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Biomedical subjects

M J Turner

Publications and source records attributed to M J Turner.

At least 19 recordsLinked to original sources
PubMed1992

Molecular dosimetry of ethylene oxide: formation and persistence of N-(2-hydroxyethyl)valine in hemoglobin following repeated exposures of rats and mice.

The formation of N-(2-hydroxyethyl)valine (HEVal) in hemoglobin was investigated in male F344 rats (10/group) and B6C3F1 mice (20/group) exposed to 0, 3, 10, 33, 100, or 300 (rats only) ppm ethylene oxide (ETO) by inhalation for 6 h/day for 4 weeks (5 days/week) or exposed to 100 (mice) or 300 ppm (rats) ETO for 1 or 3 days, or 1, 2, or 4 weeks (5 days/week). The persistence of HEVal was studied in animals killed up to 10 days after cessation of the 4-week time-course studies. HEVal was determined by a modified Edman degradation and quantitation of the resulting pentafluorophenylthiohydantoin derivative, using gas chromatography-mass spectrometry. The resulting experimental data were compared to simulations derived with a model for the formation and removal of hemoglobin adducts (T.R. Fennell, S.C.J. Sumner, and V.E. Walker, Cancer Epidemiol., Biomarkers & Prev., 1: 213-219, 1992). Repeated exposures of rats and mice for 4 weeks to 300 and 100 ppm ETO, respectively, led to an accumulation of HEVal that was 14 (rats) and 15 (mice) times greater than that found after 1 day of exposure [28 +/- 2 (SE) and 9.4 +/- 0.4 (SE) pmol HEVal/mg globin in rats and mice, respectively]. After cessation of exposures, HEVal was lost faster than predicted by the normal erythrocyte life span alone. An initial phase of rapid decline in HEVal concentrations was consistent with the removal of older, more heavily alkylated populations of RBCs, accompanied by a burst of erythropoiesis. The dose-response curves for HEVal were linear between 3 and 33 ppm ETO, with 3.5 +/- 0.2 and 3.4 +/- 0.3 pmol adduct/mg globin formed in rats and mice, respectively, after 4 weeks of exposure to 3 ppm ETO. Above 33 ppm ETO, the slope of the dose-response curves increased. Comparison of the dose response for HEVal in rats exposed to ETO for 4 weeks to the dose-response for N tau-(2-hydroxyethyl)histidine in rats exposed to the same concentrations of ETO for 2 years (S. Osterman-Golkar et al., Teratog. Carcinog. Mutagen., 3: 395-405, 1983) suggested that exposures to ETO can reduce the life span of erythrocytes in a concentration- and time-dependent manner. Correlation of the experimental data and simulations for the formation and removal of HEVal demonstrated that perturbations in erythropoiesis and RBC life span complicate the estimation of exposures to ETO when estimates are based upon hemoglobin adduct measurements in heavily exposed individuals.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Inhalation↗
PubMed1992

Determination of mutagenicity in tissues of transgenic mice following exposure to 1,3-butadiene and N-ethyl-N-nitrosourea.

1,3-Butadiene (BD) is carcinogenic in the B6C3F1 mouse in multiple organs, including lung and liver. We conducted a study to measure the frequency of BD mutations in mouse tissues using a transgenic mouse (Muta mouse; MM). MM is a BALB/c x DBA/2 (CD2F1) mouse that has a bacteriophage lambda shuttle vector with the target gene lacZ integrated into the mouse genome. Mice were exposed by inhalation to 625 ppm BD (6 hr/day) for 5 days and the lacZ- mutant frequency (mf) was determined in lung, bone marrow, and liver. The lacZ- mf in lung increased twofold above air-exposed control animals, but the bone marrow and liver samples did not exhibit an increase above background. N-ethyl-N-nitrosourea (250 mg/kg ip) was mutagenic in all three tissues examined. Studies on the biotransformation of BD using MM liver microsomes showed that the ratio between the rates of BD bioactivation to BD monoepoxide (BMO) and hydrolysis of BMO by epoxide hydrolases was approximately 40% less than this ratio using B6C3F1 mouse liver microsomes. Quantitation of adducts of BMO to N-terminal valine in hemoglobin (Hb) in the MM revealed an adduct level of 3.7 pmol/mg globin. Using this value, the predicted Hb adduct level in MM would be approximately one-half of that measured in the B6C3F1 mouse following similar exposures. These results indicate that BD induces mutations in vivo in a known murine target tissue, but strain differences in the biotransformation of BD should be considered in comparing the susceptibility of transgenic mouse strains to mutation.

Animals↗
PubMed1992

Mammography in hospital patients: use and misuse.

