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Biomedical subjects

S Rimmer

Publications and source records attributed to S Rimmer.

At least 19 recordsLinked to original sources

Culture of dermal fibroblasts and protein adsorption on block conetworks of poly(butyl methacrylate-block-(2,3 propandiol-1-methacrylate-stat-ethandiol dimethacrylate)).

Amphiphilic block terpolymer conetworks composed of butyl methacrylate (BMA), 2,3 propandiol-1-methacrylate (GMMA) and ethandiol dimethacrylate (EDMA) were synthesized. Telechelic oligomers with the carboxylic acid end groups were made via ozonolysis of poly(BMA-co-butadiene) and then these were reacted with glycidyl methacrylate to obtain cross-linkable vinyl groups at both chain ends. Networks were then formed via free radical copolymerization with EDMA and GMMA or 2-methyl-acrylic acid 2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester (GMAc). The acetonide groups of the GMAc units were then removed, by reaction with selenium dioxide and hydrogen peroxide, to give networks with the same molecular structure as the GMMA terpolymers but different cell adhesion and protein adsorption properties. Protein adsorption was maximised in networks prepared with GMMA rather than with GMAc followed by removal of the acetonide. Block conetworks that were synthesised with GMAc were poor substrates for cell proliferation whilst the GMMA class support good levels of both cell viability and proliferation. It is suggested that the difference in behaviour is derived from changes in the surface composition.

Apoptosis↗

Isolated parenchymal lesions on cranial ultrasound in very preterm infants in the context of maternal infection.

AIM: To explore the associations between a clinical diagnosis of maternal infection (CDMI) and findings on the initial cranial ultrasound scan in very preterm infants. METHODS: Among infants born at less than 32 weeks gestation, cases of CDMI and controls were identified on the basis of routinely available obstetric data. Neonatal cranial ultrasound scans carried out soon after birth were retrospectively reviewed for evidence of parenchymal echodensity (PED), intraventricular haemorrhage (IVH) or PED contiguous with IVH. RESULTS: Any PED was identified in 20/40 (50%) cases of CDMI and 9/30 (30%) of controls. Logistic regression was used to adjust for differences between the two study groups. When compared with normal scans, isolated PED was more likely with CDMI odds ratio, OR (95% confidence interval, CI), 41.8 (2.64, 662) and lower Apgar score at 5 min 2.89 (1.05, 7.98). IVH was more likely with lower gestational age, OR for each completed week of gestation 0.64 (0.46, 0.88) and a protective effect of female sex, OR 0.25 (0.063, 0.98), PED contiguous with IVH was more likely with lower gestational age OR 0.59 (0.336, 1.04). CONCLUSIONS: CDMI may be associated with isolated PED in very preterm infants. We speculate that isolated PED (including "flares") identify infants who have sustained early brain injury because of intrauterine infection. Isolated PED may be a useful intermediate outcome in perinatal cohort studies.

Apgar Score↗

Synthesis and properties of amphiphilic networks 3: preparation and characterization of block conetworks of poly(butyl methacrylate-block-(2,3 propandiol-1-methacrylate-stat-ethandiol dimethacrylate)).

Amphiphilic conetwork polymers were prepared and studied as substrates in the culture of dermal fibroblasts. Both block and random conetworks polymers were produced by radical polymerization of either low-molecular weight monomers or oligomeric macromonomers. The oligomeric macromonomers were prepared by methacrylation of biscarboxy oligo(butyl methacrylates) (OBMA). The latter were synthesized by ozononolysis of poly(butyl methacrylate-co-butadiene) materials. The hydrophilic component was derived from copolymerization with 2,3 propandiol-1-methacrylate and cross-linking was provided by inclusion of ethandiol dimethacrylate (EDMA). None of the synthesized materials showed indications of cytotoxicity to human dermal fibroblasts. All of the block conetworks were highly phase separated and possessed pores on the micron length scale. The equilibrium water contents of the latter could be controlled by addition of EDMA. Block conetworks that did not contain EDMA were highly swollen and had smoother surfaces than those that contained EDMA. The former were poor substrates for cell proliferation (as measured by monitoring DNA content) whilst the latter class gave increasing levels of DNA during culture; an indicator proliferation. The performance of these materials in cell culture was also dependent on the fraction of OBMA in the formulation. Increasing the fractions of BMA, either in the random terpolymer or block networks, system had the effect of increasing both cell proliferation and viability (as measured by the Alamar Blue assay).

