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ZusammenfassungDie vorliegende Fassung der deutschsprachigen AWMF-Leitlinie soll unter Berücksichtigung der vorliegenden Evidenz die medizinische Versorgung von Kindern und Jugendlichen mit ambulant erworbener Pneumonie (pediatric community acquired pneumonia, pCAP) verbessern. In Mitteleuropa steht einer Prävalenz von ca. 300 Fällen pro 100 000 Kinder/Jahr eine sehr geringe Mortalität gegenüber, die Prävention umfasst Hygiene-Maßnahmen und Impfung z. B. gegen Pneumokokken, Hämophilus, Masern und Influenza. Hauptsymptome der pCAP sind Fieber und Tachypnoe, die Diagnosestellung erfolgt primär klinisch durch Anamnese, körperliche Untersuchung und Pulsoxymetrie. Das zusätzliche Vorliegen von Warnsymptomen wie stark reduzierter Allgemeinzustand, Nahrungsverweigerung, Dehydratation, Bewusstseinsstörung oder Krampfanfälle definiert die schwere pCAP in Abgrenzung zur nicht-schweren pCAP. Das Erregerspektrum ist altersabhängig, zur Differenzierung zwischen viraler, bakterieller oder gemischt viral-bakterieller Infektion stehen jedoch keine zuverlässigen Biomarker zur Verfügung. Die meisten Kinder und Jugendlichen mit nicht-schwerer pCAP und O2-Sättigung > 92 % können ohne weitere Röntgen-, Labor- und Erreger-Diagnostik ambulant betreut werden. Der Einsatz von Antiinfektiva ist nicht grundsätzlich indiziert, vor allem bei jungen Kindern, bronchialer Obstruktion und anderen Hinweisen auf virale Genese kann darauf i. d. R. verzichtet werden. Zur kalkulierten Antibiotika-Therapie sind Aminopenicilline Mittel der Wahl, bei gewährleisteter Einnahme und Resorption sind die orale (Amoxicillin) und intravenöse Verabreichung (Ampicillin) von vergleichbarer Wirksamkeit. Nach 48 – 72 Stunden ist eine Verlaufsbeurteilung notwendig, um den Behandlungserfolg und mögliche Komplikationen wie z. B. parapneumonische Ergüsse oder Pleuraempyeme, die eine Erweiterung bzw. Änderung der Therapie erforderlich machen, rechtzeitig zu erfassen.

Fieber ist im Kindesalter in bis zu 20 % der Falle der Grund fur eine Arztkonsultation. Die Hauptsteuerung der Korpertemperatur erfolgt im Zentralnervensystem. Fieber ist meist eine Abwehrreaktion auf Infektionserreger. Bei jungen Sauglingen (Alter ≤ 3 Monate) wird Fieber als eine Rektaltemperatur >38,0 °C definiert. Die klinische Entitat Fieber ohne Fokus (FOF) wird einzig bei Sauglingen und Kleinkindern beobachtet. Sie stellt eine bedeutende Herausforderung dar: Die klinische Beurteilung fuhrt zur Entscheidung, ob die Wahrscheinlichkeit fur eine schwere bakterielle Infektion, sprich fur einen gefahrlichen Verlauf, als hoch oder gering anzunehmen ist, und bestimmt somit das therapeutische Vorgehen. Standardisierte klinische Voraussagemodelle fur FOF sind ohne zusatzliche Diagnostik fur die klinische Praxis von begrenztem Wert. Erganzend zur klinischen Einschatzung verbessert die durchdachte Bestimmung von Laborparametern die Wahrscheinlichkeitsabschatzung und das therapeutische Vorgehen entscheidend.

