCAT is handled by the ileum like the natural bile acid cholic acid-taurine. Extrapolation of 75SeHCAT first-pass ileal clearance to that of the natural bile acid therefore seems justifiable. In a subsidiary experiment, ileal absorption efficiency per day for 75SeHCAT was also measured by scanning the gallbladder area on 5 successive days after the measurement of first-pass ileal clearance. In contrast with absorption efficiency per cycle, absorption efficiency per day varied widely (49%-86%), implying a possible wide variation in recycling frequency per day.

Adult↗

An analysis of neural spike-train distributions: determinants of the response of visual cortex neurons to changes in orientation and spatial frequency.

A previously unexploited method of examining neural spike-trains was applied to data obtained from cells in the visual cortex. Distributions of interspike intervals recorded extracellularly from cat visual cortex under four conditions were analyzed. Stimuli were gratings differing in orientation and spatial frequency. The probability density function of first passage time for a random walk with drift process, which is defined by its barrier height and drift coefficient, was used to characterize the generating process of axonal discharge under resting and stimulus conditions. Drift coefficient and barrier height were derived from the sample mean and standard deviation of the measured inter-spike intervals. For cells with simple receptive fields, variations in the drift coefficient were produced by changes in orientation and spatial frequency. Variations in barrier height were produced only by changes in orientation of the stimulus.

Animals↗

Ileal and jejunal absorptive function in patients with AIDS and enterococcidial infection.

Small intestinal absorptive function was investigated in six patients with the acquired immunodeficiency syndrome (AIDS) who had diarrhoea and weight loss. Proximal function was assessed by [14C]Triolein test of fat absorption. Distal function was determined by a test of bile acid absorption in which the loss of radio-labelled synthetic bile acid, 75seleno-23-homocholic acid-taurine ([75Se]HCAT), from the enterohepatic circulation was quantified by abdominal gamma-scanning and by a vitamin B12-intrinsic factor absorption test. Concurrently indirect tests of small intestinal bacterial overgrowth ([14C]glycocholate and breath hydrogen) were carried out. In addition, jejunal histological examination and stool microscopy and culture for enteropathogens were performed. Fat absorption was reduced in all six patients, four of whom had jejunal villous atrophy. Bile acid and vitamin B12 absorption were normal in four subjects. Enteropathogens were not detected in any of the four subjects with normal terminal ileal absorptive function. In contrast, reduced bile acid and vitamin B12 absorption were detected in two of six subjects. Both patients had an enteropathogen (Cryptosporidium spp. and Isospora belli) present on stool and jejunal histological examination. Neither subject had evidence of small-intestinal bacterial overgrowth. AIDS patients therefore may have normal ileal absorptive function in the presence of jejunal disease. Infection with Cryptosporidium spp. or I. belli may however, be associated with severe ileal dysfunction.

Acquired Immunodeficiency Syndrome↗

Adolescents and AIDS. Female's attitudes and behaviors toward condom purchase and use.

Condom use has been advocated as a method to prevent human immunodeficiency virus (HIV) transmission. Although condoms are not uniformly popular with adolescent males, adolescent females' beliefs about condom use are unclear. To assess the specific health attitudes and behaviors as they relate to condom purchase by adolescents, we surveyed 99 adolescent females between 12 and 19 years of age (50 black, 49 white) who were attending a comprehensive adolescent health clinic. The respondents were from low to middle socioeconomic backgrounds and 85% were sexually active. A 41-item survey was developed and focused on four areas: comfort or embarrassment with menses (EM), basic knowledge of acquired immunodeficiency syndrome (AIDS) (KA); comfort in discussing contraception with partner (CC) and risk of contracting AIDS (AR). Chi-square analyses of the four factors determined that decreased EM was related to increased age (p less than 0.05), sexual activity (p less than 0.05), and CC (p less than 0.05). Older adolescents also demonstrated greater CC (p less than 0.05). Increased KA was related to contraceptive use (p less than 0.02) as well as CC (p less than 0.02). Descriptive analyses showed that 62% of the sample reported that a fear of AIDS had influenced their contraceptive behavior, but only 17% of the females reported purchasing or using a condom to prevent AIDS transmission. These findings suggest that although adolescent females have an awareness about AIDS, their behavior remains unchanged.

Acquired Immunodeficiency Syndrome↗

Separation of synthetic cycloalkylated bases, nucleosides and nucleotides by reversed-phase high-performance liquid chromatography.

