Concept development for the ITER equatorial port visible∕infrared wide angle viewing system.

The ITER equatorial port visible∕infrared wide angle viewing system concept is developed from the measurement requirements. The proposed solution situates 4 viewing systems in the equatorial ports 3, 9, 12, and 17 with 4 views each (looking at the upper target, the inner divertor, and tangentially left and right). This gives sufficient coverage. The spatial resolution of the divertor system is 2 times higher than the other views. For compensation of vacuum-vessel movements, an optical hinge concept is proposed. Compactness and low neutron streaming is achieved by orienting port plug doglegs horizontally. Calibration methods, risks, and R&D topics are outlined.

Changes in elastic fibres in the small airways and alveoli in COPD.

Small airways are the major site of airflow obstruction in chronic obstructive pulmonary disease (COPD). This is attributed to loss of elastin in alveoli and fibrosis in small airways. In the present study, it was hypothesised that changes to elastic fibres in alveoli might be paralleled by a similar reduction in elastic fibres in small airways. Tissue blocks from patients who had lobectomy for bronchial carcinoma were studied. Patients were classified as COPD (forced expiratory volume in one second (FEV(1)) < 80% predicted, FEV(1)/forced vital capacity (FVC) < 0.7) or controls (FEV(1) > or = 80% pred, FEV(1)/FVC > or = 0.7). Elastic fibres were visualised using Elastic van Gieson staining and the volume fraction (v/f) of elastic fibres was determined as a percentage of tissue volume using point counting. Elastic fibre networks were also visualised by confocal microscopy. The v/f for elastic fibres in alveoli was 18.6% for COPD and 32.8% in controls. In the airways the v/f was 14.6% for COPD and 25.5% in controls. FEV(1)% predicted was correlated with v/f in both alveoli and small airways. The volume fraction of elastic fibres was reduced to a similar extent in small airways and alveoli in chronic obstructive pulmonary disease and both were correlated with the extent of airflow obstruction. Loss of elastic fibres in small airways may contribute to the development of airflow obstruction in chronic obstructive pulmonary disease.

Is it possible and worth keeping track of deaths within general practice? Results of a 15 year observational study.

AIM: To assess the value of maintaining a death register in a general practice with particular reference to monitoring quality of care. DESIGN OF STUDY: Observational study. SETTING: Inner London general practice. METHOD: The practice maintained a manual death register, retained medical records of all deceased patients, and requested information on cause of death from health authorities and coroners for 15 years. MAIN OUTCOME MEASURES: Number and causes of deaths; 3 yearly age standardised death rates; proportion of deaths formally notified to the practice; place of death; source of cause of death information. RESULTS: During the study period 578 patients died. Practice age standardised death rates fell significantly from 35.59 to 27.12/1000. 498 (86.2%) deaths were formally notified to the practice, 392 within 7 days of death. Of 143 deaths reported to the coroner, only 45 coroners' reports were received. 360 (64.1%) died in hospital, 139 (24.8%) at home, and 38 (6.8%) in a hospice. Death certificate cause of death information was obtained from patients' records in 33.6% (n=194) of cases and from health authority sources for 50% (n=289). The pattern of ascertained causes of deaths was similar to the national pattern. CONCLUSION: A death register can examine trends in practice deaths by age and place of death and comparisons undertaken with nationally published mortality data. An accurate picture of cause of death cannot be generated from routine data flows alone. There is delay in informing GPs of patient deaths. Meaningful and timely monitoring of deaths cannot be undertaken by individual practices. National Statistics should provide routine analysis of GP death certificate information.

Effects of varying 5-fluorouracil exposure duration on tenon's capsule fibroblasts.

PURPOSE: 5-Fluorouracil (5-FU) is used intraoperatively to improve the success of trabeculectomy Common practice is a 5-min application of 5-FU delivered via a Weck Cel sponge. The aim of this study was to determine if shorter exposure times were as effective in inhibiting Tenon's capsule fibroblast proliferation. METHODS: Samples of Tenon's capsules, obtained from young patients undergoing strabismus surgery, were immersed In vitro in 5-FU (50 mg/mL) for periods ranging from 1 to 10 min. Control samples were exposed either to growth medium (M 199) or 5-FU vehicle alone. Explants were cultured for up to 7 days and analysed for cell density, cell viability using fluoroprobe detection, and cell proliferation determined by proliferating cell nuclear antigen (PCNA)-staining. RESULTS: Exposure to 5-FU for 1 and 5 min resulted in a similar and significant inhibition of the culture-induced increase in stromal cell density (P < 0.01), a significant reduction in the percentage of viable cells (P < 0.02), and reduced PCNA indices, compared with controls. Exposure times of 3 and 10 min produced similar results. CONCLUSIONS: In vitro, under conditions of organ culture, a 1-min exposure to 5-FU had a significant antiproliferative effect on fibroblasts of Tenon's capsule, and was similar to 5 min of exposure. Optimal intraoperative 5-FU exposure time may be as little as 1 minute.

