[Indication-Related Effectivity of Cervical Occlusion Techniques in Women with Threatening Preterm Birth]. / Indikationsbezogene Effektivität von Verschlussoperationen am Muttermund.

The aim of this study was to identify which operation technique [total cervical occlusion (TMV), cerclage (C) or combination of both (TMV+C)] would lead to the greatest pregnancy prolongation in 3 different collectives of patients at risk (history of preterm birth, cervical insufficiency, prolapsing membranes). In this retrospective data collection, 200 cervical occlusions performed between 1997 and 2010 were analysed. In patients with a history of preterm birth/stillbirth (n=80) a prophylactic TMV increased the lifebirth rate from 35% without TMV to 95% with TMV (p<0.001). The risk diminuation after TMV was - 60% for stillbirth (p<0.001) and - 30% for preterm birth (p=0.01). In this subcollective the TMV seemed to be more effective in pregnancy prolongation (days) than C (139 vs. 113 days), however the combination of both (C+TMV) did not add much benefit (142 days). In patients with cervical insuffiency (n=86) the pregnancy could be prolonged by 82 (C), 79 (TMV) und 109 days (C+TMV) (p=0.003-0.017) and in patients with membrane prolaps (n=34) by 63 (C), 61 (TMV) und 76 (C+TMV) days. According to present data, the combination of cerclage and TMV has the highest benefit on pregnancy prolongation. This analysis should provide a basis for randomised controlled studies on this topic.

[Red blood cell transfusions in very low birth weight newborns]. / Transfusiones de glóbulos rojos en recién nacidos de muy bajo peso de nacimiento.

INTRODUCTION: It has been reported that 80% of very low birth weight infants (VLBWI) are receiving packed red blood cell transfusions (PRBCtr), and in 90% of cases, the indication is the replacement of the blood collected. The existence of guidelines for transfusion practices has had a great impact on the decline in the number of transfusions. The aim of this paper is to describe the characteristics of VLBW infants who are packed red blood cell transfusion receptors. PATIENTS AND METHODS: This is a descriptive cross-sectional study, which included the medical records of all VLBW newborns older than 72 hours, released from the Neonatology department of the Hospital Valdivia Base, between 2005 and 2006. Birth weight, gestational age, pulmonary surfactant, hyaline membrane, mechanical ventilation, bronchopulmonary dysplasia, sepsis and packed red blood cell transfusions were evaluated. Guidelines for packed red cell transfusions were used at the Hospital. RESULTS: 93 newborns were evaluated and 62 of them were transfused (66.7%); they received 2.1 ± 0.9 PRBC transfusion and the exposure to different donors was 2.1 ± 0.9. The VLBW infants susceptible to be PRBCtr receptor were those younger than 30 weeks' gestational age, weighing less than 1,250 g and with respiratory failure, mechanical ventilation and sepsis. CONCLUSION: The observed percentages of transfused infants with very low birth weight, median PRBCtr and exposure to different donors can be attributed to the existence of guidelines for neonatal transfusion practices and a team of highly experienced neonatologists.

Interdisciplinary Peripartum Management of Acute Respiratory Distress Syndrome with Extracorporeal Membrane Oxygenation - a Case Report and Literature Review.

Extracorporeal membrane oxygenation (ECMO) is increasingly used for the management of acute severe cardiac and respiratory failure. One of the indications is acute respiratory distress syndrome (ARDS) for which, in some severe cases, ECMO represents the only possibility to save lives. We report on the successful long-term use of ECMO in a postpartum patient with recurrent pulmonary decompensation after peripartum uterine rupture with extensive blood loss.

Evaluation of contraceptive methods in women with congenital heart disease in Germany, Hungary and Japan.

