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Biomedical subjects

R L Kennedy

Publications and source records attributed to R L Kennedy.

At least 19 recordsLinked to original sources
PubMed1992

Thyrotoxicosis and hyperemesis gravidarum associated with a serum activity which stimulates human thyroid cells in vitro.

OBJECTIVE: To investigate in-vitro thyroid stimulatory activity in the serum of patients with hyperemesis gravidarum and thyrotoxicosis. DESIGN: Serum from hyperthyroid patients was incubated with cultures of human thyroid cells. Attempts were made to neutralize stimulatory activity with antisera to hCG. PATIENTS: Five patients presenting in early pregnancy with hyperemesis and thyrotoxicosis. MEASUREMENTS: Serum concentrations of thyroid hormones (total and free), TSH and hCG. Accumulation of extracellular cAMP in response to serum. RESULTS: All five patients had biochemical hyperthyroidism with no evidence of an underlying autoimmune disease. The mean cAMP accumulation over 4 hours with sera from 12 non-pregnant controls was 130.6 (121.8-142.8), from 12 pregnant controls 132.4 (118.1-143.8), compared with values of 144.7, 159.1, 166.2, 178.9 and 320.5 for the thyrotoxic patients. The stimulatory activity could not be neutralized by addition of anti-hCG or by depleting the sera of hCG. CONCLUSIONS: Thyrotoxicosis may present with hyperemesis in early pregnancy. Clinical and biochemical features may be masked by the pregnancy or by the intercurrent illness. The hypothesis that hCG is a thyroid stimulator in patients with hyperemesis gravidarum is not supported by the immuno-neutralization data in this study.

Cells, Cultured↗
PubMed1992

Human chorionic gonadotropin may not be responsible for thyroid-stimulating activity in normal pregnancy serum.

Although hCG can activate thyroid cells in culture there is considerable doubt as to whether it is responsible for the changes in thyroid function which occur during normal pregnancy. Thyroid-stimulating activity (TSA), measured using iodide uptake into FRTL-5 cells, was demonstrated in 32/51 (63%) first and 15/29 (52%) third trimester sera. Free T3 was increased (P less than 0.001) and TSH decreased (P less than 0.01) in first trimester. In the early pregnancy group there was a positive correlation between hCG and TSA (r = 0.594, P less than 0.001) and a negative correlation between hCG and TSH (r = -0.329, P less than 0.02). In third trimester hCG concentration was often below that required to produce TSA in vitro and TSA could not be neutralized by antibodies to hCG. There was no correlation between hCG and TSH or thyroid hormones in the third trimester. In 26 women TSA decreased in parallel with serum hCG concentration after termination of pregnancy (P less than 0.001). Free T3 also decreased (P less than 0.01) and TSH increased (P less than 0.05) after termination. TSA persisted in many patients even after hCG was either very low or undetectable. Purified hCG stimulated iodide uptake in a concentration-dependent manner. Stimulation of iodide uptake by TSH was inhibited by the simultaneous presence of low concentrations of hCG while activity was restored with high concentrations. hCG may contribute to the thyroid changes in early pregnancy. However the poor correlation between TSA and thyroid tests suggests that other factors may be involved. The partial agonist activity of hCG may account for some of the inconsistencies observed but TSA in serum from late pregnancy or after termination of pregnancy is almost certainly due to another hormone or growth factor.

Adult↗
PubMed1992

Release of interleukin-6 by human thyroid epithelial cells immortalized by simian virus 40 DNA transfection.

Interleukin-6 (IL-6) has actions on a variety of endocrine tissues. The cytokine is secreted by cells of the anterior pituitary and endocrine pancreas and has recently been shown to be produced by cultures of thyroid epithelial cells. In this study we have examined some of the factors which regulate IL-6 release from an immortalized human thyroid line (HTori3). IL-6 release over 24 h was stimulated by TSH (5000 microU/ml), by forskolin (0.01 mmol/l), by fetal calf serum (1-20%) and by epidermal growth factor (20 ng/ml). Stimulation was also apparent with gamma-interferon and with tumour necrosis factor at concentrations known to enhance class II major histocompatibility antigen expression by thyroid epithelium. The most potent factor tested was interleukin-1 (IL-1), which controls IL-6 release from other cell types. Threefold stimulation was found with 1 U/ml rising to 350-fold with 1000 U/ml. The effect of IL-1 took 2 h to develop and was blocked by cycloheximide (100 mumol/l). Stimulation was not markedly inhibited by pertussis toxin. Many of the actions of IL-1 are mediated by prostaglandin E2 (PGE2). At concentrations as low as 30 nmol/l, PGE2 stimulated IL-6 release but the maximum stimulation obtained with PGE2 was only threefold. The effect of IL-1 was not inhibited by indomethacin. These data provide further evidence that IL-6 is produced by human thyrocytes. The effect of IL-1 has not been demonstrated previously. Stimulation of IL-6 release by IL-1 did not appear to be mediated by prostaglandin.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Line↗
PubMed1992

