Optimization of the interface between radiology, surgery, radiotherapy, and pathology in head and neck tumor surgery: a navigation-assisted multidisciplinary network.

A navigation-assisted multidisciplinary network to improve the interface between radiology, surgery, radiotherapy, and pathology in the field of head and neck cancer is described. All implicated fields are integrated by a common server platform and have remote data access in a ready-to-use format. The margins of resection and exact locations of biopsies are mapped intraoperatively. The pathologist uses the numerical coordinates of these samples to precisely trace each specimen in the anatomical field. Subsequently, map-guided radiotherapy is planned. In addition to the benefits of image-guided resection, this model enables radiotherapy planning according to the specific coordinates of the resection defect plus any residually affected sites identified by the pathologist. Irradiation of adjacent healthy structures is thereby minimized. In summary, the navigation-assisted network described grants timely multidisciplinary feedback between all fields involved, attains meticulous pathological definition, and permits optimized coordinate-directed radiotherapy.

[The population-based mammography screening programme in Germany: uptake and first experiences of women in 10 federal states]. / Das populationsbezogene Mammografie-Screening-Programm in Deutschland: Inanspruchnahme und erste Erfahrungen von Frauen in 10 Bundesländern.

PURPOSE: Within the statutory health insurance (SHI) cancer early detection programme (KFU) an organised, population-based, quality-assured mammographic screening programme in Germany was initiated for women aged 50-69 years in 2004. The aim of the study was to evaluate uptake and first experiences of participants with this new screening approach and to evaluate the background of knowledge, attitudes and intention to address a needs-assessed communication strategy. MATERIALS AND METHODS: A representative, explorative survey within the female population was conducted in 10 federal states. A telephone survey of randomly selected 68,188 contacts was performed, 9,004 women gave informed consent to evaluate rates of invitation and uptake followed by a mailed questionnaire. Of these, 3,469 were returned and 3,226 were analysed. RESULTS: The invitation rate of the programme was 56.6%, the uptake of mammographic screening was 66%, and the screening coverage rate was 37.3%. 90% of the participants were insured by SHI, women with lower socio-economic strata were attracted in accordance with the data of the general population. 61% of all women did not know that the risk of breast cancer increases with age and 56% believed that screening prevents breast cancer. 62.1% judged their own risk to be low. A physician's recommendation to participate was significantly associated with attendance (p<0.05). 90% of the participants would follow the next invitation. CONCLUSION: The KFU targeted group of women was reached and the organised mammography screening programme was well perceived by invited women. For developing a lasting communication strategy information deficits have to be considered along with beliefs and attitudes of elegible women.

The Patients' View On Accredited Breast Cancer Centers: Strengths and Potential for Improvement.

Breast Care Centers that were accredited according to the German Cancer Society criteria were offered to participate in a standardized patient survey in 2010, which was conducted by the Institute for Medical Sociology, Health Services Research and Rehabilitation Science, Faculty of Human Science and Faculty of Medicine, University of Cologne. Patients were included consecutively between March and November 2010. The Cologne Patient Questionnaire-Breast Cancer (CPQ-BC) was used, which assesses a number of aspects of hospital care as perceived by the patients, among them provider-patient interaction, the disease-specific information provided, the quality of organization, and room amenities. 128 of 195 Breast Care Centers and 160 of 251 hospitals participated in the study. 8226 patients consented to the survey. The questionnaires of 7301 patients could be included in the analyses (89 %). Overall, the results showed that patients are satisfied with their hospital stay and that the accreditation criteria are implemented in a way that serves the patients. However, there is room for improvement for a number of issues, for example with regard to the provision of information and patient involvement in decision making. In addition, for a number of indicators substantial differences were found between the hospitals. The results of the survey provide information on the breast centers' development and can be used by the centers' surgery locations for benchmarking purposes, to identify strengths and weaknesses, and to take actions.

Age and sex as predictors of biochemical activity in acromegaly: analysis of 1485 patients from the German Acromegaly Register.

