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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

Sources of error in partial rebreathing pulmonary blood flow measurements in lungs with emphysema and pulmonary embolism.

BACKGROUND: Studies of the accuracy of partial rebreathing measurements of pulmonary blood flow (PBF) in patients with abnormal lungs have not fully explained the sources of error. METHODS: We used computer models of emphysema and pulmonary embolism incorporating both ventilation-perfusion (V/Q) and ventilation-volume (V/V) heterogeneity to investigate systematic errors in partial rebreathing PBF measurements. We studied (i) errors produced under usual conditions, (ii) effects of recirculation, (iii) effects of alveolar-proximal airway and alveolar-capillary PCO2 and VCO2 differences, (iv) effects of alveolar V/Q inhomogeneity and (v) effects of rebreathing time. RESULTS: In the pulmonary embolism model the systematic error is only acceptable (<10%) when the simulated PBF is low (2-3 litre min(-1)). In the emphysema model PBF is underestimated by more than 20% at all cardiac outputs studied. Four sources of systematic errors were found. (i) Alveolar-proximal airway PCO2 gradients and flux differences between the proximal airway and alveolar compartments contribute most to the systematic error. (ii) V/Q inhomogeneity causes PCO2 gradients between the alveolar compartments and pulmonary capillary blood, and between pulmonary capillary compartments. (iii) Rebreathing times are inadequate in the presence of V/V mismatch. (iv) The apparent effect of venous blood recirculation is small in emphysema but significant in pulmonary embolism. CONCLUSIONS: We conclude that PBF cannot be measured accurately by partial rebreathing in lungs with emphysema or embolism. Systematic errors are caused mainly by errors in end-tidal PCO2 values.

Aged↗

A tidally breathing model of ventilation, perfusion and volume in normal and diseased lungs.

BACKGROUND: To simulate the short-term dynamics of soluble gas exchange (e.g. CO2 rebreathing), model structure, ventilation-perfusion (VA/Q) and ventilation-volume (VA/VA) parameters must be selected correctly. Some diseases affect mainly the VA/Q distribution while others affect both VA/Q and VA/VA distributions. Results from the multiple inert gas elimination technique (MIGET) and multiple breath nitrogen washout (MBNW) can be used to select VA/Q and VA/VA parameters, but no method exists for combining VA/Q and VA/VA parameters in a multicompartment lung model. METHODS: We define a tidally breathing lung model containing shunt and up to eight alveolar compartments. Quantitative and qualitative understanding of the diseases is used to reduce the number of model compartments to achieve a unique solution. The reduced model is fitted simultaneously to inert gas retentions calculated from published VA/Q distributions and normalized MBNWs obtained from similar subjects. Normal lungs and representative cases of emphysema and embolism are studied. RESULTS: The normal, emphysematous and embolism models simplify to one, three and two alveolar compartments, respectively. CONCLUSIONS: The models reproduce their respective MIGET and MBNW patient results well, and predict disease-specific steady-state and dynamic soluble and insoluble gas responses.

Adult↗

Utility of red flag symptom exclusions in the diagnosis of irritable bowel syndrome.

BACKGROUND: Studies suggest that the positive predictive value of the Rome II criteria for diagnosing irritable bowel syndrome can be enhanced by excluding red flag symptoms suggestive of organic diseases. AIM: We assessed the utility of red flags for detecting organic diseases in patients diagnosed irritable bowel syndrome by their physicians. METHODS: Systematic chart reviews were completed in 1434 patients with clinical diagnoses of irritable bowel syndrome, abdominal pain, diarrhoea or constipation, who also completed questionnaires to identify Rome II criteria for irritable bowel syndrome and red flag symptoms. RESULTS: The overall incidence of gastrointestinal cancer was 2.5% (but 1.0% in those with irritable bowel syndrome), for inflammatory bowel disease 2.0% (1.2% in irritable bowel syndrome), and for malabsorption 1.3% (0.7% in irritable bowel syndrome). Red flags were reported by 84% of the sample. The positive predictive value of individual red flags for identifying organic disease was 7-9%. Excluding any patient with a red flag improved the agreement between Rome II and clinical diagnosis by a modest 5%, but left 84% of patients who were diagnosed with irritable bowel syndrome by their physicians, without a diagnosis. CONCLUSIONS: Red flags may be useful for identifying patients who require additional diagnostic evaluation, but incorporating them into the Rome criteria would not improve sensitivity and would result in too many missed irritable bowel syndrome diagnoses.

