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Biomedical subjects

R Bird

Publications and source records attributed to R Bird.

At least 19 recordsLinked to original sources
PubMed1996

Prediction of patient responses to antihypertensive drugs using genetic polymorphisms: investigation of renin-angiotensin system genes.

OBJECTIVE: To investigate whether the M235T polymorphism of the angiotensinogen (AGT) gene and the insertion/deletion (I/D) polymorphism of the angiotensin-1 converting enzyme (ACE) gene predict blood pressure response to different antihypertensive agents. DESIGN: Sixty-three patients with untreated essential hypertension were randomly assigned in a placebo-controlled crossover comparison to atenolol 50 mg once daily, lisinopril 10 mg once daily and nifedipine SR 20 mg twice daily, and the effect on blood pressure was assessed by ambulatory blood pressure monitoring (ABPM). In a further 44 patients, placebo-controlled ABPM data were available after treatment with a single agent (atenolol 50 mg once daily in 16 cases and lisinopril 10mg once daily in 28 cases). The change in systolic and diastolic blood pressure achieved by each agent was analysed for association with genotypes at the AGT and ACE gene loci. METHODS: Polymerase chain reaction (PCR) amplification of genomic DNA from each individual was used to identify the I/D polymorphism of the ACE gene. The M235T polymorphism of the AGT gene was detected by Tth111I digestion of PCR product. RESULTS: There was no significant association between response to any drug and either the AGT M235T or ACE I/D polymorphisms. CONCLUSIONS: The large variability between individuals in the observed blood pressure response to these agents cannot be attributed to the polymorphisms analysed at the ACE and AGT loci.

Alleles↗
PubMed1994

Within-patient correlation between the antihypertensive effects of atenolol, lisinopril and nifedipine.

OBJECTIVE: To investigate whether there are definable subgroups of patients with essential hypertension who respond specifically to particular antihypertensive drugs. DESIGN: Randomized cross-over comparison of the antihypertensive effect of 50 mg atenolol per day, 10 mg lisinopril per day and 20 mg nifedipine retard twice a day. Ambulatory blood pressure monitoring was used to assess the blood pressure level both for recruitment and at the end of each treatment period. The treatment periods lasted 4 weeks and were preceded by 4 weeks of placebo. PATIENTS: Seventy-two untreated hypertensive patients with a mean age of 52 (SD 8.4) years were recruited from six general practices and from the hospital outpatient clinic. Sixty-eight patients completed the trial. MAIN OUTCOME MEASURES: To assess the within-patient correlations among the blood pressure responses to each drug and explore the possible role of simple characteristics, such as the initial blood pressure, plasma renin concentration and age, in identifying the responders to a particular drug. RESULTS: Systolic/diastolic blood pressure fell significantly with each agent (P < 0.001): atenolol reduced it by 16.3 +/- 13.3/9.9 +/- 8.8, lisinopril by 14.8 +/- 15.0/9.4 +/- 9.1 and nifedipine by 11.6 +/- 12.3/6.7 +/- 8.3 mmHg. There was a low degree of correlation between the changes in blood pressure with the three drugs in individual patients. With each drug there was a small percentage (8.9-14.7%) of non-responders. The initial level of systolic blood pressure was weakly correlated with the antihypertensive effect of nifedipine (r = 0.47, P < 0.001) and plasma renin concentration was related to the effect of atenolol (r = 0.32, P < 0.01). Age did not predict the blood pressure response to any agent. CONCLUSIONS: The low level of the correlation between the blood pressure changes with the three drugs suggests that different mechanisms may be involved in the aetiology of essential hypertension. Plasma renin concentration and the initial level of systolic blood pressure contribute only weakly to the identification of responders to the three drugs.

Adolescent↗
PubMed1992

Antihypertensive effect of carvedilol: a preliminary dose-response study.

The blood pressure (BP) lowering effect of low doses of antihypertensive agents is not usually explored because of the difficulty in detecting small changes in BP. Since ambulatory blood pressure monitoring in a cross-over trial design can reliably detect differences of 5 mmHg with less than 20 subjects, we have used this technique to assess the dose-response curve of a new beta-blocker, carvedilol. Twenty subjects were enrolled after diagnostic ambulatory BP monitoring had shown a day-time average diastolic BP of over 90 mmHg. Three doses of carvedilol (6.25, 12.5 and 25 mg daily) and placebo were then given double-blind in random order for periods of 4 weeks each. No period effects were detected. The antihypertensive effect was statistically significant at doses of 12.5 mg and 25 mg daily. There was, however, no evidence that 25 mg/day produced the peak effect. The lowest dose (6.25 mg/day) produced a small fall in both systolic and diastolic BP but neither of these were significant. We conclude that doses of 12.5 and 25 mg carvedilol once a day are adequate for the treatment of hypertension.

Adrenergic beta-Antagonists↗
PubMed1991

Cell cycle, cell size and mitochondrial activity of hybridoma cells during batch cultivation.