Of 1433 consecutive patients who underwent mammography, 90 were subsequently found to have histologically confirmed carcinoma of the breast (85 invasive carcinoma, three lobular carcinoma in situ, two intraduct carcinoma). Sixty (67%) of the mammograms of the patients with cancer were reported correctly as carcinoma. There were 27 (30%) false negative reports and three (3%) equivocal reports. In 14 (16%) patients with false negative reports the biopsy was delayed by between 2 and 24 months. The false reassurance of the mammogram report was responsible for the delay in diagnosis in nine and may have contributed in the remainder. The mammogram was most likely to be misleading when used as an investigation for a palpable lump in the breast. The mean age of patients with a false negative mammogram (44 years) was significantly less than that of patients with a true positive mammogram (57 years). In 23 of the 60 patients with positive mammograms management was changed as a result of the investigation. The mammogram was most helpful when no breast lump was palpable and there was either some other clinical evidence of local malignancy (ten patients, 11%) or metastatic disease (three patients, 3%), or the mammogram had been performed to screen a high-risk patient (three patients, 3%). The positive mammogram was also useful in two patients with residual or recurrent disease following local excision of a breast cancer. There were 15 patients with bilateral breast cancer (17%). Three (3%) were diagnosed within 2 months of the first tumour but mammography did not contribute to the diagnosis of any of these.

Breast Neoplasms↗
PubMed1992

Outpatient loop diathermy conization as an alternative to inpatient knife conization of the cervix.

A knife cone biopsy of the cervix is usually performed as an inpatient procedure under general anesthesia and is associated with significant morbidity. Loop diathermy conization was performed under local anesthesia on colposcopy outpatients as an alternative to knife conization. In 33 consecutive patients studied the procedure was well tolerated, there were no operative complications, and a satisfactory specimen for histologic examination was obtained in every case. One case of unsuspected invasive cancer and two of suspected microinvasive cancer were diagnosed. The diagnosis of cervical precancer was made in 24 (73%) of the cases. The introduction of outpatient loop diathermy conization of the cervix instead of knife conization would decrease hospitalization costs, avoid the need for general anesthesia and potentially reduce short-term patient morbidity.

Adult↗
PubMed1991

Outcome of the second labour in patients whose first labour was prolonged: the Dublin experience.

This observational study examined the outcome of the second delivery in patients whose first labour was prolonged. The onset of labour was defined as that time when the diagnosis of labour was made on admission to the delivery unit. The first labour was defined as prolonged when delivery occurred more than 12 h later. The study was confined to those patients (n = 66) who had a prolonged first labour with a single, live fetus and cephalic presentation during 1984-1987 and who had a subsequent labour. Sixty-one of the 66 patients (92%) delivered vaginally, and 5 were delivered by emergency caesarean section. Forty-six (70%) delivered within 6 h of admission. Although all 66 had received oxytocin in their first labour, only 8 (12%) required oxytocin in their second labour. Fourteen (82.4%) of the 17 patients with a previous caesarean section had a vaginal delivery. These results indicate that compared to the first labour the duration of the second labour and the oxytocin requirements in the second labour were significantly reduced. These findings are reassuring for patients who have had a long difficult first labour.

Delivery, Obstetric↗
PubMed1991

Evidence that patients presenting with dyskaryotic cervical smears should be screened for genital-tract infections other than human papillomavirus infection.

One hundred and fifty-four women with dyskaryotic cervical smears were referred for colposcopy from two distinct population groups, namely those who initially had attended a sexually transmitted disease (STD) clinic, and those who came from general practitioners and family planning and gynaecology clinics (non-STD group). They were investigated to determine the prevalence and pattern of concomitant lower genital-tract infections. The mean age in each group was 25 years. Microbiological studies revealed that 79 (51%) of the women were infected, more than one infection occurring in 16 (10%) of them. Infection was present in 40% of the non-STD group and 66% of the STD group. The pattern of infection was remarkably similar in each group. Bacterial vaginosis was the most common disease in each group and accounted for more than one-third of all infections detected. Six patients had genital warts, 15 harboured Chlamydia trachomatis and 4 had gonorrhoea. Two-thirds of those with C. trachomatis and half of those with gonorrhoea were asymptomatic. We conclude that an abnormal cervical smear is frequently a marker of concomitant lower genital tract infection. Comprehensive microbiological investigations in order to effect appropriate treatment are easily achieved on women in the STD group, but the cost may be seen as prohibitive for those in the non-STD group. For these women we suggest a less comprehensive microbiological approach that provides a compromise strategy of management.

Chlamydia Infections↗
PubMed1991

Evidence for superoxide formation during hepatic metabolism of tamoxifen.

