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Biomedical subjects

R C Smallridge

Publications and source records attributed to R C Smallridge.

At least 73 records · Page 4Linked to original sources
PubMed1990

Malabsorption of thyroxine, calcium, and vitamin D in a thyroparathyroidectomized woman: efficacy of therapy with medium-chain triglyceride oil.

A 28-year-old woman with surgically induced hypothyroidism and hypoparathyroidism required large doses of replacement medications due to malabsorption from short bowel syndrome. Malabsorption of thyroxine was documented using the technique of double isotope radioiodothyronine turnover studies. Therapy with medium-chain triglyceride oil improved her malabsorption and favorably influenced the absorption of her medications.

Adult↗
PubMed1989

Thyroid hormone resistance in a large kindred: physiologic, biochemical, pharmacologic, and neuropsychologic studies.

PURPOSE: Thyroid hormone resistance affects the pituitary gland and a variety of other tissues. We studied a large kindred with this disorder and measured a number of clinical markers of tissue metabolism to determine if these markers were useful in elucidating the sites and degree of resistance. PATIENTS: A kindred of 89 persons in four generations was identified; 44 had thyroid function tests, and 14 (five to 67 years old) were found to have thyroid hormone resistance. RESULTS: The inheritance pattern was autosomal dominant, with no common HLA haplotype. Physiologic measurements in five affected members showed marked heterogeneity. Four patients had normal baseline cardiac contractility, but only two experienced a shortening of their QKd interval into the hyperthyroid range with triiodothyronine (T3) therapy. Intrathyroidal 127I content was increased in two patients and was normal in two. Bone mineral content was normal in two men, but two women had marked osteopenia. The propositus, hypothyroid after inappropriate 131I therapy, had a hypothyroid ventilatory response to hypercapnea. This response became low normal during T3 (100 micrograms/day) administration but not during long-term thyroxine (T4) (300 micrograms/day) administration. Three other patients had values within normal limits and one had a hyperthyroid ventilatory response. Peripheral biochemical markers of thyroid hormone action were measured in 13 affected and 19 unaffected family members. Sex hormone-binding globulin was increased in zero of 13 affected patients (versus 19 of 20 hyperthyroid, chi 2:p less than 0.001); ferritin was elevated in two of 13 patients (versus 11 of 20 hyperthyroid, p less than 0.02); angiotensin converting enzyme activity was increased in one of 13 patients (versus 12 of 20 hyperthyroid, p less than 0.025). The eldest patient had marked cardiac sensitivity despite normal biochemical markers. We attempted to suppress the integrated thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) using T3 (72 and 100 percent suppression in two patients), dopamine (40 percent suppression in one), 3,5,3'-triiodothyroacetic acid (TRIAC) (94 percent suppression in one), and verapamil (10 percent and 40 percent suppression in two). Neuropsychologic function was studied in 14 individuals (11 affected, three unaffected). Although mild impairments were detected, they were not specific for thyroid hormone resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1989

Rapid release of multiple hormones from rat pituitaries perifused with recombinant interleukin-1.

Previous studies demonstrated a direct action of interleukin-1 (IL-1) on release of hormones from rat anterior pituitary cells in monolayer culture. To rule out any possibility of a paracrine effect from the elevated hormones in the static monolayer system, and to examine further the dynamics of hormone release elicited by IL-1, studies were conducted with rat anterior pituitary tissue in a computer-controlled automated perifusion system. In experiments performed on the same day as sacrifice, IL-1 stimulated the release of adrenocorticotrophic hormone (ACTH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), growth hormone (GH) and prolactin (PRL) in a dose-related manner. Peak levels were achieved within 6 minutes of exposure to IL-1. However, PRL was not increased over the baseline fluctuations when pituitaries were perifused with IL-1 after 72 hours of incubation. Hormone release did not appear to undergo desensitization after multiple short pulses of IL-1. Heat-denatured IL-1 had no effect on hormone release. The rapid response suggests that IL-1 acts acutely to release preformed hormone stores.

Animals↗
PubMed1989

Effects of elevated gonadotropin levels on thyroid function in the male rat.

In order to determine if thyroid disease in hypogonadal men is the result of chronic elevation of serum gonadotropins, thyroid histology and serum thyroid hormone levels were evaluated in male rats that had been castrated either 2 weeks or 15 months previously. Despite significantly elevating serum LH levels, castration did not affect thyroid structure or function. Serum total T4 levels were reduced with age in both short and long-term castrate animals but returned to the levels seen in young rats when testosterone was replaced. Testosterone replacement also increased free T4 levels in both the young and old castrate rats. Neither age nor testosterone replacement affected serum T3 or TSH levels.

