Biomedical subjects
Publications and source records attributed to A Murray.
In September 1989, I entered the competition sponsored by Orthologic Ltd which is held annually at the British Orthodontic Conference. This involves presentation of three cases treated by an edgewise system, either conventional or pre-adjusted, and is judged on the quality of the result and the standard of records that form the presentation. The prize, which I was lucky enough to win, is 2000 pounds towards travel to visit centres of excellence.
In January 1991 the winter meeting of the Surgical Research Society was held at St. Bartholomew's Hospital and the Institute of Education, London. During the meeting a symposium was held entitled 'Shedding light on lasers'. Speakers addressed the general principles of lasers, laser-tissue interactions and the applications of lasers in gastro-enterology and in vascular disease. This was followed by an open discussion of the current indications, complications and outcome, together with future possible applications for lasers in medicine.
A flashlamp-pumped pulsed dye laser operating at either 480 or 504 nm, coupled to an integral ball-tipped optical fibre, was used to recanalize occluded lower limb arteries. All channels created by the laser were augmented with balloon dilatation. We have treated 78 limbs in 71 patients; 46 limbs (59 per cent) had rest pain and 22 (48 per cent) of these had tissue loss. The median occlusion length was 18 (range 0.5-58) cm. Technical success was achieved in 58 limbs (74 per cent) with clinical success in 46 (59 per cent). Success rates fell with increasing length of occlusion. Two patients died in the perioperative period. A subgroup of 22 patients with marked discrete arterial calcification had a lower technical success rate than the subgroup without calcification (50 per cent versus 84 per cent, P less than 0.01). Both subgroups displayed a similar pattern of reclosure during follow-up. The cumulative patency rate after technical success was 67 per cent at 6 months and 45 per cent at 12 months. Forty-six (59 per cent) limbs avoided bypass surgery or amputation. Laser-assisted angioplasty may offer an alternative to femoropopliteal bypass, although the former procedure is not as durable.
Although fetal monitoring is a common clinical procedure, there is little quantitative evidence that it can detect changes occurring during labour. We present quantitative data comparing the first and second stage of labour, from 21 labours resulting in a normal fetal outcome. A range of fetal heart rate variables was calculated from the output of a fetal heart rate monitor. Significant changes were detected in baseline fetal heart rate (P less than 0.005), heart rate variability (P less than 0.05), number of dips (P less than 0.01) and their depth (P less than 0.01). The results encourage confidence in the sensitivity of fetal monitoring for the detection of changes in a number of fetal heart rate variables during the course of labour.
We have characterized in detail, the epitope of the secreted antigen GP28.5 recognized by the mouse monoclonal antibody TG 17-179 using synthetic peptides and a truncated recombinant fusion protein. The screening of a T. gondii expression library with TG17-179 mAb led to the isolation of cDNAs clones, all encoding for the C-terminal region of GP28.5 and with one encoding for only the five last C-terminal residues. Competitive ELISA with longer peptides revealed that the immunoreactivity was retained for peptides of eight residues or longer, and lost when the peptide was reduced to the six last C-terminal residues or less. Experiments with the octapeptide lacking the carboxy-terminal glutamine residue showed it to be 64-fold less active. Moreover, neither addition of residues in the carboxy-end nor substitution of COOH function changed the immunoreactivity of the epitope. Competition experiments between TG17-179 mAb and sera from infected individuals demonstrates that the epitope defined by a mouse monoclonal probe is also a major epitope for human polyclonal antibodies. These results describe the sequence requirements within a probably linear epitope and give rise to some general question concerning experimental test for epitope mapping.
Although functional replacement of the heart and lungs by a pump and oxygenator is a widespread surgical procedure, no widely accepted technique for describing gas exchange in oxygenators exists. In this study, 8 types of commercially available membrane oxygenator (2 flat sheet membrane, 4 gas in hollow fibre membrane and 2 blood in hollow fibre membrane) have been studied during clinical cardiopulmonary bypass. O2 transfer increased with blood flow rate but the O2 transfer at a given blood flow was lower than that obtained by the manufacturers in laboratory studies. Overall O2 transfer coefficients were calculated from the ratio of O2 transfer rate to an O2 difference expressed either as an O2 partial pressure or an O2 concentration. Specific O2 transfer coefficients (overall coefficient divided by membrane area) were similar for oxygenators with a flat sheet or gas in hollow fibre membrane configuration. The two types of oxygenator with blood in hollow fibre membranes had significantly lower (P less than 0.01) specific O2 transfer coefficients. This study shows that oxygenator gas transfer characteristics can be studied in the clinical environment and that O2 transfer coefficients can be related to oxygenator design features.
