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Biomedical subjects

M J Elliott

Publications and source records attributed to M J Elliott.

At least 91 records · Page 5Linked to original sources
PubMed1995

Incidence of neurological complications of surgery for congenital heart disease.

A total of 523 cardiac surgical discharge summaries were searched for recorded evidence of adverse neurological events occurring between operation and time of discharge. Neurological events were recorded in 31 and included one or more of seizure disorder (n = 16), pyramidal signs (n = 11), extrapyramidal signs (n = 8), coma (n = 6), and neuro-ophthalmic deficits (n = 6). There were significantly more adverse neurological events after repairs for arch anomalies (16.6% of cases). There was also an association with the length of cardiopulmonary bypass and a period of low perfusion pressure either intraoperatively or postoperatively. Of the 19 out of 23 survivors in whom long term outcome data were available, four were normal and six had persisting neurological problems directly related to the perioperative period. In a further nine of the 19 survivors, established preoperative neurodevelopmental abnormality probably contributed to their present neurological status, in addition to perioperative events. In view of the way these data were collected, this study must represent the minimum incidence of neurological events in children undergoing cardiac surgery.

Blood Pressure↗
PubMed1995

Heart transplantation for dilated cardiomyopathy.

Between 1988 and 1994, 23 patients underwent heart transplantation for dilated cardiomyopathy. The age of the 13 boys and 10 girls was from 8 months to 16 years (mean 7.1 years). Selection criteria included failure to thrive despite maximal antifailure treatment and/or intravenous inotrope dependence. The aetiology of cardiomyopathy was idiopathic (n = 13), congenital (n = 3), anthracycline induced (n = 4), Barth's syndrome (n = 1), and maternal systemic lupus erythematosus (n = 2). The waiting period of heart transplantation ranged from one day to 147 days (mean 22 days). Maintenance immunosuppression included cyclosporin, azathioprine, and prednisolone. Follow up after transplantation was from one month to 62 months (median 27 months) with a mean actuarial survival of 95% at one year and 87% at three years. Four patients developed coronary artery disease, one of whom died as a consequence 15 months after heart transplantation. Heart transplantation has emerged as an acceptable therapeutic option, at least in the short term, for patients with dilated cardiomyopathy.

Adolescent↗
PubMed1995

Supravalvar mitral stenosis: risk factors for recurrence or death after resection.

OBJECTIVE: To assess the medium term outcome in infants and children after surgical resection of supravalvar mitral stenosis with special reference to risk factors for mortality or recurrence of supravalvar mitral stenosis. No detailed follow up has been previously reported in this uncommon condition. DESIGN: Prospective cross sectional clinical and echocardiographic follow up. SETTING: Paediatric cardiothoracic unit. PATIENTS AND METHODS: 23 consecutive children (14 male, nine female, mean age 3 years 2 months at surgery) who underwent resection of supravalvar mitral stenosis between 1978 and 1993. RESULTS: Follow up was for a mean of 58 months (range 0.5-167) after resection of supravalvar mitral stenosis. Four patients developed recurrent supravalvar mitral stenosis: this has not been reported previously. This was recognised 14-108 months after resection and confirmed at repeat operation. Three of these patients had successful reoperations but one died. Five other patients died. On multivariate analysis the only variable associated with survival free of recurrent supravalvar mitral stenosis was older age (18 months or more) at time of surgery (hazard ratio 0.17, 95% confidence interval (CI) 0.03 to 0.95, P < 0.05). Five year actuarial survival free of recurrent obstruction when supravalvar mitral stenosis was resected at age less than 18 months was only 39% (95% CI 9 to 69%) compared with 73% (95% CI 24 to 93%) in older patients. CONCLUSION: Supravalvar mitral stenosis is part of a spectrum of obstructive lesions affecting the left heart. Recurrent supravalvar mitral stenosis can develop after surgical resection. The prognosis in those who require resection within the first 18 months of life is poor: mortality is high, as is the risk of recurrent supravalvar mitral stenosis in survivors, probably because of continuing turbulent flow across a small left ventricular inflow tract.

Age Factors↗
PubMed1995

Endoscopic plantar fascia release: an anatomical study.