Biocompatible Materials↗

The value of ultrasonic examination of the lumbar spine in infants with specific reference to cutaneous markers of occult spinal dysraphism.

AIM: To present part of the rationale behind the recent update to the M12 guideline in The Royal College of Radiologists' publication "Making the best use of a department of clinical radiology", 4th edition 1998, which stated that ultrasound was useful in screening for dysraphism in infants with cutaneous markers such as sacral dimple or hairy patch. MATERIALS AND METHODS: Over a 10-year period a total of 223 infant lumbar spines were scanned, for various clinical indications. Forty of these patients had already had abnormalities detected antenatally by foetal ultrasonography. One hundred and eight-three patients had abnormalities detected on postnatal clinical examination; most of these had various cutaneous markers, some had other congenital abnormalities. RESULTS: There were a total of 29 patients with dysraphism; 24 were detected antenatally and five postnatally. Of the five, two had two or more cutaneous markers and three had anorectal anomalies. All 86 of the patients with simple sacral dimples, pits or sinuses were normal. CONCLUSION: As an isolated abnormality, simple dimples or pits are not useful markers of spinal dysraphism. The authors suggest a new imaging protocol, resulting in improved diagnostic efficiency.

Female↗

Aqueous compatible polymers in bionanotechnology.

Core-shell molecularly imprinted particles (CS-MIPs) have been synthesised using the technique of emulsion polymerisation with caffeine and theophylline being used in the surface template polymerisation with ethylene glycol dimethacrylate and oleylphenyl hydrogen phosphate. A radiolabelling study with caffeine-8-14C showed that the template was completely located at the particle surface during polymerisation. Caffeine could be specifically bound to a caffeine-imprinted CS-MIP to give a biphasic Scatchard binding curve, whereas the binding profile to a theophylline-imprinted CS-MIP was monophasic. The nanoparticles have the potential to be used in the molecular recognition of small molecules in a complex biological matrix. Water soluble highly-branched imidazole end-chain functionalised polymers of nanodimensions have also been synthesised via reversible addition-fragmentation chain transfer polymerisation. The polymers have lower critical solution temperatures which occur at sub-ambient temperatures and have proven useful in the affinity precipitation of proteins which are particularly temperature sensitive, e.g. the histidine-tagged protein fragment BRCA1. An overview of both of these areas of research is described outlining the diversity of these aqueous compatible polymers in molecular recognition processes at the nanoscale.

Biopolymers↗

Synthesis and properties of amphiphilic networks 2: a differential scanning calorimetric study of poly(dodecyl methacrylate-stat-2,3 propandiol-1-methacrylate-stat-ethandiol dimethacrylate) networks and adhesion and spreading of dermal fibroblasts on these materials.

A series of amphiphilic networks was prepared by radical copolymerisation of dodecyl methacrylate, 2,3-propandiol-1-methacrylate and ethandiol dimethacrylate. DSC studies on these materials, swollen in water. revealed that only materials containing more than 27 wt% of water displayed melting endotherms due to the melting of ice-like structures of water (freezing water). In materials that did produce a melting endotherm the peak was generally bimodal. Changing thermal history and heating rate did not effect the shape of the two peaks, nor the relative contribution of each peak to the total endothermic response. These observations and the narrow peak width of the low temperature endotherm suggested that the bimodality was an artefact of the DSC experiment and may be due to the promotion of the glass transition once a fraction of the water has frozen. The morphology of transformed human dermal fibroblasts grown on these materials was then examined by scanning electron microscopy. Compositions that contained only non-freezing water were found to allow cell adhesion and spreading. Cells with well-spread morphologies were obtained on materials containing small fractions of freezing water and dodecyl methacrylate. These fibroblasts displayed surface features such as microvilli and filapodia. However, all compositions of poly(2,3-propandiol-1-methacrylate-co-ethandiol dimethacrylate) (i.e. hydrogels that do not contain dodecyl methacrylate repeat units) were poor substrates for cell growth and examination of these materials showed that very few cells had adhered and those that did were highly rounded.

