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Biomedical subjects

N O Theve

Publications and source records attributed to N O Theve.

At least 19 recordsLinked to original sources

Effects of early discharge from hospital after surgery for primary breast cancer.

OBJECTIVE: To evaluate the effects of early discharge from hospital on women being operated on for primary breast cancer. DESIGN: Open study in self-selected patients. SETTING: Karolinska and Sabbatsberg Hospitals, Stockholm. SUBJECTS: 169 consecutive patients operated on for primary breast cancer. MAIN OUTCOME MEASURES: All patients were asked to fill in a questionnaire about their perception of their disease and factors associated with the operation. RESULTS: 118/169 patients participated, and of these 28 (24%) chose early discharge with the drain still in place. They were compared with the 90 patients (76%) who were discharged without a drain. The median stay in hospital for those who chose early discharge was 2 days, and for those who remained in hospital until the drain was removed, 6 days. There were no differences between the groups in type or incidence of complications, and the groups were equally satisfied with their length of hospital stay and their treatment in hospital. Those who opted for early discharge were significantly younger than those who did not (mean SD) 52 (14) compared with 62 (13) years, p = 0.001). CONCLUSION: Early discharge from hospital with the drain still in place after operation for primary breast cancer was not found to be associated with any untoward events.

Age Factors↗

The estrogen binding protein in human pancreas: concentrations in subcellular fractions of normal pancreatic tissue, in duodenal juice during pancreatic stimulation and in peripheral serum in normal and pathological conditions.

The steroid binding properties of the human pancreatic estrogen binding protein (hEBP) in cytosol were studied by equilibrium dialysis. A high ligand specificity of the protein was revealed. hEBP in cytosol binds unconjugated steroid estrogens with a medium affinity (Kd = 10(-7) M) but does not bind conjugated estrogens or unconjugated androgens, gestagens, glucocorticoids or cholesterol. Quantitation of hEBP by radioimmunoassay in subcellular fractions of human pancreatic tissue indicated that the protein is translocated into different subcellular compartments. Duodenal juice taken from patients following stimulation of pancreatic secretion by food ingestion (Lund's test) showed high hEBP concentrations, and the levels of hEBP changed concomitantly with the levels of pancreatic isoamylase, indicating that hEBP secretion was stimulated by food ingestion. The levels of hEBP in peripheral serum from healthy subjects showed no sex difference, but were positively correlated to age. Highly elevated (10-20-fold) hEBP levels were found in serum from patients with acute pancreatitis, while normal serum hEBP values were found in other abdominal diseases. It is speculated that hEBP might have a specific role in the transport of estrogens from the peripheral circulation via the pancreas to the duodenum. The elevated hEBP levels in patients with acute pancreatitis indicate that this protein may be used as a marker of cellular damage in the pancreas.

Carrier Proteins↗

Analysis of an estrogen binding macromolecule in human pancreas by radioimmunoassay.

A radioimmunoassay for quantitation of the human pancreatic estrogen binding protein (hEBP) was developed using polyclonal rabbit hEBP antiserum and iodinated purified hEBP. Parallel dose-response curves were obtained when serial dilutions of human serum and of cytosols obtained from human pancreas, prostate and colon were analyzed simultaneously with serial dilutions of purified hEBP standard. Very high levels of hEBP (500-1000 mg/kg wet weight) were found in normal pancreas. High as well as medium levels were found in pancreatic carcinoma tissue and medium values (0.1-1 mg/kg wet weight) in prostate, colon and ovarian tissue. Other tissues and serum from healthy volunteers showed low values, usually below 0.1 mg/kg. When serial dilutions of rat pancreatic cytosol were analyzed in the hEBP assay, [125I]hEBP was displaced by the rat preparation, but the dose-response curves were not parallel to the standard curves, indicating similarity but non-identity between the estrogen binding proteins in human and in rat pancreas.

Animals↗

Serum and tissue concentrations of doxorubicin after IV administration of doxorubicin or doxorubicin-DNA complex to patients with gastrointestinal cancer.

Blood and tissue concentrations of doxorubicin (DOX) were assayed after an intraoperative IV test dose of either free DOX 10 mg or its DNA complex 10 mg to patients with gastrointestinal cancer. After administration of the free drug, blood DOX levels decreased in an at least biphasic way, while DOX-DNA gave higher blood concentrations, which decreased slowly with no clear inflexion point on the concentration-time curve within the first hour. Tissue concentrations of DOX did not differ significantly after the two forms of the drug, liver being the tissue with the highest levels, followed by lymph node metastases, tumor tissue, muscle, and normal intestinal mucosa. If skeletal muscle can be used as a substitute for myocardium, lower cardiotoxicity of DOX-DNA than of DOX is not likely to be due to a difference in tissue uptake and retention between the two forms of DOX.

DNA↗

Comparative pharmacokinetics of doxorubicin and epirubicin in patients with gastrointestinal cancer.

