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Biomedical subjects

C M Castleden

Publications and source records attributed to C M Castleden.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1979

The effect of ageing on the hepatic clearance of propranolol.

1. Plasma propranolol concentrations were measured in healthy old and young subjects following single oral doses of 40 mg, single i.v. infusions of 0.15 mg kg-1 and after nine 40 mg oral doses given four times daily. 2. In each of the three studies, the elderly had higher plasma propranolol concentrations than the young despite having similar apparent volumes of distribution. 3. The terminal half-life of propranolol was similar in the two groups after oral propranolol but significantly shorter in the young after intravenous dosing (P less than 0.05). 4. The bioavailability assessed from the concentration-time curves after i.v. and oral dosing was greater in the elderly (P less than 0.05). 5. The differences between peak concentrations observed in old and young subjects after single oral doses were maintained during chronic therapy and there was a correlation between the individual values obtained on multiple therapy with that after a single dose (P less than 0.05). 6. Ageing appears to affect the pharmacokinetics of propranolol in two ways. Firstly, distribution to the tissues appears to be slowed. Secondly, the increased bioavailability following oral administration suggests diminished intrinsic clearance by metabolism.

Administration, Oral↗
PubMed1979

Chlormethiazole--no hangover effect but not an ideal hypnotic for the young.

The hangover effects of 768 mg chlormethiazole, an hypnotic with a half-life of approximately 4 hr, were compared with those of placebo in a double-blind cross-over study in 8 young subjects. Ten hours after dosing there were no differences between the preparations in the subjects' psychomotor performance, EEG sleep scores, or visual analogue ratings. Thus, an hypnotic which is rapidly removed from the body may confer considerable advantages. However, all 8 subjects had unpleasant nasal symptoms following chlormethiazole, and it is therefore not an ideal hypnotic for this age group.

Adult↗
PubMed1978

Contribution of individual differences in gastric emptying to variability in plasma propranolol concentrations.

1 No correlation was found between the rate of gastric emptying and peak plasma propranolol concentrations in six hypertensive patients after single oral doses of 80 mg. 2 In four normal subjects given oral propranolol the peak plasma concentration was highest when a simultaneous injection of metoclopramide and lowest when propantheline was given. The mean time to peak was 1.5 h after metoclopramide, 2.8 h after normal saline and 4.5 h after propantheline. 3 Gastric emptying has some influence on the time of peak plasma propranolol concentrations but individual variation in its bioavailability is determined mainly by first-pass metabolism in the liver.

Administration, Oral↗
PubMed1977

A second look at emepronium bromide in urinary incontinence.

Response to oral and intramuscular emepronium bromide was assessed cystometrically in nine patients with urinary incontinence caused by an uninhibited bladder. Oral therapy had no effect, whereas intramuscular administration increased bladder capacity and significantly delayed the onset of bladder spasm and the desire to void. Plasma-propranolol response was delayed and concentrations were reduced after an oral 40 mg dose of propranolol in 3 patients who had received oral emepronium bromide. These results indicate that although oral emepronium bromide had some anticholinergic effect--i.e., in reducing gastrointestinal motility--absorption of an oral dose was not sufficient for the bladder to be affected.

Administration, Oral↗
PubMed1977

Increased sensitivity to nitrazepam in old age.

The effects of a single 10 mg oral dose of nitrazepam were compared with those of a placebo in healthy young and old people. Both the young and the elderly slept better on three successive nights after nitrazepam but they felt less awake at 12 and 36 hours (P less than 0-01). Elderly people made significantly more mistakes in a psychomotor test than did the young, despite similar plasma concentrations of nitrazepam and half lives in the two groups. This difference in response to psychomotor testing is probably explained by an increased sensitivity of the ageing brain to the action of nitrazepam.

Adult↗
PubMed1977

The effect of ageing on drug absorption from the gut.

Single oral doses of aspirin and practolol were given to young and old subjects. The results of the plasma concentration-time curves were subjected to pharmacokinetic appraisal. There was no difference with either drug between the two age-groups in the mean absorption rate constant and the time at which maximum concentration in the plasma occurred. However, the amount of drug in the plasma of the elderly group was the same or higher than that in the younger group. It is concluded that ageing has no significant effect on the rate or amount of these drugs absorbed.

Administration, Oral↗