Biomedical subjects
Publications and source records attributed to J D Mitchell.
A patient health questionnaire was developed for use in family practice to help identify lifestyle risk factors, assess health care needs, and better understand patients. This article discusses the questionnaire's development and practical application.
The placement of left atrial catheters following cardiopulmonary bypass (CPB) allows accurate monitoring of left ventricular filling pressures, as well as access for the infusion of vasoactive drugs. While the left atrial administration of norepinephrine (NE) is thought to provide higher systemic arterial NE levels while minimizing any pulmonary vasoconstriction, no study critically compares central venous and left atrial NE infusion following cardiopulmonary bypass. A canine model was used to compare central venous and left atrial NE infusion at three dosages (0.2, 0.4, and 0.6 microgram/kg/min) both prior to CPB and following 2 hr of hypothermic CPB at 27 degrees C. Prior to CPB, there was no difference in the hemodynamic efficacy of central venous and left atrial NE infusion at any dosage. The pulmonary circulation metabolized 16-29% of circulating NE. Only at the 0.2 microgram/kg/min dose was there a difference in the arterial NE level between central venous (3474 +/- 486 pg/ml) and left atrial (5504 +/- 751 pg/ml, P = 0.019) NE administration. Above this dose, no difference in the arterial NE level was identified. Following 2 hr of CPB, the pulmonary endothelium metabolized a significantly higher percentage of circulating NE (35-42%). Despite this increased extent of pulmonary metabolism, there was no difference in the hemodynamic efficacy or the resulting arterial NE level of central venous and left atrial NE infusion at a given dose. In conclusion, the results demonstrate: (1) increased pulmonary NE uptake following CPB, and (2) no difference in hemodynamic efficacy between central venous and left atrial NE infusion over a wide range of three doses in a model with normal lungs.
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There have been no reports of changes in free radical inactivating enzymes in the anterior horn of the spinal cord in ALS despite great interest in the possibility that free radicals might be important in the aetiology of the disease. In this study we have measured copper/zinc superoxide dismutase (Cu/ZnSOD), manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GSHPX) activities in anterior horn tissue obtained from patients with ALS and from controls. Total SOD activity was no different in the anterior horn of ALS cases compared to controls, but Cu/ZnSOD activity was reduced, and that of MnSOD increased, at thoracic cord level only. No detectable activity of GSHPX or cytochrome P450 (unpublished data) was found. These latter negative findings are important because they suggest that generation of free radicals from exogenous chemicals is not important in ALS and further that the neurone (as compared to other cell types) is poorly protected against the toxicity of hydrogen peroxide.
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Possible changes in brain metabolites in motor neurone disease/amytrophic lateral sclerosis (MND/ALS) were investigated using 1H magnetic resonance spectroscopy (MRS). A series of normal, healthy volunteer controls and MND patients have been studied using a spin echo (SE) 135 ms sequence, acquiring spectra from the region of the motor cortex. A further limited series of studies have been made for similar groups of volunteers and MND patients using a STEAM 20 ms sequence (stimulated echo). Analysis of the SE 135 ms spectra indicates there are statistically significant differences in the ratios of N-acetyl-aspartate to creatine and N-acetyl-aspartate to choline between controls and MND patients. Furthermore, metabolites identified using the STEAM 20 ms may be of great importance in the investigations of free radical mediated mechanisms, which have been postulated as being important contributors to the disease process. Preliminary results indicate that 1H MRS may provide important data to help understand the disease processes in MND and it could form a useful method for monitoring the effects of future trial treatment regimens.
