Editorial comment on Geographical differences in cancer incidence in the Belgian Province of Limburg by Bruntinx and colleagues.
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Belgium↗
Biomedical subjects
N Best
Publications and source records attributed to N Best.
Comparison of UK paediatric cardiac surgical performance by analysis of routinely collected data 1984-96: was Bristol an outlier?
BACKGROUND: Reports of high mortality after paediatric cardiac surgery at the Bristol Royal Infirmary, UK, led to the establishment of an independent public inquiry. A key question was whether or not the mortality statistics in Bristol were unusual compared with other specialist centres. To answer this question, we did a retrospective analysis of mortality in the UK using two datasets. METHODS: Data from the UK Cardiac Surgical Register (CSR; January, 1984, to March, 1996) and Hospital Episode Statistics (HES; April, 1991, to December, 1995) were obtained for all 12 major centres in which paediatric cardiac surgery is done in the UK. The main outcome measure was mortality within 30 days of a cardiac surgical procedure. We estimated excess deaths in Bristol using a random-effects model derived from the remaining 11 centres. Additionally, a sensitivity analysis was done and case-mix examined. FINDINGS: For children younger than 1 year, in open operations, the mortality rate in Bristol was around double that of the other centres during 1991-95: within the CSR, there were 19.0 excess deaths (95% interval 2-32) among 43 deaths; and in HES, there were 24.1 excess deaths (12-34) among 41 deaths recorded. There was no strong evidence for excess mortality in Bristol for closed operations or for open operations in children older than 1 year. INTERPRETATION: Our results suggest that Bristol was an outlier, and we do not believe that statistical variation, systematic bias in data collection, case-mix, or data quality can explain a divergence in performance of this size.
Adolescent↗
Spatial variation and temporal trends of testicular cancer in Great Britain.
Increases in testicular cancer incidence have been reported in several countries over a long period. Geographical variability has also been reported in some studies. We have investigated temporal trends and spatial variation of testicular cancer at ages 20-49 in Britain. Temporal trends in testicular cancer incidence were examined, 1974 to 1991 and in mortality, 1981-1997. Spatial variation in incidence was analysed across electoral wards, 1975 to 1991. We used Poisson regression to examine for regional and socio-economic effects and Bayesian mapping techniques to analyse small-area spatial variability. Incidence increased from 6.5 to 11.1 per 100 000 in men at ages 20-34, and from 5.6 to 9.7 per 100 000 in men at ages 35-49, while mortality declined by 50% in both age groups. Risks of testicular cancer varied across regional cancer registries, ranging from 0.79 (95% CI: 0.73-0.84) to 1.32 (95% CI: 1.25-1.38), and was higher in the most affluent compared with the most deprived areas. Analyses within 2 regions (one predominantly urban, the other predominantly rural) did not indicate any localized geographical clustering. The increasing incidence contrasted with a decreasing mortality over time in Great Britain, similar to that found in other countries. The higher risk in more affluent areas is not consistent with findings on social class at the individual level. The absence of any marked geographical variability at small area scale argues against a geographically varying environmental factor operating strongly in the aetiology of testicular cancer.
Adult↗
Stillbirth and neonatal mortality due to congenital anomalies: temporal trends and variation by small area deprivation scores in England and Wales, 1986-96.
