Search PubMed⌕ Search

Biomedical subjects

E Wilander

Publications and source records attributed to E Wilander.

At least 127 records · Page 7Linked to original sources
PubMed1988

Treatment of malignant endocrine pancreatic tumors with a new long-acting somatostatin analogue, SMS 201-995.

Ten patients with malignant endocrine pancreatic tumors were treated with SMS 201-995 at doses of 50 micrograms twice daily, administered subcutaneously. Four out of 10 patients (40%)-1 patient with the Zollinger-Ellison syndrome and 3 of 6 with the watery diarrhea syndrome--responded objectively with more than 50% reduction of peptide levels, with a median duration of 15.5 months. All four patients improved symptomatically, with decreasing dyspeptic symptoms and decreasing diarrhoea. Three additional patients had a clear relief of symptoms without an effect on tumor-secreted peptides. The disease progressed in three patients during treatment. No reduction of tumor mass was seen in any of the patients. The main side effect noted was a slight but maintained increase in fasting blood glucose in four patients. In conclusion, SMS 201-995 had a beneficial effect in more than half of the patients and seems to be a valuable adjunct to other causal therapy in this patient category, especially in acute situations and weak patients because of its very few side effects.

Aged↗
PubMed1987

A study of the histopathogenesis of carcinoid tumors of the small intestine and appendix.

A specimen from the small intestine with multiple (three) classic carcinoid tumors and one appendiceal carcinoid tumor displaying argentaffinity, argyrophilia (Grimelius stain), and serotonin and neuron specific enolase immunoreactivity was examined by light microscopy with regard to the tumor cell histopathogenesis. The smallest tumor (diameter 0.5 cm) from the small intestine was cut into 512 and the appendiceal tumor into 511 serial sections, which were stained with the argyrophil technique. In the small intestine an increased number of endocrine cells and small proliferating aggregates of endocrine cells were observed among nonendocrine enterocytes in the crypts of Lieberkühn. They seemed to grow initially inside the crypts and to later infiltrate through the basement membrane into the lamina propria of the mucosa. This finding suggests that classic carcinoid tumors of the small intestine develop from mucosal endocrine (enterochromaffin) cells. Since proliferating argentaffin cells were also seen in the mucosal crypts in one of the other two carcinoid tumors (2 cm in diameter) in the same intestine specimen, it is suggested that when multiple carcinoid tumors occur in the small intestine they arise from multiple sites. There was no apparent connection between the mucosal crypts and the carcinoid tumor of the appendix. Thus in this particular case, the appendiceal carcinoid tumor did not appear to derive from the mucosal endocrine cells but from the subepithelial endocrine cells that are present in the lamina propria and submucosa of the appendix wall. Supporting this view is the fact that S-100 protein immunoreactive cells are found both in close relation to subepithelial endocrine cells and as an integral component of appendiceal carcinoid tumors.

Appendiceal Neoplasms↗
PubMed1987

Treatment of hormone-producing adrenocortical cancer with o,p'DDD and streptozocin.

Three patients with advanced adrenocortical carcinoma were treated with a combination of intermittent streptozocin and continuous o,p'DDD. Two patients were treated preoperatively and the primary tumors, initially considered as inoperable, could be resected after 19 and 5.5 months, respectively. In the patient with the longer treatment (35 months), lung and lymph node metastases disappeared and she has no evidence of recurrent disease 6.5 years after start of therapy. One patient was followed by magnetic resonance imaging (MRI) and urinary steroid secretion. The MRI gave a good visualization of the tumor. Measurements of relaxation times showed a significant decrease in T1 values. The urinary steroid profile showed an increased secretion of 3 beta-hydroxy-5-ene steroids and tetrahydro-11-deoxy-cortisol. Treatment with streptozocin and o,p'DDD initially increased 16-oxygenation of dehydroepiandrosterone and androst-5-en-3 beta,17 beta-diol, followed by a decrease in the secretion of all urinary steroids. The third patient received postoperative treatment with no effect on metastatic disease in the lungs, she died 9 months after start of treatment. The therapeutic approach with the combination regimen of streptozocin and o,p'DDD pretreatment plus aggressive surgery has to be further evaluated, as well as MRI and urinary steroid profile as methods to monitor the effect of therapy.