Adult↗

Outcome of clinical pregnancies after ovulation induction using metformin.

The objective of this study was to review the first 50 clinical pregnancies of women with polycystic ovarian syndrome (PCOS) who had ovulation induced either with metformin alone, or in combination with clomifene. The study was confined to women with PCOS attending our infertility service. A register of clinical pregnancies was maintained of women who conceived after metformin therapy. The metformin was continued throughout the first trimester. The outcome of pregnancy was determined by individual chart review. Of the 50 women, 21 conceived with a combination of clomifene and metformin, and 29 with metformin alone. Seven women had a first trimester loss and 43 had a live birth. There were no perinatal deaths, no neonatal seizures and no congenital malformations. There were also no multiple pregnancies. The overall caesarean rate was 37%, and none of the babies had an Apgar score less than 7, at 5 min. This study found no evidence of any adverse clinical effects when metformin is continued in the first trimester of women with PCOS following ovulation induction. There was also no evidence of an increase in the rate of miscarriage or multiple pregnancy.

Adult↗

How useful is external cephalic version in clinical practice?

We reviewed retrospectively all women with a singleton breech presentation after 36 weeks' gestation who were referred for an external cephalic version (ECV) in the 3 years from 2001 - 2003. The number (n = 107) referred was low and the overall success rate of 24.5% was also low. Over the 3 years, our practice of ECV prevented only 15 caesarean sections and thus made little contribution to reducing the hospital's overall caesarean section rate. This audit highlights the need for a review of current practices in our hospital. ECV is recommended by the guidelines of the RCOG and it is a concern that the results achieved by enthusiasts of ECV may not be achieved in everyday obstetric practice.

Breech Presentation↗

Effects of alveolar dead-space, shunt and V/Q distribution on respiratory dead-space measurements.

BACKGROUND: Respiratory dead-space is often increased in lung disease. This study evaluates the effects of increased alveolar dead-space (Vd(alv)), pulmonary shunt, and abnormal ventilation perfusion ratio (/) distributions on dead-space and alveolar partial pressure of carbon dioxide (Pa(co(2))) calculated by various methods, assesses a recently published non-invasive method (Koulouris method) for the measurement of Bohr dead-space, and evaluates an equation for calculating physiological dead-space (Vd(phys)) in the presence of pulmonary shunt. METHODS: Pulmonary shunt, / distribution and Vd(alv) were varied in a tidally breathing cardiorespiratory model. Respiratory data generated by the model were analysed to calculate dead-spaces by the Fowler, Bohr, Bohr-Enghoff and Koulouris methods. Pa(co(2)) was calculated by the method of Koulouris. RESULTS: When Vd(alv) is increased, Vd(phys) can be recovered by the Bohr and Bohr-Enghoff equations, but not by the Koulouris method. Shunt increases the calculated Bohr-Enghoff dead-space, but does not affect Fowler, Bohr or Koulouris dead-spaces, or Vd(phys) estimated by the shunt-corrected equation if pulmonary artery catheterization is available. Bohr-Enghoff but not Koulouris or Fowler dead-space increases with increasing severity of / maldistribution. When alveolar Pco(2) is increased by any mechanism, Pa(co(2)) calculated by Koulouris' method does not agree well with average alveolar Pco(2). CONCLUSIONS: Our studies show that increased pulmonary shunt causes an apparent increase in Vd(phys), and that abnormal / distributions affect the calculated Vd(phys) and Vd(alv), but not Fowler dead-space. Dead-space and Pa(co(2)) calculated by the Koulouris method do not represent true Bohr dead-space and Pa(co(2)) respectively, but the shunt-corrected equation performs well.

Adult↗

Management of third degree perineal tear and choice of mode of delivery in subsequent pregnancies.

This study evaluates the management of third/fourth-degree obstetric tears and choice of mode of delivery in subsequent pregnancies amongst obstetricians practising in Ireland. Of the 185 obstetricians who were sent questionnaires 133 replied, giving a response rate of 72%. The consultant obstetricians were significantly more likely to suture third-degree tears in the labour ward than the non-consultant counterpart, P=0.04. There was no statistically significant difference between the two groups on the repair technique, P=0.397. The non-consultant obstetricians were significantly more likely to prescribe laxatives and diclofenac (Volterol) after repair of third/fourth-degree tears. There were significant differences between the two groups of obstetricians in terms of choice of mode of delivery in subsequent pregnancies, and the appropriate person to conduct labour, P=0.044 and 0.017, respectively. Instrumental intervention and use of episiotomies were similar in the two groups. Our study also shows that Fellows and Members of the Royal College of Obstetricians and Gynaecologists (RCOG) are not adhering to the guidelines on the repair of third/fourth-degree tears. We conclude that there is variation in the management of third-degree obstetric tears and choice of mode of delivery in subsequent pregnancies among the obstetricians.