AIMS: For women with congenital heart defects (CHD), pregnancy may pose a health risk. Sexually active women with CHD without the desire for own children or for whom pregnancy would imply considerable health risks require adequate counselling regarding appropriate contraception. This study gathers data on the contraceptive behaviour of women with CHD from three different cultural regions. METHODS AND RESULTS: 634 women with CHD from Germany, Hungary and Japan were surveyed regarding contraception and contraceptive methods (CM) used. The patients were divided into groups according to different criteria such as pregnancy associated cardiovascular risk or "safety" of the contraceptive methods used. 59% of the study participants had already gained experience with CM. The average age at the first time of use was 18.4 years; the German patients were significantly younger at the first time of using a CM than those from Hungary and Japan. Overall the condom was the method used the most (38%), followed by oral contraceptives (30%) and coitus interruptus (11%). The range of CM used in Japan was much smaller than that in Germany or Hungary. Unsafe contraceptives were currently, or had previously been used, by 29% of the surveyed patients (Germany: 25%, Hungary: 37%, Japan: 32%). CONCLUSION: Most women with CHD use CM. There are differences between the participating countries. Adequate contraceptive counselling of women with CHD requires considering the individual characteristics of each patient, including potential contraindications. For choosing an appropriate CM, both the methods' "safety", as well as the maternal cardiovascular risk, are important.

Common polymorphisms in checkpoint kinase 2 are not associated with breast cancer risk.

A substantial proportion of the familial risk of breast cancer may be attributable to genetic variants each contributing a small effect. Polymorphisms in DNA repair genes are good candidates for such low penetrance breast cancer susceptibility alleles. Checkpoint kinase 2 (CHEK2) is a kinase in which the yeast counterpart regulates a cell cycle checkpoint and causes cells to arrest proliferation after DNA damage. A rare, protein truncating mutation in the CHEK2 gene has recently been shown to confer a modest risk of breast cancer. The aim of this study was to determine whether common polymorphic variants in CHEK2 are associated with an increase in breast cancer risk. We assessed two variants in CHEK2 using a case control study design (n = 1786 cases and 1828 controls). No differences in genotype frequencies were found between cases and control for either the IVS1 + 38insa or the a1013g polymorphisms (P = 0.3 and 0.2 respectively), and no genotype-specific risk was significantly different from unity. The haplotype frequency distribution in cases and controls were also similar (P = 0.3). We conclude that the CHEK2 polymorphisms IVS + 1a and a1013g do not confer an increased risk of breast cancer. It is also unlikely that other, as yet unidentified, common polymorphisms that affect risk are present in the gene in the British population.

Isolated leukemia cutis and CNS involvement in combination with cytogenetic findings of trisomy 8--two case reports.

We describe two patients who showed a very similar, but atypical course of acute myelogenous leukemia. They demonstrated skin nodules, spinal fluid and CNS involvement whereas bone marrow and blood remained clear. Nonetheless both had cytogenetic findings of trisomy 8 in the marrow and were resistant to a combination of cytarabine, idarubicin, fludarabine, and granulocyte-colony stimulating factor.

Prevention and therapy for BRCA1/2 mutation carriers and women at high risk for breast and ovarian cancer.

