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Biomedical subjects

A Massey

Publications and source records attributed to A Massey.

17 recordsLinked to original sources

Terodiline: a dose titrated, multicenter study of the treatment of idiopathic detrusor instability in women.

Idiopathic detrusor instability is a common cause of lower urinary tract symptoms at all ages and in both sexes. Treatment initially is conservative and often includes drug therapy. Terodiline has the theoretical advantage of being a drug with anticholinergic and calcium channel blocking effects. Theoretically, by using a drug with dual action the beneficial effect of reduced detrusor overactivity might occur at a dosage below that likely to lead to the troublesome side effects experienced by patients who take pure anticholinergic agents. A total of 70 female patients completed a study characterized by extremely strict inclusion criteria and a tight protocol. Other novel elements to the study were the extensive use of urinary diaries for symptom evaluation, standardized urodynamic studies agreed upon by the participating centers and the dose titration design of the trial. Terodiline has been demonstrated to be a safe, well tolerated and effective drug in the treatment of idiopathic detrusor instability. Drug treatment led to significant decreases in urinary frequency and incontinence episodes. Pre-micturition symptoms, such as urgency, were markedly reduced and the voided volume was significantly increased. Although there were consistent trends towards greater improvement in the urodynamic measurements, when the terodiline and placebo groups were compared these did not reach statistical significance, partly due to a large improvement in the placebo group. Nevertheless, terodiline has been shown to be a useful drug for conservative management of patients with detrusor instability.

Adult

Acoustic nerve conduction abnormalities in Guillain-Barré syndrome.

We recorded brainstem auditory evoked potentials (BAEPs) in two patients with Guillain-Barré syndrome (GBS). One patient was acutely deaf with total absence of BAEP waveforms indicative of acoustic nerve conduction block. Hearing improved during early convalescence, and there were prolonged wave I latencies. Normal BAEPs were recorded on recovery. A second patient had bilaterally prolonged wave I latencies. These BAEP findings suggest that acoustic nerve conduction abnormalities from demyelination may occur in GBS.

Adult

Relationship between gastric emptying and serum concentrations of emepronium in dogs and human volunteers.

Clinical trials with increased dosages, relative to the standard regimen, of the anticholinergic drug emepronium (Cetiprin Novum) resulted in a clear improvement in micturition- and urodynamic parameters in urinary incontinent patients. In the present study possible effects on the gastric emptying were tested in dogs and in human volunteers. In dogs a wide dose range of emepronium (5-100 mg/kg p.o.) was used to establish a relationship between serum concentration and effect on the gastric emptying. Gastric emptying was slightly decreased after 25 mg/kg (peak conc. of emepronium about 100 micrograms/l) and markedly decreased after 50 mg/kg (500 micrograms/l) and 100 mg/kg (5000 micrograms/l). In the volunteers no effect of emepronium on gastric emptying was observed, either after 200 mg q.i.d. or after 400 mg q.i.d. (about 3 and 6 mg/kg q.i.d.), which resulted in peak serum concentrations of 100-300 micrograms/l).

Adult

Urodynamics of the female lower urinary tract.

The symptoms associated with voiding disorders and incontinence in female patients are notoriously misleading. Even experienced urodynamicists are unable to achieve a 50 per cent success rate for predictive diagnosis based on symptoms and physical examination in any group except pure stress incontinence. Urodynamic studies are an essential part of the investigative sequence required to make an accurate diagnosis. If this is not made, then treatment will be empirical and the success of therapy correspondingly disappointing. The advent of urodynamic investigations has allowed a more rational approach to treatment with documented improvement in the success of therapy. However, our precise understanding of the pathophysiology of incontinence and voiding disorders remains incomplete. Nevertheless, a systematic scheme of investigation using standardized record-keeping and urodynamic techniques allows an accurate diagnosis in most patients. It is essential that additional testing should be performed when the urodynamic investigations fail to explain the patient's complaints. It is hoped that advanced techniques and in particular the electrophysiologic approach may provide the explanation for phenomena as yet ill-understood, such as bladder instability. This article has outlined the importance of a thorough basic assessment of each female patient with a symptomatic inquiry guided by urodynamic insight and a careful physical examination. The basic techniques of flow studies, cystometry, both filling and voiding, and urethral profilometry were described, and the more complex and difficult electrophysiologic tests were outlined.

