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Background: In young patients with native aortic coarctation (CoA), the management of choice is surgery. However, in re-coarctation (re-CoA) surgery is associated with increased morbidity and even mortality. Some children with native CoA present relative contraindications for surgery., Methods: From 2006 to 2017, thirty-four patients (male n = 20; 59%) from two centres with re-CoA (31) and native CoA (3) were managed by stent implantation with premounted balloon expandable stents. Inclusion criteria were age < 3 years and >1 month, weight < 16 kg. Median age was 6,5 months (min. 1; max. 34 months), median weight 6,2 kg (min. 3,7; max. 16 kg). Thirteen patients (38%) had Re-CoA and hypoplastic left heart syndrome (HLHS). In three patients (9%) the native CoA was stented due to contraindications for surgical treatment., Results: All procedures were successful. The median peak invasive systolic pressure gradient declined from 31 mm Hg (max. 118; min. 4) to 0 mm Hg (max. 32; min.-7) (p < 0.001). The median minimal diameter of the narrowed segment of aorta increased from 3 mm (max. 6,9; min. 1,0) to 7 mm (max. 11,5; min. 3,5) (p < 0.001). There were no serious complications. The median follow-up time was 12,5 months (max. 88; min. 0 month). During this time ten patients (29%) required re-dilatation and two of them re-stenting., Conclusion: Percutaneous stent implantation for Re-CoA and in selected patients for native CoA can be performed successfully in very young patients with a good immediate hemodynamical result. However, repeated stent angioplasties and further on interventional 'opening' of the stent is necessary to augment the aorta to adult size., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to develop a method for retrieval of the new meshed nitinol atrial septal defect occluders - Ceraflex and Occlutech., Background: The newly developed atrial septal defect occluders have potential benefits considering implantation, but concerns regarding their removal in case of embolisation have been raised., Methods: Over 21 years, 1449 patients underwent interventional atrial septal defect occlusion in our institution. We reviewed the cases of embolisation of the device, developed a strategy for device removal, and tested it on the benchside and in animal tests., Results: In 11 patients (0.8%), the intended atrial septal defect occlusion was complicated by an embolisation of the device. In contrast to the Amplatzer septal occluders, retrieval of Occlutech devices larger than 16 mm with snare techniques was impossible. In benchside tests, this was confirmed and a new method for removal of large meshed devices was developed. This involved the commercially available Maslanka® biopsy forceps. The feasibility of this technique in vivo was tested in a pig model. During animal tests, using the Maslanka biopsy forceps it was possible to interventionally retrieve embolised Ceraflex and Occlutech devices of different sizes - 10, 16, 30, and 40 mm - into a 12-F sheath., Conclusion: It was impossible to retrieve Occlutech and Ceraflex devices larger than 16 mm into a large sheath in vivo and during benchside tests. However, this was feasible on the bench and in vivo using the Maslanka biopsy forceps even with the largest available devices.

This report describes a premature newborn with pulmonary atresia and an intact ventricular septum who presented with a significant fistula between the right ventricle and the left anterior descending coronary artery (LAD). The right ventricle was not decompressed to prevent myocardial damage. After 2 months, the fistula had closed spontaneously. The pulmonary valve was opened, and biventricular circulation was achieved.

Background: Aortic valvuloplasty (AoVP) is an established procedure regarded as a valid alternative for surgical management of congenital aortic valve stenosis. However, its long-term efficacy in preventing or postponing aortic valve surgery remains uncertain for the individual patient. Therefore, the aim of this study was to study the long-term results of AoVP in pediatric patients and its efficacy in preventing or postponing aortic valve surgery., Methods and Results: We reviewed up to 17.5 years of follow-up data of all 188 patients who received AoVP at the Deutsches Herzzentrum München. The patients were divided into those < 1 month of age (group < 1 month; n=68) and those > or = 1 month of age (group > or = 1 month; n=120) at the time of AoVP. After the first and second AoVP, moderate and severe aortic regurgitation developed in 29% and 14%, respectively, of the patients in group < 1 month and in 19% and 29%, respectively, of the patients in group > or = 1 month. Survival after 10 years free from aortic valve surgery was 59% (95% confidence interval, 45 to 73) in group < 1 month and 70% (95% confidence interval, 59 to 81) in group > or = 1 month., Conclusions: This study shows that the long-term results of AoVP of congenital aortic valve stenosis in pediatric patients and its efficacy in preventing or postponing aortic valve surgery are very good. About two thirds of the patients are free from aortic valve surgery 10 years after AoVP.

