Screening, ethics, and the law.
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Ethics, Medical↗
Biomedical subjects
D A Jones
Publications and source records attributed to D A Jones.
Incidence of leukaemia and other cancers in birth and schools cohorts in the Dounreay area.
OBJECTIVE: To determine whether a raised incidence of leukaemia in the Dounreay area occurred in children born to local mothers (birth cohort) or in those who moved to the area after birth (schools cohort) and also whether any cases of cancer have occurred in children born near Dounreay who may have moved elsewhere. DESIGN: Follow up study. SETTING: Dounreay area of Caithness, Scotland. SUBJECTS: 4144 children born in the area in the period 1969-88 and 1641 children who attended local schools in the same period but who had been born elsewhere. MAIN OUTCOME MEASURES: Cancer registration records linked to birth and school records with computerised probability matching methods. RESULTS: Five cancer registrations were traced from the birth cohort compared with 5.8 expected on the basis of national rates (observed to expected ratio 0.9, 95% confidence interval 0.3 to 2.0). All five cases were of leukaemia (2.3, 0.7 to 5.4). In the schools cohort three cases were found (2.1, 0.4 to 6.2), all of which were of leukaemia (6.7, 1.4 to 19.5). All eight children were resident in the Dounreay area at the time of diagnosis; thus no cases were found in children who were born in or had attended school in the study area but who subsequently moved away. CONCLUSION: The raised incidence of leukaemia in both the birth and schools cohorts suggests that place of birth is not a more important factor than place of residence in the series of cases of leukaemia observed near Dounreay area.
Child↗
Oxidative damage to plasma constituents by ozone.
The reaction of ozone (O3) with human blood plasma was studied to help understand possible events that could occur in the respiratory tract. Uric acid (quantitatively the most important scavenger) and ascorbic acid were oxidized quickly, protein-SH groups were lost more slowly, and there was no loss of bilirubin or alpha-tocopherol. There was little formation of lipid hydroperoxides and no detectable formation of 4-hydroxynoneal, hexanal or nonanal, or changes in lipoprotein electrophoretic mobility. Uric acid in human upper airway secretions may play a significant role in removing inhaled O3. Oxidative damage to lipids must not be assumed to be the key mechanism of respiratory tract O3 toxicity.
Adult↗
Reperfusion injury in skeletal muscle: a prospective study in patients with acute limb ischaemia and claudicants treated by revascularization.
A study was carried out to document the occurrence of rhabdomyolysis and renal complications in patients undergoing vascular reconstruction. Indices of muscle damage and renal function were monitored before, during and for up to 10 days after vascular reconstruction for a variety of conditions ranging from intermittent claudication to acute ischaemia. Seven patients with acute limb ischaemia (group 1) and nine with intermittent claudication (group 2) were studied prospectively. In group 1, median creatine kinase (CK) and myoglobin levels were markedly raised 24-48 h after surgery (CK, 29,370 units/l; myoglobin, 8.17 mg/l). Myoglobin reached its peak concentration and declined more quickly than CK, but both indices gave similar information about the extent of muscle damage. In contrast, patients undergoing elective surgery for claudication showed no significant departure from reference values for myoglobin or CK. All patients in group 1 underwent fasciotomy to relieve raised compartmental pressures and five were treated with alkali and mannitol to produce diuresis. Despite these measures, two patients suffered renal failure (peak creatinine levels 611 and 590 mumol/l) after successful revascularization and subsequently required haemodialysis; these patients did not have diuresis. One of these patients died following a stroke 8 days after surgery; the other survived and was discharged with a normal limb and restored renal function. There was no evidence of muscle damage or renal complications in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Kidney Injury↗
Measurement of fibre pennation using ultrasound in the human quadriceps in vivo.