Survey of injectable methadone prescribing in general practice in England and Wales.

Little is known about the extent and conduct of general practice prescribing of injectable methadone to opiate users in England and Wales. A postal questionnaire survey of general practitioners (GPs) was conducted in 1999 to ascertain how many GPs were prescribing injectable methadone, to describe their prescribing practices and to explore their perceptions of the service they provided. Four hundred and seven GP practices in 77 out of 105 health authorities were apparently prescribing injectable methadone. The difficulties in identifying, and obtaining a response from, GPs prescribing injectable methadone are discussed. Analysis of 93 usable returned questionnaires showed a range of GP characteristics and experience. The GPs were treating 211 patients with injectable methadone and a further 2003 patients with oral methadone. Prescribing practice and monitoring arrangements did not always follow national guidelines. A minority of GPs had received training in the management of drug dependency. They were most likely to decide to prescribe injectable treatment on the recommendation of a specialist drug agency, and to discontinue prescribing if there was a suspicion of diversion of prescribed ampoules. Although significant numbers of GPs felt unsure about their skills and the support available to them, most appeared to be managing their patients thoughtfully and with appropriate outcomes in mind. Recent policy documents from the Department of Health and the Home Office have questioned the place of injectable methadone in the treatment of opiate misuse, particularly in a general practice setting. A Home Office licence will shortly be required to prescribe injectable methadone. This survey suggests a minority of GPs would apply for such a licence. More research into the effectiveness of injectable methadone treatment in a range of settings is needed before conclusions can be drawn about the appropriateness of providing this treatment in general practice.

Comparison of deposits of versican, biglycan and decorin in saphenous vein and internal thoracic, radial and coronary arteries: correlation to patency.

BACKGROUND: Matrix proteoglycans versican, biglycan and decorin are important determinants of vessel-wall structure and pathology. Thickened myxoid intimas typical of restenosis and early atherosclerosis are enriched in versican and biglycan, proteoglycans that promote proliferation and migration of smooth muscle cells and bind lipoproteins. In contrast, compact fibrous intimas are characterized by decorin. OBJECTIVE: To compare the distribution patterns of these matrix proteoglycans, and changes induced by organ culture in coronary artery, saphenous vein, internal thoracic artery (ITA), and radial artery, and correlate differences to patency. METHODS: Vessels were collected at the time of bypass surgery and heart transplantation and either fixed for immunohistochemistry or prepared for organ culture. Vessels in culture were labelled with [3H]-glucosamine and processed for autoradiography and immunohistochemistry. Distribution patterns for proteoglycans and radio-labelling were determined morphometrically. RESULTS: Distribution profiles in coronary artery and saphenous vein were similar, with relatively high levels of subendothelial versican and biglycan and low levels of decorin. In culture subendothelial incorporation of [3H]-glucosamine and immunostaining for versican and biglycan, but not decorin, were significantly increased. In contrast, the thin intima of the ITA was relatively enriched in decorin compared with the medial layers and in culture intimal staining for decorin increased markedly compared with a modest increase for biglycan and no change for versican. There was an even distribution in radial artery of all three proteoglycans across the intima without subendothelial accumulations. In culture there was an increase in staining intensity for proteoglycans of the radial artery. Neither the ITA nor radial artery exhibited an increase in subendothelial incorporation of [3H]-glucosamine in culture. CONCLUSIONS: The distributions of proteoglycans, and responses to culture correlate to the known differences in patency between grafted saphenous vein and ITA and predict that the radial artery will outperform the saphenous vein but might not be as good as the ITA for long-term patency.

Effect of TGF-beta(1) antisense S-oligonucleotide on synthesis and accumulation of matrix proteoglycans in balloon catheter-injured neointima of rabbit carotid arteries.