Early shunt stenosis may occur after a Norwood-Sano operation. We report our experience with three patients who were treated successfully by stent implantation into the Sano shunt. Hence, a surgical shunt revision could be avoided.

Aims: The current study was designed to assess midterm results of stent implantation into the aorta for native and recurrent coarctation (CoA) in children and young adults., Methods and Results: Forty-three patients (native CoA, 8; female, 12) were treated with stent implantation at a median age of 16.8 years (range 7.9-44.8 years). Only stents dilatable to an adult size aorta were implanted. All but two patients with functionally univentricular hearts had arterial hypertension. Exercise tests, 24-h blood pressure, clinical examination, echocardiography, and elective catheterization were used to assess follow-up. The narrowed segment was widened significantly from a median of 8 to 12.4 mm (P < 0.0005). The peak-to-peak gradient between the ascending and the descending aorta was lowered significantly from a median of 22 mmHg to 1 mmHg (P < 0.0005). No major complications occurred. The systolic blood pressure at the right arm was lowered significantly (P < 0.0005) from 144 mmHg before stent implantation to 128 mmHg at the last visit. At a median follow-up of 30 months (3-72 months), 68% of all patients were classified to be normotensive., Conclusion: Stent implantation for selected patients with recurrent and native CoA is safe and may effectively reduce the blood pressure gradient across the CoA site. We suggest using only stents dilatable to an adult size aorta. However, arterial hypertension persists in a significant number of the patients. Impaired elastic properties of the aorta may be the cause for this finding.

This study was designed to investigate the impact of postoperative coronary sinus drainage pressure on coronary flow reserve (CFR) assessed by Doppler guidewire in patients long term after Fontan operation. Twenty-nine patients (median age, 17.4 years female, 11) at a median of 10.6 years after Fontan operation were examined with intracoronary Doppler guidewire during cardiac catheterization. Fourteen patients had coronary sinus (CS) drainage to the systemic venous atrium and 15 patients had CS drainage to the pulmonary venous atrium after Fontan operation. Median CS drainage pressure was significantly higher in systemic venous CS drainage compared to pulmonary venous CS drainage (11 vs 5 mmHg, p < 0.0001). Median CFR values for the right and left coronary artery did not differ significantly with respect to CS drainage. There was a positive correlation between coronary flow reserve and pulmonary arteriolar resistance (p < 0.05) in multivariate regression analysis. The site of coronary drainage into the systemic atrium or the pulmonary venous atrium did not significantly affect CFR. Our data do not support a surgical strategy of elective redirection of coronary sinus blood to a low-pressure compartment but support an early staged approach. The positive correlation between CFR and pulmonary resistance demands further evaluation.

We report on successful stenting of a proximally stenosed Sano shunt in a newborn with hypoplastic left heart syndrome after a stage I Norwood operation.

Patients after arterial switch operation for transposition of the great arteries are at risk for coronary artery stenosis or obstruction due to intraoperative manipulation. This case describes an infant with impaired left ventricular function 8 months after arterial switch operation. A hemodynamically significant left coronary artery stenosis was excluded by determination of coronary flow reserve using an intravascular Doppler guidewire.

The rational choice of an inhalation device is a cornerstone in the effective management of asthma and COPD. In this publication, we describe the development of a new system, the Inhalation Manager, which, for the first time, offers the possibility to assess the entire inhalation maneuver of patients using original devices under everyday conditions. So far the Inhalation Manager allows the measurement of inspiratory maneuvers of patients through placebo inhalation devices of the most common breath-actuated CFC-free inhalers in the market for the three main glucocorticosteroids Budesonide [Turbohaler (TH), dry powder inhaler (DPI)], Beclomethasone dipropionate [Autohaler (AH), breath-actuated pressurized metered dose inhaler (pMDI)], and Fluticasone propionate [Diskus (DI), DPI] by means of a pneumotachometer. In addition, it allows allocation of the individual maneuver to the expected drug delivery values (mass output and particle size distribution) of these three devices. In a field trial, the inhalation technique of 628 (TH), 794 (AH), and 795 (DI) patients, respectively, was tested in 72 pulmonologist practices with the Inhalation Manager. For patients in the 18-59-year-old group, the Inhalation Manager detected the following percentages needing improvement: 1.5% for the Autohaler device, 16.7% for the Diskus, and 38.9% for the Turbohaler. In the 60-99-year-old group, percentages needing improvement were 1.5%, 31.5%, and 66.1% for the Autohaler, Diskus, and Turbohaler, respectively. Therefore, the Inhalation Manager could become an essential tool in asthma management by finding the most suitable inhaler for an individual patient and by training the optimal inhalation technique.

