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G Bastert

Publications and source records attributed to G Bastert.

At least 91 records · Page 5Linked to original sources
PubMed1997

Low frequency of BRCA1 germline mutations in 45 German breast/ovarian cancer families.

In this study we investigated 45 German breast/ovarian cancer families for germline mutations in the BRCA1 gene. We identified four germline mutations in three breast cancer families and in one breast-ovarian cancer family. among these were one frameshift mutation, one nonsense mutation, one novel splice site mutation, and one missense mutation. The missense mutation was also found in 2.8% of the general population, suggesting that it is not disease associated. The average age of disease onset in those families harbouring causative mutations was between 32.3 and 37.4 years, whereas the family harbouring the missense mutation had an average age of onset of 51.2 years. These findings show that BRCA1 is implicated in a small fraction of breast/ovarian cancer families suggesting the involvement of another susceptibility gene(s).

Adult↗
PubMed1997

Tumor-cell number and viability as quality and efficacy parameters of autologous virus-modified cancer vaccines in patients with breast or ovarian cancer.

PURPOSE: We investigated quality and efficacy criteria of an autologous, physically and immunologically purified, Newcastle disease virus (NDV)-modified, irradiated tumor-cell vaccine (ATV-NDV) by analyzing three independent cohorts (a through c) of patients vaccinated between 1991 and 1995. MATERIALS AND METHODS: Included were 63 patients with primary breast cancer (a), 27 with metastatic pretreated breast cancer (b), and 31 with metastatic pretreated ovarian cancer (c). In addition to vaccine, cohorts b and c received nonspecific immunotherapy as supportive treatment. After cryoconservation and purification, the vaccines varied in applied numbers of viable cells and dead cell contaminations. We retrospectively hypothesized that an immunogenic vaccine should contain at least 1.5 x 10(6) viable tumor cells and viability should be at least 33%. Each cohort was thus divided into two groups; one that received vaccine type A (A), fulfilling both criteria; and the other type B (B), missing one or both criteria. RESULTS: Conventional prognostic factors were wall balanced between A and B in cohorts a and c. In cohort a, there was a benefit in survival (P = .026) and disease-free survival (P = .089) for A. In addition, in cohort a, the relative risk of dying in the group that received A as compared with B was 0.2 (univariate Cox model). There were also survival trends in favor of A versus B (P = .18 and P = .09, respectively) in cohorts b and c, with relative risks of 0.5 and 0.42, respectively. In cohort b, the survival benefit could not be ascribed to vaccine quality alone, because of prognostic imbalance in favor of A. CONCLUSION: In cohort c, like in cohort a, the survival benefit for A may be ascribed to the ATV-NDV vaccine quality, since prognostic factors were not biased. This could imply clinical effectivity in breast and ovarian cancer with ATV-NDV high-quality vaccine. Furthermore, the data provide clinically relevant information for standardization and quality control of autologous tumor-cell vaccines. A randomized study is urgently needed.

Breast Neoplasms↗
PubMed1997

German family study on hereditary breast and/or ovarian cancer: germline mutation analysis of the BRCA1 gene.

Women harboring BRCA1 germline mutations carry an 85% lifetime risk of developing breast cancer and a 63% risk of ovarian cancer. In this first systematic study of familial breast and/or ovarian cancer in Germany we investigated 29 families for germline mutations in the BRCA1 gene. We identified mutations in three breast cancer families and in four breast-ovarian cancer families. The mutations include one missense mutation, one frameshift mutation, one splice mutation, and four nonsense mutations cosegregating with breast and/or ovarian susceptibility in five of ten (50%) families showing positive evidence of linkage to chromosome band 17q21 and in two of 19 (11%) families where linkage data was not available. Two apparently unrelated families carried the same nonsense mutation at codon 1835 and three families harbored a C to T transition at nucleotide 49 of the untranslated exon 4. Allelotyping of the markers D17S855, D17S1322, D17S1323, and D17S1327 located within or near BRCA1 revealed that all affected individuals in the two families harboring the mutation at codon 1835 shared at least one allele indicating a founder mutation. With respect to the overall mutation spectrum, no mutations were identified in exon 11 (0/7) in this set of German families. These findings differed significantly from those in British (17/32)(P = 0.012) and Southern Swedish (13/15) (P < 0.001) families. The lack of BRCA1 mutations in exon 11 which represents 61% of the entire coding sequence may provide additional insight into BRCA1 associated breast and ovarian tumor development.

