Biomedical subjects

J E Scott

Publications and source records attributed to J E Scott.

At least 19 recordsLinked to original sources

PubMed2004

Stachybotrys chartarum alters surfactant-related phospholipid synthesis and CTP:cholinephosphate cytidylyltransferase activity in isolated fetal rat type II cells.

Stachybotry chartarum, a fungal contaminant of water-damaged buildings commonly grows on damp cellulose-containing materials. It produces a complex array of mycotoxins. Their mechanisms of action on the pulmonary system are not entirely clear. Previous studies suggest spore products may depress formation of disaturated phosphatidylcholine (DSPC), the major surface-active component of pulmonary surfactant (PS). If S. chartarum can indeed affect formation of this phospholipid, then mold exposure may be a significant issue for pulmonary function in both mature lung and developing fetal lung. To address this possibility, fetal rat type II cells, the principal source of DSPC, were used to assess effects of S. chartarum extract on formation of DSPC. Isolated fetal rat lung type II cells prelabeled with 3H-choline and incubated with spore extract showed decreased incorporation of 3H-choline into DSPC. The activity of CTP:cholinephosphate cytidylyltransferase (CPCT), the rate-limiting enzyme in phosphatidylcholine synthesis was reduced by approximately 50% by a 1:10 dilution of spore extract. Two different S. chartarum extracts (isolates from S. chartarum (Cleveland) and S. chartarum (Hawaiian)) were used to compare activity of CPCT in the presence of phosphatidylglycerol (PG), a known activator. PG produced an approximate two-fold increase in CPCT activity. The spore isolate from Hawaii did not alter enzyme activity. S. chartarum (Cleveland) eliminated the PG-induced activation of CPCT. These results support previous observations that mold products alter PS metabolism and may pose a risk in developing lung, inhibiting surfactant synthesis. Different isolates of the same species of fungus are not equivalent in terms of potential exposure risks.

Animals↗

PubMed2003

Elasticity in extracellular matrix 'shape modules' of tendon, cartilage, etc. A sliding proteoglycan-filament model.

Connective tissues (CTs), which define bodily shape, must respond quickly, robustly and reversibly to deformations caused by internal and external stresses. Fibrillar (elastin, collagen) elasticity under tension depends on molecular and supramolecular mechanisms. A second intra-/inter-molecular pair, involving proteoglycans (PGs), is proposed to cope with compressive stresses. PG interfibrillar bridges ('shape modules'), supramolecular structures ubiquitously distributed throughout CT extracellular matrices (ECMs), are examined for potential elastic properties. L-iduronate residues in shape module decoran PGs are suggested to be molecular springs, cycling through alternative conformations. On a larger scale, anionic glycosaminoglycan (AGAG) interfibrillar bridges in shape modules are postulated to take part in a sliding filament (dashpot-like) process, which converts local compressions into disseminated tensile strains. The elasticity of fibrils and AGAGs, manifest at molecular and larger-scale levels, provides a graduated and smooth response to stresses of varying degrees. NMR and rheo NMR, computer modelling, electron histochemical, biophysical and chemical morphological evidence for the proposals is reviewed.

Aggrecans↗

PubMed2002

Tetrahydrocannabinol (THC) alters synthesis and release of surfactant-related material in isolated fetal rabbit type II cells.

