PubMed Health⌕ Search

Biomedical subjects

C Juhlin

Publications and source records attributed to C Juhlin.

82 records · Page 5Linked to original sources

Surgery for sporadic primary hyperparathyroidism in the elderly.

Retrospective analysis has been performed on 108 consecutive patients operated for primary hyperparathyroidism (HPT) at 75 to 85 years of age (mean 79 years). The preoperative serum calcium value averaged 2.99 mM, and six patients had hypercalcemic crisis. Psychic disturbances were seen in 60 patients (56%), 40% of whom demonstrated dementia. Skeletal and muscular complaints were registered in 29% and 19%, respectively, and only 6% were overtly asymptomatic. Cardiovascular diseases were presented by 69% of the patients, 13% had diabetes mellitus, and 26% were institutionalized prior to surgery. Bilateral neck exploration disclosed a single adenoma in 69%, which was of the oxyphil cell type in 13%, and water-clear (n = 3) or chief cell hyperplasia in 27%. The total glandular weight averaged 1085 mg. Altogether 72 patients operated on after 1980 demonstrated a perioperative (30-day) mortality of 1.4%; the corresponding morbidity of 8.7% mainly included infections as well as a vocal cord paralysis in one patient and two incisional hematomas. Analysis for mean 3.1 years postoperatively displayed reversal of hypercalcemia in 95% of the patients; 2.8% of those operated after 1980 had persistent disease. Symptoms seemed to be alleviated in 62%, with a similar rate attained in patients with dementia. Altogether 60 patients died from mainly cardiovascular diseases mean 4.2 years after the operation. Those succumbing the first postoperative year (n = 21) showed overrepresentation of cardiac diseases and diabetes mellitus. The results demonstrate prevalent psychic disturbances, oxyphil adenomas, and multiglandular parathyroid disease in elderly patients with primary HPT and favor rather liberal application of parathyroid surgery among these individuals.

Aged↗

Surgical treatment of mid-gut carcinoid tumors.

Coincident with medical antitumor treatment of 138 patients suffering from mid-gut carcinoid tumors, 51 patients were subjected to surgery with the principal aims of removing primary tumors and debulking mesenteric or liver metastases. Sixteen patients had previously been operated with intestinal resection or, when the tumors had been considered inexcisable, with intestinal bypass or laparotomy alone. Apart from exhibiting symptoms related to the carcinoid syndrome, the majority (approximately 60%) of the 51 patients had generally intermittent, subileus-like abdominal pain and weight loss. In 18 patients, these symptoms were pronounced and associated with intestinal obstruction or severe malnutrition. Computed tomography and arteriography efficiently demonstrated mesenteric and liver metastases. At laparotomy, the primary intestinal tumors were small, mainly less than 1 cm in diameter, and they were multiple in 39% of the patients. Mesenteric metastases measuring up to 12 cm in diameter were present in 86% of the patients. These metastases were frequently associated with a pronounced mesenteric and retroperitoneal fibrosis causing fixation, angulation, and obstruction of the bowel as well as incipient intestinal gangrene in 8 patients. In all but 6 patients, the primary tumors could be removed by comparatively limited intestinal resections although bulky mesenteric metastases were often dissected from the mesenteric vessels. Liver metastases, found in 49% of the patients, were generally bilateral and multiple, and major hepatic metastases were resected in 6 patients. The results support a role for surgery also in the more compromised patients with mid-gut carcinoid tumors and that such intervention may be associated with considerable symptomatic relief and substantial periods of survival.

Adult↗

Monoclonal antibodies raised against mid-gut carcinoid tumor cells.

Three monoclonal IgG 2a antibodies were produced after immunization of mice with dispersed cells from a human mid-gut carcinoid tumor. Acetone-fixed cryosections of 57 primary and metastatic mid-gut carcinoid tumors as well as 2 hind-gut (rectal) carcinoids showed a conspicuous immunoreaction while a thymic carcinoid was essentially unstained with the antibodies. The 3 antibodies yielded a similar pattern of immunostaining. The immunoreaction comprised more than 95% of the carcinoid tumor cells, and it was more uniform and intense in primary tumors than in mesenteric, hepatic, and ovarian metastases of the mid-gut carcinoid tumors. Immunofluorescence studies on suspended carcinoid tumor cells showed that the antibodies bound to the surface membrane of the cells. The antibodies immunostained enterocytes of the small and large bowel, intestinal metaplasia of the stomach mucosa as well as colorectal adenocarcinomas. Endocrine pancreatic tumors producing vasoactive intestinal polypeptide, gastrin, somatostatin, and/or pancreatic polypeptide as well as the epithelium of pancreatic ducts were also stained with the antibodies, whereas a large number of other normal and abnormal human tissues, including benign and malignant insulinomas, were unreactive. The findings indicate that the antibodies recognize differentiation antigens on the carcinoid tumor cell surface preserved also on endocrine and nonendocrine cells of the normal bowel mucosa. The restricted tissue reactivity of the antibodies suggests that they may constitute useful tools in the histological characterization of carcinoid tumors. Further studies may reveal if they are applicable for immunolocalization and perhaps even immunotherapy of these neoplasms.

