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Biomedical subjects

S Kullander

Publications and source records attributed to S Kullander.

At least 19 recordsLinked to original sources

Experimental kerma coefficients for carbon deduced from microscopic cross sections at 96 MeV incident neutron energy.

The double-differential cross sections for (n, px), (n, dx), (n, tx), (n, 3Hex) and (n, alphax) reactions in carbon have been measured at 96 MeV incident neutron energy. The various charged particles (inclusive spectra) were identified using deltaE-E techniques. From the experimental data, energy- and angle-differential as well as production cross sections were determined, and subsequently the partial and total kerma coefficients. The deduced partial and total kerma coefficients were compared to previous experimental results and theoretical calculations. The findings indicate that the deduced kerma coefficients for the hydrogen isotopes are in good agreement with those deduced from a previous measurement, and that the kerma coefficient values, in particular of the hydrogen isotopes, are systematically higher than values obtained from recent model calculations, which consequently resulted in a total kerma coefficient which is up to 30% higher than predicted by the calculations.

Algorithms↗

Exclusive measurement of the pp --> pppi(+)pi(-) reaction near threshold.

The pp-->pp pi(+) pi(-) reaction has been measured exclusively near threshold at CELSIUS. The total cross sections are nearly an order of magnitude lower than expected from previous inclusive measurements. The differential cross sections reveal pp-->pp(*)(1440)-->pp sigma = pp(pi(+)pi(-))(I = l = 0) as the dominant process as well as significant contributions from p(*)-->Delta(++)pi(-)-->psigma. The observed anisotropy in the proton angular dependence is consistent with heavy-meson exchange. In the invariant mass spectra, no narrow structures of statistical relevance (3sigma) are found.

Journal Article↗

Metronidazole prophylaxis to prevent infections after total abdominal hysterectomy.

METHODS: In a randomized double-blind study, 134 patients were given 500 mg metronidazole as an intravenous infusion immediately before operation for abdominal total hysterectomy and again 8 hours later and 124 patients received placebo. RESULTS: There was more wound infection, postoperative hospitalization was longer and the sedimentation rate on the sixth postoperative day was significantly higher in the placebo group. There was no difference in postoperative temperature. Postoperative wound infections occurred in 12% in the placebo group and 6% in the metronidazole group. Eight percent in the total material had urinary tract infections, the diagnosis was based on urine cultures. CONCLUSIONS: Prophylaxis with intravenous infusion of metronidazole is recommended in total hysterectomies.

Anti-Infective Agents↗

Steroid release from two human epithelial ovarian tumors: evidence for an intrinsic production in vitro.

Tissue specimens from the primary tumor and metastasis (histological examination: cystadenocarcinoma) of two postmenopausal women were cut into pieces and were incubated or superfused for 3- to 4-hr periods. The incubation and superfusion procedures were performed in the absence and presence of human chorionic gonadotropin (hCG, 10 IU/ml). After incubation, the medium concentrations of progesterone (P), testosterone (T), androstendione, and 17beta-estradiol (E2) were determined by radioimmunoassay, while after superfusion the medium concentrations of cyclic AMP (cAMP), P, T, and E2 were analyzed. HCG stimulated the production of cAMP in the superfused tissue of the first case and in the second case the addition of hCG to the incubation medium caused a significant drop in testosterone release by the primary tumor and in androstendione release by the metastasis. These results suggest that tissues from primary tumor and metastasis were capable of releasing steroids into the media, supporting the contention that tissue from epithelial ovarian cancers can produce and/or release steroids in its own right.

Aged↗

Luteinizing hormone-releasing hormone agonist triptorelin in combination with cytotoxic chemotherapy in patients with advanced ovarian carcinoma. A prospective double blind randomized trial. Decapeptyl Ovarian Cancer Study Group.

