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To show the equivalence of the transpulmonary thermodilution method to the direct Fick principle in children.Prospective single-centre study.A 16-bed paediatric cardiac ICU and a cardiac catheterisation laboratory at an university affiliated centre for paediatric cardiology and congenital heart disease.We consecutively investigated 18 patients (mean age 12.1 +/- 6.4 years) during cardiac catheterisation and after corrective cardiac operation.We prospectively defined limits of equivalence for cardiac index (CI) for both methods of +/- 0.25 l/min x m(2). We measured oxygen consumption for determination of CI by Fick as the clinical "gold standard" and performed a set of three transpulmonary thermodilution measurements. The mean CI(Fick) was 2.88 +/- 1.07 l/min x m(2) (range 1.10-4.62 l/min x m(2)) and CI(TPID)was 2.85 +/- 1.03 l/min x m(2)(range 1.02-4.49 l/min x m(2)). The mean difference between CI(Fick) and CI(TPID)was 0.030 +/- 0.168 l/min x m(2), and limits of agreement -0.306 to 0.366 l/min x m(2)(90% confidence interval -0.040 to 0.099 l/min x m(2)). The regression equation was : CI(Fick)=1.0244 x CI(TPID)-0.040, r(2) = 0.976, P0.0001. The intraclass coefficient of reliability for three repeated measurements of CI(TPID) was 0.97, the corresponding lower limit of the 95% confidence interval was 0.94.We demonstrated the equivalence of CI measurement by transpulmonary thermodilution and the Fick principle in children. This new method may improve hemodynamic monitoring and management in seriously ill children.

Efficient inhalation therapy depends on successful delivery of the drug to the lung. The efficacy of drug delivery is not only influenced by the characteristics of the inhalation device, but also by the patient's handling of the device and by the inspiratory maneuver achieved through the device. We analyzed the output characteristics of three different chlorofluorocarbon (CFC)-free breath-actuated inhalers for inhaled glucocorticosteroids (BUD Turbohaler, FP Diskus/Accuhaler and HFA-BDP Autohaler, respectively). Mass output and particle size distribution of drug aerosol delivered by the inhalers were determined depending on different inhalation parameters in vitro using an Andersen cascade impactor. We found that, beside the peak inspiratory flow (PIF), other factors such as flow acceleration and inhalation volume also have significant effects on aerosol generation with respect to mass output and particle size distribution. Thus, these parameters should be taken into account when a suitable device for an individual patient is to be selected. The dependency on inspiratory parameters was most pronounced for the dry powder inhalers. The Turbohaler showed by far the highest variance in particle output (fine particle fraction ranging from 3.4% to 22.1% of label claim), whereas the Diskus was less dependent on variations in inhalation (10.6% to 18.5% of label claim). The most constant aerosol output was found for the Autohaler, which also released the highest fine particle fraction (43.1% to 56.6% of label claim).

Objective: Most studies have found survival after local recurrence of breast cancer to be poorer after mastectomy than after breast-conserving surgery. We studied whether this is the case because patients undergoing mastectomy have a more unfavorable risk profile and whether it applies also to patients with early stage disease. Methods: We conducted a matched-pair analysis (breast-conserving surgery vs. mastectomy) of 62 patients with local recurrence of early stage (pT1 -pT2 NO) breast cancer without evidence of systemic disease. Patients were matched for tumor size, histologic grade and age. Prognostic parameters at the time of primary diagnosis and at recurrence were evaluated with univariate and multivariate analyses with respect to survival after recurrence. The median follow-up was 7.5 years. Results: There were no significant differences between the two groups in the size of the primary tumor, histologic grading, and size of recurrent tumor. The disease-free interval between primary diagnosis and local recurrence was 8 months shorter in patients after mastectomy than in those after breast-sparing surgery (p = 0.35). Survival after recurrence was shorter in the patients after mastectomy but this difference was not statistically significant (98 vs. 208 months, respectively; p = 0.11). The disease-free interval before local recurrence (but not the type of primary surgery) was the only independent prognostic factor for subsequent survival in both the univariate (p = 0.02) and the multivariate (p = 0.01) analyses. Conclusion: The difference in survival after local recurrence after mastectomy compared with breast-sparing surgery for early breast cancer is small and appears to be associated with different disease-free intervals before local recurrence.