We investigated the variation of stillbirth and neonatal mortality due to congenital anomalies in relation to small-area measures of deprivation in a population-based study in England and Wales, 1986-96. We found 10 954 stillbirths and neonatal deaths from all non-chromosomal and chromosomal anomalies during the study period out of a total of 7 487 007 live and stillbirths. The extended perinatal mortality rate (EPM rate) (defined as babies who were stillborn or died within 28 completed days after birth per 10 000 total live and stillbirths) for all chromosomal and all non-chromosomal anomalies was 1.5/10 000 and 13.2/10 000, respectively, over the whole period. The rate for non-chromosomal anomalies halved over the decade while the rate for chromosomal anomalies remained unchanged. The relative risks of EPM for chromosomal and non-chromosomal anomalies were 0.71 [0.80, 0.95] and 1.17 [95%CI 1.06, 1.30], respectively, in the group of wards with highest deprivation compared with the least deprived group. Increasing gradients of EPM with increasing deprivation were observed for (1) grouped non-chromosomal anomalies including neural tube defects, all renal and urinary anomalies, all musculoskeletal anomalies, and multiple anomalies, and (2) several specific non-chromosomal anomalies including anencephaly, limb reduction defects, diaphragm and abdominal wall defects. This study provides strong evidence that increased deprivation is associated with increased EPM due to most non-chromosomal anomalies; the finding of decreased relative risk for chromosomal anomalies is probably related to differences in maternal age distribution between deprivation groups.
Chromosome Aberrations↗
Use of routinely collected data on trihalomethane in drinking water for epidemiological purposes.
OBJECTIVES: To explore the use of routinely collected trihalomethane (THM) measurements for epidemiological studies. Recently there has been interest in the relation between byproducts of disinfection of public drinking water and certain adverse reproductive outcomes, including stillbirth, congenital malformations, and low birth weight. METHOD: Five years of THM readings (1992--6), collected for compliance with statutory limits, were analysed. One water company in the north west of England, divided into 288 water zones, provided 15,984 observations for statistical analysis. On average each zone was sampled 11.1 times a year. Five year, annual, monthly, and seasonal variation in THMs were examined as well as the variability within and between zones. RESULTS: Between 1992 and 1996 the total THM (TTHM) annual zone means were less than half the statutory concentration, at approximately 46 microg/l. Differences in annual water zone means were within 7%. Over the study period, the maximum water zone mean fell from 142.2 to 88.1 microg/l. Mean annual concentrations for individual THMs (microg/l) were 36.6, 8.0, and 2.8 for chloroform, bromodichloromethane (BDCM), and dibromochloromethane (DBCM) respectively. Bromoform data were not analysed, because a high proportion of the data were below the detection limit. The correlation between chloroform and TTHM was 0.98, between BDCM and TTHM 0.62, and between DBCM and TTHM -0.09. Between zone variation was larger than within zone variation for chloroform and BDCM, but not for DBCM. There was only little seasonal variation (<3%). Monthly variation was found although there were no consistent trends within years. CONCLUSION: In an area where the TTHM concentrations were less than half the statutory limit (48 microg/l) chloroform formed a high proportion of TTHM. The results of the correlation analysis suggest that TTHM concentrations provided a good indication of chloroform concentrations, a reasonable indication of BDCM concentrations, but no indication of DBCM. Zone means were similar over the years, but the maximum concentrations reduced considerably, which suggests that successful improvements in treatment have been made to reduce high TTHM concentrations in the area. For chloroform and BDCM, the main THMs, the component between water zones was greater than variation within water zones and explained most of the overall exposure variation. Variation between months and seasons was low and showed no clear trends within years. The results indicate that routinely collected data can be used to obtain exposure estimates for epidemiological studies at a small area level.
Analysis of Variance↗
A study of the variation in tuberculosis incidence and possible influential variables in Manchester, Liverpool, Birmingham and Cardiff in 1991-1995.
SETTING AND OBJECTIVE: The reversal of the decline in United Kingdom tuberculosis rates has sparked a resurgence of interest in the epidemiology and prevention of tuberculosis in the UK. In this paper we quantify the primary factors explaining the variability in the electoral ward level relative risk of tuberculosis in Manchester, Liverpool, Birmingham and Cardiff. DESIGN: Ecological analysis of the incidence of tuberculosis in 397 wards using hospital admissions data as a proxy for tuberculosis incidence. Admissions were evaluated from the financial years 1991/1992 to 1994/1995. Ward level covariates included measures of country of birth, ethnicity and various socio-economic measures. RESULTS: Separate analyses were carried out for pulmonary and non-pulmonary tuberculosis. For pulmonary tuberculosis the final model included measures of the ward population born in India and Pakistan, overcrowded housing and not-owner-occupied housing. For non-pulmonary tuberculosis the covariates were ward population born in India and Pakistan, overcrowded housing and the proportion of households with no car. CONCLUSIONS: The country of birth of the ward population is the single most influential explanatory factor in the variability of the ward rates for both pulmonary and non-pulmonary tuberculosis in these four cities. Measures of poverty are of secondary importance.