BACKGROUND: Several lines of evidence suggest that the proliferation of ovarian carcinoma might be stimulated by gonadotrophins. A number of Phase I/Phase II clinical trials have reported that the suppression of endogenous luteinizing hormone and follicle-stimulating hormone secretion by luteinizing hormone-releasing hormone (LHRH) analogs induced objective remissions and/or disease stabilization in 10-30% of patients with advanced refractory ovarian carcinoma. The current study was performed to evaluate whether the addition of LHRH agonist treatment to standard platinum-based chemotherapy could prolong survival of patients with surgically treated Stage III or IV epithelial ovarian carcinoma. METHODS: One hundred and thirty-five patients with Stage III or IV epithelial ovarian carcinoma participated in this prospective randomized double blind trial. After cytoreductive surgery, 69 patients received monthly injections of a depot preparation of the LHRH agonist [D-Trp6] LHRH (triptorelin, 3.75 mg) and 66 patients received placebo until their deaths or termination of trial, respectively. All patients were treated with a standard platinum-based chemotherapy, and, if necessary, with second- or third-line cytotoxic regimens. RESULTS: Endogenous gonadotrophins were reliably suppressed in patients treated with triptorelin. However, their progression free and overall survival were not significantly different from that of patients receiving placebo injections (statistical power > 80% for a difference between both groups of > or = 20%). CONCLUSIONS: The results of this trial suggest that the suppression of endogenous gonadotrophins by conventional doses of an LHRH agonist produces no relevant beneficial effects in patients with advanced ovarian carcinoma who receive standard surgical cytoreduction and cytotoxic chemotherapy.

Adult↗

Treatment of endometrial cancer with GnRH analogs.

Given the small number of side effects, GnRH may be a useful and ideal drug for new therapeutic hormonal approaches in many cases of both invasive and noninvasive endometrial cancer. The hypoestrogenic state thus induced as well as a local effect may lead to pronounced regression of the tumor. Any future therapy should, however, always be tailored to meet individual needs. The use of GnRH agonists may be advocated in the following circumstances: 1. In pronounced endometrial hyperplasia and adenomatous hyperplasia (particularly relevant in those cases where hysterectomy is not desirable, e.g., in young patients who have not yet completed their families). 2. In patients with endometrial cancer where surgery is contraindicated or refused. 3. In addition to or as a substitute for radium treatment preoperatively to reduce uterine volume (myomas) to make surgery technically easier; to devitalize the tumor, stop menorrhagia, and improve anemia. 4. In advanced cases as an adjunct to radiotherapy and gestagens. It is possible that this will produce synergistic effects. 5. As adjuvant treatment (replacing gestagens?) in primary stages. 6. In relapses of endometrial cancer, refractory to conventional therapy, and in pulmonary metastases.

Adult↗

Intracellular actions of steroid hormones and their therapeutic value, including the potential of radiohalosteroids against ovarian cancer.

The biological activities of steroid hormones are effected via intracellular receptors. The receptors are part of a ligand-activated family of transcription regulator proteins that are critical for steroid-regulated cell differentiation. With recombinant cDNA technology, yeast and cultured animal cells can be made to express mammalian cDNA steroid receptors from cDNA clones that contain deletions and substitutions. Among the leading problems addressed in these models is the characterization of sequences that promote association or interaction with other transcription regulating molecules, including oncogene products. Recently it has been found that heat shock proteins may serve not only to stabilize the receptor proteins but also to precondition the activation imparted by ligand binding. Aberrant receptor proteins can be found in ovarian cancer. Whether aberrant receptor proteins are associated with transformation in general or with a variable clinical response to steroidal or anti-steroidal therapy is not known. Even after chemotherapy, steroid receptors are expressed in the metastases of ovarian cancers seen clinically, and they may have potential uses for localization and treatment of receptor-rich cancers. Radioligand pharmaceuticals appropriate for imaging or for site-directed radiocytotoxicity can be sequestered to the nuclei of receptor-rich cancers. Initial clinical imaging and therapy trials with such pharmaceuticals have been approved and begun. In the use of halogenated estrogen radiopharmaceuticals, liver metabolism and enterohepatic recirculation are important considerations. Ascites prolongs retention of a radiohalogenated estrogen in the abdominal cavity. Distant metastases have been localized with [123I]-estrogen in breast cancer patients in pre-operative procedures. Receptor-mediated cytotoxicity occurs when estrogen receptor radioligand pharmaceuticals that are Auger electron emitters are used in vitro.

Animals↗

Specific low affinity binding sites for gonadotropin-releasing hormone in human endometrial carcinomata.