Comparison of left anterior oblique, anterior and geometric mean methods for determining gastric emptying times.

The accurate determination of gastric emptying time requires correction or compensation for tissue attenuation. The gold standard for tissue attenuation correction for gastric emptying is the geometric mean of the gastric counts from the anterior and posterior views. For reasons of efficiency, many community hospitals acquire only the anterior projection. This study addressed the hypothesis that, using the left anterior oblique view alone, one can minimize the effect of variation in attenuation as the meal moves from the fundus to the stomach to the more anterior antrum to a degree equal to that of the geometric mean technique. We studied 42 consecutive patients using a standardized 300-g meal labeled with 650 muCi of 99mTc-sulfur colloid. The patients were imaged in the anterior (ANT), posterior (POST) and left anterior oblique (LAO) views every 15 min for 90 min. Linear regressions were obtained using the ANT, LAO and GM data. Cross-correlation of the T1/2 for 35 cases showed an R value for the GM versus LAO of 0.95 and GM versus ANT of 0.84. The p value greater than 0.49, for the paired two-tailed t-test of the LAO and GM methods. The p value for the ANT and GM methods is 0.0058 indicating a significant difference between these methods. The cross-correlation, F-test p and t-test p values support the hypothesis that there is no significant difference between the geometric mean and left anterior oblique gastric emptying times. It is therefore reasonable to substitute the left anterior oblique for routine GET when using a solid meal in patients with normal gastric anatomy, albeit altered physiology.

Adult↗
PubMed1991

The role of hCG in regulation of the thyroid gland in normal and abnormal pregnancy.

There is strong evidence that at least some forms of hCG can interact with and stimulate the thyroid both in vitro and in vivo. Changes in thyroid tests are sufficiently common in normal pregnancy for us to regard them as physiologic. The evidence that hCG is the agent responsible for these changes remains largely circumstantial but is now supported by an increasing body of evidence from laboratory studies. Trophoblastic tumors secrete variant forms of hCG that can stimulate the thyroid, but we do not know if they have any role in the extreme examples of thyroid stimulation encountered in normal pregnancy. Preparations of hCG from pregnancy urine bind to thyroid membranes from a wide variety of species, but they do not activate adenylate cyclase in all assay systems. The enzyme in human thyroid cells or membranes is, at best, only weakly stimulated by hCG. There are ample in vitro data that hCG can stimulate the thyroid, but studies using human thyroid cells have yielded conflicting results. The most direct evidence comes from the study of thyroid tests in normal pregnancy. In early pregnancy, when hCG concentrations are highest, free thyroid hormones are increased and serum TSH concentration is decreased. An inverse correlation exists between serum hCG and TSH concentrations, but hCG generally correlates poorly with individual thyroid tests. An activity in pregnancy serum related to hCG is able to stimulate FRTL-5 cells and may account for the changes in thyroid function observed in pregnancy. Structural considerations, along with data from biologic assays and sensitive thyroid function tests, suggest that hCG has significant thyroid-stimulating activity. This information suggests that the thyroid may be under dual control from both hCG and TSH in early pregnancy.

Chorionic Gonadotropin↗
PubMed1990

Uptake and distribution of lidocaine in fetal lambs.

