Biomedical subjects
J M Morgan
Publications and source records attributed to J M Morgan.
Autosomal dominant polycystic kidney disease: new information for genetic counselling.
We evaluated the accuracy of ultrasonographic diagnosis of autosomal dominant polycystic kidney disease (ADPKD) and factors influencing its prognosis in members of 17 Newfoundland families originally described in 1984. In 10 families showing genetic linkage between ADPKD and markers for the PKD1 locus, rates of false negative ultrasonographic diagnosis are estimated as 36% below the age of 10 years and 8% or less thereafter, comparable with findings of genetic linkage studies of a subset of family members. At ages above 30 years, false negative ultrasonographic diagnosis of PKD1 disease is unlikely. In 2 families in which ADPKD is not co-inherited with PKD1 markers, only 11% of members aged less than 30 years had kidney cysts. The mean (SE) age of onset of ESRD is 56.3 (1.8) years for persons with the PKD1 form of ADPKD, and 68.7 (1.7) years for affected members of families in which ADPKD is not co-inherited with PKD1 markers (P = 0.01). In the PKD1 families, age of onset of end stage renal disease (ESRD) was unrelated to the sex of the affected individual but was earlier in persons inheriting the disease from their mothers than from their fathers (50.5 vs. 64.8 years, P = 0.004), consistent with an influence of genetic imprinting on disease progression. In females with a PKD1 mutation, onset of ESRD was not influenced by parity. In PKD1 families, resemblance in age of onset of ESRD was apparent; variation was less within than between families (F = 13.0, P less than 0.0001), and risk of false negative ultrasonographic diagnosis appears largely restricted to families in which ESRD occurs relatively late.
Frontocentral DC-potential shifts predicting behavior with or without a motor task.
This study was designed to investigate the predictive value of the event-related potentials (ERPs) preceding the initiation of a difficult perceptual-memory task and to investigate whether these ERPs require a motor movement on the part of the subject for their occurrence. Across 4 conditions the DC-potential shifts were recorded from 23 right-handed subjects using DC amplifiers. Although the start of each trial began with a ready signal, the conditions differed in that the subjects initiated the task by a button press in 2 conditions and the computer initiated it in 2 others without a press. The results showed that, especially in the frontocentral electrode sites, the DC-potential shifts which began those trials ending in correct performance were more negative relative to those trials ending in an incorrect response. Those conditions which required the subjects to self-initiate the trial and those which were initiated by the computer showed similar results indicating that the negative DC-potential shifts preceding correct performance are neither produced by nor depend on a task initiating motor movement. The onset of the DC-potential shifts preceded task initiation by up to 4.1 sec indicating that they were more than the Bereitschaftspotential.
Dispersion of monophasic action potential duration: demonstrable in humans after premature ventricular extrastimulation but not in steady state.
Abnormal dispersion of repolarization may contribute to the arrhythmogenic physiologic substrate of ventricular arrhythmia. Geographic dispersion of monophasic action potential duration was determined in steady state (drive cycle lengths 600 and 430 ms) between widely spaced right ventricular endocardial sites (geographic dispersion) in 10 control patients with right ventricular disease and complicating ventricular tachycardia (n = 9), 6 patients with right and left ventricular disease and complicating ventricular tachycardia and 7 patients with ischemic heart disease and complicating ventricular tachycardia. No significant difference in geographic dispersion could be demonstrated among the groups. Difference of monophasic action potential duration at adjacent right ventricular endocardial sites (adjacent dispersion) was determined after ventricular extrastimulation during construction of simultaneous electrical restitution curves in the same patient groups. Maximal adjacent dispersion over the electrical restitution curve was compared between disease and control groups. There was a significant difference in observations of maximal adjacent dispersion in patients with right ventricular disease and complicating ventricular tachycardia (range 5 to 85 ms, median 22.5; 14 pairs of sites; p less than 0.05) and patients with right and left ventricular disease and complicating ventricular tachycardia (range 5 to 50 ms, median 17.5; 14 pairs of sites; p less than 0.05) compared with control patients (range 5 to 20 ms, median 10; 15 pairs of sites). This difference was not evident when patients with ischemic heart disease and complicating ventricular tachycardia (range 5 to 25 ms, median 12.5; 12 pairs of sites) were compared with control patients. Maximal percent monophasic action potential shortening from steady state was significantly greater (p less than 0.001) in both groups with greater adjacent dispersions, and prolongation of activation time at monophasic action potential recording sites after premature extrastimulation tended to be greater in patients with right or right and left ventricular disease and complicating ventricular tachycardia. It is concluded that in disease, exaggeration of monophasic action potential shortening after premature ventricular extrastimulation may contribute to the electrophysiologic arrhythmogenic substrate.
