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Biomedical subjects

C Cooper

Publications and source records attributed to C Cooper.

At least 397 records · Page 22Linked to original sources

Oxidised low density lipoproteins induce iron release from activated myoglobin.

Recent reports have detected the presence of iron in human atherosclerotic lesions [Biochem. J. 286 (1992) 901-905]. This study provides evidence for a biochemical mechanism whereby iron is released from myoglobin by low density lipoprotein (LDL) which has become oxidised by the ferryl myoglobin species. The haem destabilisation and iron release are inhibited by monohydroxamate compounds and desferrioxamine through their ability to inhibit the propagation of LDL oxidation. Thus, iron may derive from the myoglobin released from ruptured cells in the oxidising environment of the atherosclerotic lesion.

Electron Spin Resonance Spectroscopy↗

Population-based study of survival after osteoporotic fractures.

Vertebral fractures are the most frequent of the fractures associated with osteoporosis, yet little is known of their impact on health in the United States. To aid in this understanding, the authors examined the survival rate of 335 residents of Rochester, Minnesota, who had an initial radiologic diagnosis of vertebral fracture between 1985 and 1989. Seventy-six died during 809 person-years of follow-up. The overall survival rate was worse than expected, and diverged steadily from expected values throughout the course of the study. At 5 years after diagnosis, the estimated survival was 61% compared with an expected value of 76% (relative survival = 0.81, 95% confidence interval (CI) 0.70-0.92). The 5-year relative survival after a hip fracture in Rochester was a comparable 0.82 (95% CI 0.77-0.87), but there was a much greater excess of deaths within the first 6 months as compared with patients with vertebral fractures. The 5-year relative survival rate after a distal forearm fracture was 1.00 (95% CI 0.95-1.05). Clinically diagnosed vertebral fractures are rarely fatal, and the reduced survival seen subsequently could related to comorbid conditions. Nonetheless, the excess mortality should be accounted for in assessing the public health impact of osteoporosis.

Arm Injuries↗

Detection of point mutations in the p53 gene: comparison of single-strand conformation polymorphism, constant denaturant gel electrophoresis, and hydroxylamine and osmium tetroxide techniques.

A comparison was made between the 3 most commonly used techniques for the detection of point mutations: single-strand conformation polymorphism (SSCP), constant denaturant gel electrophoresis (CDGE), and hydroxylamine and osmium tetroxide used in amplification mismatch cleavage analysis (HOT). Using human DNA samples containing known mutations in the p53 gene, SSCP detected 90% of mutations (18/20), CDGE detected 88% (15/17) pre-decoding of the samples but 100% when the mutations were known and the CDGE conditions optimized, and the HOT technique was 100% accurate, although 1 mutation was missed through careless examination of the gel. The positive and negative aspects of each of the techniques are considered and suggestions are made regarding the particular situations in which each of them is most useful.

DNA, Single-Stranded↗

Epidemiology and prevention of osteoporosis in urbanized Asian populations.

The incidence rate of hip fracture in Hong Kong in 1989 was calculated from hospital admission data and the census population. The incidence rate has increased 3-fold since 1966 to reach 9 per 1000 in men and 13 per 1000 in women 80 years and over. The age-adjusted rate was comparable to that in Singapore but higher than that in Japan. A case-control study was conducted on 280 women and 120 men with hip fracture and 800 controls. The relative risk for hip fracture increased with a low calcium intake, being 2.9 (95% confidence interval 1.9 to 4.6) in the lowest quartile. The relative risk for hip fracture was also significantly increased in subjects who did not perform load-bearing activity every day. Osteoporosis may be prevented by an adequate calcium intake and load-bearing activity in urbanized Asian populations.

Adult↗

Prevalence and incidence of vertebral deformities.