Arterial matrix proteoglycans (PG) are necessary for the maintenance of viscoelastic properties of the vessel wall, but excess levels, particularly of versican and biglycan in primary and restenotic intimal thickenings, are correlated with increased tissue volume and with atherogenicity. There is good evidence that the primary stimulus to increased PG synthesis, including versican and biglycan, is transforming growth factor-beta(1) (TGF-beta(1)). The aim of this study was to determine the effects of reducing endogenous TGF-beta(1) on rates and patterns of PG synthesis and on versican, biglycan and decorin accumulation in vivo. Rabbit common carotid arteries subjected to balloon catheter injury were treated with a TGF-beta(1) antisense phosphorothioate oligonucleotide applied in a pluronic gel to the adventitia. Control animals received a nonsense oligonucleotide or gel alone. TGF-beta(1) antisense (1) significantly (p < 0.005) inhibited, at day 2, the balloon catheter-induced increase in TGF-beta(1) mRNA relative to beta-actin mRNA; (2) inhibited intimal thickening at 23 days by approximately 40% (p < 0.05); (3) inhibited (p < 0.05) PG synthesis, measured by autoradiographic detection of [(3)H]glucosamine, in the media of day 2 ballooned carotids and in the subendothelial zone of day 23 neointima, and (4) decreased immunostaining intensity for versican (p < 0.03) and TGF-beta(1) (p < 0.001) in the neointima. Biglycan was reduced to a lesser extent but not significantly and decorin was not affected. Proliferating cell nuclear antigen indices were variable and not significantly changed. These findings confirm a role for TGF-beta(1) in developing neointima and demonstrate a specific effect on the synthesis, distribution, and accumulation of matrix PG, particularly versican.

GaN-Based Solar-Ultraviolet Detection Instrument.

We report on the fabrication of a solar-UV monitoring system that uses GaN-based photodetectors. GaN photoconductors, p-n junction photodiodes, and Schottky barrier photodiodes have been fabricated and characterized as UV sensors. The best performances are obtained in Schottky photodiodes, which show a linear response, a flat responsivity of 100 mA/W, a visible rejection ratio higher than 10(3), and a noise-equivalent power of 1 nW/Hz(-1/2). Preliminary data on Al(x)Ga(1-x)N (x = 0.15, 0.22) detectors are also presented. Using GaN Schottky diodes, we fabricate and evaluate a complete solar-UV detection head.

Detection of viable and non-viable cells in connective tissue explants using the fixable fluoroprobes 5-chloromethylfluorescein diacetate and ethidium homodimer-1.

The efficacy of connective tissue explants is difficult to determine, particularly where autopsy material is required for research or clinical applications. We report here an optimised protocol using 5-chloromethylfluorescein diacetate (CMFDA) and ethidium homodimer-1 to distinguish viable and non-viable cells in a range of connective tissue explants. Biopsies and explants of corneae, arteries, cartilage and skin were loaded with fluoroprobes for extended periods (< or = 24h) at low temperatures (4 degrees C), fixed in paraformaldehyde, and processed using a variety of embedding, sectioning, autoradiographic, and immunohistochemical procedures. Detection of fluorescent green CMFDA and red ethidium homodimer was achieved using epi-illuminated light or dual channel confocal microscopy, and clearly differentiated live from dead cells throughout the explants. Furthermore, the intracellular distribution of CMFDA provided superior images of cell shape and morphology not previously available using conventional histochemical techniques. Adaptations of this protocol could prove valuable in a variety of research and clinical applications.

Fluoroprobe quantification of viable and non-viable cells in human coronary and internal thoracic arteries sampled at autopsy.

Viable and non-viable cells in coronary and internal thoracic arteries, collected at autopsy 7-24 h post-mortem from individuals 15-81 years of age, were detected using the fixable fluoroprobes 5-chloromethylfluorescein diacetate (green) and ethidium homodimer-1 (orange/red). Viability status of individual endothelial and smooth muscle cells was confirmed by simultaneous autoradiographic detection of incorporated [3H]glucosamine. Twenty-five percent of coronary and 42% of internal thoracic arteries contained viable cells up to 24 h following death. For the majority of viable vessels the mean percentage of viable cells ranged between 60 and 80% with no significant difference between coronary and internal thoracic arteries and no relationship with either age of the donor or with time to autopsy. Non-viable cells were usually distributed fairly evenly amongst viable cells but this pattern could not be assumed. In a number of vessels non-viable cells were variably clustered in different regions of vessel wall. These findings confirm that vessels sampled at autopsy can be used for metabolic studies with the caveat that assessment of cell viability is a necessary prerequisite for interpretation of results.