Spin trapping of free radicals during the hepatic metabolism of tamoxifen was investigated; the spin trap employed in this study was 5,5-dimethyl-1-pyrroline-1-oxide (DMPO). The spin adduct 2-hydroxy-5,5-dimethyl-1-pyrrolidinyloxyl (DMPO-OH) was detected in an in vitro incubation mixture of phenobarbital-treated rat hepatocytes containing tamoxifen, dimethyl sulfoxide, and DMPO. However, since the spin adduct 2,5,5-trimethyl-1-pyrrolidinyloxyl (DMPO-CH3) was not observed, the DMPO-OH resulted from the cellular bioreduction of 2-hydroperoxy-5,5-dimethyl-1-pyrrolidinyloxyl (DMPO-OOH) by glutathione peroxidase. Addition of superoxide dismutase (SOD) to the in vitro system indicated that superoxide production was intracellular. When noninduced hepatocytes were utilized, free radical production was not evident. Thus, the cytochrome P450 monooxygenase system was responsible, in part, for the intermediacy of superoxide anion during hepatic metabolism.

Animals↗
PubMed1991

Crystallization and preliminary X-ray analysis of an intact soluble-form variant surface glycoprotein from the African trypanosome, Trypanosoma brucei.

The intact variant surface glycoprotein (VSG) ILTat 1.24 from Trypanosoma brucei has been crystallized. An amino-terminal domain of the protein comprising two thirds of the sequence had been crystallized previously after proteolytic digestion. Now intact VSG crystals have been grown from 50 mM-Mes (pH 6.5) containing 62% (w/v) saturated ammonium sulfate. The crystals are demonstrated to contain the intact VSG by h.p.l.c. gel filtration and reaction with an antibody to the inositol phosphate oligosaccharide on the VSG carboxy terminus. The space group of the crystals is P6(2)22 (or P6(4)22) with unit cell dimensions a = b = 184 A and c = 214 A. Preparative isoelectric focusing may have facilitated crystallization.

Ammonium Sulfate↗
PubMed1991

Fetal acidosis in labour: a prospective study on the effect of parity.

The effect of parity on intrapartum fetal scalp pH was investigated in 6466 patients in labour with a live fetus who were delivered in 1987. 350 (5.4%) required fetal scalp blood sampling for pH (FBS), 236 primigravidae (10.4%) and 114 multigravidae (2.7%) (P less than 0.001). Fetal acidosis (pH less than 7.20) was detected in 35 patients, 27 primigravidae (11.4%) and 8 multigravidae (7.0%) (P less than 0.001). The incidence of intrapartum acidosis in the 2275 primigravidae and the 4191 multigravidae was 1.2 and 0.2% respectively (P less than 0.001). The two deaths from birth asphyxia and three cases of neonatal seizures occurred in primigravidae. In primigravidae requiring FBS, fetal acidosis was not associated with the use of oxytocin or with increased duration of labour. Neonatal seizures were more common overall in primigravidae than in multigravidae and more common in patients requiring FBS than in those not requiring FBS (P less than 0.05). The higher incidence of FBS, fetal scalp acidosis and neonatal seizures in primigravidae has important implications for intrapartum fetal monitoring.

Acidosis↗
PubMed1991

Myelin basic protein specific T cell lines and clones derived from the CNS of rats with EAE only recognize encephalitogenic epitopes.

The epitope specificities of myelin basic protein (BP) specific T cell lines derived from the spinal cords (SC) and lymph nodes (LN) of rats with experimental autoimmune encephalomyelitis (EAE) were compared. To induce EAE, Lewis rats were immunized with guinea pig (GP)-BP and complete Freund's adjuvant. Mononuclear cells from the SC and LN of these animals proliferated in response to BP and the purified protein derivative (PPD) of mycobacterium. After initially being cultured in growth medium, SC mononuclear cells had an enhanced response to BP and lost their response to PPD. LN cells cultured in identical conditions lost their response to both BP and PPD. LN-derived BP specific cell lines recognized only two epitopes of GP-BP: an encephalitogenic epitope in residues 72-89 and a non-encephalitogenic epitope in residues 43-68. SC-derived BP specific cell lines and clones recognized the 72-89 epitope and a second encephalitogenic epitope contained in residues 87-99 but not the non-encephalitogenic 43-68 epitope. Unlike those from LN, BP-specific T cell lines and clones derived from the CNS appear to recognize only encephalitogenic epitopes, including epitopes not recognized by LN lines.

Animals↗
PubMed1991

Effect of airway inertance on linear regression estimates of resistance and compliance in mechanically ventilated infants: a computer model study.