Modified eggs are compatible with a diet that reduces serum cholesterol concentrations in humans.
The National Cholesterol Education Program (NCEP) guidelines recommend dietary restriction of fat and cholesterol to reduce high circulating cholesterol concentrations in adult Americans. Thus, diet counselors recommend consumption of fewer than four egg yolks per week. The present protocol was designed to determine whether the efficacy of an NCEP diet would be reduced by the incorporation of 12 modified eggs per week, and whether the resulting low fat, high cholesterol diet would increase serum lipid concentrations in adults with initial undesirably high (5.17-7.76 mmol/L) concentrations of serum total cholesterol. Feeding a controlled ration to laying hens produced modified eggs that consistently contained more vitamin E and iodine, and more unsaturated fat, than generic eggs. Subjects were randomly assigned to and NCEP diet including either no whole eggs or 12 whole study eggs a week. Ninety-eight subjects completed the parallel study. Subjects in both groups significantly reduced their serum total, LDL and HDL cholesterol (P < 0.001 for total and LDL cholesterol, P < 0.02 for HDL cholesterol) over the 6 wk of study. No significant differences were found between diet groups. We conclude that the study eggs did not adversely affect measured lipid concentrations when added to a low fat diet that favorably alters lipid profiles in hypercholesterolemic subjects.
Onycholysis in a case of atopic eczema treated with PUVA photochemotherapy.
Onycholysis following the ingestion of psoralens and subsequent exposure to natural sunlight has been reported on several occasions and was first reported following photochemotherapy in 1978 by Ortonne and Baran from France and in 1979 by Mackie from Scotland. Mackie commented that she hoped to stimulate further reports of onycholysis induced by PUVA photochemotherapy in order to establish whether or not it was a definite complication of such treatment. Since then, there has been a dearth of similar reports. We describe a patient with severe atopic eczema and alopecia totalis who developed onycholysis of all finger nails and a toe nail during PUVA photochemotherapy.
Electrical restitution in the endocardium of the intact human right ventricle.
OBJECTIVE: To characterise electrical restitution in the intact human heart. PATIENTS AND METHODS: A series of monophasic action potential electrical restitution curves were constructed from a single right ventricular endocardial site in eight patients (three men) without structural heart disease aged 52-68 (mean 55 years). A combination pacing/monophasic action potential electrode was used to pace and record monophasic action potentials at drive cycle lengths of from 350 ms to 1500 ms. Ventricular extrastimuli were delivered at 20 cycle intervals and decreased from the longest coupling interval attainable without escape beats. RESULTS: Restitution curves shifted downward and towards the left; steady state action potential duration shifted from the restitution plateau and descended the curve, the amount of shift being linearly related to drive cycle length in two patients in whom the relation could be assessed; the amount of monophasic action potential shortening was a function of the degree of prematurity and that relation was unaffected by drive rate; the magnitude of restitution and the time constant of the restitution curve were not changed significantly by altered drive cycle length. CONCLUSION: In the intact heart in vivo, electrical restitution (of the monophasic action potential) has similar characteristics to those (of the transmembrane action potential) in cellular preparations in vitro. Thus the alteration of action potential plateau currents by instantaneous rate change or drug effects, which can be directly observed by techniques available to the cellular electrophysiologist, may be indirectly assessed in vivo by characterisation of the effect of these on electrical restitution.