The anatomical relationship of neurovascular structures to the plantar fascia after endoscopic fasciotomy was studied in 13 adult fresh-frozen cadaver feet. Using a single portal technique, an endoscopic system was placed into the plantar compartment through a 1-cm medial incision. Under direct endoscopic visualization, the plantar fascia was released. The feet were then dissected and the anatomic relationship of the neurovascular structures to the area of release was studied. The average amount of plantar fascia released was 81%. The average distance of the release to the lateral plantar nerve, and the nerve to the abductor digiti minimi was 10.5 and 12.3 mm, respectively. The flexor digitorum brevis muscle was partially transected in 46% of the cases, and the average amount of muscle transected was 0.8 mm. The endoscopic approach to the release of the plantar fascia provides adequate release and does not appear to pose any danger to underlying neurovascular structures.

Adult↗
PubMed1995

Neutrophil activation in paediatric extracorporeal circuits: effect of circulation and temperature variation.

OBJECTIVE: Upregulation of neutrophil adhesion molecules (CD11b and L-selectin) and release of a modulating cytokine (IL8) have been reported in vivo and in vitro in adult cardiopulmonary bypass. The aim of this study was to determine whether paediatric bypass preparations have similar influences and whether neutrophil-endothelium interactions are required for IL8 release. METHODS: In vitro paediatric cardiopulmonary bypass circuits (n = 15) were constructed (identical to those used clinically), as well as static loops (n = 15) using donor blood. The effects of circulation and temperature (17 degrees C, 25 degrees C, 37 degrees C) on the initiation of acute inflammation were examined. Cellular expressions of neutrophil adhesion molecules CD11b and L-selectin were assayed by immunofluorescence technique, and serum IL8, IL6, TNF-alpha, leucocyte elastase, and terminal complement complex were measured by ELISA. RESULTS: In all experiments, an immediate increase in CD11b expression occurred [median values, in relative fluorescence units: 64.9 (range 45.3-212.9) at rest; 365.2 (205-835.4) at 10 min; P < 0.001], along with a decrease in L-selectin expression [153.5 (115.5-220.7) at rest; 42 (12-134) at 10 min; P < 0.01]. Serum concentrations of the following increased gradually and were higher in circulation than in static loops: IL8 [1500 (500-2500) pg.ml-1 in circuit v 600 (180-1500) pg.ml-1 in loop, P < 0.001]; TNF-alpha P < 0.05]; and terminal complement complex [25.9 (6.8-120) v 4.7 (0-21.6) AU.ml-1, P < 0.01]. Cooling decreased and rewarming increased upregulation of CD11b and downregulation of L-selectin and release of IL8. IL6 was undetectable. CONCLUSIONS: In the absence of endothelium, in vitro paediatric cardiopulmonary bypass causes profound acute inflammatory changes in donor blood with release of IL8. These changes were greater than in adult cardiopulmonary bypass. Temperature variation and circulation modulate the responses.

Adult↗
PubMed1994

Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis.

Tumour necrosis factor alpha (TNF alpha) is a critical inflammatory mediator in rheumatoid arthritis, and may therefore be a useful target for specific immunotherapy. In support of this hypothesis, we previously observed beneficial responses in patients with active rheumatoid arthritis after open-label administration of a chimeric monoclonal antibody to TNF alpha (cA2). We now report the results of a four-centre, randomised double-blind trial of a single infusion of 1 or 10 mg/kg cA2 compared with placebo in 73 patients with active rheumatoid arthritis. The primary endpoint of the study was the achievement at week 4 of a Paulus 20% response, an amalgam of six clinical, observational, and laboratory variables. Intention-to-treat analysis of data from individual patients showed only 2 of 24 placebo recipients responding at this time, compared with 11 of 25 patients treated with low-dose cA2 (p = 0.0083) and 19 of 24 patients treated with high-dose cA2 (p < 0.0001). Over half of the high-dose cA2 patients responded by the more stringent 50% Paulus criteria at this time (p = 0.0005). The magnitude of these responses was impressive, with maximum mean improvements in individual disease-activity assessments, such as tender or swollen-joint counts and in serum C-reactive protein, exceeding 60% for patients on high-dose treatment. There were two severe adverse events. 1 patient on 1 mg/kg cA2 developed pneumonia ("possibly" treatment-related) and 1 on 10 mg/kg had a fracture ("probably not" treatment-related). The results provide the first good evidence that specific cytokine blockade can be effective in human inflammatory disease and define a new direction for the treatment of rheumatoid arthritis.