Respiratory inertance (I) is usually ignored when resistance (R) and compliance (C) of mechanically ventilated infants are estimated by least squares linear regression. Values of I that have been reported for these patients can cause impedances whose magnitudes approximate respiratory resistance. We show theoretically that if inertance is neglected no error is expected in resistance estimates, but a positive bias in compliance can be, proportional to the inertance, the compliance, and the sinusoidal frequency at which the measurements are made. To determine the errors in parameter estimates when the pressure waveform is non-sinusoidal, we simulated linear regression based on non-inertive and inertive models. R, C, and I of the simulated lung were varied over the range expected in an infant intensive care unit. The ventilator was simulated as a critically damped second order system with a square pulse input. The rise time (TR) of the pressure pulse was varied over the range reported in infant ICUs. Simulated measurements confirmed that resistance is correctly estimated if inertance is neglected. Maximum error in compliance estimates (13%) occurred when TR and R were low, and C and I were high. The variation in the error in estimated compliance was consistent with the theory. Coefficients of variation of the parameters, the standard errors, and R2 of the regressions tended to deteriorate with increasing compliance error, but the relationships were not single valued. These statistics may alert investigators to possible bias in compliance caused by neglected inertance, but cannot be used to correct any bias.

Airway Resistance↗
PubMed1991

Species comparison of acrylonitrile epoxidation by microsomes from mice, rats and humans: relationship to epoxide concentrations in mouse and rat blood.

Acrylonitrile (ACN) has been shown to cause tumors of the brain, stomach and Zymbal's gland in rats in several bioassays, but it has not been tested in other species. The carcinogenic risk of humans exposed to ACN is unclear. ACN is metabolized in the liver to 2-cyanoethylene oxide (CEO), which is believed to be the proximate or ultimate carcinogenic species. Therefore, the kinetics of CEO formation were studied with liver and lung microsomes from mice and humans using a GC-MS assay for CEO, and the data were compared with previously obtained kinetic parameters for rat microsomal enzymes. The rate of CEO formation by human liver microsomes was comparable to that of rat liver microsomes, but less than that of mouse liver microsomes. Liver microsomes produced more CEO than lung microsomes with all three species. CEO formation by microsomes from mice was approximately 4 times greater than that by microsomes from rats or humans, suggesting that mice would have higher CEO concentrations in blood than rats after ACN exposure. However, after oral administration of ACN, the concentration of CEO in mouse blood was one-third that in rat blood at all doses and time points examined. These results show that CEO circulates via the blood, providing exposure to distant sites. The blood concentrations of CEO do not appear to correlate with rates of microsomal CEO formation. This suggests that species differences in the detoxication of CEO may play an important role in determining circulating CEO concentrations and distant organ exposure.

Acrylonitrile↗
PubMed1991

The miscarriage clinic: an audit of the first year.

We preview the results of the first year in a Miscarriage Clinic set up in 1989 in an effort to improve the support and counselling of women who have a miscarriage. Of 381 patients referred, 79% attended. The only statistically significant difference between the women who attended and those who did not attend was in the proportion of women who had planned their pregnancies (65% versus 33%, P less than 0.01). Of the 300 patients who attended, 4% reported no grief reaction; 75% experienced a reaction which had resolved within one month and 21% experienced a reaction which had not resolved. No factor was identified which could predict the duration of the grief reaction. This audit demonstrates that there is a strong demand and need for this service for couples who experience a miscarriage.

Abortion, Spontaneous↗
PubMed1991

Purification and characterization of a protective antigen from Eimeria tenella.

Chickens were partially protected against coccidiosis induced by Eimeria tenella by using extracts prepared from sonicated sporulated oocysts or from sonicated sporozoites. Following gel filtration of either extract, most of the protective antigens were confined to a single pool of proteins in the molecular mass range between 20 and 30 kDa. Further purification of proteins from the protective pool of sporulated oocyst extract yielded a protective polypeptide with a molecular mass of 26 kDa. An antiserum raised to this pool identified a polypeptide with a molecular mass of 22 kDa in the protective pool from a similarly prepared extract of sporozoites of E. tenella. In subsequent studies, this antiserum was used as an aid in cloning protective polypeptides.

Animals↗
PubMed1990

Dynamic skinfold thickness measurement in infants fed breast-milk, low- or high-sodium formula.

A stratified sample of normal infants born at term at Johannesburg Hospital, who attended the hospital for a routine 6-week follow-up visit, were selected to include 43 infants who were exclusively breast-fed, 42 fed a low-sodium formula and 39 fed a high-sodium formula (greater than 10 mmol sodium/l). Dynamic skinfold thickness measurements (DSTM), designed to assess the amount of interstitial fluid, were performed on each infant by the application of a skinfold caliper for a 3-second sampling period at two sites. The curves generated by these applications were recorded and analysed by microcomputer. There were no differences between any of the feeding groups for DSTM measurements of blood pressure suggesting that the range of sodium ingested by these groups of infants had no significant effects on extracellular water content. However, using multiple linear regression, both DSTM and blood pressure were best predicted by body weight and not by age or any other anthropometric measurement. Thus the normal postnatal decrease in extracellular fluid volume and increase in blood pressure appears to be most closely related to an increase in body weight.

Animals↗