Biomedical subjects
Publications and source records attributed to C Cooper.
This case report describes the occurrence of non-specific upper limb symptoms, in a 47-year-old female scientific officer, associated, with manual pipetting. The discussion considers the difficulty of risk assessment and reduction for this common procedure.
Osteoporosis is a common condition, which is recognised by the occurrence of fragility fractures and leads to considerable mortality and morbidity with huge financial implications world-wide. Based on predicted demographic changes, the implications of this disease are set to increasingly affect the healthcare budgets of all nations. The determinants of fracture are skeletal factors, such as peak bone mass, the rate of bone loss and extra-skeletal factors, which include trauma and the response to that trauma. Some of these factors are genetically determined, but several have environmental origins, which could, theoretically, be manipulated. There are two potential means whereby osteoporotic fractures might be prevented. Measures could be targeted at the entire population, with the aim of shifting the distribution of bone mass in a beneficial direction, through modifying the behaviour of all individuals. The alternative is a high risk approach, whereby intervention is targeted only at those considered to have the greatest risk of future fracture. Mass bone density screening falls into the second approach. Bone density is a good predictor of future fracture risk, and cost-effectiveness analyses of the high risk approach suggest economic benefits of policies targeting pharmacological treatment to those individuals at highest risk. However, there are important concerns about the levels of compliance achievable with such therapeutic interventions, the balance of risks and benefits for some of these interventions (for example, hormone replacement therapy), and the outcome when treatment is discontinued. On current evidence, it is certainly not appropriate to target hormone replacement therapy for women at the menopause on the basis of a bone density screening programme. However, newer bone-specific agents are being developed which might be administered at later ages, closer to the time when fracture incidence rates rise steeply. Bone densitometry has been shown to predict fractures even in the elderly, and high risk strategies for the targeting of such agents (for example, the bisphosphonates or selective oestrogen receptor modulators) will remain important research issues for the future.
BACKGROUND: We investigated the validity of routine hospital and mortality hip fracture data in one English Region and estimated trends in hip fracture between 1978-1981 and 1993-1995. METHODS: We identified from Hospital Episode System (HES) data for 1993-1995 all hip fracture episodes relating to individual patients aged over 65 years resident in Wessex. We determined from the discharge method code whether an individual had died during that admission. The number of individual regional and district admissions and deaths were compared with those presented in the Public Health Common Data Set. We compared regional admission rates with data for 1978-1981 from a previous study. RESULTS: National comparative indicators for hip fracture overestimated individual admissions in Wessex by 17 per cent (in health authorities by 1-56 per cent). National comparative indicators for hip fracture mortality underestimated individual deaths in Wessex by 48 per cent. Between 1978-1981 and 1993-1995 the age-sex-standardized hip fracture rates rose from 1.90 to 2.63 per 1000 per year for men and from 5.70 to 7.70 per 1000 per year for women. Rates increased in all age groups except those aged 65-69 years. There was also a small fall in absolute mean annual numbers in this age group. The rates also fell in females aged 70-74. CONCLUSIONS: It is possible to adjust routine national HES data to take account of multiple episodes within a single admission. These methods should be applied to national comparative indicators for hip fracture admission and deaths. Hip fracture rates continue to rise in those aged over 70 years. There may be a cohort effect with those born after 1925 showing stable rates which needs further investigation.
Although osteoporosis is generally regarded as a disease of women, up to 30% of hip fractures and 20% of vertebral fractures occur in men. Risk factors for osteoporotic fractures in men include low body mass index, smoking, high alcohol consumption, corticosteroid therapy, physical inactivity, diseases that predispose to low bone mass, and conditions increasing the risk of falls. The key drugs and diseases that definitely produce a decrease in bone mineral density (BMD) and/or an increase in fracture rate in men are long-term corticosteroid use, hypogonadism, alcoholism and transplantation. Age-related bone loss may be a result of declining renal function, vitamin D deficiency, increased parathyroid hormone levels, low serum testosterone levels, low calcium intake and absorption. Osteoporosis can be diagnosed on the basis of radiological assessments of bone mass, or clinically when it becomes symptomatic. Various biochemical markers have been related to bone loss in healthy and osteoporotic men. Their use as diagnostic tools, however, needs further investigation. A practical approach would be to consider a bone density more than one SD below the age-matched mean value (Z < -1) as an indication for therapy. The treatment options for men with osteoporosis include agents to influence bone resorption or formation and specific therapy for any underlying pathological condition. Testosterone treatment increases BMD in hypogonadal men, and is most effective in those whose epiphyses have not closed completely. Bisphosphonates are the treatment of choice in idiopathic osteoporosis, with sodium fluoride and anabolic steroids to be used as alternatives.
