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Biomedical subjects

O H Clark

Publications and source records attributed to O H Clark.

At least 163 records · Page 9Linked to original sources
PubMed1989

TSH binding correlates with TSH-stimulated thyroid adenylate cyclase activity in human thyroid tissues.

Thyroid-stimulating hormone (TSH) stimulates adenylate cyclase (AC) activity and the growth and differentiation of thyroid cancers of follicular cell origin. Thyroid neoplasms generally have higher TSH-stimulated AC activity than normal thyroid tissue from the same patients. To determine whether differences in TSH receptors could account for the differences in AC activity, we studied the 8000 g membrane particulate fraction from 28 thyroid tissues (10 papillary carcinomas, 6 multinodular goiters, 4 follicular adenomas, 3 follicular carcinomas, 2 Graves, 1 normal, 1 Hürthle cell adenoma, and 1 thyroiditis). TSH receptors were measured by competitive inhibition using radioactive iodine-labeled bovine TSH (125I-bTSH). Maximal binding capacity (Bmax) and dissociation constant (Kd) were calculated by Scatchard analysis. AC activity was measured by the conversion of alpha-[32P]-ATP to [32P]-cAMP in the maximally (300 mU/ml) TSH-stimulated state. The basal and forskolin-stimulated (100 mmol/L) AC activity were also measured, and the ratios to TSH-stimulated AC activity were calculated (TSH/Basal ratio and TSH/Forskolin ratio). We found a strong correlation between the percent specific binding (%SB) of 125I-bTSH and TSH/Basal ratio (r = 0.70, p = 0.0001), between Bmax and the TSH/Basal ratio (r = 0.71, p = 0.001), between %SB and TSH/Forskolin ratio (r = 0.44, p = 0.02), and between Bmax and TSH/Forskolin ratio (r = 0.65, p = 0.0002). This strong correlation between TSH binding and the TSH-stimulated AC activity suggests that in some thyroid neoplasms the higher AC response to TSH may be due to an increased number of TSH receptors.

Adenylyl Cyclases↗
PubMed1989

Primary hyperparathyroidism. A surgical perspective.

Primary hyperparathyroidism is a common disorder and one that can usually (approximately 95%) be successfully treated by parathyroidectomy. PTH assays have become quite accurate for confirming the diagnosis. In patients with malignancy-associated hypercalcemia, parathyroid-like protein levels are usually increased, and radioimmunoassays being developed to quantitate serum levels of this protein will make the diagnosis easier. Treatment for a parathyroid adenoma is removal of the tumor and identification of the normal parathyroid glands. Treatment for primary or secondary hyperplasia is usually subtotal parathyroidectomy. Recurrent hyperparathyroidism is uncommon, except in patients with familial hyperparathyroidism, MEN-1 parathyroid carcinoma, or renal failure and secondary hyperparathyroidism. Persistent hyperparathyroidism is more common and is usually due to surgeon inexperience, but it is also caused by ectopically situated parathyroid glands, multiple abnormal parathyroid glands, or supranumerary parathyroid glands. Preoperative localization studies using ultrasound, thallium-technetium scanning, MRI, or CT scanning are reliable in patients with solitary parathyroid adenomas, but often fail to detect all of the abnormal parathyroid tissue in patients with multiple abnormal parathyroid glands. Intraoperative use of urinary cyclic AMP assays and rapid PTH assays have recently been used experimentally during parathyroid explorations to determine whether all hyperfunctioning parathyroid tissue has been removed, but these methods are not yet reliable or fast enough to be generally accepted. Most patients with primary hyperparathyroidism who are successfully treated by parathyroidectomy experience psychological, clinical, and metabolic benefits.

Calcium↗
PubMed1988

Mediastinal parathyroid tumors.

