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R Kimmig

Publications and source records attributed to R Kimmig.

67 records · Page 4Linked to original sources
PubMed1995

Variations of steroid hormone metabolites in serum and urine in polycystic ovary syndrome after nafarelin stimulation: evidence for an altered corticoid excretion.

To evaluate the clinical relevance of testing pituitary-ovarian responses in patients suffering from polycystic ovary syndrome (PCOS) with the GnRH agonist nafarelin, a 1.2-mg dose of nafarelin was given intranasally to 19 women with PCOS and 15 healthy premenopausal women. The subsequent analysis of steroids in both serum and urine during the test was carried out at several time points for up to 24 h. Serum levels of 17 alpha-hydroxyprogesterone were elevated at all time points of the test in PCOS patients vs. controls [at baseline, 3.5 +/- 0.2 vs. 1.8 +/- 0.1 nmol/L (P < 0.001); at 24 h, 9.9 +/- 0.9 vs. 4.9 +/- 0.3 nmol/L (P < 0.001)]. Basal levels of androstenedione were higher in the patient group, but there was no significant change during the test in either group. Serum testosterone levels were also found to differ in PCOS patients compared with the control values at baseline (2.2 +/- 0.2 vs. 1.5 +/- 0.1 nmol/L; P < 0.05) and after nafarelin treatment (at 24 h, 3.2 +/- 0.4 vs. 1.8 +/- 0.2 nmol/L; P < 0.05). Serum estradiol levels rose significantly in both groups during the test; the posttest levels were significantly higher in PCOS than in controls. The PCOS patients displayed a significant increase in androgen and gestagen metabolites as well as in glucocorticoid metabolites excreted in the urine during the 24 h. In the control subjects, except for 17 alpha-hydroxypregnanolone, which rose significantly, none of the urinary steroids investigated showed relevant changes during the nafarelin test. The posttest excretion of allo-tetrahydrocortisol (1.4 +/- 0.2 vs. 0.3 +/- 0.1 mumol/g creatinine; P < 0.001) and the increase in 17 alpha-hydroxypregnanolone excretion (1.4 +/- 0.2 vs. 0.3 +/- 0.1 mumol/g creatinine; P < 0.001) were distinctly higher in PCOS patients than in the controls; the diagnostic sensitivity of the combination of both parameters was 89% at a 93% specificity. Thus, measurements of 17 alpha-hydroxyprogesterone levels in serum and of urinary allo-tetrahydrocortisol and 17 alpha-hydroxypregnanolone after nafarelin treatment make this stimulation test a valuable diagnostic tool for identifying PCOS patients. The significant changes in the excretion of urinary androgen and gestagen metabolites, unmasked by GnRH agonist stimulation, suggest a functional alteration of the pituitary-ovarian axis. The reason for the increased excretion of glucocorticoid metabolites after nafarelin stimulation remains to be clarified.

Administration, Intranasal↗
PubMed1994

Flow cytometric DNA analysis of breast cancer by two colour method using cytokeratin labeling for identification of tumour cells.

Flow cytometric assessment of DNA-ploidy and S-phase fraction in breast cancer is compromised by the heterogeneity of cell subpopulations derived from the malignant and surrounding connective tissue, e.g. tumour, stromal and inflammatory cells. To identify tumour cell subpopulations, epithelial cells were labeled by a FITC-conjugated cytokeratin antibody (CK6, CK18) prior to flow cytometric cell cycle analysis in 205 fresh specimens of primary breast cancer. We found 158/205 (77%) DNA-aneuploid tumours compared to 127/205 (62%) without identification of cytokeratin positive cells (P < 0.001). In addition, the number of detected DNA-multiploid tumours rose from 31 (15%) to 51 (25%) after gating for cytokeratin positive cells. In DNA-diploid tumours, S-phase and G2M-phase fractions were significantly higher in cytokeratin positive (tumour) cells compared to total cell populations (4.4% and 5.8% vs. 3.2% and 4.4%; P < 0.001). Cytokeratin negative cells were found in all tumours and can be used as internal standard for calculation of ploidy and for quality control (CV, linearity) of each individual sample. We conclude that at least 20% of DNA-aneuploid tumours would not have been diagnosed without cytokeratin labeling. In addition, influence of non-tumourous cell elements on cell cycle analysis can be markedly reduced. Therefore, both determination of DNA-ploidy and cell cycle analysis can be optimized by cytokeratin labeling.