Adrenal Cortex↗
PubMed1987

Islet amyloid polypeptide-like immunoreactivity in the islet B cells of type 2 (non-insulin-dependent) diabetic and non-diabetic individuals.

A novel peptide, islet amyloid polypeptide (IAPP), with structural resemblance to calcitonin gene-related peptide has recently been purified from amyloid deposits in an insulinoma and from islets of Langerhans. By immunohistochemical methods, using antisera to a synthetic undecapeptide of IAPP and to insulin, we show that freshly fixed islet B cells in man, guinea pig, rat, mouse and hamster exhibit strong IAPP-immunoreactivity while A cells are unreactive. In human autopsy material, all of 11 non-diabetic individuals had IAPP immunoreactivity of the islets. In comparison 8 of the 13 patients with Type 2 (non-insulin-dependent) diabetes had no IAPP immunoreactive cells. The proportion of islet cells having IAPP immunoreactivity exceeded 10% in only 1 of the 5 remaining diabetic patients while in all 13 patients substantially more than 10% of the islet cells contained immunoreactive insulin. IAPP-positive amyloid deposits were found in 20-99% of the islets in 12 of the Type 2 diabetic patients while 6 of 11 non-diabetic subjects had amyloid in 3-11% of their islets. In islets with IAPP-immunoreactive amyloid, very few IAPP-cells were seen despite a strong reaction of the B cells with antiserum to insulin. This study shows that IAPP is a normal islet B cell component and that IAPP immunoreactivity in B cells is diminished in Type 2 diabetes while IAPP is deposited as amyloid fibrils in the islets of Langerhans. Although the function of IAPP is unknown, its occurrence in the islet B cells and its structural relation to calcitonin gene-related peptide makes a hormonal nature probable.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Tachykinin production by carcinoid tumours in culture.

Tissue specimens from 5 patients with metastatic midgut carcinoid tumours were kept in organ culture for up to 6 months. The tumour cells were confined to the suspension in the form of condensed cell clusters and appeared to retain their endocrine characteristics. Radioimmunoassay for tachykinin immunoreactivity showed high concentrations in 4 out of 5 culture media. The concentrations were highest in the beginning of the experiment, but subsequently decreased. The 4 patients from which these tumours were taken had all elevated tachykinin concentrations in extracted plasma. The fifth culture medium had low tachykinin concentration, and the concentration in extracted plasma from this patient was within the normal range. Reversed-phase high-performance liquid chromatography of the culture media with elevated tachykinin concentrations revealed immunoreactive components with the characteristics of synthetic neuropeptide K, neurokinin A and eledoisin, components also found in plasma and tumour tissues of carcinoid patients. Our findings indicate that carcinoid tumour cells produce tachykinins. These peptides are biologically very active, resulting in flush and hypotension when infused intravenously into normals, and might contribute to the clinical symptoms of the carcinoid syndrome.

Carcinoid Tumor↗
PubMed1987

Nuclear DNA recordings in gastric carcinoids. A cytofluorometric study on single tumour cells.

Cytofluorometric nuclear DNA analyses were performed on single tumour cells from eight argyrophilic gastric carcinoids. Three tumours displayed grossly diploid DNA values, with a fraction of S-phase cells of 1-8%. Four other tumours were also mainly diploid, but showed an increased number of tetraploid cells, and one tumour was aneuploid with a stem-cell line of triploid cells. These and previous results indicate that gastric carcinoids are relatively heterogenous with respect to their morphology, nuclear DNA profiles and biological behaviour, in contrast to most intestinal "classical" carcinoids. Furthermore, the results are in accordance with the suggestion that gastric carcinoids may represent a highly differentiated variety within a spectrum of neuroendocrine neoplasia analogous to the corresponding variety observed in the bronchus (carcinoid-small cell, undifferentiated carcinoma).

Adult↗
PubMed1987

Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells.