The hereditary breast (BC) and ovarian (OC) cancer syndrome (HBOC) includes genetic alterations of various susceptibility genes such as TP53, ATM, PTEN or MSH2, MLH1, PMS1, PMS2, MSH3 and MSH6, BRCA1 and BRCA2. Germline mutations of the cancer-susceptibility genes BRCA1 and BRCA2 seem to be the major aetiology of the HBOC. Genetic counselling and identification of high-risk families may be essential (1) to provide the best method for genetic testing by explaining the sensitivity and specificity of the methods, (2) to offer the opportunity to participate in specific early cancer detection programmes (breast (self) palpation, ultrasound, mammography and magnetic resonance tomography for breast cancer; vaginal exploration and ultrasound for ovarian cancer), (3) to inform them about prophylactic medication (oral contraceptive pill (OCP), chemoprevention (tamoxifen, raloxifen, aromatase inhibitors)) or surgery (bilateral prophylactic mastectomy or oophorectomy) and (4) to provide individualized psychological support. To fulfil these broad demands, an inter-disciplinary counselling approach (gynaecological oncology, human genetics, molecular biology, psychotherapy) in the setting of a cancer genetic clinic seems the most appropriate. There, participation in predictive genetic testing or the use of preventive or therapeutic options may be discussed extensively with the subjects. In particular, preventive options are emotionally disturbing for the subjects, and in cases of previous cancer. BC chemoprevention for high-risk women does not seem to be as effective as expected. However, OCP reduces the risk for OC. For prophylactic surgery, various points have to be considered, including: (1) individual risk assessment and gain in life expectancy, (2) value of screening and early detection methods or medical prevention, (3) disease characteristics and prognosis, and (4) anxiety and quality of life. Decisions regarding these options have to be individualized and psychological support must be offered during the period of decision and follow-up.

int-2 and c-erbB-2 gene amplification detected in 70 frozen human breast carcinomas by quantitative polymerase chain reaction.

Gene amplification is a common mechanism of proto-oncogene activation and contributes to tumor progression. Analysis of such genetic alterations is relevant to our understanding of tumor genetics and can provide prognostic information for the patients. A rapid, non-radioactive approach based on qdPCR and fluorescent DNA technique was applied for determination of int-2 and c-erbB2 gene amplification and correlated with other prognostic factors in 70 breast cancer samples. ER and PgR were analysed by immunohistochemistry. The mixed template assay showed 96% concordance between calculated and measured gene copy number. int-2 gene and c-erbB2 amplification were both found in 24% of the tumors. The amplification did not correlate with any of the other prognostic factors. 8% of the tumors showed amplification of both genes without significant correlations to any of the other parameters. The fd-PCR assay is a valuable tool for determination of amplification of int-2 and c-erbB2 genes. Therefore, more detailed information about individual tumour biology and outcome may be acquired by this routine assay and probably provide prognostic impact.

[Breast cancer: assessment of individual risk and possibilities for prevention]. / Mammakarzinom: Ermittlung des individuellen Erkrankungsrisikos und Möglichkeiten der Prävention.

Today, prevention of breast cancer (BC) is a great demand. The exact estimation of the individual BC-risk is a prerequisite for the participation on early cancer detection or the use of preventive medication or surgery. Various models for risk assessment of BC development or the presence of a predisposing mutation (i.e. BRCA1 or BRCA2) are used, but the statistical individual risk assessment still remains uncertain. Calculating an elevated risk or detection of a predisposing mutation leads to the recommendation of preventive measurements. After detailed assessment, prophylactic bilateral mastectomy is an option to consider for mutation carriers. For women with low BC-risk, chemoprevention can be discussed. Chemoprevention with tamoxifen (TAM)--indirectly supported by BC data from the raloxifen (RLX) prevention trial for osteoporosis and cardio-vascular disease--points to the right direction. Results from the three published TAM prevention trials are variable. Life time risk, age and life style have to be considered in the adapted individual risk-benefit assessment. The lack of long term risk data for chemoprevention and the effect on survival are arguments contra the routine use of TAM as a chemopreventive agent.

Transfusiones de glóbulos rojos en recién nacidos de muy bajo peso de nacimiento / Red blood cell transfusions in very low birth weight newborns