The levels of doxorubicin (DOX) and epirubicin (epi-DOX) in serum, tumors, and normal tissues were assayed by high-performance liquid chromatography after peroperative administration of test doses (10 mg) to 14 patients with gastrointestinal cancer. Large interindividual variations were found. The drug levels also varied markedly between tissues from the same patient, with normal liver consistently having the highest drug concentration, followed by tumors and striated muscle, which had similar levels. In serum, a rapid initial distribution phase, with a half-life of about 5 minutes for DOX and 4 minutes for epi-DOX, was followed by a slower decrease in the drug levels. The concentration versus time curves were not influenced by the presence of liver metastases. No metabolites of DOX or epi-DOX were found during the time period studied, in most cases 2 hours after drug administration. Our pharmacokinetic results give no explanation for the claimed superiority of epi-DOX in the treatment of gastrointestinal cancer.

Aged↗

Preoperative short-term radiotherapy in rectal carcinoma. A preliminary report of a prospective randomized study.

Between 1980 and 1983, 373 patients with clinically resectable rectal adenocarcinoma entered a prospective randomized study aimed to evaluate the effect of short-term preoperative radiotherapy. Protocol violations were identified in 21 instances. Of the remaining 352 patients, 182 were randomized to surgical treatment only (S-group). Immediately, before surgery, 170 patients were irradiated to the pelvic region with 25 Gy (2500 rad) during a 5-day period (RT-group). Of these patients, 59% underwent abdominoperineal excision, 38% anterior resection, and 3% laparotomy only. At surgery distant metastases were discovered in 32 patients (9%). There were no significant differences between the groups in the distribution of age, sex, operative methods, and tumor stage according to the original Dukes' classification. During the follow-up time, ranging between 6 months and 3 years, tumor recurrence occurred in 35 patients, 19 in the S-group and 16 in the RT-group. Fifteen patients in the S-group had pelvic recurrence compared to 10 patients in the RT-group. Distant metastases occurred in six and eight patients, respectively. Two patients in each group had both pelvic and distant recurrence. There was no correlation between tumor recurrence and type of operation. Median time interval from diagnosis to pelvic recurrence was 10 months in the S-group and 16 months in the RT-group. Postoperative complications in the form of wound sepsis were slightly more common in the RT-group. In summary, the applied treatment regimen, is well-tolerated and apparently does not affect the Dukes' stage of the tumor. Although there is no statistically significant difference, there is a trend of less pelvic recurrence in patients receiving preoperative radiotherapy.

Adenocarcinoma↗

Adjuvant tamoxifen treatment in postmenopausal patients with operable breast cancer.

Between November 1, 1976 and December 31, 1981, 826 post-menopausal females with operable breast cancer were included into a trial comparing tamoxifen 40 mg daily for 2 years with no endocrine treatment. Patients without axillary lymph node metastases and tumors less than 30 mm received no other treatment whilst those with more advanced disease were in addition superrandomised to receive postoperative irradiation or 12 courses of CMF. With a mean follow-up of 44 months tamoxifen significantly reduced the incidence of recurrence. There was no significant interaction between the effect of tamoxifen and any other treatment or prognostic subgroup.

Antineoplastic Combined Chemotherapy Protocols↗

Further characterization of the estrogen binding macromolecule in human pancreas.

The estrogen binding protein in human pancreas has been purified from pancreatic cytosol by chromatography on Concanavalin-A-Sepharose and hydroxyl-apatite followed by ion-exchange chromatography carried out using a fast-protein liquid chromatography apparatus (FPLC). The purified protein, still able to bind labelled [3H]estradiol, appeared as one single band corresponding to 31 K in SDS-gel electrophoresis. Total amino acid analysis revealed high levels of histidine, glutamic acid and leucine. The capacity of the purified protein to bind estrogens could be increased more than 4-fold by addition of a cytosolic factor, probably being a small peptide, that is present in crude cytosol, but lost during the purification procedure. The iodinated protein does not bind to DNA-cellulose or phosphocellulose, and shows no similarities to estrogen receptor proteins.

Amino Acids↗

Breast-conserving treatment for breast cancer in Stockholm, Sweden, 1977 to 1981.

Since 1977 patients living in Stockholm with Stage I breast cancer fulfilling specific criteria are offered breast-conserving treatment. The treatment includes a partial mastectomy and a low-axillary dissection followed by radiotherapy, 5000 rad, to the remaining breast. Between 1977 and 1981, 262 patients underwent the breast conserving therapy. One hundred eighty-six patients had pathologic Stage I tumors. Radiotherapy was given to 158 of those patients. During the follow-up time (6 months to 5 years), 4 of 186 patients had recurrence to the breast. Two of those had not received radiotherapy. Recurrent tumor in regional lymph nodes occurred in 4/186, and distant metastases in 10/186 patients. Six patients have died of their disease. The cosmetic results were favorable overall, but often impaired when surgical complications occurred. A comparison between these results and those obtained in similar patients treated with modified radical mastectomy with a low-axillar dissection followed by radiotherapy to the remaining breast seems to be an alternative treatment to modified radical mastectomy. Longer follow-up time is needed before final conclusions can be drawn.