Adolescent↗
PubMed1994

Repeated therapy with monoclonal antibody to tumour necrosis factor alpha (cA2) in patients with rheumatoid arthritis.

Our in-vitro, animal, and early clinical data suggest that tumour necrosis factor alpha (TNF alpha) is an important target for specific biological therapy in rheumatoid arthritis. We report the results of repeated treatment with a chimeric monoclonal antibody to TNF alpha (cA2) in patients having disease flares. 7 patients originally enrolled in an open-label trial completed two to four cycles, each of which was followed by a good clinical response, with median improvements in the swollen-joint count and C-reactive protein exceeding 80%. cA2 may be useful therapy in the control of acute disease flares in rheumatoid arthritis and treatment programmes including cA2 may be effective in the long-term management of this disease.

Antibodies, Monoclonal↗
PubMed1994

Tricuspid valve abnormalities in patients with atrioventricular discordance: surgical implications.

From 1975 to 1990, 90 patients (age, 6 months to 30 years; mean, 9.1 years) underwent operation for defects associated with atrioventricular discordance. Twenty-one had an anatomically abnormal tricuspid (systemic) atrioventricular valve (SAVV) of the following types: Ebstein, 11; straddling, 6; and dysplastic, 4. Sixteen valves were regurgitant: regurgitation was trivial to mild in nine and moderate to severe in seven. Two patients underwent a successful Fontan-type operation. None of the 5 patients with a competent SAVV underwent valve repair or replacement; 1 of these patients died. A ventricular septal defect was closed in 14 and an extracardiac valved conduit was placed in 7. Sixteen had a regurgitant valve: it was replaced in 10 and repaired in 2 (early mortality, 25%). All 4 patients who did not undergo repair or replacement of their regurgitant SAVV died. Two patients died late after repeat replacement. Four other reoperations (closure of a residual ventricular septal defect, SAVV replacement, left ventricle-to-pulmonary artery conduit replacement, and a redo Fontan procedure) were successful. Two patients are lost to follow-up, and 9 have been followed up for them 27 to 156 months (median, 117 months). All were well when last seen. We suggest that an abnormal regurgitant SAVV should be replaced. Alternatively, a "double-switch" procedure that leaves the tricuspid valve in the pulmonary circulation may be used.

Adolescent↗
PubMed1994

Cerebral blood volume response to changes in carbon dioxide tension before and during cardiopulmonary bypass in children, investigated by near infrared spectroscopy.

Neurological impairment may occur following cardiopulmonary bypass (CPB) and the effect of CPB on cerebrovascular control may be important in the mechanism of cerebral injury. We have used near infrared spectroscopy (NIRS) to observe cerebral haemodynamics non-invasively before and during CPB. We measured the change in cerebral blood volume (CBV) associated with changing PaCO2 (CBVR). Patients (n = 19) were aged from 1 to 135 (median 14) months. The cerebral blood volume response was determined pre-operatively at normothermia under the influence of standardised anaesthesia employing isoflurane (up to ET conc 0.5%) and during steady-state hypothermic bypass (22-32 degrees C) at an arterial pump flow rate of 1.9-2.4 lm-2.min-1. Complete data was available for 10 patients. The relation between CBV, arterial carbon dioxide tension (PaCO2), mean arterial pressure (MAP) and central venous pressure (CVP) was examined using analysis of covariance (P < or = 0.05) was accepted as significant). The change in CBV associated with changing PaCO2 was corrected for the effects of MAP and CVP. Preoperatively the median CBVR was 0.130 (25th-75th percentile 0.079-0.243) ml.100 g-1.kPa-1 and during hypothermic bypass the median CBVR was 0.093 (25th-75th percentile 0.026-0.255) ml.100 g-1.kPa-1. These values were compared with our reference range derived for normal conscious children using the Kruskal-Wallis test. There was not statistically significant difference between the three groups (P = 0.35). These results, indicating preservation of CBVR during the conditions of anaesthesia and bypass used, are consistent with the observations of previous authors who measured cerebral blood flow response to carbon dioxide by a variety of other methods. Near infrared spectroscopy is proving to be a reliable, non-invasive technique for the investigation of cerebral haemodynamics during CPB.

