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Biomedical subjects

T W Burns

Publications and source records attributed to T W Burns.

At least 19 recordsLinked to original sources

Pancytopenia due to vitamin B12 deficiency associated with Graves' disease.

Pancytopenia has a broad differential diagnosis, which can be narrowed depending on the cellularity of the bone marrow. The authors describe a complex patient with a history of Graves' disease who presented with pancytopenia, initially suspected of being due to aplastic anemia. He was later diagnosed with Vitamin B12 deficiency as a result of pernicious anemia. The potentially striking hematologic effects of cobalamin deficiency and the autoimmune basis for concurrent Graves' disease and pernicious anemia are reviewed.

Biopsy, Needle↗

Multiple hamartoma syndrome (Cowden's disease) associated with renal cell carcinoma and primary neuroendocrine carcinoma of the skin (Merkel cell carcinoma).

A case of multiple hamartoma syndrome (Cowden's disease) associated with renal cell adenocarcinoma and primary neuroendocrine carcinoma of the skin is described. Neither of these neoplasms has been documented previously in association with this genodermatosis. A search for epidermal growth factor receptor (c-erb-B protooncogene) gene abnormalities in the kidney, liver, and thyroid, as well as in tissue of the primary neuroendocrine carcinoma, was negative. Serum obtained from the patient before his death contained elevated levels of both chromogranin A (2641 ng/mL; normal level, less than 20 ng/mL) and calcitonin (517 pg/mL; normal level, less than 200 pg/mL), suggesting that the patient's principal tumor was neuroendocrine in origin.

Aged↗

Diabetes mellitus and lipoatrophy.

Insulin resistance may occur in a wide variety of conditions. Some conditions such as obesity or the presence of insulin antibodies are common. We have reported three unusual cases in which the patients exhibited marked insulin resistance, absence of subcutaneous fat, absence of ketosis, and substantial hyperglycemia despite normal insulin levels.

Adolescent↗

Persistence of low serum thyroid hormone levels in a Graves' disease patient receiving supraphysiologic L-thyroxine replacement therapy.

A patient with Graves' disease was treated with radioactive iodine. For several years following treatment, the patient displayed clinical hypothyroidism and persistently low serum thyroxine (T4) and triiodothyronine (T3) levels despite large T4 replacement dosage (0.3-0.4 mg L-thyroxine daily). A defect in T4 absorption was considered unlikely since absorption of fat soluble materials (vitamins A and E) was essentially normal as reflected by their serum concentrations. Abnormalities in serum protein binding of T4 especially by immunoglobulins were suspected; however, thyroid hormone binding antibodies were absent. Thyroxine binding prealbumin (TBPA) levels were either frankly elevated or in the upper normal range and such variations were mirrored by retinol binding protein (RBP) concentrations. Thyroxine binding globulin (TBG) concentration was normal. A surprising finding was an elevated percent dialyzable thyroxine (.041%; normal range, .018-.034%) in spite of a normal concentration of TBG. Serum free fatty acid levels were also elevated. The marked increase in percent free T4 (FT4) fraction together with a low serum total T4 concentration resulted in normal or marginally elevated FT4 levels. An increase in T4 metabolic clearance as suggested by the elevated percent FT4 fraction was corroborated by steady state serum T4 values observed following changes in T4 dosage.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Comparative effects of forskolin and isoproterenol on the cyclic AMP content of human adipocytes.

Alterations in adipocyte cyclic AMP concentrations in response to 100 microM forskolin and 10 microM isoproterenol over a 4 hour period were found to be similar; with each agent, a peak response was noted within 30 minutes. In general, the greater the magnitude of peak response, the more rapid the decline of cyclic AMP concentration during the ensuing 3 1/2 hours. Alpha-2 adrenergic activation, achieved with 10 microM clonidine or 10 microM epinephrine, substantially reduced the cyclic AMP concentrations in cells stimulated by 100 microM forskolin or 10 microM isoproterenol. Isoproterenol-stimulated cells appeared to be more sensitive to alpha adrenergic inhibition than did forskolin-stimulated cells. Cells preincubated for 3 hours with 100 microM forskolin were markedly less responsive to a second exposure to the diterpine. Cells exposed to forskolin for 3 hours also had a reduced response when incubated with isoproterenol; thus, desensitization to forskolin appears to be heterologous. Forskolin desensitization did not appear to be dependent on cellular ATP depletion since cells mildly stimulated during preincubation were as severely desensitized as those adipocytes strongly stimulated. Maximum desensitization required a preincubation time of 1-2 hours with either isoproterenol or forskolin.