This study examined the effects of cyclical etidronate, when used in routine clinical practice, on the prevention of fracture. Information was obtained from 550 general practices in the UK that provide their medical records to the General Practice Research Database. A total of 7977 patients taking cyclical etidronate treatment and 7977 age-, sex- and practice-matched control patients with a diagnosis of osteoporosis were analysed. People taking cyclical etidronate had a significantly reduced risk of non-vertebral fracture (by 20%) and of hip fracture (by 34%) relative to the osteoporosis control patients. The relative risk of non-vertebral fracture was 0.80 (95% confidence interval 0.70-0.92), that of hip fracture 0.66 (0.51-0.85) and that of wrist fracture 0.81 (0.58-1.14). When fracture incidence rates were compared between the two groups, the rate of non-vertebral, hip and wrist fracture decreased significantly (P < 0.05) with increasing etidronate exposure. The results of this study complement and extend clinical observations supporting the anti-fracture efficacy of cyclical etidronate therapy.
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OBJECTIVE: Geographic differences in the prevalence of hip osteoarthritis (OA) have been ascribed to differences in the frequency of acetabular dysplasia among different ethnic groups. However, there are few data on the shape of the acetabulum in various populations around the world. We examined this issue in samples of pelvic radiographs from Britain and Japan. METHODS: Measurements were made on the pelvic radiographs of 1303 men and 195 women, aged 60-75 yr, who attended for i.v. urography in two British centres. These were compared with 99 men and 99 women aged 60-79 yr who were included in a population-based study in a rural community in Japan, and who agreed to undergo standardized pelvic radiography. Acetabular dysplasia was assessed by morphometric measurement of the centre-edge (CE) angle and acetabular depth. RESULTS: The mean CE angle among men was 36 degrees (95% CI 35-37 degrees ) in Britain and 31 degrees (95% CI 29-32 degrees ) in Japan; that in women was 37 degrees (95%, CI 36-38 degrees ) in Britain and 31 degrees (95% CI 29 33 degrees ) in Japan. The mean values of acetabular depth were also significantly (P < 0.001) lower in Japan than in Britain. However, the prevalence of hip OA was lower in Japan (0% in men, 2% in women) than in Britain ( 11% in men, 4.8 / in women). In a random effects model, there were negative relationships between measures of acetabular dysplasia and minimum joint space among individuals. CONCLUSIONS: We conclude that there are marked differences in pelvic morphometry between Britain and Japan. The acetabular dimensions of Japanese subjects are considerably shallower than those of their British counterparts of similar age and sex. Nevertheless, hip OA is more frequent in Britain than in Japan. Further studies are required on the risk factors for hip OA in Oriental populations, in order that the aetiology of this disorder can be better understood.
BACKGROUND: Recent epidemiological studies suggest that post-menopausal hormone replacement therapy might reduce the risk of hip osteoarthritis (OA) in women. However, the association of the disorder with other reproductive variables is controversial. We addressed this issue in a population-based case control study among 413 female cases and 413 age- and sex-matched controls. METHODS: A total of 413 women listed for hip replacement because of primary OA over an 18 month period were compared with an equal number of controls selected from the general population and individually matched for age and general practice. Information about reproductive variables was obtained by questionnaire administered at interview. RESULTS: The risk of hip OA was significantly elevated among women who had had an oophorectomy (OR = 1.9, 95% CI 1.0-3.7). After adjustment for body mass index, the presence of Heberden's nodes, previous hip injury and past leisure sporting activity (all independent risk factors for hip OA), and for other reproductive variables, there was a non-significant, protective effect of long-term hormone replacement therapy, such that > or =5 yr of use was associated with a 40% reduction in risk (OR = 0.6, 95% CI 0.2-1.8). Paradoxically, short-term HRT use (up to 5 yr duration) was associated with an excess risk of hip OA (OR = 1.7, 95% CI 0.9-3.3). There was no association between the risk of hip OA and use of oral contraceptives, parity or hysterectomy. CONCLUSIONS: These data are consistent with previous studies suggesting a protective effect of long-term hormone replacement therapy on the risk of hip OA. By contrast, an elevation of risk in short-term users was demonstrated. Our results also suggest that risk is increased among women who have undergone unilateral or bilateral oophorectomy. Studies are required to investigate the mechanisms underlying these associations.
