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Biomedical subjects

S Senior

Publications and source records attributed to S Senior.

15 recordsLinked to original sources
PubMed1999

Gastric emptying and intestinal transit of pancreatic enzyme supplements in cystic fibrosis.

OBJECTIVE: To investigate gastric emptying and intestinal transit of pelleted pancreatin in relation to food boluses. METHODS: Dual isotope scintigraphy combined with breath hydrogen sampling was used to track the concurrent gastric emptying and intestinal transit of 111indium labelled microspheres and a 99mtechnetium labelled tin colloid test meal. Twelve pancreatic insufficient cystic fibrosis patients aged 5 to 38 years performed the study. RESULTS: 50% gastric emptying times showed patient to patient variation. The mean discrepancy in 50% gastric emptying times between the two labels was > 67 minutes. Mean small bowel transit time for the food bolus was prolonged at 3.6 minutes. A significant correlation was seen between weight standard deviation score and 50% emptying time for pancreatin (r = +0.73). CONCLUSION: Gastric mixing of food and pancreatin may be limited by rapid emptying of microspheres. Patients with high dosage requirements could benefit from changing the pattern of their pancreatin supplementation.

Adolescent↗
PubMed1998

The use of dual-isotope imaging to compare the gastrointestinal transit of food and pancreatic enzyme pellets in cystic fibrosis patients.

Cystic fibrosis patients require pancreatic enzyme supplements to aid food digestion. It is suspected that incorrect delivery of this enzyme may result in both significant malabsorption and the development of strictures in the proximal colon caused by the high-dose supplement reaching this region before the food. Investigations into the drug's delivery were performed using dual-isotope imaging; a method was developed to directly label the enteric-coated enzyme pellets with 111In, re-applying the enteric coating afterwards, and this was then ingested with a pancake meal labelled with 99Tcm-tin colloid. Consecutive image data, acquired over a period of > or = 4 h using a dual-headed gamma camera, were analysed to assess intestinal transit. In-vitro stability checks on these labelling techniques were encouraging, showing < 2% 99Tcm and < 7% 111In elution over 90 min in hydrochloric acid. In 5 of the 12 patients studied to date, the pellets were seen to pass through significantly faster than the food, with a mean difference in 50% gastric emptying time of greater than 93 min. The mean absolute difference in emptying time for all 12 patients was > 67 min. Thus, a technique has been developed to effectively radiolabel pancreatic enzyme pellets, and analysis of dual-isotope images using this preparation, together with radiolabelled solid food, has demonstrated significant differences in the transit of these two substances through the gastrointestinal tract of some cystic fibrosis patients.

Adolescent↗
PubMed1996

Time resolution of binding and membrane insertion of a mitochondrial signal peptide: correlation with structural changes and evidence for cooperativity.

Utilizing a recently developed novel fluorescence technique [Wall et al. (1995) Mol. Membr. Biol. 12, 183-192], it is shown that the interactions of p25, the leader peptide of subunit IV of cytochrome c oxidase, with phospholipid membranes can be identified in real time. p25 is observed to bind following stopped-flow mixing of the peptide with phospholipid membranes with rate constants up to about 700 s-1 and then insert into the membrane with rate constants on the order of 0.4 s-1. Comparison of these processes with similarly time-resolved experiments performed with a stopped-flow CD spectrometer revealed that p25 does not become alpha-helical upon binding to the membrane. Following membrane insertion, however, p25 was observed to adopt an alpha-helical configuration. The temperature dependency of these processes was then found to yield activation energies for the respective components of the p25-membrane interaction.

Cell Membrane↗
PubMed1995

Continuous quality improvement in a day ward.

