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Biomedical subjects

I Norheim

Publications and source records attributed to I Norheim.

27 records · Page 2Linked to original sources
PubMed1986

Treatment of malignant carcinoid tumors with human leukocyte interferon: long-term results.

Thirty-six patients with malignant carcinoid tumors were treated with human leukocyte interferon (IFN) im at doses of 3-6 megaunits/day. The origins of the primary tumors were as follows: mid-gut (29 patients); pulmonary (four); rectal (one); ovarian (one); and unknown (one). Nineteen of the 36 patients had previously been treated with cytotoxic agents, streptozocin plus 5-fluorouracil or doxorubicin, but showed progressive disease. With IFN objective tumor responses were seen in 17 of the 36 patients (47%): in 14 of the 29 patients with mid-gut carcinoids (48%) and in three of the four patients with lung carcinoids (75%). The median duration of response was 34 months. Stable disease was noted in 14 of 36 patients (39%), all presenting mid-gut carcinoids. The median duration of stable disease was 25 months. Progressive disease from the start of IFN therapy was seen in five patients (14%). All responders except one had a greater than 50% reduction of urinary 5-hydroxyindoleacetic acid or alpha-human chorionic gonadotropin, whereas four patients also had a significant reduction of tumor size on computerized tomographic scan or at laparotomy. Two patients achieved complete remission. Improvement of clinical manifestations of the carcinoid syndrome was seen in all patients with objective response. Adverse effects including influenza-like syndrome, reduction of blood cells, chemical signs of liver dysfunction, and disturbed lipid metabolism occurred but were reversible or could be circumvented by dose reduction. Autoimmune phenomena were also noted such as development of thyroid autoantibodies with thyroiditis, SLE syndrome with antinuclear factors, and parietal cell antibodies with pernicious anemia. IFN therapy seems to be very effective in controlling tumor-secreted substances and thus giving relief of clinical symptoms. It also arrests tumor growth for extended time periods (median, 2 years). The adverse effects are surmountable and less severe than with cytotoxic therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Interferon-induced nuclear DNA alterations in malignant carcinoid tumors in vivo.

Tumor cell specimens were obtained by ultrasonically guided percutaneous needle liver biopsy from 23 patients with metastatic small intestinal carcinoid tumors. The patients were admitted to the hospital for antitumor therapy (streptozocin, 5-fluorouracil, and leukocyte interferon). The tumor cell samples were used for DNA cytofluorometry. All tumors (12 cases) from untreated patients exhibited diploid DNA stem lines with low proliferative activity. The mean number of tetraploid cells was 8%. Altered nuclear DNA records were obtained in tumors of 8 patients, all of which were treated with leukocyte interferon at 3-6 X 10(6) IU/day for 4-32 months. The DNA records in these tumors varied, but they were mainly in the range between diploid and tetraploid values. In some cases several nuclear DNA peaks were observed within the limits for the cell cycle. It is assumed that the interferon treatment was responsible for the development of altered DNA cell lines because: 1) all untreated tumors yielded regular diploid DNA histograms, 2) interferon was the only drug administered to all patients with tumors displaying altered DNA records, and 3) modal diploid DNA values were observed prior to the interferon treatment in some patients. It is suggested that interferon in vivo blocked carcinoid tumor cell populations in different phases of the cell cycle. This result might explain the nuclear DNA profiles registered in the treated patients as well as the therapeutic effect obtained by interferon.

Adult↗
PubMed1985

Neuropeptide K: a major tachykinin in plasma and tumor tissues from carcinoid patients.

Evidence is presented for the presence of an entire family of tachykinin-immunoreactive peptides in plasma and tumor tissues from patients with carcinoid tumors. The peptides include in addition to substance P and neurokinin A; neurokinin B, an eledoisin like peptide and neuropeptide K--a 36 amino acid long tachykinin which contains neurokinin A at its C-terminus. Neuropeptide K seems to be the tachykinin which is present in highest concentrations in plasma as well as in acetic acid extracts of tumor tissues. It is highly biologically active, and may therefore contribute to the clinical symptoms of carcinoid tumors.

Carcinoid Tumor↗
PubMed1985

Nuclear DNA in intestinal carcinoid tumors. A study before and after cytotoxin (streptozotocin and 5-fluorouracil) treatment.

Imprint cytology specimens of metastases of intestinal carcinoids obtained by percutaneous biopsy were analysed cytofluorometrically with regard to nuclear DNA records. All untreated tumors (nine cases) exhibited diploid DNA values with a relatively low proliferative activity (less than 2% nuclei in S-phase region). The mean number of tetraploid cells was 5%. Cytofluorometry also was performed on five tumor metastases treated with the cytotoxin streptozotocin and 5-fluorouracil. After treatment, an increase in the number of tetraploid cells (mean value, 30%) was noted, indicating that the cytotoxin treatment (possibly streptozotocin) on the tumor cells in vivo blocked progression from G2 to M phase. The current cytofluorometric analyses show that diploid nuclear DNA records and a low proliferative activity is a characteristic of malignant carcinoid tumors of the intestine. Due to regular DNA histograms in the carcinoid tumors, it is suggested that reliable studies are permitted of the effect of cytotoxins on the different phases of the cell cycle in vivo.