BRCA1 Protein↗
PubMed1997

[Cardiotocographic changes after umbilical cord puncture and umbilical cord transfusion].

In connection with umbilical cord punctures and transfusions the degree of pathology still tolerable after these procedures as well as the influence on subsequent obstetric management has to be discussed. In a prospective study we evaluated 98 cordocenteses with (n = 44) and without (n = 54) transfusion (25-37 week of gestation). 30-160 ml of blood were transfused. In all cases the umbilical vein was punctured at the point of insertion into the placenta (46x posterior and 52x anterior wall placenta). A CTG was performed prior and after the punction and was evaluated according to the Fischer score. After the procedure, the course of pregnancy was normal in all puncture patients and in 52 of 54 patients who also underwent a transfusion. Because of a pathological CTG due to a severely hydroptic fetus, a caesarean section had to be performed in one woman seven hours after umbilical cord transfusion. In another patient an emergency section was necessary immediately after the umbilical cord transfusion, due to persistent fetal bradycardia. In the puncture group mean Fischer score values decreased from 9.1 to 7.5, in the transfusion. In another patient an emergency section was necessary immediately after the umbilical cord transfusion, due to persistent fetal bradycardia. In the puncture group mean Fischer score values decreased from 9.1 to 7.5, in the transfusion group from 8.6 to 7.4. The results were more unfavorable when amplitude and occurrence of accelerations were considered, especially in the transfusion group. In one fifth of the puncture cases and one fourth of the transfusion patients the criterium of baseline crossings improved after the procedure. In summary, a pathological CTG is to be expected after umbilical cord punctures and transfusions, with however, only the necessity of surveillance. Only in cases of persistent fetal bradycardia an active obstetric management is indicated.

Blood Transfusion, Intrauterine↗
PubMed1997

[Telecommunication--a medium for improving prenatal diagnosis and gynecologic ultrasound diagnosis? Initial experiences].

To establish the requirements for real-time transfer of an ultrasound examination via telecommunication network the following tests were performed: The ultrasound data were transferred from the video out of an ultrasound system to a basis terminal of the German Telekom. Simultaneously, an external video camera filmed the positioning and movements of the ultrasound transducer, and the verbal comments were recorded. These informations were transmitted to Karlsruhe and London, where they were rerouted to the examination room in Heidelberg. Here the informations were received on a Telecom reception unit/terminal and compared directly with the initial signal. The quality was sufficient if the moving ultrasound images and the camera image of the transducer as well as the oral comment were transmitted over 2 parallel ISDN lines. The delay to a real-time transmission of the examination process is only in the range of milliseconds. If only one ISDN line is used, the image quality is unsatisfactory, three parallel lines do not bring significant improvement of image quality. Telemedicine seems a new possibility to bring the knowledge of specialized centers to the practicing gynaecologists thus avoiding unnecessary referrals. Still unanswered, however, are the problem of liability, data protection and costs.

Adult↗
PubMed1997

[Paraneoplastic retinopathy in 2 patients with breast carcinoma].

Paraneoplastic retinopathies are rare paraneoplastic phenomena resulting in retinal degeneration. They occur in association with different tumor types, yet most frequently encountered in small cell carcinoma of the lung. Clinical symptoms may be present before the diagnosis of the underlying malignancy. They are characterized clinically by progressive visual loss with ring scotomas, photopsia and night-blindness. An autoimmune disorder is suggested. In the sera of patients antiretinal antibodies may be detected that are sometimes reactive with the 23 kD retinal antigen recoverin, a photoreceptorprotein. We report on two patients with breast cancer who developed paraneoplastic retinopathy during the course of disease. Immunologic tests showed antiretinal antibodies that were not reactive with the 23 kD retinal antigen recoverin.

Autoantibodies↗
PubMed1997

[Doppler score for evaluating perinatal risk].

