PubMed Health⌕ Search

Biomedical subjects

C G Thomas

Publications and source records attributed to C G Thomas.

At least 19 recordsLinked to original sources
PubMed1992

Selective determination, in plasma, of artemether and its major metabolite, dihydroartemisinin, by high-performance liquid chromatography with ultraviolet detection.

A sensitive and selective reversed-phase high-performance liquid chromatographic method for the determination of artemether and its major metabolite dihydroartemisinin in plasma has been developed. It involves extraction of plasma with dichloromethane, solid-phase separation of the two analytes and acid decomposition prior to chromatography on a C18 Spherisorb column with a mobile phase of acetonitrile-water (50:50, v/v). Run time is 30 min. The assay satisfies all of the criteria required for use in clinical pharmacokinetic studies.

Artemether↗
PubMed1991

Efficacy of quinine for falciparum malaria according to previous chloroquine exposure.

Chloroquine has been reported to antagonise the anti-parasitic action of quinine against Plasmodium falciparum in vitro. We looked for evidence of any such antagonism in vivo. In 123 Malawian children with cerebral malaria treated with parenteral quinine, the likelihood of survival and the rate of recovery were much the same in patients who had taken chloroquine and those who had not. In these circumstances we found no evidence of chloroquine/quinine antagonism.

Animals↗
PubMed1990

The effects of temperature on the viscoelastic properties of the rabbit medial collateral ligament.

There are disparate views on the effects of temperature on the mechanical properties of ligaments and tendons. We attempted to resolve the inconsistencies by testing the medial collateral ligaments of twelve, three-month old New Zealand white rabbits in both elastic-dominated and viscous-dominated tests between 25 degrees C and 55 degrees C. We found that in elastic-dominated monotonic loading, the loading portions of the load-extension curves were mathematically similar. Differences could be accounted for through a base-line shift of the origin caused by additional relaxation and thermal contraction/expansion of the apparatus and specimen. In tests where the viscous component of behavior was manifest, we found results similar to those of other investigators. Thus we conclude that in assessing the effects of temperature on the mechanical properties of tissues it is important to account for both temperature and initial positions of the apparatus and specimen, and to consider the effects of both relaxation and thermal contraction/expansion.

Animals↗
PubMed1990

Pediatric thyroid cancer.

A review was undertaken of the clinical, gross, and microscopic features of thyroid carcinoma in all patients younger than 21 years of age seen at North Carolina Memorial Hospital from 1952 to 1987 (N = 32). These patients had papillary carcinoma, well-differentiated follicular carcinoma with Hürthle cell change, medullary carcinoma, and an unclassifiable aggressive malignancy. In spite of the presence of lymph node metastases at diagnosis in more half the patients with papillary carcinoma, the prognosis of pediatric papillary thyroid carcinoma appears to be excellent with treatment by surgical debulking and hormonal thyroid suppression. Flow cytometric study of 26 cases showed tumor aneuploidy in 8 of 21 papillary carcinomas and 2 of 3 follicular carcinomas. Aneuploidy did not, however, correlate with clinical outcome in this group of pediatric patients, who were followed for 1 to 29 years. Analysis of multiple tissue blocks of tumor does appear to increase the probability of identifying aneuploid populations.

Adenocarcinoma↗
PubMed1989

Twenty-three-year follow-up of separated ischiopagus tetrapus conjoined twins.

This paper presents a 23-year follow-up of the separation of ischiopagus tetrapus conjoined twins reported in Annals of Surgery in December 1966. One twin died of septicemia at age 2 years after bilateral pelvic osteotomies for the treatment of her marked pelvic diastasis. The surviving twin has done reasonably well, and her most significant problem is related to her musculoskeletal system. She has an increasing T7-10, L-1 apex right congenital scoliosis with wedged vertebra at T-10, as well as marked pubic diastasis and bilateral subluxation of her hips. This has resulted in a somewhat aberrant physical appearance and a "waddling" gait. Her colostomy functions well and she has normal renal and bladder function. This patient's history illustrates that many problems remain after successful separation of conjoined twins. However these problems are manageable and do not preclude the possibility that such a patient may be a productive member of society.

Adult↗
PubMed1989

In vitro NMR evaluation of human thyroid lesions.

