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Biomedical subjects

G Jackson

Publications and source records attributed to G Jackson.

At least 235 records · Page 13Linked to original sources
PubMed1990

Simultaneous determination of Bordetella pertussis toxin and filamentous haemagglutinin concentrations by hydroxyapatite high-performance liquid chromatography.

A simple and rapid method for the simultaneous determination of Bordetella pertussis toxin (PT) and filamentous haemagglutinin (FHA) concentrations in fermentation broths has been developed. The rapid single-step analysis performed by hydroxyapatite high-performance liquid chromatography using a salt gradient with UV detection allows both the separation of PT from FHA and the measurement of their respective concentrations. The assay is highly reproducible. Over 35 lots of acellular B. pertussis vaccine production lots were examined and PT concentrations measured by high-performance liquid chromatography were found to be in good agreement with the values obtained by sodium dodecyl sulphate-polyacrylamide gel electrophoresis densitometry. The chromatographic conditions have been optimized to separate the intact holotoxin from its B-oligomer subunits.

Amino Acids↗
PubMed1990

Ventricular stroke work loss: validation of a method of quantifying the severity of aortic stenosis and derivation of an orifice formula.

Because aortic stenosis results in the loss of left ventricular stroke work (due to resistance to flow through the valve and turbulence in the aorta), the percentage of stroke work that is lost may reflect the severity of stenosis. This index can be calculated from pressure data alone. The relation between percent stroke work loss and anatomic aortic valve orifice area (measured by planimetry from videotape) was investigated in a pulsatile flow model. Thirteen valves were studied (nine human aortic valves obtained at necropsy and four bioprosthetic valves) at stroke volumes of 40 to 100 ml, giving 57 data points. Valve area ranged from 0.3 to 2.8 cm2 and mean systolic pressure gradient from 3 to 84 mm Hg. Percent stroke work loss, calculated as mean systolic pressure gradient divided by mean ventricular systolic pressure x 100%, ranged from 7 to 68%. It was closely related to anatomic orifice area with an inverse exponential relation and was not significantly related to flow (r = -0.15). An orifice formula was derived that predicted anatomic orifice area with a 95% confidence interval of +/- 0.5 cm2 (orifice area [cm2] = 4.82 [2.39 x log percent stroke work loss], r = -0.94, SEE = 0.029). These results support the clinical use of percent stroke work loss as an easily obtained index of the severity of aortic stenosis.

Aortic Valve↗
PubMed1990

QT prolongation on the electrocardiogram in diabetic autonomic neuropathy.

Patients with Type 1 diabetes and autonomic neuropathy have an increased risk of sudden death for which the mechanism remains obscure. Prolongation of the QT interval on the electrocardiogram may occur with sympathetic dysfunction and is also associated with ventricular arrhythmia and sudden death. We have therefore measured the QT interval in patients with Type 1 diabetes with normal, borderline, and definitely abnormal autonomic function tests and in non-diabetic control subjects. The maximum QT interval was measured on 12-lead electrocardiograms recorded at rest and then plotted against the RR interval. The QT interval was above the upper 95% limit for the non-diabetic control subjects in 5 diabetic patients with abnormal autonomic function tests (33%), but in no cases with normal or borderline tests. Multivariate analysis confirmed that autonomic score contributed significantly (p less than 0.025) to the variance in QT interval. The raw Valsalva ratio alone also contributed significantly to the variance in QT interval (p = 0.025). Heart rate variability, heart rate response to standing, age, sex, and the presence of symptoms of autonomic neuropathy did not contribute significantly.

Arrhythmias, Cardiac↗
PubMed1990

Echocardiographic appearance of pulmonary artery stenosis.

Colour flow Doppler mapping can show abnormalities of flow even when the echocardiographic image is equivocal. Routine echocardiography in two patients who were thought to have pulmonary valve stenosis and a ventricular septal defect initially appeared to be normal. Colour flow Doppler mapping, however, showed multiple flow aliasing within the pulmonary artery, approximately 1.5 cm downstream from the pulmonary valve. More detailed examination by cross sectional echocardiography showed a membrane at this level in both patients. It is possible that more cases of this uncommon anomaly will come to light with increasing use of Doppler techniques.

Adult↗
PubMed1990

Limitations of Doppler ultrasound in the assessment of the function of prosthetic mitral valves.

