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Biomedical subjects

N W Thompson

Publications and source records attributed to N W Thompson.

At least 37 records · Page 2Linked to original sources

Absence of the palmaris longus muscle: a population study.

We examined 300 Caucasian subjects (150 males, 150 females) aged 18-40 years to assess the incidence of palmaris longus absence. The presence or absence of palmaris longus was assessed by clinical inspection. Forty-nine subjects had unilateral absence of palmaris longus (16%). The tendon was absent bilaterally in 26 subjects (9%). Unilateral and bilateral absence was more common in males, however this was not statistically significant (p = 0.25 and 0.56 respectively). In those subjects with unilateral absence, the right side was found to be more commonly affected however no statistical significance was evident (p = 0.25).

Adolescent↗

Granular-cell tumor of trachea masquerading as Hurthle-cell neoplasm on fine-needle aspirate: a case report.

We report on a case of extraluminal tracheal granular-cell tumor which was interpreted as a Hurthle-cell neoplasm of the thyroid on fine-needle aspirate. Review of the literature reveals only one other such case. The patient was a 35-yr-old female who presented with an enlarged thyroid. Aspiration cytology revealed a syncytium of cells with abundant granular cytoplasm interpreted as a thyroid follicular neoplasm with Hurthle-cell change. However, histology of the resection specimen with immunohistochemistry confirmed it as a granular-cell tumor. The cytologic differential diagnosis of neoplasms with oncocytoid cytoplasm in and around the thyroid should include granular-cell tumor of the trachea.

Adenoma, Oxyphilic↗

Complications of thyroid surgery: how to avoid them, how to manage them, and observations on their possible effect on the whole patient.

Surgery of the thyroid takes place in an area of complicated anatomy and in which a number of vital physiologic functions and special senses are controlled. Thyroidectomy rarely is associated with mortality; but unless the surgeon performing it is well trained in operative surgery and is knowledgeable of the gland and its function, pathology, and anatomy, excellent results cannot be achieved. Failure to observe cardinal surgical principles may result in legal difficulties, which can be avoided. It is well to observe the principles and avoid problems. We address this issue herein.

Humans↗

Serum thyroglobulin levels after thyroxine withdrawal in patients with low risk papillary thyroid carcinoma.

We hypothesized that elevated levels of serum thyroglobulin (Tg) are frequently found as the only index of residual neoplasm in patients with low-risk papillary thyroid carcinoma. The records of patients operated on for papillary thyroid carcinoma over a 2-year period were reviewed, and the patients were allocated to risk groups by a validated staging method that does not include Tg levels. Of the 35 patients who manifested a low-risk carcinoma, 9 (26%) exhibited elevated Tg concentrations (11-53 ng/mL) during thyroxine withdrawal after therapies, while clinical, scintigraphic, and radiographic studies at least 1 year later showed no evidence of tumor. Prior scintigraphic imaging of therapeutic doses of 131I in 8 of 9 patients demonstrated no distant metastases, further confirming the low-risk status of this group. The staging method predicts that only 0.9% of patients with low-risk papillary carcinoma will have a cause specific death in 20 years. Elevated Tg concentrations have not been shown to forecast independently the survival of patients with low-risk papillary carcinoma. Thus, although frequently encountered, elevated Tg concentrations are unlikely to predict shortened survival in patients with papillary carcinoma for whom low risk has been determined from other data.

Adult↗

Endoscopic ultrasound is highly accurate and directs management in patients with neuroendocrine tumors of the pancreas.