The fetal uptake of lidocaine was measured continually and quantitatively during and after a constant rate intravenous (iv) maternal infusion into five chronically prepared pregnant ewes. Lidocaine, 6 mg/kg (base), was infused at a constant rate for 1 h and measurements continued to 5 h. Rate of fetal uptake was determined from the product of the umbilical venous (UV) and fetal aortic (FA) concentration difference and umbilical blood flow (Qu). Total fetal uptake was determined by integrating fetal uptake rate with respect to time. Maternal and fetal protein binding was determined, and its effect on fetal blood concentrations was evaluated. Mean total fetal uptake as it related to time and infused dose increased linearly (r = 0.998, P less than 0.001) with a constant, weight-normalized fetal-maternal dose fraction of 0.45 during the infusion. Despite rapidly declining blood concentrations after the infusion, uptake increased an additional 17%. The sevenfold variation in uptake appeared to be inversely related to the biodegradation rate of lidocaine. Fetal-maternal concentration ratios (F/M) increased during declining blood concentrations. Protein binding determinations for maternal and fetal blood were 43.6 +/- 2.48% and 26.9 +/- 1.59%, respectively. These values were used to calculate the F/M in conjunction with the maternal and fetal pH. At maternal-fetal equilibrium the calculated F/M, 1.0 +/- 0.05, closely approximated the observed, 1.0 +/- 0.03. Variations in lidocaine concentrations among the vital organs 4 h after the infusion were small, but high concentrations of metabolites were found in the lungs and kidneys. The results challenge the validity of placental transfer estimates commonly based on the F/M and umbilical cord blood concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Thyroid function in choriocarcinoma: demonstration of a thyroid stimulating activity in serum using FRTL-5 and human thyroid cells.

Hyperthyroidism is a well recognized complication of gestational trophoblastic tumours (GTT) and may be due to high circulating concentrations of human chorionic gonadotrophin (hCG) or its variants. We have studied 24 clinically euthyroid women with GTT. Eight were biochemically hyperthyroid with low or undetectable serum thyrotrophin (TSH) and had a mean serum hCG of 361.2 x 10(3) IU/l compared to 76.2 x 10(3) IU/l in the other patients (P less than 0.01). Purified hCG stimulated iodide uptake into FRTL-5 cells with 25 x 10(3) IU/l being equivalent in potency to 1 mU/l of thyrotrophin (TSH). Sixteen out of the 24 sera (67%) stimulated iodide uptake when applied to the cells at a 1:10 dilution. Sera from all eight hyperthyroid patients contained thyroid stimulating activity. The mean hCG concentration in the 16 stimulatory sera was 238.2 x 10(3) IU/l compared to 37.1 x 10(3) IU/l in the other eight sera (P less than 0.01). Six men with hCG-secreting testicular tumours were biochemically euthyroid although three of their sera stimulated iodide uptake into FRTL-5 cells. In human thyroid cells the mean cAMP production over 4 h with sera from five healthy controls was 54.2 +/- 1.81 pmol/mg cell protein compared to 67.0 +/- 3.8 pmol/mg protein with sera from five choriocarcinoma patients (P less than 0.02). Serum from patients with gestational trophoblastic tumours contains a thyroid stimulating activity which may be hCG and whose presence correlates with hyperthyroidism.

Adolescent↗
PubMed1990

Thyroid-stimulatory effects of human chorionic gonadotrophin in early pregnancy. In vivo and in vitro studies.

Human chorionic gonadotrophin (hCG) shares structural similarity with pituitary thyrotrophin (TSH) and may act as a thyroid stimulator. We have studied serum hCG levels, thyroid function tests and the ability of serum to stimulate cultured thyroid cells in 40 subjects between 6 and 12 weeks of pregnancy. Serum free tri-iodothyronine was increased and serum TSH reduced in pregnancy samples (both p less than 0.05). hCG was detectable in all pregnancy sera with a mean level of 105.6 X 10(3) U/l. Serum from 24 of the 40 (60%) patients stimulated iodide uptake into cultured FRTL-5 thyroid cells. The potency of sera in stimulating cells correlated with the hCG level (r = 0.710, p less than 0.01). The stimulatory activity in some, but not all, sera could be specifically neutralized with antiserum to hCG. Partially purified hCG stimulated iodide uptake and growth of thyroid cells at concentrations of 50 X 10(3) U/l and above. In these experiments, 25 X 10(3) U/l of hCG produced equivalent stimulation to 1 mU/l of TSH. In 8 patients tested before and after termination of pregnancy, the thyroid-cell-stimulatory activity of serum declined rapidly in parallel with serum hCG. hCG may stimulate the thyroid gland at concentrations which prevail in normal pregnancy. Its potential as a physiological regulator of the thyroid gland is not widely appreciated and requires further study.