Mediastinal parathyroid tumors are a frequent cause of failed parathyroid operations. I therefore reviewed my experience with 285 consecutive patients treated surgically for hyperparathyroidism from January 1981 to Dec 31, 1986. Two hundred eighty-eight operations were performed on these patients (246 primary, 38 secondary, one error in diagnosis, and 53 reoperations). Mediastinal parathyroid tumors were present in 64 (22%) of the entire group of 285 patients with hyperparathyroidism, and 20 (38%) of 53 patients requiring reoperation for persistent or recurrent hyperparathyroidism. Fifty-two parathyroid tumors were situated in the anterior mediastinum and 12 were found in the posterior mediastinum; 56 of the mediastinal tumors were removed via a cervical approach. In four patients the mediastinal tumor was a fifth histologically documented parathyroid gland. Mediastinal tumors were identified by preoperative localization studies (ultrasonography, three [16%]; thallium-technetium, five of 17 [29%]; computed tomography, eight of 14 [57%]; magnetic resonance imaging, three of seven [43%]; and selective venous catheterization for parathyroid hormone, ten of 11 [91%]). Awareness of the relatively high occurrence of mediastinal tumors (52 anterior, 12 posterior) should decrease the risk of failed parathyroid operations.

Adolescent↗
PubMed1988

Thyroid cancer: the case for total thyroidectomy.

Since there are no prospective studies concerning the treatment of thyroid cancer, there continues to be a considerable disagreement about the 'best' or most appropriate form of surgical treatment for patients with papillary or follicular thyroid cancer. Some surgeons recommend selective treatment depending upon the type of thyroid tumor and stage of the disease. Some advocate thyroid lobectomy and isthmusectomy, some near total thyroidectomy, and some total thyroidectomy for patients with papillary and follicular thyroid cancer. Total thyroidectomy for thyroid cancer would be the treatment of choice for virtually all patients with thyroid cancers if it could be done without complications. We therefore reviewed 160 consecutive patients who had total thyroidectomy for suspected or proven thyroid cancer to determine the complication rate of total thyroidectomy. One hundred and three patients had primary operations, 57 had reoperations with completion of total thyroidectomy and 124 had thyroid cancer. Serious complications (i.e. vocal cord paralysis or hypoparathyroidism) included two cases of transient bilateral recurrent nerve palsy, two patients with presumed transient unilateral vocal cord paralysis, three recurrent laryngeal nerves that were purposely sacrificed because of invasion of the nerve, and one case of permanent hypoparathyroidism. Two other patients developed postoperative wound infections. Only one of the permanent complications, the case of permanent hypoparathyroidism, could have been avoided by a lesser procedure. The experienced surgeon can perform a total thyroidectomy with minimal morbidity, and this procedure has certain theoretical and practical advantages. It should not be done, however, if it will result in a significant complication rate and, in selected patients, it may be preferable to leave a small amount of thyroid tissue to protect the blood supply to the parathyroid glands or recurrent laryngeal nerve.

Humans↗
PubMed1988

Localization of parathyroid glands.

Parathyroid localization tests are helpful for all patients with primary hyperparathyroidism before parathyroid exploration, and they are essential for patients who have had previous parathyroid or thyroid operations. The selection of specific localization tests depends on whether the patient is undergoing an initial or a reoperative procedure, as well as on the availability of the specialized equipment and expertise of the physicians and technicians performing and interpreting these studies.

Diagnostic Imaging↗
PubMed1988

Recurrent thyroid carcinoma: characteristics on MR images.

Magnetic resonance (MR) imaging was used in 32 patients, including eight with benign disease, after partial or total thyroidectomy to determine sensitivity and specificity of MR imaging in the detection of tumor recurrence, to compare signal intensities of scar versus recurrent tumor qualitatively and quantitatively, and to define the extent of recurrent tumor. Findings from surgery (n = 23), needle biopsy (n = 1), or clinical follow-up (n = 8) were used for verification. Of 24 patients with primary thyroid carcinoma, 15 had recurrence and nine had a normal postsurgical thyroid bed. Diagnosis from MR images was correct in 20 cases, but false positive in three and false negative in one. Local recurrence was characterized by low to medium intensity on short repetition time (TR)/short echo time (TE) images and medium to high intensity on long TR/long TE images. Scar in the normal postsurgical thyroid bed showed low intensity on both short and long TR/TE images. Local recurrence of thyroid carcinoma and lymph node metastasis produced positive contrast compared with muscle on short TR/short TE (31 + 19%) and long TR/long TE (85 + 30%) images; fibrosis produced negative contrast, particularly on long TR/long TE (-56, -80%) images. These results indicate the capability of MR imaging in the evaluation of recurrence of thyroid tumors and in the differentiation of abnormal tissue due to tumor recurrence from postoperative fibrosis by means of signal contrast relative to a reference tissue.

