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Biomedical subjects

M G Scott

Publications and source records attributed to M G Scott.

At least 109 records · Page 6Linked to original sources
PubMed1989

Captopril versus perindopril: a double blind study in essential hypertension.

This was a double blind, parallel group, multicentre comparison of the therapeutic efficacy and acceptability of perindopril and captopril in essential hypertension. After one month of placebo, 165 patients with supine diastolic blood pressure (DBP) between 95 and 125 mmHg were randomised to perindopril 4 mg once daily or captopril 25 mg twice daily orally. The perindopril group (n = 82) had significantly higher pretreatment DBP (105.4 +/- 0.8 mmHg vs 102.3 +/- 0.6 mmHg) but other demographic variables were similar. Assessment was monthly for three months: 'uncontrolled' patients (DBP greater than 90 mmHg) had the dose doubled and then hydrochlorothiazide added. Two of the six withdrawals were attributed to drug side effects and were in the captopril group. There was no significant difference in the number of withdrawals or incidence of side effects between the drugs. The final titrated treatments were similar and monotherapy normalised DBP in 49% of each group. The final 'control' rate was higher with perindopril than captopril: 75% vs 57%, P = 0.016. The overall fall in DBP was greater in the perindopril group: 26.5 +/- 1.9 mmHg vs 18.9 +/- 1.9 mmHg, P = 0.005. The doses of diuretic were similar in the two groups. The DBP of patients who received only monotherapy for three months also fell more in the perindopril group (-17.5 +/- 1.4 mmHg vs -13.9 +/- 1.0 mmHg, P less than 0.01). At the doses studied, perindopril was more effective than captopril in lowering DBP, either as monotherapy or in combination with a diuretic.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Stratus automated creatine kinase-MB assay evaluated: identification and elimination of falsely increased results associated with a high-molecular-mass form of alkaline phosphatase.

We compared the performance of an automated assay of creatine kinase MB isoenzyme (CK-MB) mass (Stratus) with that of a CK-MB enzymatic assay routinely used at our institutions. Both of these assays use the same CK-MB-specific monoclonal antibody to immunocapture CK-MB, thus providing a direct means of comparing a mass assay with an activity assay. Routine CK-MB measurements for 206 samples within the analytical range of both assays revealed the following relationship: Stratus (micrograms/L) = 0.67 (activity U/L) + 0.18 (r = 0.95, Sx.y = 4.45). The linearity, sensitivity, and precision of the Stratus assay were acceptable for routine clinical use. Icteric, lipemic, and hemolyzed samples do not interfere with the assay. During our evaluation we identified a single, clinically significant false-positive sample. Because this patient had alkaline phosphatase values greater than 1100 U/L, we investigated additional samples with increased activities of alkaline phosphatase and found that samples from 12 of 23 patients selected for alkaline phosphatase values greater than 460 U/L produced falsely increased CK-MB values. We determined that a membrane-associated, high-molecular-mass form of alkaline phosphatase was a cause of these falsely increased values and instituted an approach to identify falsely increased Stratus CK-MB values. Samples from 23 of 1933 patients were falsely increased, the increase being clinically significant in samples from 14 of these patients. Consultation with the manufacturer resulted in the successful reformulation of the substrate/wash solution to minimize interferences from high-molecular-mass forms of alkaline phosphatase.

Alkaline Phosphatase↗
PubMed1988

A simple in situ cyanogen bromide cleavage method to obtain internal amino acid sequence of proteins electroblotted to polyvinyldifluoride membranes.

We report a simple method to obtain internal amino acid sequences from larger proteins electroblotted to polyvinyldifluoride membranes. To demonstrate this method, immunoglobulin heavy and light chains are separated by gel electrophoresis and electroblotted to the membrane. The separated chains, immobilized to the membrane, are cleaved in situ by cyanogen bromide and the resulting fragments are subsequently eluted from the membrane. The fragments are separated by gel electrophoresis, electroblotted and subjected to gas-phase microsequence analysis.

Amino Acid Sequence↗
PubMed1988

Monoclonal antibodies specific for non-glycosylated porcine prolactin and for pituitary porcine prolactin.

