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Biomedical subjects

D J Griffiths

Publications and source records attributed to D J Griffiths.

At least 55 records · Page 3Linked to original sources

Cerebral aetiology of urinary urge incontinence in elderly people.

We have examined 73 elderly incontinent patients (mean age 79 years) and 27 continent subjects (mean age 78 years) of similar cognitive status. Among the incontinent patients, 20 were shown objectively to have urge incontinence with normal bladder filling sensation, 14 had objectively demonstrated urge incontinence with reduced bladder sensation, and 39 had other types of incontinence. We compared cognitive function (by Mini-mental State Examination: MMSE) and regional brain perfusion (by SPECT scanning) in these four groups. Patients with objectively demonstrated urge incontinence and reduced bladder sensation stood out as being different from the rest: their mean MMSE score was significantly lower than that of any of the other three groups; perfusion of the frontal cortex was significantly poorer than that in the continent and other incontinent groups; global cortical perfusion was significantly poorer than in the other incontinence groups. This was not found in patients with urge incontinence and normal bladder sensation. The observations support the hypothesis that in elderly people urge incontinence with reduced bladder sensation can be a consequence of cortical neuropathy, especially in the frontal lobes.

Aged↗

Transrectal ultrasound versus magnetic resonance imaging in the estimation of prostatic volume.

OBJECTIVE: To establish which method of determining prostatic volume (transrectal ultrasound [TRUS] or magnetic resonance imaging [MRI]) and which calculation formula give the most exact and least variable results; to determine the size and the source of the variability: and to establish which method is the more sensitive to drug-induced changes in prostate volume. PATIENTS AND METHODS: Prostatic size was estimated by TRUS and MRI in 21 patients treated medically (either active treatment or placebo) for benign prostatic hyperplasia. Each patient was examined at baseline, and after 3 months and 6 months of treatment. Prostatic volume was calculated at every visit using different formulae proposed in the literature. RESULTS: With some of these formulae, including the classical ellipsoid formula, there was a strong correlation (r > 0.8) between TRUS and MRI volume estimates. For others the correlation was much weaker, suggesting unreliability. MRI gave a significantly larger volume than TRUS because of larger values for the cephalocaudal and anteroposterior diameters. For patients on placebo the visit-to-visit variability of the prostate volume was 10-12% of the mean volume, whether calculated by TRUS or MRI. Part of this variability was apparently due to natural variation of prostate size. CONCLUSION: The classical ellipsoid formula is adequate for determining prostate volume. MRI and TRUS give different volumes. Visit-to-visit variability is similar for both methods and is partly due to real, natural variation. MRI is better able than TRUS to detect drug-induced changes in prostate volume.

Double-Blind Method↗

The rad16 gene of Schizosaccharomyces pombe: a homolog of the RAD1 gene of Saccharomyces cerevisiae.

The rad10, rad16, rad20, and swi9 mutants of the fission yeast Schizosaccharomyces pombe, isolated by their radiation sensitivity or abnormal mating-type switching, have been shown previously to be allelic. We have cloned DNA correcting the UV sensitivity or mating-type switching phenotype of these mutants and shown that the correcting DNA is encompassed in a single open reading frame. The gene, which we will refer to as rad16, is approximately 3 kb in length, contains seven introns, and encodes a protein of 892 amino acids. It is not essential for viability of S. pombe. The predicted protein is the homolog of the Saccharomyces cerevisiae RAD1 protein, which is involved in an early step in excision-repair of UV damage from DNA. The approximately 30% sequence identity between the predicted proteins from the two yeasts is distributed throughout the protein. Two-hybrid experiments indicate a strong protein-protein interaction between the products of the rad16 and swi10 genes of S. pombe, which mirrors that reported for RAD1 and RAD10 in S. cerevisiae. We have identified the mutations in the four alleles of rad16. They mapped to the N-terminal (rad10), central (rad20), and C-terminal (rad16 and swi9) regions. The rad10 and rad20 mutations are in the splice donor sequences of introns 2 and 4, respectively. The plasmid correcting the UV sensitivity of the rad20 mutation was missing the sequence corresponding to the 335 N-terminal amino acids of the predicted protein. Neither smaller nor larger truncations were, however, able to correct its UV sensitivity.