Three pediatric patients (8.5 years, 3 years, and 1 month) presented with congenital coronary arterial fistulas. In all cases the fistulas entered into the right side of the heart (main pulmonary artery, n = 1; right ventricle, n = 2). In the first patient, the fistula and an open ductus arteriosus were closed during the same intervention. The second patient presented with a single left coronary ostium and residual shunt from the coronary artery system to the right ventricle after surgery. The third child had pulmonary atresia with intact ventricular septum and a fistula from the left coronary artery to the right ventricle. The fistulas in all patients were managed with coil occlusion. Fistula occlusion was documented with angiocardiography.

Objective: To show the equivalence of the transpulmonary thermodilution method to the direct Fick principle in children., Design: Prospective single-centre study., Setting: A 16-bed paediatric cardiac ICU and a cardiac catheterisation laboratory at an university affiliated centre for paediatric cardiology and congenital heart disease., Patients: We consecutively investigated 18 patients (mean age 12.1 +/- 6.4 years) during cardiac catheterisation and after corrective cardiac operation., Methods and Results: 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, P < 0.0001. 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., Conclusion: 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).

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.

Objectives: We undertook this study to assess the immediate and long-term outcome of balloon angioplasty performed for recurrent or residual coarctation of the aorta, and to assess the changes in the vessel wall caused by this procedure., Methods: Clinical, echocardiographic, angiographic and hemodynamic data from 71 patients who underwent balloon angioplasty for recoarctation between January 1987 and January 1998 were analysed retrospectively., Results: Angioplasty was performed after a median of 82.6 months (range 1.4 mo-20.9 y, mean 88.5 mo) following surgery for coarctation. Mean systolic pressure gradients were reduced from 27 +/- 15 mmHg to 11 +/- 11 mmHg after angioplasty (p < 0.0001). The mean diameter at the site of recoarctation increased from 5.5 +/- 2.5 to 7.5 +/- 2.7 mm (p < 0.0001). Outpouchings of contrast agents, indicating the disruption of the inner layers of the vessel wall, were defined as extravasations. They were observed in one-quarter of the angiograms performed immediately after the intervention. Immediate success of angioplasty was achieved in 71%, and persisted in 69% of patients during long-term follow up. The main determinant for immediate success was the age at the time of the procedure (p < 0.05), while the main determinant for long-term success was the increase achieved in diameter. Extravasations did not progress to aneurysms, neither acutely nor during echocardiographic follow-up studies. For further follow-up, more sensitive imaging techniques will be necessary to delineate the morphology of the site of extravasation observed immediately after angioplasty.

Introduction: Recent studies have renewed an old controversy about the efficacy of adjuvant radiotherapy following mastectomy for breast cancer. Radiotherapy is usually recommended for advanced disease, but whether or not to use it in pT1-T2 pN0 situations is still being debated. This study was designed to clarify whether or not routine radiotherapy of the chest wall following mastectomy reduces the risk of local recurrence and if it influences the overall survival rate., Methods: Retrospective analysis of patients treated with mastectomy for pT1-T2 pN0 tumors and no systemic treatment. Patients treated with radiotherapy of the chest wall following mastectomy (Group A) are compared with those treated with mastectomy alone (Group B)., Results: A total of 918 patients underwent mastectomy. Patients who received adjuvant radiotherapy after mastectomy (n = 114) had a significantly lower risk for local recurrence. Ten years after the primary diagnosis, 98.1% of the patients with radiotherapy were disease free compared to 86.4% of the patients without radiotherapy. The average time interval from primary diagnosis until local recurrence was 8.9 years in Group A and 2.8 years in Group B. The Cox regression analysis including radiotherapy, tumor size and tumor grading found the highest risk for local recurrence for patients without radiotherapy (p < 0.0004). In terms of overall survival however, the Kaplan-Meier analysis showed no difference between the two groups (p = 0.8787) and the Cox regression analysis failed to show any impact on overall survival., Conclusion: With observation spanning over 35 years, this study shows that adjuvant radiotherapy of the chest wall following mastectomy reduces the risk for local recurrence in node-negative patients with pT1-T2 tumors but has no impact on the overall survival rate.