Glycosylated and non-glycosylated forms of porcine pituitary prolactin were prepared using Concanavalin A Sepharose chromatography. Anti-prolactin monoclonal antibodies were screened for their ability to distinguish these two forms. One monoclonal antibody (17D9) exhibited high affinity binding for the non-glycosylated form of porcine prolactin, but little or no affinity for the glycosylated form. Using this antibody in conjunction with other monoclonals which equally recognize both forms, we developed immunoassays which can be used to determine the amount of the glycosylated vs. non-glycosylated prolactin in serum or other tissue samples.

Animals↗
PubMed1988

A double-blind and cross-over comparison of once daily doxazosin and placebo with steady-state pharmacokinetics in elderly hypertensive patients.

The alpha 1-adrenoceptor antagonist doxazosin has been compared with placebo in 40 elderly hypertensive patients (mean age 71.4 years). At the end of 10 weeks once daily treatment with doxazosin the mean 24-h post-dose changes in standing and supine blood pressure compared with placebo were -6.9/-5.6 mmHg (systolic/diastolic) and -6.2/-5.5 mmHg respectively. The reductions in standing and supine diastolic blood pressures were statistically significant compared with placebo. At the end of treatment steady-state pharmaco-kinetics were evaluated in 18 patients. The plasma elimination half-life during the dose interval in these patients was 16.1 h (range 10.1-27.1 h) and the median time to peak plasma concentration was 3 h (range 1-4 h). One patient was withdrawn because of adverse effects (headache, weakness, and sweating) during doxazosin treatment. Once daily doxazosin reduced diastolic blood pressure and was well tolerated in these elderly hypertensive patients.

Aged↗
PubMed1988

Human IgG subclasses and their relation to carbohydrate antigen immunocompetence.

Human IgG responses to carbohydrate antigens, such as those found on many infectious bacteria, are primarily restricted to the IgG2 subclass. This phenomenon, known as isotype restriction, has led us and others to examine the prevalence of IgG2 deficiency among infection-prone individuals. IgG2 deficiency (below 3 SD of the age group mean) is fairly common among patients suffering from chronic bacterial infections and suggests the utility of IgG subclass measurements in evaluating such patients. However, we also describe exceptions to isotype restriction in human responses to carbohydrate antigens. Furthermore, we describe individuals who, while responding very poorly to carbohydrate antigens, have normal IgG2 levels for their age group. These findings indicate the complexity of IgG subclass regulation and suggest that evaluation of infection-prone individuals should include measurements of both IgG subclasses and antibodies to carbohydrate antigens such as phosphocholine.

Antigens↗
PubMed1987

Human antibodies to phosphocholine. IgG anti-PC antibodies express restricted numbers of V and C regions.

We examined the IgG subclass composition and isoelectric focusing (IEF) spectrotype pattern of naturally occurring human IgG antibodies that bind phosphocholine (PC) and found direct evidence for restricted expression of both V and C regions among these antibodies. In most individuals, the isotype of these IgG anti-PC antibodies was primarily IgG2. However, serum from some individuals contained significant amounts of IgG1 and IgG3 anti-PC antibodies. We also found that in individual sera, anti-PC antibodies are pauciclonal, as demonstrated by restricted spectrotypic patterns of the anti-PC antibodies. The IEF pattern of these antibodies were for the most part unique for each individual. In some sera, certain anti-PC antibodies with isoelectric points of basic pH bound PC conjugated to bovine serum albumin (PC-BSA) but did not bind pneumococcal C-carbohydrate bearing PC determinants. In two individuals, we found that the spectrotypes that bound only PC-BSA were of the IgG1 subclass. Taken together, these findings demonstrate that within individual sera, human antibodies to PC are quite restricted in both V and C region expression, and furthermore, these V and C regions of human Ig may not randomly associate.

Autoantibodies↗
PubMed1987

Subclass distribution of human antibodies to Haemophilus influenzae type b capsular polysaccharide.

The polysaccharide (PS) capsule of Haemophilus influenzae type b (Hib) is a "simple" antigen, polyribosylribitolphosphate. Although similar carbohydrate antigens have been reported to elicit IgG antibodies relatively restricted to the IgG2 subclass in man, we report here that Hib PS elicits substantial quantities of both IgG1 and IgG2 serum antibodies in most individuals. Because the determination of IgG subclass distribution can be technically difficult, we used four different approaches to establish our finding. First, we used an IgG subclass-specific, antigen-specific "sandwich assay." Second, we measured IgG subclasses of purified antibodies to Hib PS. Third, we showed that significant amounts of IgG anti-PS can be absorbed with a monoclonal anti-IgG1 affinity column. Fourth, we showed that IgG1 and IgG2 fractions of immune sera have clonally restricted anti-Hib PS antibodies that are easily distinguishable by their isoelectric points. The data indicate that both IgG1 and IgG2 contribute substantially to the IgG antibody response of most adults to immunization with Hib PS.

