Nerve mediated relaxation in human detrusor muscle.
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Carbon Dioxide↗
Biomedical subjects
C M Castleden
Publications and source records attributed to C M Castleden.
Interarm blood pressure difference in acute hemiplegia.
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Aged↗
The effects of dopamine and a low protein diet on glomerular filtration rate and renal plasma flow in the aged kidney.
The aims of this study were to determine the effects of dopamine and a low protein diet on glomerular filtration rate and effective renal plasma flow in the aged kidney. Effective renal plasma flow was measured using 125I-labelled hippuran and glomerular filtration rate using 51Cr-labelled EDTA. Low-dose continuous intravenous dopamine 3 micrograms.kg-1.min-1 in 10 healthy elderly volunteers caused a significant increase in effective renal plasma flow but not in the mean glomerular filtration rate when compared with baseline. However, glomerular filtration rate did increase substantially in 5 subjects (mean 14.4, SD 1.3). This implied that the elderly kidney was working maximally without reserve capacity in half the elderly. Since renal function is likely to be even more reduced in elderly patients with congestive cardiac failure, dopamine infusions may have little place in this condition in some older patients. A low protein diet (0.69 g.kg-1) in the same volunteers reduced glomerular filtration rate, suggesting that protein restriction may help to reduce the increased filtration rate in the remaining nephrons, thereby leading to structural and functional preservation in the aged kidney.
Age Factors↗
The direct effects of diethylstilboestrol and nifedipine on the contractile responses of isolated human and rat detrusor muscles.
We have studied the direct effect of 2 mumol.l-1 diethylstilboestrol on isolated rat and human detrusor muscles. Diethylstilboestrol significantly reduced the amplitude of the contractile response of rat detrusor muscle to stimulation with acetylcholine, carbachol, electrical field stimulation, and 5-hydroxytryptamine. In isolated human bladder it also significantly reduced contractions stimulated with acetylcholine, carbachol, and electrical field stimulation. In depolarized rat detrusor muscle stimulated with different concentrations of calcium ions, the contractile responses were significantly reduced by the addition of diethylstilboestrol. Diethylstilboestrol also significantly reduced the amplitude of contractile response to potassium chloride. The inhibitory action of diethylstilboestrol was enhanced by the reduction of extracellular calcium ions, the maximum contractile response to acetylcholine, carbachol, and electrical field stimulation being reduced by a further 32%, 23%, and 45% respectively. Diethylstilboestrol did not have a significant effect on carbachol-induced contractions in depolarized rat detrusor muscle suspended in a calcium-free environment. Diethylstilboestrol was effective in blocking rat and human detrusor muscle contraction. The likely mechanism is a reduction of the influx of calcium ions into the cell during contraction rather than an effect on intracellular calcium release. These results give support for treating incontinent patients with drugs that block calcium ion uptake, and may suggest a further beneficial effect of oestrogen therapy in postmenopausal women.
Acetylcholine↗
Renal prostaglandins, effective renal plasma flow and glomerular filtration rate in healthy elderly subjects.
This study tests the hypothesis that the age-associated reduction in glomerular filtration rate (GFR) and the presence of glomerulosclerosis renders effective renal plasma flow (ERPF) prostaglandin dependent. Ten healthy elderly volunteers were studied in a single-blind placebo-controlled manner using indomethacin to suppress the renal prostaglandins. There was no significant difference in ERPF or GFR following indomethacin when compared with placebo. These results suggest that blocking renal prostaglandins does not significantly alter ERPF or GFR in healthy elderly people.
Aged↗
The effect of in vivo oestrogen pretreatment on the contractile response of rat isolated detrusor muscle.
1. The effect of oestradiol pretreatment was investigated on the response of rat isolated detrusor muscle to cholinergic, electrical and 5-hydroxytryptamine (5-HT) stimulation with and without diethylstilbestrol (DES) (2 microM) in the organ bath. 2. Virgin female Wistar rats were injected subcutaneously for 8 days with oestradiol benzoate 150 micrograms kg-1. Control rats received no injections or injection only with the vehicle, ethyl oleate. 3. Detrusor muscle from treated rats showed a decreased sensitivity to acetylcholine (ACh) and carbachol-induced contractile responses. The dose-response curves to these agonists showed a 44% reduction in maximum contractile response for ACh (P < 0.001), and a 38% reduction in maximum contractile response for carbachol (P < 0.05). The addition of 2 microM DES to the bathing medium further significantly reduced the maximum contractile response by 56 and 57% of control respectively. 4. Electrically stimulated detrusor muscle from treated rats showed a significant 49% reduction in the maximum contractile response (P < 0.001). The addition of 2 microM DES to the bathing medium further significantly reduced the maximum contractile response by 66% of control. The tetrodotoxin resistant responses were smaller in pretreated rats, suggesting a reduced sensitivity of the smooth muscle to direct electrical stimulation. 5. The response to 5-HT stimulation by detrusor muscle samples from oestradiol-treated rats showed a non-significant reduction in maximum contractile response, but the addition of 2 microM DES to the bath chamber resulted in a 67% reduction in the response (P < 0.001). 6. Oestradiol pretreatment did not affect the potassium dose-response curve.7. Oestradiol pretreatment reduced the rat detrusor muscle sensitivity to the blocking effect of atropine on the response to electrical field stimulation. Pretreatment also reduced the potentiating effect of physostigmine on the same response.8. These results suggest that oestradiol pretreatment had a modulating effect on cholinergic responses.The addition of oestrogen to the tissue environment enhances this inhibitory effect.