OBJECTIVE: We evaluated the German Acromegaly Register for clinical variables associated with the initial biochemical activity of patients with acromegaly. DESIGN: Retrospective analysis of data in the registry. PATIENTS: A total of 1485 patients with acromegaly (males 45.6%, females 54.4%) were treated in 42 German endocrine centres until November 2005. Linear regression models were used to estimate the influence of various parameters on biochemical activity. RESULTS: Male patients with acromegaly were significantly younger at the time of diagnosis than female patients (41 vs. 47 years, P < 0.0001) and had significantly higher random GH levels than females (21 vs. 14 ng/ml, P < 0.005) and IGF-1 levels (773 vs. 679 ng/ml, P < 0.0001), respectively. Age at initial presentation turned out to be the most important independent risk factor associated with random GH levels, oral glucose tolerance test-suppressed GH levels, IGF-1 levels, body mass index (BMI), tumour size and prevalence of hypopituitarism. Sex was an independent risk factor for IGF-1 levels, BMI and prevalence of hypopituitarism. Tumour size was an independent risk factor for both GH and IGF-1 levels. CONCLUSIONS: In summary, initial biochemical activity of acromegaly is influenced by patient's age and to a lesser degree by patient's sex. Male patients are on an average 6 years younger than females.

[Risk factor calculator for medical underwriting of life insurers based on the PROCAM study]. / Risikofaktorenrechner für die Risiko prüfung in der Lebensversicherung auf Basis der PROCAM Studie.

For its electronic manual GEM, used to perform medical risk assessment in life insurance, SCOR Global Life Germany has developed an innovative and evidence-based calculator of the mortality risk depending on cardiovascular risk factors. The calculator contains several new findings regarding medical underwriting, which were gained from the analysis of the PROCAM (Prospective Cardiovascular Münster) study. For instance, in the overall consideration of all risk factors of a medically examined applicant, BMI is not an independent risk factor. Further, given sufficient information, the total extra mortality of a person no longer results from adding up the ratings for the single risk factors. In fact, this new approach of risk assessment considers the interdependencies between the different risk factors. The new calculator is expected to improve risk selection and standard acceptances will probably increase.

Intravenous lipid and heparin infusion-induced elevation in free fatty acids and triglycerides modifies circulating androgen levels in women: a randomized, controlled trial.

BACKGROUND: The polycystic ovarian syndrome (PCOS) is characterized by hyperandrogenism and associated with obesity and impaired glucose metabolism. Despite the high prevalence of PCOS and the considerable clinical impact, the precise interplay between metabolism and hyperandrogenemia is not entirely clear. OBJECTIVE: The objective of the study was to analyze the effects of iv lipid and heparin infusion on circulating androgen levels in healthy women. DESIGN: This was a randomized, controlled, crossover trial. SETTING: The study was conducted at an endocrinology center. PATIENTS: Patients included 12 healthy young women during the early follicular phase of two subsequent cycles. INTERVENTION: After an overnight fast, a 20% lipid/heparin or a saline/heparin infusion was administered in random order for 330 min. MAIN OUTCOME MEASURES: A detailed characterization of androgen metabolism was performed. RESULTS: Elevations in free fatty acids and triglycerides, induced by lipid/heparin infusion, elevates the levels of androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), testosterone, 5alpha-dihydrotestosterone, estrone, and 17beta-estradiol. Urinary excretion of DHEA, DHEAS, 5-androstene-3beta,17beta-diol, and the sum of urinary excreted DHEA and its 16-hydroxylated downstream metabolites, 16alpha-hydroxy-DHEA and 5-androstene-3beta,16alpha,17beta-triol, were reduced. CONCLUSION: The mechanism of iv lipid and heparin infusion-induced elevation of circulating androgens described here might contribute to the development of hyperandrogenism in women with PCOS and suggests that lowering of hyperlipidemia might be a potential therapeutic target in patients with PCOS to treat hyperandrogenemia.

[Guideline for the Early Detection of Breast Cancer in Germany 2008. Recommendations from the short version]. / Stufe-3-Leitlinie Brustkrebs-Früherkennung in Deutschland 2008 : Auszug aus der Kurzfassung: Handlungsempfehlungen.

