PubMed Health⌕ Search

Biomedical subjects

D B Frewin

Publications and source records attributed to D B Frewin.

At least 19 recordsLinked to original sources
PubMed1992

Antihypertensive efficacy and safety of perindopril in mild-to-moderate essential hypertension: results of a double-blind multicenter study versus atenolol.

A 3-month double-blind multicenter trial compared the efficacy and safety of perindopril, a new angiotensin-converting enzyme (ACE) inhibitor, with atenolol in mild-to-moderate essential hypertension. A total of 190 patients, 49 of whom were diabetic, entered the perindopril-atenolol comparison. Of these, 163 had been previously treated and had a 4-week run-in period on placebo; 27 had previously been untreated and received placebo for 2 weeks. At entry, all patients who had a supine diastolic blood pressure (DBP) of 95-115 mm Hg were randomized to receive perindopril 2 mg or atenolol 25 mg, once daily. Patients were assessed at 2 weekly intervals for the first month and then monthly for 2 more months. If supine DBP was greater than 90 mm Hg, treatment was increased by stepwise doubling of dose up to 8 mg perindopril or 100 mg atenolol once daily, and later by the addition of hydrochlorothiazide 25 mg, (indapamide 2.5 mg in diabetic patients) once daily. The two groups were homogeneous prior to treatment except for supine and erect heart rate, which were higher in the perindopril group than in the atenolol group (p less than 0.05). Mean supine DBP was 101.1 +/- 0.6 mm Hg in the perindopril group (n = 94) and 99.9 +/- 0.6 mm Hg in the atenolol group (n = 96). After 3 months' active treatment, 74% of patients in the perindopril group achieved a supine DBP of less than or equal to 90 mm Hg and 73% of patients in the atenolol group achieved the same goal. Monotherapy controlled supine DBP in 67% of the perindopril group and 63% of the atenolol group. The decrease in supine DBP was not significantly different between the two groups (-12.9 +/- 0.9 versus -14.7 +/- 0.9 mm Hg) but the decrease in erect DBP was lower in the perindopril group (-10.3 +/- 0.9 versus - 13.4 +/- 1.0 mm Hg, p less than 0.02). Heart rate was reduced in the atenolol group (p less than 0.001). Sixteen patients withdrew from the study; nine were attributed to adverse events, two in the perindopril group and seven, including one death, in the atenolol group. Cough was spontaneously reported by 13% patients of the perindopril group and 1% patients of the atenolol group. In 5% of the perindopril cases this was mild and associated with upper respiratory tract infection. The nature and incidence of other symptoms were similar with both drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1992

Effect of alpha 1-adrenoceptor blockade on the development of hypertension in the spontaneously hypertensive rat.

There is a large body of evidence to suggest that the sympathetic nervous system plays a critical role in the development of hypertension and vascular medial hypertrophy in the spontaneously hypertensive rat (SHR). The synthesis of a water soluble, specific alpha 1-adrenoceptor antagonist (terazosin) has permitted an examination of the influence of alpha 1-adrenoceptors on those two phenomena. Thus, in the present study, terazosin (43 mg/kg per day) was administered to SHR and Wistar-Kyoto (WKY) rats from 4.5 to 12 weeks of age, and a number of assessments made in vitro and in vivo. In the SHR, the development of hypertension was not prevented by terazosin. The drug did not influence blood pressure in the WKY. This was despite the fact that animals which had been chronically treated with terazosin displayed marked alpha-adrenoceptor blockade in vivo. The response of systolic blood pressure to tyramine and noradrenaline was significantly reduced in animals which had been chronically treated with terazosin. In both the SHR and WKY, chronic administration of terazosin did not influence vascular concentrations of 3-methylhistidine, a biochemical marker for contractile proteins and vascular medial hypertrophy. The results therefore argue against a role of alpha 1-adrenoceptors in the development of hypertension and vascular medial hypertrophy in the SHR.