Adolescent↗
Five-year incidence and prediction of dementia and cognitive decline in a population sample of women aged 70-79 at baseline.
OBJECTIVE: To determine the incidence of dementia and cognitive decline and their predictors in a population sample. SETTINGS: A rural geographically defined population served by a single health centre. SAMPLE: 75% of the 70-74-year-old, 100% of the 75-79-year-old women registered with the practice. METHOD: Interview the total sample using an augmented version of CAMDEX, including informant interview, and reaction times at baseline and 5 years later. IQ was estimated at baseline only. RESULTS: 365 women were interviewed at baseline, 237 at follow-up. Incidence of dementia of all severities was 3.1% per annum (95% CI, 2.2-4.3). CAMCOG declined by 12.6 points in those who became demented, MMSE by 3 points. Observed, self-reported and informant-reported cognitive difficulty at baseline all predicted later incidence of dementia. The additional use of estimated IQ and reaction times did not increase the efficiency of either cross-sectional detection of dementia or prediction of dementia at 5 years. CONCLUSIONS: The incidence of dementia was in the range reported by other studies; slight cognitive decline was noted in the total population, increasing with age and marked in incident dementia. Of clinical importance was the finding that both the individuals and the informants of those who subsequently demented were aware of decline 5 years earlier. Simple and relatively easily administered cognitive tests were found to be the most efficient method of detection of dementia.
Aged↗
Hippocampal NPY neurons project to the fascia dentata in organotypic cultures.
The distribution of neuropeptide Y immunoreactive (NPY-ir) neurons in organotypic cultures of hippocampi from neonates was compared to that seen in adult rats. In addition to the known NPY-ir neurons in the hippocampus proper and in the hilus of the fascia dentata, isolated, large, multipolar, NPY-ir neurons were observed in the subiculum and in areas CA1 and CA3. Their axons projected into stratum radiatum of the hippocampus proper and into the molecular layers and hilus of the fascia dentata where they branched profusely. These NPY-ir neurons were regularly distributed throughout the septo temporal extent of the hippocampus and were present in both neonates and adult hippocampi. The hilar NPY-ir neurons have always been considered the source of the NPY-ir plexus in the outer molecular layer of the dentate gyrus. However, our results show that there is also a contribution from the NPY-ir neurons in the hippocampus proper.
Animals↗
The limiting mobility of DNA sequencing fragments for both cross-linked and noncross-linked polymers in capillary electrophoresis: DNA sequencing at 1200 V cm-1.
The mobility of DNA sequencing fragments was measured in Long-Ranger gels at an electric field ranging from 200 to 1200 V cm-1 and in noncross-linked polyacrylamide at electric fields ranging from 100 to 300 V cm-1. In both cases, N*, the fragment length that denotes the onset of biased reptation with orientation, is inversely proportional to electric field. The inverse dependence of N* is inconsistent with the original biased reptation model but is consistent with modern models of DNA migration. While separation speed increases dramatically with electric field, the number of bases determined in a separation decreases in proportion to field strength. We present a DNA sequencing run at an electric field of 1200 V cm-1. Roughly 200 bases of sequence are determined in 3.5 min.
Base Sequence↗
Pre-exposure to subtoxic levels prevents kainic acid lesions in organotypic hippocampal slice cultures: effects of kainic acid on parvalbumin-immunoreactive neurons and expression of heat shock protein 72 following the induction of tolerance.