Aorta-coronary bypass grafting for Takayasu's aortitis.
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Outcome following incomplete revascularisation by coronary balloon angioplasty in patients with multivessel coronary artery disease.
When performing coronary angioplasty in patients with multivessel disease, there is an increasing trend to attempt balloon dilation of only ischaemia producing coronary stenoses (a strategy generally associated with incomplete revascularization) rather than attempting to dilate all anatomically significant stenoses (complete revascularization strategy). However the clinical efficacy of the former strategy has been questioned. To explore further this issue, we reviewed the records of 64 consecutive patients with multivessel coronary artery disease undergoing their first angioplasty at our centre in the 15 month period, October 1st 1987 to December 31st 1988. In 59 of these 64 patients, a strategy of incomplete revascularisation [attempted dilation of at least one stenosis > or = 70% but with one or more residual stenoses > or = 70% that were not attempted] was pursued. Of these 59 patients, 18 (31%) has three vessel coronary artery disease [stenoses > or = 70% in all three major coronary artery territories] and 19 (32%) had undergone previous coronary bypass surgery. In all 59 patients, prior to angioplasty, it was attempted to identify the ischaemia producing (so-called 'culprit') lesion(s). In the 59 patients, 66 culprit lesions in 63 vessels were identified. At angioplasty, in all patients, attempted dilation was confined to the culprit lesion(s). Clinical success (successful dilation of all attempted lesions without the occurrence of in-hospital myocardial infarction, death, or coronary bypass surgery) was achieved in 53 (90%) patients. At one year following successful angioplasty, no patient had died or suffered a myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
Sudden cardiac death while taking amiodarone therapy: the role of abnormal repolarization.
Torsade de pointes may occur as a complication of amiodarone therapy. We report a patient receiving amiodarone who was resuscitated from cardiovascular collapse and documented ventricular fibrillation. At subsequent electrophysiology study, while the patient was taking amiodarone therapy, monophasic action potentials with early after depolarisations were recorded which were not present when the patient was restudied 6 weeks after discontinuation of amiodarone. Early after-depolarisations may be important in the genesis of polymorphic ventricular tachycardia complicating amiodarone therapy.
Comparison of patients with idiopathic calcium phosphate and calcium oxalate stones.
Our primary objective was to test the hypothesis that a defect in acidification is more common in patients who have idiopathic calcium phosphate kidney stones than in those whose stones are formed mainly of calcium oxalate. Additionally, other risk factors might differ for these 2 stone types. Urine pH was measured serially over 24 hours, and along with ammonium and titratable acid, it was measured before and serially after ingestion of ammonium chloride in 3 groups of subjects: 24 patients with predominantly calcium phosphate stones, 30 patients with calcium oxalate stones, and 15 health non-stone-formers. Twenty-six parameters potentially related to stone formation and acidification were assayed on urines collected over 24 hours, and 15 parameters on blood. The data base was a computerized list of 5900 analyses of stones from patients living in Newfoundland. Patients not known by their physician to have had urinary tract infection, anatomical abnormality, hyperparathyroidism, or renal tubular acidosis were asked to participate in the study. Differences between means were considered significant if p values were less than 0.05 for F by analysis of variance and also less than 0.01 by t-test. In all patients with calcium oxalate stones and all non-stone-formers, urine acidified to pH less than 5.25, but in 8 of the 23 phosphate stone formers who completed the ammonium chloride study urine failed to acidify to pH less than 5.25. As all 8 had normal values for venous pH, total CO2, and chloride, they were considered to have incomplete renal tubular acidosis (IRTA). The 8 phosphate stone formers with IRTA had greater mean values for urine pH on all 9 specimens collected serially over 24 hours (all means greater than 6.2), and after administration of ammonium chloride (p less than 0.01), as well as lower mean values for urine titratable acid excretion (p less than 0.01), both after administration of ammonium chloride and in 24-hour urine samples, compared with the remaining phosphate stone formers whose urine acidified and the oxalate and non-stone-forming control groups. Nearly all the phosphate stone formers had 1 or more risk factors for stone formation, but with frequencies not significantly higher than those found in the oxalate group. Hypercalciuria and hypocitruria were the commonest, but increased oxalate or urate also occurred. Thus, idiopathic calcium phosphate stone formation can be associated with 1 or more of several risk factors, and, with the possible exception of those with IRTA, treatment should be similar to that given to patients with calcium oxalate stones.