Objective: Chest wall irradiation after mastectomy for breast cancer is now usually reserved for patients with extensive carcinomatous lymphangiosis or positive surgical margins. However, recent studies suggest that the reduced risk for local recurrence following radiotherapy of the chest wall might improve the survival of these patients. We studied the influence of chest wall irradiation on local recurrence and overall survival rates in patients with breast cancer treated with mastectomy. Methods: We reviewed 1964 patients with pT 1-2 breast cancer treated with mastectomy since 1963. Patients treated before 1979 routinely received chest wall irradiation while those treated after 1979 received irradiation only if there was histologic evidence of extensive carcinomatous lymphangiosis or positive surgical margins. The groups were compared with Kaplan-Meier analysis and the log-rank test. Results: Patients, who received adjuvant radiotherapy had a significantly lower rate of local recurrence regardless of the nodal status. Ten years after primary diagnosis, 98% of patients who received irradiation are free of local recurrence, compared with 86% of those who did not (p

Between 1963 and 1993, 3720 women were treated both at the Universitats-Frauenklinik Berlin-Charlottenburg and at the I. Frauenklinik der Universitat Munchen for a malignant condition of the breast. 187 of these (5%) exhibited stage p Tis, 102 (54.5%) of whom had an axillary lymphadenectomy. One patient had a micrometastasis (pN1a). During the observation period of up to 24 years, 11 patients (5.9%) developed local recurrence. In none of the patients a regional or generalised recurrence could be observed within this period. On the basis of our own results and those from the literature, we conclude that, under the aspect of a risk-adapted tumour surgery, axillary lymphadenectomy is no longer necessary under certain conditions: an invasive carcinoma should be excluded with high certainty in the tumourectomy specimen as well as in the remaining breast. Therefore, a histological work-up in serial sections must be provided to exclude multifocality (multicentricity) and a tumour diameter larger than 25 mm.

Ziel: Die Praktikabilität und Effektivität einer standardisierten, unmittelbar präoperativ durchgeführten isovolämischen Hämodilution wurde bei großen gynäkologischen Eingriffen (Wertheim-Operation u. a.) untersucht. Design: Prospektive klinische Studie mit historischer Vergleichsgruppe. Rahmen: Operations-saal einer gynäkologischen Universitätsklinik. Patienten und In-terventionen: Bei 48 Patientinnen (mittleres Alter: 53 Jahre) wurde in Allgemeinanästhesie eine Hämodilution auf eine H-ämoglobinkonzentration von 9 g/dl durchgeführt (Abnahmemen-ge 900 ± 210 ml). Intraoperativ wurde bei Unterschreiten eines Hb-Wertes von 7 g/dl Eigenblut bzw. Fremdblut transfundiert. Ergebnisse: Gegenüber dem Vergleichskollektiv von 57 Patientinnen ohne Hämodilution wurde die Gesamtzahl an Fremdbluttransfusionen signifikant reduziert. Perioperativ konnte bei 65% aller Patientinnen jegliche Fremdblutübertragung vermie-den werden (Kontrollgruppe: 21%). Unerwünschte Nebenwir-kungen traten nicht auf. Schlußfolgerungen: Die Untersuchung zeigt, daß die akute isovolämische Hämodilution bei großen gynäkologischen Eingriffen ein sicheres, leicht zu handhaben-des und effektives Verfahren ist, das erlaubt, bis zu einem Ge-samtblutverlust von 1300 bis 1400 ml – in Einzelfällen auch dar-über – gänzlich auf eine Fremdbluttransfusion zu verzichten.

From January 1988 to December 1991, 343 women were operated for genital carcinoma at the 1st Gynaecological Department of the University Munich. Additionally to the corresponding cancer operations, pelvic or pelvic and paraaortic lymphadenectomy was performed. In a postoperative systematic and prospective study with ultrasound, we detected a high incidence of 48% of postoperative lymphocysts. Only a few were symptomatic and even less required therapy. In this study we were especially interested in the influence of closure of the pelvic peritoneum on the incidence of lymphocysts. Thus, we inaugurated a prospective study in 1991 with 49 patients with an open peritoneum and compared these results to 294 women who had standard closure of the peritoneum. There was a significantly higher rate of lymphocysts in patients with peritoneal closure (45.2%) in comparison to 20.4% lymphocysts in patients without peritoneal closure. In the study group (open peritoneum) 6.1% of the patients with lymphocysts showed symptoms, only 4.1% needed therapy. In the control group (closed peritoneum), 14.6% of the patients with lymphocysts were symptomatic and 8.2% needed therapy. These differences are not statistically significant. Other complications such as haemorrhage, fever or ileus were comparable in both groups. Our results do not supply sufficient proof, that leaving the peritoneum open significantly reduces symptomatic lymphocysts.