Adrenergic alpha-Antagonists↗
PubMed1992

A comparison of the effect of lisinopril and hydrochlorothiazide on electrolyte balance in essential hypertension.

The effects of lisinopril 10-20 mg or hydrochlorothiazide 25-50 mg (each given once daily) on blood pressure, serum sodium, potassium and magnesium concentrations, total body potassium and urinary cation excretion were compared in a group of hypertensive patients using a double blind randomised crossover design. Each active treatment phase lasted six weeks and a total of sixteen patients completed the study. Both lisinopril and hydrochlorothiazide produced clinically significant decreases in blood pressure. However, lisinopril treatment produced a mean reduction of 14 mmHg in sitting diastolic pressure compared with a 7 mmHg reduction for hydrochlorothiazide treatment. This difference was statistically significant. The decrease in the concentration of serum potassium during hydrochlorothiazide treatment was greater than that during lisinopril treatment (0.53 vs 0.01 mmol.1). The absolute value of serum potassium was significantly lower on hydrochlorothiazide than on lisinopril therapy. Neither treatment had an effect on serum magnesium concentrations, nor was there any significant effect of either treatment on urine volume or urinary excretion of sodium, potassium or magnesium. There was a trend towards increased total body potassium concentration on lisinopril compared with a decrease in total body potassium on hydrochlorothiazide. However, this difference was just outside the range of statistical significance. Both treatments were equally well tolerated. The results indicate slight superiority of lisinopril over hydrochlorothiazide with regard to control of diastolic blood pressure with a better effect on overall electrolyte balance.

Adolescent↗
PubMed1992

The relationship between the concentration of temazepam in cerebrospinal fluid and sedation in man.

Twenty-six patients received oral temazepam and subsequently spinal anaesthesia. Blood and lumbar cerebrospinal fluid temazepam levels were measured together with the degree of sedation. The plasma and cerebrospinal fluid concentrations correlated well with the temazepam dose but even better with the weight standardised dose (r = 0.65, p = 0.0003 and r = 0.75, p = 0.00001 respectively). Both the plasma and cerebrospinal fluid concentrations of temazepam were correlated with the patient's sedation (r = 0.42 p = 0.037, and r = 0.46 p = 0.021 respectively), but neither was strong. Thus, although the drug concentration at the receptor may be a major factor in producing sedation, other factors, possibly the receptor population or their responsiveness, are also important contributors.

Administration, Oral↗
PubMed1992

The influence of chronic captopril treatment and its withdrawal on endothelium-dependent relaxation.

The current experiments were designed to explore the relationship between the renin angiotensin system (RAS) and prostanoid formation in aortic ring preparations from spontaneously hypertensive rats (SHR). A further aim was to examine the mechanisms responsible for the reversal of the impaired acetylcholine (ACh) mediated relaxation induced by chronic administration of the angiotensin converting enzyme inhibitor captopril and the relationship of the ACh response to blood pressure. Rats were administered captopril (100 mg/kg/day) and their blood pressures monitored from 5 to 17 weeks of age. ACh-mediated relaxation was determined in aortic ring preparations from untreated and treated rats, and drug withdrawn rats. The influence of indomethacin, saralasin, SQ29548 and captopril on ACh-mediated responses was determined. It was found that chronic captopril treatment produced a marked suppression of the development of hypertension in the SHR. After the withdrawal of the drug the blood pressure remained significantly lower than in untreated animals for 4 weeks. ACh relaxation was impaired in SHR ring segments; this was reversed with captopril treatment and returned to the impaired state upon withdrawal of the drug. In vitro inhibition of the RAS did not significantly influence ACh relaxation. In contrast, impairment of the prostanoid system in vitro reversed the impaired relaxation. The results suggest that the influence of captopril on enhancing ACh relaxation in the SHR does not involve an acute interaction of local angiotensin II synthesis with prostanoid mechanisms. Importantly, the results highlight a dissociation between the impaired ACh relaxation and elevated blood pressure in the SHR.