Adult

Urodynamics of the lower urinary tract.

The symptoms associated with voiding disorders and incontinence in female patients are notoriously misleading. Even experienced urodynamicists are unable to achieve a 50% success rate for predictive diagnosis based on symptoms and physical examination in any group expect pure stress incontinence. Urodynamic studies are an essential part of the investigative sequence required to make an accurate diagnosis. If this is not made, treatment will be empirical and the success of therapy correspondingly disappointing. The advent of urodynamic investigations has allowed a more rational approach to treatment, with documented improvement in the success of therapy. However, our precise understanding of the pathophysiology of incontinence and voiding disorders remains incomplete. Nevertheless, a systematic scheme of investigation, using standardized record-keeping and urodynamic techniques, allows an accurate diagnosis in most patients. It is essential that additional testing should be performed when the urodynamic investigations fail to explain the patient's complaints. It is hoped that advanced techniques, and, in particular, the electrophysiological approach, may provide the explanation for phenomena as yet ill understood, such as bladder instability. The chapter outlines the importance of a thorough basic assessment of each female patient with a symptomatic enquiry guided by urodynamic insight and a careful physical examination. The basic techniques of flow studies, cystometry, both filling and voiding, and urethral profilometry are described. The more complex and difficult electrophysiological tests are outlined.

Electromyography

Acute urinary retention--a urodynamic assessment.

Thirty male patients with acute urinary retention were studied by standard urodynamic techniques on admission to hospital. Ten individuals also underwent cystography and sequential urodynamic testing over 96 h. Twenty-three per cent of patients did not require subsequent prostatectomy. Inability to initiate a voiding contraction during cystometry at the time of admission was associated with a prolonged duration of retention and a greater retained volume. The internal urethral meatus is closed in retention, and release of the retention results in an increase in profile length and maximum urethral closure pressure and a decrease in maximum urethral pressure. Free catheter drainage was associated with a reduction in bladder capacity and the appearance of detrusor instability.

Acute Disease

The structure and binding characteristics of serum amyloid protein (9.5S alpha 1-glycoprotein).

No difference have been observed in the properties of amyloid P-component (AP) and its serum counterpart (SAP) which might account for the deposition of the former in amyloidosis. Purified by nonselective techniques, preparations of AP and SAP were shown to have similar molecular weights and peptide composition, identical morphology in the electron microscope (EM) and to be antigenically indistinguishable. Both proteins were soluble in EDTA but readily precipitated in the presence of calcium ions, forming characteristic two-dimensional arrays in the EM. In serum however, SAP was not aggregated and sedimented at 9.5S in Ca2+ as did the purified protein in EDTA. Precipitation of purified SAP by calcium could be prevented by pretreatment with acid hydrolysates of agarose or SP Sephadex, matrices for which SAP has a calcium-dependent affinity. It is proposed that SAP circulates in combination with a low molecular weight natural ligand which prevents its aggregation. While the identity of natural ligand for SAP is as yet unknown, it is likely to resemble the glycosidic subunits in agarose.

Agglutination Tests

Puberty delay by a urinary cue from female house mice in feral populations.

Urine produced by wild female house mice, living in high- and low-density populations and confined to areas within a highway cloverleaf, was tested for its ability to delay puberty in juvenile female mice. Only urine collected from females in the dense population at its maximum density delayed puberty in test females. Urine collected when the population was less dense, or from a population that remained sparse, failed to delay puberty. These results suggest that a urinary factor present at high densities may delay puberty and thus help to slow further population growth.

Animals

Assessment of complement binding by anti-D and anti-M antibodies employing labelled antiglobulin antibodies.

The presence of small amounts of C3d on freshly obtained normal red blood cells (RBC) was demonstrated by a radio-labelled antiglobulin technique; this increased 1.5-fold after incubation in fresh normal serum. No significant further increase in bound C3d was demonstrated for cDE/cDE, CDe/CDe, -D-/-D- RBC maximally sensitized with any of three potent anti-D antibodies. When anti-c, anti-D and anti-E antibodies were used in combination to sensitize cDE/cDE RBC, bound C3d increased by approximately 22%; however, a similar increase occurred with cde/cde RBC and was therefore considered non-Rh specific. Umbilical cord RBC from four infants severely affected by anti-D haemolytic disease of the newborn did not exhibit more bound C3d than cord RBC from normal controls. One serum containing IgM anti-M bound a small amount of complement in vitro; two IgG anti-M sera did not.