Antibodies, Monoclonal↗

Cellular physiology and pathophysiology of the parathyroid glands.

This report provides insight into parathyroid gland physiology and the pathophysiology of hyperparathyroidism (HPT). Increases in the extracellular calcium concentration constitute the primary physiological signal for inhibition of parathyroid hormone (PTH) release. Transduction of the external signal into a cellular response involves activation of a cation receptor mechanism on the plasma membrane with rapid rise in the cytoplasmic calcium concentration of the cells. This recently discovered parathyroid calcium receptor has been characterized as a glycoprotein of unusually high molecular weight, which may play a key role in calcium homeostasis since it is also expressed in the kidney and placenta. Binding of external calcium to the receptor is associated with mobilization of intracellular calcium as well as calcium influx into the cells and phosphoinositol hydrolysis. These events rapidly interfere with the release process through essentially unknown mechanisms and probably also at sustained stimulation inhibit PTH gene transcription. The relative calcium insensitivity of the PTH release in HPT is associated with a deranged regulation of cytoplasmic calcium within pathological parathyroid cells. The molecular basis for this disturbance comprises down regulation of the cation receptor, whereby external calcium is translated into abnormally low levels of cytoplasmic calcium and insufficient inhibition of PTH release. Studies on expression of the functionally important cation sensing glycoprotein and its associated cellular signal systems may provide novel means for interference with the pathophysiological derangements of HPT.

Animals↗

The role of the pathologist in diagnosis and surgical decision making in hyperparathyroidism.

Hyperparathyroidism has been diagnosed with increasing frequency in recent decades. The concomitant awareness that the disease may be the cause of a concealed morbidity and even an increased mortality has resulted in more liberal indications for surgery. Many patients currently undergo surgery on the grounds of only mild hypercalcemia and in the absence of any apparent clinical symptoms. This policy of early surgical treatment has emphasized the importance of a histopathological parathyroid diagnosis, since many of these patients exhibit chief cell hyperplasia and minimal glandular enlargement. Light microscopic examination of frozen sections stained with hematoxylin-eosin and with stains for demonstration of cytoplasmic fat in the parathyroid chief cells, and appropriate weight estimates of the parathyroid glands, constitute the conventional, intra-operative basis for the diagnosis. The use of specific antiparathyroid antibodies is an important new tool in the histopathological parathyroid examination, mainly because of the ability to demonstrate the cause of increased parathyroid hormone release from the pathological parathyroid tissue. A careful histopathological examination in combination with gross inspection of the parathyroid glands by an experienced eye should contribute to adequate surgical treatment and minimize errors in operative management in patients with hyperparathyroidism.

Adenoma↗

Findings and long-term results of parathyroid surgery in multiple endocrine neoplasia type 1.

Forty-two patients with primary hyperparathyroidism (HPT) of multiple endocrine neoplasia type 1 (MEN-1) were evaluated a mean of 8.9 years after subtotal parathyroid resection (SPX, n = 34) or total parathyroidectomy with autotransplantation to the forearm (TPX, n = 23). TPX as the primary operation revealed asymmetric and mainly nodular enlargement of the parathyroid glands with the presence of at least one normal-size gland in half of the individuals. TPX and SPX were accompanied by resolution of the hypercalcemia in 78% and 38% of the patients. Persistent and recurrent HPT occurred in 22% and 61% of the patients, while hypoparathyroidism requiring oral supplements occurred in 30% and 12% of the patients, respectively. Intact serum parathyroid hormone (PTH) in the arm of parathyroid autograft was high in the normocalcemic patients, somewhat lower in the patients with recurrent HPT, and normal to very low in the hypoparathyroid patients. Ratios of intact PTH between the grafted and non-grafted arms varied from 1 to 56.3, with average of 28.1 in the normocalcemic individuals, 8.2 in the patients with recurrent HPT, and 3.3 in those requiring supplements to maintain normocalcemia. These findings substantiate an 80% to 92% reversal of hypercalcemia during long-term follow-up of MEN-1 patients undergoing total parathyroidectomy or subtotal resection of 3-4 parathyroid glands as primary operative procedures and demonstrate the usefulness of intact serum PTH for functional evaluation of parathyroid autografts.