Risk Cervical Carcinoma: Patients with carcinoma of the cervix and histologically proven blood vessel invasion have a poor prognosis. At the 1. Frauenklinik der Universitat Munchen, 34 women were enrolled for a prospective study and were alternatively treated with or without adjuvant chemotherapy (carboplatin and 5-fluorouracil). Of the 28 patients included in the follow-up (14 with/14 without chemotherapy), 12 patients died (5 with/7 without chemotherapy). The disease-free interval was 18.6 months in the group treated with chemotherapy compared to 29.3 months in the group without chemotherapy. There is no statistically significant difference in the survival of patients with blood vessel invasion in relationship to adjuvant chemotherapy following radical hysterectomy.

Primary hepatocellular carcinoma is a very rare disease, especially in association with a pregnancy. We report on a 22-year-old primigravida, who underwent Caesarean section in the 29th week of pregnancy in conjunction with tumour-reductive surgery for hepatocellular carcinoma. The further course of the disease was characterised by an early recurrence and lung metastases. Under palliative chemotherapy with 5-fluorouracil, the patient has been in a state of stable disease for several months. Typical risk factors for the hepatocellular carcinoma do not exist in the patient. Alternative explanations for the aetiology of the disease are discussed.

Background: Local recurrence remains a major concern after primary treatment of breast cancer and has a major impact on subsequent survival. While most studies report a poorer survival rate in patients with a local recurrence after mastectomy than after breast conservation, it remains controversial whether different risk profiles at the time of primary diagnosis may account for this difference. Method: Matched pair analysis of 134 patients with newly diagnosed locoregional recurrence of breast cancer without evidence of systemic disease. Matching criteria included the primary surgical treatment, tumor size, nodal status, and age. The significance of various prognostic parameters at the time of primary diagnosis and at the time of recurrence were evaluated, by univariate and multivariate analyses, with respect to survival after recurrence. The median follow-up was 8.4 years. Results: Risk factors at the time of presentation, such as tumor size and lymph node status, were comparable between both groups. Local recurrence occurred on an average 9 months earlier in patients after mastectomy (P=0.08). Univariate analysis showed that lymph node status (P=0.0001) and disease-free interval from primary treatment to local recurrence (P=0.0002) were the most significant single prognostic factors for subsequent survival after local recurrence. The primary surgical treatment modality was shown to be of marginal statistical influence (only P=0.05). Conclusion: Local recurrence after mastectomy seems to be associated with worse survival than after breast-conserving therapy. Early onset of chest-wall recurrence, moreover, represents the highest independent risk for cancer-associated death.

Patients with carcinoma of the cervix and histologically proven blood vessel invasion have a poor prognosis. At the I. Frauenklinik der Universität München, 34 women were enrolled for a prospective study and were alternatively treated with or without adjuvant chemotherapy (carboplatin and 5-fluorouracil). Of the 28 patients included in the follow-up (14 with/14 without chemotherapy), 12 patients died (5 with/7 without chemotherapy). The disease-free interval was 18.6 months in the group treated with chemotherapy compared to 29.3 months in the group without chemotherapy. There is no statistically significant difference in the survival of patients with blood vessel invasion in relationship to adjuvant chemotherapy following radical hysterectomy.

The practicability and efficiency of a standardized, preoperative isovolemic hemodilution was investigated during major gynecological operations (Wertheim's operation, etc.).Prospective clinical trial with a historical control group.Operating room of a gynecological university hospital.Under general anesthesia hemodilution to a hemoglobin concentration of 9 g/dl was performed in 48 patients (mean age: 53 years). Shed blood volume amounted to 900 +/- 210 ml. Transfusion of autologous or homologous blood was provided when Hb concentration decreased beyond 7 g/dl intraoperatively.Compared to a control group of 57 patients without hemodilution the total number of PRBC units transfused was significantly reduced. Moreover, in 65% of all patients the transfusion of homologous blood could completely be avoided perioperatively (control group: 21% of patients). Adverse effects did not occur.The data reflect that acute isovolemic hemodilution before major gynecological operations represents a safe, easy to handle and effective procedure to avoid transfusion of homologous blood up to a total blood loss of 1,300-1,400 ml.