The prion protein (PrP), first identified in scrapie-infected rodents, is encoded by a single exon of a single-copy chromosomal gene. In addition to the protein-coding exon, PrP genes in mammals contain one or two 5'-noncoding exons. To learn more about the genomic organization of regions surrounding the PrP exons, we sequenced 10(5) bp of DNA from clones containing human, sheep, and mouse PrP genes isolated in cosmids or lambda phage. Our findings are as follows: (1) Although the human PrP transcript does not include the untranslated exon 2 found in its mouse and sheep counterparts, the large intron of the human PrP gene contains an exon 2-like sequence flanked by consensus splice acceptor and donor sites. (2) The mouse Prnpa but not the Prnpb allele found in 44 inbred lines contains a 6593 nucleotide retroviral genome inserted into the anticoding strand of intron 2. This intracisternal A-particle element is flanked by duplications of an AAGGCT nucleotide motif. (3) We found that the PrP gene regions contain from 40% to 57% genome-wide repetitive elements that independently increased the size of the locus in all three species by numerous mutations. The unusually long sheep PrP 3'-untranslated region contains a "fossil" 1.2-kb mariner transposable element. (4) We identified sequences in noncoding DNA that are conserved between the three species and may represent biologically functional sites.
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AIM: To determine whether fetal and infant growth, as assessed by weight at birth and weight at 1 year, are related to intraocular pressure. METHODS: 717 men and women born in Hertfordshire between 1920 and 1930, for whom records of birth weight and weight at 1 year were available, were examined. Visual fields were assessed using the Takagi central 25 degrees 75 point static threshold screening program. Tonometry was performed using the Perkin's tonometer. The disc was assessed by direct ophthalmoscopy through dilated pupils. RESULTS: A significant inverse relation was found between systolic blood pressure and birth weight. However, no association was found between birth weight or weight at 1 year and intraocular pressure, cup/disc ratio, or visual field defects. CONCLUSIONS: There was no evidence to support fetal or infant growth as being important factors for the subsequent development of raised intraocular pressure.
PURPOSE: To investigate the three-point Dixon technique as a method for obtaining fat-nulled images of contrast material-enhancing breast lesions with a 0.5-T open magnetic resonance (MR) imager. MATERIALS AND METHODS: Real and imaginary source images were obtained with an interleaved gradient-echo sequence with a repetition time of 550 msec and echo times of 12.8, 19.8, and 26.8 msec. Twenty-four to 28 sections were obtained in the sagittal plane with a 90 degrees flip angle, 256 x 192 matrix, 3-4.5-mm section thickness, and acquisition time of 10 minutes 54 seconds. A three-point Dixon reconstruction algorithm was used to generate water-specific, fat-specific, and combined images from the raw image data. Twelve breasts in 10 patients and one healthy volunteer were imaged. RESULTS: Three-point Dixon images were superior to extended two-point Dixon and fat-suppressed images and to images generated by means of subtraction of three-dimensional fast spoiled gradient-echo images obtained before contrast material injection from those obtained after. CONCLUSION: Three-point Dixon imaging provides a robust method for creating fat-nulled images of enhancing breast lesions in the 0.5-T open MR environment. Water-specific three-point Dixon images are successful in regions of B0 heterogeneity and are superior to fat-suppressed images. They are much less susceptible to motion artifact than are subtraction images.
