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Biomedical subjects

D A Jones

Publications and source records attributed to D A Jones.

At least 163 records · Page 9Linked to original sources
PubMed1994

Principles of screening and congenital dislocation of the hip.

The call for screening for an increasing number of surgical diseases is becoming louder and more frequent. There is a general perception that screening is 'good' but it is important to consider the evidence carefully. There is one surgical disease that provides considerable experience of the process of screening over a period of 30 years and this is congenital dislocation of the hip (CDH). In retrospect, it is clear that screening for this disease has not been a total success. Although some specialised centres have achieved excellent results, in the country as a whole screening has been a failure. The reasons for this are analysed and emphasis is placed on the principles of screening which are briefly summarised. The results of various studies on screening and experiments on the basic functional anatomy of the neonatal hip are described. The initial results of our method of selective ultrasound screening appear to be encouraging and some evidence of a possible collagen abnormality in CDH is presented. As a general principle, however, it is suggested that strict randomised controlled trials should take place before national screening programmes are started.

Collagen↗
PubMed1993

Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines.

Prostaglandin endoperoxide synthase (PHS) catalyzes the committed step in the biosynthesis of prostaglandins and thromboxane. We recently observed dissociation of PHS activity and enzyme mass measured in an immunoassay of endothelial cells exposed to tumor necrosis factor. These data and observations by others suggested that endothelial cells express an alternate PHS. We now report the molecular cloning of human PHS type II from an endothelial cell cDNA library. The protein encoded by this cDNA shares 61% identity with the human PHS I. Southern analysis demonstrated a single copy of PHS II and we found a polymorphism in approximately 5% of the population. PHS II mapped to chromosome 1, in contrast to PHS I, which is on chromosome 9. The PHS II cDNA hybridized strongly to a 4.3-kilobase (kb) message from endothelial cells. Stimulation of the cells with tumor necrosis factor, phorbol 12-myristate 13-acetate, lipopolysaccharide, or interleukin-1 increased mRNA levels for PHS II, and this change correlated well with increased prostacyclin biosynthesis. Cycloheximide induced PHS II mRNA without a corresponding activity increase demonstrating that translation of the 4.3-kb message is required for increased prostacyclin biosynthesis. We conclude that expression of PHS II may have important pathophysiological effects in the vasculature.

Amino Acid Sequence↗
PubMed1993

Muscle disease, HIV and zidovudine: the spectrum of muscle disease in HIV-infected individuals treated with zidovudine.

Eleven patients with AIDS or AIDS-related complex who developed muscle-related symptoms whilst taking zidovudine were investigated. The clinical details of a further ten patients who did not undergo muscle biopsy are also outlined. The clinical features, quantitative muscle strength testing, electromyographic findings, serial creatine kinase levels, muscle biopsy appearance on light microscopy and the effects of zidovudine withdrawal and rechallenge are described. The spectrum of muscle disease encountered included four cases of frank myopathy diagnosed using clinical, electrophysiological and histological criteria, four patients with mild weakness and myalgia in whom muscle biopsies were normal, three patients with myalgia only and a mild increase in the interstitial cell infiltrate shown by biopsy. The patients presenting with myopathy showed no improvement on withdrawal of zidovudine but responded to immunosuppressive therapy with steroids and, in one case, thalidomide prescribed incidentally. At present, it is not yet possible to clinically define a specific zidovudine-induced myopathy that is distinct from the other effects of HIV infection on muscle structure and function. Our experience suggests that zidovudine may be implicated as a myotoxin in some patients, particularly those with myalgia and mild weakness. In those patients with severe weakness, and with biopsy findings of necrosis and inflammation, the drug effects may be difficult to separate from the primary effects of HIV.

AIDS-Related Complex↗
PubMed1993

Assessment of hip abductor function in relation to peritrochanteric heterotopic ossification after closed femoral nailing.

The relationship between peritrochanteric heterotopic ossification and the strength of hip abduction after closed intramedullary nailing for femoral shaft fractures was investigated in 25 patients after a mean follow-up of 2 years (range 9 months to 4 years). The power of hip abduction was assessed and compared with the normal hip. Of the 21 patients with heterotopic ossification, 16 had measurable weakness of hip abduction. Grade III heterotopic ossification resulted in 8-20 per cent weakness of hip abduction, but this was not associated with any disability or symptoms. Clinically important abductor weakness is more likely to be due to ipsilateral fractures or a long nail rather than heterotopic ossification.

Adolescent↗
PubMed1993

Fibre areas and histochemical fibre types in the quadriceps muscle of paraplegic subjects.

With the advent of functional electrical stimulation (FES) there is the possibility of paraplegic patients regaining some degree of locomotor activity. It is of interest to document the changes in composition histochemistry and size of muscle fibres in such patients both before and after such therapy. We have examined biopsy specimens from quadriceps muscles obtained from 7 male patients, age range 24-47 years, who had been paraplegic for times ranging from 11 months to 9 years and we report the histochemical appearance of the muscle the fibre type composition and the mean fibre areas. In 5 of the 7 subjects there was a marked or complete predominance of fibres which stained as type 2 with the ATPase reaction at pH 9.4. At acid pH these fibres were seen to be predominantly 2B (fast fatigable). The 2 subjects who had been paralysed for the shortest periods had proportions of type 1 fibres which were relatively well preserved. The mean fibre areas of type 2 fibres were below the normal range (2500-7500 microns 2) in every case as were the type 1 fibres in the 4 patients in which these were still present. There was no relationship between the length of time the patient had been paralysed and the mean fibre areas which suggests that atrophy occurs fairly quickly following loss of voluntary control and precedes the loss of type 1 characteristics. Our findings provide an explanation for the rapid onset of fatigue in paraplegic patients taking part in FES programmes since muscles deficient in type 1 fibres will be unable to maintain force for any length of time.

