[What factors determine the direct medical costs of patients with systemic lupus erythematosus in Germany? Subanalysis of the LUCIE study]. / Welche Faktoren bestimmen die direkten Krankheits-kosten bei Patienten mit Systemischem Lupus Erythe-matodes in Deutschland? - Subanalyse der LUCIE-Studie.

OBJECTIVES: The aim of this study was to evaluate annual direct medical costs of adult SLE patients with active autoantibody positive disease on medication in Germany. METHODS: A multicentre, observational, retrospective European study with German sub-analysis was performed. Costs were assessed according to national tariffs. RESULTS: 10 German centres included 77 patients. The mean (SD) annual direct medical costs of patients were € 3 452.21 (3 777.07), and were 3.4 times higher in severe than non-severe patients (€ 5 291.07 vs. 1 564.97; p<0.001). Cost of medication (€ 2 349.40) represented 68.1% of the total cost. Flares, especially severe flares, were identified as cost predictors. Each flare increased the annual total cost by € 2 164,01 (p<0,001). CONCLUSION: The annual direct medical cost of SLE patients in Germany is linked to disease severity. Medical treatments and severe flares were identified as the cost predictors and drivers, respectively.

The RACHS-1 risk categories reflect mortality and length of hospital stay in a large German pediatric cardiac surgery population.

OBJECTIVES: The Risk Adjusted classification for Congenital Heart Surgery (RACHS-1) was published in January 2002, based on 4370 operations registered by the Pediatric Cardiac Care Consortium. It is designed for being easily applicable also for retrospective analysis of hospital discharge data sets; the classification was not developed for patients with heart transplantations, ventricular assist devices or patients above 18 years. We apply this classification to our 2368 correspondent procedures that were performed consecutively on 2223 patients between June 1996 and October 2002 in Bad Oeynhausen and analyze its relation to mortality and length of hospital stay. METHODS: The procedures were grouped by the 6 RACHS-1 categories. Groping criteria were mainly the performed procedures; for few procedures age or diagnoses are needed in addition. The classification process itself took less than 10 working hours. Risk group frequencies in our/ the PCCC population were 1: 368/964 (15.5%/22.0%), 2: 831/1433 (35.1%/33.1%), 3: 744/1523 (31.4%/34.7%), 4: 284/276 (12.0%/6.3%), 5: 4/4 (0.2%/0.1%), 6: 137/168 (5.3%/3.8%). 18.8%/19.2% were under 1 month, 37.5%/31.6% 1-12 months of age, respectively. RESULTS: Hospital mortality (%) in our population/ the PCCC Group 1-6 was: 0.3/0.4, 4.0/3.8, 5.6/8.5, 9.9/19.4, 50.0/0, 40.1/47.7%. Geometric means of total (13.1, 19.6, 23.5, 29.1, 31.5, 52.6 days, respectively) and postoperative length of stay of survivors show significant differences between the single risk groups. The prediction capacity of the score as expressed by the area under the receiver-operator curve was nearly equal to the value found for the American hospital discharge data sets. Length of stay rises exponentially with the RACHS-1 category. However, the RACHS-1 category explains only 13.5% of the total and 16.8% of individual postoperative lengths of hospital stay in survivors. CONCLUSION: The RACHS-1 classification is applicable to European pediatric populations, too. Category Distribution, outcome class distinction capacity, distribution and mortality are similar. RACHS-1 is able to classify patients into significantly different groups concerning total and postoperative hospital stay duration, although there remains a large variability within the groups.

Stage 1 palliation of hypoplastic left heart syndrome: implications of blood gases.

OBJECTIVE: To estimate ratios of pulmonary-to-systemic blood flows (Qp/Qs) after stage I palliation (Norwood operation) for hypoplastic left heart syndrome and to determine whether early postoperative death can be associated with abnormalities of Qp/Qs ratios. DESIGN: Retrospective. SETTING: University hospital. PARTICIPANTS: Patients who underwent stage I palliation (Norwood operation) for hypoplastic left heart syndrome (n = 76). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The results of the last intraoperative blood gas analysis were compared between patients who survived the day of operation (58 of 76) and the patients who died intraoperatively or within 4 hours after operation (18 of 76). Qp/Qs ratios were calculated using the Fick principle from arterial and venous oxygen saturations at estimated pulmonary venous oxygen saturation of 95%. A lower arterial oxygen saturation (SaO(2), 69.0 +/- 20.5% v 77.3 +/- 8.5%; p < 0.05) and more marked metabolic acidosis (pH, 7.244 +/- 0.115 v 7.298 +/- 0.095; p < 0.05; base excess, -6.8 +/- 4.4 v -3.0 +/- 4.2; p < 0.05) were observed in nonsurvivors. Calculated Qp/Qs ratios ranged between 0.2 and 6.5 in survivors and between 0.6 and 1.9 in nonsurvivors. CONCLUSIONS: Postoperative excessive pulmonary blood flow was not implicated as a cause of death based on blood gas data and Qp/Qs ratios. In nonsurvivors, low cardiac output and hypoxemia were assumed to be major problems.

