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M J Denton

Publications and source records attributed to M J Denton.

49 records · Page 3Linked to original sources

The use of field-inversion gel electrophoresis for deletion detection in Duchenne muscular dystrophy.

Deletion is a common cause of Duchenne muscular dystrophy (DMD). Field-inversion gel electrophoresis, in conjunction with Southern blot hybridization, was used to detect large SfiI DNA fragments in the DMD locus. Two unrelated boys with DMD were found to have abnormal sized DNA fragments resulting from deletions. Some of the female relatives of these patients were also shown by this method to have deletions in the DMD locus.

Chromosome Deletion↗

Palpation of the femoral and popliteal pulses: a study of the accuracy as assessed by agreement between multiple observers.

Six vascular surgeons independently examined 44 legs in patients with suspected peripheral arterial disease. Each surgeon recorded whether the femoral and popliteal pulses were present or absent, and if thought to be present, whether they were normal or reduced in amplitude. Interobserver agreement was determined by calculating both observed agreement (Po) and agreement after correction for chance (kappa-k). The results were calculated both for each possible pair of surgeons and as an overall value for all possible pairs combined. Agreement as to whether pulses were present or absent was significantly better than expected by chance but was only moderately good (overall kappa for femoral pulse = 0.53, and overall kappa for popliteal pulse = 0.52). More often than not, agreement as to whether the pulses were normal or reduced was no better than expected by chance (overall kappa for femoral pulse = 0.15, and overall kappa for popliteal pulse = 0.01). For each assessment, agreement was no better for the more experienced than the less experienced pairs of surgeons. The results indicate that more objective methods than pulse palpation are required to determine whether there is significant disease in the aorto-iliac and femoro-popliteal arterial segments.

Arterial Occlusive Diseases↗

In situ femoropopliteal and distal vein bypass for limb salvage--experience of 50 cases.

The aim of this paper is to assess the in situ technique of saphenous vein femoropopliteal (and femorotibial) bypass for limb salvage, and to compare it with the reversed vein method of bypass. In our 3-year study, we have operated on 50 cases resulting in a graft patency and limb salvage rate of 78 per cent at 18 months and 72 per cent overall. There was a 2 per cent perioperative and 10 per cent overall mortality. Graft thrombosis was associated with a variety of factors, mostly notably a small vein (les than 4 mm), a low calf vessel anastomosis, wound sepsis and progressive proximal (inflow) disease. However, the strongest correlation was that between graft thrombosis and the extent of distal disease, as 11 of 12 cases with thrombosed grafts had grade 2 or 3 run-off. In our experience the in situ technique offers haemodynamic and technical advantages over the reversed vein method of performing straightforward femoropopliteal bypass. Moreover, the in situ technique has wider application in that it allows a smaller vein (greater than 2.5 mm) to be used and also makes anastomosis to a small calf vessel easier. In this series, 16 per cent of cases would have been considered unsuitable for the reversed vein method if 4 mm was accepted as the lower limit of size for a reversed vein graft.

Aged↗

An experimental study of the use of a carbon fibre patch as a hernia prosthesis material.

Carbon fibre patches were inserted as prostheses into the dorsal lumbar fascia of rabbits. Their incorporation into the tissues was observed over a period of 15 weeks, and their mechanical properties were compared with those of implants made of a conventional Mersilene mesh. Although the mechanical properties of carbon fibre patches are initially poor, the development of a superior connective tissue response after several weeks suggests that a layered composite of carbon fibre and Mersilene with the latter giving initial strength may provide a useful material for clinical use as a hernia prosthesis.

Animals↗

Effect of posture and sleep on pharmacokinetics. I. Amoxycillin.

The pharmacokinetics of amoxycillin in normal male volunteers was studied during the states of bedrest, sleep and ambulation. The absorption and disposition of amoxycillin in ambulatory subjects was found to be comparable to that reported previously by other workers. Serum amoxycillin concentrations were found to be significantly greater during ambulation than during bedrest and sleep. The difference in serum levels resulted from an increased apparent total serum clearance and amoxycillin renal clearance during bedrest and sleep compared to ambulation. No significant differences in the clearance was found between the states of bedrest and sleep. The change in renal clearance of amoxycillin during ambulation was attributed to a diminished renal blood flow. Although the terminal half-life of amoxycillin did not differ significantly, the apparent volume of distribution appears to be much greater during bedrest and sleep than during ambulation. This difference could be explained pharmacokinetically using a two compartment model. No significant difference was found between the rates of absorption of amoxycillin as reflected by the lag time and time to peak serum amoxycillin. The actual values for these parameters would suggest, however, that the absorption of amoxycillin is faster during ambulation than in bedrest and that the absorption rate during sleep is slowest. The clinical implications of the effect of posture and sleep on the pharmacokinetics of amoxycillin are discussed.

Adult↗

Biochemical and enzymic changes during erythrocyte differentiation. The significance of the final cell division.

1. The haemoglobin content of developing erythroblasts was shown to increase rapidly when the cells completed the final cell division of erythroid development and passed from the dividing into the non-dividing cell compartment. 2. The activity of carbonic anhydrase was measured and shown to increase continually throughout erythroid differentiation. The activity increased most rapidly in the polychromatic stage. 3. Catalase activity did not increase significantly during erythroid differentiation until the reticulocyte stage. 4. The activity of four enzymes, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, adenosine deaminase and nucleoside phosphorylase, exhibited a similar pattern of change during erythroid differentiation. In the dividing cell compartment their activity was relatively high but exhibited a steep decline between the polychromatic stage and the orthochromatic stage, that is, as the cell completed its final cell division and moved from the dividing to the non-dividing compartment. After this the activity of these enzymes was stabilized at a relatively low value, and this activity persisted at such a value until the reticulocyte stage. 5. Lactate dehydrogenase activity also declined after the cell had crossed from the dividing into the non-dividing stage, but in this case the decline was less than in the case of the above four enzymes. 6. Adenylate kinase activity was relatively constant in the dividing cell compartment but exhibited a 60 percent increase when the cell passed from the dividing into the non-dividing compartment. 7. The cessation of cell division appears to coincide with a set of complex biochemical changes.

Adenosine Deaminase↗

Analysis of deletions in DNA from patients with Becker and Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder for which the biochemical defect is as yet unknown. Recently, two cloned segments of human X-chromosome DNA have been described which detect structural alterations within or near the genetic locus responsible for the disorder. Both of these cloned segments were described as tightly linked to the locus and were capable of detecting deletions in the DNA of boys affected with DMD. In an attempt to determine more precisely the occurrence of these deletions within a large population of DMD patients and the accuracy of one of the segments, DXS164 (pERT87), in determining the inheritance of the DMD X chromosome, the subclones 1, 8 and 15 were made available to many investigators throughout the world. Here we describe the combined results of more than 20 research laboratories with respect to the occurrence of deletions at the DXS164 locus in DNA samples isolated from patients with DMD and Becker muscular dystrophy (BMD). The results indicate that the DXS164 locus apparently recombines with DMD 5% of the time, but is probably located between independent sites of mutation which yield DMD. The breakpoints of some deletions are delineated within the DXS164 locus, and it is evident that the deletions at the DMD locus are frequent and extremely large.

Chromosome Deletion↗