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Biomedical subjects

D H Edwards

Publications and source records attributed to D H Edwards.

12 recordsLinked to original sources
PubMed1992

A murein hydrolase is the specific target of bulgecin in Escherichia coli.

A deletion in the structural gene for the soluble lytic transglycosylase, the predominant murein hydrolase in the soluble fraction of Escherichia coli, has been constructed. The mutant grows normally but exhibits increased sensitivity toward mecillinam, a beta-lactam specific for penicillin-binding protein 2. In the presence of furazlocillin or other beta-lactams with a specificity for penicillin-binding protein 3 which normally cause filamentation, bulges were formed prior to rapid bacteriolysis. Similar morphological alterations are known to develop in wild type E. coli cells when furazlocillin is combined with bulgecin, an antibiotic of unusual glucosaminyl structure. It turned out that bulgecin specifically inhibits the Sl-transglycosylase in a noncompetitive manner. Since bulgecin shows some structural analogy to the murein subunits we postulate that the soluble lytic transglycosylase, in addition to its active site, has a recognition site for specific murein structures. The possibility of an allosteric modulation of the activity of the enzyme by changes in the structure of the murein sacculus is discussed.

Amdinocillin↗
PubMed1992

Impaired cyclic nucleotide-mediated vasorelaxation may contribute to closure of the human umbilical artery after birth.

1. The mechanical and biochemical effects of agents that relax vascular smooth muscle either through elevation of guanosine 3':5'-cyclic monophosphate (cyclic GMP) or adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels were compared in isolated ring preparations of human umbilical artery and rat aorta. Tone was established by preconstriction with 5-hydroxytryptamine. 2. The endothelium-dependent vasodilator calcium ionophore (A23187) (which stimulates endothelium-derived relaxing factor [EDRF] release and thus acts through soluble guanylyl cyclase), sodium nitroprusside (which stimulates soluble guanylyl cyclase directly), and atrial natriuretic peptide (which stimulates particulate guanylyl cyclase) relaxed rat aorta but not human umbilical artery. 3. Sodium nitroprusside, 10 microM, increased cyclic GMP levels from 10 to 390 pmol mg-1 protein at 2 min in rat aorta, as compared with a slower, relatively attenuated rise from 5 to 116 pmol mg-1 protein after 15 min in human umbilical artery. The rise in cyclic GMP in the umbilical artery was not significantly augmented by the cyclic GMP phosphodiesterase inhibitor, MB22948. Atrial natriuretic peptide increased cyclic GMP levels in rat aorta but not in human umbilical artery. 4. Forskolin, 10 microM, which stimulates both soluble and particulate adenylyl cyclase, maximally relaxed rat aorta and increased cyclic AMP levels from 15 to 379 pmol mg-1 protein at 15 min, but did not significantly relax or increase cyclic AMP levels in human umbilical artery. After preincubation with the cyclic nucleotide phosphodiesterase inhibitor, IBMX, 10 microM forskolin increased cyclic AMP levels to 1365 pmol mg-1 protein at 30 min in human umbilical arteries, but these high levels were not accompanied by mechanical relaxation.5. 8-Bromo-cyclic GMP and 8-bromo-cyclic AMP which are lipophilic analogues of cyclic GMP and cyclic AMP, both maximally relaxed the rat aorta at a concentration of 10 microM, but did not significantly relax the human umbilical artery.6. The findings indicate that elevated cyclic nucleotide levels are not associated with mechanical relaxation of the post-partum human umbilical artery, as in other vessels such as rat aorta. This impaired response to cyclic nucleotides may contribute to closure of the umbilical artery after birth.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

The effect of chronic subarachnoid hemorrhage on basal endothelium-derived relaxing factor activity in intrathecal cerebral arteries.

The authors have investigated the hypothesis that loss of endothelium-derived relaxing factor (EDRF) activity contributes to cerebral vasospasm after subarachnoid hemorrhage. Adventitial exposure to hemoglobin was studied angiographically by injecting purified hemoglobin solution or autologous whole blood into the cisterna magna of anesthetized pigs. Both interventions induced intra- but not extracerebral vasoconstriction, which persisted for 2 and 7 days, respectively. Cyclic guanosine monophosphate (cGMP) levels were measured in isolated buffer-perfused pig intrathecal arteries to quantify inhibition of basal EDRF activity by hemoglobin. Adventitial exposure was less effective than intimal exposure, 10 microM hemoglobin applied adventitially for 30 minutes having an effect equivalent to that of 1 microM applied intraluminally for 5 minutes. The depression of cGMP levels by hemoglobin was reversible and equivalent to the effect of endothelial denudation or incubation with NG-nitro-L-arginine methyl ester, so that the effects of hemoglobin can be attributed to a specific action on EDRF rather than interaction with a nitric oxide-like substance produced by vascular smooth muscle or adventitial nerves. Cyclic GMP levels in isolated arteries were unchanged after in vivo exposure to hemoglobin for either 2 or 7 days or to whole blood for 2 days, and were reduced by intraluminal perfusion with 1 microM hemoglobin. In contrast, after 7 days of in vivo exposure to whole blood, cGMP levels were already depressed, and not further reduced by intraluminal perfusion with 1 microM hemoglobin. The findings support the view that adventitially applied hemoglobin can inhibit basal EDRF activity and that in vivo adventitial exposure to whole blood leads to a reduction in basal cGMP levels in association with vasoconstriction of intrathecal arteries. Both mechanisms could contribute to the clinical syndrome of cerebral vasospasm after subarachnoid hemorrhage.