Over the years, there has been a great deal of interest in the biological consequences of marijuana use. While evidence indicates that cannabinoids may have therapeutic uses in alleviating certain disease discomfort, there is little recent information on potential health risks, particularly related to the developing fetus. The present study was undertaken to determine the effects of delta 9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana on fetal lung development specifically related to surfactant production. The rationale for the choice of this model lies in the importance of adequate lung development and surfactant production for the successful transition of the fetus to an air-breathing environment. Lung type II cells, the source of pulmonary surfactant, were isolated from fetal rabbit lungs on the 24th gestational day and incubated concurrently with various concentrations of THC and [3H]choline to label disaturated phosphatidylcholine (DSPC) the major surface-active phospholipid of surfactant. Under these conditions THC significantly reduced radiolabelling of DSPC and at the highest concentration (10(-4) M) induced release of DSPC. Pulse-chase studies were also conducted. Cells were prelabelled with [3H]choline, removed to fresh medium with THC (10(-4) M) and incubated for various time periods. Aqueous- and organic-soluble intermediates of DSPC formation were isolated. THC induced a significant increase in radiolabelling of CDPcholine, the rate-limiting conversion in DSPC synthesis. Radiolabelling of total phosphatidylcholine and DSPC was also significantly increased. Assay of CTP: cholinephosphate cytidylyltransferase which enzymatically converts cholinephosphate to CDPcholine showed that THC and phosphatidylglycerol (PG) both induced activation of the enzyme in fetal lung cytosol but not in the membranes. This effect of THC and PG was not additive. THC activated the enzyme only in fetal and not adult rabbit lung. The ability of THC to induce release of surfactant related material was also examined. In cells prelabelled with [3H]choline, THC induced release of [3H]DSPC in both cultured and freshly isolated fetal type II cells. These results suggest THC reduces formation of surfactant DSPC, probably through alterations in membrane dynamics. However, intracellular THC may actually increase formation of DSPC through an effect on the rate-limiting enzyme. THC also increases release of previously formed surfactant-related material.

Animals↗

PubMed2002

The first and second 'laws' of chemical morphology, exemplified in mammalian extracellular matrices.

Tissues are supramolecular organisations. The permanent and semi-permanent biopolymers therein function collaboratively in specifically bonded frameworks of macromolecules according to the physico-chemical laws that govern the behaviour of all molecules. In this paper two 'laws' or principles are discussed which give insights into the development and function of tissues, particularly the extracellular matrices (ECMs) of connective tissues. The first 'law' is qualitative;- The shape of a tissue is implicit in the shapes of the biopolymers from which it is constructed. The tissue biopolymers are jigsaw pieces, if they don't fit precisely, there is no picture. The second 'law' is quantitative;-The composition of a tissue is determined by the stable, specific interactions between the macromolecules of which it is constructed. These basic ideas underlie the discipline of chemical morphology. The term chemical morphology implies both the chemistry of shape and the shape of chemicals. The first meaning is well exemplified in the ECMs of connective tissues, in which the shape of an organism is defined and maintained. Specific relationships between the fibrillar (collagenous) components and the soluble polymers (proteoglycans) are set in the context of the first law. Tissue electron histochemistry (the morphology of the tissue) and knowledge of secondary and tertiary structures of the participating biopolymers (the shapes of the chemicals) together provide a model susceptible to quantitative testing. Simple calculation shows that the amount of any ligand (e.g. a proteoglycan) specifically bound at a single binding site per unit of collagen fibril length (the D period) increases linearly with the fibril diameter. Given the amount of collagen (measured as hydroxyproline) and its density, the constant of proportionality is approximately 42. Comparisons of the quantitative relationship between collagen and proteoglycans predicted from the model agree well with those obtained by biochemical analyses of different tendons from three species at all stages of development. Thus, the second 'law' appears to hold in this case.

Animals↗

PubMed2001

Development of an internally quenched fluorescent substrate and a continuous fluorimetric assay for Streptococcus pneumoniae signal peptidase I.

Signal peptidase (SPase) I is responsible for the cleavage of signal peptides of many secreted proteins in bacteria and serves as a potential target for the development of novel antibacterial agents due to its unique physiological and biochemical properties. In this paper, we describe a novel fluorogenic substrate, KLTFGTVK(Abz)PVQAIAGY(NO2)EWL, in which 2-aminobenzoic acid (Abz) and 3-nitrotyrosine (Y(NO2)) were used as the fluorescent donor and acceptor, respectively. The substrate can be cleaved by both Streptococcus pneumoniae and Escherichia coli SPase I. Upon cleavage of the fluorogenic substrate by SPase I, the fluorescent intensity increases and can be monitored continuously by spectrofluorometer. Kinetic analysis with S. pneumoniae SPase I demonstrated that the K(m) value for the substrate is 118.1 microM, and the k(cat) value is 0.032 s(-1). Mass spectrometric analysis and peptide sequencing of the two cleaved products confirmed that the cleavage occurs specifically at the predicted site. More interestingly, the positively charged lysine in the N-terminus of the substrate was demonstrated to be important for effective cleavage. Phospholipids were found to stimulate the cleavage reaction. This stimulation by phospholipids is dependent upon the N-terminal charge of the substrate, indicating that the interaction of the positively charged substrate with anionic phospholipids is important for maintaining the substrate in certain conformation for cleavage. The substrate and assay described here can be readily automated and utilized for the identification of potential antibacterial agents.