Pressure half time has been assumed to be a relatively flow-independent measure of orifice area, but it may also be influenced by atrial and ventricular factors. Pressure half time and peak left ventricular inflow velocity were measured by continuous wave Doppler ultrasound in 164 patients with normally functioning Carpentier-Edwards, Björk-Shiley, and Starr-Edwards mitral prostheses. Pressure half time was shorter in the Björk-Shiley than in the other value types and peak transmitral velocity was highest in the Starr-Edwards prostheses. These differences, however, were partly explained by coexistent differences in transmitral flow. Filling time accounted for 19% and stroke volume for 15% of the variance in pressure half time compared with only 5.6% for prosthetic design and 0.4% for annulus diameter when each of these variables was considered alone. The design of the prosthesis explained 18% of the variance in peak transmitral velocity, while cardiac output and annulus diameter did not contribute significantly. With Doppler ultrasound it is impossible to define reliable normal ranges for prosthetic function independently of atrial and ventricular function. Formulas for orifice area based on peak transmitral velocity and flow seem more likely to reflect the behaviour of normally functioning prostheses than those based on pressure half time.

Blood Flow Velocity↗
PubMed1989

Improvement of platelet counts in steroid-unresponsive idiopathic immune thrombocytopenic purpura after short-course therapy with recombinant alpha 2b interferon.

In 13 patients with severe steroid-refractory idiopathic immune thrombocytopenia (ITP), a short course of recombinant alpha 2b interferon (IFN), given at a dose of 3 MU for 12 doses, caused a significant increase in platelet count in 11 patients. The rise in platelet count occurred following completion of the short course of IFN in 10 patients and occurred during therapy in one patient. Three patients showed an increase to normal platelet counts within 14 days of discontinuing the drug, eight showed a partial response, with a platelet count increase from 30 to 100 x 10(9)/L, and two patients showed minimal response. One complete responder relapsed at 5 months from initial response, and a further course of alpha 2b IFN caused a second prompt response with a rise of platelet count to supranormal levels. Short-course alpha 2b IFN can be recommended as a therapy for severe ITP. Responses are seen in splenectomized and nonsplenectomized subjects, and thrombocytopenia is not exacerbated during treatment.

Autoimmune Diseases↗
PubMed1989

Severe renal toxicity due to intermediate-dose methotrexate.

Methotrexate (MTX) is a drug widely used in the treatment of patients with malignant disease. Its well-known side effects include myelosuppression, mucositis and renal damage. These problems are primarily dose-related, tending to occur more frequently when high doses (greater than 1 g/m2) are given. We present four cases in whom severe renal and mucosal toxicity occurred with intermediate doses (200 mg/m2) of MTX despite folinic acid rescue. Possible reasons for this occurrence are discussed and means of avoiding such toxicity are suggested. Three of four patients developed severe loin pain within a few hours of injection; the significance of this symptom in relation to subsequent renal toxicity has implications for early recognition of the problem.

Adult↗
PubMed1989

Efficacy of aortic balloon valvoplasty: direct measurement of orificial area in a model with pulsatile flow.

The efficacy of balloon valvoplasty of calcific aortic stenosis remains controversial. We studied, therefore, 5 human aortic valves obtained at necropsy in a positive-displacement pulse duplicator which delivered stroke volumes of 40-100 ml with a quasiphysiological waveform of flow. All valves had three leaflets without commissural fusion and were preserved in antibiotic solution before study. Orificial area was planimetered from videotape of opening of the valve and varied with flow in all cases. Valvoplasty with a 20 mm diameter balloon had no effect on the orifice of the normal valve but increased the orifice of 2 mildly calcified valves from 0.70-1.77 cm2 (range) at baseline to 1.06-1.95 cm2. In 2 valves with severe calcification of the leaflets, the orifice was increased from 0.31-0.82 cm2 to 0.73-1.07 cm2. Dual balloon valvoplasty achieved a variable but small further increase in orificial area. No valve showed tears of the leaflets or fracture of calcific deposits after valvoplasty. We conclude that balloon valvoplasty can acutely increase orificial area, independently of any change in stroke volume. In valves without commissural fusion, its mechanism appears to be an increase in the pliability of the leaflets which does not require macroscopic fracture of calcific deposits.

Adult↗
PubMed1989

A randomised double-blind crossover study of isosorbide mononitrate and nifedipine retard in chronic stable angina.

