PubMed Health⌕ Search

Biomedical subjects

B Skogseid

Publications and source records attributed to B Skogseid.

68 records · Page 4Linked to original sources
PubMed1991

Genetic and clinical characteristics of multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN 1) is an inherited disorder of autosomal-dominant type encompassing tumors of the parathyroid glands, anterior pituitary and endocrine pancreas. The genetic defect responsible for MEN 1 maps to the long arm of chromosome 11 (11q13). Constitutional heterozygosity for the MEN 1 region is lost in proliferating pancreatic endocrine and parathyroid tissue, which suggests that the MEN 1 gene belongs to the group of tumor suppressor genes (antioncogenes). Genetic screening by linkage analysis using RFLP markers allows selection of gene carriers with high degree of accuracy and makes it possible to concentrate the laborious biochemical screening efforts to family members at risk of developing the MEN 1 syndrome. Biochemical screening of the MEN 1 lesions in young asymptomatic individuals decreases the age at diagnosis with many years (decades) and therapeutic intervention can be instituted early. Although it still remains to be established whether early intervention will have an impact on mortality, our long-term experience with 20 MEN 1 kindreds suggests a reduced morbidity as a result of thorough biochemical screening.

Adult↗
PubMed1990

Medical treatment and long-term survival in a prospective study of 84 patients with endocrine pancreatic tumors.

A prospective study was performed on 84 patients with neuroendocrine pancreatic tumors. Fifty-nine (70%) had malignant tumors and received causal medical treatment. Streptozotocin in combination with 5-fluorouracil or doxorubicin was used as first-line treatment and produced overall objective responses in 20 of 44 (45%) patients with a median duration of response of 27.5 months. Thirty-two patients who failed on chemotherapy subsequently received interferon treatment and 20 (63%) responded objectively with a median duration of 20.5 months. Octreotide, third-line treatment in 14 patients, produced objective responses in four patients (28%) (median duration of response, 16 months). The median survival from diagnosis in malignant cases was 6.7 years. Even if none of the current medical therapies are curative for patients with malignant endocrine pancreatic tumors, a prolonged survival would be observed during the last decade. Since the age at diagnosis has not been dramatically reduced despite improvements in diagnostic methods, the prolonged survival might be attributed to causal medical treatment.

Adolescent↗
PubMed1990

Localization of the MEN1 gene to a small region within chromosome 11q13 by deletion mapping in tumors.

The gene for multiple endocrine neoplasia type 1 (MEN1), an inherited predisposition to neuroendocrine neoplasm of the parathyroid glands, the pancreatic islet parenchyma, and the anterior pituitary gland, was recently mapped to chromosome 11q13 based on genetic linkage in families. We now show that the pathogenesis of MEN1-associated parathyroid lesions involves unmasking of a recessive mutation at the disease locus and that sporadic primary hyperparathyroidism shares the same mechanisms. By examination of allele losses in MEN1-associated lesions, we could define deletions of chromosome 11 and map the MEN1 locus to a small region within chromosome band 11q13, telomeric to the PYGM locus. In contrast, a low incidence of deletions involving the MEN1 gene was found in sporadic pituitary adenomas.

Adenoma↗
PubMed1990

Neuroendocrine pancreatic tumours: clinical presentation, biochemical and histopathological findings in 84 patients.

A prospective study has been performed on 84 patients with endocrine pancreatic tumours evaluated at the Medical Department in Uppsala. Available information concerning the patients' presenting symptoms, age at diagnosis, clinical syndrome, tumour location, location of metastases, diagnostic radiology, biochemical and histopathological findings has been analysed. Our results indicate that most patients initially show rather vague and non-specific symptoms, with dyspepsia and pain being the most frequent presenting features. The median delay between appearance of the first symptom and diagnosis was 2 years; the delay was 35 months in sporadic cases and 14.5 months in familial cases. In spite of improvements in diagnostic methods, the median age at diagnosis (53 years) has not been reduced, and most patients are encountered when the tumour has reached an advanced stage. There is a need for a method of screening patients with still uncharacteristic abdominal symptoms for a neuroendocrine tumour. The presence of elevated levels of plasma chromogranin in all patients with a proven tumour suggests that such possibilities exist, and the use of this biochemical marker in the future might reduce the age at diagnosis and thus improve the likelihood of cure and survival of patients with endocrine pancreatic tumours.