Introducción: Se ha reportado que el 80% de los recién nacidos de muy bajo peso de nacimiento (RNMBPN) es receptor de transfusiones de glóbulos rojos desplasmatizados (trGRD) y en el 90 por ciento de ellos, la indicación de transfusión es la reposición de sangre extraída. La acción en salud que mayor impacto ha tenido sobre el descenso del número de transfusiones, es la existencia de guías para la práctica transfusional. El objetivo de este trabajo es describir las características de los RNMBPN receptores de trGRD. Pacientes y Método: Estudio transversal descriptivo, que incluyó las fichas clínicas de todos los RNMBPN, mayores de 72 h de vida, egresados de Neonatología, Hospital Base Valdivia, entre el año 2005 y 2006. Se evaluaron el peso de nacimiento, edad gestacional, surfactante pulmonar, membrana hialina, ventilación mecánica, displasia broncopulmonar, sepsis y transfusiones de GRD. Se utilizó la Guía para la Práctica Transfusional de GRD en neonatos del Centro Base. Resultados: Fueron evaluados 93 neonatos, siendo transfundidos 62 de 93 neonatos (66,7 por ciento recibiendo 2,1 +/- 0,9 trGRD, la exposición a donantes diferentes fue de 2,1 +/- 0,9. Los RNMBPN susceptible de ser receptor de trGRD fueron de edad gestacional < 30 sem, peso inferior a 1.250 g, con falla respiratoria, ventilación mecánica y sepsis. Conclusión: Los porcentajes observados de RNMBPN transfundidos, la media de trGRD y de exposición a diferentes donantes, podrían ser atribuidos a la existencia de guías para la práctica transfusional neonatal y a un equipo de neonatólogos altamente sensibilizado.

Introduction: It has been reported that 80 percent of very low birth weight infants (VLBWI) are receiving packed red blood cell transfusions (PRBCtr), and in 90 percent of cases, the indication is the replacement of the blood collected. The existence of guidelines for transfusion practices has had a great impact on the decline in the number of transfusions. The aim of this paper is to describe the characteristics of VLBW infants who are packed red blood cell transfusion receptors. Patients and Methods: This is a descriptive cross-sectional study, which included the medical records of all VLBW newborns older than 72 hours, released from the Neonatology department of the Hospital Valdivia Base, between 2005 and 2006. Birth weight, gestational age, pulmonary surfactant, hyaline membrane, mechanical ventilation, bronchopulmonary dysplasia, sepsis and packed red blood cell transfusions were evaluated. Guidelines for packed red cell transfusions were used at the Hospital. Results: 93 newborns were evaluated and 62 of them were transfused (66.7 percent); they received 2.1 +/- 0.9 PRBC transfusion and the exposure to different donors was 2.1 +/- 0.9. The VLBW infants susceptible to be PRBCtr receptor were those younger than 30 weeks' gestational age, weighing less than 1,250 g and with respiratory failure, mechanical ventilation and sepsis. Conclusion: The observed percentages of transfused infants with very low birth weight, median PRBCtr and exposure to different donors can be attributed to the existence of guidelines for neonatal transfusion practices and a team of highly experienced neonatologists.

[Hereditary cancer syndromes in gynecology: what the practitioner needs to know!]. / Hereditäre Karzinomsyndrome in der Frauenheilkunde: Was der Praktiker wissen sollte!

During the last 5 years progress in molecular genetics has offered the possibility of genetic testing for inherited mutations of cancer-predisposing genes. The exact cellular function and carcinogenic potential of these genes is yet not completely understood. Only in 5-20% of all cancers inherited genetic mutations play an important role in the polygenic and multifactorial nature of the disease. Identification of inherited cancer syndromes, predictive genetic testing, and counselling of women and family members at increased risk is of clinical importance. The debate surrounding presymptomatic diagnostic testing and adequate programmes for early cancer detection, prevention or clinical follow-up continues.

Apparent human BRCA1 knockout caused by mispriming during polymerase chain reaction: implications for genetic testing.

We report an apparent BRCA1 homozygous knockout that, on further analysis, was found to be an artefact of the polymerase chain reaction. This finding has two important implications. First, it challenges results of a previous study that reported a homozygous knockout associated with the same BRCA1 mutation. Second, our findings suggest that mispriming caused by mismatched primers at the site of single-nucleotide polymorphisms, leading to preferential amplification of one allele, may represent a significant proportion of instances of mutation-detection insensitivity. This may have major implications for the sensitivity of all polymerase chain reaction-based mutation-detection methods in clinical genetic testing laboratories.