Cell cycle, cell size and rhodamine 123 fluorescence in cell populations of two batch cultures were analysed and quantified with a fluorescence-activated cell sorter (FACS). Two cultures derived from either exponential or stationary phase innocula were investigated in order to demonstrate the dependency of the subsequent cell growth on innoculum condition. The results demonstrated that the level of activity of cells in the innoculum culture could have a significant effect on cellular activity during the initial phase of the inoculated culture, as it advances through its growth cycle. Positive correlation was found between the cell size and mitochondrial activity (as measured by rhodamine 123 uptake) with S and G2 fractions as the cell progressed through the cell cycle. The enumeration of the fractions of cell cycle phases has helped in prediction of the changes in cell numbers following perturbation of the culture condition.

Animals↗
PubMed1991

New concepts in monoclonal antibody based radioimmunodiagnosis and radioimmunotherapy of carcinoma.

It is now generally agreed that while numerous monoclonal antibodies (MAbs) have been shown to efficiently target tumors in patients, much still needs to be accomplished to optimize MAb based tumor targeting and the use of MAbs in the therapy of human carcinoma. This article will review some recent studies undertaken in our laboratory in an attempt to generate novel recombinant constructs and test new principles to aid in optimizing MAb based diagnosis and therapy. Three areas will be covered: (a) the analysis of dose fractionation protocols; (b) the generation of recombinant/chimeric (rec/chi) MAbs including the generation of a single chain antigen binding protein (SCA); and (c) the use of recombinant interferons (rec IFNs) to selectively up-regulate tumor antigen expression. Each of these topics has been previously described in detail and appropriate references to these articles are included.

Amino Acid Sequence↗
PubMed1991

Ambulatory blood pressure monitoring: validation of the accuracy and reliability of the TM-2420 according to the AAMI recommendations.

The accuracy of the TM-2420 ambulatory blood pressure monitor (A&D Co, Japan) has been assessed by the indirect method according to the recommendations of the Association for the Advancement of Medical Instrumentation (AAMI). Ninety subjects (43 men and 47 women), aged 19-89 with a range of systolic blood pressures (SBP) of 81-211 mmHg and diastolic blood pressures (DBP) of 32-113 mmHg were studied. The monitor was compared with two observers using the Hawksley random zero sphygomomanometer. The standard deviation of the difference (SDD) between the observers was 3.0 mmHg for SBP and 2.3 mmHg for DBP. The mean differences between observers were -0.31 mmHg for SBP and 0.32 mmHg for DBP (both NS). The average of three readings for each subject recorded by the monitor was compared with the average of the simultaneous readings by the observers. The SDD was 7.2 mmHg for SBP and 5.5 mmHg for DBP (within the recommendations for accuracy). The differences between methods were -0.98 mmHg for SBP and 0.18 mmHg for DBP; these differences were not significant (NS). The monitor was also assessed against direct intra-brachial artery pressure in 12 subjects (36 readings). The mean difference between the monitor and simultaneous individual intra-arterial reading was -9.5 mmHg for SBP (P less than 0.001) and 3.7 mmHg for DBP (P less than 0.001). The SDD's between methods were 12 mmHg for SBP and 5.0 mmHg for DBP. Use of the monitor in general clinical practice in 100 patients was also assessed. The rate of errors was low (6.8%), and the device found to be acceptable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

In vivo tumor targeting of a recombinant single-chain antigen-binding protein.

We describe here the first in vivo targeting of tumors with a single-chain antigen-binding protein. The molecule, which was constructed and expressed in Escherichia coli, is a novel recombinant protein composed of a variable light-chain (VL), amino acid sequence of an immunoglobulin tethered to a variable heavy-chain (VH) sequence by a designed peptide. We show that this protein, derived from the DNA sequence of the variable regions of the antitumor monoclonal antibody B6.2, has the same in vitro antigen-binding properties as the B6.2 Fab' fragment. Comparative pharmacokinetic studies in athymic mice demonstrate much more rapid alpha and beta phases of plasma clearance for the single-chain antigen-binding protein than for the Fab' fragment, as well as an extremely rapid whole-body clearance. Half-life values for alpha and beta phases of single-chain antigen-binding protein clearance were 2.4 minutes and 2.8 hours, respectively, versus 14.8 minutes and 7.5 hours for Fab'. Furthermore, the single-chain antigen-binding protein molecule did not show accumulation in the kidney as did the Fab' molecule or, as previously shown, the F(ab')2 molecule. Despite its rapid clearance, the single-chain antigen-binding protein showed uptake in a human tumor xenograft comparable to that of the Fab' fragment, resulting in tumor to normal tissue ratios comparable to or greater than those obtained with the Fab' fragment. These studies thus demonstrate the in vivo stability of recombinant single-chain antigen-binding proteins and their potential in some diagnostic and therapeutic clinical applications in cancer and other diseases.

Amino Acid Sequence↗
PubMed1990

Lisinopril and enalapril in hypertension: a comparative study using ambulatory monitoring.

