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Biomedical subjects

R Kolb

Publications and source records attributed to R Kolb.

At least 55 records · Page 3Linked to original sources
PubMed1984

[Surgical therapy of breast cancer: to operate radically or to preserve the breast?].

Surgical treatment, i.e. partial resection (R) versus modified radical mastectomy (M) in lymph node negative T1/2 patients and M versus the classical Halsted procedure (RM) in lymph node positive cases, as well as adjuvant treatment forms, namely chemotherapy (B) and chemoimmunotherapy (C) versus a control group treated by surgery only (A) have been evaluated in 241 patients with breast cancer follow up over a median observation time of 48 months. Whereas M showed significantly better results than R, no difference was detected between M and RM. The incidence of recurrence in the R group did not appear to be markedly reduced by cytotoxic treatment. In the same way, the data from a retrospective study on non-randomized patients treated by breast resection, showed a relatively high local recurrence rate (23.6%) at a median observation level of 10 years. Considering the various forms of surgical treatment for operable breast cancer by analysing the data from retrospective studies and prospective randomized trials from the literature as well as our own results, the only recommendation for the standard treatment of patients with primary operable breast cancer should be nothing less than modified radical mastectomy. Breast-conserving treatment forms should be tested only within the framework of controlled clinical trials.

Breast Neoplasms↗
PubMed1984

Plasma mevalonate as a measure of cholesterol synthesis in man.

Measurement of mevalonic acid (MVA) concentrations in plasma or 24-h urine samples is shown to be useful in studies of the regulation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and cholesterol synthesis. Plasma MVA concentrations, measured either at 7-9 a.m. after an overnight fast, or throughout the 24-h cycle, were compared with cholesterol synthesis rates that were measured by the sterol balance method: plasma MVA concentrations were directly related to the rate of whole body cholesterol synthesis (r = 0.972; p less than 0.001; n = 18) over a tenfold range of cholesterol synthesis rates. Moreover, hourly examination of MVA concentrations throughout the day demonstrated that interventions such as fasting or cholesterol feeding cause suppression of the postmidnight diurnal rise in plasma MVA concentrations, with little change in the base-line of the rhythm. Thus, the daily rise and fall of plasma MVA appears to reflect changes in tissues and organs, such as the liver and intestine, that are known to be most sensitive to regulation by fasting or by dietary cholesterol. The hypothesis that short-term regulation of HMG-CoA reductase in tissues is quickly reflected by corresponding variations in plasma MVA was tested by using a specific inhibitor of HMG-CoA reductase, mevinolin, to block MVA synthesis. Mevinolin caused a dose-dependent lowering of plasma MVA after a single dose; and in patients who received the drug twice a day for 4 wk, it decreased 24-h urinary MVA output. Significant lowering of plasma cholesterol was achieved through administration of mevinolin at doses that only moderately limit MVA production.

Cholesterol↗
PubMed1983

Treatment of familial hypercholesterolemia by portacaval anastomosis: effect on cholesterol metabolism and pool sizes.

Measurements of the key parameters of cholesterol homeostasis and the mass of the body pools of cholesterol were carried out in two patients with familial hypercholesterolemia (FH), one homozygote and one heterozygote, before and 28 and 18 months, respectively, after portacaval anastomosis (PCA). In both patients the procedure significantly reduced the plasma concentrations of total and low density lipoprotein cholesterol and the daily rate of whole body cholesterol and bile acid synthesis. In addition, PCA caused a net efflux of accumulated tissue cholesterol as demonstrated by reductions in the rapidly exchangeable and total exchangeable masses of body cholesterol. Shunt patency was verified by demonstration of increased bile acids in serum from fasting patients and from patients 2 hr after a meal and by increased plasma glucagon before and after arginine infusion. Other than a persistently increased level of serum alkaline phosphatase, liver function tests have fallen within the normal range in both patients; there has been no evidence of hepatic encephalopathy. In the homozygous patient there has also been a striking resolution in xanthoma size and distribution. These multiple effects on cholesterol homeostasis and pool sizes strongly suggest that PCA can reverse the progressive accumulation of cholesterol in body tissues of FH patients.