Doppler sonography now has a definite place in the surveillance of risk pregnancies. Uniform clinical management is sometimes difficult especially in borderline cases. The following study demonstrates the possibility of standardizing and systematizing Doppler results using a score. In a collective of 253 pregnant women we performed Doppler examinations in the fetal aorta, umbilical artery, middle cerebral artery, internal carotid artery. The results were divided into 4 groups and correlated to the fetal outcome. There was a highly significant worsening in prognosis regarding duration of pregnancy, birth weight and rate of cesarean sections with increasing Doppler score. In the event of pathological and highly pathological scores, the average duration of pregnancy was 23 and 48 days shorter than normal. As a result, there was a highly significant reduction in the average birth weight compared to fetuses with normal Doppler scores: by 1060.7 g in the case of a pathological score and by 1633.5 g in the case of a highly pathological score. There was a highly significant correlation concerning the rate of cesarean sections and the indication "fetal distress". The average interval between diagnosis and birth was 6.3 days in the case of pathological Doppler findings and 2.3 days in the case of highly pathological findings. The difference was highly significant. In the case of highly pathological scores all fetuses were delivered after at least 5 days, compared with after at least more than 10 days in those with only pathological Doppler findings. This reflects the fact that there is none room for discretion in case of a highly pathological flow. In summary the Doppler score allows better estimation of fetal risk and can improve fetal prognosis by special monitoring and earlier obstetric intervention.

Birth Weight↗
PubMed1997

[Increased AFP in maternal serum as an indication for invasive diagnosis].

The association of increased maternal serum alpha-fetoprotein levels (MS-AFP) with certain morphologic anomalies of the fetus is fully established. These anomalies are abdominal wall defects (e.g. omphalocele, gastroschisis, complete eventration), neural tube defects (anencephalus, spina bifida, encepalocele) and other malformations (e.g. coccygeal teratoma). The present study compares MS-AFP levels with amniotic fluid alpha-fetoprotein (AF-AFP) and acetylcholinesterase activity, the results of ultrasound, genetic and morphologic examination. Between April 1992 and November 1995 60 patients were referred to our clinic for further diagnosis after detection of elevated MS-AFP. After an ultrasound examination was carried out amniocentesis (AC) was performed in 54 cases, AC + placentesis (PC) in 3 patients and PC only in 3 cases with anhydramnion. Mean maternal age was 29 years (range 20-37 years). Punction was performed at a median of 19 + 1 weeks of gestation (15 + 2-23 + 2 weeks of gestation). MS-AFP, AF-AFP and acetylcholinesterase activity was measured. MS-AFP and AF-AFP were given as multiples of the median (MoM). Values < or = 1-2.0 MoM were considered normal. Elevated levels were defined to be greater than 2 MoM. In all cases the chromosomal finding was normal or norm variant. Sonographical anomalies were detected in 7 fetuses (3 cases with spina bifida, 1 case with omphalocele and 3 cases with abdominal wall defects in connection with other malformations). All sonographic diagnoses were confirmed post partum. The MS-AFP varied between 0.9-6.0 MoM. In 7 cases MS-AFP previously (referring center) evaluated as increased was found to be within normal range in our department. This cases included normal values were found in 30 cases and 25 findings were pathological. 2 out of 7 structurally abnormal fetuses had normal values, 5 of them had elevated MS-AFP. In the group of normal fetuses the highest MS-AFP we found was 6.6 MoM. In the AC-group the AF-AFP ranged between 0.7-8.7 MoM, it was within normal range in 50 and pathological in 8 cases. In the group of fetuses without structural anomalies the highest AF-AFP was 7.5 MoM. In the group of fetuses with structural anomalies the AF-AFP values were 1x normal and 3x pathological (> 3.5 MoM). Acetylcholinesterase activity in the amniotic fluid was negative in 51 cases, positive in 4 cases and faint positive in 2 cases. In all fetuses with structural anomalies in which an AC could be performed, acetylcholinesterase activity was positive. On the other hand we found only 1 of the structurally normal fetuses with positive acetylcholinesterase activity. Elevated MS-AFP and AF-AFP may be an indicator for morphological anomalies. Yet there were many positive results without any sonographical findings. The determination of a positive acetylcholinesterase activity in the amniotic fluid is more specific. All malformations have been detected by ultrasound examination before the results of the AF-AFP were available.

