Biomedical subjects

M J Turner

Publications and source records attributed to M J Turner.

At least 91 records · Page 5Linked to original sources

PubMed1996

The equilibrium CO2 rebreathing method does not affect resting or exercise blood pressure.

The equilibrium CO2 rebreathing technique has been widely used for the noninvasive determination of cardiac output. Recently, several investigators have used this technique in conjunction with auscultatory blood pressure measurements to calculate total peripheral resistance. To examine the validity of this approach, we attempted to determine whether the CO2 rebreathing procedure has a significant effect on blood pressure. The participants in the present study were 10 male subjects, 24 +/- 1 yr of age (mean +/- SE). Each subject performed two trials-one with CO2 rebreathing and one without. Both trials consisted of three stages (rest, 25%, and 50% VO2peak), each stage lasting 15 min. During the rebreathing trial, the CO2 rebreathing technique was administered at 10 min into each stage. There were no statistically significant differences in the heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure responses between the two trials. These results indicate that the equilibrium CO2 rebreathing technique does not alter auscultatory blood pressures at rest and during exercise up to intensities of 50% VO2peak.

Adult↗

PubMed1995

Conjugation of acrylonitrile and 2-cyanoethylene oxide with hepatic glutathione.

The glutathione (GSH) conjugation of the rat carcinogen acrylonitrile (ACN) and its epoxide metabolite 2-cyanoethylene oxide (CEO) by rat, mouse, and human liver enzymes was characterized in vitro since GSH conjugation is the major disposition pathway for these chemicals in vivo. Mass spectral analyses indicated that S-(2-cyanoethyl)GSH was the product from reaction of GSH and ACN and that S-(cyanohydroxyethyl)GSH reaction products were formed from CEO. Because of the rapid nonenzymic reactions of ACN and CEO with GSH at pH 7.3, the steady-state kinetics of hepatic GSH conjugation were determined at pH 6.5 by HPLC analysis of the products. Hyperbolic kinetics were observed with respect to GSH for the reactions catalyzed by mouse or rat hepatic cytosols at pH 6.5, whereas sigmoidal kinetics were observed with respect to ACN or CEO. This kinetic pattern is consistent with the random sequential kinetic mechanism that has been described for GSH S-transferases. Estimates of the maximal velocities of the reaction at pH 6.5 showed that mouse enzymes had a 4- to 6-fold greater capacity for GSH conjugation of ACN and CEO than rat enzymes. ACN appeared to be conjugated with GSH more efficiently than CEO under these conditions. At physiological pH (7.3), rapid nonenzymic conjugation of GSH (10 mM) with ACN or CEO (5 mM) was observed (approximately 25 and 15 nmol product/min, respectively). Addition of hepatic cytosols or microsomes from rats or mice increased the velocity of GSH conjugation approximately 1.6-fold. A similar velocity enhancement was observed with human liver cytosols for the GSH conjugation of ACN, but not for CEO. Human liver microsomes did not enhance the velocity of GSH conjugation of either substrate. These results suggest that ACN is a better substrate for human liver GSH S-transferases than CEO. Estimation of the initial velocities of the GSH conjugation reactions in intact rodent liver from the in vitro data at pH 7.3 suggests that the enzyme-mediated GSH conjugation of ACN and CEO will be approximately 4-fold greater than the velocity of the direct chemical reaction with GSH.

Acrylonitrile↗

PubMed1995

Morphology of the deciduous tusk (tush) of the African elephant (Loxodonta africana).

The tusk of the African elephant is preceded by a deciduous tooth generally known as the tush. Tushes from nine elephant fetuses and six calves younger than 1 year were exposed by dissection and described morphologically. All tushes consisted of a crown, root and pulpal cavity, the formation of which is completed soon after birth. They reached a maximum length of 5 cm, appeared not to erupt through the skin and were pushed aside and resorbed during enlargement of the distally located primordium of the tusk. Dental enamel, which covered the crown, could easily be removed and consisted of rods with an interwoven arrangement; the dentine-enamel junction was flat. Cellular cementum extended for variable distances over the crown and the dentine was tubular in nature. Although the tush apparently has no function, it provides the anlage and orientation for the development of its permanent successor.