Structural heterogeneity of the diffuse intimal thickening and correlation with distribution of TGF-beta 1.

This study examines the ultrastructural features of diffuse intimal thickenings of human coronary arteries and correlates structural heterogeneity along the radial axis with the distribution and known actions of transforming growth factor beta 1 (TGF-beta 1). Morphometric and immunohistochemical data were collected from thickenings of varying widths, sampled at autopsy from 19 persons ranging in age from 3 months to 81 years. Thickenings were characterised by an inner proteoglycan layer (PGL), up to approximately 70 mm wide, and an underlying variable-width musculofibrous layer (MFL). The PGL was characterised by low volume fractions (v/fs) for collagen, elastin, basement membranes and cells and a high v/f for matrix space; v/fs for the MFL components were more evenly distributed. Proteoglycans were visualised by ruthenium red staining, quantified and sized. Densities of large (versican; > 20 nm) and small (< 20 nm) granules changed little across intimal thickenings. Mean diameters of matrix space granules increased with increasing intimal thickness and notably were significantly (p < 0.001) larger in the PGL than the MFL. In contrast, diameters of collagen-associated small granules (decorin) did not differ between the PGL and MFL. TGF-beta 1 staining was detected in 70% of vessels examined and occurred almost exclusively in the PGL, although showed a patchy distribution. Both the distribution of TGF-beta 1 and its known differential effects on versican and decorin synthesis suggest that it may play a significant role in the formation and maintenance of the PGL.

B-mode ultrasound images of the carotid artery wall: correlation of ultrasound with histological measurements.

B-mode ultrasound is being used to assess carotid atherosclerosis in epidemiological studies and clinical trials. Recently the interpretation of measurements made from ultrasound images has been questioned. This study examines the anatomical correlates of B-mode ultrasound of carotid arteries in vitro and in situ in cadavers. Twenty-seven segments of human carotid artery were collected at autopsy, pressure perfusion fixed in buffered 2.5% glutaraldehyde and 4% paraformaldehyde and imaged using an ATL UM-8 (10 MHz single crystal mechanical probe). Each artery was then frozen, sectioned and stained with van Gieson or elastin van Gieson. The thickness of the intima, media and adventitia were measured to an accuracy of 0.01 mm from histological sections using a calibrated eye graticule on a light microscope. Shrinkage artifact induced by histological preparation was determined to be 7.8%. Digitised ultrasound images of the artery wall were analysed off-line. The distance from the leading edge of the first interface (LE1) to the leading edge of the second interface (LE2) was measured using a dedicated programme. LE1-LE2 measurements were correlated against histological measurements corrected for shrinkage. Mean values for the far wall were: ultrasound LE1-LE2 (0.97 mm, S.D. 0.26), total wall thickness (1.05 mm, S.D. 0.37), adventitia (0.35 mm, S.D. 0.16), media (0.61 mm, S.D. 0.18), intima (0.09 mm, S.D. 0.13). Ultrasound measurements corresponded best with total wall thickness, rather than elastin or the intima-media complex. Excision of part of the intima plus media or removal of the adventitia resulted in a corresponding decrease in the LE1-LE2 distance of the B-mode image. Furthermore, increased wall thickness due to intimal atherosclerotic thickening correlated well with LE1-LE2 distance of the B-mode images. B-mode images obtained from the carotid arteries in situ in four cadavers also corresponded best with total wall thickness measured from histological sections and not with the thickness of the intima plus media. In conclusion, the LE1-LE2 distance measured on B-mode images of the carotid artery best represents total wall thickness of intima plus media plus adventitia and not intima plus media alone.

Visual problems in the elderly population and implications for services.