Between 1963 and April 1994, 3823 women were treated both at the Universitäts-Frauenklinik Berlin-Charlottenburg as well as at the I. Frauenklinik der Universität München, for a malignant condition of the breast gland. 161 of these (4.2%) exhibited an intraductal carcinoma stage pTis, whilst 99 (61.5%) were axillary lymphadenectomised. During the observation time-span of up to 24 years, 9 patients (5.6%) developed local recurrence. In neither patients of the group with axillary nor without axillary dissection could a regional recurrence be observed within this period. Also, a generalisation of this condition was not recorded in any patient. On the basis of our own results and those from the literature we postulate that, under the auspices of a risk adapted tumor surgery, axillary lymphadenectomy is no longer necessary under certain conditions in non-invasive breast carcinoma.

Between 1963 and 1993, 3720 women were treated both at the Universitäts-Frauenklinik Berlin-Charlottenburg and at the I. Frauenklinik der Universität München for a malignant condition of the breast. 187 of these (5%) exhibited stage p Tis, 102 (54.5%) of whom had an axillary lymphadenectomy. One patient had a micrometastasis (pN1a). During the observation period of up to 24 years, 11 patients (5.9%) developed local recurrence. In none of the patients a regional or generalised recurrence could be observed within this period. On the basis of our own results and those from the literature, we conclude that, under the aspect of a risk-adapted tumour surgery, axillary lymphadenectomy is no longer necessary under certain conditions: an invasive carcinoma should be excluded with high certainty in the tumourectomy specimen as well as in the remaining breast. Therefore, a histological work-up in serial sections must be provided to exclude multifocality (multicentricity) and a tumour diameter larger than 25 mm.

Primary hepatocellular carcinoma is a very rare disease, especially in association with a pregnancy. We report on a 22-year-old primigravida, who underwent Caesarean section in the 29th week of pregnancy in conjunction with tumour-reductive surgery for hepatocellular carcinoma. The further course of the disease was characterised by an early recurrence and lung metastases. Under palliative chemotherapy with 5-fluorouracil, the patient has been in a state of stable disease for several months. Typical risk factors for the hepatocellular carcinoma do not exist in the patient. Alternative explanations for the aetiology of the disease are discussed.

From January 1988 to December 1991, 343 women were operated for genital carcinoma at the 1st Gynaecological Department of the University Munich. Additionally to the corresponding cancer operations, pelvic or pelvic and paraaortic lymphadenectomy was performed. In a postoperative systematic and prospective study with ultrasound, we detected a high incidence of 48% of postoperative lymphocysts. Only a few were symptomatic and even less required therapy. In this study we were especially interested in the influence of closure of the pelvic peritoneum on the incidence of lymphocysts. Thus, we inaugurated a prospective study in 1991 with 49 patients with an open peritoneum and compared these results to 294 women who had standard closure of the peritoneum. There was a significantly higher rate of lymphocysts in patients with peritoneal closure (45.2%) in comparison to 20.4% lymphocysts in patients without peritoneal closure. In the study group (open peritoneum) 6.1% of the patients with lymphocysts showed symptoms, only 4.1% needed therapy. In the control group (closed peritoneum), 14.6% of the patients with lymphocysts were symptomatic and 8.2% needed therapy. These differences are not statistically significant. Other complications such as haemorrhage, fever or ileus were comparable in both groups. Our results do not supply sufficient proof, that leaving the peritoneum open significantly reduces symptomatic lymphocysts.