Studies on anterior horn dissected from MND patients have demonstrated that MnSOD activity is increased when expressed as a percentage of total SOD activity when compared to controls. Total SOD activity (mean +/- SD) in controls = 414 +/- 105 U mg-1 tissue and in MND patients = 373 +/- 115 U mg-1 tissue, whereas CuZnSOD activity was higher in controls (290 +/- 91 U mg-1 tissue) than in MND patients (197 +/- 81 U mg-1 tissue). The reduction in CuZnSOD was compensated for by a concomitant elevation of MnSOD activity (control = 123 +/- 40.5 U mg-1 tissue, MND patients = 175 +/- 47 U mg-1 tissue). These data not only show an important deficit in anterior horn cell body protection against free radical-mediated cell damage, but are also are the first measurements of SOD isoenzymes in anterior horn neurones.
We report a family with type 2 neurofibromatosis and late onset tumours. Five members of this family have developed hearing loss late in life, two of whom have only been shown to have the diagnosis in their seventies, and three other obligate gene carriers died undiagnosed at 64, 72, and 78 years of age. A missense mutation at the C-terminal end of the NF2 protein has been identified in this family and segregates with disease. The use of highly polymorphic markers for predictive testing is also shown. There appears to be an autosomal dominant form of spinocerebellar degeneration which is segregating separately to NF2 in this family, which created a diagnostic dilemma.
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OBJECTIVES: The purpose of this study was to demonstrate the feasibility of in vivo three-dimensional reconstruction of ventricular septal defects and to validate its quantitative accuracy for defect localization in excised hearts (used to permit comparison of three-dimensional and direct measurements without cardiac contraction). BACKGROUND: Appreciating the three-dimensional spatial relations of ventricular septal defects could be useful in planning surgical and catheter approaches. Currently, however, echocardiography provides only two-dimensional views, requiring mental integration. A recently developed system automatically combines two-dimensional echocardiographic images with their spatial locations to produce a three-dimensional construct. METHODS: Surgically created ventricular septal defects of varying size and location were imaged and reconstructed, along with the left and right ventricles, in the beating heart of six dogs to demonstrate the in vivo feasibility of producing a coherent image of the defect that portrays its relation to surrounding structures. Two additional gel-filled excised hearts with defects were completely reconstructed. Quantitative localization of the defects relative to other structures (ventricular apexes and valve insertions) was then validated for seven defects in excised hearts. The right septal margins of the exposed defects were also traced and compared with their reconstructed areas and circumferences. RESULTS: The three-dimensional images provided coherent images and correct spatial appreciation of the defects (two inlet, two trabecular, one outlet and one membranous Gerbode in vivo; one inlet and one apical in excised hearts). The distances between defects and other structures in the excised hearts agreed well with direct measures (y = 1.05x-0.18, r = 0.98, SEE = 0.30 cm), as did reconstructed areas (y = 1.0x-0.23, r = 0.98, SEE = 0.21 cm2) and circumferences (y = 0.97x + 0.13, r = 0.97, SEE = 0.3 cm). CONCLUSIONS: Three-dimensional reconstruction of ventricular septal defects can be achieved in the beating heart and provides an accurate appreciation of defect size and location that could be of value in planning interventions.
Various materials have been suggested for pericardial closure following cardiac surgery to limit postoperative adhesion formation. Unfortunately, these devices have caused difficulties with infection, calcification, and epicardial scar formation. A bioabsorbable membrane with a short in-vivo persistence time, acting as a barrier to adhesion formation until mesothelial healing occurs, might obviate many of these problems. We examined the efficacy of a bioabsorbable membrane containing hyaluronic acid in the prevention of experimental pericardial adhesions; hyaluronic acid solutions have been shown experimentally to reduce adhesions following abdominal, orthopedic and cardiac surgery. Eleven dogs underwent sternotomy and pericardiotomy followed by 2-h protocol of desiccation and abrasion of pericardial and epicardial surfaces. In five dogs, the epicardial surfaces were covered with the test material, followed by pericardial and sternotomy closure. Six dogs served as controls. All animals underwent resternotomy 8 weeks after surgery; intrapericardial adhesions were graded on a severity scale (0-4). The test animals (mean adhesion score 1.4 +/- 0.5) had either no adhesions or filmy, avascular adhesions easily taken down with blunt dissection. In contrast, dense adhesions were found in the control animals (mean score 3.2 +/- 0.4), frequently obscuring tissue planes and epicardial anatomy. Use of the bioabsorbable membrane significantly reduced adhesion formation (test vs control, P < 0.001, Mann-Whitney test). We conclude that a hyaluronic acid membrane reduces postoperative pericardial adhesions in this canine model, and that the use of a bioabsorbable barrier in the prevention of pericardial adhesions warrants further investigation.