Bile Acids and Salts↗
PubMed1983

Clinical and experimental aspects of hormone receptors in breast carcinoma patients.

Estrogen (ER) and progesterone (PgR) receptor contents were determined in 214 patients with primary mammary carcinoma. Premenopausal and postmenopausal females (43 and 48%, respectively) were found to be ER and PgR positive. ER levels between 100 and 500 fmol/mg protein were observed in 37% postmenopausal and 14% premenopausal patients, respectively. ER distribution between lymph node-positive and -negative patients did not differ significantly. Subjects without detectable ER had recurrences earlier than did subjects with ER. On the other hand, no differences in recurrence rates were noted when PgR-positive and -negative patients were compared. In addition, the determination of ER did not permit selection of patients for adjuvant cytotoxic chemotherapy. Furthermore, the action of tamoxifen was investigated in the rat pituitary as a model system. Tamoxifen was found to act as antiestrogen at the level of transcription by inhibiting the accumulation of estrogen-stimulated preprolactin mRNA. Combined data suggest that patients with positive lymph nodes and positive receptors may benefit from combined endocrine plus cytotoxic adjuvant chemotherapy.

Animals↗
PubMed1982

Mevalonic acid in human plasma: relationship of concentration and circadian rhythm to cholesterol synthesis rates in man.

We tested the hypothesis that the rate of cholesterol synthesis in tissues determines the concentrations of mevalonic acid (MVA) in plasma. We found that plasma MVA concentrations were correlated (i) with increased rates of whole-body cholesterol synthesis (measured by sterol-balance methods) in patients treated with cholestryamine resin (ii) with decreased rates of whole-body sterol synthesis (indicated by conversion of labeled acetate to sterol in freshly isolated mononuclear leukocytes) in out-patients after 4 weeks on a cholesterol-rich diet. In addition, a diurnal rhythm of plasma MVA concentrations was observed in patients whose activities were strictly controlled on a metabolic ward. At the peak of the rhythm (between midnight and 3 a.m.) MVA concentrations were 3-5 times greater than at the nadir (between 9 a.m. and noon). Furthermore, a relationship between the diurnal rhythm of plasma MVA and endogenous cholesterol synthesis is suggested by our finding that the plasma MVA rhythm was suppressed by cholesterol feeding (1,200 mg/day) and abolished by a 12-day fast. The presence in human plasma of MVA, an obligate precursor of cholesterol, in amounts apparent related to the rate of cholesterol synthesis offers a noninvasive, nonisotopic method for studying cholesterol synthesis in man.

Cholesterol↗
PubMed1982

Generation of suppressor cells for natural killer activity in cancer patients after surgery.

Natural killer (NK) cell activity was examined in breast cancer patients before and after surgery, and the cells involved in the postoperative depression of cytotoxicity were characterized. NK activity against K562 target cells determined in 4-hour 51Cr release assay of blood lymphocytes from preoperative patients was comparable to that of normal donors. After surgery the patients showed a decrease in NK activity but not in number of large granular lymphocytes in the effector cell populations. When blood mononuclear cells from postoperative patients were depleted of monocytes by adherence to a serum-coated plastic dish and a Sephadex G10 column and then cultured for 24 hours, they showed an increase in NK activity. Furthermore, adherent blood cells of postoperative patients, but not of normal donors or preoperative patients, suppressed the lytic function of NK cells of normal individuals. Twenty-four-hour preculture of suppressor and effector cells was required for suppression of cytotoxicity. Neither postoperative sera nor culture supernatants of suppressor monocytes and effector cells suppressed NK activity. In contrast, the lymphoproliferative response to mitogen was not affected by surgery, and postoperative blood monocytes did not inhibit the mitogenic response of normal lymphocytes. The results suggest that the appearance of suppressor monocytes in the circulation could be one cause of depression of NK activity in postoperative cancer patients.

Adult↗
PubMed1981

[Steroid receptor levels in human breast carcinomas in relation to serum hormone levels in postmenopausal patients (author's transl)].