Adult↗
PubMed1987

The assessment in man of the beta-adrenoceptor blocking activity and cardioselectivity of H-I 42 BS, a long acting beta-adrenoceptor blocking drug.

The pharmacokinetic and pharmacodynamic effects of the beta-adrenoceptor antagonist H-I 42 BS were examined in healthy subjects. In an open dose ranging study, H-I 42 BS 50, 100, 200 and 400 mg were given as single oral doses to four subjects. H-I 42 BS 400 mg caused maximum reduction in exercise heart rate (20.4 +/- 1.0%--mean +/- s.d.) at 4 h and still reduced exercise heart rate at 96 h (18.4 +/- 7.2%). Seven subjects received in double-blind, randomised order, single oral doses of H-I 42 BS 50, 100 and 200 mg, atenolol 50 and 100 mg and placebo. H-I 42 BS 400 mg was given in a single blind manner as the last dose of the study. Both H-I 42 BS and atenolol reduced supine and standing heart rate and systolic blood pressure (P less than 0.05) although atenolol had the more marked effect. The maximum percent reduction of exercise heart rate after H-I 42 BS 50 mg was 10.9 +/- 7.1%, after 100 mg was 18.7 +/- 5.8%, after 200 mg was 20.6 +/- 6.4% and after 400 mg was 21.9 +/- 8.2%. H-I 42 BS 400 mg still caused 11.0 +/- 3.5% reduction at 168 h. Atenolol 50 mg caused maximum percent reduction of exercise heart rate of 26.0 +/- 6.0% but did not reduce exercise heart rate after 24 h. The mean peak plasma concentrations for all doses of H-I 42 BS occurred at 5.1 +/- 1.5 h. The plasma elimination half-life was 47.6 +/- 8.1 h. There was a linear correlation between the dose and AUC0-infinity (r = 0.97). The cardioselectivity of H-I 42 BS and atenolol was compared. Six subjects received in double-blind random order H-I 42 BS 100 and 400 mg, atenolol 50 mg and placebo. After each dose, graded infusions of isoprenaline were given until the heart rate increased by 50 beats min-1. Dose-response curves for heart rate, diastolic blood pressure, forearm blood flow and finger tremor were constructed. There was no difference in the dose-response curves for forearm blood flow or finger tremor after H-I 42 BS 400 mg or atenolol 50 mg. Atenolol 50 mg caused more attenuation (P less than 0.01) of the diastolic blood pressure response. These results indicate that H-I 42 BS is a cardioselective beta-adrenoceptor antagonist with a long duration of action in man.

Adrenergic beta-Antagonists↗
PubMed1987

Specific immunoradiometric assay of insulin-like growth factor I with use of monoclonal antibodies.

We identified two monoclonal antibodies that bind spatially distinct epitopes on insulin-like growth factor I (IGF-I). Using these two antibodies, we developed a simultaneous, two-site immunoradiometric assay (IRMA) specific for IGF-I. This IRMA has no detectable cross reactivity with insulin, proinsulin, prolactin, or somatotropin, and less than 2% crossreactivity with IGF-II. The assay response varies linearly with IGF-I concentrations of 0-800 micrograms/L in serum; the detection limit is about 10 micrograms/L. A comparison of 26 IGF-I serum values from the IRMA and from a previously reported IGF-I specific RIA gave a correlation coefficient of 0.96 with no substantial bias (slope = 1.10). IGF-I values for serum, as an aid in assessing growth abnormalities, are easily (only three pipetting steps) obtained in less than 4 h.

Animals↗
PubMed1986

Patterns of contraceptive pill taking in an inner city practice.

A total of 161 patients completed a questionnaire about their pattern of taking the oral contraceptive pill. Only 28% (45) of patients were taking the pill according to the manufacturer's instructions, and in the event of the pill being missed only 26% of patients would use a sheath. A tenth of the patients believed that amenorrhoea always indicated pregnancy, but 35% believed that amenorrhoea was harmful to the body. This group did not differ in their pill taking from the remaining 65% of patients.