The success of ventricular operation in ablating drug-refractory ventricular tachycardia secondary to ischemic heart disease varies with surgical technique, the presence of certain identified risk factors, and patient selection biases. Forty-eight patients with drug-refractory ventricular tachycardia secondary to ischemic heart disease underwent directed ventricular operation. All patients had previous myocardial infarction, and 46 of 48 patients had a left-ventricular aneurysm. Mapping was done in 81% of patients. Patients underwent a combination of subendocardial resection, aneurysmectomy, and cryoablation. The operative mortality rate was 8%. Age greater than 65 years was the only risk factor for operative mortality. Forty-one patients underwent postoperative programmed electrical stimulation. In 26 patients (63%) tachycardia was noninducible, whereas it was inducible in 15 patients (37%). Stepwise logistic regression identified septal and inferior focus location as the most significant predictors of outcome. Septal focus location was a significant (p = 0.008) predictor of surgical success whereas inferior focus location was a significant (p = 0.015) predictor of surgical failure. Other identified independent risk factors for surgical failure were (1) use of cardioplegia, (2) lack of a completed intraoperative endocardial map, and (3) decreased ejection fraction. This generated model to predict success or failure had a sensitivity of 93.3% and a specificity of 92.4%. The success of ventricular operation is affected by the presence of certain risk factors. In the management of those patients at high risk for failure, other surgical options such as the placement of implantable cardioverter-defibrillator electrode patches at the time of ventricular operation or the alternative placement of a palliative implantable cardioverter-defibrillator should be considered.
Postoperative pericardial adhesions complicate reoperative cardiac procedures. Topical application of solutions containing hyaluronic acid have been shown to reduce adhesions after abdominal and orthopedic surgery. The mechanism by which hyaluronic acid solutions prevent adhesion formation is unknown but may be due to a cytoprotective effect on mesothelial surfaces, which would limit intraoperative injury. In this study, we tested the efficacy and safety of hyaluronic acid coating solutions for the prevention of postoperative intrapericardial adhesion formation. Eighteen mongrel dogs underwent median sternotomy and pericardiotomy followed by a standardized 2-hour protocol of forced warm air desiccation and abrasion of the pericardial and epicardial surfaces. Group 1 (n = 6) served as untreated control animals. Group 2 (n = 6) received topical administration of 0.4% hyaluronic acid in phosphate-buffered saline solution at the time of pericardiotomy, at 20-minute intervals during the desiccation/abrasion protocol, and at pericardial closure. The total test dose was less than 1% of the circulating blood volume. Group 3 (n = 6) served as a vehicle control, receiving phosphate-buffered saline solution as a topical agent in a fashion identical to that used in group 2. At resternotomy 8 weeks after the initial operation, the intrapericardial adhesions were graded on a 0 to 4 severity scale at seven different areas covering the ventricular, atrial, and great vessel surfaces. In both the untreated control (group 1, mean score 3.2 +/- 0.4) and vehicle control (group 3, mean score 3.3 +/- 0.2) animals, dense adhesions were encountered. In contrast, animals treated with the hyaluronic acid solution (group 2, mean score 0.8 +/- 0.3) characteristically had no adhesions or filmy, transparent adhesions graded significantly less severe than either the untreated control (group 2 versus group 1, p < 0.001) or vehicle control (group 2 versus group 3, p < 0.001) animals. In separate experiments, six baboons were infused with 0.4% hyaluronic acid in phosphate-buffered saline solution in volumes equivalent to 2.5%, 5%, and 10% of the measured circulating blood volume. The 2.5% and 5% infusions had no effect on the parameters measured; infusion of the 10% volume produced transient hemodynamic, coagulation, and gas exchange abnormalities. Hyaluronic acid solutions are efficacious in the prevention of pericardial adhesions in this model, and they appear safe in doses five times the amount needed to prevent adhesions. Further studies investigating the mechanism by which these solutions prevent adhesions, their optimal dose and method of application, and documentation of their safe use in humans are warranted.