The increasing usage of short-stay facilities within Australia has focused attention upon the efficiency of surgical day wards. Although the Australian Council on Healthcare Standards (ACHS) is actively promoting the development of clinical indicators for same-day facilities, there is a concern that these measurements relate to efficiency rather than to humanitarian aspects of the quality of service. We have established a programme of continuous quality improvement (CQI) in a surgical day ward with the nursing and clerical staff being empowered as core members of the team. Reviews and audits have identified a number of targets for our activity. Some issues have been resolved very easily (ward clerks telephoning patients to confirm admissions the next day) but the solution to some other problems has required lengthy negotiations between various groups (the construction of clearly written pre-admission guidelines for patients). Activities aimed at improving the service provided to patients attending surgical day wards must extend beyond the mere collection of information about clinical indicators.

Ambulatory Surgical Procedures↗
PubMed1993

Quantification of disease activity in Crohn's disease by computer analysis of Tc-99m hexamethyl propylene amine oxime (HMPAO) labelled leucocyte images.

The reliability and clinical applications of computerised image analysis measurement of bowel uptake of Tc-99m HMPAO labelled leucocytes has been examined as a measure of disease activity in Crohn's disease. In 54 studies carried out on 33 patients with established Crohn's disease, the mean 'scan score', a quantitative assessment of image intensity, was 82.1 SEM (13.6), in patients with clinically active disease compared to 24.7 (7.0) in those with quiescent disease, p < or = 0.0005. A significant correlation was found between the scan score and Crohn's Disease Activity Index (rs = 0.52, p < 0.0001), and Harvey and Bradshaw Simple Index (rs = 0.4, p < 0.004). A low scan score correctly identified seven patients whose raised Crohn's Disease Activity Index incorrectly indicated active disease because symptoms used in calculation of the index were not caused by active inflammation. Of the laboratory measurements, the scan score correlated with the haemoglobin (rs = 0.66, p < 0.0001), albumin level (rs = -0.6, p < 0.0001), C-reactive protein (rs = 0.7, p < 0.0001), alpha-acid glycoprotein (rs = 0.57, p < 0.001), and platelet count (rs = 0.47, p < or = 0.006), but not with the erythrocyte sedimentation rate (rs = 0.2, p < or = 0.25). The scan score was raised in all patients who had clinically active disease but normal laboratory tests. The results of this study indicate that the scan score provides an objective indicator of disease activity in Crohn's disease which may be superior to clinical indices, and also to laboratory tests which although objective are often normal in the presence of active disease.

Acute Disease↗
PubMed1992

99Tcm HMPAO-labelled leucocyte imaging in Crohn's disease: a subtraction technique for the quantification of disease activity.

A new technique for the quantitative analysis of labelled leucocyte images from patients with inflammatory bowel disease is described. The method involves the computer generation of a 'background' image which, after appropriate registration, is subtracted from the patient's image to leave a residue which represents abnormal uptake in the bowel. Quantification of the residual activity yields a scan score which can be related to the level of disease activity in patients with Crohn's disease. In 54 investigations on 33 patients the scan scores correctly agreed with a clinical assessment of disease activity in 16 of 20 cases with inactive disease and 32 out of 34 cases with active disease. Most of the discrepancies reflected inaccuracies in the clinical assessment of activity rather than shortcomings of the imaging technique.

Crohn Disease↗
PubMed1988

The electrophysiologic properties of esmolol, a short acting beta-blocker.

Although beta-blockers have established efficacy in treating ventricular ectopy and PSVT, their applicability for acute antiarrhythmic interventions in patients with organic heart disease or COPD, is frequently limited by negative inotropic or bronchospastic side effects. The development of an ultrashort acting beta-blocker with rapid reversibility of its side effects would widen their applicability. Therefore, we tested the electrophysiologic properties of such a new short acting beta-blocker, esmolol, in 14 patients (10 with organic heart disease) with a mean EF of 47.6 +/- 17%, undergoing standard clinical electrophysiologic studies for various indications. Like most other beta-blockers, esmolol's major direct effects were on sinus node function and AV nodal conduction characteristics; significantly prolonging sinus cycle length, cycle length to Wenckebach and AH interval in sinus rhythm and at a paced cycle length of 600 ms. In contrast to most other beta-blockers, following termination of its infusion, esmolol shortened parameters of sinus node function and AV nodal refractoriness, with respect to the control values, suggesting a possible rebound phenomena. These effects occurred within 5 min of terminating the intravenous drug infusion. Esmolol had no significant effect on systolic blood pressure, electrocardiographic intervals and had rare adverse reactions. We conclude that esmolol is an ultra-short acting beta-blocker, with typical direct electrophysiologic effects on sinus node and AV nodal function, and a possible rebound phenomena following its discontinuation that may make it particularly suited to acute antiarrhythmic interventions in patients susceptible to adverse beta-blocker side effects.