Epidemiological studies suggest that retarded growth in infancy is associated with low adult bone mass. The mechanism underlying this association is unknown, but the programming of GH secretion or sensitivity by environmental influences during early development may play a role. We examined this issue in a sample of 37 healthy men, aged 63-73 yr, whose weight gain in infancy had been recorded. Venous blood samples were obtained under standard conditions every 20 min over a 24-h period. Measurements were made of the GH secretory profile, insulin-like growth factor I (IGF-I), IGF-binding protein-1 and -3, and GH-binding protein. Bone mineral density was measured at the lumbar spine and femoral neck using dual energy x-ray absortiometry. There was a statistically significant association between peak GH concentration (r = 0.46; P < 0.01) and fasting IGF-I concentration (r = 0.46; P < 0.01) with femoral neck bone density. After allowing for the peak GH concentration, median GH was negatively (P < 0.05) associated with bone mineral density. Weight at 1 yr was not related to peak GH, but was strongly related to the median GH concentration (r = 0.42; P = 0.01). These observations are consistent with a dual effect of GH secretion on bone density. High peak GH values drive IGF-I production and maintain bone mineralization in adult life. However, integrated GH secretion, after adjusting for the effect of pulse amplitude, is negatively associated with bone density in adult life. This particular characteristic of the GH secretory profile correlates with growth during infancy and might be programmed by environmental factors during intrauterine or early postnatal life.
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OBJECTIVE: We conducted a survey of the members of the Society of Computed Body Tomography/Magnetic Resonance to assess current techniques in liver imaging using helical CT. MATERIALS AND METHODS: The survey, which was designed to update earlier surveys from 1987 and 1993, included a questionnaire distributed to 77 members of the Society of Computed Body Tomography/Magnetic Resonance. RESULTS: Forty-nine members responded, representing 28 institutions. In 1993, 19% (5/26) of institutions used helical scanners, compared with 82% (23/28) in 1996. The group of institutions with helical CT served as the focus of this survey. In 1993, 58% of institutions used 1-cm collimation: in 1996, 78% (18/23) used thinner, 7- to 8-mm collimation. In 1987, 41% used power injectors compared with 85% in 1993 and 100% in 1996. In 1996, monophasic injections were used by 96% (22/23) of institutions. In 1993, most institutions used a contrast material injection rate of 1.5-2.0 ml/sec; in 1996, most used a 2.5-3.0 ml/sec injection rate. In 1993, 96% of institutions used 125-150 ml of contrast material; in 1996, 57% (13/23) of institutions used 125-150 ml and 30% of institutions used less than 125 ml of contrast material. A delay time of 21-45 see was used by 83% of institutions in 1993, whereas in 1996, 83% (19/23) of institutions used a longer delay time of 50-80 sec. In 1996, 13% of institutions used an individual scan delay technology and all institutions performed multiphasic scanning of hypervascular lesions. CONCLUSION: The availability of helical CT has changed radiologists' approach to liver imaging. The greatest effects of which are a more widespread use of power injectors, longer delay times, thinner collimation, increased contrast material injection rates, decreased contrast material volumes, and multiphasic scanning.
Plasma concentrations of lipoprotein (a) [Lp(a)] are increased in patients on renal replacement therapy. Lipoprotein (a) is increasingly being recognized as an independent cardiovascular risk factor. In an effort to explore the mechanism for elevation of Lp(a) in patients on dialysis we have performed turnover studies of Lp(a) with radioactive iodine. Lp(a) was isolated from 1 patient on hemodialysis (HD) and 1 patient on continuous ambulatory peritoneal dialysis (CAPD); the protein was labeled with 125I and returned to each patient. Lipoprotein (a) was subsequently isolated from the patients over a 15-day period and the decay of the specific radioactivity of Lp(a) was used to determine the fractional catabolic rate (FCR), which was 0.27 (pool/day) for the HD patient and 0.28 (pool/day) for the CAPD patient. These rates are indistinguishable from those measured in 4 patients with hypercholesterolemia (0.29, SEM = 0.01) and in 4 other familial hypercholesterolemic patients (0.29, SEM = 0.02) studied previously using the same method by Knight et al. (7). We found no difference in the FCR of patients on dialysis when compared to patients with hyperlipidemia and normal renal function. Increased plasma concentration of Lp(a) in our patients on renal replacement therapy is not due to decreased catabolism, but is caused by increased synthesis.
Fourteen cases of an atypical myeloproliferative disorder associated with consistent translocations involving 8p11-12 have previously been described. A t(8;13)(p11;q11-12) was the most common, but variant t(8;9)(p11-12;q32-34) and t(6;8)(q27;p12) were also reported. Here we have used a series of yeast artificial chromosomes (YACs) derived from the 8p11 and 13q11-12 regions to analyse one of the t(8;13) cases by fluorescence in situ hybridization (FISH). YACs flanking the 13q11-12 breakpoint and spanning the 8p11 breakpoint have been isolated. These YACs will facilitate characterization of the genes involved in this rearrangement.
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