Adolescent↗

Technical aspects of magnetic resonance imaging in parathyroid gland lesions.

Two patients with primary hyperparathyroidism were examined before parathyroid surgery with magnetic resonance imaging at 0.35 tesla in order to analyse optimal methods of visualization. Two large parathyroid glands in the neck had long transverse relaxation times which rendered them clearly visible in T2-weighted images as structures of a signal intensity higher than that of the surrounding. Large parathyroid lesions may thus be easily detected by magnetic resonance imaging provided proper examination parameters are employed.

Adult↗

P-glycoprotein expression and activity of resistance modifying agents in primary cultures of human renal and adrenocortical carcinoma cells.

Tumor cells from patients with renal or adrenocortical carcinomas were tested in vitro for sensitivity to doxorubicin (Dox) and vincristine (Vcr), as well as for the modulation of this sensitivity by resistance modifiers and the immunohistochemical expression of the multidrug resistance associated P-glycoprotein (Pgp). Normal adrenocortical cells from one patient and Pgp-expressing cells of Dox-resistant myeloma RPMI 8226 sublines were included for comparison. The normal adrenocortical cells and cells from one adrenocortical carcinoma showed high Pgp expression, comparable to the most Dox-resistant myeloma cell line, whereas the other tumor samples showed variable but lower expression. The normal adrenocortical as well as the adrenocortical and renal tumor cells were highly resistant to Dox and Vcr. Whereas the cytotoxic effect of Dox was considerably increased by verapamil, cyclosporin A and its non-immunosuppressive analogue SDZ PSC 833 in the Pgp-expressing Dox-resistant sublines, comparatively small effects on the Dox and Vcr sensitivity were observed in the patient samples, irrespective of their Pgp expression. The results indicate that the Dox and Vcr resistance in human adrenocortical and renal carcinomas is mediated by mechanisms other than Pgp and that resistance modulating agents targeting Pgp may be much less efficient in the clinic than in Pgp-expressing cell lines, at least for the tumor types described in the present study.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Immunohistochemical expression of insulin-like growth factor 1 and its receptor in normal and neoplastic human adrenal cortex.

BACKGROUND: Insulin-like growth factor 1 (IGF-1) may influence cellular growth, differentiation and secretion. MATERIAL AND METHODS: Cryosectioned normal human adrenal glands (n = 6), cortical adenoma (n = 21), and carcinoma (n = 17) were stained immunohistochemically for IGF-1 and its receptor, and human adrenocortical cancer cells expressing the receptor were analysed for influences on proliferation. RESULTS: Normal cortical parenchyma generally displayed faint IGF-1 reactivity and intracellular receptor staining. Similar labelling encompassed the adenomas, but only 6 of them were receptor reactive. IGF-1 expression was conspicuous in 11 carcinomas, and 6 of them displayed cell surface receptor reactivity. All aldosterone producing lesions were receptor antibody unreactive. Recombinant IGF-1 dose-dependently stimulated the cell proliferation, and this effect was reversed by the receptor antibody. CONCLUSION: IGF-1 may interact with function and proliferation of the human adrenal cortex with particular reference to cortical carcinomas lacking discernible aldosterone excess.

Adenoma↗

Identification of a 35 kD tumor-associated autoantigen in papillary thyroid carcinoma.

Despite its tendency to metastasize and grow multifocally, papillary thyroid carcinoma (PTC), the most common endocrine malignancy, usually displays an indolent clinical course. Although this behavior probably reflects the inherent low growth potential of PTC cells, it has been postulated that the striking inflammatory reaction often present in PTC represents the activation of a protective, tumor-induced immune response. In a recent immunohistochemical study, we reported that immunoglobulin (IgG) and complement (C3d, C4d and C5) are specifically deposited in PTC tumor tissue. Endeavors were then made to isolate and identify tumor-associated antigens. Immunoprecipitation employing the serum and tumor tissue of PTC patients produced two bands by SDS-PAGE, at approximately 34.5 and 35 kD, which were not present in normal thyroid tissue. Three tryptic peptides of the 35 kD band were sequenced, identifying it as a fragment of cytokeratin 1, a structural protein not normally expressed in the thyroid. The results indicate a tumor-specific antibody response against an aberrantly expressed protein in PTC.

Amino Acid Sequence↗