Amino Acid Sequence↗

Urinary incontinence in the elderly: the brain factor.

Recent research has shown that urge incontinence is common in the elderly and is often combined with reduced bladder sensation. It is associated with cognitive impairment and with underperfusion of the frontal lobes of the cortex. To test for an expected preferential association with particular aspects of cognitive function, 47 incontinent patients (25 men and 22 women, median age 78 y) underwent cognitive testing, 24-hour monitoring of bladder function and videourodynamics. Median CAMCOG score was 72/107. Median urine loss in 24 h was 36 g (range 11-1347 g). 17 patients had urodynamic proof of urge incontinence, 8 with normal and 9 with reduced bladder sensation. Impaired orientation in time was more strongly associated with proven urge incontinence than overall cognitive impairment; it was the only significant predictor (P < 0.00005). Praxis, calculation ability, abstract thinking or recent memory were less closely involved. Thus dysfunction of the frontal cortical lobes and impairment of temporal orientation appear to constitute a "brain factor" underlying geriatric urge incontinence, particularly in combination with reduced bladder sensation.

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Relationship of fluid intake to voluntary micturition and urinary incontinence in geriatric patients.

The aim of this study was to investigate, in a group of geriatric inpatients with established incontinence, the relationships among urine loss, voided volumes, frequency of voiding, and fluid intake. The investigated included 128 patients: 76 women and 52 men, with a median age of 79 years. One-half had significant cognitive impairment. Patients underwent 24-hr monitoring of fluid intake, urine loss, and voiding, as well as conventional videourodynamic testing. Diurnal and nocturnal voiding frequencies were significantly but relatively weakly related to fluid intake. Diurnal and nocturnal voided volumes were more closely related, however, to the fluid intake. There was a strong and easily interpretable relationship among nocturnal voided volume, nocturia, cystometric bladder capacity, and evening fluid intake. Sixty of 128 patients had urodynamically proven urge incontinence, and this group was studied separately. They were more cognitively impaired and had significantly greater urine loss and smaller fluid intake than was true of the other incontinent patients. Urine loss was significantly related to fluid intake in this group. Nocturnal urine loss increased by an average of 28 ml/dl of evening fluid intake and decreased by 17 ml/dl voided at night. These results suggest that nocturnal toileting and evening fluid restriction may reduce nocturnal urine loss by a small but useful amount in carefully selected older patients with severe urge incontinence.

Aged↗

Effect of transurethral resection of the prostate on detrusor instability and urge incontinence in elderly males.

Detrusor instability is common in men with evidence of outflow obstruction due to benign prostatic hypertrophy and typically reverses in about two thirds of patients after transurethral resection of the prostate (TURP). It is also common among the elderly without outflow obstruction and may lead to urge incontinence. To determine whether TURP has an effect on detrusor instability and urge incontinence in elderly men, or whether these abnormalities are due to other age-associated changes, 12 males (mean age 80 years) with urge incontinence or frequency and urgency of micturition, and symptomatic benign prostatic hypertrophy, were studied by 24-hour monitoring of incontinence and videourodynamic examination, before and after TURP; 7/12 patients were significantly cognitively impaired. Preoperatively, all patients showed detrusor instability, which reversed postoperatively in only one patient, a significantly smaller proportion than that consistently reported in younger patients. Preoperatively, 11/12 patients were incontinent. After TURP, 8/11 patients had an improvement in the amount of incontinence, by up to 458 g in 24 hours. Those who improved had been urodynamically more severely obstructed preoperatively. Those with the most improvement were also cognitively impaired. We conclude that, in the geriatric population, detrusor instability and urge incontinence may be the result of age-associated changes and not secondary to obstruction. Detrusor instability is likely to persist following TURP. Preoperative urodynamic assessment of obstruction in the incontinent male with benign prostatic hypertrophy may be useful since the severity of incontinence responds well to TURP if there is marked obstruction. Cognitive impairment should not be a deterrent to operation.

