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Biomedical subjects

C J Pearce

Publications and source records attributed to C J Pearce.

34 records · Page 2Linked to original sources
PubMed1984

Total and free thyroid hormone concentrations in patients receiving maintenance replacement treatment with thyroxine.

Total and free serum concentrations of thyroxine and triiodothyronine were measured in 122 subjects with hypothyroidism who were clinically well while receiving conventional replacement treatment with thyroxine. In a third of patients concentrations of total and free thyroxine were raised, often considerably; nevertheless concentrations of total and free triiodothyronine were usually normal. Though significant correlations were obtained between total triiodothyronine concentrations and total thyroxine concentrations (p less than 0.001) and between the triiodothyronine concentrations and free thyroxine concentrations (p less than 0.001) the slope of the line of the regression equation describing these correlations was small, hence large increases in both total and free thyroxine concentrations were accompanied by only modest increases in total and free triiodothyronine concentrations. The presence of total or free thyroxine concentrations above normal in patients taking thyroxine therefore are not necessarily of clinical consequence. In the assessment of adequacy of replacement treatment with thyroxine the most logical combination of in vitro thyroid function test results may be a normal thyrotrophin concentration and normal free triiodothyronine concentration.

Adult↗
PubMed1984

Total serum thyroxine and triiodothyronine; a comparison between Graves' disease and hyperthyroxinaemia due to thyroxine replacement.

Serum concentrations of total thyroxine (T4) and total triiodothyronine (T3) were measured in a group of patients (n = 113) presenting with untreated hyperthyroidism due to Graves' disease and in subjects receiving oral T4 replacement (n = 93) in whom the total T4 concentration was supraphysiological (greater than 150 nmol/l). The mean total T4 concentration in the hyperthyroid group was 226 nmol/l, SD 59, range 151-420, and the mean total T3 concentration was 6.8 nmol/l, SD 2.73, range 3.1-17.5. For the group receiving T4 the mean total T4 concentration was 175 nmol/l, SD 25, range 150-258, and the mean total T3 concentration was 2.66 nmol/l, SD 0.45, range 1.7-4.2. In the hyperthyroid group a highly significant linear correlation was found between total T4 and total T3, T3 = 0.0354 T4 - 1.21, r = 0.761, P much less than 0.001, while in the patients taking T4 this correlation was less close, T3 = 0.0073 T4 + 1.39, r = 0.398, P much less than 0.001. The two groups are readily distinguished by expressing total T4 as a molar ratio of total T3. In the hyperthyroid group the mean T4:T3 ratio was 35.6, SD 7.8, range 19.9-56.1, compared to the patients on T4 where the mean T4:T3 ratio was 67.0, SD 11.7, range 44.3-114 (t = 22.5, P much less than 0.0001). An arbitrarily chosen value of 50 for the T4:T3 ratio affords a simple and convenient means of distinguishing the two categories: in only 3 patients with Graves' disease (2.6%) was the ratio above this, and it was below in only 5 patients (5.4%) taking T4.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1983

Free thyroid hormone concentrations in subjects with various abnormalities of binding proteins: experience with amerlex free-T4 and free-T3 assays.

Free thyroid hormone concentrations measured by Amerlex assays were studied in subjects with inherited disorders of thyroxine-binding globulin (TBG) synthesis, variant albumins with a high avidity for T4, and iodothyronine-binding autoantibodies. Free T4 (fT4) and free T3 (fT3) levels were normal in euthyroid subjects with TBG deficiency and excess. Free T3 concentration was in the low normal range in subjects having a variant albumin but fT4 (Amerlex) was erroneously elevated because of the enhanced affinity of the 125I-T4 analogue employed in the assay for the abnormal albumin. The 125I-T3 analogue used in the fT3 assay does not bind more strongly to this variant albumin than to normal albumin. Amerlex assays for fT4 and fT3 in patients with iodothyronine-binding autoantibodies to thyroglobulin give variable results according to the specificity of the autoantibodies: non-specific antibodies cause extraordinarily high values even in hypothyroid patients; fT3 measurements may be appropriate in patients with T4-specific antibodies and even in some with T3-specific antibodies. The presence of such antibodies should be suspected if the results of Amerlex assays for fT4 and fT3 are discordant or are inconsistent with the clinical picture or TSH levels.

Autoantibodies↗
PubMed1981

Autoantibodies to thyroglobulin cross reacting with iodothyronines.

Serum thyroxine was consistently unmeasurable by radioimmunoassay in an elderly patient with myxoedema after successful treatment with oral thyroxine. Abnormal binding of thyroxine was suspected and shown to be due to the presence in serum of antibodies of the IgG variety. The characteristics of these antibodies with respect to their binding of thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and human thyroglobulin (Tg) were systematically studied. Three preparations of Tg, and t4, T3 and rT3 were examined for their ability to compete with 125I-Tg, 125I-T4, 125I-T3 and 125I-rT3 for binding to the antibodies. For each tracer used the order of competitive efficiency was Tg greater than T4 greater than T3 greater than rT3. This provides for the first time direct evidence that iodothyronine reacting antibodies occurring in man are generated against Tg. All three iodothyronines were able to inhibit tracer binding of labelled iodothyronines completely, the order of effectiveness being T4 greater than T3 greater than rT3, suggesting antibodies with one type of binding site and that these were probably raised against a Tg sequence incorporating T4, although there was some evidence for the existence of a minor subpopulation of antibodies with higher specificity for T3. Complete displacement of labelled Tg by cold iodothyronines, however, was not possible. The experimental evidence suggests two classes of Tg antibodies, 70% of which were directed towards the T4 containing region, and 30% directed against other part(s) of the Tg molecule. Despite the presence of such Tg antibodies conventional haemagglutination tests of the patient's serum for Tg antibodies were negative.