Gene expression patterns associated with the metastatic phenotype in rodent and human tumors.

Using subtractive technology, we have generated metastasis-associated gene expression profiles for rat mammary and pancreatic adenocarcinomas. Several genes whose expression is thought to be related to tumor progression such as c-Met, urokinase-type plasminogen activator receptor, ezrin, HMG-1, oncomodulin, cathepsin, and caveolin were thereby isolated. Half of the metastasis-associated clones showed no significant homology to genes with known function. Notably, several of the metastasis-associated clones were also expressed in metastatic lines but not in nonmetastatic lines of other tumor models. Furthermore, in situ hybridization using selected clones documents the relevance of these results for human cancer because strong expression in tumor cells including metastases was detected in human colorectal cancer samples and, to a lesser extent, in mammary cancer samples. These data support the concept that tumors express a "metastatic program" of genes.

When to operate in carotid artery disease.

Carotid endarterectomy has proved to be beneficial in the prevention of stroke in selected patients. The procedure is indicated in symptomatic patients with carotid-territory transient ischemic attacks or minor strokes who have carotid artery stenosis of 70 to 99 percent. With a low surgical risk, carotid endarterectomy provides modest benefit in symptomatic patients with carotid artery stenosis of 50 to 69 percent. Platelet antiaggregants and risk factor modification are recommended in symptomatic patients with less than 50 percent stenosis. In the Asymptomatic Carotid Atherosclerosis Study, carotid endarterectomy was beneficial in patients who had asymptomatic carotid artery stenosis of 60 percent or greater and whose general health made them good candidates for elective surgery, provided that the arteriographic and surgical complication rates were low. However, in asymptomatic patients, surgery reduced the absolute risk of stroke by only 1 percent per year.

Results after Norwood procedure and subsequent cavopulmonary anastomoses for typical hypoplastic left heart syndrome and similar complex cardiovascular malformations.

OBJECTIVE: From October 1989 to June 1998, 60 patients have undergone the Norwood procedure (stage I) at our institution. The results of the staged surgical reconstruction and risk factors were analysed. Typical hypoplastic left heart syndrome (HLHS) and complex lesions with aortic hypoplasia were compared with each other. PATIENTS: Typical HLHS: N = 48, median age 15 days (5-190 days), median weight 3.6 kg (2.6-5.3 kg). Complex lesions (dominant left ventricle): N = 12, median age 59 days (10-884 days), median weight 3.4 kg (2.4-12 kg). RESULTS: Typical HLHS: The stage-I hospital survival was 73% (35/48). It improved from 60% (95% confidence interval: 49-71%) during 1989-1994 to 91% (95% CI: 81-100%) during 1997-1998. Seven patients were lost late. The right ventricular end diastolic diameter (P = 0.015), shortening fraction (P = 0.027), and the presence of an obstructed pulmonary venous return (P = 0.0032) were significant risk factors. 23 children underwent stage-II operation with four (17%) deaths. All survivors experienced an improvement of their statomotoric development. Stage-III operation was performed in 13 patients with no hospital death. Follow up after stage-III procedure was 7 months to 7 years. 4 year actuarial survival, including hospital mortality and deaths at subsequent stages, improved from 28% (95% CI: 18-38%) during 1989-1994 to 58% (95% CI: 48-68%) during 1994-1997. No patient had signs of myocardial insufficiency. Complex lesions: Stage-I hospital survival was 83% (10/12) with no late death. Stage-II was performed in 8 and stage-III in 6 patients with no death respectively. CONCLUSION: In typical HLHS the results have improved over time. Both size and function of the right ventricle determined significantly stage-I survival. An early operation prevents the natural progression of pulmonary blood flow and may weaken all three risk factors. Patients with complex lesions seemed to have better chances of surviving the early postoperative period. The multistage reconstructions have become a realistic option for patients with HLHS and similar lesions, regardless of the morphologic subtype or diminutiveness of the aorta, and lead to an acceptable quality of life.

Temperature adaptation of house keeping and heat shock gene expression in Neurospora crassa.