Anal Canal↗

Pharmacokinetics of sevoflurane uptake into the brain.

Two recent studies have examined the pharmacokinetics of sevoflurane in adults. Lu et al.(Pharmacokinetics of sevoflurane uptake into the brain and body, Anaesthesia 2003; 58: 951-6) observed that jugular bulb sevoflurane concentration initially rose unexpectedly rapidly and then approached arterial concentrations unexpectedly slowly, suggesting that a blood-brain diffusion barrier exists. They also observed a large alveolar-arterial sevoflurane gradient, suggesting that an alveolar-arterial diffusion barrier exists. Nakamura et al. (Predicted sevoflurane partial pressure in the brain with an uptake and distribution model: Comparison with the measured value in internal jugular vein blood. Journal of Clinical Monitoring and Computing 1999; 15: 299-305) found no diffusion barriers. We used a computer model to analyse both data sets and show that the observations of Lu et al. can be explained by contamination of jugular samples with extracerebral blood. It is possible that the alveolar-arterial gradients observed by Lu et al. are due to discrepancies in conversions between blood concentrations and gas partial pressures. Our study suggests that there is no blood-brain diffusion barrier for sevoflurane and that the data of Lu et al. must be interpreted with caution.

Anesthetics, Inhalation↗

Air travel in pregnancy: the 'air-born' study.

An increasingly common question posed by patients antenatally is whether air travel can be considered safe in pregnancy. The aim of this study was to assess whether any agreed standards or policies exist between airlines with respect to flying in pregnancy. Sixty-eight international airlines were surveyed, of whom seventeen (25%) replied. Three of seventeen (17.5%) airlines applied no restrictions at all to pregnant passengers; the remainder applied restrictions to air travel with varying gestations (28 to 36 weeks). A full delivery kit was carried by 5/17 airlines (29%), and some form of training in the management of a delivery was provided to the cabin crew in 12/17 airlines (70%). Experience of in-flight obstetric emergencies was reported by 11/17 airlines (65%). This study highlights a lack of consensus regarding restrictions on air travel in pregnancy. The low response rate also suggests an unwillingness on the part of the airline industry to openly declare their policy on this issue.

Aerospace Medicine↗

Analysis of fetal DNA in the maternal venous blood for abnormalities of chromosomes 13, 16, 18 and 21 in first-trimester spontaneous miscarriage.

We investigated whether fetal DNA from the maternal blood can be used to diagnose abnormalities of chromosomes 13, 16, 18 and 21 in spontaneous miscarriage. Venous blood was obtained from 50 women with a diagnosis of spontaneous miscarriage. The evacuated products of the uterus were also sampled. DNA was extracted from both blood and tissue samples. Polymerase chain reaction (PCR) was performed using microsatellite markers for selected chromosomes. A novel technique using a capillary sequencer was employed. The electrophoretogram created was analysed using GeneScan software. The result obtained from the maternal blood samples was compared to the result obtained from uterine samples. Forty-two of the 50 (84%) cases were found to have a trisomy of one or more of the chromosomes tested on analysis of maternal blood. Compared to the overall result obtained on the uterine products of conception, the sensitivity was 97.6 and specificity 1.0. Trisomy 16 was the most common abnormality detected. These results suggest that the incidence of genetic abnormalities complicating miscarriage may be higher than suspected hitherto.

Abortion, Spontaneous↗

Acceptability of antenatal HIV testing in Ireland.