Animals↗

PubMed1995

Are babies of normal birth weight who fail to reach their growth potential as diagnosed by ultrasound at increased risk?

The objectives of this study were to identify, by means of two third-trimester scans, fetuses with ultrasound evidence of inadequate growth but who were born with birth weights above the 10th centile for gestational age; and to determine if these infants constitute a high-risk group by comparing the incidence of obstetric intervention, of intrapartum complications and of neonatal morbidity between this group and the group of infants who showed no ultrasound evidence of intrauterine growth restraint. A total of 285 women with singleton pregnancies who were referred for a third-trimester ultrasound examination were included in this prospective study. Fetal weight was estimated by ultrasound twice in the third trimester and at each examination was assigned a centile score. A fall of > 20 centiles was taken as evidence of inadequate growth. The outcomes measured were the incidence of abnormal umbilical artery Doppler, induction of labor, meconiumstaining of the liquor, intrapartum fetal blood sampling, operative vaginal delivery, Cesarean section, Apgar score of < 7 at 5 min and admission to the neonatal intensive care unit. Seventy-five patients showed a drop of > 20 centiles between the first and second scans. The incidence of admission to the neonatal intensive care unit was greater in those infants who had ultrasound evidence of growth restraint. We conclude that infants of normal birth weight with inadequate growth diagnosed on ultrasound are not at increased risk, they have an increased incidence of admission to the neonatal intensive care unit, and they are more commonly found in mothers with diabetes mellitus.

Apgar Score↗

PubMed1995

Effect of graded epinephrine infusion on blood lactate response to exercise.

In an attempt to determine whether the lactate threshold (LT) is the result of a sudden increase in plasma epinephrine (Epi), eight healthy college-aged males (22.4 +/- 0.4 yr) were recruited to perform three cycle ergometer exercise tests. Each subject performed a graded exercise test (GXT) to determine LT, Epi threshold, and norepinephrine threshold (64.6 +/- 2.4, 62.5 +/- 2.4, and 60.8 +/- 4.3% peak oxygen uptake, respectively). Each subject also completed, in random order, two 30-min submaximal (20% peak oxygen uptake below LT) exercise tests. During one test, graded Epi infusions were carried out at rates of 0.02-0.12 micrograms.kg-1.min-1; the other served as a control test. Infusion resulted in plasma Epi concentrations similar to those observed during GXT. The increase in blood lactate with Epi infusion was significantly greater than that during the control test (3.0 +/- 0.3 vs. 1.4 +/- 0.1 mmol/l at minute 30) but did not approach levels exhibited during GXT. We suggest an interaction of the increasing plasma Epi with other factors may be responsible for the sudden increase in blood lactate during graded exercise.

Adult↗

PubMed1995

[Peripartum hysterectomy. Report of eleven cases].

A series of hysterectomies performed during labor or shortly after delivery, all as emergencies is reported. The study covered the ten years 1982-1991, during which 65,488 deliveries resulted in infants with a birth weight of 500 g or more. There were no hysterectomies among the 21,998 primipara, the incidence in multipara being 1 per 3,954 deliveries. Five operations were performed for rupture of the uterus and six for cataclysmic bleeding. Seven of the 11 patients had history of caesarean section. In multipara, the existence of a caesarean scar multiplied the risk of emergency hysterectomy by a factor of 18. There were no maternal deaths but all patients required transfusion with more than 6 units of packed cells. These results emphasize the fact that a history of caesarean is the principal etiologic factor in patients experiencing complications of pregnancy which require emergency peri-partum hysterectomy.

Blood Transfusion↗

PubMed1995

Benefits of using hypertext in a health care environment.

This "hyperdemo" shows the development, management, and business benefits of using hypertext in a healthcare environment. The demonstration shows how existing information has been made available in both primary and secondary care; we cover two application areas.

Information Systems↗

PubMed1994

Measurement of respiratory mechanics in a mechanically ventilated infant lung simulator: effects of variations in the frequency response of the flow measurement system.