Congenital heart diseases are starting to benefit from the major advances provided by the advent of molecular biology methods. It is now possible to identify genes which are responsible for congenital heart diseases. The gene responsible for supravalvular aortic stenosis--an autosomal dominant trait--was cloned last year. It is the elastin gene. DiGeorge and Shprintzen syndromes, conotruncal anomaly face and some cardiac malformations have a common cause: a deletion of the 22q11 region resulting in a monosomy. Although the region of deletion is large, it is possible that monosomy of only one gene results in these conditions. Studies are underway to evaluate the impact of this new genetic factor on the incidence of congenital heart malformations. Studies on familial bundle branch block, and lateralization defect with midline anomalies are soon going to show a chromosomal region with the gene defect. Discovering the genes and their protein products which are implied in the cardiac morphogenesis will definitively change our understanding of these cardiac malformations.

In der klinischen Abklarung suspekter Zervixveranderungen stellt die Portioabschabung mit anschlisender Zervixcurettage (PA/CC) eine Form der diagnostischen Biopsie dar. Diese Methode zeichnet sich durch ihre hohe diagnostische Zuverlassigkeit, Komplikationsarmut und einfache operationstechnik aus. Durch die PA/CC konnen vielfach unnotige Konisationen und deren Folgen vermieden werden. Daher fuhren wir zur Abklarung suspekter zytologischer Abstriche der Zervix wahrend der Schwangerschaft zunachst eine PA/CC durch.

Behandlungsmethoden bei bosartigen Neubildungen der weiblichen Brustdruse werden nicht zuletzt danach beuerteilt, ob mit ihrer Hilfe die Tumorerkrankung beherrscht werden kann. Operationen wie auch Bestrahlung dienen der lokoregionaren Sanierung. Am eigenen Patientengut sind wir der Frage der Haufigkeit des lokalen Wiederauftretens der Erkrankung nach Ablatio mammae sowie der weiteren Prognose der Patientinnen nach einem derartigen Ergenis nachgegangen (3).

Die brusterhaltende Therapie stellt heute eine allgemein anerkannte Behandlungsmethode des Mammakarzinoms dar. Wir berichten aufgrund unserer fast 30-jahrigen (1963–1992) Erfahrungen uber Haufigkeit der Nebenwirkungen und Komplikationen nach chirurgischer und radiologischer Therapie.

An astoundingly high frequency of micrometastatic cells have been found in bone marrow aspirates of patients with colon carcinomas (G. Schlimok et al., J. Clin. Oncol., 8:831-837, 1990), although these tumors very rarely metastasize to the skeleton. This observation has raised questions about the malignant potential of such cells. In a first attempt to characterize this potential, we have assessed the expression of major histocompatibility complex (MHC) class I antigens on bone marrow micrometastases, inasmuch as down-regulation of these molecules is a potential mechanism to escape from MHC class I-restricted lysis by cytotoxic T-cells. The two groups of cancer patients compared were those with tumors known to rarely (stomach and colon cancer) or frequently (breast cancer) manifest skeleton metastases. Bone marrow aspirates taken from these patients were probed for individual disseminated tumor cells using the immunoalkaline phosphatase technique with monoclonal antibody CK2 to the epithelial differentiation antigen cytokeratin 18 (CK-18), as described previously (G. Schlimok et al., Proc. Natl. Acad. Sci. USA, 84:8672-8676, 1987). Specimens containing CK18-positive cells were colabeled with monoclonal antibody W6/32 directed to a framework (or nonpolymorphic) antigenic determinant of MHC class I heavy chains associated with beta 2-microglobulin. W6/32-positive CK-18-positive cells could be detected in 25 of 54 patients (46.3%) with significantly higher incidences in 26 breast cancer patients (61.9%) as compared to 28 patients with carcinomas of the stomach and colon (27.3 and 29.4%). Independent from the origin of the primary carcinoma, the incidence of W6/32-negative CK18-positive cells was positively correlated to both the differentiation grade of the primary tumor (P less than 0.05) and appeared to be linked to the occurrence of regional lymph node metastases (statistically not significant) determined by conventional histological examination. The present results demonstrate for the first time that down-regulation of MHC expression on individual micrometastatic cells correlates to the differential pattern of metastasis obtained by comparing breast and gastrointestinal carcinomas. This finding together with the suggestive link to clinical risk factors supports the significance of reduced MHC class I expression for the survival of residual metastatic cells which is a major determinant of prognosis for patients with solid tumors.

