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Biomedical subjects

H Salzer

Publications and source records attributed to H Salzer.

At least 19 recordsLinked to original sources

Scintimammography enhances negative predictive value of non-invasive pre-operative assessment of breast lesions.

AIMS: The aim of this study was to develop a criterion with a high negative predictive value for the evaluation of breast lesions. We aimed to determine the value of combining three non-invasive tests, mammography (MM), ultrasonography (USS) and 99mTc-methoxyisobutylisonitrite (99mTc-MIBI) scintimammography (scinti-MM). METHODS: We included 94 consecutive patients with suspected lesions detected by mammography or on physical examination. MM, USS and scinti-MM were performed no more than 4 weeks prior to excisional biopsy in all patients. We then compared the biopsy results with a score calculated for each patient, derived from the results of the three tests, which we termed 'mamma malignancy index' (MMI). RESULTS: Each of the three exams yielded a score ranging from 0 to 2, with 0 representing an almost certainly benign lesion, 1 an indeterminate finding and 2 a likely malignant lesion, and hence giving a total score ranging from 0 to 6. The biopsy results showed that the lesions in 64 patients were benign. Forty-nine (77%) of these patients had received an MMI score of 0 or 1. The negative predictive value for malignancy in patients with a score less than 2 was 100%. CONCLUSIONS: Since the smallest detected lesion was 9 mm in diameter, we conclude that MMI may be a highly useful diagnostic tool in the delineation of breast lesions > or =1 cm which should not be routinely referred for biopsy but may be followed non-invasively. Although fine needle aspiration has limitations, we would recommend it as a less invasive method to evaluate suspected lesions smaller than 1 cm.

Adult↗

Oral contraceptives that contain ethinyl estradiol (0.035 mg) and cyproterone acetate (2 mg) inhibit leukocyte transmigration through endothelial cell monolayers.

OBJECTIVE: To investigate the influence of ethinyl estradiol and cyproterone acetate in oral contraceptives on leukocyte migration through endothelial cell monolayers. DESIGN: Experimental in vitro prospective study. SETTING: An academic research laboratory. INTERVENTION(S): Endothelial cells were cultured on microporous membranes to produce monolayers. Polymorphonuclear leukocytes were used in a previously described migration assay (n = 7). The amount of untreated polymorphonuclear leukocytes that migrated through untreated endothelial cell monolayers was used as a control and set at 100%. In addition, a leukocyte adhesion assay was used. MAIN OUTCOME MEASURE(S): Leukocyte adhesion to and transmigration through endothelial cell monolayers. RESULT(S): Ethinyl estradiol and cyproterone acetate inhibited the migration of polymorphonuclear leukocytes through endothelial cell monolayers significantly (67% +/- 6.4%) when both cell types were treated to simulate in vivo conditions. The adhesion assay produced similar results. CONCLUSION(S): Ethinyl estradiol and cyproterone acetate were identified as potent inhibitors of leukocyte migration through endothelial cell monolayers.

Cell Adhesion↗

[Hormones and cancer: risk-benefit].

The influence which female sexual steroids, especially estrogen, have on the development of cancer has not only been shown epidemiologically, but also by experimental findings. Hormones, in spite of a known marginal increase in the risk of thrombosis and endometrial cancer, play an important role in the preventive cancer medication (oral contraceptives: ovarian and endometrial cancer; chemoprevention: high-risk breast cancer patients). Basically, hormone replacement therapy should be administered to all patients suffering from gynecological malignomas. In the case of patients suffering from breast cancer, the advantages of hormone replacement therapy (e.g., less risk of cardiovascular complications) need to be weighed against the disadvantages.

Contraceptives, Oral↗

[Influence of adjuvant hormonal therapy on the whole female organism: benefit versus potential injury].

Not only do patients suffering from hormone receptor-positive tumors of the mammary gland show an increased survival rate, but patients with endometrial as well as ovarian cancer also benefit from hormone replacement therapy. On the one hand, hormonal treatment as well as any other medical treatment influences the tumor, and on the other hand it influences the whole body, which sometimes leads to unfavorable events (increased rate of endometrial cancers during tamoxifen therapy vs. increase of bone density in postmenopausal women). Therefore, hormonal cancer treatment is often suspect. As unfavorable events are rare, and since the benefit is convincing, doctors have to inform women about all the pros and cons of this treatment option, which leads to well-informed and cooperative patients.