Amyloid deposits localized to the islets of Langerhans are typical of non-insulin-dependent human diabetes mellitus and of diabetes mellitus in adult cats. Amyloid deposits also commonly occur in insulin-producing pancreatic tumors. We have purified a major protein--insulinoma or islet amyloid polypeptide (IAPP)--from human and cat islet amyloid and from amyloid of a human insulinoma. IAPP from human insulinoma contained 37 amino acid residues and had a theoretical molecular mass of 3850 Da. The amino acid sequence is unique but has greater than 40% identity with the human calcitonin gene-related peptide. A partial amino acid sequence of cat islet IAPP corresponding to positions 1-27 of human insulinoma IAPP was identical to the human IAPP except for substitutions in three positions. An antiserum raised to a synthetic human insulinoma IAPP-(7-17) undecapeptide showed specific immunohistochemical reactivity with human and cat islet amyloid and with islet B cells. The significance of this pancreatic neuropeptide-like protein is unknown, but it is suggested that it may exert an important endocrine regulatory effect.

Adenoma, Islet Cell↗
PubMed1987

Gastric carcinoid associated with the syndrome of hypergastrinemic atrophic gastritis. A prospective analysis of 11 cases.

The prevalence of gastric carcinoid in fundic atrophic gastritis is probably greater than previously recognized. To help elucidate the clinicopathology of this syndrome, we report a series of 11 patients with solitary or multicentric carcinoid tumors. In these patients, basal gastrin levels and density of fundic mucosal endocrine cells were greater than that for patients with uncomplicated fundic atrophic gastritis (p = 0.02 and p = 0.002, respectively). The polypoid tumors, of which the largest measured 30 mm, frequently showed characteristic endoscopic features. They were all situated in the fundic mucosa, which showed micronodular endocrine cell hyperplasia. Small, endoscopically evident tumorlets, or "early carcinoids," limited to the lamina propria were observed in some patients. These lesions may represent intermediate stages between micronodules and invasive carcinoids, all of which infiltrated at least into the muscularis mucosae of the gastric wall. Although some consistent characteristics features were noted, there were structural variations. The cells were argyrophil but nonargentaffin and did not stain with conventional mucus stains. They did not stain significantly for carcinoembryonic antigen (CEA). The secretory product of these tumors remains to be identified. Ultrastructurally, some tumors were mainly composed of enterochromaffinlike (ECL) cells, but in other tumors most of the cells could not be classified.

Carcinoid Tumor↗
PubMed1987

Malignant carcinoid tumors. An analysis of 103 patients with regard to tumor localization, hormone production, and survival.

In a prospective study of 103 patients with carcinoid tumors consecutively referred for medical treatment, the most common sites of the primary tumors were the ileum (73%), bronchi (7%), and jejunum (4%). All patients had local metastases, and 96 (93%) also had liver metastases. The most common initial symptoms were diarrhea (32%), ileus (25%), and flush (23%). The overall frequency of diarrhea was 84% and of flush was 75%. Heart insufficiency caused by cardiac valve disease was seen in 33% of the patients. The carcinoid syndrome, including flush, diarrhea, and elevated urinary 5-hydroxyindole acetic acid (5-HIAA) concentrations, was manifested by 69 patients (67%), 64 of whom (93%) had carcinoid tumors of mid-gut origin. Elevated urinary 5-HIAA was found in 91 patients (88%), of which 89 displayed liver metastases. The plasma concentration of the tachykinin neuropeptide K (NPK) was elevated in 67 patients (66%), 63 of whom had tumors of the mid-gut region. Serum pancreatic polypeptide (PP) and human chorionic gonadotrophin alpha levels were elevated in 43% and 28% of the patients, respectively, and the highest levels were found in patients with metastatic bronchial carcinoid tumors. Thirty-nine of the 103 patients are now dead; 18 died of tumor progression, whereas 14 patients died of heart failure secondary to a carcinoid tricuspidal valve insufficiency. The estimated median survival from the time of histologic diagnosis was 14 years, and from the time of carcinoid syndrome was 8 years.