Antibodies, Anti-Idiotypic

Quantitation of C3 subcomponents on red cells coated with complement in vitro.

In order further to characterise and evaluate the reproducibility of human red cells coated with complement in vitro, the number of molecules of C3 subcomponents/red cell were determined by Scatchard analysis of equilibrium concentrations of bound and free antibody using (125)I-labelled goat anti-rabbit IgG. A 1:1 combining ratio was assumed. Red cells coated via the classical pathway had twice as much bound C3b and C3d as alternative pathway-coated cells. Assays using different anti-C3d sera gave different amounts of bound antigen, but results with any one antiserum versus one cell type were reproducible. Anti-C3d sera raised to C3d-tryp and to C3d-KAF detected significantly different amounts of bound C3d on the same cells. Both trypsinisation and serum KAF treatment of classical pathway-coated cells resulted in marked reduction of C3b molecules/cell (over 90% in both cases). Similar reduction in bound C3b was seen after trypsinisation of alternative pathway-coated cells, but serum KAF treatment of such cells had no significant effect. K(0) values were lower with anti-C3c than with anti-C3d. Anti-C3d K(0) values with the various cells coated with complement in vitro were not statistically different (approximately 10(7) litres/mol), with the exception of trypsinised alternative pathway-coated cells (approximately 10(8) litres/mol, the same order of magnitude observed with cells coated with C3d in vivo). A non-linear relationship between antiglobulin titre and antigen strength was observed. The minimal number of C3d molecules/red cell detectable by agglutination with the various anti-C3d sera ranged from 200 to 670 molecules. The minimal number of C3b molecules detectable by agglutination was approximately 9000 molecules/cell.

Animals

Complement components detected on normal red blood cells taken into EDTA and CPD.

Normal red blood cells (RBC) from fresh EDTA and CPD blood and from stored CPD blood were examined for the presence of bound subcomponents of C3 and C4. By serologic agglutination tests, only C3d was detectable on the cells. Incubation in compatible fresh normal serum (FNS) at 37 degrees C appeared to increase the amount of 3Cd on the RBC. C3b was serologically detectable only on stored CPD cells and only after incubation in compatible FNS. No. C4 components were detected on the cell surfaces in agglutination tests. Using an indirect labeling technique, small, but significant, amounts of C3d and C4d were found on all three types of untreated cells. C3b was present on stored CPD cells only. The indirect labeling technique showed a significant increase in C3d and C4d on all cells following incubation i- compatible FNS, whereas bound C3b was significantly increased only with stored CPD cells. There was no increase in bound C4b following serum incubation. The average number of C3d molecules per cell on normal EDTA cells was 557 and average Ko was 3.6 x 10(7) l/mol.

Animals

Activation of the alternative pathway by gluten. A possible aetiological factor in dermatitis herpetiformis.

Gluten fractions are shown to activate the alternative pathway of complement when added to normal human serum. Breakdown of C3 and Factor B occur in a manner analogous to that when activated by zymosan, in the presence of MgEGTA and in serum devoid of classical pathway activity. The suggestion is made that bypass activation may be the primary event when gluten enters the serum across a damaged gut mucosa. Immune complexes containing non-complement fixing IgA antigluten antibody are carried to the skin where it is proposed that complexed gluten activates C3 and initiates an inflammatory reaction.

Antigen-Antibody Complex

Differences in specificities of anti-C3d sera raised to C3d antigens prepared in different ways.

Anti-C3d sera were raised to different C3d antigens or to the same C3d antigen by different methods. Although identical by immunoprecipitation studies, the various anti-C3d sera showed differences in specificities against bound C3d antigen. Such differences were observed wih red blood cells coated with C3d in vivo and in vitro. Antisera made to the C3d-KAF antigen detected fewer molecules/cell on C3d-tryp cells than did antisera made to the C3d-tryp antigen. The converse was true for C3d-KAF cells. "Saturation" experiments indicated that different anti-C3d detected different "subpopulations" of bound C3d. C3d bound to red blood cells in vivo was, in at least one case, detectable by some anti-C3d sera but not by others. Such differences in anti-C3d specificity may be important in determining the optimal characteristics of anti-C3d antiglobulin serum for routine laboratory use.

Animals