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Biomedical subjects

R Lilford

Publications and source records attributed to R Lilford.

At least 55 records · Page 3Linked to original sources
PubMed1996

Offering patients entry in clinical trials: preliminary study of the views of prospective participants.

OBJECTIVE: To ascertain attitudes to different methods of obtaining informed consent for randomised clinical trials (RCTs). DESIGN: Structured interviews with members of the public, medical secretaries and medical students. SETTING: The public were approached in a variety of public places. Medical secretaries and students were approached in their place of work. SUBJECTS: Fifty members of the public, 25 secretaries and 25 students. MAIN OUTCOME MEASURES: Views on RCTs were elicited, with particular emphasis on how subjects thought the concept of randomisation should be explained. Each participant was presented with descriptions of proposed clinical trials and asked to select his or her preference from a range of options. RESULTS: Written information was preferred over verbal information in 91% of replies. Most respondents (86%) would prefer to sign a consent form. Of the seven statements explaining randomisation, a significant difference was found in favour of explanations that were less explicit about the play of chance (ANOVA; p = 0.0004). Eighty-three per cent of participants thought that randomised trials were morally acceptable when there was no prior medical preference between treatments. However, over half (55%) thought they would find it upsetting to be offered entry in such a trial and a quarter thought the outcome of treatment might be adversely affected. CONCLUSIONS: Our results offer some support for the idea that "economy with truth" is less unsettling than a frank description of the stark reality of what randomisation means. It is a matter of debate as to whether, if we are correct, autonomy should have precedence over beneficence. The offer of entry in a clinical trial is likely to affect the experience of care for many people, especially if the process of randomisation is described explicitly. Potential participants should be given a detailed written explanation of the rationale for the trial and be asked to sign a consent form if they agree to take part.

Analysis of Variance↗
PubMed1995

Allelic drop-out and preferential amplification in single cells and human blastomeres: implications for preimplantation diagnosis of sex and cystic fibrosis.

Previously the diagnosis of sex and cystic fibrosis status has been studied on single cells using the polymerase chain reaction (PCR). It has been suggested that allelic drop-out (PCR failure of one allele) and/or preferential amplification (hypo-amplification of one allele) may contribute to poor reliability and misdiagnosis, although this remains controversial as some reports suggest that allelic drop-out does not occur. We investigated an improved method of diagnosing sex and cystic fibrosis in single cells using a new technology (fluorescent PCR) to determine the base level of PCR artefacts (allelic drop-out and preferential amplification) which, in combination with improved sensitivity, should improve PCR reliability and accuracy. Fluorescent PCR gives high reliability (approximately 97%) and accuracy rates (approximately 97%) in somatic cells for both sex and cystic fibrosis diagnosis and its lower detection threshold allows allelic drop-out and preferential amplification to be easily distinguished. We also achieved high reliability and accuracy in diagnosing cystic fibrosis in human blastomeres. This study confirms earlier reports of both allelic drop-out and preferential amplification in single cell analysis. We demonstrate that both allelic drop-out and preferential amplification occur in somatic cells and suggest these are separate phenomena. Preferential amplification appeared common in single cell PCR while allelic drop-out apparently occurred at random in each allele. Preferential amplification was mainly amplification of the larger allele. We suggest that some inaccuracy/misdiagnosis may be due to both preferential amplification as well as allelic drop-out. Other findings were variability in drop-out between PCR and that amplification of signals from human blastomeres may be linked to embryo quality. We suggest that allelic drop-out is dependent on the number of cells within the sample.

Alleles↗
PubMed1995

Non-syncytial sources of fetal DNA in transcervically recovered cell populations.