UNLABELLED: Preoperative localization of pancreatic neuroendocrine tumors with traditional imaging fails in 40-60% of patients. Endoscopic ultrasound (EUS) is highly sensitive in the detection of these tumors. Previous reports included relatively few patients or required the collaboration of multiple centers. We report the results of EUS evaluation of 82 patients with pancreatic neuroendocrine tumors. METHODS: We prospectively used EUS early in the diagnostic evaluation of patients with biochemical or clinical evidence of neuroendocrine tumors. Patients had surgical confirmation of tumor localization or clinical follow-up of >1 yr. RESULTS: Eighty-two patients underwent 91 examinations (cases). Thirty patients had multiple endocrine neoplasia syndrome type 1. One hundred pancreatic tumors were visualized by EUS in 54 different patients. The remaining 28 patients had no pancreatic tumor or an extrapancreatic tumor. Surgical/pathological confirmation was obtained in 75 patients. The mean tumor diameter was 1.51 cm and 71% of the tumors were < or =2.0 cm in diameter. Of the 54 explorations with surgical confirmation of a pancreatic tumor, EUS correctly localized the tumor in 50 patients (93%). Twenty-nine insulinomas, 18 gastrinomas, as well as one glucagonoma, one carcinoid tumor, and one somatostatinoma were localized. The most common site for tumor localization was the pancreatic head (46 patients). Most tumors were hypoechoic, homogenous, and had distinct margins. EUS of the pancreas was correctly negative in 20 of 21 patients (specificity, 95%). EUS was more accurate than angiography with or without stimulation testing (secretin for gastrinoma, calcium for insulinoma), transcutaneous ultrasound, and CT in those patients undergoing further imaging procedures. EUS was not reliable in localizing extrapancreatic tumors. CONCLUSIONS: In this series, the largest single center experience reported to date, EUS had an overall sensitivity and accuracy of 93% for pancreatic neuroendocrine tumors. Our results support the use of EUS as a primary diagnostic modality in the evaluation and management of patients with neuroendocrine tumors of the pancreas.

Adenoma, Islet Cell↗

Periprosthetic femoral fractures in Northern Ireland.

Twenty-five patients with periprosthetic femoral fractures were admitted to the Ulster Hospital between August 1998 and May 2000. Average age was 77 years (range, 42-96 years) with a female to male ratio of 2:1. Twenty-four of the fractures occurred following primary joint arthroplasty on average 7.6 years from insertion of the primary prosthesis. One patient sustained an intraoperative fracture during revision surgery. In the majority (80%), the periprosthetic femoral fracture was associated with a traumatic event. On average, two days elapsed from the time of injury until admission to our unit. Time from admission to surgery was on average 4 days. All patients were treated by open fracture fixation. Duration of stay in the fracture unit was on average 20 days. Prior to their fracture 92% of patients were living at home and 84% were mobile either unaided or with the use of a stick. At most recent review, 72% are back living at home and 60% are mobile either unaided or with the use of a stick. We emphasise that there is the likelihood of an increase in periprosthetic femoral fractures due to the increasing number of primary arthroplasties being performed on a more active, ageing population. Preventative measures and cost implications are also discussed.

Adult↗

TRAIL death pathway expression and induction in thyroid follicular cells.

To determine whether programmed cell death in thyroid follicular cells can be related to activation of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway, we examined the expression and function of this pathway in primary thyroid follicular cells and a papillary thyroid carcinoma cell line in vitro. Despite the expression of TRAIL receptors death receptor 4 and death receptor 5, purified TRAIL could not induce programmed cell death (PCD) in any of the thyroid follicular cells examined. However, pre-incubation with cycloheximide before TRAIL facilitated the induction of rapid and massive PCD. This suggested that despite the presence of a labile inhibitor of the TRAIL pathway, TRAIL could mediate PCD under appropriate conditions. To determine whether there were sources of TRAIL in the thyroid that could interact with thyroid follicular cell TRAIL receptors, RNase protection assays were used to determine TRAIL mRNA expression. TRAIL message was expressed in intrathyroidal lymphocytes isolated from a patient with thyroiditis, and unexpectedly, thyroid follicular cells themselves could be induced to express abundant TRAIL message in the presence of the inflammatory cytokines interferon gamma, tumor necrosis factor alpha, and interleukin 1beta. Furthermore, the papillary thyroid carcinoma cell line could be induced to kill the TRAIL-sensitive lymphoma cell line BJAB through a TRAIL-dependent mechanism.