Adrenergic beta-Antagonists↗
PubMed1988

Flecainide acetate: critical care administration guidelines.

Flecainide may play an important role in the treatment of ventricular arrhythmias because of its convenient dosing regimen and high rate of efficacy in controlling ventricular ectopic activity. In stable patients with normal or mildly reduced left ventricular function, flecainide has proved to be promising. In those patients with severe left ventricular dysfunction, lethal arrhythmias, and preexisting conduction system disease, caution must be exercised.

Arrhythmias, Cardiac↗
PubMed1987

Influence of left ventricular dysfunction on flecainide therapy.

Seventy-six patients with ventricular tachyarrhythmias (40 sustained and 36 nonsustained) were treated with oral flecainide. Radionuclide left ventricular ejection fraction was 30% or less in 33 patients and greater than 30% in 43 patients. Before flecainide, compensated heart failure was present in 23 patients (ejection fraction less than or equal to 30% in 15 and greater than 30% in 8). Flecainide mean dose was 150 mg twice daily and mean plasma concentration was 720 ng/ml. New or worsened congestive heart failure occurred in seven patients on flecainide therapy, all with an ejection fraction of less than 30%; six had a previous history of compensated heart failure and of these, three died. Ejection fraction was the only independent variable that significantly influenced efficacy and tolerance of flecainide. After 1 year of therapy, efficacy and tolerance was 58% (25 of 43) in patients with an ejection fraction greater than 30% and 12% (4 of 33) in patients with an ejection fraction of 30% or less (p less than 0.001). Thus, congestive heart failure can occur during flecainide therapy, particularly in patients with a previous history of congestive heart failure and ejection fraction of less than 30%, and may particularly limit therapy in these patients. Clinical efficacy and tolerance were significantly lower in patients with an ejection fraction of less than 30%.

Adult↗
PubMed1986

Flecainide: steady state electrophysiologic effects in patients with remote myocardial infarction and inducible sustained ventricular arrhythmia.

The effect of flecainide in 24 patients with inducible sustained ventricular arrhythmia and a history of remote myocardial infarction was determined. Flecainide was administered in oral doses individually adjusted to suppress all spontaneous ventricular tachycardia and 80% of ventricular premature complexes on 24 hour ambulatory (Holter) electrocardiography. Antiarrhythmic therapy, as assessed by Holter monitoring, was adequate in 20 (83%) of the study patients at a mean dose of 144 +/- 28 mg every 12 hours; the mean plasma flecainide level was 583 +/- 329 ng/ml. In 18 patients, the mean sinus cycle length, sinus node recovery time and atrial, atrioventricular nodal and ventricular refractory periods were unchanged. The AH interval increased by 15 +/- 15%, the HV interval by 35 +/- 32% and the QRS duration by 24 +/- 21%. Toxicity or failure to suppress ventricular premature complexes and ventricular tachycardia by Holter monitoring precluded electrophysiologic study with flecainide in four patients; two patients refused electrophysiologic study with flecainide for nonmedical reasons. Ventricular tachycardia was not inducible in 4 (22%) of 18 patients receiving flecainide. Sustained arrhythmia remained inducible in 14 patients (78%) despite evidence of antiarrhythmic efficacy on Holter monitoring, but the rate of the induced ventricular tachycardia was slower and symptoms were alleviated during ventricular tachycardia in 10 (56%) of 18 patients. The 4 patients who had no inducible ventricular tachycardia with flecainide, and the 10 patients who had inducible ventricular tachycardia with a longer cycle length and alleviation of their symptoms, have been followed up as outpatients for 16 +/- 7 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Electrophysiology of esmolol.