Breast Neoplasms↗
PubMed1994

[Treatment of endometriosis with the GnRH agonist leuprorelin acetate depot (Enatone-Gyn monthly depot): a multicenter study].

In an open, non-randomized prospective phase-III-study the clinical and endocrine efficacy as well as the safety of leuprorelin acetate depot (Enantone-Gyn Monats-Depot) were investigated. The therapeutic results of 198 patients, gathered from 5 university institutions and two city hospitals, are reported. Endometriosis was classified by the revised American Fertility Society score (r-AFS) before and at the end of treatment. Serum levels of LH, FSH, prolactin, estradiol, progesterone, androstenedione, testosterone and leuprorelin acetate were determined by radioimmunoassay. The mean total r-AFS score changed as follows: before surgical intervention during first-look laparoscopy 21 +/- 24 at the end of first-look laparoscopy 15 +/- 19 at the end of the GnRH-treatment 8 +/- 14 During leuprorelin acetate treatment the r-AFS stages changed as follows: [table; see text] Using the scoring system 85.2% of the patients improved. Relief of dysmenorrhoea could be achieved in 95.4%, relief of dyspareunia in 64% and of pelvic pain in 69.4% of patients. Baseline hormone levels dropped sharply during treatment. [table; see text] Androstenedione, testosterone, blood pressure, body weight, haematological parameters, liver enzymes, creatinine, electrolytes and HDL-/LDL-cholesterin remained more or less unchanged. Side effects being hot flushes, sweating, sleeplessness, headache, nausea, depression and vaginal dryness were due to estradiol deprivation. In 135 patients resumption of menstruation occurred in 95.6% within the first three months post-treatment. 23 patients of whom 21 were judged as infertile, became pregnant immediately after treatment was finished. The study results confirm the efficacy of leuprorelin acetate depot in the treatment of even advanced stages of endometriosis.

Adolescent↗
PubMed1994

[Requirements in preoperative diagnosis of gynecologic diseases of the pelvis].

Correct diagnosis of disease, staging of malignancies and detection of primary or secondary abnormalities of the adjacent pelvic organs are the basic requirements of preoperative diagnostic procedures in gynecological disorders. The latter is usually done by ultrasound, intravenous pyelography and endoscopic examination of the bladder and the colon. The diagnosis of disease with respect to malignancies of the uterus, vagina and vulva can usually be made by clinical examination and histology obtained by biopsy. On the other hand, ovarian tumors cannot be sufficiently differentiated by clinical methods. Ultrasound, magnetic resonance imaging and computed tomography may be helpful, but definitive diagnosis usually requires a surgical approach. This is also true for staging of gynecological malignancies. Nevertheless, improvements in preoperative diagnostic procedures allow individualized planning of surgery and improved staging in patients treated primarily by radiotherapy.

Diagnosis, Differential↗
PubMed1992

Treatment of endometriosis with leuprorelin acetate depot: a German multicentre study.