The frequency responses of systems used to measure flow and pressure in ventilated infants may differ, and hence affect estimates of resistance and compliance. We estimated resistance and compliance in 16 ventilated mechanical lung models using linear regression while varying the frequency response of the flow measurement system. Lung models comprised combinations of four sections of tubing and four bottles filled with steel wool. The cut-off frequencies of a filter in the flow measurement system were chosen to yield time delays of 0, +/-3, +/-6, and +/-9 ms relative to the pressure signal. When the phase lags in the measurement systems were not equal at 10 Hz, a bias in resistance approximately (relative delay) x (elastance) ensued. The bias in the resistance estimate when resistance is 5 Pa ml-1 s and compliance is 2 ml kPa-1 is approximately 28% per ms of delay mismatch. Time-shifting the flow data to eliminate the phase discrepancy reduced the resistance bias by 85%. The residual resistance bias was assumed to be due to inappropriate amplitude response. Compliance measurements were affected by less than 8% and less than 2% after time correction of the flow data. Pressure and flow signals must be synchronized to within 1 ms at 10 Hz and the amplitude responses of the measurement systems must be adequate for reliable resistance measurement.

Adult↗

PubMed1994

Uterine rupture in pregnancy reviewed.

Uterine rupture is associated with maternal and fetal mortality and morbidity. In developed countries there have been many recent advances in the management of labour. This study, therefore, reviewed this Hospital's experience of uterine rupture in the decade 1982 to 1991. Excluding cases of asymptomatic scar dehiscence, there were 15 cases of uterine rupture in 65,488 deliveries, giving an overall incidence of 1 in 4,366. There was no case of rupture in 21,998 primigravidas. Of the 15 cases, only two occurred in 39,529 multigravidas without a previous uterine scar (1 in 19,765), and 13 cases occurred in the 3,961 multigravidas with a previous caesarean section scar (1 in 304). Twelve of the 13 ruptures after caesarean section occurred in the delivery immediately after the section. There were no maternal deaths but five (33%) patients required a hysterectomy. Three of the five perinatal deaths were attributable to the rupture. Ten of the 15 patients had labour induced, and a total of 13 patients received an oxytocic agent. Of the 15 cases, 8 were diagnosed during labour and 7 postpartum. Compared with earlier reports from Dublin, the incidence of uterine rupture was low due to a decrease in the number of ruptures associated with trauma or obstetric manipulation. The main associated feature was previous caesarean section. This review highlights the risk of uterine rupture when an oxytocic agent is administered to a multigravid patient with a previous caesarean section scar.

Female↗

PubMed1994

Monitoring exposure to acrylonitrile using adducts with N-terminal valine in hemoglobin.

Human exposure to acrylonitrile (ACN), a carcinogen in rats, may occur in industrial settings, through waste water and tobacco smoke. ACN is an electrophilic compound and binds covalently to nucleophilic sites in macromolecules. Measurements of adducts with hemoglobin could be utilized for improved exposure assessments. In this study, a method for quantification of N-(2-cyanoethyl)valine (CEVal), the product of reaction of ACN with N-terminal valine in hemoglobin has been developed. The method is based on the N-alkyl Edman procedure, which involves derivatization of the globin with pentafluorophenyl isothiocyanate and gas chromatographic-mass spectrometric analysis of the resulting thiohydantoin. An internal standard was prepared by reacting valylglycylglycine with [2H3]ACN, spiked with [14C]ACN to a known sp. act. Levels of CEVal were measured in globin from rats exposed to 3-300 p.p.m. ACN in drinking water for 105 days and from humans (four smokers and four non-smokers). CEVal was detected at all exposure levels in the drinking water study. The relationship between adduct level and water concentration was linear at concentrations of 10 p.p.m. (corresponding to an average daily uptake of c. 0.74 mg ACN/kg body wt during the 65 days prior to sacrifice) and below, with a slope of 37.7 pmol CEVal/g globin/p.p.m. At higher concentrations, adduct levels increased sublinearly, indicating saturation of a metabolic process for elimination of ACN. Comparison of adduct formation with the estimated dose (mg/kg/day) of ACN indicated that at low dose (0-10 p.p.m.) CEVal = 0.508 x ACN dose + 0.048 and at high dose (35-300 p.p.m.) CEVal = 1.142 x ACN dose - 1.098. Globin from the smokers (10-20 cigarettes/day) contained about 90 pmol CEVal/g, whereas the adduct levels in globin from non-smokers were below the detection limit. The analytical sensitivity should be sufficient to allow monitoring of occupationally exposed workers at levels well below the current Occupational Safety and Health Administration standard of 2 p.p.m.