Outcome of extensive coronary artery dissection during coronary angioplasty.
A total of 32 (3.6%) patients of 880 undergoing coronary angioplasty during a nine year period at one hospital had extensive dissection (defined as a dissection extending beyond the limits of the dilated angioplasty balloon) in the coronary artery in which the angioplasty procedure was performed. Two (6.25%) of the 32 patients (both of whom were undergoing angioplasty because of unstable angina that was refractory to medical treatment) died as a consequence of the coronary artery dissection. Twelve (38%) needed immediate coronary artery bypass surgery and 11 (34%) had a myocardial infarction, which in four was minor in extent. During follow up, 20 of the 32 patients were successfully managed by medical treatment; only two needed further angioplasty procedures. There were no late deaths. Extensive coronary artery dissection is a serious complication of coronary angioplasty, with a high early mortality and a high incidence of infarction and requirement for bypass surgery. None the less, patients with extensive dissection who are free from the manifestations of acute ischaemia at the end of the procedure can be managed conservatively and have a good immediate and medium term outlook. Attempts should be made to stabilise extensive dissection during coronary angioplasty so that surgical intervention can be delayed or avoided altogether if possible.
Adenosine as a vasodilator in primary pulmonary hypertension.
BACKGROUND: The acute administration of vasodilator drugs to patients with primary pulmonary hypertension has been advocated to identify those with reversible pulmonary vasoconstriction. Unfortunately, the usefulness of the drugs currently available is limited by accompanying systemic hypotension. A vasodilator with effects confined to the pulmonary circulation would therefore be advantageous in such patients. METHODS AND RESULTS: The purine nucleoside adenosine was infused into the pulmonary artery in seven patients with primary pulmonary hypertension (baseline pulmonary vascular resistance [PVR], 442-1,295 dyne/cm/sec-5) to determine its effect on PVR. In all patients, there was a dose-dependent and significant reduction (mean maximal percent decrease from baseline, 38.9%; p less than 0.001) in PVR mediated through a decrease in pulmonary artery pressure and an increase in cardiac output. Systemic vascular resistance (SVR) also decreased, but the ratio of PVR to SVR decreased (maximal mean percent decrease from baseline) by 10.5% (p less than 0.025), indicating that adenosine has a preferential vasodilator effect on the pulmonary circulation when administered in this manner. CONCLUSIONS: Because of its pharmacokinetic and vasodilator properties, adenosine may have a specific role in the investigation of primary pulmonary hypertension.
Hypoxic pulmonary vasoconstriction in systemic sclerosis and primary pulmonary hypertension.
