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Biomedical subjects

D B Frewin

Publications and source records attributed to D B Frewin.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1989

Extra-adrenal phaeochromocytoma: report of three interesting cases.

The clinical, laboratory and operative findings from three cases of extra-adrenal phaeochromocytoma are reviewed. Some of the difficulties encountered in localizing such a neoplasm are highlighted. Data from intraoperative catecholamine monitoring on the three patients are also presented. Adequate alpha and beta blockade produced stable cardiovascular parameters during surgery in all three individuals.

Abdominal Neoplasms↗
PubMed1988

A general-practice study of the efficacy and tolerability of metoprolol in mild essential hypertension.

The efficacy and tolerability of metoprolol (100 mg once a day) were assessed in general practice in 6713 newly-diagnosed or previously-treated hypertensive patients in an open study of eight weeks' duration. In 3534 mildly-hypertensive patients who were eligible for the efficacy analysis, the mean blood pressure level was reduced by 19/10 mmHg; 68% of the patients achieved diastolic blood pressures below 90 mmHg by the end of the assessment period. Of 6557 patients who were eligible for the tolerability analysis, only 5.6% of patients withdrew because of adverse events. The incidence of adverse events diminished considerably from the clinic assessment at four weeks (20%) to that at eight weeks (11%). At the completion of the study, 92% of the mildly-hypertensive patients were to continue with metoprolol, either as monotherapy (including 64% of patients who were receiving 100 mg once a day and 6% of patients who were receiving 50 mg once a day), or as combination therapy. Analysis of the large subgroup of mildly-hypertensive elderly patients (n = 1214) and of moderately-hypertensive patients, whose diastolic pressures exceeded the set upper limits (n = 2505), showed similar efficacy and tolerability results. Sixty-eight per cent of the former and 47% of the latter demonstrated satisfactory control of blood pressure. These results show that the majority of mildly-hypertensive patients can be controlled with 50-100 mg of metoprolol once a day.

Adolescent↗
PubMed1988

The effect of renal and hepatic impairment and of spironolactone on digoxin immunoassays.

The effect of renal and/or hepatic dysfunction, and of concomitant spironolactone therapy, on seven commercial digoxin assays was evaluated in 45 patients taking both these drugs, and a comparison made with the digoxin concentrations measured using the same assays in 30 patients taking digoxin in the absence of spironolactone. The study showed that increasing renal dysfunction resulted in increasing inaccuracy in assay results with the methods tested. The influence of concomitant spironolactone was to produce a further distortion, which was shown to be additive in patients with impaired renal and/or liver function. The results highlight the unresolved specificity problems which persist in many, if not all, of the immunoassays currently offered to clinical laboratories which, if not recognised, could significantly influence digoxin therapy and patient management.

Aged↗
PubMed1988

Pharmacokinetics of a new sublingual formulation of temazepam.

The pharmacokinetics of a new 10 mg sublingual tablet formulation of temazepam and those of a currently marketed 10 mg oral capsule formulation were evaluated in a group of ten healthy volunteers. No significant differences were observed between the two formulations with respect to any of the pharmacokinetic parameters assessed. Lethargy and somnolence were reported on both capsule and tablet by several subjects at a time which corresponded with the maximum concentration of drug in plasma. The data indicate that the sublingual tablet and orally administered capsule have a similar pharmacokinetic and pharmacodynamic profile.

Administration, Oral↗
PubMed1988

Adverse reactions during intravenous urography: are these due to histamine release?

The effects of four different radiographic contrast media (Urovison 58%, Hexabrix 320, Iopamiro 370 and Omnipaque 300) have been examined with respect to histamine release, cardiovascular changes and adverse drug reaction (ADR) in a group of 200 patients undergoing intravenous urography. Each patient received only one of the four agents, which were allocated on a random basis. Urovison produced the greatest number of ADRs. Iopamiro caused the least. No significant correlation between the magnitude of the change in plasma histamine following injection of radiographic contrast medium and the production of a particular ADR could be demonstrated. Heart rate increased significantly following the administration of Urovison, Hexabrix and Iopamiro in the absence of any appreciable change in blood pressure. These results and our earlier findings would favour the use of the low-osmolality contrast media in intravenous urography to minimize ADRs, histamine release and patient discomfort.

Blood Pressure↗
PubMed1987

The pharmacokinetics of ketoconazole after chronic administration in adults.

We have studied the pharmacokinetics of the anti-mycotic ketoconazole in seven patients who took it for 1-6 months at a dose of 200 mg daily. The mean elimination half-life of the drug was 3.3 h, and although the ketoconazole was given only once daily, a satisfactory clinical response was obtained in all seven individuals. Only a small fraction of the absorbed drug (mean 0.22%) was excreted unchanged in the urine, suggesting almost complete metabolism. Our results support the concept that anti-mycotic activity in the tissues continues after the plasma drug concentration has fallen below a critical level. Our results also support the concept of a change in pharmacokinetics with chronic dosing.

Adult↗
PubMed1987

The effects of substituting frusemide for a thiazide diuretic in the drug regimens of patients with essential hypertension.

Eighteen patients with mild to moderate hypertension on a drug regimen which included a thiazide diuretic had the latter substituted by frusemide for twelve weeks after an initial two-week placebo wash-out period. Blood pressure and heart rate and a number of plasma and urinary biochemical indices were measured. Significant findings included a reduction in standing blood pressure and an elevation of plasma sodium, potassium, chloride, osmolarity, creatinine and alkaline phosphatase levels at the end of the twelve week frusemide phase relative to the values on the thiazide. However the means for all the biochemical indices remained within the normal laboratory reference limits. In the 24-hour urinary studies, no significant findings emerged, apart from an elevated calcium. The foregoing suggest that frusemide is an effective component of an anti-hypertensive drug regimen and that in a dose of 40 mg/day it produces no detectable perturbations of plasma electrolytes. The significance of the enhanced levels of urinary calcium excretion in conjunction with the augmented plasma alkaline phosphatase is unclear.

Adult↗
PubMed1987

Spironolactone as a source of interference in commercial digoxin immunoassays.

Eight commercial digoxin immunoassay methods were tested in 17 subjects taking spironolactone (but not digoxin) to evaluate cross-reactivity from parent drug and/or metabolites. Four of these methods showed significant (up to 1.9 nmol/L) and variable "apparent digoxin" concentrations, despite the absence of digoxin in the drug regimen. The results suggest that clinical laboratories require a knowledge of their method with respect to spironolactone-related cross-reactivity and should exercise caution when interpreting digoxin results where spironolactone is coadministered. Further, the presence of concurrent renal and/or hepatic impairment could delay clearance of spironolactone metabolites (as well as digoxin metabolites and endogenous substances) and further distort a genuine digoxin result.

Adult↗
PubMed1987

Effect of microfiltration on the histamine levels in stored human blood.

Plasma and whole blood histamine levels and white cell counts have been monitored over a 6-week period of storage in standard citrate-phosphate-dextrose supplemented with adenine (CPDA) blood packs, add-back blood packs, and also CPDA and add-back packs which were subjected to a microfiltration process at the time of collection. Our results indicate that the plasma histamine level rises and the white blood count falls progressively with time, the former being most marked after the 3rd week of blood storage. At 6 weeks, there was no significant difference between the plasma and whole blood histamine level, suggesting that the entire complement of histamine in blood was now in plasma. Microfiltration substantially reduced the white cell count in the packs, and this was reflected in a greatly reduced whole blood and (subsequently) plasma histamine concentration.

Blood Preservation↗