Aged↗
PubMed1980

A comparison of three methods for quantitation of variant hemoglobin fractions.

Three methods, cellulose acetate electrophoresis-densitometry (CAE-D), cellulose acetate electrophoresis-elution (CAE-E), and microchromatography (MGC), were evaluated to determine the best method for quantitating variant hemoglobins. Evaluations were performed in two phases. In Phase I samples of known hemoglobins were obtained and Hb S and/or Hb C were quantitated by the three methods to evaluate agreement of results. In Phase II reference samples were prepared. The Hb S concentrations from each method were compared to the reference value to determine the effect of varying concentrations of Hb S on the methods. Cellulose acetate electrophoresis-densitometry proved to be the best method for quantitating variant hemoglobins in which the concentration was greater than 35 percent. Microchromatography was shown to be the best method when Hb S was approximately 30 percent. Either the microchromatography or the cellulose acetate electrophoresis-elution method proved to be a good method for quantitating approximately 25 percent Hb S.

Anemia, Sickle Cell↗
PubMed1978

Sub-unit assembly in the biosynthesis of neomycin. The synthesis of 5-O-beta-D-ribofuranosyl and 4-O-beta-D-ribofuranosyl-2,6-dideoxystreptamines.

The preparation of the deoxy- analogues of two pseudodisaccharide fragments of neomycin, 5-O-beta-D-ribofuranosyl-2,6-dideoxy-streptamine and 6-deoxyneamine is described. When added to the growth medium of a deoxystreptamine-idiotroph of Streptomyces rimosus forma paromomycinus only the latter was incorporated into antibiotic, suggesting an obligatory order for the assembly of sub-units. 4-O-beta-D-Ribofuranosyl-2,6-dideoxystreptamine was also prepared. When added to the growth medium of a deoxystreptamine-idiotroph of Streptomyces fradiae it was converted into the 6-deoxyneomycins, apparently after hydrolysis to 2,6-dideoxystreptamine. The structure of the protected derivatives of the ribofuranosyl 2,6-dideoxystreptamines, potentially useful intermediates for the synthesis of novel antibiotics, was shown by using 15C NMR spectroscopy.

Hexosamines↗
PubMed1976

The role of the pseudo-disaccharide neamine as an intermediate in the biosynthesis of neomycin.

By using wild-type and deoxystreptamine-negative mutants of Streptomyces fradiae grown in media containing [6(-3)H]glucose or [U-14C]glucose, and by subsequent hydrolysis of the labelled neomycin produced, neamines labelled with 3H in both rings I and II, but with 14C in ring I only, were prepared. A mixture of these two forms of neamine was converted by deoxystreptamine-negative Streptomyces rimosus forma paromomycinus into neomycin (not paromomycin) with a 30% yield. The3H: 14C ratio in this neomycin was the same as the measured in neamine produced by hydrolysis of the neomycin, and in unused neamine reisolated from the incubation medium. The 3H:14C ratio in the neomycin was not affected by the presence of unlabelled deoxystreptamine during the incubation. The radioactivity in the neomycin was associated with rings I and II only. It is concluded that the added neamine is incorporated into antibiotic intact, without initial hydrolysis, and that the probable first step in the subunit assembly of neomycin is the formation of neamine.

Disaccharides↗
PubMedDate not supplied

The biosynthetic origins of rebeccamycin.

Experimental evidence is presented to demonstrate that the antitumor-antibiotic rebeccamycin is biosynthesized by Saccharothrix aerocolonigenes from one unit of glucose, one of methionine, and two of tryptophan. Evidence is presented that suggests that the alpha-amino group of neither tryptophan unit provides the nitrogen of the phthalimide system.

Aminoglycosides↗
PubMedDate not supplied

Labetalol and other agents that block both alpha- and beta-adrenergic receptors.

BACKGROUND: Labetalol, a compound that blocks both alpha- and beta-adrenergic receptors, is the only drug of its class currently available in the United States. OBJECTIVE: To review the pharmacology of labetalol and related compounds. SUMMARY: Unlike "pure" beta blockers, labetalol maintains cardiac output, reduces total peripheral resistance, and does not decrease peripheral blood flow. It has been used to treat hypertension of all degrees of severity and may be especially useful in black patients, elderly patients, patients with renal disease, and in pregnancy. It can be used in conditions that produce catecholamine crises, such as pheochromocytoma, clonidine withdrawal, and cocaine overdose. Its hemodynamic profile is attractive for use in myocardial ischemia. The parenteral form is useful in situations where blood pressure must be lowered quickly. The major side effect is orthostatic hypotension, and hepatotoxicity has been reported. CONCLUSIONS: Labetalol has several advantages over pure beta-blocking drugs and offers an alternative in managing hypertension that is difficult to control.

Humans↗