Bone Density↗

[The Roma birthing wheel: 1 year clinical experience in a specialty hospital].

OBJECTIVE: To test the safety and practicability of spontaneous deliveries with the Roma birthing wheel (RBW). METHOD: The results of 1 year's clinical experience (1.12.1995-30.11.1996) with the RBW at the Department of Obstetrics and Gynecology, Wilhelminenspital, Vienna, were compared with the results of a group of head-first deliveries before procuring the RBW. RESULTS: Out of 1,555 births, 1,377 (89%) were spontaneous; 209 (15%) women used the RBW. Compared with the figures before the RBW was available, the total duration of labor was reduced by about one third; the birth canal was intact in 44% and the use of painkillers reduced by a range between 8 and 27%. CONCLUSIONS: In spontaneous births the use of the RBW definitely has advantages, e.g., shortening of the procedure and acceptance on the part of the women; also, safety for both mother and child remains unchanged.

Austria↗

Prediction of toxicity but not of clinical course by determining carboplatin exposure in patients with epithelial ovarian cancer treated with a combination of carboplatin and cisplatin.

We present the data from 105 patients with primary epithelial ovarian cancer, who received up to 6 cycles of carboplatin (300 mg/m2) and cisplatin (100 mg/m2) as one treatment arm of a prospective randomized trial. Values for first-course carboplatin area-under-the-curve (AUC) were determined retrospectively. WHO grade 3-4 thrombocytopenia was found in 10% of patients with low AUC (AUC <4 mg/ml x min), but in 44.6% of patients with high AUC (AUC 4 mg/ml x min) (chi-square p<0.0001). No single case of ototoxicity was found in the low AUC group but in 12% of patients in the high AUC group (chi-square p=0.003). Determination of carboplatin AUC may prevent ototoxicity and severe thrombocytopenia for the first cycle of combined treatment with carboplatin and cisplatin.

Antineoplastic Combined Chemotherapy Protocols↗

[Survival prognosis in ovarian carcinoma Figo stages III and IV: 1980-1985 versus 1986-1993. A comparison of 2 treatment periods].

We examined the survival prognosis of 638 patients who had ovarian carcinoma Figo stages III and IV. We considered two separate time periods, 1980-1985 versus 1986-1993, including the size of the postoperative residual tumor, polychemotherapy with and without platinum, histological grading 1 versus 2 and 3, Figo stage III versus IV, and ascites present versus no ascites. Since 1986, 96% of the patients received platinum-containing polychemotherapy at a dosage of > or = 75 mg/m2, whereas between 1980 and 1985, only 76% of these patients received platinum-containing polychemotherapy at a dosage of 50 mg/m2, and 24% of the patients received polychemotherapy without platinum. The size of residual tumor masses and also the time period of treatment had an independent influence on survival prognosis. Patients treated from 1980 to 1985 had a relative risk to die which was 1.44 times higher than for the patients who were studied from 1986 to 1993.

Adult↗

Prenatal effects of betamethasone-L-carnitine combinations on fetal rat lung.

Lungs of fetal rats between the 18th and 20th gestational day (total gestation lasting 22 days) were examined. There was a significant increase (p < 0.01) of the dipalmitoyl phosphatidylcholine content from day 19 to day 20 of gestation. In the second trial, pregnant rats were treated with different doses of betamethasone, L-carnitine, betamethasone-L-carnitine combinations, and saline (controls) for three days before Cesarean section on the 19th gestational day. Maternal injections of 0.10 mg/kg body weight betamethasone and 100 mg/kg body weight L-carnitine significantly (p < 0.05, p < 0.01 respectively) increased the dipalmitoyl phosphatidylcholine content of fetal lungs. Combinations of either 0.05 or 0.10 mg/kg body weight betamethasone with 100 mg L-carnitine also significantly increased the dipalmitoyl phosphatidylcholine content of the fetal lungs above control values (p < 0.001) and values achieved with betamethasone alone (p < 0.05). Maternal treatment with a betamethasone-L-carnitine combination on day 19 of gestation resulted in dipalmitoyl phosphatidylcholine levels comparable to those found on the 20th gestational day during normal lung maturation. Fetal rats delivered on the 20th gestational day survived, while fetuses delivered on the 19th gestational day did not survive.