Amino Acid Sequence↗

PubMed2001

Periprosthetic bone mineral density changes with femoral components of differing design philosophy.

We measured the bone mineral density in 22 patients with the cylindrical stemmed cobalt-chrome AML prosthesis (collared) and in 22 patients with the tapered stem titanium CLS prosthesis (collarless). DEXA scanning was undertaken at a mean of 40 months in the AML and 52 months in the CLS group from the time of implant insertion. In both groups the greatest mean loss of BMD was found in Gruen zone 7 and the least change in Gruen zone 5. In all zones the BMD loss was greater in the AML group but only statistically significant in zones 6 (P<0.05) and 7 (P<0.01). Although numerous factors affect BMD changes around cementless implants, this study suggests that less bone loss can be associated with the titanium CLS stem.

Absorptiometry, Photon↗

PubMed2001

Analysis of pulmonary surfactant by Fourier-transform infrared spectroscopy following exposure to Stachybotrys chartarum (atra) spores.

Lung cells are among the first tissues of the body to be exposed to air-borne environmental contaminants. Consequently the function of these cells may be altered before other cells are affected. As gas exchange takes place in the lungs, changes in cellular function may have serious implications for the processes of oxygen uptake and carbon dioxide elimination. In order for these processes to occur, the lung must maintain a high degree of expandability. This latter function is accomplished in part by the pulmonary surfactant which is synthesized and released by alveolar type II cells. Earlier studies have shown that exposure to gas phase materials such as smoke or organic solvents can alter the composition and function of the surfactant. The present study examines the ability of highly toxigenic mold spores to alter surfactant composition. Stachybotrys chartarum spores suspended in saline were instilled into mouse trachea as described earlier. After 24 h, the lungs were lavaged and the different processing stages of surfactant isolated by repeated centrifugation. Intracellular surfactant was isolated from the homogenized lung tissue by centrifugation on a discontinuous sucrose gradient. Samples were extracted into chloroform-methanol, dried and analyzed by Fourier-Transform infrared spectroscopy (FTIR). Exposure to S. chartarum induced an overall reduction of phospholipid among the three surfactant subfractions. The intermediate and spent surfactant fractions in particular were reduced to about half of the values observed in the saline-treated group. The relative distribution of phospholipid was also altered by spore exposure. Within the intracellular surfactant pool, higher levels of phospholipid were detected after spore exposure. In addition, changes were observed in the nature of the phospholipids. In particular strong intramolecular hydrogen bonding, together with other changes, suggested that spore exposure was associated with absence of an acyl chain esterified on the glycerol backbone, resulting in elevated levels of lysophospholipid in the samples. This study shows that mold spores and their products induce changes in regulation of both secretion and synthesis of surfactant, as well as alterations in the pattern of phospholipid targeting to the pulmonary surfactant pools.

Animals↗

PubMed2001

Structure and function in extracellular matrices depend on interactions between anionic glycosaminoglycans.

