The measurement of bone lead content in patients with end stage renal failure.
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Biomedical subjects
Publications and source records attributed to S J Jones.
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This study explored the microstructure of human cranial bone at different ages, and the survival, remodelling and modelling of cranial bone grafts. A combination of reflection and fluorescence confocal optical microscopy and scanning electron microscopy in the backscattered electron imaging mode was employed to examine highly polished block faces of plastic-embedded bone fragments as harvested for grafting, or recovered after a period in situ as a graft. The methods enabled remarkably detailed information on bone content, maturation and turnover to be gleaned from tiny scraps of bone. Microfractures in the harvested bone were repaired at the graft site, with welding of old and new bone indicating revascularization. Human cranial bone grafts successfully stimulated bone cell differentiation, supported new bone formation on resorbed and unresorbed surfaces, and underwent bone turnover. The type and organization of new bone reflected the growth rate and maturation of the graft rather than the age of the patient.
Spinal somatosensory evoked potentials were recorded in 35 neurologically normal patients undergoing surgery for scoliosis. The recording electrodes were placed in the dorsal epidural space. Stimulation was of the tibial nerve in the popliteal fossa and the posterior tibial and sural nerves at the ankle. At thoracic levels the response consisted of at least 3 components with different peripheral excitation thresholds and spinal conduction velocities (range 35-85 m/sec). All components were conducted mainly in tracts ipsilateral to the stimulus, component 1 being most laterally located. At low stimulus intensity only the fastest activity was recorded but higher intensities elicited additional, slower conducting components. Component 1 was much less prominent when the posterior tibial nerve was stimulated at the ankle and absent from the (cutaneous) sural nerve response. Component 1 is likely to be due to the stimulation of group 1 muscle afferents which terminate in the dorsal horn and activate second-order neurones, many of whose axons go to form the ipsilateral dorsal spinocerebellar tract. Components 2 and 3 are believed to be largely cutaneous in origin and to be conducted mainly in the dorsal columns.
Eighty-nine and a half per cent of the population of a general practice over the age of 49 years were screened for glaucoma and high risk ocular hypertension requiring treatment. Screening took place using semi-automated intraocular pressure and visual field equipment operated by non-ophthalmologically trained staff. An experienced ophthalmologist examined all patients in a single blind manner to reduce false negatives to a minimum. Patients suspected of requiring treatment on the grounds of raised intraocular pressure, abnormal visual fields or suspicious optic discs were subsequently examined in a hospital clinic. Treatment criteria, as commonly practiced, were carefully defined and the sensitivities and specificities of the methods of screening used were calculated. One and three tenths per cent of the practice population were known to be receiving treatment prior to the study and a further 1.4% were found to require treatment after screening. The sensitivity and specificity of the non-contact tonometer were 91.7% and 95.6% respectively with a predictive power of 22.5% for a positive result. The mean time taken to perform the test in both eyes was two minutes. Seventy per cent of the patients with pressures over 22 mmHg in both eyes on screening were found to require treatment. The routine use of the field screener did not increase either the sensitivity or specificity of the screening process but its use in cases with raised intraocular pressure is advised to indicate the degree of urgency of the referral. An algorithm based on the results of the study is suggested when planning the use of semi-automated equipment to screen for ocular disease related to raised intraocular pressure.
The cost of detecting a case of glaucoma in a community based screening programme was calculated using data from a pilot study on a population aged 50 and over. The cost per screen was estimated at 3.35 pounds with a total cost of 311 pounds per case detected. These estimates include the cost of both the algorithmically based screening programme and the hospital assessment of true and false positives. These costs are considered to compare favourably with the potential costs incurred by paying optometrists to screen high risk groups whilst providing the opportunity to detect over twice the number of cases of occult glaucoma.