The updated 2008 German Guideline for Early Detection of Breast Cancer provides evidence-based and consensus-based recommendations of the knowledge gained by the German Society for Surgery and the German Society of Plastic, Aesthetic, and Reconstructive Surgeons together with 29 professional societies, associations, and nonmedical organizations. The guideline is meant to assist physicians, healthy women, and patients in medical decisions with recommendations regarding the diagnostic chain in early detection of breast cancer. In addition to these recommendations, the guideline also includes descriptions of quality assurance for resources, procedures, outcomes, and evaluation using a set of quality indicators. It updates the previous version from 2003. The guideline's recommendations are presented. They are described in detail in the full publication (in German) Geburtsh Frauenh 2008; 68:251-261. The long version of the Guideline, methods report, and evidence report are available on the internet at www.awmf-leitlinien.de (reg. no. 077/001) with free access.

Assessing risk of myocardial infarction and stroke: new data from the Prospective Cardiovascular Münster (PROCAM) study.

OBJECTIVES: Based on the data of the Prospective Cardiovascular Münster (PROCAM) study, a prospective study of men and women at work in the north-west of Germany, we aimed (i) to develop a refined scoring scheme for calculating the risk of acute coronary events among adult and elderly men and women; and (ii) to generate a new scoring scheme for calculating the risk of ischaemic stroke or transient ischaemic attack (TIA). METHODS: The coronary risk score was derived from a Weibull function using data from 18 460 men and 8515 women who were recruited before 1996 and had a mean follow-up period of 12+/-6 years. The stroke score was derived using a Cox proportional hazards model using data of 5905 men and 2225 women aged 35-65 years with at least 10 years of unbroken follow-up. RESULTS: The coronary risk score was based on 511 major coronary events, 462 (168 fatal, 294 non-fatal) in men and 49 (18 fatal, 31 non-fatal) in women and included the risk factors LDL cholesterol, HDL cholesterol, systolic blood pressure, smoking status, triglycerides and diabetes mellitus status. It was accurate in both sexes over an age range from 20 to 75 years with an area under the receiver-operating characteristics (ROC) curve of 0.82. The stroke score was based on 85 cerebral ischaemic events (21 TIAs, 64 ischaemic strokes) and included the risk factors age, sex, diabetes mellitus status, smoking status and systolic blood pressure. It had an area under the ROC curve of 0.78 and identified a high-risk group comprising only 4% of the study population that contained 31% of all cerebral ischaemic events. CONCLUSION: Both new PROCAM risk scores provide simple and effective ways to assess the risk of acute coronary events and ischaemic stroke in the general population and will improve the ability of physicians to target measures in an effort to prevent these potentially devastating conditions.

Expression of urocortin in the extravillous human trophoblast at the implantation site.

Urocortin (UCN) is a 40 amino acid peptide which is closely related to corticotropin-releasing hormone and binds with high affinity to both CRH type 1 and type 2 receptors. UCN is expressed in human reproductive tissues including endometrium, ovary, and placenta. This study was designed to investigate the cellular localization of UCN at the implantation site of the human blastocyst, as well as the regulation of the UCN promoter by two major intracellular signaling pathways, the cAMP/PKA and diacylglycerol/PKC pathways, in cells of placental origin. For this reason, immunohistochemistry was performed on tissue sections from paraffin-embedded human first trimester placentas and freshly isolated human invasive extravillous trophoblast cells (EVT) were analyzed for UCN expression using RT-PCR and immunofluorescence. Finally, UCN promoter activity was analyzed in the JEG3 human choriocarcinoma cell line. Immunohistochemistry revealed expression of UCN in the cytotrophoblast, the EVT and decidual cells. Both UCN mRNA and peptide were detectable in freshly isolated EVT. Finally, a human UCN promoter luciferase reporter construct transfected into JEG3 cells was significantly inducible by phorbol ester plus ionomycin, but not by phorbol ester alone or by forskolin. Collectively, the present study reports the expression of UCN in EVT and the activation of the UCN gene promoter by the diacylglycerol/PKC pathway. The functional significance of urocortin for the physiology of EVT requires further investigation.