In den letzten Jahren werden bei der Operation gynakologischer Malignome uber die Exstirpation des Primartumors und der regionaren Lymphknoten hinaus auch die paraaortalen Noduli exstirpiert. Seit 1984 entfernen wir bei der malignen Geschwulst der Zervix zusatzlich die paraaortalen und bei der des Endometriums sowie des Ovars die pelvinen und paraaortalen Lymphknoten. Nach sorgfaltiger Blutstillung legen wir vor Verschlus des Peritoneums in den retroperitonealen Wundraum Redondrainagen mit mildem Sog.

Parental permission for cardiac catheterization assumes detailed information about the character and frequency of all potential and inevitable threatening complications despite of maximal care. However, data on this subject were derived mainly from older and/or retrospective studies. In order to evaluate the actual risk we performed a prospective study lasting 11 months. All complications occurring during the 24 h following this invasive procedure were recorded. During 462 consecutive cardiac catheterizations in 421 patients (including 24 balloon-atrio-septostomies and five myocardial biopsies) there were complications requiring treatment in 18.2% of all examinations. There was no lethal complication. The following complications were documented: arrhythmia 6.5%, acidosis 6.1%, problems due to catheterizing an arterial or venous vessel 3.9% and 0.4% respectively; acute blood loss 1.5%, and problems concerning the probe in general 1.1%. In a frequency of less than 1% we encountered hypoxic spells, myocardial ischemia, hypoventilation/respiratory failure, febrile reaction, and allergic reactions due to contrast media. Contrary to data of the literature we could show a significant reduction of the risks involved in this examination. The following factors have contributed to this improvement: 1) a more careful patient selection for this invasive procedure; 2) a more experienced examiner; 3) better monitoring during the procedure; 4) a more detailed diagnostic work-up prior to the examination; and 5) better premedication of the patient.

A digoxin-like immunoreactivity (DLIS) was measured by two routinely used clinical digoxin-immunoassays (radio- and enzymeimmunoassay) in cord blood of 255 newborns, in sera of their mothers at birth and in sera of 211 newborns during the first two postpartal weeks. The highest DLIS levels were found in serum of neonates at the first day of life (median: 0.23 ng/ml, 25% and 75% percentile: 0.19 and 0.28 ng/ml) and in cord blood (median: 0.21 ng/ml, 25% and 75% percentile: 0.19 and 0.24 ng/ml); maternal serum was shown to have three times less DLIS (median: 0.08 ng/ml, 25% and 75% percentile: 0.05 and 0.10 ng/ml). There was no significant correlation between DLIS concentrations in serum of newborns, cord blood or pregnants. The DLIS serum levels of preterms with birthweight less than 2500 g and gestational age less than 37 weeks were significantly lower than those of normal neonates at term (p less than 0.01); concomitantly the lowest DLIS levels were found in maternal serum of preterms (p less than 0.01). These observations strongly suggest rather a DLIS origin in the newborn than in the mother. During the first two postpartal weeks the DLIS concentration of a vast majority of the 211 newborns (91%) decreased continuously to one half of the starting value. Within the second postpartal week preterms were found to have a significantly delayed decrease in the DLIS serum levels (p less than 0.01). Small for date newborns showed no difference in their postpartal DLIS time course compared to normal neonates.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-six women, most of them with advanced endometriosis (Stage III according to Acosta), were treated for six months with the LH-RH agonist Buserelin. After initially increased liberation both of the gonadotropins as well as of the sexual steroids there was consecutive inhibition of gonadal function, especially after inhibition of FSH secretion. Within two to four weeks estradiol production was completely and lastingly suppressed in 21 of the 26 women. In three women it lasted for three months and in two women estradiol again rose up to three times during the period of observation. Correspondingly, 22 of the women suffered from hot flushes as early as within the first two months. Twenty of the 26 women became completely free of symptoms within four to six weeks, and a clear regression of the pain was recorded in another four. In two women the complaints persisted without change. Withdrawal bleeding of short duration occurred simultaneously with the intermittent increases in estradiol levels; however, this bleeding usually caused little or no pain. Eleven of the 19 endometrium biopsies performed during therapy revealed a dormant endometrium, and only in one case was proliferated endomedium found, in the third month of treatment, in a stage of transition to hyperplasia. The remaining seven biopsies were insufficient for assessment. In seven women with advanced endometriosis, laparotomies were performed after drug treatment. Histologic study of the endometriosis tissue thus obtained revealed, except in the two nonresponders, cicatrized tissue with atrophic glands and severely reduced stroma.(ABSTRACT TRUNCATED AT 250 WORDS)