Acetylcholine↗
Factors delaying hospital admission after stroke in Leicestershire.
BACKGROUND AND PURPOSE: Use of thrombolysis and acute treatments for cerebral infarction may require that acute stroke be treated as a medical emergency. To assess the factors influencing the time to admission in acute stroke, we conducted a prospective study of all such patients admitted to the hospitals in Leicester, UK, over a 12-month period. METHODS: Factors assessed were age, sex, time of stroke onset, stroke severity, home circumstances, and routes of admission. Initial between-group comparisons were made with the Mann-Whitney U test. The individual contribution of each of these variables was assessed with multiple linear regression analysis. RESULTS: An accurate time of stroke onset was identified in 374 (70%) of 535 registered patients (median age 77 [range, 29-98] years; 332 men, 203 women). Median time from onset to admission was 6 hours, with 25% of the patients arriving in less than 2.5 hours and 75% in less than 11.5 hours. Multiple regression confirmed that only admission through the bed allocation bureau (p less than 0.001), living alone (p less than 0.001), and nocturnal onset (p = 0.003) prolonged delay time. Despite patients over 70 years of age taking a median of 7 hours from onset to admission compared with 4 hours for those under age 70 (p less than 0.001), the effect of age appeared to be dependent on these three factors. Age, sex, level of consciousness, rural domicile, and place of admission did not influence the delay time independently. CONCLUSIONS: We have identified some of the factors affecting the hospital admission delay time for stroke. With the possible advent of effective early treatments for stroke, these factors will need to be addressed.
Adult↗
Tamoxifen and partial oestrogen agonism in postmenopausal women.
The effect of tamoxifen on the vaginal mucosa and on serum oestrone, oestradiol and gonadotrophin concentrations was investigated in a group of nine postmenopausal women with non-metastatic breast cancer. Compared with fit age-matched controls, the vaginal pH in the tamoxifen-treated group was significantly lower and was comparable to levels in fertile women. Two thirds of tamoxifen-treated women had well oestrogenized vaginal smears compared with none in the control group. Follicle-stimulating hormone was significantly reduced, whilst oestrone and oestradiol levels remained unchanged. We conclude, therefore, that tamoxifen has oestrogen-agonistic properties particularly evident in postmenopausal women, even though it is primarily an antioestrogenic drug.
Aged↗
Oxybutynin and urinary incontinence.
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Aged↗
Care of the elderly person with diabetes: a questionnaire study comparing geriatricians with diabetic specialists.
The management of elderly diabetic patients by 100 geriatricians and 100 diabetologists was assessed by a postal questionnaire. Replies were initially received from 54 geriatricians and 81 diabetologists (p less than 0.001); geriatricians were re-contacted increasing replies to 71. The geriatricians were less likely to check the visual acuities (p less than 0.001), less likely to dilate the pupils for fundoscopy (p less than 0.025), less likely to refer a patient with maculopathy to an ophthalmologist (p less than 0.001), more likely to discharge a stable diabetic to general-practitioner care (p less than 0.05), less likely to use insulin (p less than 0.01) or antidepressants (p less than 0.01) in treating painful peripheral neuropathy, and more likely to use glibenclamide instead of a shorter-acting sulphonylurea (p less than 0.001).
Aged↗
Pharmacological treatment of urinary incontinence.
Urinary incontinence (UI) is a major problem especially to the elderly. The only absolute indications for drug therapy in this condition are infection and atrophic urethritis. Other causes of UI should be treated with behavioural remedies and physiotherapy. If these measures are impractical or fail to improve the condition, then we would recommend additional drug therapy.
Aged↗
Drug therapy in patients with recent stroke.
At present the treatment of the acute stroke is limited to managing the consequences of the primary event and attempting secondary prevention. The routine use of agents to reverse the cause or ameliorate the effects of stroke appears to be very controversial, and the value of secondary preventative measures is still far from clear. A large number of therapeutic trials have been performed in the past with no clear advantage for any drug. However, more recent studies are helping to clarify some aspects of treatment and may suggest that the active treatment of stroke is drawing near. This chapter discusses the treatments that have been tried in acute stroke, the reasoning behind their use and their performance so far. It also looks at newer treatments which may be important in the future.
Aged↗
Handicaps associated with incontinence: implications for management.