Effect of clinical mastitis on the lactation curve: a mixed model estimation using daily milk weights.

The objective of this study was to estimate the milk production losses associated with clinical mastitis using mixed linear models and correlation structures that have not been available previously. Data used included computer-recorded daily milk yields and detailed and accurate recordings of clinical mastitis cases. Two commercial Holstein dairy farms in New York State participated in the study, one with 650 lactating cows and another that began the study with 830 lactating cows and increased to 1120 cows by the end of the study. Cows on both farms were housed in free stall barns and milked 3 times daily in milking parlors. Electrical conductivity was used as a diagnostic aid for clinical mastitis on both farms. Date of clinical onset was recorded for every episode of clinical mastitis as well as for 8 other diseases defined using standardized case definitions (dystocia, milk fever, retained placenta, metritis, ketosis, displaced abomasum, lameness, and cystic ovarian disease) during the study period of October 1, 1999 to July 31, 2001. The mixed linear model for explaining variation in the outcome variable daily milk yield relative to non-mastitic herdmates found the terms for all 9 diseases studied, including clinical mastitis, significant. The model with an autoregressive correlation structure was preferred based on -2 * log likelihood, Akaike's information criterion, and Bayesian information criterion as well as savings in degrees of freedom. Separate analyses were run for first lactation cows and for second-plus lactation cows because their lactation curves were shaped differently. Adjusting for the effects of the other 8 diseases, milk production loss from clinical mastitis during the whole lactation was estimated as approximately 598 kg for second-plus lactation cows. However, cows that contracted mastitis had a daily production advantage of 2.6 kg over their herdmates until they contracted the disease. When compared with this potentially higher milk production, the total loss from clinical mastitis was estimated as 1181 kg.

Intermittent aortic cross-clamping for coronary artery bypass grafting: a review of a safe, fast, simple, and successful technique.

Since the very beginning of coronary artery bypass grafting, the search for optimal myocardial protection has fascinated both clinicians and basic researchers. This retrospective review of a large patient cohort aims to display the advantages of one of the protective procedures, namely simple, intermittent aortic cross-clamping (IAC). Thus, this review aims to significantly contribute to daily bypass surgery. This review reports on coronary patients who were all operated on in international centers using IAC such that this review presents the state of the art on IAC. In addition, this review reports on the usage of IAC for more than 2 decades in the clinic of Dr. Bircks, Duesseldorf (DE) and the clinics of his former students. A meta-analysis of published data of international centers summarizes 7 837 operated patients with a total mortality of 123 (=1.6%). This excellent outcome compares well to the results of the Bircks'-related centers, where between 1978 and 2001, a total of 41 573 patients were revascularized with the help of IAC according to the original protocol. The total mortality was 778 (1.9%), with the lowest mortality rate (1.2%) in the largest center (Bad Oeynhausen, DE). According to the presented experience, IAC for coronary revascularization proves to be a highly effective method for myocardial protection; it has convincingly proven to be simple, safe and cost-efficient.

Arguments in favour of a homologous concept for hemodialysis access procedures. Feasibility and results.

OBJECTIVES: Autologous arterio-venous (AV) fistulas seem to be superior to prothetic grafts in hemodialysis access surgery. We used an algorithm which enabled us to use autologous vein in over 99% of all fistula operations. DESIGN: All patients undergoing hemodialysis surgery during a three year period (n = 102) were enrolled in an open prospective observation study with the end points feasibility, perioperative complications and patency. MATERIALS: One hundred and two patients were followed until the end of the observation period (30/6/01). METHODS: All relevant data were recorded prospectively. The status of the individual fistula was recorded twice a year until the end of the observation period. Fistula-patency was calculated by life-table-analysis according to Kaplan-Meier. RESULTS: Except one patient presenting with a recurrent shunt aneurysm, no patient received prothetic material. At the end of the observation period all patients alive and under dialysis could use their autologous fistula. There was no perioperative mortality. One reoperation was required for a septic anastomotic rupture. Otherwise, only minor complications were observed. Cumulative 1-year and 3-year patency were 78.5 and 62.8% respectively for the Cimino and 75.2 and 66.8% for elbow fistulas. CONCLUSIONS: An autologous approach is nearly always possible. Besides fewer complications, the approach seems to be cost effective.