Contraceptives, Oral↗
PubMed1986

Turbidimetric assay of IgG with use of single monoclonal antibodies.

We describe a turbidimetric assay for quantifying total immunoglobulin G (IgG) in serum with use of a single monoclonal antibody. The reaction, monitored by a centrifugal analyzer, is technically simple, rapid, and precise. Buffer of low ionic strength and polyethylene glycol are required for formation of detectable antibody-antigen complexes. We measured IgG concentrations in 49 polyclonal sera (Group 1) and 84 sera containing monoclonal IgG (Group 2) in assays in which we used either of two anti-IgG monoclonal antibodies (HG6 or HG8). Results compared well with those obtained with a nephelometric assay involving polyclonal antiserum, except for sera from four persons of Group 2 whose immunoglobulins were not detected by antibody HG6. HG6 bound IgG from these four sera in a solid-phase binding assay. HG6 and HG8 recognize epitopes on the Fab and Fc regions of IgG, respectively, and they do not compete for binding to the whole molecule. However, use of the two monoclonal antibodies combined failed to improve the sensitivity or range of the assay. We conclude that light-scattering assays of IgG can be validly performed with a single monoclonal antibody.

Animals↗
PubMed1986

Spontaneous secretion of IgG subclasses by intestinal mononuclear cells: differences between ulcerative colitis, Crohn's disease, and controls.

Spontaneous IgG and IgG subclass secretion patterns by isolated intestinal mononuclear cells (MNC) from control and inflammatory bowel disease (IBD) specimens were examined. Intestinal MNC from IBD specimens spontaneously secreted more total IgG than did control intestinal MNC. This increased spontaneous IgG secretion by ulcerative colitis intestinal MNC was primarily due to markedly increased production of IgG1. Slightly increased secretion of IgG3, but not IgG2 by ulcerative colitis intestinal MNC was present when compared with control and Crohn's disease intestinal MNC. In contrast, Crohn's disease intestinal MNC exhibited increased spontaneous secretion of all the IgG subclasses examined, with IgG2 being predominant.

Colitis, Ulcerative↗
PubMed1985

Correlation of serum immunoglobulin subclass concentrations with antibody responses of children to immunization with Haemophilus influenzae type b polysaccharide-pertussis vaccine.

Children less than 24 months of age respond poorly to immunization with the capsular polysaccharide of Haemophilus influenzae type b. Because human antibodies to polysaccharide antigens are relatively restricted to IgG2, a late-maturing subclass, we examined the relationship between serum subclass concentrations and anticapsular antibody responses of 41 healthy children, 9 to 38 months of age, following immunization with type b polysaccharide mixed with pertussis vaccine. Both total and IgG anticapsular antibody responses correlated significantly with preimmune serum concentrations of IgG2 but not with those if IgG1. This correlation was age dependent, however, and after the effect of age was removed by partial correlation, the correlation between anticapsular antibody responses and serum IgG2 concentrations was no longer significant. These findings indicate that the ability to respond to this vaccine coincides with maturation of the ability to secrete immunoglobulin of the IgG2 subclass; however, individual variation in IgG2 that is independent of age does not correlate with antibody response to the type b polysaccharide.

Age Factors↗
PubMed1985

Relation of age, race, and allotype to immunoglobulin subclass concentrations.

Concentrations of IgG1, IgG2, and total IgG were measured by a solid phase radioimmunoassay in sera from 36 healthy adults and 114 healthy children. As expected, IgG2 and total IgG had a positive correlation with age in children. In addition to age, several other factors were associated with significant differences in serum subclass concentrations. Female children had higher concentrations of IgG1 than males, and black subjects had significantly higher concentrations of IgG1, IgG2, and total IgG than whites. Although Km(1) and Gm(23) immunoglobulin allotypes had no relation to subclass concentrations when tested as single factors, the Km(1) allotype interacted significantly with race so that Km(1)-positive black children had higher IgG2 concentrations than other subjects. Our findings may explain, in part, recent observations of an association of the Km(1) allotype with altered immune responses of blacks to certain vaccines containing bacterial polysaccharides. In addition, our data indicate the need to control factors such as sex, race, and allotype in studies of subclass concentrations or immune responses.

Adolescent↗