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Exploratory investigations of hypervelocity intact capture spectroscopy.

The ability to capture hypervelocity projectiles intact opens a new technique available for hypervelocity research. A determination of the reactions taking place between the projectile and the capture medium during the process of intact capture is extremely important to an understanding of the intact capture phenomenon, to improving the capture technique, and to developing a theory describing the phenomenon. The intact capture of hypervelocity projectiles by underdense media generates spectra, characteristic of the material species of projectile and capture medium involved. Initial exploratory results into real-time characterization of hypervelocity intact capture techniques by spectroscopy include ultra-violet and visible spectra obtained by use of reflecting gratings, transmitting gratings, and prisms, and recorded by photographic and electronic means. Spectrometry proved to be a valuable real-time diagnostic tool for hypervelocity intact capture events, offering understanding of the interactions of the projectile and the capture medium during the initial period and providing information not obtainable by other characterizations. Preliminary results and analyses of spectra produced by the intact capture of hypervelocity aluminum spheres in polyethylene (PE), polystyrene (PS), and polyurethane (PU) foams are presented. Included are tentative emission species identifications, as well as gray body temperatures produced in the intact capture process.

Aluminum↗

Polypharmacy and its effect on urinary incontinence in a geriatric population.

The relationship between medication and incontinence was studied retrospectively in 128 elderly patients enrolled in an incontinence study. Patients were taking up to 18 non-topical medications but most of these were unlikely to have a significant urological effect. Nevertheless, 62% of patients were receiving, for other medical problems, up to 4 drugs which could potentially affect the lower urinary tract. These were classified by their mode of action. The most common types of urologically active medication, apart from diuretics, were calcium channel blockers, used by 21% of patients, and tricyclic antidepressants, used by 12%. The urodynamic findings in patients on different types of medication were compared. Patients with urodynamically proven urge incontinence who were on calcium channel blockers had significantly less urine loss than those not on the drug. Tricyclic antidepressants have been used in the treatment of urge incontinence; in this study urine loss was less severe among those receiving tricyclics, although the differences were not significant. A few patients on beta-blockers apparently had more severe urge incontinence. Drugs prescribed to the elderly for non-urological medical problems can affect the lower urinary tract and may have some effect, either beneficial or adverse, on incontinence.

Adrenergic beta-Antagonists↗

Characteristics of urinary incontinence in elderly patients studied by 24-hour monitoring and urodynamic testing.

Characteristics of urinary incontinence have been studied in 100 elderly incontinent patients using invasive video-urodynamics and noninvasive 24-h monitoring of incontinence, fluid intake, voiding and residual urine. Incontinence was of the urge type in 51 patients, including 24 with reduced bladder sensation. Noninvasive 24-h monitoring showed satisfactory reproducibility and high sensitivity (88%) for detecting urine loss. Urodynamically proven urge incontinence, especially in combination with reduced sensation, and recent bacteriuria were associated with severe urine loss on 24-h monitoring. On 24-h monitoring, urine output was significantly larger at night and nocturia was common. In urge incontinence urine loss was predominantly nocturnal and the amount depended significantly on the previous evening's fluid intake and on nocturia. Noninvasive 24-h monitoring showed that post-void residual was common and was often largest in the early morning. It also yielded many free-voiding flow curves. Normal flow curves with small residual urine make dysfunction of voiding itself unlikely. Thus noninvasive monitoring provides information about incontinence and voiding that is suitable for designing intervention and management strategies. Invasive testing may be necessary however to confirm the urodynamic type of incontinence or suspected voiding dysfunction.

Aged↗

Effect of void-size distribution on the Hugoniot state at low shock pressures.