In vitro analysis of spin-lattice relaxation times (T1), water self-diffusion coefficients (DH2O), and proton NMR spectroscopy were performed in a study of 88 patients with thyroid lesions in order to determine the usefulness of these parameters in the differentiation of benign and malignant tissues. Thyroid tissue sample proton NMR spectral patterns were examined at 360 MHz. Proton NMR spectra were different for normal thyroid tissues, benign, and cancerous lesions. Significantly prolonged T1 (0.5T) and decreased DH2O were found in cancerous thyroid lesions relative to normal thyroid tissues. Considerable overlap was found, however, in comparing T1 and DH2O values for benign and malignant thyroid lesions. This study suggests that proton NMR spectroscopy may be more useful than T1 and DH2O in differentiating benign and malignant thyroid lesions.

Adenoma↗
PubMed1988

Effects of 2'-deoxy-5-fluorouridine on regenerating liver following partial hepatectomy in the rat.

UNLABELLED: This study evaluated the effect of 2'-deoxy-5-fluorouridine (FUDR) on the regeneration of the liver following partial (68%) hepatectomy in the rat. Male Sprague-Dawley rats weighing between 190 and 240 g underwent partial hepatectomy under ether anesthesia. Twelve hours postoperatively rats received intraperitoneal injections of 2'-deoxy-5-fluorouridine or 0.9% NaCl solution as follows: Group I, 0.9% NaCl solution (n = 49); Group II, 89 mg 2'-deoxy-5-fluorouridine/kg of body weight (n = 25); and Group III, 178 mg 2'-deoxy-5-fluorouridine/kg of body weight (n = 24). Sham groups underwent celiotomy and liver palpation followed by 0.9% NaCl solution injections (n = 5) or low dose 2'-deoxy-5-fluorouridine (n = 5) and high dose 2'-deoxy-5-fluorouridine (n = 5). The regenerative ability of the liver was evaluated by weight and deoxyribonucleic acid synthesis in the liver remnant. RESULT: Both low and high dose 2'-deoxy-5-fluorouridine delayed the peak of deoxyribonucleic acid synthesis from 36 to 72 hr as compared to control animals which had maximal synthesis at 25 to 36 hr postoperatively (P less than 0.01). Weight of the liver remnants demonstrated a similar pattern. CONCLUSION: High doses of 2'-deoxy-5-fluorouridine administered intraperitoneally delay, but do not inhibit, liver regeneration following partial (68%) hepatectomy as reflected by DNA synthesis and weight of the remnant.

Analysis of Variance↗
PubMed1987

Alpha 1-adrenergic regulation of TSH-stimulated cyclic AMP accumulation in rat thyroid cells.

Addition of epinephrine to cultured FRTL-5 rat thyroid cells led to a concentration-dependent reduction of TSH- and forskolin-stimulated cAMP accumulation. Clonidine, which preferentially activates the alpha 2-adrenoreceptor, had no effect on cAMP levels. The reduction of cAMP levels by epinephrine was selectively blocked by prazosin, an alpha 1-adrenoreceptor antagonist, but not by yohimbine, an alpha 2-adrenoreceptor antagonist. Pretreatment of FRTL-5 cells with pertussis toxin failed to abolish the inhibitory effect of epinephrine on cAMP accumulation. The bioactivity of the pertussis toxin preparation in this cell line was verified by its ability to ADP-ribosylate the alpha-subunit of the inhibitory guanine nucleotide regulatory protein, Ni, as well as its ability to abolish the inhibitory effect of N6-[L-2-phenylisopropyl]-adenosine on TSH-stimulated cAMP formation. The inhibitory effect of epinephrine on cAMP levels was dependent on Ca2+ and was reversed by 3-isobutyl-1-methylxanthine. Taken together, these results suggest that epinephrine reduces cAMP levels via alpha 1-adrenoreceptors. The failure of pertussis toxin to abolish this alpha-adrenergic effect is consistent with the conclusion that epinephrine-induced attenuation of cAMP accumulation occurs through activation of a Ca2+-calmodulin-sensitive phosphodiesterase and does not involve Ni or Ni-like proteins.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Further studies on the covalent crosslinking of thyrotropin to its receptor: evidence that both the alpha and beta subunits of thyrotropin are crosslinked to the receptor.