Adolescent↗
PubMed1989

Topical bupivacaine and etidocaine analgesia following fallopian tube banding.

The purpose of this study was to compare the effectiveness and safety of etidocaine and bupivacaine for postoperative analgesia after laparoscope sterilization. The study was performed in 22 healthy patients who received either one per cent etidocaine, 2 mg.kg-1, or bupivacaine 1.5 mg.kg-1 in a double-blind, randomized fashion. The local anaesthetic was dropped onto the fallopian tubes from uterus to fimbriae before tubal occlusion. To establish safety, blood concentrations of the parent drug and its metabolites were measured before application and at 1, 3, 6, 10, 15, 30, 60 and 120 min. The mean peak concentrations were 501.8 +/- 71.3 (SEM) for etidocaine with a range of 225 to 905 ng.ml-1. For bupivacaine, the mean peak concentration was 468 +/- 73.8 SEM with a range from 191 to 1005 ng.ml-1. The mean values are one eighth of the toxic convulsive dose for humans. Etidocaine was metabolized at a faster rate than bupivacaine with a rapid appearance of 2-amino-2'-butyroxylidide (ABX). The bupivacaine metabolite 2,6-pipecoloxylidide (PPX) was detected in low concentrations in the 60-minute samples. We conclude that the topical application of either etidocaine or bupivacaine is a safe procedure in the doses and concentrations used during general anaesthesia for laparoscopic tubal banding.

Abdominal Pain↗
PubMed1989

Inverse correlation between activated T cells and TSH receptor antibodies in Graves' disease.

TSH receptor antibodies and peripheral blood lymphocyte subsets have been measured in fourteen patients with untreated Graves' thyrotoxicosis. CD8 (suppressor) cells were reduced (p less than 0.01) and helper/suppressor cell ratio was increased in Graves' patients. Increased levels of 4F2 positive (activated) T cells were found in the patients compared to controls (p less than 0.001) and there was a negative correlation between 4F2 positive cells and TSH receptor antibodies (TBII). It may be possible, with multiple immunological markers, to identify different stages in the pathogenesis of autoimmune thyroid disease.

Adolescent↗
PubMed1989

Amiodarone and the thyroid.

An antiarrhythmic drug, amiodarone, contains 37% iodine by weight and is structurally similar to the thyroid hormones. The drug inhibits hepatic 5'-deiodinase, resulting in increases in serum thyroxin and "reverse" triiodothyronine, whereas the concentration of triiodothyronine in serum is decreased. There is a significant incidence of either hypothyroidism or hyperthyroidism in patients who are being treated with the drug. This is largely the effect of iodine released from the drug during chronic therapy, but in susceptible individuals amiodarone may unmask autoimmune thyroid disease. Some effects of the drug suggest that it may interfere with the action of thyroid hormones at the cellular level, inducing a state of localized hypothyroidism.

Amiodarone↗
PubMed1988

Autoantibodies in feline hyperthyroidism.

Thyroid autoantibodies have been demonstrated by indirect immunofluorescence in the sera of 10 of 29 (34 per cent) cats with hyperthyroidism. Antinuclear factor, rare in healthy cats, was found in a further four animals. Twenty-eight of the cats had a palpable goitre at first presentation. In 16 cases the goitre was unilateral, while in the others it was bilateral. Lymphocytic infiltration was present in nine of the 27 (33 per cent) thyroids examined histologically. Five of the sera gave a particularly strong reaction for thyroid antibodies. Four of these cases had bilateral goitres and lymphocytic infiltrations were found in four of the five thyroids (P less than 0.05). Twenty-one of the cats were followed up for a mean period of 11 months after operation, during which time three cats developed recurrent hyperthyroidism. Two had bilateral goitres with lymphocytic infiltration and the serum of both was strongly positive for thyroid microsomal antibodies. The third had unilateral goitre with lymphocytic infiltration and serum which was positive for antinuclear factor. In this case, the recurrence involved the lobe which had been previously operated on. Some cases of feline hyperthyroidism may be immunologically mediated and the condition is thus a potential model for some aspects of autoimmune thyrotoxicosis in man.

Animals↗