Animals↗
PubMed1989

Atropine pharmacokinetics are affected by moderate hemorrhage and hypothyroidism.

Atropine is used both to treat a variety of clinical disorders and as an antidote to cholinesterase poisoning. While various conditions affect the physiologic responses to atropine, little is known of the pharmacokinetics of this drug except under resting conditions. Pharmacokinetic studies were performed in mongrel dogs under two experimental conditions, moderate hemorrhage and hypothyroidism, to determine whether im absorption and elimination of atropine (0.05 mg/kg body weight) were affected by changes in hemodynamic or metabolic status. Using a randomized, crossover experimental design, it was found that during hypovolemia the mean volume of distribution was reduced by 22% (2.50 +/- 0.62 vs. 3.21 +/- 0.63 L/kg), with no changes in peak serum level, total atropine availability, elimination half-life, or whole-body clearance. Hypothyroidism was associated with a significant increase in peak serum atropine concentration (26.4 +/- 3.9 vs. 20.6 +/- 4.9 ng/ml) and drug bioavailability (48.5 +/- 8.8 vs. 30.0 +/- 10.7 ng/ml.h), while the clearance was reduced by 39% (426 +/- 34 vs. 696 +/- 187 ng/ml.min). These results suggest that atropine kinetics are not altered appreciably during moderate hemorrhage. In hypothyroidism, alterations in atropine pharmacokinetics may warrant modification of drug dose and frequency of administration.

Animals↗
PubMed1989

Alterations in sympathetic nervous system activity with intraoperative hypothermia during coronary artery bypass surgery.

To determine how intraoperative hypothermia associated with coronary bypass surgery (CABS) alters sympathetic nervous system (SNS) activity, we prospectively studied 21 adult CABS patients and measured preoperative, intraoperative, and postoperative circulating catecholamine concentrations. Because thyroid hormone levels change rapidly following CABS, we also serially measured these hormone levels. The measured plasma concentrations for each of the above variables were corrected for hemodilution during CABS by using serum albumin changes as a reference. It was concluded that important alterations in SNS activity and thyroid hormone homeostasis occur in humans during CABS and deep hypothermia, and that changes in core temperature may contribute to these findings. We speculate that these hormonal changes may influence the response to adrenergic receptor therapy in hypothermic patients and may contribute to arrhythmias during rewarming and the immediate postoperative period.

Acetylcholinesterase↗
PubMed1988

The value of serum antimicrosomal antibody testing in screening for symptomatic postpartum thyroid dysfunction.

We investigated the value of a screening program for postpartum thyroiditis in a heterogeneous American population and used serum antithyroid antibodies to identify postpartum women at risk. Blood was drawn from 1034 consecutive women on their second postpartum day and tested for antimicrosomal and antithyroglobulin antibodies by hemagglutination. Seventy-two women (7.0%) were seropositive for antimicrosomal antibodies, but only seven (0.7%) had antithyroglobulin antibodies. There was a significant difference in the racial prevalence of antimicrosomal antibodies, with seropositivity in 52 of 588 white women (8.8%) versus nine of 367 black women (2.5%; p less than 0.001). Thirty-four of 51 (67%) antimicrosomal seropositive women followed at least 6 months post partum developed biochemical thyroid dysfunction and 20 of these patients required treatment for hypothyroidism. The mean (+/- SEM) serum thyroxine and thyrotropin levels in these patients before treatment were 3.0 +/- 0.3 micrograms/dl (normal 6.1 to 12.3 micrograms/dl) and 77 +/- 17 mU/L (normal 0.3 to 4.0 mU/L), respectively. Psychologic interviews revealed a significant increase in impaired concentration, carelessness, depression, and total complaints when patients with postpartum hypothyroidism were compared with postpartum euthyroid women. Medical evidence now suggests that postpartum thyroiditis is a common event and causes significant symptoms in women who develop hypothyroidism. Therefore, we propose that serum antimicrosomal antibody testing of postpartum women provides a feasible cost-effective screening method of identifying women likely to suffer from this disease.

Autoantibodies↗
PubMed1988

Effect of exercise in sheep on the absorption of intramuscular atropine sulfate.