Estradiol estrone and progesterone levels in serum and tissue were determined radioimmunologically from 160 endometrium and serum samples taken at various phases of the menstrual cycle in female patients who had undergone either curettage or hysterectomy for medical reasons. In addition the cytoplasmatic estradiol and progesterone receptor concentrations and the (17beta-HSD) 17-beta-hydroxysteroid dehydrogenase activities in the endometrium were measured. In 132 cases it was possible to correlate the endometrial histological findings and serum hormone levels with a particular phase of the cycle. The serum concentrations of sexual steroids displayed the usual biphasal pattern for estradiol and estrone with the postovulatory increase in progesterone. The tissue levels of these hormones followed a course partly paralled to and partly opposed to the serum levels. The progesterone profile in tissues essentially matches that in the serum except that the endometrium concentrations showed a marked prevulatory increase with no appreciable postovulatory rise. The midcycle estradiol peak was also observed in the endometrium. After ovulation the estradiol concentration in the tissue declined significantly. The changes in estrone levels in the secretory endometrium were at variance with those in the serum increasing sharply after ovulation. The cytoplasmic estradiol receptor concentration exhibited a maximum in the middle of the proliferative phase and declined steadily over the rest of the cycle. The number of progesterone-binding receptors is only enhanced at midcycle. The concentration changes in the progesterone receptors could be clearly correlated with the estradiol peak in serum and tissue at midcycle. A 10-fold increase in 17beta-HSD activity is observed after ovulation affecting changes in the tissue/serum estradiol and estrone ratios. The estradiol shifts ratio in favor of the serum during postovulatory phase whereas the estrone ratio is displaced in favor of the tissue. A regulatory model for the endometrial cells during the menstrual cycle is suggested on the basis of the results obtained. (Authors modified)

In order to find out whether digoxin therapy of nursing mothers might produce discomfort in suckling infants we have investigated the kinetics of the transfer of digoxin from plasma to milk in 11 nursing mothers. After intravenous or oral application of a single dose of 0.5 mg or 0.75 mg digoxin simultaneous serum, fore- and hindmilk samples were taken. Obviously, a rapid equilibrium occurred between the serum and the milk compartments and there was no difference between fore- and hindmilk. All three digoxin concentration profiles ran parallel with a milk to serum ratio of 0.6 to 0.7. The curves could best be fitted by the sum of two exponential functions. For predicting the digoxin intake into the suckling infant, simulations were carried out on the basis of two coupled compartment models. When the kinetic milk data as well as the kinetic data obtained in infants were fitted by this model it could be shown that even in the case of long half-lives only about 3% of the therapeutic drug levels were reached in the baby. Thus, one can conclude that digoxin accumulation to toxic concentrations should not occur in infants of women treated with appropriate doses of digoxin.

Giant cell reactions in the short tubular bones comprise mainly enchondromas, aneurysmal bone cysts and giant cell tumours. In both cases a history of trauma can be related. We therefore agree with Aegerter and Lorenzo that an intra-osseous haematoma due to minor trauma is likely to be of pathogenic significance.

The results of 552 amniocenteses during the second trimester of pregnancy are reported. The amniocentesis were carried out under direct ultra-sonographic control. Six abnormal karyotypes were found and the pregnancies were terminated. Three spontaneous abortions due to intra-uterine infection following amniocentesis occurred. There were no maternal complications and no fetal injuries. 430 amniotic fluids were tested bacteriologically. Two samples showed E-coli and two samples grew staph epidermidis. The IGM values of 148 newborns with previous amniocentesis showed the same values as the IGM in newborns without amniocentesis during the pregnancy. Fetal monitoring prior and following the amniocentesis showed a temporary increase in uterine motility in 25% of the cases. Our observations and the review of the literature convinced us that complications of amniocentesis in the second trimester are rare. However, when complications occur the fetus and the pregnant woman are a serious risk. The fetal wastage caused by second trimester amniocentesis is approximately 0.5 to 1%. Therefore the patients must be informed about the risks very carefully prior to a second trimester amniocentesis.