Severe fetal cytomegalovirus infection associated with cerebellar hemorrhage.

Cytomegalovirus (CMV) is the most common cause of congenital infection worldwide. We report on a fatal fetal manifestation of primary maternal CMV infection including cerebellar hemorrhage and hydrops. The diagnosis was established by maternal serological tests, culture and polymerase chain reaction testing of amniotic fluid and fetal blood. The pregnancy was terminated. Postmortem examination confirmed the diagnosis.

[Tumor risk consultation for predisposed women from high risk cancer families]. / Tumorrisikosprechstunde für prädisponierte Frauen aus Krebsrisikofamilien.

Germline mutations of the cancer susceptibility genes BRCA1 and BRCA2 seem to lead to a very high risk for breast and/or ovarian cancer. Therefore, genetic counselling and identification of high-risk families may be essential to offer the opportunity to participate in a specific early cancer detection program and to provide individualized psychological support. In a two year period (August 1994-August 1997) 304 consultees present for genetic counselling at the interdisciplinary cancer genetic clinic (Department of Obstetrics & Gynecology and Human Genetics, Heinrich-Heine-Universität, Düsseldorf). For genetic testing a BRCA1/2 mutation detection strategy including protein truncation test (PTT), single strand conformation polymorphism (SSCP), and direct DNA sequencing is used. 161 families fulfilled the inclusion criteria; at present, 72 families for whom complete analytical material is available are analyzed. Although genetic testing for BRCA1 and BRCA2 is technically challenging, women with a family history of multiple sporadic breast/ovarian cancers and those with a hereditary BRCA1 and BRCA2 gene defect may be distinguished. For the first group of consultees this may ease their concern, for the second group preventive measures including an early cancer detection or prevention program, psychological support or prophylactic surgery may be discussed.

Hormone replacement therapy after treatment of breast cancer: effects on postmenopausal symptoms, bone mineral density and recurrence rates.

PURPOSE: Breast cancer (BC) is the most frequent female carcinoma and the major cause of death in women aged 35--50 years. The total number of patients surviving BC and especially the morbidity rate of patients below the age of 55 years has increased significantly in the last several years. As a consequence, the number of BC patients suffering from the long-term effects of estrogen deficiency due to adjuvant treatment is increasing. At present, hormone replacement therapy (HRT) following BC treatment is applied individually and mainly depends on the severity of postmenopausal symptoms (PMS) experienced by these patients. PATIENTS AND METHODS: In a retrospective study (total n = 185 BC patients, 64 with and 121 without HRT), the effect of HRT during or after adjuvant therapy [chemotherapy and/ or (anti-) hormonotherapy] has been investigated. The surveillance period was up to 60 months. Evaluated were HRT effects on (1) PMS measured by a comprehensive life quality questionnaire, (2) bone mineral density (BMD) measured by osteodensitometry and (3) morbidity as well as mortality rates. RESULTS: Both groups did not differ with regard to tumor stage, lymph node involvement, metastasis, grading, and steroid hormone receptor status. A reduction in PMS was significant in women taking HRT (p < 0.001), especially in the subgroup of women < or =50 years (p < 0.0001). For both age groups, the median reduction in BMD (z-score) was less in women receiving HRT (< or =50 years: without HRT -1.99 vs. with HRT -0.95, p < 0.05; >50 years: without HRT -2.29 vs. with HRT -1.19, p < 0.01). There were no statistically significant differences regarding morbidity and mortality (p = 0.29). CONCLUSION: In this study of BC patients, the use of HRT shows positive effects on PMS and BMD. There was no significant influence on morbidity or mortality. However, a reevaluation of HRT in the routine management of BC patients should await the results of prospective randomized trials.