Adolescent↗
PubMed1994

Comparison of single- and multi-dose crystalloid cardioplegia to protect the immature myocardium.

The primary objective of this study was to compare the protective effects of single-dose and multi-dose St. Thomas' Hospital cardioplegic solution number 1 in the ischemic and reperfused neonatal rabbit heart. In addition, the effect of including bicarbonate (a component of St. Thomas' Hospital cardioplegic solution number 2) was also studied. Hearts (n = 8 per group) were excised from rabbits (7-10 days old) and aerobically perfused in the working mode with crystalloid media for 20 min (37 degrees C). After assessing cardiac function, the hearts were arrested by an infusion of cold cardioplegic solution (2 min at 15 degrees C) with or without the addition of bicarbonate (10 mmol). The hearts were then subjected to 6 h of hypothermic ischemia (15 degrees C) and, during this period, some hearts received multiple infusions (2 min/h at 15 degrees C) of cardioplegic solution. All hearts were reperfused for 35 min (15 min Langendorff plus 20 min working), cardiac function was then re-assessed and expressed as a percent of the preischemic value. The coronary effluent, collected during the first 15 min of reperfusion, was assayed for creatine kinase activity. At the end of the reperfusion period, the hearts were freeze clamped and taken for metabolic analysis. With multi-dose cardioplegia (without bicarbonate) the postischemic recovery of cardiac output was 67.0 +/- 6.5% and with single-dose the value was 39.3 +/- 10.0% (NS). The same pattern of postischemic recovery (that varied between 30% and 60%) for aortic flow, stroke volume and stroke work was observed with both multi-dose and single-dose infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

New directions for biological therapy in rheumatoid arthritis.

Advances in our understanding of the pathogenesis of rheumatoid arthritis (RA), together with developments in hybridoma and molecular technology have opened the way for more directed therapy in this disease. In reviewing the experience so far with T-cell-directed biological agents, we show that the early promise displayed by anti-CD4 monoclonal antibodies in open clinical trials has not been sustained in controlled studies. This outcome provides a challenge to the concept that CD4+ T cells are of prime importance in RA, and prompts a search for alternative therapeutic targets. Agents directed towards other leucocyte antigens such as CD5, CDw52 or the receptor for interleukin 2 have induced clinical responses in early studies, but at the expense of significant toxicity. Newer therapies targeting the monokines tumour necrosis factor alpha (TNF-alpha), IL-1 and IL-6, and the leucocyte adhesion molecule intercellular adhesion molecule 1 (ICAM-1) have provided encouraging clinical improvements and, in the case of anti-TNF-alpha and anti-IL-6, impressive modulation of the acute-phase response. Strategies allowing long-term blockade of such molecules, including antibody reshaping and the use of soluble cytokine receptors are discussed. Finally, the potential for using biological agents in combination with other therapies is outlined.

Antibodies, Monoclonal↗
PubMed1994

Chronic exposure to tumor necrosis factor (TNF) in vitro impairs the activation of T cells through the T cell receptor/CD3 complex; reversal in vivo by anti-TNF antibodies in patients with rheumatoid arthritis.