Apoptosis↗

Evaluation of retinoblastoma and Ki-67 immunostaining as diagnostic markers of benign and malignant parathyroid disease.

Assessment of the malignant potential of parathyroid tumors in the absence of metastases can be difficult using morphologic criteria alone. In this study we have examined a total of 58 parathyroid tumors (31 benign, 15 malignant, and 12 equivocal) from 54 patients using immunohistochemistry with monoclonal antibodies directed against the retinoblastoma (RB) protein and the cell cycle-associated antigen Ki-67 to evaluate their role as diagnostic markers. RB protein immunoreactivity was not useful for distinguishing between benign and malignant parathyroid tumors. Analysis of the proliferation marker Ki-67 showed that there was a trend toward more intense staining in the malignant cases. The Ki-67 labeling index was highest in the parathyroid cancers (median 33) and lowest in the sporadic primary adenomas (median 2). An observation that might have clinical implications is that tumors from patients with familial hyperparathyroidism linked to chromosome 1q showed a high Ki-67 index, indicating strong proliferative activity (median 25). This correlates well with the clinical observation of tumors with malignant potential in this syndrome. Because of the considerable overlap between groups of tumors, Ki-67 is not suitable for definitive differentiation between benign and malignant tumors. However, Ki-67 may give valuable information about which patients should be followed more closely.;1999>

Antibodies, Monoclonal↗

Expression of matrix metalloproteinase gelatinase A messenger ribonucleic acid in parathyroid carcinomas.

BACKGROUND: The incidence of parathyroid cancer in patients with hyperparathyroidism is less than 1%. However, these few cases cause diagnostic problems in the absence of clear-cut invasion of adjacent organs or metastasis. New markers are needed to increase diagnostic accuracy. METHODS: Thirty-one parathyroid tumors from patients with primary hyperparathyroidism were collected worldwide. Eighteen tumors were classified as unequivocal cancers, whereas 13 tumors were considered equivocal because of a lack of infiltrative growth or evidence of recurrence. Paraffin sections were hybridized with a 35S-labeled riboprobe complementary to gelatinase A mRNA, dipped in photographic emulsion, developed, counterstained, and then evaluated by light- and dark-field microscopy. RESULTS: Fourteen of the 18 unequivocal parathyroid cancers expressed gelatinase A, as compared with the equivocal tumors, of which only 4 of 13 showed expression. The strongest hybridization signal was seen in stromal cells at the tumor border, most likely fibroblasts and macrophages. No expression was detected in tumor cells. CONCLUSIONS: Invasive growth of many tumors is facilitated by proteolytic enzymes, such as gelatinase A. The presence of gelatinase A mRNA in parathyroid tumors strengthens the suspicion of malignancy but cannot be used as a definitive marker of malignancy.

Adult↗

Diabetes mellitus with hyperparathyroidism: another indication for parathyroidectomy?

BACKGROUND: Patients with hyperparathyroidism have alterations in carbohydrate metabolism characterized by insulin resistance, hyperinsulinemia, and glucose intolerance. The clinical significance of these findings in the management of patients with diabetes mellitus (DM) after parathyroidectomy for hyperparathyroidism has been controversial. METHODS: A retrospective review identified 87 patients with DM and hyperparathyroidism who underwent parathyroidectomy. The follow-up documentation of 70 patients who underwent diabetic management was then evaluated to assess the benefit of parathyroidectomy on glucose management. RESULTS: Thirteen patients had type 1 DM, and 74 patients had type 2 DM. Primary hyperparathyroidism was present in 93% of patients with type 2 DM; 64% of patients with type 1 DM had secondary hyperparathyroidism. At follow-up, glucose control was stable in 40% of patients, had improved in 37% of patients, and had deteriorated in 23% of patients (P = .003). Improved glucose control was not dependent on age, duration of DM, duration of hyperparathyroidism, length of follow-up, or calcium levels. The patients with decreased requirements had a significantly lower parathyroid hormone level (P = .05). Improved glucose control was most significant in patients whose condition was managed with oral hypoglycemics (P = .05) or insulin (P = .03). CONCLUSIONS: The clinical and laboratory investigations on the influence of hyperparathyroidism on DM support the benefit of parathyroidectomy in patients with DM. Patients with type 1 and type 2 DM show improvement in glucose control after parathyroidectomy. The presence of DM and hyperparathyroidism is an indication for parathyroidectomy because it results in either stabilization or improved glucose control in 77% of patients.