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.

Objective: The practicability and efficiency of a standardized, preoperative isovolemic hemodilution was investigated during major gynecological operations (Wertheim's operation, etc.)., Design: Prospective clinical trial with a historical control group., Setting: Operating room of a gynecological university hospital., Patients and Interventions: 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., Results: 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., Conclusions: 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 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.

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.

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.

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.

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.

The association of c-erbB-2 gene amplification product (p185) with histologic tumor type in 100 patients with primary breast cancer was determined. In 49 patients with infiltrating ductal carcinoma p185 detection was correlated with histologic findings (tumor grade, lymphnode status, receptor status). Strong positive staining for p185 protein was found in 10 patients (20%) with infiltrating ductal breast carcinoma and correlated with complete negative estrogen/progesterone receptor status and with histologic grade G3. There was neither an association with lymphnode involvement nor was there any to negative estrogen and progesterone receptor status alone. At present, we cannot say whether or not there is a correlation between the degree of c-erbB-2 gene amplification and prognosis. Follow-up studies are necessary to determine whether c-erbB-2 gene amplification allows definition of a specific subset of women who could benefit from adjuvant therapy.

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.

Chest-X-ray films of 61 children with isolated total anomalous pulmonary vein connection (TAPVC) were re-evaluated retrospectively. A small heart silhouette with normal pulmonary perfusion and signs of pulmonary oedema is typical of TAPVC with obstruction. There is no typical pattern in TAPVC without obstruction. The "snowman" or "figure of eight" does not develop within the first months of life.

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.

Human vaginal epithelium provides a good model to study hormonally regulated differentiation. Differentiation in this tissue can be characterized by the expression of the keratins 1 and 13 which represent the epidermal and nonkeratinizing pathway in stratified epithelia, respectively. In the present study immunohistochemistry was applied on sections of vaginal epithelium derived from women at various stages of the menstrual cycle or during pregnancy. Our results demonstrate that both pathways are realized simultaneously during sexual maturity and that the maximum for synthesis of keratins 1 and 13 is seen during the first half of the cycle. In contrast keratin 1 is not detectable at the end of pregnancy, thus reflecting a completely suppressed epidermal differentiation. As the levels of the female sex hormones, i.e. estrogens, is significantly increased in pregnant women over that in nonpregnant women, these results suggest a possible role of estrogens in downregulating the epidermal differentiation pathway.

Hemodynamic and hormonal effects of captopril were prospectively studied in 12 children (median age 5.8 years, range 4 weeks to 15 years) with dilated cardiomyopathy. A mean dose of 1.83 mg captopril/kg body weight was administered in three or four single doses depending on age. Left ventricular volume, ejection fraction (EF), cardiac index (CI), and systemic vascular resistance (SVR) were noninvasively determined by two-dimensional (2D) and Doppler echocardiography before and 2 days and 3 months after the onset of treatment. Blood pressure and heart rate were recorded as well. Additionally, on the day hemodynamic measurements were made, plasma renin activity (PRA), serum aldosterone, and plasma atrial natriuretic peptide (ANP) concentrations were determined. Plasma catecholamines were measured before and 2 days after captopril treatment. Concomitant medication was kept constant during the short-term phase of captopril treatment. During long-term therapy, diuretics were reduced according to the clinical status. Stroke volume (SVI) (-7%), end-systolic (ESVI) (-31%), and end-diastolic (EDVI) (-21%) volume indexes were significantly reduced (p less than 0.05) during short- and long-term therapy. The remaining hemodynamic parameters showed only minor, statistically not significant, changes. During short-term therapy, median serum aldosterone levels fell from 138-88.5 pg/ml (p less than 0.05), and plasma ANP decreased from 144-94 pg/ml (p less than 0.05). After 3 months these effects were less marked and statistically no longer significant. Changes in PRA and plasma catecholamines were not statistically significant at any time.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

In 55 high-risk neonates of different birth-weight and gestational age, transcutaneous pO2 (tcpO2) was continuously monitored during transports from the Obstetric Units to the Neonatal Intensive Care Units. We were able to demonstrate that the need for oxygen was overestimated in most of the children and thus FiO2 could be reduced in nearly all cases. In this way, FiO2 can be adapted to the real need of the children and hypoxemias can be avoided as far as possible frequency and duration of hyperoxemias can be reduced. Moreover, valuable knowledge about further management of mechanical ventilation may be obtained. Complications, as e.g. obstruction of endotracheal tube, are more rapidly recognized than by ECG-monitoring alone.