Connective tissue extracellular matrices define and maintain shape. Collagen fibrils transmit and resist pulling forces and soluble interfibrillar carbohydrate-rich polymers (anionic glycosaminoglycans AGAGs) resist compressive forces. This article shows that AGAGs (chondroitin, dermochondan and keratan sulphates) form supramolecular organisations which take tensile stresses as well, helping to maintain shape as part of 'shape modules'. Specific interactions with collagen fibrils tie down the AGAGs but conversely they orientate and maintain the organisation of collagen fibrils by forming interfibrillar bridges. The shapes of the AGAG chains in solution, shown by NMR to be two-fold helices, are completely complementary, allowing duplexes and higher aggregates to form spontaneously, providing participating AGAGs are oriented head-to-head i.e. antiparallel to each other. These tertiary structures are exact analogues of the beta-sheets are the basic structure of the interfibrillar bridges in the shape modules. In the absence of key shape module components, in a genetic disorder, extracellular matrices do not form an ordered tissue.

Anions↗

PubMed2001

Antenatal renal pelvic measurements: what do they mean?

OBJECTIVE: To analyse data on cases with urological abnormalities recorded over a 15-year period (1984-98) by the Northern Region Congenital Abnormality Survey (NorCAS), with special reference to fetal renal pelvic measurements. MATERIALS AND METHODS: Data on all urological cases recorded in the NorCAS database and in notification documents forwarded from hospitals in the Northern Region were extracted and incorporated in a separate unattributable database for analysis. Specific fields for filing recorded fetal renal pelvic measurements with their corresponding gestational ages were inserted; it was ensured as far as possible that these measurements were made in the anteroposterior plane. RESULTS: The total number of cases analysed was 2737; a measurement of the fetal renal pelvis was recorded in 813, and more than once in 468, giving 1301 measurement episodes with the corresponding gestational ages, pregnancy and postnatal outcome. The male/female (M/F) ratio was significantly higher in those cases which had a fetal renal pelvic measurement recorded than in those which had not. This was because there was a 12/1 M/F ratio in measured cases of vesico-ureteric reflux (VUR). Few cases of VUR had a fetal renal pelvic measurement recorded. The difference in the fetal renal pelvic measurements between those cases which were normal postnatally and those which had a structural abnormality, an obstructive lesion or VUR became significant at 7 mm and at 18 weeks of gestational age. Over the whole period the proportion of cases in which micturating cysto-urethrography was technically possible and might have contributed to the diagnosis was 28.5%; the highest was 44.1% in 1998. CONCLUSIONS: Antenatal renal dilatation occurs infrequently in the presence of VUR and when it does, the fetus will probably be male. Antenatal ultrasonography is unlikely to contribute to detecting VUR in females, the gender in whom early diagnosis is particularly desirable. Other means of suspecting VUR antenatally, e.g. the family history or genetic coding, may be more valuable. A measurement of the fetal renal pelvis of > or = 7 mm at a gestational age of 18 weeks should prompt subsequent careful ultrasonography during the pregnancy and early postnatal investigation of the urinary tract. The diagnosis of VUR should not be excluded because the fetal renal pelvis is only minimally dilated if the fetus is female.

Female↗

PubMed2001

The influence of congenital heart disease on survival of infants with oesophageal atresia.

OBJECTIVE: To examine the prevalence of congenital heart disease in babies with oesophageal atresia and its influence on outcome. DESIGN: Retrospective analysis. SETTING: The resident population of one health region. RESULTS: A total of 153 babies with oesophageal atresia were identified from 509 975 live births (0.30 per 1000); 26 (17%) had cardiac defects. Survival of babies with normal hearts was 97%, 97%, and 95% at one week, one month, and one year. Survival of babies with congenital heart disease was 85%, 85%, and 67% at one week, one month, and one year, but only one of ten deaths was the result of the congenital heart disease. The remaining deaths were due to other congenital malformations, respiratory disease, or chromosome abnormalities. CONCLUSIONS: There is a high prevalence of congenital heart disease in babies with oesophageal atresia. Congenital heart disease is associated with a higher mortality in oesophageal atresia but it is not the cause of it.

Cause of Death↗

PubMed2000

The effect of epidermal growth factor on the fetal rabbit mandibular condyle and isolated condylar fibroblasts.

