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Biomedical subjects

J V Felicetta

Publications and source records attributed to J V Felicetta.

32 records · Page 2Linked to original sources

Thyroid changes with aging: significance and management.

A number of changes in thyroid physiology occur with normal aging, including a modest fall in T3 levels and a reduction in the rate of turnover of thyroid hormones. Additionally, the diagnosis of either hyperthyroidism or hypothyroidism can be more difficult in the elderly because the symptoms may be more subtle. Hyperthyroidism may be disguised by a very apathetic presentation, without many of the typical adrenergic symptoms such as tachycardia and nervousness. Some of the many ways in which hypothyroidism may present include occult congestive heart failure or a severe fecal impaction.

Aged↗

Cholecystographic agents and sulfobromophthalein inhibit the binding of L-thyroxine to plasma membranes of rat hepatocytes.

Cholecystographic agents and sulfobromophthalein (BSP) cause a major discharge of labeled T4 from the liver in man in vivo. In the present study we sought to determine if this discharge is partially due to inhibition of T4 binding to plasma membrane sites. Plasma membranes were isolated from hepatocytes of female Sprague-Dawley rats, and 5'-nucleotidase levels were measured to demonstrate plasma membrane viability. Specific binding of T4 (Ka, 1.01 X 10(8) M) was confirmed by displacement of labeled T4 by unlabeled hormone (10(-10)-10(-5) M). Displacement of labeled hormone was also produced by addition of tyropanoate, iopanoate, ipodate, or BSP. At 5-mM concentrations of inhibitor, the Ka for T4 declined to 4.00 X 10(7) M with BSP, 5.07 X 10(7) M with ipodate, 5.62 X 10(7) M with tyropanoate, and 7.43 X 10(7) M with iopanoate. Thus, a portion of the discharge of hepatic T4 after administration of these agents may be due to competitive inhibition of binding to plasma membrane sites.

Animals↗

Effects of cholecystographic agents and sulfobromophthalein on binding of thyroid hormones to serum proteins.

A number of interactions between thyroid hormones and cholecystographic agents have previously been demonstrated. In the present study we show that cholecystographic agents also interfere with the binding of thyroid hormones to serum proteins. A commercial kit (Tri-Tab) was used in which the uptake of labeled hormone from serum by a silicate adsorbent tablet is measured. In the presence of cholecystographic agents or sulfobromophthalein (BSP), the amount of labeled hormone bound to adsorbent increased in a dose-dependent fashion, reflecting displacement from protein-binding sites. The order of potency was BSP greater than ipodate greater than iopanoate greater than tyropanoate. Displacement of hormone was confirmed by a second methodology in which graded amounts of unlabeled T4 were added to the system. This allowed a Scatchard analysis to be performed for binding sites on T4-binding globulin. The cholecystographic agents and BSP caused displacement of the Scatchard slopes, again demonstrating interference with binding to serum protein sites. A method is described in which the change in Scatchard slope produced by an inhibitor is employed to compute the association constant between T4-binding sites on T4-binding globulin and the inhibitors. The values were: BSP, 14.6 X 10(3) M-1; ipodate, 4.7 X 10(3) M-1, iopanoate, 2.2 X 10(3) M-1; and tyropanoate, 0.1 X 10(3) M-1. Because of these relatively low values and the rapidity with which these agents are normally cleared from serum, it seems likely that effects on free hormone levels would be transient and of small magnitude during routine cholecystography. Also, ipodate, in the 1 g/day dose that has been employed experimentally to treat hyperthyroidism, should have a negligible effect on protein binding. On the other hand, when high levels of these compounds are used in experimental settings to study other aspects of thyroid hormone metabolism, changes in protein binding can occur and confound interpretation of results.

Blood Proteins↗

Inhibition of hepatic binding of thyroxine by cholecystographic agents.

Subsequent to studies indicating that cholecystographic agents and sulfobromophthalein (BSP) inhibit uptake of thyroxine (T(4)) by rat liver slices, the effect of such compounds on hepatic storage of T(4) in man has been examined. After intravenous administration of [(125)I]T(4) to five normal subjects, hepatic radioactivity, estimated by external gamma counting, rose to a peak in approximately 4 h and then declined in parallel with serum radioactivity. When a 6-g dose of the cholecystographic agent, tyropanoate (Bilopaque), was administered orally 3 d later, estimated hepatic extravascular radioactivity fell 50-60% within 4 h and then rose toward the pretyropanoate value. Concomitant with the fall in hepatic radioactivity, serum radioactivity rose 57-70%, as did stable T(4) levels in serum, suggesting that hormone discharged from the liver entered the serum. Both uptake of T(4) and discharge by tyropanoate were much less in two patients with liver disease. Ipodate (Oragrafin), 12 g orally in two subjects, caused much smaller changes in hepatic and serum radioactivity. However, ipodate also caused a doubling of the percent free T(4) in the serum as judged by equilibrium dialysis, and the ratio of hepatic radioactivity to free [(125)I]T(4) in serum declined markedly after ipodate, similar to the fall in hepatic:serum (125)I ratios after tyropanoate. BSP, 20 mg/kg i.v. in three subjects, caused a smaller change; the decline in hepatic T4 content averaged 19%. We conclude that these organic anions, tyropanoate, ipodate, and BSP, all can displace T(4) from the liver. The results imply a link between T(4) transport and organic anion transport, and indicate a mechanism for altering hepatic T(4) content in man that could be the site of physiologic regulation or of disease. A method is described whereby analysis of the change in hepatic and plasma radioactivity after tyropanoate could be employed to estimate hepatic T(4) content in diverse clinical circumstances.