Adult↗

Permanent indwelling Celestin tubes in malignant esophageal strictures.

Eighteen patients with unresectable carcinoma of the esophagus were surgically intubated with the Celestin tube. Twelve patients (66.7%) had good palliation and relief of dysphagia. The operation mortality rate was 16.7%, which is in accordance with figures reported for endoscopic intubation of malignant strictures of the esophagus.

Aged↗

Permanent indwelling tubes in benign oesophageal stricture.

Permanent intubation of benign oesophageal stricture seems to be rather frequently used, but there are few reports on indications and results. The limited experience from 9 intubations in 7 patients presented, is not encouraging. Massive gastro-intestinal bleeding, peptic reflux and tube migration were seen, and 4 of the tubes had to be sacrificed within 6 weeks. Two patients only had full and lasting benefit of the treatment without serious tube complication. Indwelling tubes should be considered in benign strictures only as an alternative to gastrostomy, particularly in those patients feeling strong aversion to permanent stomy.

Aged↗

Adenocarcinoma of the pancreas--a hormone sensitive tumor? A preliminary report on Nolvadex treatment.

There are indications of possible effects of sex hormones on the pancreas. These include reports on steroid receptor proteins in pancreatic tissue, the purification and characterization of a highly specific, high capacity oestrogen binding protein in the human pancreas and capacity of human pancreatic tissue to convert the main peripheral oestrogen, oestrone sulphate, into the terminal biologically active oestradiol-17 beta. Furthermore, experiments in mice have shown accumulation of an anti-oestrogen, tamoxifen, in the pancreas. With this background, we have tried tamoxifen in 14 patients with unresectable adenocarcinoma of the pancreas. The median survival time was 8.5 months and three patients had a remarkably long survival time of 22 months. In a historical control group the median survival time was 2.5 months and no patients survived for more than 21 months. We have therefore started a randomized trial with tamoxifen in patients with unresectable pancreatic cancer. Even if anti-oestrogens are not the optimal form of therapy, other sorts of hormonal manipulation ought to be tried in pancreatic cancer.

Adenocarcinoma↗

The distribution and metabolism of 14C-labelled tamoxifen in spayed female mice.

The distribution and metabolism of 14C-tamoxifen (a non-steroidal triaryl ethylene anti-oestrogen) have been investigated in ovarieectomized mice. The autoradiograms showed accumulation of radioactivity in the liver and the bile as an indication of an excretory pathway, but a rapid and high accumulation was also seen in the lung and the adrenals, organs normally not considered as target organs for tamoxifen. The liver and sebaceous glands could be detected on the autoradiograms up to fourteen days after a single intravenous dose. However, in most organs the amount of retained radioactivity was very low after 24 hours. By using the autoradiograms as a guideline a metabolic study was performed. High concentrations of unmetabolized tamoxifen was detected in the lung and the adrenals as well as in the pancreas. Relatively high amounts of a compound tentatively identified as 4-hydroxy-tamoxifen were present in the pancreas and the liver and there were also indications for the presence of N-desmethyl-tamoxifen in these tissues. These metabolites are considered to possess anti-oestrogenic activity.

Animals↗

Effects of tamoxifen on the serum levels of oestrogens and adrenocortical steroids in postmenopausal breast cancer patients.

Peripheral serum levels of cortisol, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHA-S), oestradiol-17 beta and total oestrone were measured in 17 postmenopausal breast cancer patients and on age-matched healthy controls. In the breast cancer patients analyses were performed before and after 1, 2, 4, 8 and 12 weeks of treatment with tamoxifen. Basal DHA levels were significantly higher in breast cancer patients than in controls; otherwise no significant differences were noted. Treatment with tamoxifen resulted in significantly elevated levels of cortisol throughout the period of treatment; this effect was probably solely due to an increase in transcortin levels. A transient but significant elevation in total oestrone, probably related to liver function, was observed after one week of treatment. No significant effects of tamoxifen were noted on serum DHA, DHA-S or oestradiol-17 beta. The results indicate that tamoxifen does not affect the adrenocortical steroid biosynthesis in postmenopausal women. The oestrogenic effects of tamoxifen upon FSH, prolactin and the oestrogen induced Pregnancy Zone Protein (PZP) in postmenopausal women, described in a previous communication from this group, are probably not due to any increase in the serum oestrogens since this increase is transient and hardly impressive. The weak oestrogenic effect of the tamoxifen-receptor complex itself may thus be sufficient to produce net oestrogenic effects in subjects with low endogenous oestrogens such as postmenopausal women.

Adrenal Cortex Hormones↗