Adaptation of house keeping and heat shock gene expression was determined in Neurospora crassa during continuous exposure to different temperatures. Steady-state values of total protein synthesis differed little after incubation for 24 h at temperatures between 15 and 42 degreesC. Adaptation kinetics at 42 degreesC showed an initial, transient inhibition of total protein synthesis. Similar kinetics were observed with actin synthesis and tubulin mRNA. A priming 1-h heat shock of 42 degreesC 2 h prior to a second continuous exposure to 42 degreesC abolished the inhibitory effect of the second treatment and resulted in "acquired translational tolerance." Steady-state values of HSP70 synthesis rates revealed increasing levels with increasing temperatures after incubation for 24 h at different temperatures. Adaptation kinetics of the synthesis rates of different HSPs in vivo revealed maximal rates after 2 h and then a decrease to the elevated steady-state levels. The total amount of the major constitutive and inducible HSP70 isoform as determined by Western blots reached a maximum 2 h after the beginning of 42 degreesC exposure and only a slight decrease (25%) of the maximal value after 24 h. The inducible isoform of HSP70, in contrast, reached a maximum after 4-8 h and then decreased strongly after 24 h. HSP mRNAs reached maximal amounts 45-60 min after the beginning of 42 degreesC exposure and then declined after 8 h as determined by in vitro translation. Northern blots revealed maximal mRNA amounts of the inducible HSP70 after 30 min and zero amounts after 4 h exposure to 42 degreesC. After a shift to 42 degreesC HSP70 isoforms were immediately translocated into the nucleus and reshuttled into the cytoplasm during the following 6 h. The nuclear content of HSP70 remained elevated during the adapted steady state at 24 h. It is concluded that the adapted state after 24 h is based on enhanced amounts of constitutive isoforms in the cytoplasm and in the nucleus, whereas the inducible isoforms of HSP70 show faster adaptation kinetics.

[Anatomic and functional hypoplastic left heart syndrome and its surgical Norwood and Fontan treatment]. / Das anatomische und funktionelle hypoplastische Linksherz-Syndrom und seine chirurgische Behandlung nach Norwood und Fontan.

UNLABELLED: The surgical therapy of newborns with hypoplastic left heart syndrome (HLHS) is still regarded with some distrust. The complete heart conserving palliation includes not only the Norwood operation during the newborn period but also the complete separation of both circuits by the Fontan operation some time later. Our experiences with each surgical step are presented. From 1989 to 1996, 43 infants with anatomical (n = 33) or functional (n = 10) HLHS underwent the Norwood operation. Functional HLHS were: Mitralatresia with double outlet right ventricle and subaortic stenosis (n = 2), atrioventricular septal defect with hypoplastic left ventricle, subaortic stenosis, and aortic coarctation (n = 1), hypoplastic, subaortic right ventricle with restrictive ventricular septal defect and aortic hypoplasia (n = 7). The median age at operation was 15 days (5 to 182 days), mean weight was 3.3 kg (3.0 to 4.9 kg). Total operative mortality was 32% (n = 14) with 16% since 1994 (3/19 patients). Five infants (12%) died 2 weeks to 6 months later, and 2 patients underwent cardiac transplantation. Up to now, 19 out of the 22 long term survivors underwent the bidirectional cavopulmonary anastomosis (Hemi-Fontan) at a median age of 7 months (2 to 14 months). Two infants died (10%). Up to now, 12 out of the remaining 17 survivors received the total cavopulmonary anastomosis after a mean period of 12 months. All children survived, and they are now completely palliated. The longest follow up after the complete Fontan operation is 6 years. CONCLUSION: With increasing experience the results of the Norwood operation improved. The following two-stage Fontan procedure bears only a low risk and leads to good quality of life.

A high throughput screening for rarely transcribed differentially expressed genes.

A novel method combining elements of suppression subtractive hybridization with high throughput differential screening permits the efficient and rapid cloning of rarely transcribed differentially expressed genes. The experimental strategy virtually excludes the possibility of isolating false positive clones. The potential of the method is demonstrated by the isolation of 625 differentially expressed cDNAs from the metastatic adenocarcinoma cell line Bsp73-ASML when subtracted from its non-metastatic counterpart Bsp73-1AS. Northern analysis of 72 randomly selected clones demonstrated that 68 were differentially expressed with respect to Bsp73-ASML, indicating a true positive rate of 94%. Additionally, a large proportion of these clones represented rare transcripts as determined by the exposure time required to detect a signal. Sequence data indicated that of the 625 clones obtained, 92 clones scored perfect or near perfect matches with already known genes. Two hundred and eighty one clones scored between 60 and 95% homology to known human and mouse genes, whereas 252 clones scored no match with any sequences in the public databases. The method we describe is ideally suited whenever subtle changes in gene expression profiles need to be determined.