[Recognizing patients at high risk for myocardial infarct]]. / Die Erkennung des Hochrisikopatienten für den Herzinfarkt.

Several controlled intervention trials proved the benefit of antihypertensive and hypolipidemic drugs for the prevention of coronary heart disease (CHD). International guidelines for the prevention of CHD agree in their recommendations for secondary prevention and recommend to lower blood pressure below 140/90 mm Hg and LDL-cholesterol below 3 mmol/l (or even < 2.6 mmol/l) in patients with manifest CHD. Novel recommendations for primary prevention are focused on the treatment of the presymptomatic high risk patient with an estimated risk of higher than 2% per year. For the calculation of this risk, the physician must record the following risk factors: gender, age, family history of premature myocardial infarction, smoking, diabetes, blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride. This information allows computing the absolute risk of myocardial infarction by using scores or algorithms which have been deduced from results of epidemiological studies.

[A guideline for guidelines--methodological report and use of the guideline women's information]. / Eine Leitlinie für Leitlinien: Die methodische Entwicklung und Anwendung der Leitlinie Fraueninformation.

UNLABELLED: Information and education is needed to empower autonomy and self-determination of patients (informed consent). Furthermore reliable and accurate medical information is necessary for patients who want to take an active part in medical decision-making. The aim of this work is to define the requirements helping to assure the development of good qualified information material relevant for women and female patients as "a guideline on women information". An example of its use is given by embeding this guideline in the guideline for early detection of breast cancer in Germany by defining the specific elements required for developing qualified information on this issue for women. METHODS: A systematic, stepwise methodological process according to a level two guideline of the German Association of the Scientific Medical Societies (AWMF) and the Agency for Quality in Medicine (AZQ) was performed with the following elements: 1. Establishing an expert panel, 2. Generating the guideline statements by a formal, consensus based nominal group process, 3. External review process and finding supportive partners for the guideline on women information, 4. Using the guideline for guidelines: implementing the concept in the guideline of early detection of breast cancer in Germany. RESULTS: The "guideline women information" comprises nine elements of quality assuring requirements for the development of gender-specific information material and eleven specific elements which directly relate to the guideline statements on early detection of breast cancer. After external review 30 organisations gave their written support for future implementation of the guideline. The "guideline women information" was integrated as a tool for quality assurance of lay information into the "guideline for early detection of breast cancer in Germany". CONCLUSION: The "guideline women information" is a systematically developed, consensus-based recommendation to improve the development of qualified lay information at the point of its process by defining gender-specific aspects required for good lay information and its evaluation. As a guideline for guidelines its use is demonstrated by integrating this guideline into the "guideline for early detection of breast cancer in Germany" to ensure the development of qualified guideline compliant information.

Perioperative levels of atrial natriuretic peptide and troponin-T in patients with uncomplicated coronary artery surgery.

HYPOTHESIS: increased ANP levels after uncomplicated coronary artery surgery (CAS) indicate functional reduction. EXPERIMENTAL DESIGN: prospective, randomized. Preoperative upto the 12 week postoperative. SETTING: Thoracic and Cardiovascular Surgery, University of Düsseldorf. PATIENTS: 15 patients (mean age: 58+/-6.1 years; 13 months, 2 weeks; no myocardial infarction, no congestive heart failure) with 3 vessel disease. INTERVENTIONS: levels of atrial natriuretic peptide (ANP) (pg/ml; radioimmunoassay), Troponin T (TnT) (ng/ml; ELISA test), haemodynamic parameters, ECG monitoring, m-mode echocardiography (Echo). MEASURES: increase of ANP, TnT levels during extracorporeal circulation (ECC), decrease after operation. RESULTS: Maximal increase of ANP from preoperative 90+/-10 (M+/-SEM) pg/ml (p<0.05) up to intraoperative 380+/-38 pg/ml. Ten days postoperative ANP (26+/-33 pg/ml) still threefold increased compared to preoperative level. Increasement of TnT from preoperative 0.02+/-0.01 ng/ml upto intraoperative 3.44+/-0.47 ng/ml. Ten days postoperative TnT concentration normal (0.13+/-0.11 ng/ml). Correlation of ANP and TnT five min after bypass up to 6 hrs postoperative (p<0.05, r =3.4). Increase of left atrial diameter preoperative 42.2+/-1.1 mm up to 46.8+/-1.2 mm (p<0.05) 10 days postoperative. LVEDD, EF changed from preoperative 51.1+/-0.9 mm, 73+/-2% to 54.5+/-1.2 mm, 65+/-4% 10 days postoperative. CONCLUSIONS: Threefold increase of ANP 10 days postoperative and return of TnT levels to normal under consideration of datas of echo show, that ANP is suitable to indicate the meanterm, functional, myocardial reduction. Increased ANP levels, atrial dilatation and dysfunction are important signs of cardial functional reduction after CAS.