OBJECTIVE: To determine the prevalence of visual disability and common eye disease among elderly people in inner London. DESIGN: Cross sectional random sample survey. SETTING: Inner London health centre. SUBJECTS: Random sample of people aged 65 and over taken from practice's computerised age-sex register. MAIN OUTCOME MEASURES: Presenting binocular Snellen 6 m distance acuity and best monocular 3 m Sonksen-Silver acuity to classify prevalence of blindness by World Health Organisation criteria (less than 3/60 in better eye) and American criteria for legal blindness (better eye equal to 6/60 or less) and of low vision by WHO criteria (best acuity 6/18) and visual impairment by American criteria (less than 6/12 or 20/40 but greater than 6/60 or 20/200 in better eye). Principal cause of visual loss by diagnosis, referral indication by cause to hospital eye service, and proportion of cases known to primary care. RESULTS: 207 of 288 (72%) eligible people were examined. 17 (8%) housebound subjects were examined at home. The prevalence of blindness was 1% by WHO criteria and 3.9% by American criteria. The prevalence of low vision (WHO criteria) was 7.7%. The prevalence of visual impairment (American criteria) was 10.6%. Cataract accounted for 75% of cases of low vision. Only eight out of 16 patients with low vision were known by their general practitioner to have an eye problem. 56 subjects (27%) would probably have benefited from refraction. Comparisons with studies in the United States and Finland suggested higher rates in this sample, mainly due to the prevalence of disabling cataract. CONCLUSION: There seems to be a considerable amount of undetected ocular disease in elderly people in the community.

Chondrons extracted from canine tibial cartilage: preliminary report on their isolation and structure.

We report on the morphology and structure of single and multiple chondrons isolated from homogenized samples of fresh and fixed canine tibial cartilage. Phase contrast, Nomarski, and scanning electron microscopy observations show each chondron to be composed of a chondrocyte and its pericellular matrix enclosed within a "felt-like" pericellular capsule. The extraction of intact chondrons from cartilage homogenates confirms the structural validity of the chondron concept and emphasizes the intrinsic mechanical strength of the capsule. Frayed collagen fibers radiate from multiple chondron columns suggesting a shear-resistant, structural interrelationship between capsular components and type II collagen fibers. Future development of chondron extraction procedures could provide a unique model with which to study the structure, biochemistry, and function of articular cartilage chondrocytes and their pericellular microenvironment.

Chondrons in cartilage: ultrastructural analysis of the pericellular microenvironment in adult human articular cartilages.

A combination of scanning and transmission electron microscopy was used to investigate the morphology and ultrastructure of normal human articular cartilage sampled from adult amputation specimens. This study confirms our previous observations on canine articular cartilage, which showed middle and deep layer chondrocytes surrounded by a pericellular matrix and enclosed within a pericellular capsule composed of filamentous and fine fibrillar materials. Pores in the "felt-like" organization of the capsular weave progressively decreased in size from the inner to the outer border of the capsule. Matrix vesicles were found embedded within the capsular weave and distributed throughout the territorial matrix. It is suggested that the chondrocyte, its pericellular matrix, and capsule together constitute the "chondron," a primary functional and metabolic unit of cartilage that acts hydrodynamically to protect the integrity of the chondrocyte and its pericellular microenvironment during compressive loading.

Changes in the morphology and synthetic activity of cultured rat tail tendon.

Isolated single fascicles from tail tendons of young rats were freed of epitenon cells and cultured in vitro for up to 7 days. The tissue remained viable, as judged by the structural integrity of cell organelles and the ability to synthesize DNA and glycosaminoglycans (GAG). The rate of DNA synthesis peaked after 2 days in culture and decreased slowly thereafter. Concomitantly, an increase in cell number was noted at the periphery of the fascicle. GAG production also increased during culture, sulphated GAG being increased proportionately more than hyaluronic acid. Dermatan sulphate was the predominant sulphated GAG in freshly isolated fascicles, but in cultured tissue, the newly synthesized sulphated GAG was more sensitive to degradation by chondroitinase AC and had an increased electrophoretic mobility. fine structural changes were observed in cultured tissues such as the retraction of cell processes. rounding up of cell bodies and the appearance of gaps between collagen fibrils. Cultured tenocytes also frequently contained apparently phagocytized collagen fibrils which were not seen in freshly isolated fascicles, and this appearance was suggestive of collagen degradation occurring in vitro, although no change in the total hydroxyproline content was noted. The data show that when individual fascicles are cultured in vitro they undergo a process of matrix remodelling which has features in common with events occurring in vivo when tendons have been surgically manipulated.