The effects of kainic acid on the survival of principal neurons and parvalbumin-immunoreactive (PARV-IR) neurons, and on the expression of heat shock protein 72 immunoreactivity (HSP72-IR) were investigated in organotypic hippocampal slice cultures. Untreated cultures displayed an organotypic organization and the development and morphology of PARV-IR neurons in the hippocampus paralleled that reported to occur in vivo, with the exception of the hilar region of the dentate gyrus which exhibited a marked lack of PARV-IR neurons. No constitutive expression of HSP72 was found in untreated cultures. The lesion of CA3 neurons and the reduction in numbers of PARV-IR neurons in both CA3 and CA1 after chronic exposure to 5 microM kainic acid were similar to those reported to occur in vivo. Exposure to 1 microM doses of kainic acid resulted in a widespread appearance of HSP72-IR and the induction of tolerance to a previously toxic dose of kainic acid. These results suggest the presence of endogenous neuroprotective mechanisms, activated by a stress response which induces HSP72, and is reminiscent of the induced tolerance reported to occur after a mild ischaemic insult.
Animals↗
Separation of fragments up to 570 bases in length by use of 6% T non-cross-linked polyacrylamide for DNA sequencing in capillary electrophoresis.
Non-cross-linked polyacrylamide is a very convenient medium for the separation of DNA sequencing fragments in capillary electrophoresis. We demonstrate DNA sequencing with this matrix at an electric field of 200 V/cm and at room temperature. Resolution is observed to decrease exponentially with fragment length. Fragments 570 bases in length generate a resolution of 0.5, which is adequate for sequence identification.
Cross-Linking Reagents↗
Ultrastructure of parvalbumin-immunoreactive neurons in the CA1 area of the rat hippocampus following a kainic acid injection.
Non-pyramidal neurons which contain the calcium-binding protein parvalbumin (PV) were examined, at the ultrastructural level, in the CA1 area of the normal hippocampus and following a unilateral intracerebroventricular kainic acid (KA) injection. Many degenerating PV-immunoreactive (IR) neurons were identified in the ipsilateral strata oriens and pyramidale at 3 days post-lesion and some were seen in stratum oriens of the contralateral CA1 area. A few PV-IR neurons remained resistant to the effects of KA. A chronic, almost total loss of PV-IR terminals was detected around the soma of the ipsilateral CA1 pyramidal neurons. However, the PV-IR terminals around the axon initial segments of the CA1 pyramidial neurons remained intact at all post-lesion survival times in both ipsilateral and contralateral tissue. The examination of serial ultrathin sections established the origin of the PV-IR terminals around the axon initial segments to be the KA-resistant PV-IR neurons in stratum pyramidale. This data provides evidence for the loss of non-pyramidal neurons following a KA lesion together with evidence for a surviving inhibitory circuit that could, if functional, provide a very strong inhibitory control of pyramidal neurons.
Animals↗
Changes in parvalbumin-immunoreactive neurons in the rat hippocampus following a kainic acid lesion.
Changes in a sub-population of hippocampal non-pyramidal neurons following a unilateral lesion with kainic acid were examined using an antibody raised against the Ca-binding protein parvalbumin. A loss of 71-97% of the parvalbumin-immunoreactive neurons occurred at the three post-lesion times studied (1, 2 and 4 weeks) in all areas of the ipsilateral hippocampus, but no such loss was observed in the dentate gyrus. Resistant parvalbumin-immunoreactive neurons occurred principally in stratum pyramidale and displayed altered morphology from the normal with swollen dendrites and dendritic varicosities. The contralateral hippocampus exhibited losses of parvalbumin-immunoreactive cells, but this was restricted to stratum oriens of CA1. This data demonstrates the loss of a specific and important population of non-pyramidal neurons which might be responsible for the chronic loss of functional inhibition seen in this animal model of temporal lobe epilepsy.