Identification of an upstream pituitary-active promoter of human somatostatin receptor subtype 5.

Somatostatin receptor subtype 5 (sst5) has been linked to inhibition of PRL and insulin secretion. We characterized the genomic structure of the human sst5. The transcription start site was located 94 nucleotides upstream of the initiator ATG codon. Sequence analysis of 5'-inverse PCR products revealed the presence of a 6.1-kb intron in the 5'-untranslated region. RT-PCR analysis indicated tissue-specific activation of the newly identified upstream promoter in pituitary, but not in small intestine, lung, or placenta. A -1741 promoter directed significant levels of luciferase expression in GH(4) rat pituitary cells, Skut-1B endometrium cells, and JEG3 chorion carcinoma cells, which was absent in COS-7 monkey kidney cells. A minimal -101 promoter was sufficient to allow tissue-specific expression. Its activity in COS-7 cells was not enhanced by cotransfection of the pituitary-specific transcription factor Pit-1. Analysis of deletion constructs revealed a GC-rich region immediately upstream of the transcription start site, which is necessary for promoter activity. Somatostatin led to a significant inhibition, and forskolin and thyroid hormone to a significant stimulation of pituitary-specific promoter activity. Further mapping suggested a cAMP-responsive element located between -101 and the transcription start site, and thyroid hormone-responsive elements between -1741 and -1269 and between -317 and -101. These studies identified an upstream promoter of the sst5 gene with tissue-specific activity.

Elastase release following myocardial ischemia during extracorporeal circulation (ECC) -- marker of ongoing systemic inflammation?

BACKGROUND: 'Post-Perfusion Syndrome' (PPS) after cardiopulmonary bypass (CPB) is known to be evoked by inflammatory reactions. The hypothesis of a pathogenetic role for the neutrophil granulocytes in this inflammation would be strengthened if elevated concentrations of a neutrophil product such as elastase could be demonstrated, particularly in case of a PPS or a systemic inflammatory response syndrome (SIRS). METHODS: In a randomized prospective double-blind study, 40 patients undergoing aortocoronary bypass grafting (CABG) were divided into 4 groups of 10 patients each. One group served as the control group, one received prostacyclin (PGl 2 ), the third group was substituted with high-dosed aprotinin and the last group was treated with a combination of PGl 2 and aprotinin. 6 blood samples were taken from every patient perioperatively, and plasma elastase (PE), procalcitonin (PCT), C 1 -esterase inhibitor (CEI) and parameters of coagulation and fibrinolysis were determined. RESULTS: Levels of elastase increased significantly in all intra- and postoperative blood samples compared to the preoperative baseline values (< 30 microg/l, p < 0.05). The elastase release was even more pronounced in the control and aprotinin group (170 +/- 23 microg/l; 175 +/- 14 microg/l during ECC) compared to patients who received prostacyclin (142 = 21 microg/l, p < 0.05). Duration of myocardial ischemia could be directly correlated to elastase levels at the end of CPB. 10 of the 40 patients suffered postoperatively from a PPS or a SIRS; in these patients, elastase levels at the end of CPB were significantly higher (188 +/- 26 microg/l vs. 138 +/- 22 microg/l, p < 0.05). Immediately after the operation, these 10 patients also showed significant changes in the cascades of coagulation and fibrinolysis resulting in a hypercoagulatory state. Levels of PCT and CEI did not change significantly during and after ECC. CONCLUSIONS: Our results indicate that CPB initiates an elastase release that can be suppressed by prostacyclin. Increased intraoperative elastase levels in patients with PPS show that elastase may be an indicator of ongoing systemic inflammation, possibly causing complications due to a hypercoagulatory state. Myocardial ischemia seems to be one reason for this elastase release. It can be speculated that early PGl2-infusion could be a therapeutic option in inflammatory diseases caused by ECC.