Highly purified alpha- and beta-subunits of thyrotropin were individually radioiodinated and, subsequently, recombined with their unlabeled complementary subunits. This procedure resulted in the formation of [125I]thyrotropin(TSH) hybrid molecules which were labeled on only one hormone subunit. Characterization of the binding properties of these two hybrid molecules demonstrated that both yielded nonlinear Scatchard plots with Kd and Bmax values similar to those obtained with radioiodinated native TSH and that both were capable of interaction with the high- and low-affinity binding components of the TSH receptor. The recombined [125I]TSH molecules were then crosslinked to the TSH receptor using disuccinimidyl suberate. Following electrophoresis and autoradiography, two labeled TSH-receptor complexes with Mr of 68,000 and 80,000 were observed. These two complexes exhibited hormone specificity and electrophoretic mobility identical to those previously observed using native [125I]TSH. Crosslinking with increasing concentrations of disuccinimidyl suberate suggested that the formation of the 68,000 and 80,000 complexes was sequential with the 68,000 appearing before the 80,000. Furthermore, the two bands were labeled regardless of which TSH subunit of the hybrid TSH was radioiodinated. These data strongly suggest that the 68,000 and 80,000 TSH-receptor complexes are the result of crosslinking to the TSH alpha-beta dimer and not to one subunit in the case of the 68,000 complex and to the TSH alpha-beta dimer in the case of the 80,000 complex, as had been hypothesized previously.

Animals↗
PubMed1987

Stimulation of inositol phosphate formation in FRTL-5 rat thyroid cells by catecholamines and its relationship to changes in 45Ca2+ efflux and cyclic AMP accumulation.

Catecholamines specifically stimulated the rapid formation of inositol phosphates, bisphosphates and trisphosphates in a concentration-dependent manner in FRTL-5 thyroid cells. Further analysis by high performance liquid chromatography revealed the presence of two isomers of inositol trisphosphate, 1,4,5- and 1,3,4-trisphosphate, suggesting that the 1,4,5-trisphosphate of inositol is further metabolized to the 1,3,4-trisphosphate isomer. The alpha 1-adrenoreceptor antagonist, prazosin, inhibited the effects of epinephrine, while the alpha 2-adrenoreceptor antagonist, yohimbine, was without effect. Treatment of FRTL-5 cells with pertussis toxin (to inhibit Ni) did not abolish the epinephrine effect on inositol trisphosphate formation. Carbachol, N6-[L-2-phenylisopropyl]-adenosine and forskolin were without effect on phosphoinositide metabolism. Both epinephrine and the calcium ionophore A23187 stimulated 45Ca2+ efflux from 45Ca2+-loaded FRTL-5 cells. The time-course of the epinephrine effect indicates that inositol 1,4,5-trisphosphate formation (t1/2 approximately 1 s) precedes both the efflux of 45Ca2+ (t1/2 approximately 30 s) as well as the reduction of cyclic AMP levels (t1/2 approximately 90 s) in response to epinephrine. These results strongly suggest that inositol 1,4,5-trisphosphate has the appropriate properties to act as a second messenger by which alpha 1-adrenergic hormones, through mobilization of intracellular Ca2+ and activation of cyclic AMP phosphodiesterase, reduce cyclic AMP levels in FRTL-5 cells.

Animals↗
PubMed1987

Current management of the patient with autonomously functioning nodular goiter.

Autonomously functioning thyroid nodules (AFTNs) are presumably independent of TSH for growth and function and appear "hot" on scintiscan because they selectively concentrate radionuclide to a greater extent than the remaining thyroid gland, which is controlled by the normal TH-TSH feedback mechanism. Such autonomously functioning tissue may occur in "patchy" areas, as a solitary nodule, or as multiple nodules (classic Plummer's disease), with the mass of hyperfunctioning tissue and the related secretion of thyroid hormones determining whether the patient is euthyroid or hyperthyroid. Important diagnostic tests include a 99mTc thyroid scan, T4 RIA, T3 uptake, FTI, TSH RIA, and occasionally T3 RIA ("T3 thyrotoxicosis"). Solitary autonomous nodules in adult patients characteristically progress slowly over many years, with toxicity rarely developing in nodules less than 2.5 cm in diameter and occurring primarily in nodules 3 cm or larger and in older patients. The decision to treat a solitary nodule depends upon the size and degree of function of the nodule and the patient's age. Surgery and radioactive iodine are effective therapies. Hyperfunctioning thyroid nodules in children and adolescents (under age 18) have a more rapidly progressive course than those in adults and should be treated by thyroid lobectomy at the time of diagnosis. Subtotal thyroidectomy is the preferred treatment for most patients with toxic multinodular goiter, because it achieves prompt control of the hyperthyroidism and removes the goiter. Radioiodine therapy and long-term antithyroid drug therapy are alternative forms of treatment for patients who are poor surgical risks or who develop recurrent hyperthyroidism following thyroid surgery.

Adenoma↗
PubMed1987

Evaluation and redesign of a system to rank applicants for surgical residencies.