To assess the acceptability of antenatal HIV testing. A questionnaire based study. Obstetric outpatient clinic at the Portiuncula Hospital, Galway, Ireland. Women attending the antenatal clinic between May and November 2000. The participating women received pamphlets explaining HIV testing in pregnancy before completing the questionnaire. The questions included assessment of their views towards prenatal HIV testing, perceived benefits and acceptability. Seven hundred and forty-eight questionnaires were distributed. Of these 715 (96%) completed questionnaires were returned out of which 32 (4.5%) were discarded because they were improperly completed. 683 (96%) correctly completed questionnaires were analysed. 650 (95.2%) women agreed that prenatal HIV testing was a good idea and that test was necessary, 17 (2.5%) said test was not a good idea, 30 (4.4%) said test was unnecessary and 16 (2.3%) and 3 (0.4%) women were unsure whether or not test was a good idea and necessary respectively. Three hundred and sixty two (53%) women were of the opinion that prenatal HIV testing was of benefit to the mother and her baby; 301 (44%) to the mother, baby and the health workers; 14 (2%) to the baby; and 3 (0.4%) only to the mother. Only 3 (0.4%) women reported that prenatal HIV testing was of no benefit. The majority of the women, 436 (63.8%) had second level education, 202 (29.6%) received third level and 45 (6.6%) had only primary education. Antenatal HIV testing is acceptable to the majority of the obstetric population studied.

Adult↗

The effects of ventilation pattern on carbon dioxide transfer in three computer models of the airways.

We investigate the effects on arterial P(CO(2)) and on arterial-end tidal P(CO(2)) difference of six different ventilation patterns of equal tidal volume, and also of various combinations of tidal volume and respiratory rate that maintain a constant alveolar ventilation. We use predictions from three different mathematical models. Models 1 (distributed) and 2 (compartmental) include combined convection and diffusion effects. Model 3 incorporates a single well-mixed alveolar compartment and an anatomical dead-space in which plug flow occurs. We found that: (i) breathing patterns with longer inspiratory times yield lower arterial P(CO(2)); (ii) varying tidal volume and respiratory rate so that alveolar ventilation is kept constant may change both PA(CO(2)) and the PA(CO(2))-PET(CO(2)) difference; (iii) the distributed model predicts higher end-tidal and arterial P(CO(2)) than the compartmental models under similar conditions; and (iv) P(CO(2)) capnograms predicted by the distributed model exhibit longer phase I and steeper phase II than other models.

Animals↗

Evaluation of liquid-based cytology in cervical screening of high-risk populations: a split study of colposcopy and genito-urinary medicine populations.

A split study evaluated the ThinPrep(R) PapTesttrade mark (TP; Cytyc Corp., Boxborough, MA) compared with current methodologies of cervical cytology in two high-risk cohorts. One thousand, three hundred cases from a colposcopy clinic and a genito-urinary medicine outpatient clinic were examined. The TP reported increased detection of all grades of dyskaryosis (mild, moderate and severe; + 4.5%) and a decrease in borderline and unsuitable cases (- 4.9%). Four cases of high-grade dyskaryosis (moderate or severe) were detected only using the TP, while an additional four cases classified as high-grade dyskaryosis with the TP were reported as borderline by our conventional methods. The split-study finding of increased sensitivity with the TP provides for improved clinical management of patients in our high-risk cohorts.

Cell Nucleus↗

Dendritic cells transduced with HSV-1 amplicons expressing prostate-specific antigen generate antitumor immunity in mice.

There is currently much interest in generating cytotoxic T lymphocyte (CTL) responses against tumor antigens as a therapy for cancer. This work describes a novel gene transfer technique utilizing dendritic cells (DCs), an extremely potent form of antigen-presenting cell (APC), and herpes simplex virus-1 (HSV-1) amplicons. HSV-1 amplicons are plasmid-based viral vectors that are packaged into HSV-1 capsids, but lack viral coding sequences. Amplicon vectors have been constructed that encode the model tumor antigen ovalbumin (HSV-OVA) and human prostate-specific antigen (HSV-PSA), a protein that is expressed specifically in prostate epithelium and prostate carcinoma cells. These amplicons were packaged using a helper virus-free system that produces vector stocks that are devoid of contaminating cytotoxic helper virus. Transduction of DCs with HSV-OVA or HSV-PSA and co-culture with CTL hybridomas results in specific activation, indicating that transduced DCs express these transgenes and process the tumor antigens for class I MHC presentation to CTL. Mice immunized with HSV-PSA-transduced DCs generate a specific CTL response that can be detected in vitro by a (51)Cr-release assay and are protected from challenge with tumors that express PSA. These results indicate that DCs transduced with HSV-1 amplicon vectors may provide a tool for investigation of the biology of CTL activation by DCs and a new modality for immunotherapy of cancer.

Animals↗