Experiments were designed to test the hypothesis that chronic exposure to tumor necrosis factor alpha (TNF) alters the function of activated T lymphocytes. Pretreatment of tetanus toxoid-specific T cell clones with TNF for up to 16 d impaired rechallenge proliferative responses to antigen in a dose- and time-dependent fashion. IL-2 and PHA responses were preserved. Prolonged treatment with TNF impaired production of IL-2, IL-10, IFN gamma, TNF, and lymphotoxin (LT) following stimulation with immobilized OKT3, and resulted in suboptimal expression of the IL-2R alpha chain (Tac) but not CD3, CD4, or HLA-DR antigens, when compared to untreated control cells. By contrast, pretreatment of T cells for prolonged periods in vitro with neutralizing anti-TNF monoclonal antibodies (mAb) enhanced proliferative responses, increased lymphokine production, and upregulated Tac expression following stimulation with OKT3. To determine whether TNF exerts immunosuppressive effects on T cells in vivo, we studied cell-mediated immunity in patients with active rheumatoid arthritis (RA), before and after treatment with a chimeric anti-TNF mAb. Treatment with anti-TNF restored the diminished proliferative responses of PBMC to mitogens and recall antigens towards normal in all patients tested. These data demonstrate that persistent expression of TNF in vitro and in vivo impairs cell-mediated immune responses.

Antibodies, Monoclonal↗
PubMed1994

Exercise-induced upper extremity rhabdomyolysis and myoglobinuria in shipboard military personnel.

During a 6-month Amphibious Task Force deployment to the Mediterranean Sea, five sailors and Marines were admitted to the ship's ward with severe upper extremity pain, elevated serum muscle enzymes, and a urinalysis dip positive for blood in the absence of microscopic hematuria-a finding highly suggestive of myoglobinuria. Each patient had begun a vigorous upper-extremity work-out program in the ship's weight room 1 to 3 days prior to development of symptoms. All responded well to vigorous intravenous hydration, mannitol diuresis, alkalinization of the urine, and skeletal muscle rest. No patient developed acute tubular necrosis. With increasing emphasis on physical fitness and body building, this condition is likely to become more frequent. The most important preventive measure is gradual conditioning. Awareness of this entity and early aggressive management are necessary to avoid the potentially severe complication of renal failure.

Adult↗
PubMed1994

Surgical treatment of aortic coarctation in infants younger than three months: 1985 to 1990. Success of extended end-to-end arch aortoplasty.

There remains controversy regarding the appropriate surgical treatment of coarctation of the aorta in infants. In 1985 we introduced the extended end-to-end repair into our practice and now wish to present a review of our recent experience. One hundred fifty-one infants younger than 3 months of age underwent repair of coarctation between 1985 and 1990. In 25% and 33% of the patients, there was hypoplasia of the isthmus and of the transverse arch, respectively. Surgical procedures were as follows: subclavian flap angioplasty in 15 patients, resection with a traditional end-to-end anastomosis in 43, and resection with an extended end-to-end anastomosis into the arch in 77. In 30 patients, the extension was proximal to the origin of the left carotid artery (radically extended end-to-end anastomosis). Other procedures were used in 16 patients. Mortality (13 early and 12 late deaths) was related on multivariate analysis to the presence of an associated major heart defect, preoperative resuscitation, and direct postoperative gradient over the arch. This immediate postoperative gradient was significantly lower after both extended and radically extended end-to-end anastomosis if there was a hypoplastic isthmus, and after radically extended end-to-end anastomosis if the transverse arch was hypoplastic. Actuarial freedom from recoarctation at 4 years was 57% (confidence limits 28% to 78%) after subclavian flap angioplasty, 77% (confidence limits 60% to 87%) after end-to-end anastomosis, 83% (confidence limits 66% to 92%) after extended end-to-end anastomosis and 96% (confidence limits 77% to 100%) after radically extended end-to-end anastomosis. We conclude that the extended end-to-end anastomosis and radical end-to-end anastomosis appear to offer the best prognosis for all infants with coarctation. The technique can be applied successfully to almost all types of arch anomalies.

Age Factors↗
PubMed1993

[Combination heart-lung transplantation in children: 4-year experience in London].

Since 1987, 21 children under 16 years of age have undergone combined heart and lung transplantation at Great Ormond Street Hospital, London. All children had terminal pulmonary or cardiopulmonary disease. Eight children died one day to 21 months after operation. Actuarial survival was 76% (SEM 10) at 1 year and 60% (SEM 12) at 3 and 4 years after transplantation. 13 children were alive, and all took part in all age-appropriate activities.

Adolescent↗