In most theoretical and experimental investigations into the shock response of underdense solid media, the influence of the medium's mesostructure on the resulting pressure and degree of compaction has not been taken into account. In typical cases examined, shock pressures are well in excess of 1 GPa and this approach is clearly justified. However, at low pressures, calculations show that the distribution of void sizes can affect the final state achieved upon shocking the medium from a given initial porosity. This paper analyzes the response of porous aluminum to low pressure shocking and demonstrates a dependence of the final shocked state on the distribution of void sizes.

Aluminum↗

Incontinence in the elderly: objective demonstration and quantitative assessment.

Subjective and objective methods of demonstrating incontinence and assessing its severity have been compared in a group of elderly patients with a high incidence of severe urge incontinence. It was found that 24-h in-patient monitoring of urine leakage was the most sensitive method of demonstrating incontinence, with videourodynamic testing almost as good. In comparison, a 1-h pad test was poor. Visual inspection during physical examination seldom demonstrated leakage. For quantitative assessment of severity, 24-h monitoring gave the most reproducible results; it was also able to reveal significant changes in severity in response to pharmaceutical treatment. A 1-h pad test was less reproducible and suggested changes that were only poorly consistent with 24-h monitoring. The subjective responses of the patients were not useful in assessing changes in the severity of incontinence. Twenty-four hour monitoring thus stands out as a superior method of demonstrating and assessing incontinence.

Aged↗

The role of videourodynamic studies in diagnosis and treatment of vesicoureteral reflux.

From January 1986 to January 1988, 63 children with 95 refluxing ureters have been studied in a prospective study with videourodynamic examination. All children with reflux grades I, II, and III received antibacterial treatment. Surgical treatment was adopted for reflux grades IV and V, provided detrusor instability had been excluded. However, if there was detrusor instability, anticholinergic drugs and antibacterial treatment were given in all grades of reflux and videourodynamic examination was repeated after 3 to 6 months and after 12 months of therapy. Bilateral reflux was found in 22 of 38 patients with a stable bladder, and reimplantation was performed in 11 patients with 18 refluxing ureters. In 25 children with 35 refluxing ureters of various grades of reflux, detrusor instability was found and unilateral reflux was noted more frequently than bilateral reflux. Surgery was necessary for only five children, because in the majority of the patients detrusor instability and reflux could be treated by anticholinergic drugs and antibacterial treatment. For the decision as to which treatment should be given in vesicoureteral reflux, a videourodynamic study is mandatory.

Child↗

Efficient storage of urodynamic signals by computer: application of FAN adaptive sampling.

Digital storage of urodynamic signals such as detrusor pressure and flowrate at a sufficiently high sampling rate (10 samples per second) to allow subsequent analysis requires considerable computer memory. A procedure for compressing these data by deleting redundant samples (the fan method of adaptive sampling) was tested. The method allows a flexible adaptation to specific hardware and a compromise between storage requirements and accuracy. In this study the number of samples required for adequate reconstruction of the detrusor pressure signal could be varied from 80% to 4% of the original number of samples by varying the average difference between reconstructed and original signal from 0.01 to 2 cm H2O. Fast components of the measurements (for example cough peaks) which were lost if a lower sampling rate or averaging was used to obtain equally low storage requirements were unaffected by this compression technique.

Algorithms↗

Treatment of benign prostatic hyperplasia by androgen deprivation: effects on prostate size and urodynamic parameters.

The possible effect of medical androgen deprivation in the treatment of benign prostatic hyperplasia has been studied in 12 patients. Six patients received the luteinizing hormone-releasing hormone agonist buserelin and 6 others received the antiandrogen cyproterone acetate. The treatment resulted in an average decrease in prostatic size of 29 per cent after 12 weeks as measured by ultrasonography. This decrease led to an increase in peak urinary flow rate, a reduction in residual urine volume and a decrease in daytime voiding frequency. However, it caused no decrease in urethral resistance but only an increase in the bladder contraction strength. After discontinuation of the treatment the prostates showed regrowth to the initial sizes within 6 to 36 weeks. The urodynamic changes were reversed as well. Although statistically significant, the urodynamic changes were minimal from a clinical viewpoint and did not lead to an unobstructed state after 12 weeks of treatment. For this reason the clinical indication for use of medical androgen deprivation in benign prostatic hyperplasia patients will remain limited for the time being.