The load-bearing surface of the mandibular condyle presents a unique arrangement of tissues consisting of an avascular layer composed largely of collagen bundles. Fibroblasts are interspersed amongst these bundles and are generally agreed to produce the collagen. The mechanisms controlling development of these tissues have not been determined. This study was conducted to explore the role of epidermal growth factor (EGF), which appears to be important in the development of many oral tissue types as well as in the growth and differentiation of the mandibular condyle. Superficial cells of the fibrous zone of the condyle were isolated from fetal rabbit condyles and [(3)H]thymidine incorporation into DNA measured. The application of EGF produced a significant increase in radiolabel incorporation after 2 days compared to 4 days in the controls, suggesting that EGF induced cells to enter S-phase more rapidly. Fetal condyles were also cultured on gelfoam surgical sponges for up to 21 days. Autoradiography of cultured condyles showed that cells of all three zones may potentially replicate, as indicated by incorporation of [(3)H]thymidine. All three regions displayed greater increases in cell numbers in samples exposed to EGF than in control samples. The measurement of zone thickness in condyles cultured on gelfoam sponges with or without EGF showed that this peptide was able to re-establish thickness, bringing it in line with the relation observed when the condyles were isolated initially, particularly of the intermediate zone over a period of 21 days. As very little autoradiographic labelling occurred at this time-point in any of the zones, the increase in thickness must primarily be due to matrix production. It is concluded that EGF is one factor potentially regulating both replication and differentiation in mandibular condyle and its associated cells.

Analysis of Variance↗

PubMed2000

Interaction between herpes simplex virus type 1 IE63 protein and cellular protein p32.

The herpes simplex virus type 1 (HSV-1) immediate-early gene IE63 (ICP27), the only HSV-1 regulatory gene with a homologue in every mammalian and avian herpesvirus sequenced so far, is a multifunctional protein which regulates transcriptional and posttranscriptional processes. One of its posttranscriptional effects is the inhibition of splicing of viral and cellular transcripts. We previously identified heterogeneous nuclear ribonucleoprotein (hnRNP) K and casein kinase 2 (CK2) as two protein partners of IE63 (H. Bryant et al., J. Biol. Chem. 274:28991-28998, 1999). Here, using a yeast two-hybrid assay, we identify another partner of IE63, the cellular protein p32. Confirmation of this interaction was provided by coimmunoprecipitation from virus-infected cells and recombinant p32 binding assays. A p32-hnRNP K-CK2 complex, which required IE63 to form, was isolated from HSV-1-infected cells, and coimmunoprecipitating p32 was phosphorylated by CK2. Expression of IE63 altered the cytoplasmic distribution of p32, with some now colocalizing with IE63 in the nuclei of infected and transfected cells. As p32 copurifies with splicing factors and can inhibit splicing, we propose that IE63 together with p32, possibly with other IE63 partner proteins, acts to disrupt or regulate pre-mRNA splicing. As well as contributing to host cell shutoff, this effect could facilitate splicing-independent nuclear export of viral transcripts.

Amino Acid Sequence↗

PubMed2000

Socioeconomic inequalities in risk of congenital anomaly.

AIMS: To investigate socioeconomic inequalities in the risk of congenital anomalies, focusing on risk of specific anomaly subgroups. METHODS: A total of 858 cases of congenital anomaly and 1764 non-malformed control births were collected between 1986 and 1993 from four UK congenital malformation registers, for the purposes of a European multicentre case control study on congenital anomaly risk near hazardous waste landfill sites. As a measure of socioeconomic status, cases and controls were given a value for the area level Carstairs deprivation index, by linking the postcode of residence at birth to census enumeration districts (areas of approximately 150 households). RESULTS: Risk of non-chromosomal anomalies increased with increasing socioeconomic deprivation. The risk in the most deprived quintile of the deprivation index was 40% higher than in the most affluent quintile. Some malformation subgroups also showed increasing risk with increasing deprivation: all cardiac defects, malformations of the cardiac septa, malformations of the digestive system, and multiple malformations. No evidence for socioeconomic variation was found for other non-chromosomal malformation groups, including neural tube defects and oral clefts. A decreasing risk with increasing deprivation found for all chromosomal malformations and Down's syndrome in unadjusted analyses, occurred mainly as a result of differences in the maternal age distribution between social classes. CONCLUSION: Our data, although based on limited numbers of cases and geographical coverage, suggest that more deprived populations have a higher risk of congenital anomalies of non-chromosomal origin and some specific anomalies. Larger studies are needed to confirm these findings and to explore their aetiological implications.