Pi phenotypes have been determined by isoelectrofocusing in a sample of 538 healthy individuals from Southern Germany. Further subdivision of the common PiM phenotype is described. A procedure for the delineation of six common subtypes is presented. It is assumed that the six subtypes are determined by three alleles which are provisionally called PiMa, PiMb, and PiMc. Their frequencies in this sample were 0.75, 0.06, and 0.15, respectively.

In an infant's acute theophylline intoxication following a medication error, plasma levels above 80 micrograms/ml were not associated with repetitive seizures, but also with heart rates above 200 bpm. The serum elimination kinetics were characterized by a first-order elimination process with a half-life of 15 h. Despite the exponential decay of plasma levels the heart rate remained at a high level during the first 20 h. This behavior is explained by a saturation phenomenon familiar in receptor and enzyme kinetics.

Infants require higher therapeutic doses (per unit body weight and surface area) and also tolerate higher doses of digoxin than adults. In contrast premature and even mature newborns are more susceptible to digoxin intoxications. Serum protein binding contributes to the apparent volume of distribution. Since the volume of distribution for digoxin shows an age-dependency, the present study was designed to determine the plasma protein binding of digoxin in premature and mature newborns as well as in infants and adults. Using the equilibrium dialysis method the fraction of digoxin bound to serum protein averages 30% in all groups studied. Thus protein binding could not account for the differences in dosage and susceptibility of digoxin in newborns and infants as compared to adults.

Computed tomographic findings in leiomyoma, leiomyosarcoma and benign leiomyoblastoma of the stomach are discussed. Gastroscopic biopsy was unsuccessful in every case, but CT was able to show the extragastric extension in all tumors. In one case, gastric leiomyoma and renal hypernephroma occurred simultaneously. Both tumors showed similar contrast medium enhancement, leading to a misdiagnosis.

Between 1963 and 1981, 1139 patients had surgery for unilateral breast cancer at the Charlottenburg Gynaecological Clinic of the Free University Berlin. A total of 948 patients had a simple mastectomy and 191 patients had an extended tumorectomy (or lumpectomy) with subsequent radiotherapy (40 Gy). Retrospective analysis of "matched cases" treated by tumorectomy or mastectomy showed the rate of local recurrence after tumorectomy to be nearly double that after simple mastectomy (8.7% after tumorectomy, 4.7% after mastectomy). Life expectancy with a local recurrence after conservative surgery, was however, better than that after simple mastectomy.

Hemodynamic effects of captopril were prospectively studied in 12 children suffering from dilative cardiomyopathy. Before the administration of the drug all patients were put on a stable medication of diuretics and/or glycosides. A median daily dose of 1.83 mg captopril/kg body weight was given in 3 or 4 single doses depending on age. Median body weight of the children was 18.6 kg (range 2.7-42.2) and the median age was 5.8 years (range 0.2-15). Left ventricular volume was determined in systole and diastole using 2-D echo, and the stroke volume als well as the ejection fraction were calculated. Cardiac index (CI) and systemic resistance (Rs) were measured by Doppler echo. Blood pressure and heart rate were recorded at each echo registration. ESVI (-32%), EDVI (-21%) and SVI (-7%) were significantly (p less than 0.05) reduced by short-term captopril treatment. This effect was maintained under long-term therapy. EF, CI, Rs, blood pressure and heart rate showed only minor changes under captopril. Adverse effects were recorded only in one child. They disappeared after dose reduction.

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.

Between 1963 and 1982, 1,139 patients underwent surgery for unilateral mammary malignoma at the Charlottenburg Gynaecological Clinic of the Free University Berlin. Primary therapy consisted of simple mastectomy in 948 cases and tumourectomy/quadrantectomy with subsequent radiotherapy (40 Gy) in 191 cases. We performed a retrospective analysis of "matched samples" of tumourectomy/quadrantectomy and mastectomy. The observation period of both groups spans a minimum of one year to a maximum of 20 years after primary operation. In pT1- and pT2-tumours the overall survival after tumourectomy/quadrantectomy at 5, 10 and 15 years was no worse than after total breast removal. The results of our long-term follow-up study lead us to conclude that tumourectomy/quadrantectomy and breast irradiation are suitable for primary treatment of mammary cancer.

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.

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.