Analysis of Variance↗
PubMed1991

A comparison of the efficacy of captopril and enalapril given once daily for the treatment of hypertension: a study using 24-hour ambulatory blood pressure monitoring.

Sixteen patients who had essential hypertension were stabilized on either captopril or enalapril monotherapy and had 24-hour blood pressure profiles monitored by using one of two automatic, non-invasive ambulatory systems: Spacelabs 5300 (Squibb, Princeton, NJ) or PAR Physioport II (Kardiotec, Mannheim). In four subjects (group 1), ambulatory pressures were repeated 4 to 6 weeks later using the same equipment and the same drug. In four subjects (group 2), the drug was changed (dose ratio: captopril:enalapril, 5:1) after the first measurement, but the monitoring equipment was not changed. In four subjects (group 3), the drug was constant, but the equipment was changed for the second measurement of ambulatory pressure. In four subjects (group 4), both drug and equipment were reversed after the first measurement. The results showed that both drugs (given once daily) controlled blood pressure during the 24-hour period, with no clinically significant difference between them.

Adult↗
PubMed1991

Felodipine in combination with a beta-adrenoceptor blocker as an effective substitute for triple therapy in severe hypertension. The Australian Felodipine Multicentre Study Group.

We have studied the efficacy and tolerability of felodipine plus a beta-adrenoceptor blocker in 79 patients with essential hypertension previously treated with a combination of three or more anti-hypertensive agents, one of which was a beta-adrenoceptor blocker. After a 4-week run-in period on the same beta-blocker plus placebo (as a substitute for the other agents in the regimen), felodipine was added and its dose titrated to achieve a supine diastolic blood pressure or less than 90 mm Hg. This was followed by a 12-week maintenance phase in all patients, and 47 patients entered an optional long-term follow-up for an additional 9 months. The mean supine blood pressure was 149/88 mm Hg at entry and 174/108 mm Hg after the run-in phase. Felodipine significantly reduced the blood pressure to 142/85 mm Hg after dose titration and to 141/84 mm Hg after 12 weeks, 94% of patients achieving a supine diastolic blood pressure of 90 mm Hg or below. This reduction was maintained in the patients who were followed for 12 months. The adverse events recorded were usually mild, transient, and typical for an effective precapillary vasodilator. Nine of 74 patients (11%) were withdrawn in the first phase of the study because of adverse events and 5 of 47 patients were withdrawn during the long-term follow-up. These results show that the efficacy and tolerability of a combination of felodipine with a beta-blocker allow a simplified regimen for hypertensive patients who were previously taking three or more drugs for satisfactory blood pressure control.

Adolescent↗
PubMed1991

Morphine responders with unexplained pain after cholecystectomy may have sympathetic overactivity.

In patients with unexplained pain after cholecystectomy, morphine often induces pain and may increase plasma aspartate aminotransferase activity because of exaggerated or prolonged rises in pressure within the biliary system. Previous studies have demonstrated that patients showing increases in aspartate aminotransferase have increases in plasma concentrations of noradrenaline and dopamine prior to and soon after induction of pain. The purpose of this study was to assess sympathetic activity under basal conditions in patients with (responders) and without (non-responders) increases in aspartate aminotransferase after challenge with morphine. When compared to non-responders, morphine responders had higher plasma concentrations of noradrenaline (p = 0.0001) and dopamine (p = 0.02) and higher urinary excretion of noradrenaline over 24 h (p = 0.03). Plasma and urinary levels of adrenaline were similar in the two groups. These observations indicate higher basal levels of sympathetic activity in the subgroup of patients showing increases in aspartate aminotransferase after challenge with morphine.

Aspartate Aminotransferases↗
PubMed1991

Chronic captopril treatment reverses the enhanced vascular concentrations of 3-methylhistidine in the spontaneously hypertensive rat.