Real-time ultrasound scanning was used to measure the angles of fibre pennation of vastus lateralis (VL) and vastus intermedius (VI) of the human quadriceps (n = 12) in vivo. The maximum isometric force and cross-sectional area of the quadriceps were also measured. With the knee at right-angles the mean fibre angles for VL and VI respectively were 0.133 (0.021) rad [7.6 degrees (1.2 degrees)] and 0.143 (0.028) rad [8.2 degrees (1.6 degrees)] [mean (SD)], which is within the range of angles measured on cadavers. The mean angle decreased in going from the contracted [VL, 0.244 rad (14 degrees); VI, 0.279 rad (16 degrees)] to the stretched [VL, 0.105 rad (6 degrees); VI, 0.122 rad (7 degrees)] position. There was a significant positive correlation between fibre angle and muscle cross-sectional area but no relationship between fibre angle and force per cross-sectional area. No increase in fibre angle was detected after 3 months strength training. We conclude that ultrasound can be used to measure pennation angles of superficial muscle groups but we could not demonstrate a relationship between pennation and force-generating capacity.
Exercise↗
Preliminary characterization of the lipid and protein components of the protective surface membranes of a pentastomid Porocephalus crotali.
All instars of the pentastomid Porocephalus crotali, in the tissues of rat intermediate hosts and the lung of rattlesnake definitive hosts, are covered by a vesicular or stacked membranous secretory product which is synthesized in sub-parietal cells (SPC) and channelled to the cuticle via multitudinous chitin-lined ducts. In rats this enveloping foam of vesicles survives for the duration of a cuticle. We have purified and partially characterized the lipid and protein composition of lamellate droplets from SPC of infective nymphs. Lipids in the droplets comprised a mixture of neutral and polar lipid classes with cholesterol being the major neutral lipid and phosphatidylcholine the dominant polar lipid. In addition, Triton X-114 phase separation of the protein component of droplets partitioned these into an aqueous phase (with a major band at 60 kDa), a detergent phase with two hydrophobic polypeptides (24 and 16 kDa) and an insoluble pellet containing several minor proteins and major bands at 31 and 107 kDa. Western blotting, with rabbit anti-lamellate droplet antiserum, strongly label only the 60 kDa and the two hydrophobic proteins. Significantly no proteins at all label with serum from infected rats from 50-150 days post-infection, a finding endorsed by indirect fluorescent antibody tests on sectioned V-VII stage nymphs. Possible immunomodulatory functions of SPC-derived surface membranes are discussed and, in this regard, they are compared with pulmonary surfactant, a product of alveolar Type II cells which lines all vertebrate lungs.
Animals↗
Contractile properties and susceptibility to exercise-induced damage of normal and mdx mouse tibialis anterior muscle.
1. The functional properties of tibialis anterior muscles of normal adult (C57BL/10) and age-matched dystrophin-deficient (C57BL/10 mdx) mice have been investigated in situ. Comparisons were made between tibialis anterior muscle strength, rates of force development and relaxation, force-frequency responses and fatiguability. Subjecting mdx and C57 muscles to a regimen of eccentric exercise allowed the hypothesis to be tested that dystrophin-deficient muscles are more susceptible to exercise-induced muscle damage. 2. mdx muscles were, on average, 30% stronger than C57 muscles and almost 80% heavier, but both had similar muscle lengths. Thus, although mdx muscles were stronger in absolute terms, their estimated force per unit cross-sectional area was significantly less than that of C57 muscles. 3. The force-frequency relationships of C57 and mdx muscles differed in that whilst, at 40 Hz, the former developed 70% of the force developed at 100 Hz, the latter developed only 55% of the maximal force. Twitch force was normal in mdx muscles, but contraction time was shortened, and the consequent reduction in fusion frequency probably explains the force-frequency differences observed between the two groups. 4. mdx muscles were less fatiguable than normal muscles when stimulated repeatedly at a frequency of 40 Hz. It is possible that the lower relative force at 40 Hz in mdx muscles entailed a lower energy demand and thus a slower rate of fatigue than seen in normal muscles. 5. Eccentrically exercised C57 muscles showed a large loss of maximal force for up to 12 days after exercise. Maximal force loss occurred 3 days after exercise (55% of non-exercised tibialis anterior muscle), which also corresponded with the period of greatest fibre necrosis. C57 muscles showed a significantly reduced 40 Hz/100 Hz force-frequency ratio at 1 and 3 days after exercise. This was primarily due to a reduced twitch amplitude rather than to a change in the time course of the twitch. It is unlikely, therefore, that the altered contractile characteristics of mdx muscle were a result of the presence of damaged but otherwise normal fibres. 6. C57 and mdx tibialis anterior muscles displayed similar degrees of force loss after exercise. Furthermore, the rate of recovery after the nadir of force loss was very similar for the two groups. By 12 days after exercise, force recovered to 76% and 80% of control in C57 and mdx muscles, respectively. Our findings do not support the hypothesis that dystrophin-deficient muscle is more susceptible to exercise-induced muscle damage.