Biocompatible Materials↗

Could some fetocides be avoided by more prompt referral after diagnosis of fetal abnormality?

When a fetal abnormality has been diagnosed, a woman may be offered termination of pregnancy. It is important that delays in the assessment process are avoided, as after 21 weeks' gestation fetocide must be performed as part of the termination, with only a few rare exceptions. To determine whether preventable delays in the assessment of suspected fetal abnormalities are occurring, a retrospective review of all stillbirths resulting from termination of pregnancy in 1998 and 1999 in the North Western Region of England was conducted. There were 47 terminations of pregnancy after 24 weeks gestation. Of these, 43 cases had intracardiac potassium chloride fetocide before induction of labour. One of the 47 women was not referred to the tertiary referral centre; 39 women were referred within 1 week of the diagnosis of an abnormality, but in seven cases referral was delayed for more than 2 weeks. Inappropriate and preventable delays are occurring. In some cases this may mean that a woman has to undergo fetocide, which could have been avoided had she been referred to a tertiary centre more promptly.

Abnormalities, Multiple↗

Antenatal steroids are associated with a reduction in the incidence of cerebral white matter lesions in very low birthweight infants.

AIMS: To investigate whether antenatal steroids reduce the incidence of cerebral white matter lesions in very low birthweight infants. METHODS: A total of 224 newborn infants of < 31 weeks gestational age and weighing < 1500 g was studied between January 1998 and June 2000. Obstetric and neonatal information was obtained from the case notes. The study population was subdivided into two groups according to antenatal steroid exposure. A complete course of treatment consisted of two doses of 12 mg each of betamethasone given at an interval of 12-24 hours. Infants in group 1 were born to mothers who had not received betamethasone, or were delivered within 24 hours of receiving the first dose of steroid. Infants in group 2 were born to mothers who had received one or more complete courses of betamethasone and were delivered > 24 hours after receiving the first dose of steroid. RESULTS: The two groups contained statistically similar proportions of boys and girls, and the infants had similar birth weights and survival rates. Those in group 2, compared with those in group 1, had a lower gestational age (p = 0.02) and a lower incidence of white matter lesions on cranial ultrasound scans (p = 0.03). Stepwise logistic regression analysis showed that gestational age (p = 0.0002) and a complete course of antenatal steroids (p = 0.02) had independent effects on cerebral white matter lesions. CONCLUSIONS: These observations suggest that a complete course of antenatal steroids may have a protective effect against cerebral white matter lesions in very low birthweight infants.

Analysis of Variance↗

Synthesis and properties of amphiphilic networks. 1: the effect of hydration and polymer composition on the adhesion of immunoglobulin-G to poly(laurylmethacrylate-stat-glycerolmonomethacrylate-stat-ethylene-gly col-dimethacrylate) networks.

A series of hydrogels composed of varying fractions of dodecyl methacrylate (DM) and 2,3-dihydroxypropyl methacrylate (GM) were prepared using ethylene glycol dimethacrylate (EGDMA) as the cross-linking agent. The study found that for a series of gels with the same monomer ratio, bulk hydration could be controlled by adjusting the cross-link density. The ability to control cross-link density allowed the preparation of gels with the same bulk hydration but different ratios of the two monomers. The adsorption of IgG to the gels was investigated using ELISA. The aim of the project was to investigate the effect of the bulk hydration and polymer composition on IgG adsorption. The results show that for a series of gels with the same monomer ratio, there is a clear trend towards a reduction in protein adsorption as the bulk hydration and accompanying chain mobility of the gel increases. Studies on gels of the same bulk hydration but differing ratios of monomer show higher protein adsorption as the proportion of GM increases.