Adenoma, Islet Cell↗
PubMed1989

Neuroendocrine pancreatic tumors. Clinical findings in a prospective study of 84 patients.

Endocrine pancreatic tumors are slowly growing neuroendocrine neoplasms with a malignant potential which may cause symptoms such as hypoglycemia, multiple ulcers, diarrhea, flush, hyperglycemia and skin rash. A prospective study was performed on 84 patients with endocrine pancreatic tumors. In 59 patients (70%) the tumors were malignant. Of the 84 patients, 23 had insulinomas, 25 gastrinomas, 20 nonfunctioning tumors, 14 the WDHA syndrome, 1 somatostatinoma and 1 glucagonoma. The median age at diagnosis was 53 years and the median delay from first symptom to diagnosis was 2 years. The most common site of the pancreatic primary tumor was the tail (41%), and metastases were most frequently located in the liver (60%) and lymph nodes (44%). Plasma chromogranin A + B was elevated in 94%, serum pancreatic polypeptide (PP) in 74%, plasma neurotensin in 67% and serum gastrin in 62%. Serum HCG-alpha and -beta subunits were elevated in 41 and 30% respectively, all except 3 having a verified malignant tumor. The median survival from first symptom and diagnosis was 14.2 and 8.7 years respectively. Patients with MEN-1 had a significantly better survival from diagnosis than sporadic cases (median 15.1 versus 5.8 years). Patients who received interferon after failing chemotherapy had a significantly better survival than those given chemotherapy alone (5-year survival 65 and 50% respectively).

Adenoma, Islet Cell↗
PubMed1989

Multiple endocrine neoplasia type 1 (MEN-1). Clinical, biochemical and genetical investigations.

The syndrome of multiple endocrine neoplasia type 1 is an autosomal dominantly inherited disease affecting several endocrine organs. The affected organs include the pituitary, the parathyroids and endocrine pancreas, where different types of lesions can be found, such as hyperplasia or frank carcinomas. The most life threatening lesions are the endocrine pancreatic tumors, which cause about 80% of all deaths among the MEN-1 members. In our own series of 108 members from 16 families with multiple endocrine neoplasia, 55 members had the MEN-1 trait. Among these members, pituitary lesions were found in 42%, parathyroid involvement in 89% and endocrine pancreatic tumors in 58%. Hyperparathyroidism was the presenting lesion of the MEN-1 trait. By using a specific meal stimulation test we have been able to unveil pancreatic lesions up to a median of five years previous to radiological detection. Very recently we have been able to detect a specific genetic lesion in MEN-1 members by studying DNA rearrangements with recombinant DNA technique, using the method of polymorphic restriction enzyme recognition in three large kindreds. The MEN-1 locus maps to chromosome 11q and the MEN-1 predisposition would be a constitutional mutation in heterozygous form, inherited as an autosomal dominant trait. Tumor development involves a second mutational event which involves the chromosome 11, carrying the remaining 'wild' type allele at the MEN-1 locus by means of chromosome loss event. Survival analysis demonstrates that patients with the MEN-1 syndrome had a significantly better survival from diagnosis than patients with sporadic endocrine pancreatic tumors (median 15.1 years and 5.8 years respectively, p = 0.0068). Earlier diagnosis and start of treatment might account for a longer survival in the MEN-1 group, but a possibility of differences in tumor biology between familial and sporadic endocrine pancreatic tumors cannot be ruled out. The surgical treatment of patients with MEN-1 include resection of the parathyroids with transplantation of a piece of the gland to the forearm, resection of endocrine pancreatic tumors in the tail and local enucleation of tumors in the pancreatic head and body. Total pancreatectomy should be avoided in most instances. The causative medical treatment of patients with malignant endocrine pancreatic tumors and the MEN-1 trait include chemotherapy (streptozotocin plus 5-fluorouracil), interferons and the somatostatin analogue SMS 201-995.

Female↗
PubMed1989

Localization of the genetic defect in multiple endocrine neoplasia type 1 within a small region of chromosome 11.