The electrophysiologic characteristics of esmolol were studied in 14 patients. Ten men and 4 women, mean age 57 years, were electrophysiologically evaluated at baseline, and also at 4 to 8 minutes after the administration of a maintenance infusion of esmolol. Plasma samples for esmolol blood levels were drawn at 10 minutes of the maintenance infusion, at the end of the maintenance infusion and 30 minutes after the maintenance infusion was discontinued. Results of this study showed that esmolol has typical beta-blocker electrophysiologic effects. Its major action was on sinus node function; it prolonged this basic sinus cycle length but had no significant effect on intrinsic automaticity as reflected by the corrected sinus node recovery time and sinoatrial conduction. Direct effects on atrioventricular (AV) nodal function were reflected by effects on AV nodal conduction and refractoriness. There was no direct effect on atrial function and, as expected, no effect on His-Purkinje or ventricular function. The intensity of esmolol's electrophysiologic effects on sinus node function, AV nodal conduction and AH interval is comparable to those of other beta blockers.

Adrenergic beta-Antagonists↗
PubMed1982

Immunogenic and antigenic epitopes of immunoglobulins I. Cross-reactivity of murine monoclonal antibodies to human IgG with the immunoglobulins of certain animal species.

Antibody-producing hybridoma clones have been isolated following immunization of mice with human IgG. Twenty-five monoclonal antibodies (nine anti-C gamma 3, fourteen anti-C gamma 2, one anit-kappa and one anti-lambda) were selected for study of their cross-reactivity with the IgG of fifteen mammalian species and chicken immunoglobulin. Each antibody exhibited a unique reaction profile suggesting that human IgG expresses a very large repertoire of immunogenic epitopes. Whilst some antibodies showed a very restricted cross-reactivity profile for others a very wide reactivity profile was observed-including two clones producing autoantibodies. Antibodies demonstrating cross-reactivity between human Fc gamma and 7S chicken immunoglobulin allow its definitive assignment as a homologue of human IgG. Four clones demonstrated specificity for bovine IgG subclass gamma 1 and gamma 2 and the degree of reactivity allows their application to qualitative and quantitative assay systems. These studies suggest new perspectives for the characterization of immunoglobulins and the standardization of anti-immunoglobulin reagents.

Animals↗
PubMedDate not supplied

Membrane interactions of the putative fusion peptide (MF alpha P) from fertilin-alpha, the mouse sperm protein complex involved in fertilization.

Mammalian fertilization depends upon successful binding and fusion between the membranes of the spermatozoon and the oocyte. These processes are thought to be mediated by a series of protein-protein interactions in which sperm antigens known as fertilins are thought to play a key role. Using a recently developed fluorescence technique, the interactions of the oligopeptide sequence corresponding to the fusogenic domain of mouse fertilin-alpha (MF alpha P) and phospholipid vesicles have been investigated. Following stopped-flow mixing, MF alpha P bound rapidly to phospholipid membranes in a co-operative manner with a Hill coefficient of 2.4 and binding rate constants in excess of 1000 s-1. The co-operative nature of the binding process is suggested to represent evidence of a structural mechanism to prevent egg fertilization by immature spermatozoa. The subsequent membrane insertion was found to take place over a longer time period (with rate constants of up to 6.3 s-1), and was linear with respect to peptide concentration. Comparison of these processes with similar time-resolved circular dichroism measurements revealed that changes in peptide secondary structure were very rapid. Fourier transform infrared spectroscopy measurements confirmed changes in the secondary structure of MF alpha P during interaction with PC phospholipid membranes, indicating that the peptide is mainly present in a beta-structure with a small proportion of alpha-helix. These results are consistent with the hypothesis that fertilin-alpha is the fusogenic species with an important role in fertilization.

ADAM Proteins↗