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Biomedical subjects

D Charlesworth

Publications and source records attributed to D Charlesworth.

At least 73 records · Page 4Linked to original sources

Myocardial infarction after reconstruction of the abdominal aorta.

The records of 555 patients who underwent elective abdominal aortic reconstruction were analysed to identify risk factors predisposing to cardiac complications. Perioperative myocardial infarction occurred in 35 patients (6.3 per cent), of whom 12 (2.2 per cent) died. Using multiple logistic regression, four preoperative factors that were independently predictive for postoperative myocardial infarction were identified with the following relative risk ratios: history of transient ischaemic attacks, 5.08; raised serum creatinine level, 3.66; age > 60 years, 3.00; and angina requiring regular treatment, 2.74. A scoring system using these four factors was devised that identified 150 of the 555 patients as at high risk, and included 69 per cent of those with myocardial infarction after operation and 83 per cent of those who died. A clinical risk score is a practical first step in identifying patients at risk of myocardial infarction; it would also reduce the number of patients for whom sophisticated tests of cardiac function were necessary.

Aorta, Abdominal↗

Autotransfusion in aortic surgery: the Haemocell System 350 cell saver.

Autotransfusion was performed during elective abdominal aortic reconstruction in ten patients using the recently developed Haemocell System 350. A mean of 60 per cent of total blood loss was salvaged, and during operation each patient was autotransfused 1 unit. Good preservation of cellular components, including platelets, was seen after processing with the device, which uses a vortex mixing filter for cell separation. There was no evidence of coagulopathy; mean free plasma haemoglobin levels were slightly raised (17 mg/dl) and plasma heparin concentration was negligible (0.10 units/ml) 4 h after surgery. A transient drop in plasma fibrinogen levels and the appearance of fibrin degradation products in low concentrations (mean 1.5 mg/l) were seen. Oxyhaemoglobin dissociation curves showed the salvaged red blood cells to have a normal affinity for oxygen. Renal and hepatic function remained unaltered and there were no complications attributable to autotransfusion. The device was easy to handle and a trained operator was not required.

Adult↗

The effect of deleterious mutations on neutral molecular variation.

Selection against deleterious alleles maintained by mutation may cause a reduction in the amount of genetic variability at linked neutral sites. This is because a new neutral variant can only remain in a large population for a long period of time if it is maintained in gametes that are free of deleterious alleles, and hence are not destined for rapid elimination from the population by selection. Approximate formulas are derived for the reduction below classical neutral values resulting from such background selection against deleterious mutations, for the mean times to fixation and loss of new mutations, nucleotide site diversity, and number of segregating sites. These formulas apply to random-mating populations with no genetic recombination, and to populations reproducing exclusively asexually or by self-fertilization. For a given selection regime and mating system, the reduction is an exponential function of the total mutation rate to deleterious mutations for the section of the genome involved. Simulations show that the effect decreases rapidly with increasing recombination frequency or rate of outcrossing. The mean time to loss of new neutral mutations and the total number of segregating neutral sites are less sensitive to background selection than the other statistics, unless the population size is of the order of a hundred thousand or more. The stationary distribution of allele frequencies at the neutral sites is correspondingly skewed in favor of rare alleles, compared with the classical neutral result. Observed reductions in molecular variation in low recombination genomic regions of sufficiently large size, for instance in the centromere-proximal regions of Drosophila autosomes or in highly selfing plant populations, may be partly due to background selection against deleterious mutations.

Animals↗

Changes in cortical and trabecular bone in algodystrophy.

We studied the pattern of bone loss in the hand of 77 patients with Colles' fracture using metacarpal morphometry, single photon absorptiometry and a radiographic scoring system. Forty-four patients had post-traumatic algodystrophy and the remainder served as controls. Both groups were immobilized in the same manner and for the same period of time and both showed loss of bone during immobilization. The loss of bone 7 weeks after fracture was significantly greater in algodystrophy than in controls both at cortical (P < 0.05) and at trabecular sites (P < 0.001). Recovery of bone occurred in the control patients by 19 weeks after fracture at cortical sites and by 31 weeks in trabecular bone. In contrast, the bone loss seen in patients with algodystrophy persisted for the 6-month duration of the follow-up, and up to 1 year in all nine patients studied for longer. These findings indicate that post-traumatic algodystrophy is associated with regional skeletal losses greater than those following uncomplicated fracture and may result in irreversible changes in the structure and thus the strength of the bony architecture.

Absorptiometry, Photon↗

The effect of linkage and population size on inbreeding depression due to mutational load.

Using a stochastic model of a finite population in which there is mutation to partially recessive detrimental alleles at many loci, we study the effects of population size and linkage between the loci on the population mean fitness and inbreeding depression values. Although linkage between the selected loci decreases the amount of inbreeding depression, neither population size nor recombination rate have strong effects on these quantities, unless extremely small values are assumed. We also investigate how partial linkage between the loci that determine fitness affects the invasion of populations by alleles at a modifier locus that controls the selfing rate. In most of the cases studied, the direction of selection on modifiers was consistent with that found in our previous deterministic calculations. However, there was some evidence that linkage between the modifier locus and the selected loci makes outcrossing less likely to evolve; more losses of alleles promoting outcrossing occurred in runs with linkage than in runs with free recombination. We also studied the fate of neutral alleles introduced into populations carrying detrimental mutations. The times to loss of neutral alleles introduced at low frequency were shorter than those predicted for alleles in the absence of selected loci, taking into account the reduction of the effective population size due to inbreeding. Previous studies have been confined to outbreeding populations, and to alleles at frequencies close to one-half, and have found an effect in the opposite direction. It therefore appears that associations between neutral and selected loci may produce effects that differ according to the initial frequencies of the neutral alleles.