In normal female sheep, we investigated effects of exercise on the absorption of atropine sulfate (0.02 mg/kg) given intramuscularly. The exercise regime consisted of treadmill running (20 min at 3-4 mph at 0 degrees grade) starting immediately after intramuscular atropine injection into the biceps femoris. Six normal female sheep received intramuscular atropine and 7-14 days later an identical intramuscular dose of atropine with exercise. Serum levels of atropine measured by radioimmunoassay were monitored over a 6-hour period. The time to peak concentration was significantly less with exercise than without, 2.9 +/- 2.1 and 13.7 +/- 5.4 min, respectively (p less than 0.005). In addition, peak serum atropine concentrations tended to be higher, 9.7 +/- 1.3 ng/ml with exercise versus 7.1 +/- 2.9 ng/ml without exercise; however, the difference did not attain statistical significance (p less than 0.08). This study demonstrates that exercise increases the early absorption of intramuscularly administered atropine sulfate.

Absorption↗
PubMed1988

Reversal of inhibition of prolactin secretion in cultured pituitary cells by muscarinic antagonists.

We investigated whether the inhibition of prolactin secretion from pituitary cells by carbachol, a cholinergic agonist resistant to hydrolysis by cholinesterases, would be a useful bioassay to explore an important nonneuronal action of antimuscarinic agents. Carbachol inhibited prolactin secretion from cultured rat anterior pituitary cells in a dose-dependent manner with a mean IC50 of 1.5 +/- 0.6 (S.E.) microM and maximal inhibition at 10(-5) M. Prolactin levels in media were significantly reduced by 30 min of incubation with carbachol. This inhibition persisted for 24 hr and was reversed by 2 microM atropine. The stimulation of prolactin secretion by 10(-6) M thyrotropin releasing hormone (to 1.5 times control) was inhibited by the addition of carbachol (10(-5) M). Addition of atropine (2 microM) to these agents restored maximal stimulation by thyrotropin releasing hormone. The inhibition of carbachol by atropine was competitive, whereas the inhibition of thyrotropin releasing hormone by carbachol was noncompetitive. The apparent affinities (Ki) of several antimuscarinic agents in pituitary cells were determined by their ability to reverse the carbachol inhibition of prolactin secretion: atropine 0.14 nM, scopolamine 0.26 nM, azaprophen 0.3 nM, aprophen 3.0 nM, pirenzepine 42 nM, benactyzine 80 nM and adiphenine 198 nM. These potencies correlated positively with those previously determined for inhibition of alpha amylase secretion from pancreatic acinar cells as well as with those for behavioral depressant actions of the antimuscarinics. Cultured anterior pituitary cells thus provide an effective system for testing the relative potencies of muscarinic antagonists in pituitary cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Release of multiple hormones by a direct action of interleukin-1 on pituitary cells.

Exposure to bacterial endotoxins has long been known to stimulate the release of anterior pituitary hormones; administration of endotoxin was at one time a common clinical test of anterior pituitary function. Endotoxin is a potent stimulus for production of the endogenous pyrogenic protein, interleukin-1 (IL-1), by macrophages and monocytes. The possibility that IL-1 has a direct effect on the secretion of hormones by rat pituitary cells in a monolayer culture was investigated. Recombinant human IL-1 beta stimulated the secretion of adrenocorticotropic hormone, luteinizing hormone, growth hormone, and thyroid-stimulating hormone. Increased hormone secretion into culture supernatants was found with IL-1 concentrations ranging from 10(-9) M to 10(-12) M. Prolactin secretion by the monolayers was inhibited by similar doses. These concentrations of IL-1 are within the range reported for IL-1 in serum, suggesting that IL-1 generated peripherally by mononuclear immune cells may act directly on anterior pituitary cells to modulate hormone secretion in vivo. Incubation of IL-1 solutions with antibody to IL-1 neutralized these actions. These pituitary effects of IL-1 suggest that this monokine may be an important regulator of the metabolic adaptations to infectious stressors.

Adrenocorticotropic Hormone↗
PubMed1987

Serum angiotensin converting enzyme activity in evaluation of patients with liver disease.

This study was undertaken to evaluate angiotensin converting enzyme activity in patients with liver disease, and to explore its relationship to thyroid function in patients with liver disease. Serum angiotensin converting enzyme activity and thyroid hormone levels, determined in 79 patients with intrahepatic-type liver disease and 18 patients with extrahepatic biliary obstruction, were compared with values in 129 euthyroid controls. Serum angiotensin converting enzyme activity was higher in intrahepatic disease than in extrahepatic obstruction, but statistically significant only for acute intrahepatic disease. In the patients studied, high serum angiotensin converting enzyme activity (22 units/ml or more) virtually excluded extrahepatic biliary obstruction, with a negative predictive value of 94 percent. Low serum angiotensin converting enzyme activity had a positive predictive value for extrahepatic obstruction of only 67 percent. Increased angiotensin converting enzyme activity could not be explained as a function of enhanced thyroid activity. Serum angiotensin converting enzyme activity may be useful in separating patients with intrahepatic liver disease from those with extrahepatic obstruction.