STUDY OBJECTIVE: The aim was to explore the relationship between dementia, impairment of mobility, and incontinence and the implications for management. DESIGN: The study was a survey of a sample population drawn from a general practice register. SETTING: A large general practice serving the entire population of Melton Mowbray, Leicestershire, UK. PARTICIPANTS: Of 1329 persons aged 75 or over, 1203 (90%) took part in the survey. Of non-responders, refusers accounted for 5%, deaths 4%, and failure to trace 1%. MEASUREMENTS AND MAIN RESULTS: 12% of the population complained of incontinence. No more than 24% of these cases were demented. Dementia and isolated locomotor problems were significantly associated with presence of incontinence, but 31% of cases were completely free of either problem. A minimum estimate of 56% of cases of incontinence were considered to be due to local physical disorders of the bladder. CONCLUSIONS: A search for local disorders causing incontinence is important, and more attention should be paid to the management of locomotor problems and possibly depression in the relief of incontinence.
Activities of Daily Living↗
The effect of ageing on the pharmacokinetics of dihydrocodeine.
Although poor renal function reduces clearance of dihydrocodeine in man, and renal impairment occurs with ageing, no significant differences occurred in the handling of single doses of dihydrocodeine between elderly patients and young, normal subjects. After multiple dosing, the maximum concentration was significantly different between the groups, being higher in the elderly. The increase in the area under the curve in the elderly was 25% greater than in the young on chronic therapy. This difference was not statistically significant, but was likely to be of clinical significance. The elderly patients' mean creatinine clearance (61.8 ml per min) was significantly lower than that in the young (137 ml per min), and there was a significant correlation between the half-life at single dosing and the blood urea concentration. Variability in all measurements was marked in both groups, and hence no clear guidelines can be given on therapeutic dosing. The small initial dose with alterations thereafter depending on clinical effect is the best advice.
Adult↗
Long-term follow-up of habit retraining for bladder instability in elderly patients.
Sixty patients with detrusor instability were contacted 2 to 3 years after their initial diagnosis and treatment. When first treated, 40 had improved, nine were catheterized and the remainder were unchanged. By the time of the first outpatient appointment 1 month later, a further 6% had been catheterized and 26% had lost control. Two to 3 years later, 17 of the 40 who had improved initially had maintained their improvement. The control in all the remainder had deteriorated and ten of the original 60 had died. Four of these deaths occurred in the group initially catheterized, only two of this group still had their catheter in situ, but were experiencing problems from it, and the remaining three had removed their catheter and were managing with pants and pads. Thus, two-thirds of elderly patients with bladder instability respond initially to treatment, but 2 to 3 years later only two-fifths of these are still deriving benefit.
Aged↗
Fifty six continence advisers, one peripatetic teacher.
The increasing demand for the services of a continence nurse led to a novel plan to combat such demand in Leicestershire. The district nursing service seconded a nurse to be trained as an adviser and then to return to the community to set up continence clinics in each health centre. The adviser selected nurses to run these clinics and taught them the skills required to do so. She also carried her own caseload. One hundred and one patients were seen in the clinics in the first year, of whom 30 were cured. In a further one third continence was greatly improved, and the remainder benefited from advice and consultation. The adviser has worked in only six health centres but has had a greater impact on dealing with incontinence than a series of lectures and seminars for district nurses over many years had had.
Adult↗
The effect of ageing on the disposition of nifedipine and atenolol.
1. Healthy young and elderly volunteers received 20 mg nifedipine (slow release) orally for 2 weeks with concomitant dosing of atenolol 50 mg orally during the second week. 2. Drug kinetics and dynamics were compared between the groups after a single dose of nifedipine (day 1), after chronic dosing for 1 week (day 8), and following concomitant daily dosing of atenolol (day 15). 3. Plasma profiles of nifedipine were similar within each group on each of the 3 sampling days. The elderly group had higher plasma concentrations from about 6 h but there was no difference in the maximum concentrations achieved. The half-life in the elderly was significantly longer (8.8 +/- 0.9 h) compared with that in the young (5.8 +/- 1.1 h) (P less than 0.01). 4. Blood concentrations of atenolol were higher in the elderly at 12 and 24 h post-dose (P less than 0.001) and the AUC was greater than in the young (P less than 0.001). 5. Systolic blood pressure was reduced by nifedipine in both groups but to a greater extent in the elderly (P less than 0.01); differences in diastolic blood pressure were not significant. Blood pressure was reduced further by the addition of atenolol. Atenolol reduced the heart rate in all subjects.
Adolescent↗
Suspected adverse drug reactions in elderly patients reported to the Committee on Safety of Medicines.
1. Spontaneous reports of suspected adverse drug reactions (ADRs) reported to the Committee on Safety of Medicines (CSM) have been studied in relation to patient age. 2. The proportion of reports received for the elderly increased between 1965 and 1983. 3. There was a correlation between the use of drugs and the number of ADR reports. Thus age-related prescription figures for two non-steroidal anti-inflammatory drugs (NSAI) and co-trimoxazole matched ADR reports for each drug in each age group. 4. The reported ADR was more likely to be serious or fatal in the elderly. 5. The commonest ADRs reported for the elderly affected the gastrointestinal (GIT) and haemopoietic systems, where more reports were received than would be expected from prescription figures. 6. The drug suspected of causing a GIT reaction was a NSAI in 75% of the reports. 7. Ninety-one per cent of fatal reports of GIT bleeds and perforations associated with NSAI drugs were in patients over 60 years of age.
Adolescent↗