Abdominal Muscles↗
PubMed1996

Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status.

BACKGROUND: Approximately 30% of the patients with primary breast cancer who have no axillary lymph node involvement (i.e., lymph node negative) at the time of surgery will relapse within 10 years; 10%-20% of the patients with distant metastases will be lymph node negative at surgery. Axillary lymph node dissection, as a surgical procedure, is associated with frequent complications. A possible alternative to nodal dissection in terms of prognosis may be the immunocytochemical detection of tumor cells in bone marrow. PURPOSE: In a prospective study, the value of tumor cell detection (TCD) in bone marrow was compared with axillary lymph node dissection in the prognosis of primary breast cancer after surgery. METHODS: Data from 727 patients with primary, operable breast cancer were included in the analysis. All patients had surgery, including axillary lymph node dissection, from May 1985 through July 1994 at the Women's Hospital of the University of Heidelberg (Federal Republic of Germany). Bone marrow aspiration at two sites on each anterior iliac crest was performed immediately after surgery while the patients were under general anesthesia. Most patients received some type of systemic adjuvant therapy. The monoclonal antibody 2E11, directed against the polymorphic epithelial mucin TAG12, was used to detect tumor cells in bone marrow samples. The association of TCD with recognized prognostic indicators was evaluated by means of chi-squared tests. Survival without the development of distant metastases (i.e., distant disease-free survival) and overall survival were estimated by use of the Kaplan-Meier method; the logrank test was used to compare survival curves. A multivariate Cox regression analysis with stratification according to adjuvant treatment type was used to assess the independent prognostic value of TCD in bone marrow in relation to other variables. Reported P values are two-sided. RESULTS: Tumor cells were detected in the bone marrow of 203 (55%) of 367 lymph node-positive patients and in 112 (31%) of 360 lymph node-negative patients. TCD was associated with larger tumors (P < .001), lymph node involvement (P = .001), and higher tumor grade (i.e., more undifferentiated) (P = .002). After a median follow-up of 36 months, patients with tumor cells in their bone marrow experienced reduced distant disease-free survival and overall survival (both P values < .001). TCD was an independent prognostic indicator for both distant disease-free survival and overall survival that was superior to axillary lymph node status, tumor stage, and tumor grade. Among patients with tumors less than 2 cm in diameter, TCD was the most powerful predictor of outcome. CONCLUSIONS AND IMPLICATIONS: TCD in the bone marrow of patients with breast cancer is a valuable prognostic tool associated with negligible morbidity. Prospective randomized studies should be performed to determine whether TCD might replace axillary lymph node dissection in a defined subgroup of patients with small tumors.

Adult↗
PubMed1996

Allelic imbalance on chromosome 13q: evidence for the involvement of BRCA2 and RB1 in sporadic breast cancer.

Recently, the breast cancer susceptibility gene BRCA2 has been identified in chromosome 13q, a region that also contains the retinoblastoma gene RB1. To elucidate a possible role of BRCA2 and RB1 in sporadic breast tumorigenesis, allelic imbalance (AI) at 13q loci was examined in 78 primary sporadic breast tumors. AI was found in 52-63% of tumors. Nine tumors showed AI only in the BRCA2 region but not at RB1. Six tumors showed AI at RB1 but not in the BRCA2 region. AI in the BRCA2 region correlated significantly with aneuploidy (P = 0.032) and AI at RB1 with small tumor size (P = 0.025). Our data suggest that BRCA2 and RB1 may be both distinct target loci for AI on chromosome 13 in sporadic breast cancer.

Alleles↗
PubMed1996

[Metastasis to the sternum or parasternal recurrence of breast carcinoma? Value of sonography].