Adult↗
PubMed1987

Percutaneous ultrasonography-guided cutting biopsy from liver metastases of endocrine gastrointestinal tumors.

Ultrasonography-guided cutting needle biopsy of the liver was performed in 186 instances on 95 different patients with carcinoid and endocrine pancreatic tumors. In 171 cases, biopsy specimens were taken from liver metastases found on ultrasonography, and in 93% of these the obtained material was adequate for a correct diagnosis. In the 7% for which an incorrect diagnosis was made, all but one biopsy specimen contained normal liver tissue, indicating that the needle-guiding technique, and not the sampling technique, is the most critical part of the biopsy procedure. Tumor specimens were examined with silver stains and immunocytochemistry after application of monoclonal serotonin antibodies. The argyrophil silver stain of Grimelius could be applied on all specimens and had positive results in all but one case, demonstrating the neurohormonal endocrine origin of the metastases. The argentaffin reaction and/or serotonin immunoreactivity could be applied in 152 cases and had positive results in 115 of 122 (94%) of the mid-gut carcinoid tumors and negative results in 27 of 28 (96.4%) of the non-mid-gut carcinoid tumors and endocrine pancreatic tumors. Major complications occurred in 1.5%; none was lethal or required surgery. The results show that the technique used for tumor biopsy is very accurate and provides material sufficient for multiple histopathologic and immunocytochemical analyses without exposing the patients to high complication risks. It is further concluded that the staining techniques and immunocytochemical analyses applied on the biopsy specimens are valid for the prediction of the location of the primary endocrine tumor.

Adult↗
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↗
PubMed1987

Treatment of malignant endocrine pancreatic tumors with human leukocyte interferon.

Twelve patients with malignant endocrine pancreatic tumors refractory to cytotoxic treatment were treated with human leukocyte interferon im at daily doses of 3 X 10(6)-6 X 10(6) IU. Ten of 12 patients showed an objective response with a mean duration of 15.2 months, median, 11 months (range, 2-36+). All ten patients had a decrease in tumor markers and an objective reduction in tumor size was also noted in four. Improvement of clinical manifestations was seen in all cases with an objective response. Adverse effects, including influenza-like syndrome, reduction of blood cells, and chemical signs of liver dysfunction occurred, but were reversible or could be circumvented by dose reduction. One patient developed hypothyreosis on an autoimmune basis; another patient developed liver steatosis. Although the number of patients is small, the results are promising. Interferon therapy seems to be as potent as cytotoxic treatment but with far less side effects. This study indicates that further trials with interferon in patients with less advanced stages of malignant endocrine pancreatic tumor should be performed.

Adult↗
PubMed1987

Hexokinase and adenylate kinase activities in aorta, heart muscle and skeletal muscle from uraemic rats.

The effect of parathyroidectomy and/or vitamin D on the development of arterial and myocardial lesions was studied in rats with moderate uraemia. The activities of hexokinase and adenylate kinase in the aorta, myocardium and skeletal muscle were measured and the incidence of aortic calcification and muscle cell necrosis determined. There was a decreased hexokinase activity in the aorta, myocardium and skeletal muscle from uraemic rats. Adenylate kinase showed an increased activity in the same tissues. Parathyroidectomy as well as I-alpha-hydroxycholecalciferol in a dose of 3 ng/100 g b.w. normalized these activities to a great extent. This effect did not occur when 10 ng/100 g b.w. was given. Parathyroidectomy in combination with a low dose of I-alpha-OH-D3 reduced the incidence of myocardial necrosis. Aortic calcifications were found in uraemic animals given 10 ng/100 g b.w. of I-alpha-hydroxycholecalciferol. In this group increased activity of adenylate kinase was found in calcified aortae but not in non-calcified aortae. The study shows that uraemia causes metabolic changes in the aorta, myocardium, and skeletal muscle which may partly be prevented by parathyroidectomy and by low doses of vitamin D. It also indicates some parallelism between these metabolic changes and the development of histologically demonstrable lesions in the aorta.