During the past decade, the development of various gonadotrophin-releasing hormone (Gn-RH) agonists, which induce reversible hypo-oestrogenism has opened a new area in the medical management of endometriosis. In an open, multicentre phase III study, the efficacy, tolerance and safety of the Gn-RH agonist leuprorelin acetate were tested. The preliminary results of 104 women treated in seven German centres are presented. Pelvic endometriosis was diagnosed by laparoscopy and classified according to the American Fertility Society scoring system: 33% of patients had minimal, 22% mild, 28% moderate and 8% severe endometriosis and in 9% no pathological results were obtained. The patients' mean age was 30 +/- 6 years and 66 had infertility problems. Treatment was started within the first 3 days of the menstrual cycle and consisted of a subcutaneous injection of leuprorelin acetate 3.75 mg, repeated once monthly over 24 weeks. A follow-up period of 12 months after the last injection has been completed in 70 patients, including a second laparoscopy. At all visits, symptoms were evaluated, physical examinations performed, and blood samples collected for haematological screening, serum chemistry determinations and measurement of the gonadotrophins oestradiol and progesterone and leuprorelin acetate. The median score at laparoscopy fell from 12 before operation to 8 after operation and 2 after treatment with leuprorelin acetate. Of the total number of patients, 89% had improvements in their endometriosis, 8% a deterioration and 3% no change. Patients reported improvement in the following: dysmenorrhoea 93%, dyspareunia 62% and pelvic pain 70%. However, all women complained of at least one of the following symptoms: hot flushes 86%, sleep disturbance 62%, sweating 61%, headache 41%, nausea 32% and depression 20%. Fifty-five percent of patients reported additional side effects such as vaginal dryness, fatigue and lower abdominal pain. After the third injection, amenorrhoea persisted in 94% of the women. Four weeks after the first leuprorelin acetate injection median concentrations of oestradiol fell from 45 pg/ml to 11 pg/ml, follicle-stimulating hormone from 7 U/L to 3 U/L and luteinising hormone from 5 U/L to 1 U/L and remained almost unchanged over the observation period. During the 6 months' treatment, laboratory parameters showed no significant deviations from normal; only total cholesterol, high-density lipoprotein cholesterol and alkaline phosphatase increased. Treatment results were judged as good and satisfactory in 82% and 11% of cases, respectively. On the basis of this study, it can be concluded that leuprorelin acetate treatment is safe, well tolerated and effective in the medical management of endometriosis and endometriosis-related complaints.

Adult↗
PubMed1989

Antibodies against the human papillomavirus type 16 early proteins in human sera: correlation of anti-E7 reactivity with cervical cancer.

By Western blot technique, 519 samples of human sera were tested for the presence of antibodies to the human papillomavirus (HPV) type 16 proteins E4 and E7 that had been expressed in Escherichia coli as fusion proteins. Sera were obtained from patients attending the University hospitals for reasons unrelated to HPV infections (controls), from patients with HPV-associated lesions, as well as from patients suffering from cervical cancer. Within the control population, 18.1% of them had antibodies that reacted with the E4 protein, and 3.9% of them had antibodies that reacted with the E7 protein. No sex-specific difference in the antibody prevalence was observed. The highest proportion of anti-E4 antibody-positive individuals (40.7%) was observed in the age group between 11 and 20 years. The frequency of anti-E4-positive sera was threefold higher in patients with HPV-associated genital lesions than that in age-matched controls. Antibodies against the HPV16 E7 protein were found 14 times more frequently in patients with cervical cancer, compared with age- and sex-matched controls (P less than .00001). From these data, we concluded that anti-E4 antibodies may be correlated with virus replication and that anti-E7 antibodies may represent a marker for cervical cancer development.

Adolescent↗
PubMed1988

Minor role of ketone bodies in energy metabolism by skeletal muscle tissue during the postoperative course.

To evaluate changes of peripheral ketone body (KB) metabolism after operation, muscle metabolism in postsurgical patients was studied at 3 hours (SI) and 24 hours (SII) after surgery by the forearm catheter technique. Data were compared to those of equivalent fasted controls (CI, CII). In a manner consistent with enhanced mobilization of endogenous substrate stores, arterial concentrations of free fatty acids (FFA), 3-hydroxybutyrate (3-HOB), and acetoacetate (AcAc) were markedly elevated immediately after surgery. This increase was accompanied by a rise in muscular utilization of AcAc (SI: 0.21 +/- 0.05 mumol/100 g/min; CI: 0.08 +/- 0.05, p less than 0.05) and 3-HOB (SI: 0.24 +/- 0.06 mumol/100 g/min; CI: 0.11 +/- 0.01, p less than 0.05). Surprisingly, on the first postoperative day, concentrations of AcAc and 3-HOB fell below those of fasting controls. Concomitantly, the utilization rate of AcAc by muscle (SII: 0.07 +/- 0.03 mumol/100 g/min; CII: 0.27 +/- 0.04, p less than 0.05) was significantly lower in patients than in controls. Reduction of the fractional extraction rate of AcAc (SI: 38.4 +/- 3.8%; SII: 24.0 +/- 6.1%, p less than 0.05), as well as a net production of 3-HOB by muscle (SII: -0.08 +/- 0.05 mumol/100 g/min; CII: 0.49 +/- 0.13, p less than 0.05) 24 hours after surgery indicated a reduced peripheral capacity for KB removal. Since this finding was related to a significantly higher rate of muscular glycerol production (SII: -0.13 +/- 0.03 mumol/100 g/min; CII: -0.06 +/- 0.02, p less than 0.05), one may suggest that increased intramuscular availability of FFA from triglyceride hydrolysis was responsible for the impairment of peripheral KB utilization. These results indicate that KBs contribute little to energy metabolism in skeletal muscle tissue in the late postoperative phase.