Because of the high tendency of breast cancer to develop metastatic deposits in the skeleton, space-occupying processes in the sternal region are mostly attributed to osseous metastases and not to parasternal lymph node involvement, even in case of solitary lesions, primary tumor localizations in the inner quadrants, positive axillary nodes and negative X-ray or bone scan findings. The sonographic examinations of 115 patients with breast cancer and clinical and/or scintigraphic suspicion of sternal metastasis, however, revealed the typical bone metastases of the sternum with a small soft tissue tumors in only 27.8 %, whereas 59.1 % of the cases showed parasternal recurrences; 5.2 % had both. Non-tumorous changes were seen in 6.1 %, equivocal results in 1.7 %. Solitary osseous metastasis of the sternum was rare; multiple skeletal lesions were found in the majority of this group in contrast to the patients in the parasternal relapse group, which moreover showed strong overrepresentation of the primary tumor localization in the inner quadrants. X-rays of the chest or the sternum were often false-negative and not reliable, the bone scans positive only in cases of secondary sternal invasion or skeletal metastases. Concerning reliability and cost, sonography was the imaging method of first choice for diagnosis, therapy planning and follow-up for space-occupying processes in the sternal region, with CT or MRI as adjuncts in cases of extended tumors invading the mediastinum.

Adult↗
PubMed1996

[Paraneoplastic cerebellar degeneration: case report of a patient with breast carcinoma].

Case Report on a Breast Cancer Patient: A description of medical history, diagnosis and therapy of a patient with breast cancer is presented. The patient showed primary symptoms of vertigo and truncal and gait ataxia. The cause of this cerebellar disorder was a paraneoplastic cerebellar degeneration (PCD) characterized by anti-Purkinje cell antibodies (anti-Yo) directed against specific epitops shared by Purkinje and tumour cells. The presence of these antibodies in some patients suggests an autoimmune mechanism, although their role in pathogenesis has not been established. Usually malignancies of the breast and the ovaries are associated with anti-Yo positive PCD. The intensive search for the underlying neoplasma led to the identification of a malignant tumour of the right breast. Tumour excision of subsequent immunosuppressive treatment resulted in a progression of PCD. Antibody titers remained nearly unchanged during the course of the disease.

Autoantibodies↗
PubMed1996

[Addition of ethanol to the distension medium in surgical hysteroscopy as screening to prevent "fluid overload". A prospective randomized comparative study of ablative versus non-ablative surgical hysteroscopy and different ethanol concentration].

For answering the question at which hysteroscopical procedures an intraoperative screening method is necessary to avoid a fluid overload and whether a beginning fluid absorption can be diagnosed early by adding ethanol to the distension medium, a prospectively randomised comparative study of ablative versus non-ablative operative hysteroscopy with differing ethanol concentrations was performed (n = 120). Purisole (a mannit/sorbit solution) was used a distension medium. The measuring parameters (breath alcohol, amount of absorbed fluid, haematocrit and haemoglobin values, central venous pressure, heart frequency) were intraoperatively determined at 5-minute intervals. The results of the study show that with those hysteroscopical procedures during which the endometrium is not or only minimally injured (e.g. syneciolysis, hysteroscopic proximal tubal catheterisation). Intraoperative screening is not necessary due to the low absorbing amounts. With hysteroscopical procedures such as resection of myoma, endometrium ablation and septum resection, however, an addition of ethanol of 2% to the distension medium has proved useful, because with this method absorption amounts of 400 ml and more can be detected by positive values of breath alcohol. As the result of a further absorption of fluid, delayed in time compared to the first positive value of breath alcohol, there is an increase in central venous pressure and hyponatraemia. Intraoperative ethanol monitoring is a non-invasive procedure which can be performed during ablative-operative hysteroscopies and has no negative influence on the course of the intervention and the general condition of the patients.

Adult↗
PubMed1996

[Prognostic significance of plasminogen activator inhibitor-1 (PAI-1) in primary breast carcinoma].