Adult↗
PubMed1988

Deoxyribonucleic acid cytometry helps identify parathyroid carcinomas.

It may be difficult in some patients with parathyroid tumors to distinguish between parathyroid carcinoma and parathyroid adenoma on the basis of clinical and histopathological findings. Patients initially diagnosed as having a parathyroid adenoma have subsequently occasionally developed metastases, and thereby their tumor was proven to be a carcinoma. To determine whether the nuclear DNA content would correlate with the clinical course and pathology of parathyroid tumors DNA cytometry was performed on parathyroid carcinomas (9 patients), histologically atypical adenomas (10 patients), adenomas associated with severe hypercalcemia [serum calcium, greater than or equal to 13.0 mg/dL (greater than or equal to 3.24 mmol/L); 11 patients], typical benign adenomas (11 patients), and incidentally removed normal parathyroid glands (6 patients). Sections were cut from the original paraffin-embedded surgical specimens and stained for nuclear DNA using the azure A Feulgen reaction. Nuclear DNA stain content was measured using an integrating image cytometer, and the results were plotted as histograms. Adjusted optical density (AOD) values were measured (in arbitrary units) to estimate the DNA content of whole nuclei in the specimens. The mean nuclear DNA content in the parathyroid carcinomas [24.6 +/- 2.1 (+/- SE) AOD] was significantly greater than that in the three groups of parathyroid adenomas (P less than 0.005, by unpaired t test) and in the normal parathyroid glands (P less than 0.0005). The mean nuclear DNA content in the atypical adenomas (15.8 +/- 1.6 AOD), profoundly hypercalcemic adenomas (16.8 +/- 1.3 AOD), and typical adenomas (16.0 +/- 1.1. AOD) were similar, and all were significantly greater than that in the normal parathyroid glands (11.5 +/- 0.7 AOD, P less than 0.05). Five distinct DNA histogram patterns were present in the parathyroid specimens from these 47 patients. Four of the 9 parathyroid carcinomas had an aneuploid DNA pattern, an abnormal pattern not found in any of the other groups; 2 of these tumors were originally diagnosed as atypical parathyroid adenomas. Both patients developed recurrent disease, and 1 died from a hepatic metastasis. Therefore, DNA cytometry provides valuable information in differentiating some parathyroid carcinomas from adenomas and diagnosing certain parathyroid carcinomas before the appearance of grossly invasive or metastatic tumor.

Adenoma↗
PubMed1988

Diagnosis of recurrent hyperparathyroidism: comparison of MR imaging and other imaging techniques.

Several reports have indicated good results with MR imaging of hyperparathyroidism. However, its use in recurrent hyperparathyroidism has not been assessed separately. Thirty patients with recurrent hyperparathyroidism were evaluated by MR with both T1- and T2-weighted images. Twenty-six and 23 of these patients, respectively, also had thallium-201 scintigraphy and high-resolution sonography. For the 28 patients who eventually had surgical exploration and histologic evidence of adenoma (21 cases) or hypoplasia (seven cases), MR accurately located abnormal parathyroid glands in 75% evaluated prospectively and 89% evaluated retrospectively. Scintigraphy located 68% prospectively and 76% retrospectively. Sonography detected 57% prospectively and 67% retrospectively. For patients undergoing three studies, the prospective and retrospective detection rate was significantly better (p less than .05) for MR compared with sonography but was not significantly different for MR and scintigraphy. MR detected three of four mediastinal adenomas evaluated prospectively and retrospectively. One false-positive case was seen with MR, one with scintigraphy, and one with sonography. Thus, MR can be used to locate abnormal parathyroid tissue at a rate equal to or better than scintigraphy or sonography.

Adenoma↗
PubMed1988

Stimulatory effect of vasoactive intestinal polypeptide on human normal and neoplastic thyroid tissue.