The incidence of autoantibodies to glomerular basement membrane (AGBMA) and neutrophil cytoplasmic antigens (ANCA) in the initial sera of 889 consecutive patients with a suspected diagnosis of rapidly progressive glomerulonephritis, was determined by prospective study. Forty-seven (5%) were positive for AGBMA alone, 246 (28%) were positive for ANCA alone, 576 (65%) had neither autoantibodies while 20 (2%) had both. Clinical and pathological data collected from patients with both autoantibodies suggested the coexistence of anti-glomerular basement membrane disease and systemic vasculitis. Together, assays for AGBMA and ANCA are important in the diagnosis and management of rapidly progressive glomerulonephritis and may help its further classification.
An overview of developments that have occurred in meat species identification over the last decade is presented. It starts by noting the different requirements for speciation techniques over the period, describes the complex nature of meat in terms of chemical composition and shows how the chain of events from slaughter to retail gives rise to opportunities for deliberate adulteration or innocent contamination. The limitations of techniques such as electrophoresis and isoelectrofocusing are pointed out where the analysis of mixed meats is concerned; attention then focuses on the range of techniques based on antigen-antibody interactions: agar gel immunodiffusion, counter immuno-electrophoresis and enzyme-linked immunosorbent assay (ELISA) in three formats. The choice of analyte is discussed, firstly for the analyses of raw meat materials and secondly, for heat-processed meat products. In the first example, blood serum proteins are used almost exclusively despite the limitation that their presence does not necessarily denote the presence of the corresponding muscle tissue (meat). For cooked products, a new range of antisera are necessary, based on thermally stable components derived from the tissues. By using different formats of ELISA, it is demonstrated that different responses can be obtained for heat-processed meat versus processed offal, and that determination of a species meat content in a cooked mixed meat product is possible. Techniques for improving the specificity and performance of antisera are discussed briefly, with the future introduction of thermally stable, muscle-specific monoclonal antisera being seen as the way forward.
Our studies have shown that the fluorescence mode can be used to good effect in both tandem scanning microscopes (TSM: direct view confocal microscopes) as well as confocal scanning laser microscopes (CSLM). Applications are presented which show that the two great advantages of TSM are real-time viewing and real colour, which allow faster use and interpretation. CSLM are complementary, not competitive, being currently more sophisticated for low-level fluorescence work. This is equally possible with available TSM, but requires further development using CCD cameras and image-processing systems.
Three-dimensional information is necessary for the proper investigation of the interrelationships of bone cells, and of the complex interface between these cells and the bone matrix they form and destroy. The use of fluorescence confocal microscopy was explored in the determination of the distribution of immunolabelled actin and vinculin--cytoskeletal and attachment proteins--in isolated chick bone cells cultured on dentine, and in neonate rat and rabbit calvaria. Confocal imaging, compared with conventional fluorescence imaging, greatly enhanced the interpretation possible.
The functional capacity of isolated osteoclasts is measured by determining the volume of bone or dentine which they can resorb in vitro when cultured on flat tissue slices. Previous SEM stereophotogrammetric evaluations showed that the measurement of total resorptive area per sample, number of pits per sample, area per pit, etc., may be insufficient and that the volume to area ratio may be of utmost importance. A new procedure for the 3-D description and measurement of resorption pits using confocal microscopy has been established. Osteoclasts were cultured on slices of dentine which were prepared as for SEM. They were imaged with a Tracor Northern TSM equipped with piezo-electric translators for the objective lens focusing motion, interfaced to a TN8500 computer, using a TV camera for image transfer. The procedure consisted of generating a zeta map image of the focus depth at which maximum brightness was found at each pixel. Constructing binary masks corresponding to (i) the edge of the resorption pit to define the area beneath which the volume is to be calculated, and (ii) a uniform width at a small distance outside the edge of the pit, enabled the average height of the original surface to be measured and the slice above the pit to be subtracted. After subtraction of the volume element which lay above the top of the original specimen surface, the zeta map is a measure of both the area and volume of the pit.