Animals↗
PubMed1977

A comparative study of dextran-70, warfarin and low-dose heparin for the prophylaxis of thrombo-embolism following total hip replacement.

In a randomized, controlled clinical study, dextran-70, warfarin, or low-dose heparin were administered to patients undergoing total hip replacement on one surgical unit in an attempt to prevent deep venous thrombosis and pulmonary embolism. Calf vein thrombosis was detected by the 125I-fibrinogen uptake test. None of the methods prevented calf vein thrombosis (dextran-70, 51%; warfarin, 58-6%; heparin, 52-6%). Pulmonary embolism was completely prevented in patients treated with warfarin but occurred in 4% of patients treated with dextran-70 and 15-5% of those treated with low-dose heparin. The incidence of complications of therapy was small and comparable in each group. It is suggested that calf vein thrombosis is a frequent and in itself a non-serious complication of total hip replacement surgery and that emphasis might be placed more usefully on prevention of pulmonary embolism.

Aged↗
PubMed1977

Osteochondritis dissecans patellae.

Six cases of osteochondritis dissecans patellae have been studied in five patients in an attempt to clarify the aetiology and prognosis. Assessment of the results of treatment was performed using a standard protocol. The thirty-four previous case reports in the literature are reviewed. In four of the five patients symptoms began after flexing the knee under load and three showed patellar subluxation on tangential radiographs. Thus, repetitive shearing stress on the patellar surface is thought to be an important aetiological factor. The indication for operation is a loose osteochondral fragment either wholly or partly detached from the articular surface of the patella. Vertical excision of the affected area of articular cartilage with drilling of the underlying bone gave two "good" and two "excellent" results. Healing of the drilled area and maintenance of the cartilage space was seen in radiographs of all four cases so treated. This simple method of treatment, which probably causes filling of the defect in the surface by fibrocartilage, is recommended.

Adolescent↗
PubMed1977

Arthroplasty of the hip in ankylosing spondylitis.

In fifty-six patients with ankylosing spondylitis three types of arthroplasty had been performed in ninety-nine hips. Forty-one of the patients were men and fifteen were women, their average age at operation being forty-two years. Primary pseudarthrosis produced well-satisfied patients, but only a fair result in five hips, whereas cup arthroplasty resulted in a poor outcome for eight hips, all of which needed revision. Total replacement of eighty-six hips, however, led to 73 per cent being graded as good or excellent up to ten years later. The main complications were deep infection of five hips, para-articular ossification around nine hips (six leading to bony ankylosis), and fibrous ankylosis of six hips.

Adult↗
PubMed1977

The spinal abnormalities in thalidomide embryopathy.

In 1968 a study was made of the spinal changes in 32 children with multiple congenital abnormalities due to thalidomide. Twenty-eight of these children have been traced and their spinal changes reviewed. Only four patients had normal spines on radiography. In eight children, scoliosis was present and had progressed though it was still of mild degree. Disc and end-plate abnormalities were seen in 14 children, and in some appeared to be progressive, leading to intervertebral fusion.

Abnormalities, Drug-Induced↗
PubMed1976

Cement burns.

Four cases are presented of men who sustained burns after contact with premixed concrete. The pathogenesis of the condition is discussed.

Adult↗
PubMed1976

The value of low dosage heparin for the prophylaxis of thromboembolism in patients with transcervical and intertrochanteric femoral fractures.

One hundred and ten female patients, over the age of 60, with intertrochanteric or transcervical fractures were included in a controlled, randomized, clinical trial investigating the value of low dosage heparin in the prophylaxis of deep vein thrombosis. There were 50 completed pairs. Eight (16 per cent) deep vein thromboses occurred in the heparinized group compared with 23 (46 per cent) deep vein thromboses in the control group. The incidence of pulmonary embolism was also reduced. The diagnosis of deep vein thrombosis was made on clinical grounds, supplemented by phlebography and autopsy. There was no difference in the wound hematoma or infection rate. The heparin was commenced on admission to hospital and it is suggested that in this group of patients low dosage heparin prophylaxis should start on admission and not wait until surgery.

Aged↗
PubMed1975

Prophylaxis with dextran 70 against thrombosis in patients with fractures of the upper end of the femur.

A trial was undertaken to assess the effect of dextran 70 (Macrodex) in prophylaxis against thrombosis in womem over 65 years with fractures of the upper end of the femur. The dosage used was 500 ml at operation and 500 ml on the first postoperative day. At this dosage given at this time there was no difference in the overall incidence of clinically diagnosed deep venous thrombosis in the group of patients given dextran 70 compared with the control group. There was a tendency for thrombosis to occur earlier in the control group. The mortality rates at 3 weeks and even at 6 months were less in the treated group than in the control series.

Clinical Trials as Topic↗
PubMed1975

The use of seat belts by motor car occupants involved in road traffic accidents.

Two hundred and forty-four motor car occupants involved in road traffic accidents, who sustained injuries sufficiently severe to require admission to hospital, have been investigated in order to assess the value of seat belts. The results indicated that the use of seat belts significantly reduced the mortality and the number of severe, multiple and facial injuries.

Accidents, Traffic↗