Cholestasis, Extrahepatic↗
PubMed1987

Angiotensin-converting enzyme activity decreases during fasting.

UNLABELLED: Serum angiotensin-converting enzyme (ACE) activity varies directly with thyroid hormone levels in states of altered thyroid function. Because T3 levels decrease during fasting, ACE activity was examined to ascertain if it was reduced in this low T3 condition. Eighteen obese euthyroid subjects were hospitalized and placed on a weight-maintaining diet for 4 days. Nine subjects (Group 1) underwent a fast (50 kcal/day) for 8 days. Nine (Group 2) subjects received T3 (5 micrograms q 3 h) during an identical fast. Weight loss was identical in both groups (-4.4 kg). Serum T3 fell in Group 1 from 104 +/- 8 to 50 +/- 4 ng/d/(p less than .05) but was unchanged in Group 2 (114 +/- 11 ng/dl fed vs. 120 +/- 14 ng/dl fasted). Blood pressures fell significantly in Group 1 (mean systolic: 112----104 mmHg; diastolic: 71----65 mmHg, p less than 0.05), but not in Group 2 subjects. ACE activity fell progressively in Group 1 subjects during fasting (14.4 +/- 1.6 U/ml fed vs. 12.8 +/- 1.4 U/ml fasted p less than 0.05). ACE activity was not decreased significantly early in the fast in patients given T3, but by late fast (days 6-8) was reduced to the same degree as in Group 1 subjects. Glucose and insulin levels fell similarly in both groups. CONCLUSIONS: (1) ACE activity is reduced during starvation. This effect is not mediated by T3. (2) Blood pressure reduction during fasting may result from the low T3 levels, but not from decreased ACE activity. Interpretation of serum ACE activity must be viewed in the context of a patient's diet.

Adult↗
PubMed1987

Iodide administration enhances thyrotrophin responsiveness to thyrotrophin-releasing hormone during fasting: evidence for normal pituitary feedback regulation.

Short-term fasting in humans is associated with diminished delta TSH to TRH. The purposes of the present study were to reassess basal TSH levels and TRH responsiveness during fasting utilizing a sensitive radioimmunoassay (RIA: sensitivity 0.3 microU/ml; normal range 0.66-2.98 microU/ml) and to determine if normal feedback regulation is maintained during the fasting state. Eight control subjects (C) and six iodide-treated (I) subjects (262 mg/d) were studied in the fed state and on day 10 of fasting. T3, T4, and TSH were measured by RIA, and free T4 and free T3 by equilibrium dialysis. Basal serum TSH levels in the control group were 2.0 +/- 0.3 microU/ml (mean +/- SEM) in the fed state and increased to 14.7 +/- 3.5 microU/ml 20 min after TRH administration. The fasting basal TSH level of 1.6 +/- 0.3 microU/ml was significantly decreased (P less than 0.01) compared to control, as was the level of 8.8 +/- 2.3 microU/ml (P less than 0.01) obtained 20 min after TRH. In the iodide-treated group the basal TSH level was 1.4 +/- 0.2 microU/ml during feeding which increased (P less than 0.025) to 2.9 +/- 0.7 microU/ml during fasting; the TSH value 20 min after TRH was 12.6 +/- 2.5 microU/ml while feeding and 17.3 +/- 2.9 microU/ml while fasting. Free and total T3 decreased during fasting in both groups. Total T4 was unchanged between the fed and fasted periods in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Fasting↗
PubMed1987

Persistent thyroid autoimmunity after subacute thyroiditis.

Subacute (de Quervain's) thyroiditis (SAT) is accompanied by temporary abnormalities in thyroid function and, in a minority of patients, by transient thyroglobulin and thyroid microsome autoantibody formation. In this report we have examined the sera of patients with SAT for the presence of multiple thyroid autoantibodies using qualitative immunoblotting (Western blotting). For this purpose we used a crude thyroid extract (2,000 g supernatant) as a source of antigen, in order to identify antibodies reacting with a wide range of potential autoantibodies. Eight of the 9 patients tested had autoantibodies which reacted with between 2-18 antigenic determinants (molecular weights 177-10 kd) present in the thyroid antigen preparation. None of the sera reacted with thyroglobulin or thyroid microsomes. The majority of these autoantibodies were directed against antigens which were absent from liver membrane preparations. Furthermore there was no diminution in the levels of these autoantibodies over a period of up to 39 months after the onset of SAT. The prolonged presence of these novel thyroid autoantibodies may explain the recent findings of subtle thyroid defects, such as altered gland iodine content, long after apparent clinical resolution of SAT. The accumulated evidence for a viral aetiology in this condition suggests that these sequelae may be due to a virally-induced autoimmune response.