Adenylate Kinase↗
PubMed1987

Neuron-specific enolase expression and neuroendocrine differentiation in carcinomas of the breast.

The concentration of neuron-specific enolase (NSE, gamma-subunit of enolase) in tumor extracts of 25 nonargyrophilic and seven argyrophilic carcinomas of the female breast was measured by radioimmunoassay. The mean concentration of NSE in nonargyrophilic carcinomas was 89 ng/mg of protein, (range, 9 to 281 ng/mg), and the mean concentration of NSE in argyrophilic carcinomas was 153 ng/mg of protein (range, 4 to 420 ng/mg). All carcinomas, irrespective of the silver reaction, could be grouped in regular histopathologic terms. Neuron-specific enolase immunoreactivity in sections of the corresponding fixed tumors occurred in both silver-stained and unreactive tumors, although the reaction was more prominent in the argyrophilic tumors. The results indicate that NSE in considerable amounts may be present in both argyrophilic and nonargyrophilic carcinomas of the breast, although higher concentrations are found most often in the former tumor type.

Aged↗
PubMed1986

Treatment of malignant endocrine pancreatic tumours with human leucocyte interferon.

22 patients with advanced malignant endocrine pancreatic tumours were treated with human leucocyte interferon 3-6 X 10(6) IU per day. Objective responses (more than 50% reduction in tumour markers or tumour size) were seen in 7/7 with watery diarrhoea/hypokalaemia/achlorhydria syndrome, 3/4 with the Zollinger-Ellison syndrome, 6/9 with "non-functioning" tumours, and 1 with a mixed tumour mainly producing somatostatin. The median duration of response was 8.5 months, and all responders improved clinically. Adverse effects seemed more tolerable than those of cytotoxic treatment.

Clinical Trials as Topic↗
PubMed1986

A novel peptide in the calcitonin gene related peptide family as an amyloid fibril protein in the endocrine pancreas.

Deposition of amyloid is the most constantly present alteration in the islets of Langerhans in type 2 diabetes mellitus and is also quite common in insulin-producing tumors of the pancreas and it is very likely that these two amyloids are identical. We have isolated amyloid fibrils from an insulin-secreting human tumour and purified the fibrillar protein. N-terminal amino acid sequence of the protein is unique and does not resemble insulin or its precursors. Instead it has about 50% homology with the neuropeptide CGRP (calcitonin gene related peptide).

Amino Acid Sequence↗
PubMed1986

Subepithelial neuroendocrine cells and carcinoid tumours of the human small intestine and appendix. A comparative immunohistochemical study with regard to serotonin, neuron-specific enolase and S-100 protein reactivity.

A comparative immunocytochemical study was performed of subepithelial neuroendocrine cells of the human small intestine and appendix and carcinoid tumours of these sites, using a monoclonal antibody to serotonin and polyclonal antisera against neuron-specific enolase (NSE) and S-100 protein. Subepithelial neuroendocrine cells were easily identified in the lamina propria of the appendix. These cells, which sometimes occurred in aggregates, displayed serotonin and NSE immunoreactivity and were surrounded by S-100 protein immunoreactive cells, presumably of Schwann cell origin. In the appendix scattered cells with corresponding morphological features and immunoreactivity were also observed deep in the submucosa. In addition, subepithelial neuroendocrine cells were sparsely present in the lamina propria of the small intestine, occurring only as single cells in the deeper part of the mucosa below or between the epithelial crypts. Most appendiceal carcinoid tumours (11 of 12 examined cases) were biphasic and consisted of neuroendocrine tumour cells with intermingled S-100 protein immunoreactive cells (Schwann cells) with long cytoplasmic extensions. However, small intestinal (11 cases) and caecal (10 cases) carcinoids lacked S-100 protein immunoreactive cells as an integral component. The results indicate that the appendiceal carcinoids are mostly closely related structurally to the subepithelial neuroendocrine and Schwann cell aggregates of the lamina propria and are thus presumed to be histogenetically related to this cell system, while the histogenesis of small-intestinal and caecal carcinoids remains less clear.

Appendiceal Neoplasms↗