Acrylonitrile↗

PubMed1994

Characterization of phosphodiester adducts produced by the reaction of cyanoethylene oxide with nucleotides.

Cyanoethylene oxide (CEO), a putative toxic and carcinogenic metabolite of acrylonitrile, is a direct-acting mutagen. The focus of this study was to elucidate potential adducts responsible for the mutagenic effect of CEO by characterizing products from the reaction of CEO with nucleotides. The reaction of CEO with the 5'-monophosphates of deoxyguanosine, deoxyadenosine, deoxycytidine or deoxythymidine resulted in the formation of at least one adduct for each nucleotide. Using two-dimensional NMR spectroscopy and fast atom bombardment mass spectrometry, CEO-nucleotide adducts (approximately 25% modification) were characterized as 2-cyano-2-hydroxyethyl phosphodiesters. The isolate from the reaction of deoxyguanosine-5'-monophosphate (dGMP) with CEO contained a second adduct, identified as N7-(2-cyano-2-hydroxyethyl)-dGMP. Single and double strand breaks, which were observed in supercoiled pBR322 plasmid DNA exposed to CEO (> 50 mM), may arise following formation of cyanohydroxyethyl phosphotriester adducts. The characterization of these phosphodiester adducts in vitro may provide insight into the intermediates responsible for the genotoxic effect of CEO in vivo.

Chromatography, High Pressure Liquid↗

PubMed1994

Comparison of blood concentrations of 1,3-butadiene and butadiene epoxides in mice and rats exposed to 1,3-butadiene by inhalation.

1,3-Butadiene (BD), an important commodity chemical used in the production of synthetic rubber, is carcinogenic in B6C3F1 mice and Sprague-Dawley rats, raising concern for potential carcinogenicity in humans. Mice are more sensitive than rats to the carcinogenic effects of BD. Metabolic activation of BD to form the putative DNA-reactive metabolites, butadiene monoxide (BMO) and butadiene diepoxide (BDE), is mediated by cytochrome P450. Detoxication of the epoxides occurs by glutathione S-transferase-catalyzed conjugation with glutathione and hydrolysis by epoxide hydrolase. Species differences in metabolic activation and detoxication most likely contribute to the difference in carcinogenic potency of BD by modulating the circulating blood levels of the epoxides. This study measured the in vivo concentrations of BD, BMO and BDE in the blood of male Sprague-Dawley rats and B6C3F1 mice during and following 6 h nose-only exposure to inhaled BD at 62.5, 625 or 1250 p.p.m. BD. Blood samples for BD and BMO (> or = 3 samples/time point) were collected at 2, 3, 4 and 6 h of exposure. Blood samples for BDE were collected at 3 and 6 h of exposure. After exposure, blood samples for BD, BMO and BDE were collected at 2-10 min intervals up to 30 min post-exposure. BD was quantified by gas chromatography using a vial headspace equilibration technique. BD epoxides were extracted into methylene chloride and quantified by gas chromatography-mass spectrometry. The concentration of BD in blood was not directly proportional to the inhaled concentration of BD, suggesting that the uptake of BD was saturable at the highest inhaled concentration. In both rats and mice, BD and BMO blood levels were at steady-state at 2, 3, 4 and 6 h of exposure, and declined rapidly after removal from exposure to BD. Steady-state blood concentrations of BD were 2.4, 37 and 58 microM in mice and 1.3, 18 and 37 microM in rats exposed to 62.5, 625 and 1250 p.p.m. BD respectively. Both species formed BMO from BD. In mice the respective steady-state BMO concentrations in blood were 0.6, 3.7 and 8.6 microM, compared to BMO blood concentrations in rats of 0.07, 0.94 and 1.3 microM. Mice, but not rats, had quantifiable levels of BDE in the blood. The peak concentrations of BDE in the blood of mice at 6 h were 0.65, 1.9 and 2.5 microM.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Inhalation↗

PubMed1994

Analysis of Erysipelothrix rhusiopathiae and Erysipelothrix tonsillarum by multilocus enzyme electrophoresis.