Case-Control Studies↗

PubMed1999

The multifunctional herpes simplex virus IE63 protein interacts with heterogeneous ribonucleoprotein K and with casein kinase 2.

Herpes simplex virus type 1 (HSV-1), the prototype alpha-herpesvirus, causes several prominent diseases. The HSV-1 immediate early (IE) protein IE63 (ICP27) is the only regulatory gene with a homologue in every mammalian and avian herpesvirus sequenced so far. IE63 is a multifunctional protein affecting transcriptional and post-transcriptional processes, and it can shuttle from the nucleus to the cytoplasm. To identify interacting cellular proteins, a HeLa cDNA library was screened in the yeast two-hybrid system using IE63 as bait. Several interacting proteins were identified including heterogeneous nuclear ribonucleoprotein K (hnRNP K), a multifunctional protein like IE63, and the beta subunit of casein kinase 2 (CK2), a protein kinase, and interacting regions were mapped. Confirmation of interactions was provided by fusion protein binding assays, co-immunoprecipitation from infected cells, and CK2 activity assays. hnRNP K co-immunoprecipitated from infected cells with anti-IE63 serum was a more rapidly migrating subfraction than hnRNP K immunoprecipitated by anti-hnRNP K serum. Using anti-IE63 serum, both IE63 and hnRNP K were phosphorylated in vitro by CK2, while in immunoprecipitates using anti-hnRNP K serum, IE63 but not hnRNP K was phosphorylated by CK2. These data provide important new insights into how this key viral regulatory protein exerts its functions.

Animals↗

PubMed1999

Hyaluronan forms specific stable tertiary structures in aqueous solution: a 13C NMR study.

13C NMR spectra of aqueous solutions of hyaluronan (HA) of high molecular mass, before and after digestion with testicular hyaluronidase, and of hyaluronan methyl ester were obtained at 125.8 MHz. Carbonyl peaks were assigned by using selective decoupling techniques. Spectra of digested and undigested HA showed sharp signals, except for that assigned to the acetamido carbonyl carbon in the high polymer, which was much broadened. The decreased mobility of this C==O, thus demonstrated, was caused by restricted rotation. As part of the rigid CO---NH unit, rotation of NH was therefore similarly restricted, probably because of an intermolecular H bond from NH to carboxylate groups on neighbouring HA molecules. This bond was confirmed by comparing esterified HA with unmodified HA. Methyl esterification of carboxylates was accompanied by changes in acetamido C==O resonances consistent with increased mobility of CO---NH groups. Ester C==O resonances were sharp, proving that they did not participate in sterically restricted structures such as the proposed H bonds involving unesterified carboxylate groups. C==O resonances report on the environments and on the interrelationships of amide and carboxylate groups. A detailed structure suggested for high-molecular-mass HA in aqueous solution takes account of NMR and x-ray fiber diffraction data. Antiparallel HA chains overlap in meshworks stabilized by specific H bonds and hydrophobic bonds. This highly cooperative structure, formally equivalent to beta-sheets seen in proteins, is not stable in low-molecular-mass HA solution. The results relate to structures proposed for shape modules in extracellular matrix involving chondroitin and keratan sulfates, which resemble HA in their stereochemistry.

Animals↗

PubMed1999

Calcium-PS-dependent protein kinase C and surfactant protein A in isolated fetal rabbit type II alveolar cells and surfactant-related material.