We have previously shown that fetal DNA can be detected in swabs and flushings obtained from the lower uterine pole prior to the termination of pregnancy. The presence of syncytiotrophoblast vesicles in transcervically retrieved samples suggested that this distinctive placental tissue was an abundant source of fetal DNA and a valuable resource in prenatal diagnosis strategies. In a more extensive study involving 150 terminations of pregnancy between 7 and 17 weeks gestational age, 29% of transcervically retrieved samples contained visible syncytial vesicles. Flushing of the uterine pole more frequently contained syncytia than direct aspiration (39% compared with 26% of samples) but this difference was not statistically significant. No samples > 14 weeks gestational age contained syncytia. Polymerase chain reaction analysis using Y-sequence specific-nested primers indicated the presence of fetal DNA in the absence of intact syncytial vesicles. We therefore examined samples by in-situ hybridization using Y-specific DNA probes. Positive labelling was observed in syncytial vesicles where present and in clumps of unidentified fetal cells. In addition, high numbers of naked nuclei were labelled in samples devoid of syncytia. These isolated nuclei are possibly derived from disrupted syncytia, and may be an important and hitherto overlooked contributory factor in fetal material which collects at the lower uterine pole.

Cervix Uteri↗
PubMed1994

Case-control study of whether subfertility in men is familial.

OBJECTIVE: To test the hypothesis that subfertility in men is familial and to examine the distribution of subfertility within families for consistency with a genetic cause. DESIGN: Case-control study and segregation analysis. SETTING: Two teaching hospitals in Leeds. SUBJECTS: Cases (probands) were men with an abnormal sperm count who attended a subfertility clinic and whose partners had no major factor contravening fertility. Controls were fathers of two or more children recruited through vasectomy clinics or a maternity department. MAIN OUTCOME MEASURES: The incidence of involuntary childlessness among brothers with partners and among sisters and second and third degree male relatives. When possible clinical and laboratory details were obtained from involuntarily childless brothers. RESULTS: Seventeen of the 148 (11.5%) brothers of probands but none of the 169 brothers of controls had sought medical advice for childlessness (P < 0.0005). Four probands had more than one involuntarily childless brother. There were six further brothers whose childlessness was thought to be involuntary bringing the total prevalence of subfertility among brothers of probands to 16%. Segregation analysis was consistent with an autosomal recessive mode of inheritance accounting for 60% of subfertility in men. Seventeen of the 346 (4.9%) uncles of probands and 10 of 420 (2.8%) uncles of controls were reported to be involuntarily childless (P = 0.09), but there was no difference in childlessness among sisters. In three families sperm counts from "affected" brothers confirmed the diagnosis and showed considerable similarities within but not between families. CONCLUSION: Subfertility in men has a familial component, and the observations are consistent with an autosomal recessive mode of inheritance in over half the cases. Several different genes are probably involved.

Adult↗
PubMed1994

A meta-analysis of the therapeutic role of oil soluble contrast media at hysterosalpingography: a surprising result?

OBJECTIVE: To evaluate the therapeutic effect of oil-soluble contrast media compared with water-soluble contrast media after hysterosalpingography (HSG) in infertile couples. DESIGN: Meta-analysis of four randomized clinical trials (RCTs) and six nonrandomized controlled studies evaluating pregnancy rates after the use of oil- or water-soluble contrast media during HSG. SETTING: Institute of Epidemiology and Health Services Research, Leeds, United Kingdom. PATIENTS: Four identified RCTs studied 800 patients and six nonrandomized studies comprised an additional 1,806 patients, all experiencing primary or secondary infertility. INTERVENTION: Hysterosalpingography as part of infertility investigation. MAIN OUTCOME MEASURE: Pregnancy rates after HSG. RESULTS: Pregnancy rates were significantly higher in the oil-soluble contrast media group compared with the water-soluble contrast media group in the RCTs. Inclusion of the six nonrandomized studies did not alter this conclusion. This apparent benefit was greatest for patients with unexplained infertility. CONCLUSIONS: Oil-soluble contrast media have a therapeutic effect compared with water-soluble media and this effect is greatest for patients who have been diagnosed as having unexplained infertility. New techniques for the evaluation of tubal patency support the hypothesis that tubal "plugs" may be involved in proximal tubal blockage.