Adult↗
PubMed1993

P-selectin mediates neutrophil rolling on histamine-stimulated endothelial cells.

In postcapillary venules, marginating neutrophils (PMNs) are often seen rolling along the vessel wall prior to stopping and emigrating. There is substantial evidence in vitro and in vivo that the adhesion receptors E- and L-selectin participate in this phenomenon on cytokine-stimulated endothelium, and recent evidence has shown that a closely related adhesion receptor, P-selectin, is capable of mediating neutrophil rolling on an artificial membrane. Here we demonstrate and characterize PMN rolling on monolayers of human umbilical vein endothelial cells (HUVECs) stimulated with histamine to induce surface expression of P-selectin. Peak association of PMNs with the HUVECs occurs 10 min after histamine stimulation, and at a postcapillary venular wall shear stress of 2.0 dyn/cm2 the rolling velocity is 14 microns/s. Approximately 95% of the PMNs roll on the endothelial cells, 5% adhere firmly, and none migrate beneath the endothelial monolayer. Monoclonal antibody (MAb) G1, which binds P-selectin and blocks its adhesive function, completely prevents association of the PMNs with histamine-stimulated HUVEC, whereas the nonblocking anti-P-selectin MAb S12 does not. Treatment of PMNs with the anti-L-selectin MAb DREG56 reduces PMN adherence by approximately 50%. Anti-CD54 MAb R6.5 and anti-CD18 MAb R15.7 have little effect on the number of PMNs rolling on the HUVECs but completely prevent PMNs from stopping and significantly increase rolling velocity. Nonblocking control MAbs for R6.5 (CL203) and R15.7 (CL18/1D1) lack these effects. Rolling adhesion of PMNs on histamine-stimulated HUVECs therefore appears to be completely dependent on endothelial cell P-selectin, with a minor adhesion-stabilizing contribution from intercellular adhesion molecule 1 and beta 2 integrins. The partial inhibition of rolling with DREG56 suggests that L-selectin may also play a role in neutrophil interactions with histamine-stimulated endothelium. We further characterize these interactions by determining the effects of the various MAbs and wall shear stresses on adhesion patterns, rolling velocities, and distributions of rolling velocities.

Antibodies, Monoclonal↗
PubMed1993

Autoantibodies to type VII collagen recognize epitopes in a fibronectin-like region of the noncollagenous (NC1) domain.

Autoantibodies to type VII collagen are characteristic of the blistering diseases epidermolysis bullosa acquisita and bullous systemic lupus erythematosus (SLE). Blisters in those diseases are due to defective adhesion of the lamina densa subregion of the epithelial basement membrane to the underlying dermis. Previous studies indicating that type VII collagen contributes to lamina densa-dermal adhesion by cross-linking lamina densa and dermal matrix proteins suggests that autoantibodies may contribute to blisters by interfering with type VII collagen function. That hypothesis is supported by previous studies showing autoantibodies from a small number of epidermolysis bullosa acquisita patients recognize proteolytic fragments containing the 145-kD noncollagenous domain of type VII collagen. In this study, we examined reactivity of autoantibodies from a large number of epidermolysis bullosa acquisita and bullous SLE patients with fusion proteins representing most of the noncollagenous domain of type VII collagen and that those regions are homologous to type III repeats of fibronectin. These results suggest autoantibodies binding to fibronectin homology regions within the 145-kD noncollagenous domain may interfere with the adhesion function of type VII collagen and contribute to lamina densa-dermal dysadhesion in epidermolysis bullous acquisita and bullous SLE.

Autoantibodies↗
PubMed1993

Juxtacrine interactions of endothelial cells with leukocytes: tethering and signaling molecules.

The interaction of blood leukocytes with the endothelium of post-capillary venules and other vessels involves regulated expression of molecules on both the endothelial cell (EC) and the leukocyte. This is true for each of the major classes of leukocytes, including lymphocytes, monocytes, and granulocytes. Interaction of polymorphonuclear leukocytes (PMNs), a particular subset of granulocytes, with cultured human endothelium illustrates this concept and also illustrates the diversity of structure, mechanisms of expression, and mechanisms of action of the molecules involved. One group of molecules binds, or "tethers", the PMN to the EC without requiring PMN activation; P-selectin and E-selectin, which are glycoproteins that are expressed by translocation from subcellular granules or synthesis under transcriptional regulation, respectively, are examples. A second group of molecules activates the PMN by binding to signal-transducing receptors. Platelet-activating Factor (PAF), a biologically-active phospholipid, is an example of this class. Its production is controlled by regulation of synthetic enzymes and is induced rapidly (minutes) when EC are appropriately stimulated. PAF is translocated to the EC surface, where it mediates juxtacrine activation of PMNs by binding to a "7 membrane-spanning" receptor. One consequence of juxtacrine activation of PMNs by PAF is functional upregulation of CD11/CD18 integrins on the PMN. These integrins bind to counterreceptors on the EC, enhancing the avidity of adhesion over that provided by P-selectin alone. Thus, combinations of tethering and signaling molecules regulate PMN adhesive interactions with EC. Combinations of such molecules also regulate other functional responses of the PMNs that are important in inflammation. The time-dependent expression of different patterns of tethering and signaling molecules by EC provides a general mechanism for differential adhesion and activation of different classes leukocytes in acute and subacute inflammation.

Animals↗
PubMed1993

Results of excision of calcaneal prominence.

Calcaneal prominence in 22 patients (37 heels) with moderate-to-severe symptoms was treated by excision after a minimum of 6 months of conservative treatment. There were 21 good, 12 fair and 4 poor results. Calcaneal exostectomy is a useful procedure in carefully selected patients.

Adolescent↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