Actinic granulomata in a young woman following prolonged sunbed usage.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to P Newman.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Paraffin sections from 29 lung carcinomas (28 primary and 1 metastatic) and 9 pleural malignant mesotheliomas were immunostained with antisera to human hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, met. For HGF/SF, immunoreactivity was demonstrated in all 9 mesotheliomas, 9 of 12 adenocarcinomas, and 7 of 10 squamous cell carcinomas. None of seven cases of small cell anaplastic carcinoma was positive. The adenocarcinomas frequently showed enhanced luminal staining, suggesting possible secretion of HGF/SF, and this pattern of staining was also seen occasionally in bronchial epithelium adjacent to the tumour. Stromal fibroblasts also showed immunoreactivity for HGF/SF in 6/8 cases of mesothelioma but in only 3/12 adenocarcinomas, 1/10 squamous cell carcinomas, and 1/4 small cell anaplastic carcinomas. All tumours stained for met, usually strongly. The staining was mainly cytoplasmic in nature, but some plasma membrane staining was usually evident. Adenocarcinomas showed strong luminal membrane staining, as did adjacent, histologically normal bronchial epithelium. This study demonstrates the presence of HGF/SF and met in most of the tumour types described, particularly mesotheliomas, and suggests that the HGF/SF/met signalling system may play a role in the development of these tumours, either by autocrine or by paracrine mechanisms.
Nerve injury is a rare complication of total hip replacement which may be related to the exposure used for the operation. The posterior approach is traditionally associated with injury to the sciatic nerve. We have compared the incidence of nerve injury after primary total hip replacement (THR) using either a posterior or a direct lateral approach. We studied 42 consecutive patients undergoing primary total hip replacement. The surgeons used a posterior (22 patients) or direct lateral (20 patients) approach in accordance with their normal practice. The obturator, femoral, posterior tibial and common peroneal nerves were assessed clinically and electrophysiologically by electromyography (EMG) and measurement of the velocity of nerve conduction before operation and at four weeks after. All patients were free from symptoms of nerve injury after operation but five lesions were identified in four patients by the electrophysiological studies; the obturator nerve was involved in two, the femoral in one, the common peroneal in one and the posterior tibial in one. All these injuries occurred using the lateral approach. Clinical assessment alone underestimates the incidence of nerve injury complicating THR. Our study does not confirm the association of nerve injury with the posterior approach which had been described previously.
Three procedures to ensure the correct location of components in the orifice of a hydroxyapatite-coated implant cylinder are presented. These facilitate recording of an accurate impression and the correct location of a customized abutment supporting a single-tooth crown. A technique is offered for obtaining the reproducible, comparable radiographs necessary for monitoring horizontal bone levels.
Explore the source record for details and available documents.
Several chemotaxis methods have been developed which allow the study of different aspects of cell migration. The major limitation of such methods is the lack of a sustained chemotactic signal. Long-term chemotaxis phenomena which are known to take place in vivo have remained largely uninvestigated. Ways to maintain sustained chemotactic signals were sought and the used to investigate the long-term chemotactic effect of platelet-derived growth factor BB (PDGF-BB) on human vascular smooth muscle cells (HVSMC). PDGF-BB was adsorbed onto microcarrier beads and then embedded in agar. PDGF-BB diffusion was slow and a high and sustained local concentration was maintained in the agar. When PDGF-BB-loaded beads embedded in agar were placed at the edge of a tissue culture dish with HVSMC plated in the center, preferential movement was observed in the direction of the PDGF-BB source. This method was subsequently used to study directional movement of HVSMC arising from explants. This report demonstrates that PDGF-BB if present in an anisotropic concentration induces directional cell movement from such explants. By allowing the study of the effect of sustained chemotactic signals upon cultured cells or cells arising from explants, this method may provide a suitable model for investigating in vivo chemotaxis phenomena.
Endothelin may play a role in atherosclerosis as it causes smooth muscle cell proliferation and its levels are elevated in patients with atherosclerosis. We report that interleukin-1 beta is a potent inducer of endothelin receptor expression in cultured human vascular smooth muscle cells. The effect is dose- and time-dependent and is due to an increase in receptor number. Endothelin receptor mRNA levels are also elevated. Interleukin-1 beta is a major regulator of endothelin release so, together with its effects on endothelin receptors, it may be responsible for a generalized activation of the endothelin system in diseased vessels.