The genetic diversity of 74 Australian field isolates of Erysipelothrix rhusiopathiae and 22 reference strains for serovars of E. rhusiopathiae or Erysipelothrix tonsillarum was examined by multilocus enzyme electrophoresis. Four serovar reference strains of E. tonsillarum (strains KS 20 A, Wittling, Lengyel-P, and Bano 107 for serovars 25, 3, 10, and 22, respectively) were genetically distinct from E. rhusiopathiae. However, the E. tonsillarum reference strain for serovar 14 (Iszap-4) and the reference strain for serovar 13 (Pecs-56), which has been said to represent a new genomic species, were found to cluster with typical isolates and reference strains of E. rhusiopathiae. Our reference strain for serovar 7 (Rotzunge) was also genetically typical of E. rhusiopathiae, thus indicating that these serotype reactivities cannot be relied upon as a means of identifying isolates as E. tonsillarum. Australian field isolates of E. rhusiopathiae were genetically diverse. Those recovered from sheep or birds were more diverse than those isolated from pigs, and isolates of serovar 1 were more diverse than those of serovar 2. The diversity found among isolates of the same serovar and the presence of isolates of different serovars in the same electrophoretic types (ETs) indicated that serotyping of E. rhusiopathiae was unreliable for use as an epidemiological tool. Some ETs contained isolates recovered from different animal species. ET 41 contained 32.2% of the field isolates and two reference strains, indicating that this clone of E. rhusiopathiae is both widespread and commonly associated with disease in various species of animals.

Animals↗

PubMed1994

Resistance training increases lower body negative pressure tolerance.

This study investigated whether whole body resistance training would increase tolerance to lower body negative pressure (LBNP). Twelve males (age = 19.6 +/- 0.4 yr; mean +/- SD) underwent an acute, 12-wk program of upper and lower body resistance training (ART). Pre- and posttraining, the ART group and a control group (CON; N = 8; age = 25.4 +/- 2.4 yr) underwent LBNP tolerance tests and neck pressure-suction testing. Additionally, a group of chronically resistance-trained individuals (CRT group; N = 5; age = 22.4 +/- 0.9 yr) were tested. LBNP tolerance was increased in the ART group after training and the CRT group exhibited a significantly higher LBNP tolerance than the other groups. The ART group exhibited a decreased leg circumference change at the same absolute negative pressure at which tolerance occurred pretraining. This indicated a decreased fluid pooling after ART. The CRT group exhibited a "flattened" hypotensive portion of the carotid sinus-heart rate baroreflex curve, but this appeared to be due to the increased neck muscle mass of the subjects. We conclude that whole body ART increases LBNP tolerance possibly mediated through alterations in vascular compliance. CRT results in even greater LBNP tolerance with the responsible mediating mechanisms unclear.

Adult↗

PubMed1993

A structural motif in the variant surface glycoproteins of Trypanosoma brucei.

The variable domain of the trypanosome variant surface glycoprotein (VSG) ILTat 1.24 has been shown by X-ray crystallography to resemble closely the structures of VSG MITat 1.2, despite their low sequence similarity. Specific structural features of these VSGs, including substitution of carbohydrate for an alpha-helix, can be found in other VSG sequences. Thus antigenic variation in trypanosomes is accomplished by sequence variation, not gross structural alteration; the extensive sequence differences among VSGs may be required for another reason, such as the avoidance of recognition by helper T cells. Additionally, VSG sequences are found to define families, within a VSG superfamily, which have evolved in the trypanosome genome.

Amino Acid Sequence↗

PubMed1993

Angiotensin II receptors in rabbit vascular grafts.

New Zealand White rabbits were used as a model of autologous venous bypass grafting. A section of jugular vein was sutured into the divided common carotid artery. The animals were euthanized one month after surgery. At that time histopathology showed myointimal thickening of the graft segments. Angiotensin II receptor assays showed that the AT1 receptor was present in the grafts, concentrated in the intima. These localized receptors were shown to be similar to the prototypic vascular AT1 receptor through the use of the specific antagonist DuP 753.

Angiotensin II↗

PubMed1993

Dose-dependent urinary excretion of acrylonitrile metabolites by rats and mice.