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A promoter sequence, PAN, was isolated from Mycobacterium paratuberculosis and characterized. This promoter lies adjacent to, and outside, the 3' end of an IS900 insertion element. IS900 contains an open reading frame, ORF2, on the complementary strand which codes for the putative transposase of this insertion sequence. A DNA fragment containing PAN and part of ORF2 was fused to the lacZ gene and inserted into the replicative shuttle vector pRR3. Mycobacterium smegmatis and Mycobacterium bovis BCG (BCG) transformed with this plasmid exhibited beta-galactosidase activity. However, lacZ was only expressed in Escherichia coli under the control of PAN, when ORF2 was deleted. Immunization of mice with the recombinant M. bovis BCG expressing lacZ resulted in the induction of a high humoral and cellular response directed against beta-galactosidase. The PAN-ORF2 expression system may prove to be particularly useful for cloning and expression of heterologous genes in the BCG vaccine strain.
The repeatability of commonly used electrocardiographic (ECG) related autonomic function tests was investigated in 25 diabetic subjects, mean age 44 (range 18-67) years and mean duration of diabetes 10 (< 1-35) years. Tests were based on deep breathing, the Valsalva manoeuvre, relaxed normal breathing, and standing up from a lying position. All tests were repeated twice at each session, with two sessions separated by a mean of 5 (range 3-8) months. ECG and respiratory data were recorded for subsequent analysis. Maximum (max) and minimum (min) RR intervals and instantaneous heart rate (HR) were determined. The mean and repeatability data (within-subject standard deviation) for 21 different test results were calculated, and included deep breathing sitting (max-min)RR 226 +/- 39 ms and (max-min)HR 19.3 +/- 3.2 beats min-1, Valsalva manoeuvre 1.74 +/- 0.18, and lying-to-standing RR ratio 1.19 +/- 0.07. The within-subject repeatability to between-subject variability ratios consistently demonstrated that it is better to perform the deep breathing test sitting (with the smaller mean ratio of 0.37) rather than supine (0.46), with the use of three respiratory cycles rather than a single cycle (0.33 compared with 0.50 for (max-min)RR). A significant (p = 0.037) relationship was found between variability in heart rate changes and variability in air volume breathed during the deep breathing test.
OBJECTIVE: To determine the repeatability and sources of variability of clinical tests of cardiovascular autonomic function. DESIGN: The commonly used electrocardiographic related tests of autonomic function were studied. Two repeat measurements of all tests were made on all subjects on four separate days over a four week period. SUBJECTS: Ten normal subjects with no known autonomic dysfunction were investigated. MAIN OUTCOME MEASURES: These were deep breathing (subject seated and supine), Valsalva manoeuvre, standing up from lying position, and normal relaxed breathing (subject supine). During the tests the electrocardiogram and respiratory pattern were recorded by computer. Beat to beat RR intervals were measured automatically from the electrocardiogram, and from these the results of the tests were calculated. RESULTS: Variance analysis showed significant between subject variability for all tests (p < 0.005), but some tests showed a much smaller relative within subject variability than others. Average repeatability data (within subject SD) for each test were calculated, and included deep breathing sitting (max-min) RR (46 ms), Valsalva ratio (0.17), and lying to standing RR ratio (0.11). These compare with between subject SDs of 65 ms, 0.38, and 0.13 respectively, at mean values of 305 ms, 1.92, and 1.15 respectively. The data highlighted one subject with the poorest repeatability, whose electrocardiogram turned out on closer inspection to be under atrial rather than sinus control at times. Poor repeatability in the other subjects was related to variability in the respiratory pattern, and in the deep breathing test, repeat variability was significantly correlated (r = 0.79) with variability in the respiratory amplitude (p < 0.05). CONCLUSIONS: Repeatability data should be available to each laboratory carrying out autonomic function tests. The data provided in this study could be used as a baseline. Poor repeatability highlights the need to re-examine the test procedures, or the test data from specific subjects. Variability of respiratory pattern is associated with poor repeatability, and so careful instructions on respiration should be given to each subject before the tests.