Characterization of the human somatostatin receptor type 4 promoter.

Somatostatin (SRIF) exerts inhibitory effects on virtually all endocrine and exocrine secretions. Five distinct SRIF receptor subtypes (sst 1-5) have been identified. In contrast to the other subtypes, very little is known about specific functions of sst4. We investigated structure and regulation of the human sst4 gene. A genomic clone containing the 5' region of the sst4 gene was isolated. 1.5 kb of the promoter was sequenced and putative transcription factor binding sites were identified. The transcription start site was located 88 nucleotides upstream of the translation start site. A -984 sst4 promoter directed significant levels of luciferase expression in GH4 rat pituitary cells, Skut-1B endometrium cells, and BEAS-2B human bronchial epithelial cells, whereas only low activity was detected in JEG3 chorion carcinoma cells or COS-7 monkey kidney cells. A minimal -209 promoter allowed cell specific expression, its activity in COS-7 cells is not enhanced by co-transfection of the pituitary-specific transcription factor Pit-1. An enhancer element was localized between nt -459 and -984. We did not find any regulation of the sst4 promoter region analyzed by SRIF, forskolin, TPA, IGF-1, EGF, T3, glucocorticoids or 17beta-estradiol. These studies identify the 5' region of the sst4 gene. Furthermore, specific activity of the promoter in various cell lines is demonstrated.

Repair of critical aortic coarctation in neonatal age.

BACKGROUND: The data of 111 (male: 64; female: 47) in the period of 1967 until 12/93 consecutive operated neonatals (<1 month) were studied retrospectively (mean weight 3270 g, mean age at operation 14 days). METHODS: Preductal anatomy was present in 96 patients. The coarctation was isolated in 30 patients (group I), 34 patients had additional large ventricular septal defects (group II) and 47 had complex heart disease (group III). The preoperative heart catheterization revealed a gradient of <20 mmHg in 35%, >20 mmHg in 51.4% and >50 mmHg in 12.9%. The indication for repair was conservatively untreatable heart insufficiency. In the vast majority (n=97) of patients resection and end-to-end anastomosis were performed, in 31 cases using an absorbable suture, in 18 of these using a continuous suture line. In 4 patients a subclavian flap angioplasty (SFA) was done, in 4 a patch enlargement, 4 times a repair was described as not possible and in 2 patients there was no gradient after division of the ductus. RESULTS: Early lethality was 3.3% (n=1) in group I, 24.2% (n=8) died in group II and 39.1% (n=18) in group III; after introducing Prostaglandin E1 0% in group I, 15% in II and 25% in III. Relevant recoarctation (Gradient >20 mmHg) developed in 9 (among them 4 with hypoplastic arch, 2 after SFA) of the 77 long-term survivors; 6 of these were reoperated on, 5 without residual gradient, 1 with a gradient of 25 mmHg without clinical symptoms (after 4 years). In the last 3 patients a balloon dilation was carried out without residual gradient. Mean follow-up time was 6 (0-24) years. No patient needs antihypertensive treatment. The cumulative survival rate is 96.7% (+6.6%) for group I, 77.4% (+15.0%) for II and 51.9% (+16.6%) for III. CONCLUSIONS: Resection and end-to-end anastomosis using a continuous absorbable suture is the method of choice at theoretical considerations and in our experiences. The number of recoarctations in neonatal age is relatively high; reinterventions (operation respectively dilation) can be done safely and successfully.