Morphometric studies conducted on the blood vessels of the spontaneously hypertensive rat have provided evidence that medial hypertrophy is a key characteristic of the vascular change which occurs in hypertension. In the present study, we determined whether 3-methylhistidine (3MH), a post-translationally modified amino acid which is found uniquely in the actin and myosin of muscle, could provide a biochemical marker of such change. Our results indicated that the concentrations of 3MH were selectively elevated in the blood vessels from the spontaneously hypertensive rat, when compared with concentrations in vascular tissues from the Wistar-Kyoto rat. The concentrations of 3MH in non-vascular tissues were similar in the two strains. Chronic captopril treatment prevented the development of hypertension in the spontaneously hypertensive rat and was associated with a reduction of the vascular concentrations of 3MH. We therefore conclude that blood vessel concentrations of 3MH are a useful biochemical index of the changes in vascular smooth muscle contractile protein which occur during the development of hypertension in the spontaneously hypertensive rat.

Animals↗
PubMed1990

Plasma and cerebrospinal fluid concentration of temazepam following oral drug administration.

Thirteen male patients were administered 20 mg of temazepam orally 1 to 2 h prior to undergoing spinal anaesthesia for a urological procedure. Samples of blood and CSF were drawn just before insertion of the spinal and the concentration of drug estimated in these two media. The results obtained indicated that a highly significant correlation existed between the unbound concentration of temazepam in plasma and the concentration of drug present in CSF. Temazepam appeared to be an effective light pre-medicant in all of the subjects studied.

Administration, Oral↗
PubMed1990

Interference from digoxin-like immunoreactive substance(s) in commercial digoxin kit assay methods.

We have examined the current state of interference by digoxin-like immunoreactive substance(s) (DLIS) in 10 commercially available digoxin assay methods, ie 5 radioimmunoassays (RIA) and 5 non-radioactive immunoassays. Fifty-five specimens of maternal venous blood (30 from third trimester pregnancy and 25 at delivery) and 32 cord samples from their offspring were tested (none of the subjects being medicated with digoxin). The results demonstrated a wide range of DLIS interference with values up to 1.1 micrograms.l-1 being obtained in the cord blood specimens. Of the methods tested the "Coat-a Count" RIA (Diagnostic Products Corporation) and the EMIT column method (Syva) run on the Cobas MIRA (Roche) consistently showed the least interference with respect to all 3 sources of specimens. The Delfia Method (LKB/Wallac) consistently showed the greatest crossreactivity with DLIS. The present study thus demonstrates that DLIS interference persists in several commercial digoxin methods and suggests that the use of data obtained from such methods may compromise patient management.

Blood Proteins↗
PubMed1990

The effect of exercise on circulating immunoreactive calcitonin in men.

Moderate-duration exercise increases serum catecholamine and serum calcium levels and might as a result be also expected to increase the levels of circulating serum immunoreactive human calcitonin (HCT). To explore this possibility, HCT was studied during and after moderate duration symptom-limited dynamic exercise in 13 healthy males, mean age 28 +/- 6.9 (SD) years. The mean duration of exercise using the Bruce treadmill protocol was 14.1 +/- 2.2 (SD) minutes. The mean heart rate (HR) peaked at 185 +/- 6 (SD) bpm which was 96.1% of the predicted maximal HR for age. Values for HCT, uncorrected for changes in plasma volume, showed a minimal decrease in the recovery phase, whilst HCT corrected for changes in plasma volume did not alter during exercise or recovery. The serum parathyroid hormone (PTH) also did not change. At peak exercise, uncorrected but not corrected values for plasma noradrenaline, adrenaline and dopamine had increased significantly. Corrected plasma total calcium increased during recovery. In summary, dynamic weight-bearing moderate-duration exercise did not elevate HCT in healthy males.

Adult↗
PubMed1990

Sympathetic activation: a mechanism for morphine induced pain and rises in liver enzymes after cholecystectomy?