Clinical Trials as Topic↗
PubMed1994

Differential RNA fingerprinting as a tool in the analysis of spermatozoal gene expression.

The apparent decline in human male fertility and the concomitant increase in testicular pathology have prompted discussion of the underlying molecular mechanisms which may underpin these observations. While monitoring the expression of protamine-2 genes in the human ejaculate, we found a representative complement of sperm mRNAs following sequence-independent amplification of reverse-transcribed cDNAs with the polymerase chain reaction (RT-PCR). The revelation of unique sperm-derived PCR products using this method suggests that it should now be possible to investigate gene expression in human spermatogenesis by differential RNA fingerprinting of ejaculate spermatozoa. The identification of molecular markers and the corresponding genes associated with male infertility will be considerably enhanced by these investigations while obviating the requirement for invasive biopsy.

Base Sequence↗
PubMed1993

The effect on fetal arteriolar oxygen saturation resulting from giving oxygen to the mother measured by pulse oximetry.

OBJECTIVE: To determine if pulse oximetry could detect any changes in fetal arteriolar oxygen saturation resulting from maternal administration of oxygen. DESIGN: A prospective study comparing study comparing the fetal pulse oximetry reading before and after giving 27% and 100% oxygen to the mother. The data were collected using an experimental pulse oximeter and a sensor specifically adapted to cope with the problems of fetal pulse oximetry. SETTING: Labour ward, St. Jame's University Hospital, Leeds University, UK. SUBJECTS: Twelve fetuses presenting by the vertex in normal uncomplicated labour. MAIN OUTCOME MEASURES: The change in fetal arteriolar oxygen saturation recorded by the pulse oximeter in response to oxygen administration to the mother. RESULTS: Twenty-seven percent oxygen increased the average fetal arteriolar oxygen saturation by 7.5%, the effect being reversed when the oxygen was withdrawn. One hundred percent oxygen increased fetal arteriolar oxygen saturation by 11% and when the oxygen was withdrawn oxygen saturation dropped by 10%. One hundred percent inspired maternal oxygen was more effective than 27%. The gradient of the fetal oxygen regression slope is steeper with 100% oxygen than 27% and it is steeper when oxygen is given compared to when it is withdrawn. This suggests that the fetus responds to the new placental oxygen gradient by accepting oxygen more rapidly than it gives it up. Using a quadratic regression model, it took 9 min for fetal oxygen saturation to reach its maximum value after giving the mother oxygen. CONCLUSION: This study confirms that a pulse oximeter is able to measure an increase in fetal arteriolar oxygen saturation when oxygen is administered to the mother.

Arterioles↗
PubMed1992

Do fetal pulse oximetry readings at delivery correlate with cord blood oxygenation and acidaemia?

OBJECTIVE: To assess the accuracy of a pulse oximeter in the fetus. DESIGN: A prospective descriptive study, comparing oxygenation and acidaemia of cord blood with oxygen saturation in the arteries of the fetal scalp measured by a pulse oximeter just before delivery. The data were collected using an experimental pulse oximeter and a sensor specifically adapted to cope with the problems of fetal pulse oximetry. SETTING: The labour ward in a teaching hospital. SUBJECTS: Thirty seven Caucasian fetuses presenting by the vertex in normal uncomplicated labour. MAIN OUTCOME MEASURE: Fetal pulse oximetry reading shortly before birth, umbilical cord oxygenation and pH, and Apgar scores. RESULTS: Data of sufficient quality were obtained from 28 fetuses. There was a highly significant correlation between pulse oximetry reading and umbilical vein oxygen saturation r = 0.59, P = < 0.001). There was also a significant correlation between the pulse oximeter reading and cord blood pH (vein: r = 0.57, P = 0.002, artery: r = 0.63, P = 0.001). Apgar scores were not related to the oximetry results. CONCLUSION: Pulse oximetry readings reflect fetal oxygenation at birth.

Apgar Score↗