In order to evaluate and compare the efficacy and safety of nifedipine retard and isosorbide-5-mononitrate as monotherapy in the treatment of stable angina, 18 patients with abnormal exercise electrocardiograms and angiographically proven coronary arterial disease were studied in a randomised placebo controlled double-blind crossover study comparing isosorbide 20 mg twice a day, sustained released isosorbide 40 mg once daily and nifedipine 20 mg twice a day each given for two weeks. Patients were assessed subjectively by counting the frequency of anginal attacks and glyceryl trinitrate consumed and objectively by maximal symptom-limited treadmill stress tests performed at "trough" therapeutic blood levels on the last day of each treatment period. There were no significant differences in all parameters between entry and run-out placebo. Compared to placebo, all three active treatments showed significant improvement in exercise time to 1 mm ST segment depression, amount of maximum ST segment depression and exercise duration. All three active treatments also significantly reduced the consumption of glyceryl trinitrate and frequency of anginal attacks. There were no significant differences between active treatments. Thus similar clinical improvements were produced by nifedipine retard and isosorbide, both being shown to be equally effective starting therapy for the treatment of patients with stable angina pectoris. Although anginal frequency was reduced by one third and exercise time increased residual symptoms and exercise ischaemia suggest that nifedipine retard and isosorbide may be more clinically useful in combination therapy. Neither demonstrated tolerance after two weeks of therapy.

Aged↗
PubMed1989

The Gorlin formula validated against directly observed orifice area in porcine mitral bioprostheses.

To assess the effect of fluid flow on orifice area and to test the Gorlin formula, six Carpentier-Edwards mitral valve prostheses were studied in a positive displacement pulse duplicator at 20 different rate-stroke volume combinations. Peak transvalvular velocity (V max) was measured by continuous wave Doppler ultrasound, and orifice area was determined from hard copy of video images. Orifice area was directly related to mean flow (Q), although cusp opening behavior was asymmetric and complex and varied among the individual valves. There was a strong correlation between measured orifice area (OA) and the modified Gorlin relation, Q/V max (r = 0.88; p less than 0.00001) given by the regression formula OA = 0.18 x Q/V max - 0.15. There was also a good correlation between measured orifice area and the conventional Gorlin relation, Q/root mean pressure drop. The derived empiric Gorlin constant did not vary significantly with flow.

Bioprosthesis↗
PubMed1989

The effect of flow on Doppler estimates of bioprosthetic mitral valve function in vitro.

In order to assess the effect of flow on peak transmitral velocity and pressure half time and to test the Hatle orifice area formula, four Carpentier-Edwards mitral prostheses were studied in a positive displacement flow simulator at 20 different stroke volume/rate combinations using a constant left ventricular filling curve. Peak transmitral velocity was directly related to mean flow and differed significantly between the individual values (F79 = 38; p less than 0.00001). There was, however, no significant difference in pressure half time between the four values (F79 = 0.04; p = 0.99). Pressure half time was directly related to diastolic time interval (r = 0.98, y = 0.41x - 17.84; p less than 0.00001), but was independent of stroke volume. There was only a moderate inverse correlation between pressure half time (T1/2) and orifice area (r = 0.56, y = 0.67 + 69/T1/2; p less than 0.0001). These results are consistent with the suggestion that pressure half time is more closely related to the shape of the left ventricular filling curve than to orifice area in normally functioning bioprostheses.

Bioprosthesis↗
PubMed1989

Cerebral venous malformations.

Cerebral venous malformations (CVM) are increasingly being recognised with the widespread use of CT scanning. Five cases are presented which demonstrate typical angiographic features and CT findings. These lesions when located in the cerebral hemispheres are benign and have been distinguished from the better known arteriovenous malformations on the basis of their characteristic angiographic features. CT findings have been considered nonspecific but our early post contrast CT scans demonstrate characteristic features suggesting that in many cases the diagnosis of cerebral venous malformations may be made on the CT scan alone.

Adolescent↗
PubMed1989

Genetic segregation analysis of familial mitral valve prolapse shows no linkage to fibrillar collagen genes.

Three pedigrees were identified in which mitral valve prolapse seemed to be inherited as a mendelian autosomal dominant trait. The segregation of the genes encoding the major fibrillar collagens present in valve tissue, collagens I and III, was analysed by use of restriction enzyme site variants as genetic markers. In one pedigree there was discordance between the segregation of the disease and markers for all three collagen genes. In another, there was discordance between the disease and markers for both collagen I loci. This is evidence against the disease being generally the result of mutations of the genes encoding the major fibrillar collagens.

Collagen↗
PubMed1989

Colour flow Doppler mapping in the assessment of prosthetic valve regurgitation.