1,2-Dipalmitoylphosphatidylcholine↗

[Animal experiment and clinical studies of the significance of carnitine for energy metabolism in pregnant patients and the fetus during the pre- and perinatal period].

Carnitine was discovered at the beginning of this century, but was nearly forgotten until its importance in fatty acid metabolism was established 50 years later. In the past years, several other functions of carnitine in cellular metabolism have been described. The lung contains more than 40 different cell types, most of them involved in lipid metabolism. Pulmonary surfactant, a complex of 90% lipids and 10% lung specific apoproteins, is synthesized and secreated from type II cells. Surfactant is present as a monolayer at the air-liquid interface in the alveoli and decreases surface tension. Dipalmitoyl phosphatidylcholine (DPPC) is functionally and quantitatively the most important constituent of the surfactant complex. A deficiency in fetal lung surfactant is the primary cause of the respiratory distress syndrome (RDS), the most severe complication of preterm infants. Glucocorticoids are frequently used to accelerate fetal pulmonary maturation. However, a considerable number of infants fail to respond to this therapy. Maternal administration of L-carnitine significantly increased the DPPC content of fetal rat lungs. The effect of maternal treatment with a carnitine-betamethasone combination was synergistic, especially with lower betamethasone doses. Consequently the minimal dose of betamethasone which affects the DPPC content and accelerate the morphological maturation of the fetal lung was determined. This minimal dose in combination with L-carnitine increased the DPPC content on day 19 of gestation to levels found on the 20th gestational day which allows the survival of most of the preterm rats (term 22 days). Results of clinical trials show that antenatal treatment with a low dose betamethasone-L-carnitine combination has a clear advantage over standard betamethasone therapy. A multicenter study is in progress. Plasma carnitine levels at delivery are decreased to about half of the concentrations seen in non-pregnant women. Similar low levels are found only in patients with carnitine deficiency. Already in the 12th week of gestation the mean whole blood and plasma carnitine levels were found to be significantly lower than those of controls. The reason for increased excretion of acylcarnitines during pregnancy is not known, but could be a detoxifying function similar to that found in patients with inborn errors of fatty acid metabolism and organic acidurias. Carnitine substitution (1 g daily) from the 20th gestational week up to parturition resulted in an increase of free carnitine levels in maternal plasma. A dosage of 0.5 g/day was without effect. Prolonged substitution in pregnant women, especially in risk pregnancies may be preferable to high doses of carnitine administered shortly before imminent premature delivery.

Animals↗

Pregnancy-related changes of carnitine and acylcarnitine concentrations of plasma and erythrocytes.

Total-, free-, and acylcarnitine concentrations were determined in whole blood, plasma, and red blood cells of 88 women during pregnancy. Already in the 12th week of gestation the mean whole blood carnitine level was significantly (p < 0.01) lower than those of the controls. From the 12th gestational week up to parturition there was a further significant (p < 0.01) decrease. This reduction of total carnitine in whole bloods was mainly caused by a significant (p < 0.01) decrease of free carnitine levels, since no marked changes of short chain acylcarnitine values were found throughout pregnancy. The contribution of red blood cell L-carnitine to whole blood carnitine increased significantly (p < 0.05) to 61% at delivery versus 39% (controls). In umbilical cord blood free and total carnitine levels were significantly (p < 0.05) higher than the corresponding maternal levels. The contribution of red blood cell L-carnitine to whole blood carnitine was higher in cord blood than in maternal blood. The results of the present study demonstrate that during pregnancy whole blood and plasma carnitine levels decrease to those levels found in patients with carnitine deficiency. Also the percentage of acylcarnitine on total carnitine, found in the present study, is characteristic for a secondary carnitine deficiency. Thus L-carnitine substitution in pregnant women, especially in risk pregnancies, may be advantageous.