Animals↗
The use of sodium sulphide-fixed brain tissue for immunocytochemical staining of activated microglia and reactive astrocytes.
The use of sodium sulphide-perfused material for the immunocytochemical demonstration of microglia and astrocytes is described. An intracerebroventricular injection of kainic acid (KA) was used to induce neuronal degeneration and subsequent axonal sprouting in the hippocampus. Animals under deep anaesthesia were killed by perfusion with either 4% paraformaldehyde alone or with 1% sodium sulphide followed by 4% paraformaldehyde solution. Microglial cells were identified with OX-42, a monoclonal antibody towards CR3 complement receptors, and astrocytes with a polyclonal antibody to glial fibrillary acidic protein (GFAP). The present study reveals a marked enhancement in the immunoreactivity of activated microglial cells in sodium sulphide perfused tissues compared to those observed in tissues fixed in paraformaldehyde alone. GFAP immunoreactivity of the astrocytes was not compromised by the use of sodium sulphide. The results clearly show the suitability of sodium sulphide perfused tissues for immunocytochemical procedures and should provide a useful tool for investigation of the role of neuroglial cells in axonal sprouting.
Animals↗
Comparative evaluation of propofol or methohexitone as the sole anaesthetic agent for microlaryngeal surgery.
Propofol or methohexitone was given to the same twenty patients on two separate occasions during total intravenous anaesthesia for microlaryngeal surgery. With propofol the quality of induction was superior. Fewer patients required supplementation. Heart rate and blood pressure were well controlled at levels of 110-120% baseline. There were fewer side-effects during maintenance and recovery. Patients were able to return home earlier. However, apnoea and pain on injection occurred frequently, the latter when injection was made into the dorsum of the hand. With methohexitone, apnoea, abnormal movement, nausea, vomiting, headache, restlessness and confusion were common. Cardiovascular variables were poorly maintained at levels of 170-180% baseline. The results suggest that propofol is suitable as the sole anaesthetic agent in patients undergoing microlaryngeal surgery.
Anesthesia, Intravenous↗
Complement activation during cardiopulmonary bypass by heparin-protamine interaction.
Circulating concentrations of split products of the third complement factor (C3c and C3d) were measured in five patients before, during and after cardiopulmonary bypass. In all patients, C3d concentrations increased significantly in samples obtained after the administration of protamine sulphate. Similarly, circulating C3c was seen only in those samples obtained immediately after protamine administration. In vitro experiments demonstrated that activation of the complement system was attributable to the heparin-protamine complex, and was dose-dependent. The activation of complement was not associated with any clinically detectable adverse effects.
Adult↗
Classical pathway activation during an adverse response to protamine sulphate.
A severe anaphylactoid reaction was observed following the i.v. administration of protamine sulphate in a 66-year-old male undergoing coronary artery catheterization. Serial measurements of complement factors (C3 and C4) and C3 split products (C3c and C3d) were performed by conventional electro-immunoassays and by double zone rocket immunoelectrophoresis. A parallel decrease in circulating C3 and C4 concentrations was seen for 1 h, reaching a nadir at 1.3 h. Markedly increased concentrations of C3c and C3d were observed in the first sample examined after exposure to the drug. C3c and C3d concentrations gradually declined to the normal range within 5.9 h and 21.8 h, respectively. These observations are discussed in relation to the mechanism of this adverse reaction.
Aged↗
Demonstration of antigenic determinants specific for the split products of the third complement factor, C3.
Crossed anti-C3c immunoelectrophoresis of a plasma sample with in vivo complement activation revealed a pronounced 'spur' formation towards the cathodic region of immunochemical interaction between native C3 and C3c. In situ absorption of the antibody preparation against C determinants of the 3rd complement factor using fresh normal EDTA plasma as antigen demonstrated the presence of C3 split product specific determinants.
Antibody Formation↗