Two hundred Carpentier-Edwards, Björk-Shiley, and Starr-Edwards prostheses in 173 patients were examined. Sixteen (16%) in the aortic and 24 (25%) in the mitral position were associated with clinical signs of regurgitation. A phased array system (Hewlett-Packard A77020A) with a 2.5 MHz duplex and 1.9 MHz continuous wave transducer was used. Colour flow mapping showed trivial transvalvar regurgitation in 23 (53%) metal aortic prosthesis, and only nine (20%) metal mitral prostheses. This difference was probably attributable to shielding of the left atrium by the metal components. Colour mapping confirmed abnormal regurgitation in all aortic prostheses with early diastolic numbers, but regurgitation was also shown in 25 (29%) with no diastolic murmur. Abnormal mitral regurgitation was found in 13 (54%) patients with a pansystolic murmur, but also in six (8%) with no systolic murmur. Two patients, thought on clinical grounds to have mild mitral regurgitation, had unexpectedly large jets on colour flow mapping. About one in three prostheses had paraprosthetic leaks, 65 (79%) of which were small with a jet area less than 20% of the area of the receiving chamber. The development of new paraprosthetic leaks led to the diagnosis of bacterial endocarditis in two patients. In eight patients regurgitation was first diagnosed with continuous wave Doppler, but was afterwards shown with colour mapping and in a further 10 regurgitation could only be shown by continuous wave Doppler. Colour flow mapping was less sensitive than continuous wave Doppler in detecting regurgitation,but seemed able to distinguish normal transvalvar from paraprosthetic regurgitation. Further studies in the natural course of paraprosthetic leaks and a comparison of the transoesophageal and transthoracic approaches in the assessment of mitral prostheses are needed.

Aortic Valve Insufficiency↗
PubMed1989

Epanolol. A new once-daily antianginal agent: dose finding and long term efficacy.

Epanolol is a new once-daily agent for the treatment of angina pectoris. This study was conducted in 2 parts. Firstly, a dose-finding study was performed using placebo and epanolol 100, 200, 300 and 400mg to assess the efficacy and safety of the drug. Once-daily epanolol 200mg was an effective dose, significantly reducing angina attack rate and increasing exercise duration and work output. At the same time, an improvement was noted in the patients' well-being and their ability to undertake normal daily activities. The 200mg dose regimen was used in a long term (12 months) assessment of the efficacy and safety of epanolol in the second part of this study. The efficacy of epanolol was clearly maintained throughout the full treatment period without adverse events or withdrawals as a result of treatment. The effectiveness and safety of epanolol are attributed to its selective beta 1-partial agonist activity. At rest, the degree of agonist activity (about 20% of that of isoprenaline) may prevent some of the untoward effects occasionally seen with full beta-blockers. During exercise, the antagonist activity becomes apparent and cardiac ischaemia is reduced.

Adrenergic beta-Antagonists↗
PubMed1989

Effect of partial agonist activity on the side effects of beta-blockade in patients with chronic stable angina.

Some side effects of the beta 1-adrenoceptor blocker atenolol may result from depression of cardiac output at rest. They may, therefore, be reduced by the use of drugs with beta 1-partial agonist activity, such as epanolol. We compared once-daily atenolol 100mg and epanolol 200mg in 20 patients reporting side effects while taking atenolol for chronic stable angina. A double-dummy, double-blind, crossover design was used to assess side effects by use of visual analogue scales and interviews, and antianginal efficacy by treadmill exercise tests and diary cards. In a comparison with atenolol, no significant differences in exercise time (686 +/- 11 seconds vs 685 +/- 10 seconds, maximum ST depression (1.02 +/- 0.09mm vs 1.07 +/- 0.08mm), time to 1mm ST depression (8.4 +/- 1.9 minutes vs 9.0 +/- 2.0 minutes), or days without angina (median 100% in both) were shown. All visual analogue scores were higher with epanolol (subjective energy 58.3 +/- 1.7 vs 54.3 +/- 1.5, well-being 61.8 +/- 1.8 vs 58.6 +/- 1.5 and warmth of extremities 68.4 +/- 3.6 vs 62.0 +/- 3.1). Although these differences did not attain statistical significance, 11 patients expressed a preference for epanolol and only 6 for atenolol. We conclude that, in this study, epanolol is as effective as atenolol as an antianginal agent for chronic stable angina. It improved the side effect profile in some but not all patients.

Adrenergic beta-Agonists↗