Neurofibrillary tangles are described in Guamanian and post-encephalitic forms of motor neuron disease (MND) but not in sporadic MND. We report the neuropathological findings in a 79-year-old man who died after a 1-year history of MND without extrapyramidal features or dementia. There was no family history of neurological disease and he had not visited Guam. The spinal cord showed loss of anterior horn cells, and skeletal muscle typical changes of denervation. The brain appeared macroscopically normal but histology revealed many neurofibrillary tangles, particularly in medial temporal lobe structures, insula, nucleus basalis, hippocampus, oculomotor nucleus, raphe nuclei and locus ceruleus. Neurofibrillary tangles were not seen in the primary motor cortex, which appeared histologically unremarkable. Occasional tangles were present in the substantia nigra and pontine nuclei. None were seen in the cerebellum, medulla or spinal cord. The tangles were argyrophilic, and, in sections stained with thioflavin-S, both the intracellular and the extracellular tangles fluoresced strongly under ultraviolet light. The intracellular neurofibrillary tangles reacted strongly with an antibody to tau protein, and only occasional tangles showed weak ubiquitin immunoreactivity. Scattered neuropil threads were present in the cortex in the areas of neurofibrillary tangle formation. No plaques were present in any part of the brain and no A4/beta protein immunoreactivity was detected. Ultrastructural examination revealed Alzheimer-type neurofibrillary tangles composed of paired helical filaments. The present findings further extend the spectrum of diverse neurological disorders associated with neurofibrillary tangles.
The incidence of ischemic heart disease is rising rapidly in many of the affluent Arab countries and it is known that hypercholesterolemia is a well established risk factor for coronary artery disease. This community-based study was undertaken to determine if elevated cholesterol is a problem in the United Arab Emirates in order to be able to evaluate the contribution of cholesterol as a risk factor for atherosclerosis in this environment. Volunteers were recruited at busy urban public sites. Data on age, sex, nationality, weight, blood pressure and smoking history were collected, and blood samples were taken for estimation of total cholesterol, hemoglobin and individual blood group. A raw data set was developed, with calculation of body mass index and subsequent statistical analysis carried out on a PC using the SPSS programme. In the 834 patients, there were 19 nationalities represented which were pooled into 7 groups (5 Arab and 2 non Arab) according to their ethnic origins. The prevalence of hypercholesterolemia varied from 47.2-53% in the Arab Nationals and from 22.7 to 44.5% in the non Arabs. The mean cholesterol levels of the Arab subgroups were similar and showed no difference, statistically. However, they were significantly higher than non Arabs, i.e. Indians (p < 0.001) and Iranians (p < 0.001). Similarly, within the Arab subgroups, the median cholesterol levels were no different but were higher than the non Arabs, i.e. Indians (p < 0.05) and Iranians (p < 0.001). No statistical difference was found in the distribution of cholesterol (high, borderline high or desirable levels) among the seven ethnic groups. Hypercholesterolemia appears to be a problem in most nationalities living within the UAE. Overall, it afflicts nearly 50% of the adult population. Although the ethnic Arab groupings have a wide range of socioeconomic attributes, the similarity of the distribution of cholesterol may point to an underlying innate genetic etiology or an environmental cause such as dietary overindulgence, or both. Urgent public health measures such as education, case finding and further screening programs are required.
A multi-ethnic population was screened for gestational diabetes mellitus (GDM) using a venous plasma glucose estimation, 1 h following a standard 50 g glucose load. A significant difference in the ethnic distribution of screen-positivity was found. Amongst the screen-positive group the odds ratio (OR) for special care baby facility (SCBU) admission and birthweight > 3999 g were both increased (OR = 1.87 and 1.99). Only limited diagnostic testing by a glucose tolerance test (GTT) could be achieved for the screen-positive population. For patients with confirmed GDM (two or more abnormal values on a GTT) the OR for SCBU admission was further increased to 5.1, while the OR for increased birthweight was only 1.34. Clinical attention should be directed towards outcome assessment in order to properly evaluate the nature of and place for screening for GDM in multi-ethnic populations.
alpha-Thrombin, a key enzyme of the coagulation cascade, is also a potent mitogen for many cell types. In the present study, the responsiveness to alpha-thrombin of cultured human vascular smooth muscle cells (HVSMC) derived from either vein or normal and atherosclerotic arteries was investigated. All HVSMC populations examined responded mitogenically to alpha-thrombin. However, the extent of this response varied between different cell populations. No significant differences were observed between HVSMC derived from vein versus artery or atherosclerotic versus normal tissues. The responsiveness of a specific HVSMC culture to alpha-thrombin was not affected by cell density and remained constant over several passages. Unlike platelet-derived growth factor BB (PDGF-BB), alpha-thrombin did not exhibit any significant chemotactic effects on HVSMC or induce their anchorage independent growth in semi-solid medium. The hypothesis that the observed variability in HVSMC responsiveness to alpha-thrombin is due to the heterogeneity of cultured HVSMC is raised and discussed.
