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Biomedical subjects

R L Kennedy

Publications and source records attributed to R L Kennedy.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

Uptake and distribution of bupivacaine in fetal lambs.

Direct continual measurement of placental drug transfer was introduced to evaluate more precisely the fetal uptake of a commonly used local anesthetic in obstetrics. Bupivacaine, 2.7 mg X kg-1 (base), was infused at a constant rate over 1 h into a maternal jugular vein of five chronically prepared pregnant ewes. Blood was sampled simultaneously from the umbilical vein (UV), fetal aorta (FA), and a maternal artery (MA). Fetal uptake rate was determined from the product of the bupivacaine UV-FA blood concentration difference and the umbilical flow rate (Qu). Total fetal accumulation was determined by integrating uptake rate over 5 h. Correlation of total fetal uptake and the infused mean maternal dose (r = 0.993, P less than 0.001) indicated that during the infusion, mean fetal uptake was a constant fraction (0.16) of the maternal infused dose. Total fetal uptake was linear despite wide individual changes in Qu, suggesting that within limits fetal accumulation is not Qu-dependent. Mean ovine protein binding of bupivacaine by maternal and fetal whole blood was 85.49% +/- 2.61 (SD) and by fetal blood, 40.43% +/- 9.60 (SD). Back-transfer of bupivacaine to the mother proceeded against a higher total bupivacaine concentration because unbound unionized drug concentrations in maternal blood were less than in fetal blood. At maternal-fetal equilibrium when UV and FA total blood concentrations were equal, the calculated fetal/maternal concentration ratio (f/m) (0.36) determined from the maternal and fetal protein binding and pH closely approximated the observed (0.35). The f/m increased during both fetal uptake and back-transfer and cannot be considered a good index of placental transfer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The neonatal neurobehavioral effects of bupivacaine, mepivacaine, and 2-chloroprocaine used for pudendal block.

The neonatal neurobehavioral effects of bupivacaine, mepivacaine, and 2-chloroprocaine used in random sequence for pudendal block anesthesia were studied. The neurobehavioral status of 54 infants was studied 4 and 24 hours after delivery. Except for a significant difference in the responses to pinprick, there was no significant effect of any of these agents on infant neurobehavior, and no differences were found among the agents themselves. Mean mepivacaine levels in neonatal capillary blood at 4 hours of age were low (0.10 +/- .02 microgram/ml) compared with those in previous studies because of the short interval between maternal injection and delivery (13 +/- 3 min). Bupivacaine gave higher neonatal capillary blood levels (0.15 microgram/ml at 4 hours of age) than previously reported, but the drug still produced no detectable neonatal neurobehavioral effects.

Adolescent↗

Effects of changes in maternal--fetal pH on the transplacental equilibrium of bupivacaine.

Increases in the maternal-fetal pH gradient that may occur during labor and delivery may increase the fetal concentration of local anesthetics. The authors evaluated effects of pH changes on the transplacental concentration equilibrium of bupivacaine. They increased the maternal-fetal pH gradient in each of six pregnant ewes from a control value of 0.15 to 0.54 by hyperventilating the lungs of the ewe and infusing lactic acid into her fetus. After infusion of bupivacaine, 0.15 mg/kg, intravenously into the mother, the drug rapidly appeared in fetal blood, with values significantly increased over control values at 1 and 5 min. The fetal/maternal (f/m) ratios were increased significantly at 5, 15, and 30 min. The f/m ratios had stabilized by 15 min in both control and experimental states, suggesting that equilibrium had been achieved. The consistently low f/m ratios are explained by the presumed similarity of the ovine maternal and fetal protein binding rates to those of man. It is concluded that the maternal and fetal pH values are major factors in the determination of the f/m ratios.

Alkalosis, Respiratory↗

Metabolic effects of constant hypertonic glucose infusion in well-oxygenated fetuses.

In order to investigate the metabolic effects of a constant hypertonic glucose infusion in well-oxygenated fetuses, ten experiments were carried out in nine long-term experiments in fetal lambs. It appeared that a constant hypertonic glucose infusion did not significantly affect the fetal blood gases, pH, and plasma lactate levels when fetal glucose was kept below 150 mg. per 100 ml. It was also demonstrated that glucose infusions significantly increased the fetal lactate levels and decreased the blood pH when fetal plasma glucose was over 150 mg. per 100 ml. However, there was no decrease in fetal PO2 and pco2 until fetal glucose reached values over 300 mg. per 100 ml. These studies suggest that constant hypertonic glucose infusion does not improve fetal blood gases or pH and that fetal hyperglycemia over 300 mg. per 100 ml. produces severe metabolic acidosis.

Animals↗

Epidural anesthesia with bupivacaine for Cesarean section: neonatal blood levels and neurobehavioral responses.

A recent study found no neurobehavioral change in infants whose mothers received bupivacaine epidural anesthesia (112 +/- 7 mg) for labor and vaginal delivery. The present study was undertaken to examine the possibility that the larger doses of bupivicaine necessary for cesarean section might cause neurobehavioral changes in the neonate. Ten infants delivered by cesarean section with bupivacaine epidural anesthesia (168 +/- 7 mg) was assessed by Scanlon's neonatal neurobehavioral examination. They were compared in a prospective randomized study with a control group of ten infants delivered with tetracaine spinal anesthesia. In the experimental group bupivacaine was detectable in umbilical arterial blood (.17 +/- .07 microgram/ml), umbilical venous blood (.21 +/- .09 microgram/ml), and neonatal blood samples at 4 hours of age (.04 +/- .04 microgram/ml). By 24 hours of age bupivacaine was no longer detectable in newborn blood samples. Infants in the experimental group were indistinguishable from control infants in terms of their motor organization, responsiveness to external stimuli, and habituation to repetitive stimuli. Detectable neurobehavioral effects were absent despite the fact that 1.5 times the dose of bupivacaine used for labor and vaginal delivery was employed in this study.

Adult↗