Comparative in-vivo and in-vitro 99Mo-time-differential-perturbed-angular-correlation studies on the nitrogenase MoFe protein and on other Mo species of different N2-fixing bacteria.

Klebsiella pneumoniae, Azotobacter vinelandii and Rhodobacter capsulatus were cultivated in media containing 99MoO4(2-) . The distribution of 99Mo in cells grown under conditions of repression and derepression of nitrogenase synthesis, was investigated by anion-exchange (DEAE-Sephacel) chromatography. Cells of K. pneumoniae took up MoO4(2-) only under conditions of derepression of nitrogenase thus serving the formation of the FeMo cofactor of the MoFe protein (Kp1) as the predominant Mo-containing species. In the case of A. vinelandii, under diazotrophic growth conditions, molybdenum was preferably incorporated into the nitrogenase MoFe protein (Av1). However, if excess amounts of molybdate were present in the medium, molybdenum was also bound to the Mo-storage protein. In the presence of 20 mM NH4+, conditions which completely repress nitrogenase formation, molybdenum accumulated in the Mo-storage protein exclusively. This protein proved to be unstable towards DEAE-Sephacel, apparently releasing all the molybdenum in form of MoO4(2-) during the fractionation procedure. R. capsulatus contained, in addition to the MoFe protein (Rc1), significant amounts of other not-yet-identified Mo species, which partially are formed under conditions of both, repression and derepression of nitrogenase. The Mo centers of all these compounds were characterized by measuring the nuclear quadrupole interaction of the process 99Mo(beta-)99Tc using time differential perturbed angular correlation spectroscopy. The quadrupole coupling constant (v(Q)) determined for the Mo center in MoFe proteins was consistently in the range 66-81 MHz. The values of the coupling constants determined with intact cells and with the isolated, partially purified, MoFe proteins were in very good agreement. For the Mo-storage protein of A. vinelandii, a quadrupole coupling constant of approximately 180 MHz was determined by measurements performed with nitrogenase-repressed cells as well as with gel-filtered cell-free extracts. Our work proves that the relevant study of hyperfine interactions allows the identification of the MoFe protein and also other Mo proteins in vivo as well as in vitro.

The physician's role in minimizing prehospital delay in patients at high risk for acute myocardial infarction: recommendations from the National Heart Attack Alert Program. Working Group on Educational Strategies To Prevent Prehospital Delay in Patients at High Risk for Acute Myocardial Infarction.

Physicians and other health care professionals play an important role in reducing the delay to treatment in patients who have an evolving acute myocardial infarction. A multidisciplinary working group has been convened by the National Heart Attack Alert Program (which is coordinated by the National Heart, Lung, and Blood Institute of the National Institutes of Health) to address this concern. The working group's recommendations target specific groups of patients: those who are known to have coronary heart disease, atherosclerotic disease of the aorta or peripheral arteries, or cerebrovascular disease. The risk for acute myocardial infarction or death in such patients is five to seven times greater than that in the general population. The working group recommends that these high-risk patients be clearly informed about symptoms that they might have during a coronary occlusion, steps that they should take, the importance of contacting emergency medical services, the need to report to an appropriate facility quickly, treatment options that are available if they present early, and rewards of early treatment in terms of improved quality of life. These instructions should be reviewed frequently and reinforced with appropriate written material, and patients should be encouraged to have a plan and to rehearse it periodically. Because of the important role of the bystander in increasing or decreasing delay to treatment, family members and significant others should be included in all instruction. Finally, physicians' offices and clinics should devise systems to quickly assess patients who telephone or present with symptoms of a possible acute myocardial infarction.

Automatic external defibrillators for public access defibrillation: recommendations for specifying and reporting arrhythmia analysis algorithm performance, incorporating new waveforms, and enhancing safety. A statement for health professionals from the American Heart Association Task Force on Automatic External Defibrillation, Subcommittee on AED Safety and Efficacy.

These recommendations are presented to enhance the safety and efficacy of AEDs intended for public access. The task force recommends that manufacturers present developmental and validation data on their own devices, emphasizing high sensitivity for shockable rhythms and high specificity for nonshockable rhythms. Alternative defibrillation waveforms may reduce energy requirements, reducing the size and weight of the device. The highest levels of safety for public access defibrillation are needed. Safe and effective use of AEDs that are widely available and easily handled by nonmedical personnel has the potential to dramatically increase survival from cardiac arrest.