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Children (227) undergoing endoscopy for upper gastrointestinal symptoms were investigated for the presence of Helicobacter pylori infection. The histological response to H. pylori infection and the presence of antral nodularity and peptic ulceration were noted. Symptomatic adults (258) undergoing endoscopy were also investigated for the presence of nodularity. H. pylori infection was detected histologically in 32 of 227 (14.1%) children. Of those children infected with H. pylori, half (50%) had antral nodular gastritis. Of 139 H. pylori-positive adults 22 (15.8%) showed nodularity. The active component of the histological response was found to be minimal or lacking in the majority of children infected with H. pylori. Twelve of the 227 children (5.3%) had peptic ulcer disease. Of these, nine were duodenal and three gastric ulcers. Of the nine children with duodenal ulceration three (33%) were infected with H. pylori. As a result of this study we conclude that (a) although antral nodularity occurs more frequently in children it is not exclusive to childhood, (b) the polymorphonuclear response in children is less than that reported in adults, and (c) peptic ulcer disease is rare in children and the present study would suggest that in children it is less frequently associated with H. pylori infection than in adults.
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The implantable cardioverter-defibrillator provides an alternative therapy for medically refractory ventricular tachyarrhythmias in patients who are not candidates for ventricular operations or in whom these operations have failed. Currently, however, available devices have limitations. In this report we describe our experience with a programmable, tiered therapy device with anti-ventricular tachyarrhythmia pacing and VVI pacing capabilities (Cadence V-100, Ventritex Inc., Sunnyvale, Calif.). This device offers certain advantages compared with conventional implantable cardioverter-defibrillators: (1) tiered, anti-ventricular tachyarrhythmia therapy incorporating programmable, rate-adaptive burst pacing in addition to energy-programmable cardioversion/defibrillation, (2) biphasic cardioversion/defibrillation waveforms, resulting in lower defibrillation thresholds, (3) the ability to abort therapy for nonsustained ventricular tachyarrhythmias, (4) electrogram storage of detected events for later retrieval and analysis, (5) noninvasive, device-generated programmed stimulation for system testing, and (6) backup VVI pacing capability. Forty patients (aged 14 to 79 years) with ventricular tachyarrhythmias refractory to medical therapy received this device. The mean left ventricular ejection fraction was 33% +/- 16%. Preoperative electrophysiologic testing revealed inducible monomorphic ventricular tachyarrhythmia responsive to rapid ventricular pacing in 36 patients (90%). An extrapericardial two-patch configuration was used with either epicardial screw-in or bipolar endocardial sensing/pacing wires. No operative mortality and no device-related infection occurred. During a follow-up period of 16 +/- 7 months (range 3 to 30 months), 38 patients remained active with the implanted device; one patient died of congestive heart failure 4 months after implantation, and the system was explanted in one patient who underwent cardiac transplantation. In 33 patients a total of 1815 ventricular tachyarrhythmias were detected that resulted in therapy. Rate-adaptive burst pacing was used as the initial therapy in 1470 episodes and was successful in 1352 instances (92%). Pacing-induced ventricular tachyarrhythmia acceleration occurred in 4% of episodes. The remaining ventricular tachyarrhythmia episodes were treated with cardioversion. In 18 patients (45%) cardioversion therapy was aborted after spontaneous termination of ventricular tachyarrhythmia.(ABSTRACT TRUNCATED AT 400 WORDS)
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