Reaction to medical, social, and genetic implications of Marfan syndrome was evaluated by means of two questionnaires, the first after various tests before discussion of the diagnosis, the second after full discussion of the patient's diagnosis. Thirty-seven members of a family known to be at risk for Marfan syndrome attended for both questionnaires. All patients claimed to be satisfied with the way they were informed of the results of screening; 41% of patients were more worried about their health and 48% were more worried about the future after diagnosis. Apart from 50% of the smokers reducing or stopping their intake of cigarettes there were only very minor changes in lifestyle over the first month despite the increased level of expressed anxiety. If a definitive screening test was available, 96% of patients claimed they would have chosen it, 45% felt it would have an influence on their future plans, and 78% would choose to use a method of prenatal diagnosis for Marfan syndrome if it were available.
Between 1984 and 1986 six patients with acute respiratory failure (requiring ventilation for at least 3 days) complicating acute pancreatitis were managed on the intensive care unit (median ventilation period 6 days; range 3-41 days). Between 1987 and 1989 nine similar patients were managed (median ventilation period 35 days, range 4-69 days), and a regimen of enteral tobramycin, polymyxin and amphotericin to selectively decontaminate the digestive tract (SDD) was introduced. Five of six patients treated before 1987 had serious infections (three Gram-negative, one fungal), compared with only one of nine patients treated with SDD (P < 0.05). Clinical signs of sepsis were evident for 62% of the pre-SDD period, compared with 39% of the period during SDD therapy (P < 0.001). Systemic antibiotic prescribing was reduced in the SDD group; however, mortality remained unaffected with only two patients surviving pre-SDD and three during SDD treatment. SDD reduces infection rates and sepsis in patients with acute pancreatitis and may help to improve the prognosis of this life-threatening condition.
The significance of anti-cardiolipin antibodies (ACLA) in patients with a range of autoimmune and infective disorders was investigated in this study. Although lower levels of IgG and IgM ACLA were present in 77 of 400 patients' sera (19%), high antibody levels were found in less than 5% of patients. These latter patients belonged to three clinical categories: patients with connective tissue disease (CTD), infectious mononucleosis or biological false positive serology. An assay was developed to measure lupus anticoagulant (LA) activity in serum: significant LA activity was found in the CTD patients alone (in 6 of 15 tested) and all of these had high titre ACLA. Features of the antiphospholipid syndrome (APS) were present in these six patients but also in three additional CTD patients with normal LA results and high levels of ACLA. In two CTD patients with APS features, the high ACLA were of IgM isotype. These results stress the importance of measuring both ACLA and LA in an investigation of the APS: a high positive ACLA supports the diagnosis of APS, particularly in patients with autoimmune disease, whilst a high positive ACLA in association with LA activity is specific for this syndrome.
151 primigravid patients with Bishop scores of 4 or less were induced with prostaglandin E2 gel using an initial dose of 2 mg followed by 1 mg or 2 mg at 6 hours. Eighty one patients (53.6 per cent) were in established labour or had delivered by 12 hours, and a further 31 (20.5 per cent) had achieved successful ripening of the cervix. Ninety per cent and 64.5 per cent respectively achieved vaginal delivery and although 39 patients failed to respond to this regime, 72 per cent delivered vaginally after augmentation. No case of hypertonus was recorded and only one patient had abdominal delivery for "failed induction". This regime provides an effective means of induction of labour for a difficult group of patients with little worry of overstimulation and low "failed induction" rates.
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Popliteal artery entrapment syndrome is an uncommon cause of peripheral vascular disease in young fit individuals, presenting as progressive claudication or sudden limb ischaemia. It can also present later in life with insidious symptoms relating to popliteal thrombosis or aneurysm. As a local cause of atherosclerosis in the popliteal artery it is probably under-diagnosed, as clinical and radiological features are subtle and varied. Early diagnosis and surgical division of aberrant muscular relations result in an excellent clinical result. Late surgical treatment with vein grafting is less durable. The disease incidence, clinical features, pathology, investigations, treatment and prognosis are reviewed.
Unpurified DNA derived from cultures of equine fetal kidney cells infected with either equine herpesvirus type 1 or equine herpesvirus type 4 was amplified by the polymerase chain reaction using one pair of oligonucleotide primers. Restriction endonuclease digestion of the amplified segments with PvuII, followed by electrophoresis, revealed restriction fragment length polymorphisms which enabled the two virus types to be differentiated.