Acylation↗

L-arginine reduces kidney collagen accumulation and N-epsilon-(carboxymethyl)lysine in the aging NMRI-mouse.

BACKGROUND: The aging process leads to glomerular basement membrane (GBM) thickening due to increased collagen accumulation. This mechanism can be explained by the nonenzymatic glycosylation hypothesis of collagen aging. We have published the positive effect of L-arginine on glucose-mediated cross-linking, and if the nonenzymatic glycosylation hypothesis of aging holds, the pharmacological effect of L-arginine on glucose-mediated cross-links in the aging Hannover NMRI mouse can be expected. METHODS: Animals were given L-arginine 50 mg/kg body weight/day orally and compared to a control group without treatment. RESULTS: Electron microscopical measurement of the GBM thickness showed significant differences between controls (4920 +/- 1680 A) and the experimental group (2345 +/- 815 A). Determination of the total kidney collagen content based upon 4-trans hydroxyproline revealed 13.9 +/- 3.9 mg/100 mg kidney weight (kw) in the untreated group versus 7.9 +/- 4.2 mg/100 mg kw in the treated group. For solubility studies based upon hydroxyproline determination, collagen was eluted by pepsin digestion. This revealed 18.7 +/- 3.9 mg/100 mg kw in the controls versus 7.8 +/- 4.8 mg/100 mg kw in the treated group. HPLC analysis of N-epsilon-(carboxymethyl)lysine (CML) showed in the treated group (1.847 +/- 0.247 nM/microM hydroxyproline) significantly lower concentrations than in the untreated group (3.399 +/- 0.349 nM/microM hydroxyproline). On sodium dodecyl sulfate (SDS) polyacrylamidegel electrophoresis, the eluates of the treated animals showed less high molecular weight material than their untreated mates. CONCLUSIONS: We cannot discriminate between the probable mechanisms of cross-linking but we clearly can state that L-arginine reduces cross-linking and collagen accumulation in aging collagen type IV accompanied and strongly associated with decreased CML content.

Aging↗

Antenatal betamethasone-dose-effects on fetal rat lung morphology and surfactant.

Pregnant rats received betamethasone 0.02, 0.05, 0.10, or 0.20 mg/kg body weight/day or saline (controls) for three days before delivery of fetuses at day 19 of gestation. Dose related effects on morphology, dipalmitoyl phosphatidylcholine content, and phosphatidylcholine species composition of the fetal lungs were evaluated. Injection of 0.02 and 0.05 mg/kg body weight betamethasone resulted in cellular differentiation of some cells, but the increase in dipalmitoyl phosphatidylcholine content was not significant. Dosages of either 0.10 or 0.20 mg/kg body weight resulted in markedly accelerated organ differentiation, complete cytodifferentiation of type II cells, and markedly increased numbers of lamellar bodies per alveolar type II cell. Compared to the controls, maternal administration of 0.10 or 0.20 mg/kg betamethasone caused significant increases of both fetal lung dipalmitoyl phosphatidylcholine content, and the fraction of dipalmitoyl phosphatidylcholine of total phosphatidylcholine. None of the parameters differed between the groups that were treated with 0.10 or 0.20 mg/kg body weight betamethasone respectively. Diminution of lung DNA content was significant after treatment with betamethasone in doses of 0.05, 0.10, and 0.20 mg/kg body weight. The results of the present study suggest that maternal treatment with lower doses than those in common usage may be successful in prevention of respiratory distress syndrome, and that higher dosages do not confer any additional advantage.

1,2-Dipalmitoylphosphatidylcholine↗

In vitro and in vivo evaluation of the combination of cisplatin and its analogue carboplatin for platinum dose intensification in ovarian carcinoma.