There is a need to identify vertebral fractures from radiographs taken at a single point in time, but considerable controversy surrounds the methods to be used. We extended a data set to comprise baseline radiographs of the thoracic and lumbar spine on an age-stratified random sample of 762 Rochester, Minnesota, women and used revised methods to define vertebral deformities morphometrically. Changes in the method of measuring vertebral heights, changes in the source of normal values for vertebral measurements and changes in the criteria for assessing vertebral deformity had little impact on estimated prevalence and incidence in this population. The prevalence of any vertebral deformity was estimated at 25.3 per 100 Rochester women aged 50 years and over (95% CI, 22.3-28.2), while the incidence of a new deformity in this group was estimated at 17.8 per 1000 person-years (95% CI, 16.0-19.7). Projected nationally, these data suggest that over 500,000 white women in the United States develop vertebral deformities for the first time each year and that over 7 million white women aged 50 years and over might be affected at any given time. These estimates are limited by the absence of a reliable 'gold standard' with which to determine false positive and false negative rates associated with this or any other morphometric method. Information on the health consequences of vertebral deformities of various sorts would be most helpful in choosing between alternative approaches to defining them.

Aged↗

The epidemiology of fragility fractures: is there a role for bone quality?

Fragility fractures, particularly those of the hip, vertebrae, and distal forearm, constitute a major public health problem. The two ultimate determinants of fracture are bone strength and propensity to trauma. Bone strength depends not only upon bone mass but also upon a variety of qualitative aspects of bone structure. These include its architecture, the amount of fatigue damage it has sustained, and changes in its bulk material properties, indices that are collectively subsumed into the term "bone quality." Fragility fractures show differences in their patterns of incidence by age, sex, ethnic group, geographic area, and season. Many of these differences are currently unexplained, and disorders of bone quality might contribute to them. There are two fracture sites at which evidence implicates bone quality more directly--the spine and proximal femur. Many vertebral compression fractures follow minimal trauma, and controlled studies suggest that vertebral microarchitecture contributes to fracture risk independently of vertebral bone mass. At the hip, observational studies have pointed to a role for disordered trabecular architecture, accumulation of microfractures (fatigue damage), and the accumulation of osteoid. The extent to which these phenomena act independently of bone mass, however, remains uncertain.

Adult↗

Munchausen syndrome by proxy: patterns of presentation to pediatric surgeons.

Munchausen syndrome by proxy is an increasingly reported insidious disorder in which illness in a child is fabricated and/or induced by the parent. Over a 5-year period at North Carolina Children's Hospital 10 such children were identified after having presented to the Pediatric Surgical Service. In reviewing this experience, we have identified two patterns of presentation. Apnea, seizures, and cyanosis comprised the pattern most frequently seen in infants. A history of persistent diarrhea and vomiting, although seen in two infants, was the more common pattern in older children. As they got older, four of the infants subsequently were noted to have the childhood pattern of symptoms. The mother was the perpetrator in all cases with the child's illnesses being induced by a number of different mechanisms. The most useful diagnostic tool proved to be isolation of the child from the parent. Resolution of symptoms in parental absence was a consistent finding especially in fabrication cases and was the key to diagnosis. Video telemetry confirmed the diagnosis in two infants and screens for toxins were diagnostic in three others. Awareness of patterns of presentation and parental behavior is critical to establishing an early diagnosis and avoiding needless diagnostic and operative procedures.

Adolescent↗

Oral contraceptive pill use and fractures in women: a prospective study.

It has been suggested that use of the oral contraceptive pill by women confers protection against osteoporosis later in life. However, cross-sectional studies of bone density among pill users have yielded discrepant results. We therefore investigated the relationship between pill use and subsequent occurrence of fracture in a cohort of 46,000 women enrolled in the Royal College of General Practitioners Oral Contraception Study during 482,083 person-years of follow-up. Fracture risk was lower among multiparous women, non-smokers, and those of lower socio-economic class. The risk of subsequent fractures among the women who had ever used the oral contraceptive pill was significantly greater than that among women who had never used it (relative risk 1.20, 95% confidence intervals 1.08-1.34) after adjustment for these variables. When the analysis was confined to forearm fractures, no significant effect of pill use on fracture risk was detected. Although the study only includes limited observation of older women to date, these data do not support the hypothesis that pill use protects women against the occurrence of osteoporotic fractures in later life.