Multiple endocrine neoplasia type I (MEN-1), a Mendelian disorder with an autosomal dominant mode of inheritance, causes hyperplasia in the parathyroid glands and hyperplasia or neoplasm in the anterior pituitary gland and/or the pancreatic islets. The genetic defect responsible for MEN-1 in three families was recently mapped to the long arm of chromosome II by linkage between the MEN-1 locus and the gene for skeletal muscle glycogen phosphorylase (PYGM) at 11q13. We have constructed a genetic linkage map of seven markers in the vicinity of the MEN-1 locus that has allowed us to map more precisely the gene associated with MEN-1; the target region has been narrowed to about 12 cM. The closely linked markers will be useful also for identification of likely carriers in families in which an allele responsible for MEN-1 segregates.

Chromosome Mapping↗
PubMed1988

Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma.

Multiple endocrine neoplasia type 1 (MEN-1) is a predisposition to hyperplasia of the parathyroid glands, and to hyperplasia or tumours of the anterior pituitary and the endocrine pancreas, and is inherited as an autosomal dominant trait. Here we map the MEN-1 locus to chromosome 11 by family studies, and demonstrate tight linkage with the human muscle phosphorylase gene. By comparing constitutional and tumour tissue genotypes of insulinomas from a pair of brothers who had inherited MEN-1 from their mother, we have shown that oncogenesis in these cases involves unmasking of a recessive mutation at this locus.

Adenoma, Islet Cell↗
PubMed1987

A standardized meal stimulation test of the endocrine pancreas for early detection of pancreatic endocrine tumors in multiple endocrine neoplasia type 1 syndrome: five years experience.

Forty-nine members of 6 families with multiple endocrine neoplasia type 1 (MEN 1) were investigated with a standardized meal stimulation test to detect the presence of pancreatic endocrine tumors. Fifteen age-matched subjects and 4 patients with primary hyperparathyroidism also were studied. Serum pancreatic polypeptide (PP), gastrin, and insulin as well as plasma glucagon and somatostatin concentrations were determined before and during the test meal. Patients with demonstrable pancreatic endocrine tumors had significantly increased mean basal and peak serum PP (P less than 0.001) and gastrin (P less than 0.001) responses to the meal compared with healthy family members and normal subjects. Seven of 12 MEN 1 patients with parathyroid and pituitary disease but no demonstrable pancreatic endocrine tumors had exaggerated PP and/or gastrin responses to the meal; 4 of them developed pancreatic endocrine tumors, detected by abdominal computerized tomography, 0.5-4 yr later. None of the healthy members of the MEN 1 families or the patients with primary hyperparathyroidism had responses different from those of the normal subjects. Our experience with the meal stimulation test indicates that an elevated basal or exaggerated serum PP and/or gastrin response is an earlier sign of pancreatic involvement in the MEN 1 trait than is abdominal computerized tomography.

Adenoma, Islet Cell↗
PubMedDate not supplied

Pancreatic tumors in multiple endocrine neoplasia type 1: clinical presentation and surgical treatment.

Among 33 patients with endocrine pancreatic tumors due to multiple endocrine neoplasia type 1 (MEN-1), 19 (58%) patients had hypergastrinemia, 7 (21%) patients had hyperinsulinism, and 7 (21%) patients had clinically non-functioning lesions. At least one gross tumor was found in all patients undergoing pancreatic surgery, including those with negative localization studies prior to operation. The patients also had additional macroscopic tumors as well as numerous microadenomas, and the lesions frequently were positive for immunostaining with multiple hormones, mainly pancreatic polypeptide, insulin, glucagon, and somatostatin. Duodenal endocrine lesions were found in 4 of 5 investigated patients and stained with gastrin and somatostatin antibodies. Distal, mainly subtotal pancreatic resection, was performed in 18 patients, eventually combined with caput tumor enucleation or duodenotomy, while a few patients underwent only tumor enucleation or a Whipple procedure. The long-term outcome of operation was most favorable in patients with hyperinsulinism; only 1 patient had clinical recurrence. Patients with hypergastrinemia experienced only transitory lowering of serum gastrin values after pancreatic surgery and 47% of them had or developed metastases. Such tumor spread was seen in 57% of the patients with non-functioning lesions. Nine patients died from progressive tumor disease during follow-up. Consistent with previous studies, we found that surgery is indicated in MEN-1 patients with hyperinsulinism even if a lesion is not visualized by radiology. In addition, these indications should be extended to also include patients with only biochemical markers of disease, including elevations of gastrin, as these indicate the presence of gross tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