Detecting differences in the effect of two antihypertensive agents is bedevilled by the inherent variability of blood pressure itself. Using an ambulatory blood pressure monitoring technique, we compared, in a cross-over design study, the effects of four weeks' treatment with enalapril, 10 mg once daily, to lisinopril, 10 mg once daily, on the blood pressure of 19 patients with mild to moderate hypertension. A significant reduction in blood pressure was shown by both drugs. However, lisinopril produced a greater fall in mean 24 hour systolic pressure than did enalapril (difference; 5.94 (C.I. -0.77 to -11.1) mmHg, P = 0.027). The difference of 3.3 mmHg (C.I. +0.54 to -7.10) in diastolic pressure between the two agents, though in the same direction, was not significant. Plasma renin activity did not predict the responses to either agent. Studying the prevailing information for these two drugs one might expect there to be little difference between them when administered once daily in terms of antihypertensive effect. The explanation for the superiority of lisinopril may lie in the slightly longer pharmacokinetic half-life and possibly in differences in tissue distribution or persistence. The side effects of both drugs were mild and of similar frequency to those recorded during placebo treatment, illustrating the generally well tolerated nature of this class of antihypertensive therapy. The use of ambulatory blood pressure monitoring provides a method that can detect small, but possibly important differences between drugs. In the clinical setting it allows a more thorough assessment of a particular patient's response to therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Serum angiotensin converting enzyme in sarcoidosis--its value in present clinical practice.

Angiotensin converting enzyme (ACE) has a central role in blood pressure homeostasis. It is present in low and fairly constant concentration in the serum and in high concentration in the pulmonary capillary bed. Unusually high serum angiotensin converting enzyme (SACE) activity is present in active sarcoidosis, an observation now confirmed by many investigators. In spite of its lack of specificity as a test for sarcoidosis, SACE provides a good monitor of disease activity which clinicians find useful in the management of patients with sarcoidosis. There continues to be considerable interest in SACE in sarcoidosis and with the recent development of simpler assays, more centres may be expected to offer SACE measurements as a service. In this paper we discuss the indications for estimating SACE in sarcoidosis and its relevance to current clinical practice.

Humans↗
PubMed1988

Expression of CEA, CA125, CA19-9 and human milk fat globule membrane antigen in ovarian tumours.

The expression of five different antigens in ovarian tumours was studied by means of an immunohistochemical test with anti-CEA, HMFG1 and HMFG2, NS19-9 and OC125 antibodies. Considerable variation was noted not only between different histological types and between tumours of one type but also between areas in a single tumour. HMFG1 and HMFG2 were the most reactive of all the antibodies; NS19-9 and OC125 were expressed by different populations of cells. It is concluded that specific combinations of antibodies are more effective both for the monitoring of ovarian cancer as well as for immunodiagnosis and treatment, than any single one used.

Adenocarcinoma↗
PubMed1985

Tumors of the central nervous system studied by computed tomography and ultrasound.

Intraoperative ultrasound (US) was compared to computed tomography (CT) in 41 intracranial and 6 spinal cord tumors. The studies correlated closely except for primary gliomas. Eight of the 22 primary intracranial gliomas (37%), including 1 low-grade and 7 anaplastic tumors, were larger and more extensive on US than on CT. Margins of non-enhanced primary astrocytomas were shown by US but not CT. Four anaplastic tumors (19%) exhibited echogenicity extending beyond the enhanced area. In 4 patients an enhanced lesion contained a lucent center which proved to be echogenic. Low-grade astrocytomas were relatively homogeneous on US, while anaplastic astrocytomas were more inhomogeneous. Cysts could be found in both types of astrocytomas and were often small and multiple. The echo pattern was not helpful in differentiating metastases from primary tumors, although all of them had sharp margins. Sonography of the central nervous system can provide valuable information about tumor morphology and margins.

Astrocytoma↗
PubMed1983

Angiotensin-converting enzyme and its clinical significance--a review.

There have been considerable advances in understanding the metabolic role of the endothelial lining cells of the blood vessels. Angiotensin-converting enzyme activity is concentrated in these cells, especially those lining the pulmonary circulation. The enzyme exerts control over systemic vascular tone indirectly through the powerful pressor effect of angiotensin II. A number of therapeutic agents are now available which directly inhibit converting enzyme activity and thereby effect a reduction in blood pressure. Macrophages are the source of increased angiotensin-converting enzyme activity commonly found in association with active sarcoidosis. A better understanding of this phenomenon may give fresh insight into this puzzling condition. Pulmonary endothelial metabolism is affected by lung injury and it is likely that in this situation changing activities of serum angiotensin converting enzyme may indicate the extent of damage and the response to therapy. The full clinical significance of serum ACE measurements has yet to be established. However, raised activities have been reported in a number of other conditions and diabetes mellitus and hyperthyroidism are of particular current interest. The numerous methods and reference ranges described in the literature for the measurement of serum ACE activity require further assessment, and there is a clear need for an accepted reference method.

Adolescent↗