In patients with biliary type pain after cholecystectomy, morphine often precipitates pain and may induce rises in plasma concentrations of liver enzymes because of exaggerated or prolonged rises in intrabiliary pressure. In this study, changes in plasma concentrations of catecholamines and histamine were determined after the administration of morphine in patients with and without a two-fold or greater rise in the plasma concentration of aspartate aminotransferase at four hours. Those showing rises in aminotransferase had higher concentrations of noradrenaline at 40 and 60 minutes after morphine and higher concentrations of dopamine at 40 minutes after morphine. The two groups had similar concentrations of adrenaline and histamine. Attempts to inhibit rises in aminotransferase after morphine by pretreatment with histamine, serotonin and alpha-receptor blockers were largely unsuccessful, although inhibition was observed with phenoxybenzamine in two of five patients. Higher plasma concentrations of noradrenaline and dopamine before and soon after induction of pain in patients showing rises in aminotransferase are consistent with sympathetic activation but heterogeneity appears to exist in the response to alpha-receptor blockade.

Adult↗
PubMed1989

The effect of angiotensin converting enzyme inhibitors (ACE-I) and selective beta 1-antagonists on bronchial reactivity and the cough reflex in man.

The non-specific bronchial reactivity and cough threshold of hypertensive patients on an ACE-I monotherapy regimen (either captopril or enalapril), a beta 1-antagonist monotherapy regimen (either atenolol or metoprolol) or a combination of an ACE-I with a beta 1-antagonist were determined in the present study. Forty-six hypertensives who were on these medications performed a histamine inhalation test (to assess bronchial reactivity) and a further 36 of these individuals participated in the citric acid test (to assess cough threshold). A control cohort consisting of 25 age-matched, drug-free subjects also performed the citric acid test. The incidence of bronchial hyperreactivity was not significantly different between the ACE-I monotherapy regimen and the beta 1-antagonist monotherapy regimen (Chi-squared = 0.248). However, when the monotherapy regimens were pooled and compared with the ACE-I and beta 1-antagonist combination regimen, the combination regimen was found to be associated with a significantly higher incidence of bronchial hyperreactivity (Chi-squared = 6.69). No difference was observed between the age-matched controls and the hypertensive patients in terms of their cough threshold.

Adrenergic beta-Antagonists↗
PubMed1989

Is captopril effective in controlling blood pressure when administered once daily? An assessment using 24-h ambulatory blood pressure monitoring.

Twelve patients with essential hypertension receiving captopril monotherapy or captopril in conjunction with a diuretic had their 24-h blood pressure profiles monitored using an automatic, non-invasive ambulatory method. The study examined the efficacy of once a day versus twice a day administration of the ACE inhibitor in controlling blood pressure. Six untreated subjects with borderline hypertension were also studied using the same monitoring equipment and with the same frequency, to act as controls because of the possibility of repeated use of the device causing a 'familiarisation' effect. The results obtained indicated that if anything, the once daily dosing produced marginally better blood pressure values. The amplitude of the diurnal blood pressure variation was reduced on a 'second-wearing' of the monitoring equipment suggesting some degree of familiarisation with the apparatus.

Adult↗
PubMed1989

Influence of blood storage time and plasma histamine levels on the pattern of transfusion reactions.

The data from 359 transfusion reactions reported over a 3-year period have been compared with those obtained from 359 matched units given at the same time as the former but not implicated in a reaction. It was found that patients who developed reactions which were not accompanied by a change in body temperature received units with a longer storage time than patients experiencing febrile reactions. In addition it was noted that reactions which included a skin rash also tended to be associated with units stored for longer. In a further prospective assessment plasma histamine levels were measured in a group of 71 patients experiencing 'anaphylactoid', febrile and mixed transfusion reactions as well as in individuals in whom blood transfusions did not cause a reaction. The 'anaphylactoid' reaction group demonstrated a mean plasma histamine level in excess of 1 ng/ml, whereas mean concentrations below 0.50 ng/ml were recorded in the other 3 groups. Our data also suggested that in general, more and 'older' blood was given to the 'anaphylactoid' reactors. The high plasma histamine concentrations could readily contribute to the rash, wheeze and flushing recorded in these individuals. Thus, if a long shelf-life for stored blood is required, strategies which remove histamine from the unit may be worth considering.

Blood Preservation↗