BACKGROUND: Chronic gastrointestinal (GI) symptoms are believed to be common in the general population, but Australian data are lacking. A valid instrument is required to assess GI symptoms adequately and determine their prevalence in the community. AIMS: To test the feasibility, reliability and concurrent validity of a self-report Bowel Symptom Questionnaire (BSQ) as a measure of GI symptoms, and obtain preliminary data on the prevalence of symptoms in an Australian population-based sample. METHODS: Outpatients (n = 63), volunteers (n = 163) and a random sample (n = 99) of the Penrith population, Sydney, completed the BSQ. Feasibility was evaluated in 264 subjects. Reliability was measured by a test-retest procedure (n = 43), while concurrent validity was documented by comparing self-report data with an independent interview (n = 20). The response rate in the population mail survey was 68%. Prevalence data on bowel symptoms in the community sample (n = 99) were age and gender standardised to the Australian population. RESULTS: The majority of subjects found the BSQ easy to complete (97%) and understand (97%); 90% completed the questionnaire in half an hour or less. Reliability (median kappa 0.70, interquartile range 0.20) and concurrent validity (median kappa 0.79, interquartile range 0.26) of GI symptoms were both very acceptable. The internal consistency of all GI symptom scales was good (Cronbach's Alpha range 0.51-0.74). The prevalence of the irritable bowel syndrome (defined as abdominal pain and disturbed defaecation based on two or more of the Manning criteria) was 17.2% (95% CI: 10-25%). CONCLUSIONS: The BSQ was well accepted and easy to understand; it provided reliable and valid data on GI symptoms and should prove useful in large scale epidemiological studies in Australia.
Although persuasive arguments against routine screening for gestational diabetes mellitus (GDM) have been made, it is widely but not universally performed as a part of antenatal care. There is no international agreement on methods or criteria used for screening (or for diagnosis), and administered glucose-load methods have significant practical difficulties in a busy antenatal clinic setting. However, recent evidence supports the concept of an increased level of importance being given to a diagnosis of GDM, with interest in the fetal and neonatal origins of adult disease being added to the short-term obstetric and fetal concern during pregnancy. A second generation fructosamine test, corrected for total protein, has been evaluated as a practical alternative to glucose screening for GDM in a busy, multi-ethnic antenatal clinic. This achieved a 79.4% sensitivity and a 77.3% specificity for a diagnosis of GDM confirmed by a glucose tolerance test using Carpenter's modified criteria. In view of the organizational simplicity of this sample/test requirement, a wider evaluation is suggested together with a re-evaluation of clinical outcome criteria rather than blood glucose levels alone.
BACKGROUND: Endothelin (ET), a potent vasoconstrictor peptide, is implicated in disorders of intimal hyperplasia such as atherosclerosis and restenosis. Data from animal models and in vitro studies indicate that ET may act at the level of vascular smooth muscle cell proliferation. In this study the effect of ET on human vascular smooth muscle cells (HVSMC) was investigated. EXPERIMENTAL DESIGN: The mitogenic effect of ET on 30, early passage, HVSMC lines derived from normal donors and those undergoing aorto-coronary vein bypass grafting (ACVB) operation was examined and characterized. This was correlated with the density of endothelin receptors on these cells as well as with the rate of endothelin secretion. RESULTS: There were no clear differences in the mitogenic responsiveness of cells from normal donors and those undergoing ACVB. In 10 HVSMC lines, DNA synthesis was significantly stimulated (30 to 120% stimulation above control, defined as responders), and an insignificant stimulation (< 30% above control) was observed in 20 cell lines (called non-responders); a similar pattern was observed in the cell multiplication assay. In the responder HVSMC lines, the rank order of ET isopeptides in stimulating mitogenesis was ET-1 = ET-2 > ET-3, and the effect was inhibited by the ET antagonist (BQ-123) suggesting that the ET-receptor-A (ETA) subtype was involved in mediating the actions of ET. Measurement of 125I-ET-1 binding to cells indicated there to be a strong correlation between the extent of ET mitogenic effect and receptor binding (N = 30, p = 0.034) but none with the rate of ET secretion. CONCLUSIONS: These results suggest that increased levels of ET receptors on HVSMC, as observed in atherosclerotic plaques, may predispose them to ET-stimulated proliferation.
The distal extension fixed implant supported prosthesis is now available as an alternative to a partial denture. However, not all patients will be suitable for such treatment. Limitations imposed on fixture length, the effect of gape upon instrumentation, the size of abutment components and the design of the superstructure are discussed in this article, to assist the general practitioner in case referral.