Adsorption↗

Can prognostic indicators be identified in a fetus with an encephalocele?

Encephaloceles, like other congenital malformations of the brain diagnosable in utero, can be either complicated (there being an associated chromosomal abnormality, abnormalities in the remainder of the central nervous system (CNS) and/or other organs), or isolated (no abnormalities in the chromosomes, the remainder of the CNS or other organs). Complicated cases invariably have a poor prognosis but amongst those with isolated lesions the outcome is variable with some affected children having poor mental and physical development but others who are only mildly or moderately disabled. To be able to make an informed decision about how to manage their pregnancy parents need to know what the prognosis is likely to be for their fetus with an encephalocele. To see if the necessary information could be reliably gathered by prenatal assessment of affected fetuses, a review was carried out of the medical records and ultrasound scans of 31 fetuses with encephaloceles referred to the Fetal Management Unit at St. Mary's Hospital in Manchester between January 1991 and December 1997. Eighteen of the cohort were classified as having a complicated encephalocele. Thirteen of the pregnancies were terminated; there were three intrauterine deaths, and one neonatal death. There is only one surviving child who is severely disabled. Thirteen fetuses were classified as having isolated encephaloceles, six had a mass of neural tissue in the encephalocele sac and were terminated, one died in utero and six had a cystic lesion or only a nubbin and have survived with few or no abnormalities. This study has shown that it is possible to identify fetuses with an encephalocele with a favourable outcome.

Abnormalities, Multiple↗

Pre-natal ventriculomegaly and hydrocephalus.

Ultrasonic imaging of the human fetal brain has allowed ventriculomegaly and hydrocephalus to be categorized. In this study 40 fetuses with ventriculomegaly and 21 with an Arnold-Chiari malformation and a myelomeningocele had ventriculomegaly that resolved, stabilised or progressed in utero. Within the progressive group were those with hydrocephalus, hydrocephalus being defined as expansion of the cerebral ventricular atria together with disproportionate increase in the head circumference. The prognosis for fetuses with resolving and stable ventriculomegaly was good, reflecting the fact that the ventricular dilatation in these cases was probably caused by delayed parenchymal and cerebrospinal fluid pathway development. Whereas the prognosis for progressive ventriculomegaly was generally poor, suggesting that the causes were likely to have been chromosomal, genetic, an infective agent or a catastrophic event which had an adverse effect on parenchymal development. The causes of hydrocephalus also adversely affected brain development but additional damage was caused by raised intracranial pressure.

Arnold-Chiari Malformation↗

Fetal arachnoid cysts: their site, progress, prognosis and differential diagnosis.

Arachnoid cysts are lined by arachnoid membranes and filled with cerebrospinal fluid. Etiologically, they are thought to be due to maldevelopment of the arachnoid or secondary to trauma or infection. Postnatally, many are asymptomatic and remain quiescent for years, although others expand and cause symptoms by compressing adjacent brain and/or expanding the overlying skull. Being congenital, it should be possible to identify them in the fetus, and this has proved to be so. But are they anatomically similar and do they behave the same as those detected postnatally? Fifteen fetuses with fluid-filled cysts were identified from the database of the Fetal Management Unit at St. Mary's Hospital in Manchester. Five were diagnosed at or before 20 weeks of gestation, 4 between 21 and 30 weeks, and 6 at 31 weeks or more. Thirteen cysts were in the supratentorial compartment, and 2 in the posterior fossa. Eleven fetuses were delivered, and 4 pregnancies were terminated. One of the born children had Pallister-Hall syndrome and died on day 19, and another had Aicardi's syndrome, is retarded and has fits, 1 with a posterior fossa cyst developed hydrocephalus in utero and was delivered early for the insertion of a ventriculoperitoneal shunt, he is moderately mentally delayed. Of the remaining 8 children, 1 has been lost to follow-up, and 7 appear to be reaching their early milestones on time. The 4 terminated fetuses had a postmortem examination, 2 did not have arachnoid cysts; 1 had an expanding glioependymal cyst which had destroyed most of the cerebral hemispheres, and the other had a sagittal sinus thrombosis with extensive cavitation of one cerebral hemisphere. The diagnosis of an arachnoid cyst in the fetus can be difficult and may be confused with other fluid-filled cysts.