Animals↗
Variable temperature infrared spectroscopy of cytosine-guanine base pairs: tautomerism versus polarization.
This report describes an infrared (IR) spectroscopic study of a model cytosine-guanine base pair. This base pair is part of a self-consistent experimental system based on lipophilic ribose derivatives of cytidine (C), guanosine (G) and O6-methylguanosine (O6MeG) that are soluble in non-aqueous, low dielectric solvents at appreciable concentrations. Previous experiments on this system have revealed different rotation dynamics for the amino bonds within the CG base pair, an observation that could be explained by the presence of rare tautomers (P.O. Lowdin, Reviews of Modern Physics 35,724 (1963)), or by mutual polarization of the base pairs (L.D. Williams, N.G. Williams and B.R. Shaw,J.Am.Chem.Soc. 112,829 (1990)). The IR spectra in the OH and NH stretching region indicate formation of hydrogen-bonded CG base pairs and self associates in 1,2-dichlorobenzene over a temperature range from 10 to 290K. Changes in the lineshapes and intensities of the IR bands with temperature correlate with phase transitions of the solvent, but no evidence is seen for an OH stretching band that would indicate the formation of hydroxyl tautomers within base pairs. Similarly, the relative intensities of the C = O stretching bands of CG in cyclohexane solution remain constant over this same temperature range, confirming that within the base pair, the tautomeric states of the bases remain essentially unperturbed in the 2-amino/6-keto form of G and the 2-keto/4-amino form of C. The spectra of O6-MeG aid in the band assignments, since this molecule is frozen in an equivalent of the 2-amino/6-hydroxyl tautomer, but without the OH group and its associated stretching band. We conclude that the probability of tautomerism does not appear to be sufficient to explain the different rotation dynamics for the two amino bonds of the CG base pair. Rather it is argued that mutual polarization within the base pair, which would increase the bond order of the amino bond of C within the base pair, can explain the results without the formation of unconventional tautomers.
Base Composition↗
The relationship of muscle and bone loss and activity levels with age in women.
Quadriceps strength and cross-sectional area (CSA), spine bone mineral density (BMD), bone mass in the mid- and distal femur and physical activity levels were measured in 216 healthy British women. Muscle strength, CSA and bone in the distal femur decreased linearly from the third decade. Cortical bone at mid-femur was maintained until the sixth decade. Spine BMD decreased from the fourth decade with an accelerated period of loss in the sixth decade. There were significant positive relationships between quadriceps strength and bone mass at all three skeletal sites. With age kept constant, physical activity levels did not correlate with any of the muscle or bone indices. The force-generating capacity of the quadriceps decreased with age. These results suggest a relationship between the loss of muscle and bone with age which cannot be explained by declining physical activity levels.
Adult↗
Caring for elderly dependents: effects on the carers' quality of life.
This study describes a survey of 256 informal carers and elderly people they support, and examines the impact of the caring role upon quality of life. Carers reported that many aspects of their physical and mental health as well as their social and family lives were affected by their caring. For many the caring activity was unremitting. Overall, daughters were the most likely to report deleterious effects on their lives. Dominant factors associated with stress were the relationship between carer and dependent, sex of the carer and effects on social and family life. While relationship and sex were also associated with anxiety, loneliness was the dominant factor associated with anxiety and depression. Older age of the dependent was associated with stress, carer's disability was associated with anxiety, and depression in the elderly person was associated with depression in carers. These findings indicate that community services and future policies should be oriented towards the needs of carers and their families and not solely to the needs of frail elderly people. In particular there is a need to consider an increase in the provision of flexible planned respite care.
Activities of Daily Living↗
Strength of skeletal muscle and the effects of training.