Specific low-affinity high-capacity binding sites for gonadotropin-releasing hormone (GnRH) have recently been discovered in human breast and ovarian carcinomata. We checked whether similar binding sites are present in human endometrial cancer. Plasma membrane preparations were incubated with [125I,D-Ala6-desGly10]-GnRH-ethylamide in the presence or absence of unlabelled GnRH agonists or other peptides. GnRH-binding could be demonstrated in all 12 tumor samples tested. The mathematical analysis of the binding data was consistent with a single class of low affinity (Ka = (0.8-1.4) x 10(5) M-1) and high-capacity (Bmax = (134-142) x 10(-12) M/mg membrane protein) binding sites. Native GnRH had a similar affinity to the binding sites as the GnRH agonist used. Other peptides such as oxytocin, somatostatin and thyrotropin-releasing hormone did not crossreact with the binding sites. A photolabelled derivative of [D-Lys6]-GnRH was prepared with the bifunctional photolabile reagent (4-azidobenzyl)-N-hydroxysuccinimide. Photoaffinity labelling of endometrial carcinoma membranes and subsequent sodium dodecyl sulfate electrophoresis in 10% polyacrylamide gel revealed the presence of a single molecular mass component of 62 +/- 1.9 kDa. The appearance of this photolabelled binding site could be largely suppressed by the addition of unlabelled GnRH-agonist (10(-4) M) and thus represents the specific binding site for GnRH in endometrial cancer.

Affinity Labels↗

Prolonged clearance of intraperitoneal 16 alpha-[125I]iodo-17 beta-estradiol in presence of ascites.

Radioestrogens have potential as adjunct therapeutic agents against ovarian carcinoma, because selected radionuclides can deposit lethal doses of radiation to tumor cells and many ovarian carcinomas and their metastases express estrogen receptors. Because intraperitoneal administration is a possible approach, we investigated absorption from the peritoneal cavity of a radioiodoestradiol after intraperitoneal application in rats with and without ovarian tumors and ascites and compared the distribution of the radioactivity with that obtained after intravenous injection. In the absence of ascites, 70% of the intraperitoneal dose was cleared into the intestine within 2 hours after injection, indicating fast absorption from the peritoneal cavity. In the presence of ascites, clearance of intraperitoneal radioiodoestradiol was considerably slower; at 2 hours after injection, 50% of the injected dose remained in the ascites, mostly as radioiodoestradiol. Uptake of radioactivity in estrogen receptor-rich tissues, e.g., uterus, after intraperitoneal injection was high (about 20:1 over blood), regardless of the presence of ascites, but moderately lower than that observed after intravenous injection of radioiodoestradiol.

Animals↗

Rapid liver metabolism, urinary and biliary excretion, and enterohepatic circulation of 16 alpha-radioiodo-17 beta-estradiol.

The radiohalogenated estrogen 16 alpha-[123I]iodo-17 beta-estradiol ([123I]E2) is emerging as a diagnostic tool for imaging of ER-rich malignant tumors, with potential application for site-directed radiotherapy. Clinical use requires an accurate accounting for the biodistribution of the radioactivity, including an assessment of its enterohepatic circulation. We investigated the metabolism and circulation of [125I]E2 in the enterohepatic system in swine, a pharmacokinetic model that resembles humans. With indicator dilution methods, we found that, after its injection into the portal vein, more than 99% of [125I]E2 was cleared from the blood by the liver during the first pass. Water-soluble metabolites were then partly released into the blood and partly excreted into bile. After injection of [125I]E2 into the external jugular vein, one-third of the radioactivity was excreted in bile and two-thirds in the urine. More than 90% of the radioactivity in urine and bile was that of [125I]E2-glucuronide or [125I]E2-sulfate; only a very small fraction of the excreted radioactivity was from free 125I. Radioactivity in bile collected from one swine after i.v. injection of [125I]E2, and then infused into the proximal duodenum of a second swine, was almost totally absorbed during passage through the intestine at 5-7 hr after infusion. The reabsorbed radioactivity was cleared in the urine.

Animals↗

An in vitro perfusion method for metabolic studies on human postmenopausal ovaries.