Suprathreshold field screeners are in common use for the detection of glaucomatous field loss. The predictive power of a positive result (PP+) depends on the sensitivity and specificity of the screener in the population in which it is to be used. Using data from 755 normal individuals (1510 eyes), we calculated the PP+ of the Henson CFS2000 screening programme for a population aged 50 and over. 4.3% of normal eyes failed the screening programme. Ignoring one or two misses on the screening programme immediately adjacent to the disc reduced this figure to 1.3% and significantly improved the PP+ of the programme. Calculations of the PP+ at increasing glaucoma prevalence levels indicates this to be particularly relevant at low levels such as those encountered when screening middle aged and elderly populations. Optometrists should perform routine field analysis when screening for glaucoma provided they adhere to strict protocols.
A validated postal questionnaire has been used to establish the prevalence of dyspeptic symptoms in five geographical locations from the south coast of England to the north of Scotland. The six month period prevalence of dyspepsia in the 7428 respondents to the questionnaire is 41% and equal between the sexes, with similar prevalence rates in the centres studied. There is considerable overlap between upper abdominal symptoms and symptoms of heartburn; 56% of patients with dyspepsia experience both groups of symptoms. Symptom frequency falls progressively with age in men and women, but the proportion of people seeking medical advice for dyspepsia rises with age. One quarter of the dyspeptic patients studied have consulted a general practitioner about their symptoms. This study suggests that the prevalence of dyspepsia in the community has changed little over the last 30 years, despite evidence that the frequency of peptic ulcer disease is falling. Symptom prevalence is unrelated to social class, but this factor is associated with consultation behaviour, the consultation rate rising from 17% in social class 1 to 29% in social class 4. The use of investigations--barium meal and endoscopy--is similarly related to social class; the lowest rate for ulcer diagnosis (4.7%) is found in social class 1 and the highest (17.1%) in social class 5.
The objective of this study was to determine the effect of feed restriction and repletion on myofibrillar protein turnover in cattle. Crossbred steer calves (n = 12) about 310 d of age were assigned randomly to a diet of corn and silage that was 1) provided ad libitum for 146 d (ALC) or 2) restricted so steers gained .2 kg/d for 80 d but received ad libitum access to feed thereafter for 66 d (RFC). At 27, 55, 97, 118 and 146 d a 24-h urine sample and a blood sample were obtained. Urine was analyzed for N tau-methylhistidine (N tau-MH), creatinine (C), urea nitrogen (UN) and total nitrogen (TN). Serum samples were analyzed for hydroxyproline (HYP), C and albumin (A). Body weights were lower (P less than .05) in RFC at 55, 97, 118 and 146 d. Excretion of N tau-MH was lower (P less than .05) in the RFC at 27 and 55 d but higher at 118 d. Urinary C excretion was higher in ALC at the last four sample times. Urinary UN and TN excretion were lower (P less than .05) in RFC at 55, 97 and 118 d; urinary UN also was lower (P less than .05) at d 146. Serum A was higher (P less than .05) in ALC at 55 and 118 d, respectively. Serum HYP was higher (P less than .05) in RFC at 27 and 55 d. Calculated myofibrillar protein breakdown rates (FBR) and fractional synthesis rates (FSR) were higher (P less than .05) in RFC at the last two sampling periods; FSR was lower for the RFC at the first sampling period.(ABSTRACT TRUNCATED AT 250 WORDS)
The objective of the present study was to determine whether injecting chicks with trilostane, a beta-hydroxysteroid dehydrogenase inhibitor, affected growth and protein synthesis in muscle and liver. A preliminary study was performed using a total of 72 chicks to determine the dose-response of trilostane (0, 2, 8, 32, 64 and 200 mg trilostane/kg of body weight suspended in .9% saline) on serum corticosterone concentration during a 2 wk and 2 h exposure. A second study was performed using 48 broiler chickens that were assigned at 1 wk of age to receive daily subcutaneous injections of either trilostane (65 mg/kg of body weight; TR) or .9% saline (ST). Six birds from each treatment group were killed at 2 and 3 wk of age. The pectoralis major (PM) and two leg muscles (gastrocnemius and peroneus longus; LM) were dissected and weighed, and concentrations of protein, DNA, and RNA were determined. An additional 6 birds within each time period and treatment group were killed to measure whole body proximate composition. A second experiment was performed using the same experimental design and 20 chicks, in which fractional synthesis rates were measured in 5 birds from each treatment group by infusion and incorporation of radioactive tyrosine. Serum corticosterone concentrations were lower (P less than .05) in the chicks injected with 64 and 200 mg trilostane/kg of body weight during a 2-wk period. The TR chicks gained 8 to 10% faster (P less than .05) than the ST birds.(ABSTRACT TRUNCATED AT 250 WORDS)