Adult↗

The epidemiology of vertebral fractures. European Vertebral Osteoporosis Study Group.

Vertebral fractures are recognised as a hallmark of osteoporosis, yet little is known of their epidemiology. This deficiency limits accurate characterisation of the public health importance of osteoporosis. Assessment of the impact of vertebral fractures has been hampered by the absence of formal criteria for identifying fractures on a thoracolumbar radiograph. Initial methods relying upon subjective radiological assessments have given way to morphometric measurements of vertebral heights, with deformities defined according to various algorithms. These methods have been used in a series of studies performed in Rochester, MN, to determine the incidence, outcome, and time trends of vertebral deformities. The results suggest a prevalence rate of vertebral deformity of 25.3 per 100 Rochester women aged 50 years and over (95% CI, 22.3-28.2), with an estimated incidence of 17.8 per 1,000 person-years. The incidence of clinically diagnosed vertebral fractures among women in the same population was 5.3 per 1,000 person-years, suggesting that around 30% of such deformities in women receive clinical attention. Morphometric measurement on the radiographs of women with clinically diagnosed fractures revealed that 80% had grade 2 ( > 4 SD) deformities. Comparable data on the occurrence and health impact of vertebral deformities throughout Europe are urgently required. The European Vertebral Osteoporosis Study (EVOS) is a multicentre epidemiological study that aims to address this issue. It is designed as a radiographic prevalence study in 34 European centres.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Iron speciation at physiological pH in media containing ascorbate and oxygen.

The stability of iron ascorbate solutions was investigated, under both anaerobic and aerobic conditions, with the Fe2+ and Fe3+ indicators, respectively ferrozine and mimosine, at different pH values. The species present under the differing conditions were investigated by electron paramagnetic resonance (EPR) and Mössbauer spectroscopy and by gel-filtration chromatography. At physiological pH (6.8-7.4) iron ascorbate solutions rapidly form mononuclear chelatable Fe3+ species as reflected by indicator studies and EPR. Mössbauer spectroscopy fails to detect any Fe2+ species. EPR studies show a time-dependent decrease in rhombic Fe3+, particularly in oxygenated buffers, consistent with a conversion to polynuclear Fe. O2 uptake studies show that the conversion of Fe2+ to Fe3+ in Fe-ascorbate solutions at pH > 7.0 was accompanied by rapid O2 consumption but preceded depletion of ascorbate. Addition of high concentrations of mannitol (50-200 mM) reduces the O2 consumption and partly stabilizes the rapidly chelatable Fe form. Gel filtration studies show that the oxidation of Fe-ascorbate solutions at pH 7.4 is accompanied by an increase in the apparent relative molecular mass of the Fe, presumably due to Fe polymer formation. These studies indicate that inherent instability of Fe-ascorbate solutions above neutral pH and clearly have important implications in the use of ascorbate in studies of Fe physiology.

Animals↗

Height, occupation and back pain in a national prospective study.

Back pain is an important public health problem but there is a paucity of knowledge about risk factors and causal mechanisms. Previous studies have shown that tall men are more at risk of back pain, although observations in women have been less consistent. This paper presents findings from a national longitudinal study of 3262 men and women aged 43 yr. Standing height and sitting height were related to 18-month reported prevalence of 'sciatica, lumbago or severe backache' in both men and women. The paper investigates explanations for these findings using previously collected data on childhood growth and detailed lifetime occupational histories. Neither greater susceptibility of tall men to heavy lifting, nor the timing of growth, were able to account for these relationships. To assess further the association between height and back pain, information is needed on the relationship between stature and characteristics of spinal structure.

Adult↗