The performance of any sporting activity involves a combination of skill and strength and it is very difficult to disentangle their separate contributions. The strength of an individual muscle depends on a number of factors. The major factor is the cross-sectional area of the muscle but others include the extent to which the muscle can be activated by voluntary effort, the overall length of the muscle and the position in which it is used, the fibre type composition and the velocity at which the movement takes place. Over a period of 2 to 3 months the major benefit of training is to improve the skill with which the training exercise is carried out. The effect is very specific so that there is considerable doubt as to whether weight training does anything other than train the athlete to lift weights. Increases in muscle size and strength in a healthy athlete occur relatively slowly and apart from the fact that high forces are required, little is known about the factors which stimulate growth. Accumulation of metabolites and damage to the muscle fibres are possible stimuli for growth but the prescription of optimal training regimes remains a matter of personal choice between the athlete and trainer rather than athlete and physiologist.
Humans↗
Interactive obstructive uropathy in man.
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Diuresis↗
The protective effect of damaging eccentric exercise against repeated bouts of exercise in the mouse tibialis anterior muscle.
Using a damaging eccentric exercise regime of the mouse tibialis anterior (TA) muscle we have investigated the extent and time course of protection afforded by one bout of exercise against damage resulting from a second bout of activity. Maximal force and fibre morphology were preserved if the exercise was repeated within 21 days, but by 84 days muscles once again became susceptible to damage. Low-frequency force loss had a shorter time course of protection against repeated exercise, lasting less than 21 days. The results provide evidence for different mechanisms contributing to the development of muscle damage following eccentric exercise and provide a basis for characterizing the adaptive response of muscle to damaging exercise.
Adaptation, Physiological↗
Flexor to extensor tendon transfer for curly toes. 43 children reviewed after 8 (1-25) years.
43 children treated by flexor-to-extensor transfer for a total of 130 curly toes were retrospectively reviewed after a mean period of 8 years. According to an objective scoring system, 37 patients had a satisfactory result and 6 patients had a poor result of one or more toes. We now recommend that children with mild to moderate curly toes should be observed until the age of 6 years, by which time the majority will have had spontaneous correction. The remaining patients should be operated on at that stage because children operated on later had poor results. Attention should be paid to the surgical technique because the long flexor tendons are often bipartite.
Adolescent↗
Risks and rewards of resin bonded bridges: a review of the literature and some conclusions.
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Denture, Partial, Fixed, Resin-Bonded↗
Thromboxane A2 synthase. Modification during "suicide" inactivation.
Thromboxane synthase is a ferrihemoprotein which undergoes mechanism-based inactivation during catalysis. This "suicide" process may be an important factor for limiting thromboxane A2 biosynthesis in cells. Although the kinetics have been characterized for purified enzyme and platelets, the chemical basis for inactivation has remained unclear. Protein modification or alteration of the heme prosthetic group is each compatible with the irreversible nature of suicide inactivation of thromboxane synthase. We have investigated these two possibilities using enzyme purified to homogeneity. Our data show that the Soret absorbance spectrum of thromboxane synthase is unaltered by additions of prostaglandin endoperoxide H2 which cause enzymatic inactivation. Using a coupled cyclooxygenase/thromboxane synthase system and polyacrylamide gel electrophoresis we have demonstrated that the enzyme retains radiolabel under nondenaturing gel conditions. Label incorporation is reduced by the competitive thromboxane synthase inhibitor U63557, an agent that also protects the enzyme from inactivation. Under denaturing conditions the radiolabel localizes with the released heme prosthetic group. In addition, interaction of the heme prosthetic group with cyanide was prevented by inactivating the enzyme with prostaglandin H2. In similar experiments, the lipid hydroperoxide 15(S)-hydroperoxyeicosatetraenoic acid inactivated thromboxane synthase with concurrent bleaching of the Soret spectrum. Labeling studies with a coupled soybean lipoxygenase/thromboxane synthase system indicate that, in this case, the apoenzyme is modified. These results suggest that the mechanism of thromboxane synthase inactivation during thromboxane A2 biosynthesis involves a tight, nondestructive association of substrate or product with the prosthetic heme group. Inactivation by hydroperoxides, however, appears to result from apoenzyme modification. These reactions may have important implications for cellular physiology and pathophysiology of thrombosis.
Arachidonate 15-Lipoxygenase↗