Aged↗
PubMed1985

Serum growth hormone in patients with carcinoid tumours; basal levels and response to glucose and thyrotrophin releasing hormone.

The regulation of serum growth hormone was studied in 33 consecutive patients with carcinoid tumours; both diurnal serum GH and GH responses to an i.v. glucose load and TRH were assessed. Seventeen of the patients (52%) showed disturbed regulation of serum GH and 10 had at least two abnormal tests. Four patients had clinically overt acromegaly. The diurnal mean serum GH levels were higher (P less than 0.001) in patients with carcinoid tumours than in control subjects and more than one third (41%) had levels in a range similar to that of acromegalic patients without carcinoid tumours. The disturbance in serum GH regulation might have been caused in some patient by tumour secreted growth hormone releasing factor(s) which act directly on pituitary somatotrophs, but other tumour-related non-specific stimulation must be considered. Carcinoid tumours should be considered in the aetiology of acromegaly.

Acromegaly↗
PubMed1984

Antisera raised against eledoisin and kassinin detect immunoreactive material in rat tissue extracts: tissue distribution and chromatographic characterization.

Radioimmunoassays were developed for the tachykinins eledoisin (ELE) and kassinin (KAS) using antisera raised in rabbits. The antisera exhibited low (less than 0.1%) cross-reactivities to substance P (SP) and physalaemin (PHY), but crossreacted (with one exception, antiserum K7) to varying extents with neurokinin A (NKA) and neurokinin B (NKB). In the rat, the tissue distribution of the immunoreactive material detected by antiserum (E7) raised against ELE and by another antiserum (K1) raised against KAS both resembled that previously described for SP. Using the highly KAS-specific antiserum K7, no or only very low levels of immunoreactivity could be detected in extracts of various rat tissues. Gel permeation chromatography and ion-exchange chromatography of tissue extracts indicated that all antisera (except K7) detected the same population of immunoreactive molecules. One of the components was chromatographically indistinguishable from NKA. The tissue distribution of this component also resembled that of SP. Another immunoreactive component co-chromatographed with NKB at cation exchange chromatography. Acid tissue extracts, but not neutral tissue extracts, were found to contain immunoreactive components which appeared more basic than NKA and NKB. The total levels of immunoreactivity were higher in neutral than in acid tissue extracts. However, the ratio between the amounts of immunoreactivities in the two types of extracts varied considerably between tissues, indicating that tachykinin immunoreactive components may be present in different relative proportions in various tissues.

Animals↗
PubMed1984

Antisera raised against eledoisin and kassinin detect elevated levels of immunoreactive material in plasma and tumor tissues from patients with carcinoid tumors.

Radioimmunoassays based on antisera raised against the tachykinins eledoisin (antiserum E7) and kassinin (antiserum K12) were used to measure the concentration of tachykinin-like immunoreactivity (TKLI) in plasma from 52 healthy subjects. 65 patients with carcinoid tumors (of which 46 had symptoms of both flushing and diarrhoea), and 6 patients with endocrine pancreatic tumors. The antisera did not crossreact with substance P (SP). Elevated concentrations of TKLI, as compared with healthy subjects, were found in 75% of the carcinoid patients, but in none of the patients with pancreatic tumors. Tumor metastases from 8 of the carcinoid patients all contained TKLI. Ion-exchange chromatography of plasma samples and tumor tissue extracts indicated the presence of several immunoreactive molecular forms. The elution patterns of the immunoreactivity detected by antisera E7 and K12 were similar, indicating that the same molecular species are measured by these antisera. None of the components coeluted with synthetic SP. One of the immunoreactive components in carcinoid tumor extracts coeluted with synthetic NKA. The major immunoreactive components in plasma from the patients eluted in a position different from that of all currently known mammalian tachykinins. Tachykinin immunoreactive material detected in tumor tissue and plasma of patients with carcinoid tumor may play a role in the symptomatology of the carcinoid syndrome.

Adult↗
PubMedDate not supplied

Application of silver stains to cytologic specimens of neuroendocrine tumors metastatic to the liver.

Cytologic specimens of neuroendocrine tumors metastatic to the liver were examined with regard to their silver staining properties after the application of argentaffin and argyrophil staining techniques (Masson, Grimelius and Sevier-Munger). In tumors with a content of serotonin (small intestine carcinoids), the presence of this substance was demonstrated cytologically as an argentaffin reaction in individual tumor cells; however, formalin fixation was a prerequisite for positive staining. Melanin in malignant melanoma cells displayed a positive argentaffin reaction, irrespective of the fixation used (air drying, formalin, Bouin's fluid or acetone-alcohol). Thus, serotonin and melanin can be distinguished in cytologic samples of neuroendocrine tumors by the use of the Masson argentaffin reaction with different fixatives. The nonargentaffin-positive neuroendocrine tumor cells were weakly stained or unreactive with the Grimelius argyrophil technique. The Sevier-Munger argyrophil technique was negative or gave a disturbing nonspecific background staining reaction that was difficult to interpret in the cytologic samples. Thus, the Grimelius method appears to be the most useful silver stain for identifying neuroendocrine tumor cells in cytologic material, irrespective of their hormone content, since both argentaffin-positive and argentaffin-negative cell samples were stained at least to some degree.

Adenocarcinoma↗