Adipose Tissue↗

Cowden disease: gene marker studies and measurements of epidermal growth factor.

Cowden disease (CD) is a familial syndrome characterized by tumors of the skin, oral mucosa, breast, thyroid, and intestinal epithelium. Since the syndrome is inherited as an autosomal dominant, we examined a battery of gene markers in a family with CD to detect linkage between the CD gene and known marker genes. There was no positive evidence for linkage of a CD locus with any of the markers; other investigators can add to our data to confirm and extend these findings. Additionally, we measured epidermal growth factor (EGF) in body fluids from CD patients and controls to determine if elevated EGF levels might be responsible for the widespread epithelial proliferation in CD. EGF levels in saliva, serum, plasma, and urine were similar in CD patients and control subjects. Although alterations in growth factors or their receptors may play a role in CD, excess circulating EGF is not responsible for the manifestations of the syndrome.

Adult↗

Esophageal motor function and response to acid perfusion in patients with symptomatic reflux esophagitis.

There is much evidence to suggest that peristaltic function is defective in esophagitis patients and that this defect may contribute to prolonged acid exposure, promoting esophageal mucosal injury. Abnormal peristalsis may also be related to the generation of reflux symptoms. We evaluated primary peristalsis and its relationship to symptoms under basal conditions and during saline and HCl perfusion in 15 symptomatic reflux patients with gross esophagitis and 15 healthy controls. In the basal state, LES pressure (15.3 vs 25.1 mm Hg) and peristaltic amplitude (74.2 vs 104.8 mm Hg) were significantly lower in subjects with gastroesophageal reflux disease (GERD) (P less than 0.05). During HCl perfusion, peristaltic amplitude and duration increased slightly, and peristaltic velocity slightly decreased similarly in both groups. There was no difference in the incidence of nonpropagated, segmental, or swallow-initiated simultaneous contractions, or change in resting intraesophageal pressure during HCl perfusion in control and GERD groups. This study identified abnormal contractile amplitude as a specific defect in the primary peristaltic wave of esophagitis patients but does not support a role for acid-induced motility changes in the generation of symptoms in GERD.

Adult↗

Normal free fatty acid response to isoproterenol in pseudohypoparathyroidism.

The lipolytic response to isoproterenol infusion was examined in seven normal subjects and six patients with pseudohypoparathyroidism type I [two had deficiency of the hormone receptor-cyclase coupling protein (N-protein) and four did not]. Despite blunted plasma cAMP responses to isoproterenol in both subgroups of pseudohypoparathyroidism patients, the serum FFA responses were normal. We conclude that changes in plasma cAMP do not reflect the adequacy of the lipolytic response to isoproterenol.

Adult↗

Chest pain and dysphagia in patients with prolonged peristaltic contractile duration of the esophagus.

Dysphagia and chest pain are well-described symptoms in subjects with achalasia, diffuse esophageal spasm (DES), and high-amplitude peristaltic contractions, a subset of nonspecific motor disorders (NEMD). We observed a high incidence of chest pain and dysphagia in a different NEMD subgroup characterized by prolonged peristaltic contractile duration (PPCD) and normal contractile amplitude. We compared the manometric characteristics of patients with PPCD to healthy controls and compared the clinical profile of PPCD patients to that of patients with achalasia, DES, and high-amplitude peristalsis. In 20 patients with PPCD, mean contractile duration was 7.4 +/- 0.3 sec, significantly greater than healthy controls (3.7 +/- 0.1 sec) (P less than 0.001). PPCD was associated with an 85% incidence of chest pain and 65% incidence of dysphagia. These symptoms were similar to those observed in patients with achalasia, DES, and high-amplitude peristalsis. In PPCD patients, chest pain was more frequently of long duration in comparison to achalasia and DES. PPCD was encountered more frequently than either achalasia or DES in patients referred to our laboratory. This study suggests that in symptomatic NEMD patients, abnormal duration of peristaltic contractions, rather than abnormal amplitude, may be a distinguishing manometric feature.

Adult↗

Motor disorders of the esophagus: diagnosis and treatment.