The present paper is a report of the evaluation and subsequent revision of a selection system for surgical house officers. The authors conducted a series of studies to determine the content validity, concurrent validity, and predictive validity of the system used by the surgery department prior to 1982. The results did not support the validity of that ranking system. In particular, the system was found not to evaluate candidates on criteria considered important by the faculty. Based on these findings, the department adopted a new ranking system organized around a multimethod-multitrait matrix (that is, using multiple methods to assess multiple traits) and based on a new set of traits that had been identified as important in the earlier validity studies. The new system has been used for five years, since 1982, with acceptance and favorable evaluation by the faculty. During that period, the median and mean rank of candidates who were matched to the residency program improved.

Educational Measurement↗
PubMed1987

Characterization of the subunit structure of the thyrotropin receptor in the FRTL-5 rat thyroid cell line.

Radioiodinated TSH was covalently cross-linked to monolayers of FRTL-5 rat thyroid cells using the homobifunctional cross-linking agent disuccinimidyl suberate. Analysis of the cross-linked samples by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions demonstrated the presence of three specifically labeled complexes with apparent mol wt of 68,000, 85,000, and 145,000, in addition to the TSH alpha-beta dimer and its alpha- and beta-subunits. When bound [125I]iodo-TSH was cross-linked with increasing concentrations of disuccinimidyl suberate, the formation of the 68,000 and 85,000 mol wt complexes was sequential, with the 68,000 complex appearing first. These two complexes were also observed after labeling with radioiodinated TSH hybrid molecules (alpha-beta or alpha-beta), in which the label is in only one subunit, or immuno-precipitation with antibodies against either the alpha- or beta-subunit of TSH. Similar complexes (65,000, 82,000, and 145,000 mol wt) were also formed after cross-linking with the alkaline-cleavable cross-linker (bis-[2-(succinimidooxycarbonyloxy)ethyl]sulfone. Again, the appearance of these three complexes was sequential and dependent on the cross-linker concentration. At low concentrations and under reducing conditions, the 65,000 mol wt complex was the major band. However, at high concentrations, especially under nonreducing conditions, most of the radioactivity was present in the 145,000 mol wt complex. Alkaline cleavage of these three complexes followed by electrophoresis in a second dimension resulted in the release of three components with approximate mol wt of 31,000, 17,000, and 63,000 in addition to the TSH alpha-beta dimer and its alpha- and beta-subunits. Reduction by dithiothreitol followed by electrophoresis in a second dimension resulted in the release of only the 17,000 and 63,000 components. Taken together, these results suggest that 1) both the 65,000 and 82,000 complexes are formed after incremental cross-linking of TSH alpha-beta dimer to receptor subunits; and 2) the TSH receptor may be an oligomer composed of three different subunits, 31,000, 17,000, and 63,000, of which only the 31,000 subunit binds TSH.

Animals↗
PubMed1987

Autonomously functioning thyroid nodules in childhood and adolescence.

Autonomously functioning thyroid nodules (AFTNs) in children and adolescents (under age 18) are unusual but are not as rare as earlier reports suggested. These lesions have a significantly different biologic potential than similar lesions in older patients. In the younger age group there is a more rapid progression toward toxicity and a higher incidence of thyroid carcinoma. Our experience with 12 patients is combined with those previously reported for identification of a total of 61 children and adolescents with AFTNs, of whom 53 have undergone operation. Hyperthyroidism was present in 15 patients (24.6%), and in six patients (11.3%) the AFTN was due to a well-differentiated thyroid carcinoma. Surgical treatment is advisable for all children and adolescents with AFTNs because of the risks of hyperthyroidism and thyroid carcinoma. Surgical excision (lobectomy is preferred) results in rapid restoration of a euthyroid state for the toxic AFTN and allows histopathologic diagnosis. Therapy with radioiodine is not advisable for treatment of AFTNs in this age group. Thyroid-stimulating hormone suppression should be used for all patients with a diagnosis of thyroid carcinoma.

Adolescent↗
PubMed1986

Further characterization of the low and high affinity binding components of the thyrotropin receptor.

Following cross-linking with disuccinimidyl suberate and analysis by SDS-PAGE and autoradiography, both the high- and low-affinity TSH binding components exhibited two similar 125I-TSH-labeled bands, with Mr values of 80,000 and 68,000. IgG fractions from patients with Graves' disease inhibited 125I-TSH binding to both components, while normal IgG had no effect. Although not entirely conclusive, these results suggest that the high- and low-affinity components share similar subunit composition and antigenic determinants.

Animals↗