3-Hydroxybutyric Acid↗
PubMed1983

Actions of glucagon on flux rates in perfused rat liver. 1. Kinetics of the inhibitory effect on glycolysis and the stimulatory effect on glycogenolysis.

Changes in the rates of glucose, lactate and pyruvate production following infusion of glucagon were studied in isolated livers from fed or fasted rats perfused with non-recirculating Krebs-Henseleit bicarbonate buffer. Evidence was presented that under these experimental conditions, the release of lactate plus pyruvate into the perfusate represents 80-90% of the total glycolytic flux; oxidation of pyruvate derived from glucose and/or glycogen accounts for the remaining 10-20%, whereas recycling of pyruvate to glucose is negligible. In the presence of glucagon, rates of lactate plus pyruvate production were diminished to less than 30% in the fed state (glycogen as substrate) and to less than 10% in the fasted state (glucose as substrate). Rates of pyruvate oxidation were unchanged. Although recycling of pyruvate to glucose was enhanced, it could account for not more than 20% of the decrease in lactate plus pyruvate production. The data indicate a strong inhibition of the substrate flux through glycolysis. The glucagon concentration for half-maximal inhibition of glycolysis was 0.2 nM, independent of the substrate (glucose or glycogen) and the nutritional state. The effective concentrations were within the physiological range of glucagon concentrations reported for portal venous blood. Transient state analyses indicated that the inhibition of glycolysis precedes the stimulation of glycogenolysis. When after a delay glycogenolysis was accelerated, it was followed by a transient stimulation of glycolysis. The stimulatory component in the glucagon effect on glycolysis was diminished in glycogen-depleted livers and when glucose was the main substrate. The coordinated control of glycolysis and glycogenolysis by glucagon and the interaction of the two processes in the transient state are discussed.

Animals↗
PubMed1983

Actions of glucagon on flux rates in perfused rat liver. 2. Relationship between inhibition of glycolysis and stimulation of respiration by glucagon.

The relationship between inhibition of glycolysis and stimulation of oxygen consumption by glucagon was studied in perfused rat livers. The two effects exhibit similar kinetics and dose-response curves; they are slower and less sensitive to the glucagon concentration than the stimulatory effect on glycogenolysis. A stoichiometry of 1 mol extra oxygen consumed/1.8 mol of diminished lactate plus pyruvate production was found. Under conditions where glucagon did not cause a marked inhibition of glycolysis (i.e. low glycolytic flux rates in the fasted state or in the presence of ethanol), oxygen consumption was also not markedly increased. These findings provide evidence that the major portion of glucagon-induced stimulation of hepatic respiration in the fed state is due to an enhanced demand for mitochondrial oxidative phosphorylation to compensate for the diminished extramitochondrial ATP production following inhibition of glycolysis by glucagon.

Animals↗
PubMedDate not supplied

Myomectomy as a pregnancy-preserving option in the carefully selected patient.

OBJECTIVES: To present the indications for myomectomy during pregnancy and to discuss complications possibly related and unrelated to the procedure. METHOD AND RESULTS: A 33-year-old patient at 18 weeks of gestation underwent removal of a 1,570-gram symptomatic fundic myoma. Histologically the patient had a leiomyomatous neoplasm of uncertain malignant potential. The pregnancy was continued under sequential observation with magnetic resonance imaging and ultrasound. At 36 weeks of gestation a healthy girl with an upper extremity limb defect was born via cesarean section. Follow-up of the mother and the child was uneventful. CONCLUSIONS: Certain known risk factors in pregnant women with myomas can predispose to complications during pregnancy. Women with such risk factors or women who have failed medical therapy should be offered the option of undergoing myomectomy as a pregnancy-preserving procedure.

Adult↗