Esophageal motor disorders may be clearly primary, as in achalasia or diffuse esophageal spasm (DES), or clearly secondary, as in scleroderma or intrathoracic malignancy. In patients with gastroesophageal reflux, abnormal motility of the esophageal body and stomach, and lower esophageal spasm (LES) appear to predispose patients to reflux. It is possible that esophagitis caused by refluxed gastric material then further impairs motility, propagating the injury. Therapeutically, appropriate use of recently available medications, such as calcium channel blockers and metoclopramide, and new applications of previously available agents, such as hydralazine and bethanechol, have improved our ability to relieve symptoms and at times restore more normal motility.

Bethanechol Compounds↗

Chest pain, dysphagia, and high amplitude esophageal peristalsis: a clinical and manometric study.

Recent literature has called attention to an esophageal motor abnormality characterized by high amplitude peristaltic contractions (HAPC). We characterized symptoms, manometric characteristics, and radiographic findings of 19 such patients and compared them to patients with other nonspecific esophageal motor disorders (NEMD). In the HAPC group, mean amplitude was 254 +/- 14 mm Hg, which was significantly higher than that of control subjects (94 +/- 8.9 mm Hg) and of those with other NEMD (116 +/- 10.8 mm Hg). Contractile duration of the HAPC and NEMD groups was 6.9 +/- 0.5 sec and 5.9 +/- 0.4 sec, respectively, both being significantly higher than normal. Results of esophagograms were frequently abnormal in both groups, but there was no specific abnormality separating the two groups. There was a high incidence of chest pain and dysphagia in the HAPC group. These data suggest that HAPC may represent a distinct subgroup of primary esophageal motor disorders.

Esophageal Diseases↗

Secondary achalasia: association with adenocarcinoma of the lung and reversal with radiation therapy.

A case of secondary achalasia associated with adenocarcinoma of the lung is presented. Manometric studies before, during, and at the conclusion of radiation therapy demonstrated a return of orderly peristalsis, decrease in the elevated lower sphincter pressure, and a return of normal relaxation coincident with resolution of symptoms of dysphagia. The association with adenocarcinoma of the lung and resolution with radiation therapy alone have not been previously reported in secondary achalasia.

Adenocarcinoma↗

Alpha-2 adrenergic activation inhibits forskolin-stimulated adenylate cyclase activity and lipolysis in human adipocytes.

Forskolin at 10 muM caused a 100-fold increase in the intracellular concentration of cyclic AMP and a 6-fold increase in glycerol release in the human adipocyte. These responses are comparable to those prompted by 10 muM isoproterenol. The effects of forskolin on cyclic AMP and lipolysis were dose-dependent. Alpha-2 adrenergic activation, achieved with 10 muM epinephrine and 30 muM propranolol, significantly inhibited forskolin-stimulated cyclic AMP accumulation and glycerol release, shifting the dose-response curves to the right. Forskolin at 10 muM caused a 4.5-fold increase in the adenylate cyclase activity of human adipocyte membranes. When either isoproterenol or epinephrine (0.1 mM) was combined with forskolin, the magnitude of response was substantially greater than the sum of responses achieved by each agent incubated alone.

Adenylyl Cyclases↗

Studies on desensitization of adrenergic receptors of human adipocytes.

The studies described here were undertaken to determine whether or not desensitization of human adipocyte beta and alpha-2 adrenergic receptors could be demonstrated. Cells, isolated from peritoneal adipose tissue obtained from patients undergoing elective abdominal surgery, were preincubated for 3 hr in buffer alone or in the presence of isoproterenol, 10-5M. Cells in both sets of flasks were then washed and exposed to isoproterenol for 1/2 hr; cyclic AMP was then measured as an end point of beta receptor activation. Cells which had had no prior exposure to isoproterenol responded significantly greater to isoproterenol than did cells that had had prior exposure to the catecholamine, The beta receptor characteristics of cells undergoing beta desensitization were assessed using [3H] dihydroalprenolol. Compared to control cells, adipocytes exposed to isoproterenol had a reduction in Bmax while KD values were the same. Thus desensitization of beta adrenergic receptors of human adipocytes occurs and is associated with down regulation in the number of beta receptors. In comparable studies, preincubation with epinephrine 10-5M did not affect the response of cells to a subsequent exposure to this catecholamine. In alpha-2 receptor binding assays, there was a decreased number of [3H]p-aminoclonidine binding sites, but the level of [3H]yohimbine binding was not altered following the incubation with epinephrine. Thus, desensitization of alpha-2 receptors was not demonstrated.

Adipose Tissue↗