Reversed-phase high-performance liquid chromatography was used to determine the elution profiles of a series of synthetic cycloalkylated bases, nucleosides, and their corresponding 5'-monophosphates. A 70% aqueous methanol solution proved to be the most efficient solvent system for the separation of a mixture of the bases, all of which were eluted in times ranging from 3.3 to 4.8 min at a flow-rate of 0.8 ml/min. Subsequently, the same percentage of methanol solvent, at 0.8 ml/min, eluted the nucleoside mixture as well, with retention times ranging from 3.3 to 5.0 min. Optimum separation and resolution were achieved with 70% methanol at a flow-rate of 0.6 ml/min for a mixture of the base and nucleoside series. A phosphate buffer, containing acetonitrile-tetrabutylammonium ion, was used to analyze the 5'-monophosphate derivatives. Elution times ranged from 2.6 to 6.1 min at a flow-rate of 1.0 ml/min. Three variables were considered in order to determine optimum conditions for separation and resolution: (a) the percentage of methanol in the solvent; (b) flow-rate of solvent; and (c) the size of the cycloalkylated group of each synthetic analogue. The procedures and conditions described herein have potential use as a monitoring system to detect modified nucleic acid derivative which are prevalent in the body fluids of patients with certain metabolic disorders.

Alkylation↗

Hepatic handling of a synthetic gamma-labeled bile acid (75SeHCAT).

75Se-homocholic acid-taurine (75SeHCAT) is the first available gamma-labeled bile acid, and should therefore be handled more efficiently and specifically by the liver than previous hepatoscintigraphic agents. We have measured serum and hepatic kinetics for 75SeHCAT, and compared them with those for the conventional hepatobiliary scintigraphic agent 99mTc-hepatoiminodiacetic acid, and with serum kinetics for the corresponding natural bile acid, [14C]cholic acid-taurine. We used a dynamic scintigraphic technique and serial blood sampling in 8 subjects. Initial hepatic uptake rate was identical to initial serum disappearance rate (14% dose/min) for 75SeHCAT, but significantly lower for 99mTc-hepatoiminodiacetic acid (6% vs. 14% dose/min, p less than 0.001). Hepatic transit time was shorter for 75SeHCAT (13 min vs. 22 min, p less than 0.02), net hepatic excretory rate was more rapid (1.4% vs. 0.8% dose/min, p less than 0.001), and urinary excretion was lower (1.0% vs. 9.0% dose, p less than 0.001). Initial and late-plasma disappearance rates were significantly lower for 75SeHCAT (14.3% and 1.5% dose/min) than for [14C]cholic acid-taurine (21.3% and 2.8% dose/min, respectively), and plasma clearance was also lower (275 vs. 670 ml/min). In vitro, 75SeHCAT was bound to serum proteins more completely than [14C]cholic acid-taurine (90.4% vs. 86.5%, p less than 0.005). We conclude that 75SeHCAT provides a hepatoscintigraphic agent that is handled more efficiently and specifically by the liver than the conventionally used agent 99mTc-hepatoiminodiacetic acid. It is not cleared from the serum as rapidly as [14C]cholic acid-taurine, probably due to its stronger protein binding. The clinical value of 75SeHCAT in assessing liver disease should be investigated.

Adult↗

Kinetics for the synthetic bile acid 75selenohomocholic acid-taurine in humans: comparison with [14C]taurocholate.

The "apparent" fractional turnover rate of the gamma-labeled bile acid analogue 75selenohomocholic acid-taurine (75SeHCAT) was assessed from decline in radioactivity over the gallbladder area on 4 successive days using a gamma-camera, and was compared in the same subjects with the fractional turnover rate of the corresponding natural bile acid, cholic acid-taurine, labeled with 14C ([14C]CAT) using the classical Lindstedt technique. Very similar results were obtained in 5 healthy individuals (coefficient of variation 4.8%, medians 0.35 and 0.34, respectively). By contrast, the fractional deconjugation rate assessed from zonal scanning of glycine- and taurine-conjugated bile acids on thin-layer chromatography was much less for 75SeHCAT than for [14C]CAT (0.02 and 0.13, respectively; p less than 0.05). The fractional rate for deconjugation plus dehydroxylation was also determined by zonal scanning, and gave lower values for 75SeHCAT than for [14C]CAT (0.02 and 0.12, respectively; p less than 0.05). There was a striking similarity between the fractional rate for deconjugation alone and that for deconjugation plus dehydroxylation for both bile acids in individual samples (r = 0.999, p less than 0.001), suggesting that these two processes might occur simultaneously and probably involve the same bacteria. We conclude that our scintiscanning technique provides an accurate, noninvasive method of measuring fractional turnover rate of a bile acid in humans, and that the finding that 75SeHCAT remains conjugated with taurine during enterohepatic recycling means that absorption should be specific for the ileal active transport site, thus rendering it an ideal substance for assessing ileal function.