Adult↗
PubMed1987

Hormonal changes during decompression sickness.

Changes in plasma hormone levels were studied in anesthetized dogs during decompression sickness. Hormone levels were measured in 4 groups: control (no dive, n = 9); air group (air dive, ventilated with air postdive, n = 6); helium-oxygen (He-O2) group (air dive, ventilation changed to He-O2 at 30 min postdive, n = 9); nonsurvivor group (air dive, died within 30 min postdive, n = 9). Dived animals were subjected to repetitive dives until pulmonary artery pressure doubled. Plasma epinephrine (Epi) and norepinephrine (NE) concentrations rapidly increased postdive in all animals. Serum angiotensin-converting enzyme (ACE) activity increased postdive in the He-O2 group only, and these increases were small. Diving did not alter serum concentrations of cortisol, thyroxine (T4), or triiodothyronine (T3); however, T4 and T3 fell in all animals, probably as a consequence of anesthesia. He-O2 breathing did not affect concentrations of Epi, NE, cortisol, T4, T3, or serum ACE activity.

Animals↗
PubMed1987

Thyrotropin-secreting pituitary tumors.

TSH tumors are associated with both hypothyroid and hyperthyroid states. The proposed mechanism of thyrotroph secretion is illustrated in Figure 8. Pituitary enlargement in hypothyroidism is usually due to reactive hyperplasia and correlates with the degree of TSH elevation. Although this often translates to long-standing hypothyroidism and severe symptoms, this is not always the case. Patients may be asymptomatic or present with other endocrine syndromes. Children may have precocious puberty, and adults may have amenorrhea or decreased libido. One important message to remember is that whenever a patient has evidence of a pituitary tumor, a serum T4 and TSH level must be obtained. The dramatic reduction in pituitary size and resolution of endocrine dysfunction with thyroid hormone is gratifying. Thyrotropinomas producing thyrotoxicosis are autonomous tumors. Given their infrequent occurrence, one could question the cost effectiveness of ordering a serum TSH on all new patients with hyperthyroidism. Features that might favor the possibility of there being a tumor include male sex, headaches, visual impairment, and the absence of ophthalmopathy. Unfortunately, these are not reliable clinical features to suggest the presence of this disorder, and the diagnosis requires a serum TSH determination. Fortunately, the newer assays available are able to provide the sensitivity needed. Therapy should be aimed at the pituitary gland, but currently it is less than optimal. Surgery with or without external irradiation offers the best prognosis and, hopefully, will yield better results when cases are identified earlier. Medical therapy to suppress TSH is still in its infancy. More effective agents will hopefully be discovered in the near future.

Diagnosis, Differential↗
PubMed1987

Hormonal responses to graded surgical stress.

We tested the hypothesis that selected hormonal responses to surgery reflect the degree of surgical stress. Plasma norepinephrine, epinephrine, thromboxane B2, cortisol, serum angiotensin converting enzyme, thyroxine, triiodothyronine, free thyroxine, and free triiodothyronine levels were measured preoperatively, and then one hour, 24 hours, and five days postoperatively in three groups of patients. The groups were as follows: group 1, "minimal" stress, eg, inguinal hernia repair (n = 10); group 2, "moderate" stress, eg, cholecystectomy (n = 12); and group 3, "severe" stress, eg, subtotal colectomy (n = 9). Patients in group 1 showed no significant surgery-induced changes in hormonal values. The stress-induced changes in patients in groups 2 and 3 were seen at one and occasionally 24 hours; however, by five days postoperatively, circulating hormone values had returned to preoperative levels. Increases in plasma cortisol, norepinephrine, and epinephrine, and decreases in serum angiotensin converting enzyme levels characterized the surgery-induced hormonal changes. Conclusions are as follows: hormonal responses do reflect the degree of surgical stress; the hormonal changes are transient, lasting no longer than 24 hours in patients after uncomplicated surgery; hormonal responses to minimal surgical stress are negligible.

Adult↗