Androgen Antagonists↗

Flow of urine through the ureter: a collapsible, muscular tube undergoing peristalsis.

In steady flow through nonuniform collapsible tubes a key concept is the compressive zone, at which flow limitation can occur at both high and low Reynolds numbers. Ureteral peristalsis can be considered as a series of compressive zones, corresponding to waves of active muscular contraction, that move at near-constant speed along the ureter towards the bladder. One-dimensional, lubrication-theory analysis shows that peristalsis can pump urine from kidney into the bladder only at relatively low mean rates of urine flow. Under these circumstances isolated boluses of urine are propelled steadily through the ureter (assumed uniform) by the contraction waves. At higher mean rates of flow the behavior depends on whether the frequency of peristalsis is higher or lower than a critical value. For frequencies above the critical value steady propagation of boluses that are in contact with contraction waves at both ends is possible. As the flow rate rises the urine begins to leak through the contraction waves and steady peristaltic flow breaks down. There is an upper limit to the mean flow rate that can be carried by steady peristalsis, which depends on the mechanical properties of the ureter. At high flow rates the peristaltic contractions do not pump but hinder the flow of urine through the ureter.

Muscle Contraction↗

Treatment of vesicoureteric reflux. Preliminary report of a prospective study.

Between 1982 and 1986 95 children with non-obstructive vesicoureteric reflux were treated in a prospective study. Preliminary results are reported on 94 children with 137 refluxing ureters and a follow-up period of at least 18 months. All children with reflux grade III or less had antibiotic treatment only. Those with reflux grade IV were randomised for antibiotic treatment alone versus surgery plus antibiotic treatment, while the primary treatment of reflux grade V was reimplantation. In 91 ureters treated by antibiotics alone, reflux disappeared in 49 cases; in 20 cases the grade of reflux was reduced. In 46 ureters treated by reimplantation, reflux was cured in 40 cases and no severe ureteric obstruction was seen. Conservative management of reflux grade IV seems to be less successful than surgery. The results of conservative, non-surgical treatment of reflux grade I to III are satisfactory, but for grades IV and V reflux surgery seems to be the treatment of choice if detrusor instability can be excluded.

Adolescent↗

Isolation and individual electrical stimulation of single smooth-muscle cells from the urinary bladder of the pig.

In contrast to striated muscle, measurements on strips of smooth muscle cannot be uniquely interpreted in terms of an array of contractile units. Therefore scaling down to the single-cell level is necessary to gain detailed understanding of the contractile process in this type of muscle. The present study describes the development of a method for isolating contractile single smooth muscle cells from pig urinary bladders. Contractile responses evoked by individual electrical stimulation were used as a measure of cell quality during development of the method. Responses were evaluated by measuring latency, contraction and relaxation times, as indicated by visible length changes, and stored on-line in a computer. Initial length, relative shortening and shortening speed were determined by measuring cell lengths in previously timed still video frames using a computer-controlled crosshair device. Increase of stimulus pulse duration resulted in improved responses, indicating that the observed shortening represented a physiological contractile response. Ultimately this method of evaluation was applied to two sets of cell preparations obtained by two different methods, one using only collagenase digestion, the other using mechanical manipulation as well. Both sets showed two main patterns of response to electrical stimulation: a pattern of contraction upon stimulation followed by enhanced contraction when stimulation was switched off (CK), and a pattern of contraction upon stimulation followed by relaxation when the stimulus was switched off (CR). The set of preparations containing the highest percentage of CR cells was found to be superior (i.e. greater initial length, shorter latency and contraction times, increased shortening and higher shortening speed). The method of isolation used for this set gives a high yield of contractile cells available for experimental use over a long span of time.

Animals↗