Recent investigations suggest that although thyroid-stimulating hormone (TSH) is the major regulator of thyroid gland function, it is not the only hormone that regulates the thyroid gland. Another factor regulating thyroid gland function is vasoactive intestinal polypeptide (VIP), which is present in nerves that innervate thyroid blood vessels and follicles. Previous studies have documented that VIP stimulates adenylate cyclase (AC) activity in cultured normal and hyperplastic (Graves) thyroid tissue, thus increasing intracellular cyclic AMP concentration. To our knowledge, however, there is no information concerning the effect of VIP on neoplastic thyroid tissue. Therefore we studied the effect of VIP on normal and neoplastic human thyroid tissue from 10 patients (follicular adenomas, 4; follicular carcinomas, 3; and papillary carcinomas, 3). Adenylate cyclase activity was measured in a 8000 g membrane preparation in the basal state and when incubated with VIP, TSH, and both. VIP increased AC activity in normal tissue and tumor in a dose-dependent manner, with maximal stimulation at 10(-6) mol/L (p less than 0.05). In normal tissue, 10(-6) mol/L VIP and a maximally stimulating concentration of TSH (300 mU/ml) stimulated AC to the same degree. In tumors, although both TSH and VIP increased AC activity, the response to TSH was greater (p less than 0.01). VIP and TSH had an additive effect in normal tissue (p less than 0.05), whereas in tumors the AC response to VIP and TSH was the same as with TSH alone (p = 0.66). This study documents that VIP is a potent stimulator of adenylate cyclase in both normal and neoplastic human thyroid tissues. The magnitude of this effect is similar to that produced by TSH, which implies that VIP plays a physiologically important role in the regulation of the secretion and growth of normal and neoplastic thyroid tissues.

Adenocarcinoma↗
PubMed1987

Carcinoids associated with multiple endocrine neoplasia syndromes.

Carcinoids occur in association with MEN types 1 and 2. To determine the relationship between carcinoids and MEN, we reviewed nine patients with carcinoids and other endocrine tumors. Analyzing these 9 patients and 56 other patients previously described in the literature, we found several clinically important relationships. In contrast to the usual midgut and hindgut origin, most carcinoids associated with MEN (69 percent) are of foregut origin (thymus 24 percent, bronchus 27 percent, stomach 3 percent, and duodenum 14 percent). Carcinoids are more commonly associated with MEN type 1 than MEN type 2 (59 patients and 6 patients, respectively). Thymic carcinoids associated with MEN are more common in men (15 versus 2), and most (82 percent) are malignant. Bronchial carcinoids associated with MEN are more common in women (15 versus 4), and most (74 percent) are benign. There is a strong association between thymic carcinoids and parathyroid tumors and between bronchial carcinoids and pituitary tumors. Most patients with carcinoids and hyperparathyroidism (82 percent) have had parathyroid hyperplasia or multiple parathyroid adenomas. Thus, carcinoids may occur in association with both MEN type I and MEN type II. MEN should be suspected in patients with foregut carcinoids. Patients with MEN and ectopic ACTH production should be considered to have bronchial carcinoids if they are female and thymic carcinoid if they are male. The thymus should be routinely removed in patients with MEN type I because of the possible presence of an ectopic parathyroid gland in this tissue and to prevent subsequent development of a carcinoid tumor.

Adolescent↗
PubMed1987

Factors influencing the growth of normal and neoplastic thyroid tissue.

TSH activates the adenylate cyclase and the phosphoinositide turnover-protein kinase C-calcium systems in thyroid cells and appears to have an important but variable role in controlling the growth of both normal and neoplastic thyroid tissues. Species differences, experimental conditions, and tissue or tumor cell heterogeneity may account for this variability. Although TSH seems to be an important physiologic growth factor, it is neither the exclusive growth factor for the thyroid gland nor absolutely necessary for the effect of other thyroid growth factors. TSH may work in concert with other growth factors such as EGF. Some growth factors influence thyroid growth through TSH, whereas others do not.

Adenylyl Cyclases↗
PubMed1987

Hyperparathyroidism: comparison of MR imaging with radionuclide scanning.