Genetic Linkage↗

Effects of a change in the level of inbreeding on the genetic load.

"The effects of inbreeding may not be as noticeable in the first generation as the invigoration immediately apparent after crossing". This statement, published in 1919, has received little attention, and has apparently never been tested empirically, although the reduction of the genetic load of populations by inbreeding is well known in theoretical terms. Because inbreeding increases homozygosity, and hence the effectiveness of selection against recessive or partially recessive detrimental alleles, changes in levels of inbreeding can lead to a reduction in the frequencies of such mutant alleles. This results in equilibration at higher population mean fitness and is referred to as 'purging' populations of their genetic load. Severe inbreeding can also reduce genetic load due to overdominant alleles, provided selection coefficients are not symmetrical at all loci, because alleles giving lower fitness will be reduced in frequency at equilibrium. With either fitness model, however, reduction in genetic load takes time, and the initial effect of an increase in inbreeding is reduced fitness due to homozygosity. There are few data relating to the extent to which fitness is reduced during inbreeding in a set of lines and to how long the reduction lasts before increasing again to the initial level, or higher. Inbreeding experiments involving sib mating in mice and Drosophila subobscura, and successive bottlenecks in house flies have yielded some evidence consistent with the purging hypothesis. Here, we report results of an experiment demonstrating a prolonged time-course of recovery of mean fitness under self-fertilization of a naturally outcrossing plant, and also compare our results with expectations derived by computer calculations. Our results show that the genetic load present in an outcrossing population can be explained only with a high mutation rate to partially recessive deleterious alleles, and that inbreeding purges the population of mutant alleles.

Animals↗

Assessment of broadband ultrasound attenuation in the os calcis in vitro.

1. We have examined the relationship between the attenuation of broadband ultrasound in the os calcis in vitro and its bone mineral density measured by quantitative computed tomography and by physical density. 2. Broadband ultrasound attenuation was found to correlate closely with physical density (r = 0.85, P less than 0.0001), but the correlation was less than that observed between quantitative computed tomography and physical density (r = 0.92, P less than 0.0001). Measurements of broadband ultrasound attenuation and quantitative computed tomography were significantly correlated (r = 0.80, P less than 0.0001). 3. Partial correlation analysis showed a significant relationship between broadband ultrasound attenuation and bone density, but when the effect of physical density was taken into account no significant correlation was found between broadband ultrasound attenuation and quantitative computed tomography (r = 0.08, not significant). 4. Broadband ultrasound attenuation in three prospective amputees showed a high degree of concordance between measurements in vivo and in vitro, with no interference by surrounding soft tissues. 5. The correlation between physical density and broadband ultrasound attenuation was independent of quantitative computed tomography, suggesting that the technique measures aspects of density which differ from its mineral density. Broadband ultrasound attenuation holds promise as a reproducible, rapid, radiation-free assessment of skeletal status.

Aged↗

Broadband ultrasound attenuation in the os calcis: relationship to bone mineral at other skeletal sites.

1. We have examined the relationship between broadband ultrasound attenuation in the os calcis and measurements of bone mineral in the distal forearm and lumbar spine of normal and postmenopausal osteoporotic women. 2. Values of broadband ultrasound attenuation in postmenopausal women with vertebral osteoporotic fractures were significantly lower (35%) than in normal pre- and peri-menopausal women (55.4 +/- 3.8 and 79.6 +/- 0.8 dB/MHz, respectively). 3. Broadband ultrasound attenuation correlated significantly with bone mineral content measured in the distal forearm by single-photon absorptiometry (r = 0.77, P less than 0.0001) and with bone mineral content (r = 0.66, P less than 0.0001) and bone mineral density (r = 0.72, P less than 0.0001) measured in the lumbar spine by dual-photon absorptiometry. 4. Although significant, these correlations are not sufficiently close to be predictive. However, the accuracy of broadband ultrasound attenuation in discriminating between normal subjects and patients with vertebral fracture compared very favourably with direct measurements in the spine by dual-photon absorptiometry. 5. Broadband ultrasound attenuation, but not the other measurements, correlated significantly with age in the osteoporotic patients (r = 0.50, P less than 0.05). 6. These findings may reflect the partial dependence of broadband ultrasound attenuation on the intrinsic trabecular architecture of cancellous bone, the disruption of which contributes to an increase in fracture risk.

Absorptiometry, Photon↗

Which is the best vascular prosthesis below the inguinal ligament?

Prostheses made of P.T.F.E give reasonable results when used as femoropopliteal bypass below the inguinal ligament and above the knee joint in patients with good "run-off". Human umbilical vein will probably give similar results but with reservations about its degradability. A compliant tube made from a non biodegradable stable polymer and which has a non thrombogenic internal surface seems to offer the most likely improvement.

Blood Vessel Prosthesis↗

Fatal left ventricular perforation following balloon mitral valvuloplasty.

Left ventricular perforation following a balloon mitral valvuloplasty is a rare complication. This paper reports morphological findings in such a case that was fatal. Cardiac tamponade was suspected clinically, but could not be confirmed or treated because of extensive anterior pericardial adhesions related to a previous closed mitral commissurotomy.

Balloon Occlusion↗

Venous insufficiency in a young man secondary to a traumatic arteriovenous fistula.

The medical history in a young man who developed varicose veins and venous insufficiency secondary to an acquired arteriovenous fistula in the thigh is presented. The radiological and clinical findings are discussed. The disease process in the development of varicose veins is not fully understood and cannot be satisfactorily explained as a consequence of arterial pressure within the venous system or a defect in the venous valves alone. The widespread ectatic changes seen within the venous system in our patient suggests the activation of an unknown, possibly humoral factor, resulting in morphological modifications in the vein wall.

Adult↗