Adult↗

Pheochromocytomas: imaging with 2-[fluorine-18]fluoro-2-deoxy-D-glucose PET.

PURPOSE: To assess the sensitivity of positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) in pheochromocytomas and, secondarily, to compare images obtained with FDG PET to those obtained with metaiodobenzylguanidine (MIBG) scintigraphy. MATERIALS AND METHODS: Twenty-nine patients with one or more known or subsequently proved pheochromocytomas underwent FDG PET (35 scans) and MIBG scintigraphy (35 scans). Tumor uptake of FDG was quantified on positive PET scans. RESULTS: Tumor uptake of FDG was detected in 22 of 29 patients. Most benign (seven of 12 patients) and most malignant (15 of 17 patients) pheochromocytomas and their metastases avidly concentrated FDG. In four patients whose pheochromocytomas failed to accumulate MIBG, uptake of FDG in the tumors was intense. For the majority of the 16 patients whose tumors concentrated both agents, however, ratings for MIBG images compared to FDG PET images for delineation of the tumor in comparison to background and normal organ accumulation were superior for nine patients (56%) and as good or better for 14 (88%). CONCLUSION: Most pheochromocytomas accumulate FDG. Uptake is found in a greater percentage of malignant than benign pheochromocytomas. FDG PET is especially useful in defining the distribution of those pheochromocytomas that fail to concentrate MIBG.

3-Iodobenzylguanidine↗

Characterization of FAP-1 expression and function in thyroid follicular cells.

Human thyrocytes are resistant to Fas-mediated programmed cell death (PCD). It has been reported that a labile protein inhibitor is involved in the protection of thyrocytes from PCD, and its action can be reversed by incubation of thyrocytes with cycloheximide (CHX) during treatment with agonist anti-Fas Ab. Fas-associated phosphatase-1 (FAP-1) is a protein that has been shown to interact with the negative regulatory domain of Fas and block Fas-mediated apoptosis in FAP-1 transfected Jurkat cells. We investigated the possibility that FAP-1 might be involved in protection against Fas-mediated PCD in human thyrocytes. FAP-1 mRNA was detected in primary thyrocytes using a ribonuclease protection assay. The presence of FAP-1 protein was confirmed by immunohistochemical staining and flow cytometry using a polyclonal anti-FAP-1 Ab. FAP-1 protein also disappeared from thyroid cells in response to CHX. To determine whether FAP-1 is a functional inhibitor of PCD in thyrocytes, we incubated thyrocytes with synthetic SLV (Ac-SLV) tripeptide to compete with Fas for interaction with FAP-1. Thyrocytes treated with Ac-SLV tripeptide showed significantly increased cell death as compared to cells treated with control tripeptide. In addition, in the presence of a suboptimal concentration of CHX, the Ac-SLV tripeptide yielded a strong, synergistic increase in Fas-mediated PCD as compared to thyrocytes treated with control tripeptide. These results implicate FAP-1 as a regulator of Fas-induced PCD in thyrocytes.

Apoptosis↗

1Alpha,25-dihydroxyvitamin D3 up-regulates Bcl-2 expression and protects normal human thyrocytes from programmed cell death.