The fetal lung secretes significant quantities of surfactant during late gestation to prepare for initiation of respiration at birth. However, the mechanism by which this occurs has not been determined. Since Ca2+-phosphatidylserine (PS)-dependent protein kinase C has been implicated in surfactant secretion in adult lung, the present study was done to determine whether this enzyme is also involved in the initiation of surfactant release from fetal type II cells. Type II cells isolated from gestational day-24 fetal rabbits were used. Cells were prelabelled with [32P] and [3H]choline and exposed to 4beta phorbol ester (10(-5) M) for 2 h. Secretion product and subcellular fractions were isolated by removing the culture medium, mixing with homogenate from adult rabbit lung, and subfractionating by centrifugation on a sucrose gradient. Samples of secretion product were also prepared for electron microscopy. Ca2+-PS-dependent protein kinase C was also assayed in some samples, and an add-back technique was used to determine whether enzyme activity in the intracellularly stored surfactant fraction was due to contamination. The results showed that material released by fetal type II cells after exposure to phorbol ester coprecipitated with adult rabbit lung lamellar bodies and microsomes. Morphologically, a range of forms, including lamellar-body-like structures, was detected. The released material originated largely from the lamellar body compartment of the fetal type II cells and displayed immunoreactivity with antibody to surfactant protein A (SP-A) at 35 and 70 kDa apparent molecular mass. Assay of protein kinase C in fetal type II cells showed that exposure to conditioned medium, which induces differentiation, increased activity. Incubation with phorbol ester induced translocation of activity to the microsomal fraction. Add-back assays suggested that protein kinase C activation by treatment with phorbol ester induced translocation of enzyme activity to the lamellar body fraction; none was detected prior to treatment. These results support a role for Ca2+-PS-dependent protein kinase C in initiation of surfactant release by interaction with the developing lamellar body compartment in fetal type II cells.

Animals↗

PubMed1999

Severe polyethylene wear in uncemented acetabular cup system components: a report of 5 cases.

We report 5 cases of severe failure of the polyethylene liner at 4 to 7.4 years after uncemented anatomic medullary locking (AML) total hip arthroplasty, using the acetabular cup system (ACS). The mode of failure was by a combination of wear-through to the metal backing and liner fracture. Four of the 5 cases were associated with a 32-mm head. The ACS design is flawed because of a lack of hemispherical geometry resulting in rim loading on a region of the liner that has the thinnest polyethylene. All patients with this type of implant should be monitored for evidence of excessive polyethylene wear.

Acetabulum↗

PubMed1999

Screening for fetal urological abnormalities: how effective?

OBJECTIVE: To analyse urological cases registered with the Northern Congenital Abnormality Survey (NorCAS) and thus assess antenatal diagnostic sensitivity, measure regional interhospital variation and determine whether antenatal ultrasonography has contributed to the prevention of urinary tract disease in childhood. METHODS: All notification documents forwarded to NorCAS from its inception in 1984 until 31 December 1996 were inspected and those relating to urological abnormalities were abstracted. Information about postnatal progress was often missing. Twenty-three hospitals delivering maternity services were identified and randomly allocated a code letter a-w. Data were analysed in two periods, 1984-90 and 1991-96. To quantify hospital performance an 'expected number' for each hospital was calculated from the overall incidence per 1000 births and the number of births in each hospital. RESULTS: There was a clear improvement in antenatal diagnostic sensitivity for the major urological abnormalities in the second period, but there was considerable variation among hospitals in the number of cases notified; this applied particularly to antenatal renal dilatation. Two hospitals notified significantly more cases in this category than all the others. The difference in notification rates among hospitals was caused by diagnoses such as vesico-ureteric reflux (VUR), pelvi-ureteric junction obstruction and megaureter, which often produce antenatal renal dilatation. Hospitals which notified more of these cases performed more micturating cystograms and identified more children with VUR. Measurements of the fetal renal pelvis were regularly made by only seven hospitals; one of these had difficulties with postnatal follow-up. There was evidence that moderate degrees of antenatal renal dilatation (4-10 mm) were associated with VUR; 8.5% of the children in whom VUR was diagnosed had fetal renal dilatation of this order. CONCLUSION: Antenatal renal dilatation and its significance are either not being recognized or not appreciated in some hospitals. The high incidence of VUR in cases with moderate antenatal renal dilatation indicates that children with this condition may be escaping diagnosis.

Dilatation, Pathologic↗