The dose dependence of the urinary excretion of acrylonitrile (ACN) metabolites was studied after oral administration of [2,3-14C]ACN to male F-344 rats (0.09 to 28.8 mg/kg) and male B6C3F1 mice (0.09 to 10.0 mg/kg). Urine was the major route of excretion of ACN metabolites (77 to 104% of the dose), with less than 8% of the dose excreted in the feces. Reverse-phase HPLC analysis of urine from treated animals indicated five major components (1 through 5 in order of elution) that accounted for 75 to 100% of the total urinary radioactivity. Component 4 was observed in the urine of ACN-treated mice but was only present in trace amounts in the urine of ACN-treated rats. Components 1, 2, and 3 were present in the urine of animals administered [2,3-14C]cyanoethylene oxide (CEO), indicating that these components were derived from the epoxide metabolite of ACN. The ACN urinary metabolites were isolated by HPLC and identified by chromatographic and mass spectral analysis. Component 5 was N-acetyl-S-(2-cyanoethyl)cysteine and component 4 was S-(2-cyanoethyl)thioacetic acid, both derived from the glutathione (GSH) conjugate of ACN. Component 3 contained N-acetyl-S-(2-hydroxyethyl)cysteine, N-acetyl-S-(carboxymethyl)cysteine, and N-acetyl-S-(1-cyano-2-hydroxyethyl)cysteine. Component 2 was thiodiglycolic acid. These urinary metabolites are derived from catabolism of the GSH conjugates of CEO. The polar component 1 was not identified. These results demonstrate that GSH conjugation is the major disposition pathway of ACN. The excretion of metabolites derived from CEO was an approximately linear function of dose in both species, whereas the excretion of N-acetyl-S-(2-cyanoethyl)cysteine increased nonlinearly with dose. This nonlinearity indicates the presence of a saturable pathway competing with glutathione for ACN, most likely the cytochrome P450-dependent oxidation of ACN. Thiodiglycolic acid was formed 10-fold more in mice than in rats, but this species difference in the oxidative processing of GSH conjugates is probably not of toxicological significance. The ratio of ACN epoxidation to GSH conjugation was 0.50 in rats and 0.67 in mice. This species difference in ACN oxidation could have important toxicological implications, since CEO is believed to mediate the carcinogenic effects of ACN.

Acrylonitrile↗

PubMed1993

Apparatus to measure the step and frequency responses of gas analysis instruments.

The dynamic characteristics of gas analysers are often assessed by measuring the step response. It is difficult to generate a verifiable instantaneous step change in gas composition. We constructed a 0.06 ml measurement chamber connected via high-speed valves (0.5 ms response time) to two 31 reservoirs pressurized to 50 kPa with gases containing different concentrations of CO2. An electronic system opens the valves alternately depending on the polarity of a control voltage Vc. Two walls of the chamber contain narrow-band infra-red filters centered at 4.24 microns (50% transmission points at 4.16 and 4.32 microns) where CO2 absorption is high. A photoconductive infra-red sensor and an infra-red source are positioned on either side of the chamber. The output of the sensor is amplified by an instrumentation amplifier. Signal averaging of the sensor output in either the time or frequency domain was used to overcome the noise of the infra-red sensor. Step changes in Vc yielded exponentially changing outputs with a time constant of 1.1 ms. A quadrupole mass spectrometer's response to step changes in CO2 concentration generated in the measurement chamber fitted single exponential curves well with a maximum time constant of 37.7 ms and transport delay of 194 ms. The frequency response of the infra-red system, from Vc to the sensor output, fell by 0.7 dB with a phase lag of 30 degrees between 1 and 50 Hz. Using the infra-red system to measure the true input to the mass spectrometer, the frequency response of the mass spectrometer was found to fall by 35 dB with a phase lag of over 3000 degrees between 0.2 and 50 Hz. A first-order model with delay fitted to the step response predicted the mass spectrometer frequency response well below 10 Hz but overestimated the response above 10 Hz. A third-order model with delay fitted to the frequency response predicted the step response very well. Our results suggest that low-order models cannot predict the high-frequency performance of a mass spectrometer.

Carbon Dioxide↗