The plasminogen activator system plays a key role in the proteolysis of malignant tumours. In 155 patients with primary breast cancer levels from PAI-1 and uPA were measured in cytosol with monoclonal antibodies and by an enzyme-linked immunosorbent assay. 35 tumour tissue samples form benign breast were also examined. Malignant tumours contain higher levels of PAI-1 (8.6 ng/mg) than benign tumours (1.28 ng/mg) (p < 0.01). Also the median level of uPA was significantly higher (p < 0.01) in malignant tissue (2.38 ng/mg) in comparison to benign disease (0.54 ng/mg). No correlation was found between the proteases and the classical prognostic parameters like axillary lymph node involvement, tumour size and menopausal status. However, a significant correlation (p < 0.01) was found in tumours with lymphangiosis carcinomatosa, negative hormone receptors, grade III tumour cells and high S-phase fractions (> 5%). After a median follow-up of 46 months we found that high levels of PAI-1 correlated with short DFS (p = 0.0005) and OAS (p = 0.003). However, in the Cox multivariate regression analysis only PAI-1 was significantly independent for OAS and could therefore give additional information. We conclude that levels from PAI-1 antigen measured in cytosol of primary breast cancer is an independent prognostic parameter to identify patients with high and low risk for relapse and for individualised treatment.

Adult↗
PubMed1996

Comparison of in-vitro falloposcopy with tubal histology in the diagnosis of fallopian tube pathology.

In order to assess the diagnostic quality of falloposcopy in relation to pathomorphology, a consecutive series of 30 Fallopian tubes obtained from surgical salpingectomy cases were prospectively examined by in-vitro falloposcopy and histology. Falloposcopy was performed using an over-the-wire catheterization system and a 0.5 mm falloposcope with 3000 pixels. Assessment of the specimens included the description of lumen geometry, intraluminal changes and status of the mucosal surface. Falloposcopy classified 14 tubes as normal and 16 pathological. Histology resulted in 17 normal versus 13 pathological tubes. Pathologies included lumen obstructions and dilatations, intraluminal synechiae and mucosal damage. Sensitivity and specificity of falloposcopy were calculated to be 0.85 and 0.71; positive and negative predictive values were 0.69 and 0.86. It was concluded that falloposcopic findings indeed reflect and successfully differentiate normal and pathological conditions allowing adequate and reproducible image interpretation. However, variations of the diagnostic accuracy with the type of pathology and the tubal segment have to be taken into account before clinical consequences are drawn from a falloposcopic investigation.

Endoscopy↗
PubMed1996

Maternal mortality in the main referral hospital in The Gambia, west Africa.

A retrospective analysis of 78 maternal deaths was performed during 1991-1992 to estimate maternal mortality at the maternity unit of the main tertiary level hospital in The Gambia. The non-abortion maternal mortality ratio (MMR) was 736 per 100 000 live births. Among the direct causes, haemorrhage caused most deaths (24%), followed by hypertensive disorders in pregnancy (HDP) (21%). Sepsis was the main cause of death in 15%. Anaemia led among the indirect causes of death (8%) and was a co-factor in 41% of all deaths. Substandard care factors other than medical causes were determined involving health care facilities, staff, drugs and equipment, and patient-related factors. Well known risk factors of low age (< or = 19 years) and nulliparity were highly represented in the maternal death group, and delivery by Caesarean section occurred more than threefold compared to the overall Caesarean section rate. Taking haemorrhage as an example, it is demonstrated that the way diagnoses are grouped significantly affects the statistical elaboration of maternal deaths.

Adolescent↗
PubMed1996

German family study on hereditary breast-ovarian cancer.

An estimated 5% to 10% of all breast and ovarian cancers are attributed to dominant susceptibility genes. Two such genes, BRCA1 and BRCA2, were recently identified. The involvement of these genes was studied in 43 German breast only and breast-ovarian cancer families. All families contained three or more cases of breast or ovarian cancer, with at least two diagnosed under the age of 60 years. Multipoint linkage analysis gave a maximum lod score of 2.13 at the BRCA1 locus under the assumption of genetic heterogeneity, with an estimated 50% of families being linked. Among the 33 breast only cancer and 10 breast-ovarian cancer families, the estimated proportions of linked families were 35% and 75%, respectively. Sixteen families with at least four cases of female breast cancer diagnosed under the age of 60 years, or male breast cancer diagnosed at any age, were analysed for linkage to BRCA2. Positive lod scores at BRCA2 were obtained in six families.

Adult↗