Apoptosis is thought to play an important role in the pathogenesis of autoimmune thyroid disease. 1alpha,25-dihydroxyvitamin D3 (VD3) has been shown to suppress several autoimmune diseases. However, the mechanism by which VD3 has these effects is not known. We evaluated the alterations in apoptosis, induced by VD3. Thyrocytes were treated with VD3, and the expression of the Bcl-2 family molecules was studied at both the messenger RNA and protein levels. It was found that VD3 significantly induced the expression of Bcl-2 messenger RNA and protein in thyrocytes but had no effect on the expression of Bcl-xl and Bax. The increase in Bcl-2 expression, mediated by VD3, correlated with protection of thyrocytes against the induction of apoptosis by either staurosporine or UV irradiation. VD3-induced increases in the expression of Bcl-2 could be mimicked by VD3 analogs with high nuclear receptor affinity, but not by analogs only with nongenomic actions. These data indicate a role for Bcl-2 in the regulation of apoptosis in thyrocytes and raise the possibility that VD3 or its agonists may have therapeutic benefit in thyroid disorders.

Apoptosis↗

Alternative genetic pathways in parathyroid tumorigenesis.

In this study 44 parathyroid tumors from 26 sporadic cases, 10 cases previously given irradiation to the neck, and 8 familial cases were screened for sequence copy number alterations by comparative genomic hybridization. In the sporadic adenomas, commonly occurring minimal regions of loss could be defined to chromosome 11 (38%), 15q15-qter (27%), and 1p34-pter (19%), whereas gains preferentially involved 19p13.2-pter (15%) and 7pter-qter (12%). Multiple aberrations were found in sporadic tumors with a somatic mutation and/or loss of heterozygosity of the MEN1 gene. The irradiation-associated tumors also showed multiple comparative genomic hybridization alterations and frequent losses of 11q (50%), and subsequent analysis of the MEN1 gene demonstrated mutations in 4 of 8 cases (50%). The adenomas from familial cases showed few alterations, and in 3 of these tumors a gain of 19p13.2-pter was seen as the only aberration. In this study numerical copy number alterations were frequently detected in sporadic and irradiation-associated parathyroid adenomas, although these tumors are benign. The majority of these alterations were found in tumors with confirmed involvement of the MEN1 gene locus in agreement with a role of the MEN1 gene in genomic stability. Furthermore, the frequent occurrence of MEN1 mutations (50%) in irradiation-associated parathyroid tumors suggests that inactivation of the MEN1 gene is an important genetic alteration involved in the development of parathyroid tumors in postirradiation patients.

Adenoma↗

Fas (CD95) expression is up-regulated on papillary thyroid carcinoma.

Thyrocyte apoptosis signaled through the Fas receptor has been proposed as a mechanism for the cytotoxicity observed in thyroiditis, but the role the Fas pathway plays in thyroid cancer is not known. We examined Fas expression in thyroid tissue derived from patients with papillary carcinoma and follicular cancer. More intense immunohistological staining for the Fas protein was observed on papillary cancer cells as compared with adjacent normal follicles. To further characterize the expression of Fas in papillary cancer, paired normal and cancerous thyroid tissues were obtained at thyroidectomy from several donors, digested, and placed into cell culture. Messenger RNA was analyzed by ribonuclease protection assays, and protein was identified by flow cytometry. Fas expression was detected at levels up to 3-fold higher in cancerous thyrocytes compared with paired normal cells. To determine whether the expressed Fas antigen was functional, thyrocytes were treated with a monoclonal IgM anti-Fas antibody (clone CH11; Upstate Biotechnology, Inc., Lake Placid, NY) in the presence of interferon-gamma and cycloheximide. Whereas both normal and cancerous thyrocytes were induced to die after this treatment, the cancerous thyrocytes were more sensitive to anti-Fas antibody. This work demonstrates that the Fas antigen is expressed and functional on papillary thyroid cancer cells and this may have potential therapeutic significance.

Adenocarcinoma, Follicular↗