Abdomen↗

Use of a gamma-labeled bile acid (75SeHCAT) as a test of ileal function. Methods of improving accuracy.

The object of the present study was to improve the accuracy of measurements of ileal function obtained by abdominal scanning and fecal counting after oral administration of the gamma-labeled bile acid 75seleno-homocholic acid-taurine (75SeHCAT), as current techniques do not distinguish between retention of the bile acid within the enterohepatic circulation from retention within the colon, and are also affected by incomplete stool collection when using the fecal method. We have therefore introduced the following modifications: (a) simultaneous ingestion of 51CrCl3 as a nonabsorbable correction marker for both the abdominal scanning and fecal counting methods; and (b) the use of 75SeHCAT counts over the gallbladder area on abdominal scanning, because these counts should be independent of colonic retention. We have studied 42 subjects, including 6 healthy controls, 6 ileal resection subjects, 15 ulcerative colitis patients, and 15 patients with unresected ileal Crohn's disease. Colonic retention (0%-68% per day) caused a variable overestimate of 75SeHCAT absorption. Corrected measurements of the fecal absorption index determined by a gamma-counter and of the abdominal absorption coefficient determined by a gamma-camera correlated well with each other (r = 0.92, p less than 0.0001), providing an internal validation of the 51CrCl3 modification. The fecal absorption index could also be determined from the carmine-rich stool collection of a single day, and this also correlated well with the abdominal absorption coefficient (r = 0.81, p less than 0.0001). Gallbladder scanning alone was simpler, involving only one isotope, but it correlated less well with the fecal absorption index than did the abdominal absorption coefficient (r = -0.64, p less than 0.001).

Adult↗

Effects of artificial depletion of the bile acid pool in man.

In order to elucidate the relationship between bile acid pool size and cholesterol saturation index of fasting state gall bladder bile, we artificially depleted the bile acid pool in 12 healthy volunteers. Bile acid pool size decreased from 7.6 +/- 0.9 to 5.8 +/- 0.7 mmol (mean +/- SEM, p less than 0.01), and saturation index of fasting state gall bladder bile increased from 0.93 +/- 0.07 to 1.18 +/- 0.07 (p less than 0.001). There was no alteration in saturation index of basal or stimulated hepatic bile. There was no change in gall bladder storage of basal hepatic bile, nor in the proportion of the bile acid pool stored in the gall bladder. The bile acid mass in the gall bladder fell from 4.9 +/- 0.5 to 3.4 +/- 0.4 mmol (p less than 0.05) and phospholipid mass from 1.6 +/- 0.3 to 1.2 +/- 0.2 mmol (p less than 0.05), but there was no change in cholesterol mass. The gall bladder volume fell from 30 +/- 4 to 18 +/- 2 ml (p less than 0.01). These results suggest that artificial depletion of the bile acid pool increased saturation index of fasting state gall bladder bile without altering saturation index of basal or stimulated hepatic bile; it probably increased the ratio of basal: stimulated hepatic bile within the gall bladder by decreasing gall bladder storage of stimulated hepatic bile.

Adult↗

Quantification of temocillin biliary excretion and gallbladder bile concentration in healthy subjects.

The techniques of duodenal perfusion with polyethylene glycol as a nonabsorbable marker, and cholescintiscan using 99Tc HIDA as a gallbladder bile marker, were used to measure the total duodenal output and gallbladder bile concentration of temocillin after administration of an intravenous bolus injection to each of 6 healthy subjects. We carried out 8 studies. 3 with 0.5g temocillin and 5 with 1g temocillin. The plasma half-life of temocillin was 177 (+/- 25) minutes [mean (+/- SD)] and 196 (+/- 29) minutes with the 0.5g and 1g doses, respectively. Urinary excretion accounted for 38% of the total dose given during the study period of 6 hours, and total biliary excretion was recorded as 2.2% of the given dose for both doses. The mean concentration of temocillin in gallbladder bile was 314.7 (+/- 273.2) mg/L after the 0.5g dose and 474.5 (+/- 307.3) mg/L after 1g dose. It was concluded that temocillin is highly concentrated in the normal gallbladder in man.

Adult↗