Serum levels of LH, FSH, HPRL, oestradiol, progesterone and testosterone were determined by radioimmunoassay in 45 postmenopausal patients in the morning before they were operated on for primary breast cancer. Cytosol oestradiol - (E2R) and progesterone receptor (PgR) levels were estimated by Scatchard plot analysis of saturation assays using the charcoal method. When serum hormone levels and receptor contents were correlated according to the distribution free test of Spearman, all correlations were found to be insignificant, with the exception of E2R/PgR (p less than 0.001).

Aged↗
PubMed1981

[Tumor histology and steroid receptors in breast carcinoma].

In Specimens of 115 patients with breast cancer 4 tumorparameters (tumorsize, tumorboder, nucleargrade, lymphocytic stromal reaction) 3 features of regional lymphnodes (sinushistiocytosis, T-cellreaction, lymphnode metastases) and estrogen and progesteron receptors were determined. A strong sinushistiocytosis and T-cellreaction could be verified mainly in metastases in free lymphnodes. The steroid receptor content does not correlate with histological parameters.

Breast Neoplasms↗
PubMed1980

[Oestrogen receptors and prognosis in breast cancer].

The determination of oestrogen receptors seems to be of prognostic value in the radically-operated breast cancer patient. Patients with negative receptor values exhibit early recurrence in a significantly higher percentage of cases than those with positive values. The prognostic implications of oestrogen receptor determination seem to be even higher than an assessment of axillary lymph node involvement. In metastatic breast carcinoma a correlation exists between response to hormonal therapy and receptor assay. The clinical implications for therapeutic management are discussed.

Adult↗
PubMed1980

Results with tamoxifen in advanced mammary carcinoma.

The results of a study with tamoxifen (TAM) (10 mg three times daily) in advanced breast cancer are reported. Of 44 patients, 24 showed a remission and 20 a progression. Of the 17 patients in whom an oestrogen receptor (ER) determination in tumour tissue had been carried out, 12 were receptor-positive (ER+) and five receptor-negative (ER-). Nine of the 12 ER+ cases (75%) responded to the treatment with TAM. Of the five ER- patients, one showed remission and four progression.

Bone Neoplasms↗
PubMed1980

A diffusion chamber technique for measuring concentrations of antibiotics in interstitial fluid.

A method for collecting soft tissue interstitial fluid in experimental animals for the measurement of antibiotic concentrations is described. Diffusion chambers with permeable membranes of 0.45 micron porosity were implanted subcutaneously for four days in order to determine simultaneous concentrations of ampicillin and clindamycin in serum and chamber fluid after perioral administration in rabbits and of oxytetracycline after intravenous injection in dogs. The results are discussed in view of findings from other investigators using different types of tissue cages.

Ampicillin↗
PubMed1980

Factor VIII-related antigen assay in capillary samples.

Factor VIII-related antigen was assayed in adults in venous citrated samples and in samples taken with heparinized and plain capillaries blown out in citrate. The three sampling methods gave nearly identical results in a wide range of values. Two of the sampling methods were used in newborns and again the results showed excellent correlation.

Adult↗
PubMed1980

[Prognostic value of estrogen receptors in breast cancer (author's transl)].

One hundred and ninety-one patients with operable breast cancer were followed for up to 34 months after operation and the early recurrence of disease was noted in relation to the presence or absence of estrogen receptor. Recurrence rates were significantly higher in patients whose tumors did not contain receptors than in those whose tumors did. The response to cytotoxic chemotherapy in patients with advanced breast carcinoma seems to be independent of the presence of E2R in cancer tissue.

Breast Neoplasms↗
PubMed1979

[Prognostic factors in the drug therapy of metastasizing breast cancer].

175 patients with metastatic breast cancer, treated with chemotherapy, were analyzed retrospectively to identify the characteristics of prognostic importance in predicting response to chemotherapy and survival from onset of the chemotherapy. The most significant factors were the sites of metastatic disease and an estimate of the total extent of disease.

Antineoplastic Agents↗
PubMed1979

[Various amounts of estrogen receptors in breast neoplasms].

An agar gel electrophoresis was performed to demonstrate various amounts of estrogen receptors of three different topics in 38 mammary carcinomas. A good correlation between estrogen receptors in primary mammary carcinomas and axillary lymph node metastases could be found.

Breast Neoplasms↗