Five ovaries from four postmenopausal women undergoing bilateral oophorectomy for benign conditions were prepared for vascular perfusion for 1 to 5 hours in a recirculating system containing oxygenized (5% CO2 + 95% O2) synthethic bicarbonate buffered medium (Medium 199 + 4% bovine serum albumin + antibiotics). Two histologically normal ovaries released measurable amounts of progesterone into the medium. One ovary, containing a simple cyst, released progesterone into the perfusate, and this release was further increased after the addition of hCG at a concentration of 10 IU/ml. A perfused cystadenofibroma released cAMP, progesterone, estradiol and testosterone into the perfusion medium with an augmented release of cAMP, estradiol and testosterone after the addition of hCG. hCG also had a stimulating effect on the release of prostanoids from this tumour. Fluid from tumour cysts, obtained prior to perfusion, contained measurable levels of gonadotrophins, steroids and prostanoids. The isolated perfused ovary model may provide a tool for further exploration of endocrine and oncological aspects of the postmenopausal ovary.

Chorionic Gonadotropin↗

Familial cancer aggregation in cases of adenocarcinoma corporis uteri.

In a detailed prospective interview study, all newly diagnosed cases of adenocarcinoma corporis uteri at Malmö during a 2-year period (n = 51) were analysed with regard to the occurrence of tumors in first-degree relatives. The families of the proband's male consorts were used as controls. Sisters and mothers of probands had tumors (particularly of the corpus uteri or breast) more often than had controls. Colon and prostate cancer also figured in family histories of proband relatives, more often and with earlier age at onset than in controls. Nine patients (18%) either had additional concomitant malignancies, or had had such malignancies previously. Familial cancer predisposition was associated with poorly differentiated anaplastic cancer of the corpus uteri with poor prognosis. Three cases of familial cancer (CFS) observed at Malmö are also described, in which the probands presented with adenocarcinoma corporis uteri. The findings suggest that a hereditary, cancer predisposing factor (gene) is involved in a significant proportion of cancer corporis uteri, and that it is expressed in a heterogeneous tumor pattern, predominantly at sites sensitive to hormonal influences.

Adenocarcinoma↗

Gonadal steroids, gonadotropins and endometrial histology in postmenopausal women with malignant ovarian tumors.

The concentrations of FSH, LH, 17-beta-estradiol (E2), estrone (E1) and progesterone (P) were measured in peripheral and ovarian vein sera obtained at preoperative pelvic angiography from 5 postmenopausal women with malignant ovarian tumors. In 5 others the concentrations of E2, P and testosterone (T) were also measured in ascitic fluid collected at laparotomy. The investigation showed that most of these patients had increased concentrations of E2 and/or E1 and P as well in the peripheral blood. Significant gradients between the ovarian and peripheral vein concentrations were found for E2 and for P. High levels of E2, P and T were found in the ascitic fluid. FSH and LH levels were often lowered in peripheral blood compared with normal menopausal values and a gradient to ovarian tumor venous blood - with lower concentrations in the blood coming from the tumors, was found. Endometrial histology showed signs of steroid stimulation. These cases indicate that malignant ovarian tumors and/or the ovaries harboring them, are often capable of producing different sex steroids. These steroids may be found in the peripheral blood and in the ascitic fluid compartment and therefore may be used as tumor markers. The steroid production is probably not autonomous, but gonadotropin-dependent.

Adult↗

Familial occurrence of cervical cancer, stages 0-IV.

All patients hospitalized in 1982 at the Department of Gynecology in Malmö because of malignancy of the cervix uteri attended an interview study concerning the presence of cervical cancer among their nearest relatives. In addition, these patients were questioned concerning earlier gonorrheal infection. The blood group was determined as also was the secretory status and Gm allotype. As a control group the families of the male consorts were used. Cervical cancer was found significantly more often in mothers of the patients (7.9%) than in the consorts' mothers (1.0%). Sisters, aged 20 or over, of the patients had cervical cancer significantly more often (7.5%) than sisters of the consorts (1.1%). Moreover, cervical cancer in mothers and/or sisters was found in 15.6% of the patients. In cases of invasive cancer or previously operated CIS, this figure was 17.5%. The patients did not differ significantly from the normal population regarding blood group or secretory status. A somewhat lower, although non-significant, frequency of Gm(1) allotype was found in patients with invasive cancer, compared with patients with CIS. Patients with a positive family history of cancer had more often had gonorrhea (24%) than patients with a negative family history (18%). The study indicates a multifactorial etiology for cervical cancer.

Adult↗