BACKGROUND: Cisplatin and its analogue carboplatin have been shown to cause dose-dependent growth inhibition throughout a wide dose range in the ovarian cancer cell lines OVCAR-3, 2780, HTB-77, and CRL-1572 tested. Cisplatin was 30 times more effective than carboplatin. The combination of both substances led to a less-than-synergistic effect, as was revealed by an isobologram in the OVCAR-3 cell line. Because of the different toxicity pattern, cisplatin and carboplatin theoretically are ideal candidates for combination chemotherapy in platinum-sensitive tumors. METHODS: In a Phase II study, the efficacy, the toxicity profile, and the feasibility of combining both substances were assessed in 20 previously untreated patients with ovarian cancer. The regimen consisted of carboplatin (300 mg/m2) on day 1, followed by cisplatin (100 mg/m2) on day 2 every 4 weeks. RESULTS: A total of 81 cycles were administered (median, 4 cycles; range, 1-6 cycles); four patients experienced complete remission and three experienced clinical partial remissions. Limiting toxicities were thrombocytopenia, leukopenia, and ototoxicity. The mean (+/- standard deviation [SD]) carboplatin and cisplatin dose intensities (DI) reached during the first four cycles of therapy were 58 mg/m2/week (+/- 18 mg/m2/week) and 21 mg/m2/week (+/- 7 mg/m2/week), respectively, which corresponded closely to the projected DI of 75 and 25 mg/m2/week, respectively. Based on the equivalence ratio of 4:1, the DI of carboplatin has been converted into the respective cisplatin DI, resulting in a total DI estimate. The overall DI of 37 mg/m2/week (+/- 14 mg/m2/week) was close to the projected one of 44 mg/m2/week. CONCLUSIONS: Combining cisplatin with carboplatin was found to represent a feasible and efficacious therapeutic strategy for increasing platinum dose intensity.

Anemia↗

First experience with FGF-3 (INT-2) amplification in women with epithelial ovarian cancer.

Estimation of FGF-3 oncogene amplification in DNA samples extracted from paraffin embedded sections of 136 ovarian cancer samples was carried out by a quantitative PCR method. The aim of this study was to elucidate a possible association of FGF-3 copy numbers with established prognostic factors such as age, histology, FIGO stage, grading, postoperative residual tumour mass, ascites, hormone receptor content and preoperative CA 125 serum levels. In addition, correlation of FGF-3 amplification with overall survival of the patients was assessed. There was a borderline positive correlation between preoperative CA 125 serum levels and the degree of amplification of the FGF-3 gene (P = 0.06). A statistically significant association of FIGO-stage with FGF-3 copy number could be found (P = 0.008). No correlation between FGF-3 amplification and overall survival was noted. The data combine to suggest that FGF-3 is an indicator of aggressiveness of ovarian cancer.

Actuarial Analysis↗

Etoposide and carboplatin as salvage and first-line therapy in ovarian cancer patients.

BACKGROUND: The agents etoposide and carboplatin are active against ovarian cancer and display synergistic anti-tumor activity in animal tumor models. The objective of these two phase II trials was to determine the efficacy and toxicity of the combination of etoposide with carboplatin in previously treated and untreated patients with ovarian cancer. PATIENTS AND METHODS: Etoposide (100 mg/m2) was administered as a one-hour infusion on three consecutive days and carboplatin (400 mg/m2) as a 30-minute infusion on day 2 of each monthly scheduled cycle. In 20 patients, previously treated with cisplatin-containing regimens, a total of 102 cycles was applied as salvage therapy (ST) and in 27 patients, a total of 168 cycles as first-line therapy (FLT). RESULTS: ST yielded 2 complete remissions (CR) and one partial remission (PR); in 7 patients, no evidence of disease (NED) and in 6 patients, no change (NC) were observed. The progression-free intervals (PFI) lasted a median 7.0 months (range < 2-14 months). FLT resulted in 7 CR (4 of them pathologically (p) verified), 11 NED (1 pNED), 3 PR (1 pPR) and 6 NC. The objective response rate was 63% (95% confidence interval: 36-89%). PFI lasted a median 8.0 months (range 3-25+ months); median survival had not been reached at the time of evaluation. Thrombocytopenia (WHO grade 4) was the limiting toxicity. CONCLUSIONS: Although not fulfilling the expectations of synergistic activity as shown in preclinical models, the combination of etoposide with carboplatin is an active and feasible therapy regimen in the out-patient management of ovarian cancer.

Adult↗