Twenty-three patients with hyperparathyroidism were evaluated preoperatively with magnetic resonance (MR) imaging. Twenty patients also underwent thallium-201/technetium-99m scintigraphy. Of 22 patients with primary hyperparathyroidism, 12 had persistent or recurrent disease. One had secondary hyperparathyroidism due to end-stage renal disease. MR imaging allowed accurate localization of abnormal parathyroid glands in 64% evaluated prospectively and 82% evaluated retrospectively. Scintigraphy allowed localization of 60% evaluated prospectively and 70% retrospectively. The two imaging modalities together allowed detection of 68% evaluated prospectively and 91% retrospectively. MR imaging allowed detection of two of five mediastinal adenomas evaluated prospectively and four of five retrospectively. In patients who underwent both imaging studies, MR was more successful in those with previous neck surgery (73% evaluated prospectively and 91% retrospectively) than in those with no prior surgery (57% prospectively and 71% retrospectively). Scintigraphy allowed accurate localization in 64% evaluated prospectively and 64% retrospectively in patients with previous surgery versus 57% prospectively and 86% retrospectively in patients with no prior neck surgery. Four false-positive results were obtained with MR imaging and three with scintigraphy. MR imaging was useful for parathyroid localization in patients with hyperparathyroidism, particularly in patients requiring additional surgery.

Adult↗
PubMed1987

Parathyroid variants: US evaluation.

High-resolution (10-MHz) ultrasonography was performed in 181 patients with primary or secondary hyperparathyroidism during a 4-year period and evaluated retrospectively. Thirty-seven unusual-appearing parathyroid tumors were found among 235 parathyroid glands identified as abnormal. There was pathologic correlation in 36. The typical appearance of parathyroid adenoma was that of an oval hypoechoic or anechoic lesion in the neck, aligned in a craniocaudal direction and often posterior to the thyroid. Morphologic variations from the norm included giant size (n = 11) (4.6%), cystic changes in a solid tumor (n = 9) (3.8%), calcified glands (n = 6[in three patients]) (2.5%), a multilobulated configuration (n = 5) (2.1%), an inhomogeneous pattern (n = 5) (2.1%), and a parathyroid cyst (n = 1) (0.4%). Recognizing the abnormal parathyroid variants can increase the diagnostic accuracy of sonographic examination.

Adenoma↗
PubMed1987

Parathyroid localization. Clinical review.

Recent advances in the techniques of preoperative parathyroid localization include ultrasonography, computed tomography, thallium-technetium subtraction scanning, magnetic resonance imaging, digital subtraction angiography with selective venous catheterization for PTH measurement, and ultrasound or CT-guided needle aspiration biopsy for cytological examination or PTH assay. These techniques are helpful for patients with hyperparathyroidism undergoing the initial operation, and essential for patients with persistent or recurrent hyperparathyroidism undergoing reoperation. Noninvasive procedures should be performed first, and the combination of any two positive studies localizes the tumor with near certainty. Invasive procedures have a higher risk of complications and are recommended only in selected patients before reoperation.

Biopsy, Needle↗
PubMed1987

Parathyroid carcinoma versus parathyroid adenoma in patients with profound hypercalcemia.

The metabolic manifestations and operative findings in 10 patients with a diagnosis of parathyroid carcinoma were analyzed to determine whether they differ from those in patients with parathyroid adenomas and similar degrees of hypercalcemia. Two groups of patients with parathyroid adenomas were used for comparison. Group A consisted of eight patients with "atypical" benign adenomas (mean preoperative level of serum calcium: 13.4 mg/dl); group B consisted of 13 patients with benign typical adenomas--all with preoperative serum calcium levels greater than or equal to 13.0 mg/dl (mean: 14.2 mg/dl). The patients with carcinoma (mean preoperative level of serum calcium: 15.3 mg/dl) had a frequency of osteoporosis and osteitis fibrosa cystica (50%) comparable with that of group A (33%) and group B (62%). Seventy percent of the patients with carcinoma had renal disease (nephrolithiasis, nephrocalcinosis, or impaired renal function), whereas only 38% of group A and 15% of group B had similar disorders. The patients with carcinomas had the highest frequency of combined bone and renal disease (50% versus 14% in group A and 15% in group B). Anemia, peptic ulcer disease, and hypertension occurred with similar frequencies in the three groups. Three patients with recurrent parathyroid carcinoma died of profound hypercalcemia, renal failure, or cardiac arrhythmia. In general, although patients with parathyroid carcinomas have more profound metabolic abnormalities than do patients with primary hyperparathyroidism, the metabolic manifestations in patients with parathyroid carcinoma are comparable with those in patients with parathyroid adenomas and profound hypercalcemia. Furthermore atypical adenomas share many anatomic and histopathologic features with parathyroid carcinomas, and distinguishing between the two is sometimes possible only in cases of tumor recurrence.

Adenoma↗