Adult↗

Decreased adrenal responsiveness in hypothermic patients.

We have performed ACTH simulation tests in a total of 14 subjects who were hypothermic at the time of initial presentation. Plasma cortisol values were measured before and 1 h after an iv dose of 25 U synthetic ACTH. The cortisol response was depressed in these subjects, with a mean rise of 32% and an absolute mean rise of 5.0 microgra/dl. There appeared to be a temperature threshold effect, with only minimal responses observed below 32 C. A subgroup of 5 patients with sluggish responses to ACTH while hypothermic (mean cortisol rise, 12.5%) were retested after warming and responded normally (mean rise, 166%). Thus, ACTH stimulation tests may be misleading in the hypothermic patient and should be performed only after body temperature has returned to normal.

Adrenal Glands↗

Fibromyalgia syndrome.

Fibromyalgia is a chronic rheumatologic disorder. The primary symptoms include musculoskeletal pain and aching, disturbed sleep, fatigue, morning stiffness, and local tenderness. It is frequently misdiagnosed, despite being a fairly common, chronic disorder in most primary care clinics. Failure to make this diagnosis often leads to unnecessary medical and surgical treatment. The treatment of fibromyalgia syndrome is multifaceted. Goals include reassurance, education about pain management and modification, and symptom reduction. Exercise may be beneficial. Amitriptyline is effective in reducing certain symptoms of fibromyalgia, such as pain and lack of restful sleep. Narcotics, steroids, and nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided.

Diagnosis, Differential↗

Hypothyroidism: a comprehensive review.

Hypothyroidism is a common clinical entity encountered frequently in most adult primary care settings. The reported prevalence in the general population is approximately 3% in men, but as high as 10% in women (Sawin, Geller, Hershman, Castelli, & Bacharach, 1989). The disease process affects every major organ system, contributing to a broad range of symptoms. Clinicians need to be familiar with the signs, the symptoms, and the appropriate laboratory studies, so that timely and accurate diagnoses can be made. This article reviews normal thyroid physiology and thyroid pathophysiology, as well as the diagnosis and treatment of several important clinical entities resulting in hypothyroidism. Research findings are included insofar as they relate to current clinical practice.

Humans↗

Hyperthyroidism: a comprehensive review.

Hyperthyroidism is an endocrine disorder encountered in adult primary care clinics. This article reviews normal thyroid physiology as well as the pathophysiology, diagnosis, clinical signs and symptoms, and diagnostic tests and treatment for the most common clinical hyperthyroid entities. Current research is also discussed as it relates to clinical practice.

Humans↗

Selecting antihypertensive drug therapy: the JNC-V controversy.

OBJECTIVE: To present both the supporting and the opposing arguments for the fifth set of recommendations issued by the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC). METHODS: The published studies are reviewed, and the various opinions are discussed. RESULTS: The 1993 recommendation from the JNC that diuretics or beta-adrenergic blockers be preferred for therapy in most patients with hypertension has proved controversial. This recommendation derived primarily from recent long-term studies showing convincing reductions in cardiovascular morbidity and mortality when these agents are used to control hypertension. Comparable data have not yet been obtained for newer agents, such as calcium channel blockers and angiotensin-converting enzyme inhibitors. Nonetheless, some critics of the JNC recommendation still favor the newer agents because of their putatively superior side-effect profile, from both a metabolic and a compliance standpoint. CONCLUSION: The issue of optimal antihypertensive drug therapy will not be definitively resolved until long-term studies directly comparing the various classes of agents are completed in future years.

Journal Article↗

Malignant thymic carcinoid in multiple endocrine neoplasia type I syndrome: case report and literature review.

OBJECTIVE: To describe a case of thymic carcinoid tumor in association with multiple endocrine neoplasia type I (MEN I) and discuss the various manifestations of this syndrome. METHODS: We present the clinical and laboratory data, including histopathologic and immunocytochemical findings, for our current patient and also review the literature on MEN I syndromes. RESULTS: In a 46-year-old Caucasian man with no family history of multiple endocrine neoplasia, numerous MEN I lesions developed over time. The patient had gastrinoma of the duodenum, Zollinger-Ellison syndrome, hyperparathyroidism, a nonfunctioning adrenal mass, and foregut carcinoid tumors, including gastric and malignant thymic carcinoids. He sequentially underwent partial gastrectomy in conjunction with Billroth II anastomosis, a four-gland parathyroidectomy, and palliative radiotherapy for malignant carcinoid tumor, as well as endoscopic excision of accessible tumors. CONCLUSION: The involvement in MEN I can be clinically complex. Early detection of MEN I lesions will facilitate timely implementation of treatment and help minimize complications.

Journal Article↗