Reduction of pulmonary vascular resistance by a high inspired oxygen concentration is a common, but not universal phenomenon in patients with pulmonary vascular disease of varying etiology that may determine their response to long-term domiciliary oxygen therapy. We therefore determined changes in PVR during oxygen therapy in two patient populations not previously studied: systemic sclerosis (n = 8, mean age +/- SEM, 44.5 +/- 5.4 years) and primary pulmonary hypertension (n = 7, mean age +/- SEM 38 +/- 7.8 years). All patients were hypoxemic (arterial oxygen tension, on air 9.5 +/- 1.2 kPa for SSc and 8.3 +/- 0.6 kPa for PPH, p greater than 0.05). Right atrial pressure, pulmonary artery pressure, pulmonary artery occlusion pressure, systemic arterial pressure, PaO2 and cardiac output by thermodilution were measured at three, 20-min intervals while inspiring air and again after inspiring 60 percent oxygen for 30 min. The PVR fell significantly with oxygen in patients with SSc from 797.6 +/- 179.2 to 610 +/- 151.6 dynes/s/cm-5 (p less than 0.01), and this fall correlated with baseline PAP and PaO2 prior to oxygen therapy (r = 0.86, p less than 0.025; r = 0.77, p less than 0.05, respectively). In patients with PPH, there was no significant fall in PVR with oxygen (from 969 +/- 80.2 to 851.9 +/- 91.2 dynes/s/cm-5, p greater than 0.05) and no predictor of a vasodilator response in individual patients. In SSc, hypoxic pulmonary vasoconstriction contributes more consistently to elevated PVR than in patients with PPH.
Retrospective review of hospital patient records.
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Coronary arterial occlusion and myocardial infarction in acute myocarditis.
Coronary arterial occlusion may occur experimentally during acute myocarditis but has not been documented in man. We report the case of a young female with severe myocarditis who later required cardiac transplantation and in whom coronary occlusion was demonstrated arteriographically before transplantation and by pathological examination of the heart after explantation.
The clinical features, management and outcome of persistence of the arterial duct presenting in adult life.
We have reviewed the 25 patients who, between 1973 and 1988, presented to the Brompton Hospital in adulthood with persistence of the arterial duct (ductus arteriosus). As pulmonary arteriolar resistance is the main determinant of management and prognosis in this condition, the patients were divided into groups with either normal or mild elevation of resistance (less than 10 units/m2: 19 patients) or with severe elevation (greater than 10 units/m2: 6 patients). Patients with normal pressures or mild elevation tended to be older (mean age 45 years). Many (70%) were asymptomatic, but dyspnoea with signs of left heart failure was the commonest presenting complaint. Surgical closure of the duct was performed in 16 with good result in all. Survival for the entire group, however, was long. There was a symptomatic indication for surgery (due to hyperdynamic circulation) in 5. In those with severely elevated pulmonary arteriolar resistance, the mean age of presentation was 31 years and the survival short. The commonest presenting symptom was dyspnoea. Surgical closure of the duct was attempted in two patients but with a poor outcome in both. All patients with an elevated resistance had developed this complication by the third decade of life. Significant elevation was not a feature of older patients, suggesting that, in this age group, the risk of elevation is slight. Surgery, nonetheless, may be indicated for relief of symptoms due to a large systemic to pulmonary shunt.
Choosing the pacemaker; a rational approach to the use of modern pacemaker technology.
Sophisticated pacemakers now afford greater benefit than only relief of syncope for patients with symptomatic bradyarrhythmia. For clinical reasons it is inappropriate to implant ventricular demand (VVI) pacemakers in every patient, but for both clinical and economic reasons it is also undesirable to use dual-lead or rate-responsive systems indiscriminately. However, the published guidelines for pacemaker choice and investigation are inadequate. We have analysed the clinical assessment and the investigations required in a series of 150 patients with various electrophysiological disorders, considered consecutively for pacemaker implantation using an algorithm to assist decisions. Holter electrocardiography in 77.3%, exercise testing--formal (in 9.3%) or informal (during Holter electrocardiography), electrophysiology study (EPS)--full in 15.3% and partial in 29.3%, and trial of pacing (10.7%) were all used to characterize dysfunction and to define appropriate pacing mode. 142 patients were paced--57.0% with single lead modes (12.7%) AAI, 44.3% VVI) and 43.0% dual-lead (2.8% DVI, 23.9% VDD or VAT, 16.2% DDD). Three patients received rate-responsive systems (VVIR) which, if available, would have been used in nine; four would have been suitable for AAIR and four for dual-lead responsive pacing (DVIR, DDIR or DDDR). We offer a rational approach based on published data for investigation and pacemaker choice in the management of patients with bradyarrhythmia.