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The long-term clinical outcome and costs of treatment of hyperthyroidism with radioiodine have been examined in two cohorts of patients from Sheffield and Scotland. The majority of patients in both series were considered to have Graves' disease. The Sheffield patients (660) were included in a trial of three radioiodine dose regimens of 3,500 (312), 7,000 (323) and 14,000 (25) rad determined using a formula for accurate dosimetry. The Scottish patients (3,920) drawn from five centres in Aberdeen, Dundee, Edinburgh, Glasgow and Inverness were treated using an arbitrary scale, for the activity of radioiodine administered, related to goitre size. Their results are grouped into five MBq 'dose' bands: 37-185, 186-370, 371-555, 556-740 and 741+. The proportion of patients with persistent hyperthyroidism was higher in both cohorts for low-dose radioiodine regimens, but 15-25% of patients who received high doses showed persistent hyperthyroidism. Early and late onset hypothyroidism was lower after low doses but differences between the treatment groups were small in terms of clinical benefit. Total morbidity at 10 years follow-up, in terms of hyperthyroidism, and hypothyroidism, was highest after low-dose therapy. There was little variation in total costs, but patient costs were lowest for the Scottish regimen and highest for low-dose therapy. A dose of at least 370-555 MBq which will ensure early elimination of hyperthyroidism will also limit the medical workload and total costs.
Osteoclasts were isolated mechanically from chick long bones and cultured on dentine for three days in MEM/10% FCS with or without 1 mg/l NaF, (near to therapeutic ranges for serum fluoride levels) or 15 mg/l NaF (which has been found to reduce the volume:plan-area ratios of resorption pits in vitro). The distribution of close contacts with the substratum was determined by immunolabelling of vinculin and confocal fluorescence microscopy. Four characteristic patterns of contacts were observed: infilled discs, rings, crescents and patches: these reflect the progress of the cell in the process of pit formation. Cell-substratum adherence was more extensive than previously reported with contacts often extending down the sides of pits and sometimes across the floor. This distribution explains the curved shape of unilocular pits and the kidney-shaped extensions of multilocular pits. The peripheral creeping of the contact region was more marked in the osteoclasts of the 15 mg/l NaF cultures, and these cultures showed a decrease in pit depth and inhibition of osteoclastic movement in the presence of fluoride.
A study of antithyroid drug (ATD) therapy with a mean follow-up period of 10 years (range 2-25) in 434 patients with Graves' disease has been made by linking hospital records with those of a central follow-up register. The majority (89%) were treated with carbimazole and 87% received combined therapy with triiodothyronine (T3) (73%) or thyroxine (T4) (14%). Sixty-one per cent were assessed for T3 suppression tests on completion of treatment, of whom 61% (95% CL, 55-67%) suppressed. The overall 5-year cumulative proportion developing recurrent hyperthyroidism was 54-62% with rates of 26-44% in suppressed patients and 65-79% in those not suppressed. In unsuppressed patients, most (72%) of the recurrences occurred within 1 year with only an additional 10% predicted up to 10 years. In suppressed patients 30% of recurrences occurred in the first year, 60% between 1 and 5 years and a further 10% between 5 and 10 years. Suppression with T3 is probably the best and cheapest predictor of outcome but has an accuracy of only 70% for both positive and negative tests which limits its usefulness in planning long-term follow-up and surveillance. A standard format should be adopted for the analysis and reporting of follow-up studies, based on actuarial methods of estimating the cumulative proportion with recurrences or other events, to facilitate comparisons between different centres.