Arachnoid Cysts↗

The epidemiology of open long bone fractures.

Open long bone fractures occur with a frequency of 11.5 per 100,000 persons per year. They are more common in males and they have a bimodal age distribution. Open fractures of the tibial diaphysis are the commonest, but open femoral diaphyseal, distal femoral and proximal tibial fractures tend to occur in the most seriously injured patients. Lower limb open fractures are more severe than open fractures of the upper limbs. Not only is the soft tissue damage less in open upper limb fractures, but there are fewer associated musculoskeletal injuries.

Accidents, Traffic↗

Pre-natal brain development of fetuses with a myelomeningocele.

Biometric measurements of 21 fetuses referred to the Fetal Management Unit at St. Mary's in Manchester with a diagnosis of myelomeningocele were analysed. Five fetuses had more than 3 sets of measurements carried out, the last of which were performed during the 3rd trimester. The majority of the head circumference measurements were on or below the 3rd percentile for normal head size whilst almost all of the cerebral ventricular atrial measurements were more than 10 mm, a figure generally accepted as being at the upper limit of normal, measurements above this indicate that ventriculomegaly is present. In normal fetuses the atrial measurement is constant at or below 10 mm throughout gestation, but in the fetuses with a myelomeningocele the atrial measurements got progressively larger as gestation proceeded. Because their head circumferences did not increase disproportionately quickly, there was no evidence that the fetuses were developing hydrocephalus in utero, rather the large atrial measurements were indicative of poor development of the cerebral hemispheres. These findings together with the Arnold-Chiari malformation and the abnormalities in the spinal cord indicate that the central nervous system in its entirety is abnormally developed in fetuses with a myelomeningocele.

Brain↗

Pre-natal diagnosis of occult spinal dysraphism by ultrasonography and post-natal evaluation by MR scanning.

Eight children born with occult spinal dysraphism were diagnosed in utero by ultrasonography. Post-natally, they were evaluated by MR scans. The ultrasound scans in all 8 fetuses revealed a spina bifida: the spinal cord was long in 5 and in 3 a meningocele was thought to be present, however, in 1, a post-natal MR scan revealed a lipomeningocele instead of a simple meningocele. In 3 fetuses an echogenic area was seen on the ultrasound scan which raised the possibility that an intradural lipoma was present, and was confirmed by post-natal MR scans. In 3 fetuses vertebral body anomalies and an additional ossification centre in a midline bony spur together with widening of the spinal canal were seen in the lower lumbar region. The lesions in all 8 fetuses were skin-covered. None had ventriculomegaly or an Arnold-Chiari malformation. The prognosis for fetuses with spina bifida aperta is well documented in contrast to that for those with spina bifida occulta. The ability to identify a spinal dysraphic lesion pre-natally allows a more accurate assessment to be made of the likely outcome for an individual fetus.

Female↗

Prenatal diagnosis of Smith-Lemli-Opitz syndrome.

An abnormality in cholesterol synthesis was described recently in the Smith-Lemli-Opitz (SLO) syndrome. Here we describe how the application of this finding has enabled an accurate prenatal diagnosis. We also discuss the possible use of this test in detecting heterozygotes.

Abnormalities, Multiple↗

Phacoemulsification in the standing position with loupe magnification and headlamp illumination.

A patient who could not recline from the seated position because of myotonic dystrophy and advanced interstitial lung disease presented to the UCLA Department of Ophthalmology Inpatient Consultation Service complaining of poor vision in both eyes as a result of corticosteroid-induced cataracts. We performed phacoemulsification and posterior chamber intraocular lens implantation in the standing position using magnifying loupes and fiber optic headlamp illumination. The excellent red reflex provided by the coaxial headlamp and the surgical control provided by bracing the operating hand against the cheek made this approach a viable option for this severely compromised patient. We discuss the surgical technique and its limitations.

Adult↗