The present guideline aims to improve the evidence-based management of children and adolescents with pediatric community-acquired pneumonia (pCAP). Despite a prevalence of approx. 300 cases per 100 000 children per year in Central Europe, mortality is very low. Prevention includes infection control measures and comprehensive immunization. The diagnosis can and should be established clinically by history, physical examination and pulse oximetry, with fever and tachypnea as cardinal features. Additional signs or symptoms such as severely compromised general condition, poor feeding, dehydration, altered consciousness or seizures discriminate subjects with severe pCAP from those with non-severe pCAP. Within an age-dependent spectrum of infectious agents, bacterial etiology cannot be reliably differentiated from viral or mixed infections by currently available biomarkers. Most children and adolescents with non-severe pCAP and oxygen saturation 92 % can be managed as outpatients without laboratory/microbiology workup or imaging. Anti-infective agents are not generally indicated and can be safely withheld especially in children of young age, with wheeze or other indices suggesting a viral origin. For calculated antibiotic therapy, aminopenicillins are the preferred drug class with comparable efficacy of oral (amoxicillin) and intravenous administration (ampicillin). Follow-up evaluation after 48 - 72 hours is mandatory for the assessment of clinical course, treatment success and potential complications such as parapneumonic pleural effusion or empyema, which may necessitate alternative or add-on therapy.Die vorliegende Fassung der deutschsprachigen AWMF-Leitlinie soll unter Berücksichtigung der vorliegenden Evidenz die medizinische Versorgung von Kindern und Jugendlichen mit ambulant erworbener Pneumonie (pediatric community acquired pneumonia, pCAP) verbessern. In Mitteleuropa steht einer Prävalenz von ca. 300 Fällen pro 100 000 Kinder/Jahr eine sehr geringe Mortalität gegenüber, die Prävention umfasst Hygiene-Maßnahmen und Impfung z. B. gegen Pneumokokken, Hämophilus, Masern und Influenza. Hauptsymptome der pCAP sind Fieber und Tachypnoe, die Diagnosestellung erfolgt primär klinisch durch Anamnese, körperliche Untersuchung und Pulsoxymetrie. Das zusätzliche Vorliegen von Warnsymptomen wie stark reduzierter Allgemeinzustand, Nahrungsverweigerung, Dehydratation, Bewusstseinsstörung oder Krampfanfälle definiert die schwere pCAP in Abgrenzung zur nicht-schweren pCAP. Das Erregerspektrum ist altersabhängig, zur Differenzierung zwischen viraler, bakterieller oder gemischt viral-bakterieller Infektion stehen jedoch keine zuverlässigen Biomarker zur Verfügung. Die meisten Kinder und Jugendlichen mit nicht-schwerer pCAP und O

Infection during pregnancy is common and the developing fetal brain is vulnerable to vertical transmission due to immaturity of the fetal immune system. Infection is a major cause of multiple organ abnormalities, including the neuraxis, due to the neurotropism of the infectious agents. This review sets out to give an overview of fetal infection, review the general principles of the nature and timing of the infectious insult with respect to outcomes, review the neuroimaging of infection by ultrasound and magnetic resonance imaging (MRI), and review the various pathogens involved, including the two most common, cytomegalovirus (CMV) and Toxoplasma, and also other common viral and nonviral infections.

Erratum zu: Monatsschr Kinderheilkd 2019 https://doi.org/10.1007/s00112-019-00767-0 In Tabelle 5 (Diagnostisches Vorgehen bei jungen Sauglingen imAlter ≤90 Tage mit Fieber ohne Fokus (FOF), S. 937) hat sich ein Fehler eingeschlichen. Dort ist unter „Korperliche Untersuchung“ bei „Vitalzeichen“ der …

Objectives To determine the existence of autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) in HIV patients and explore their association with biological features of HIV infection and different inflammatory biomarkers. We also evaluated their impact on CD4 + lymphocytes survival. Methods Anti-apoA-1 IgG plasma levels were assessed by ELISA in 237 HIV positive patients from a national prospective cohort with no current lipid-lowering therapy. Results 58% of patients were found positive for anti-apoA-1 IgG and were associated with lower CD4 + counts, but higher viremia and systemic inflammation. Logistic regression analyses indicated that high anti-apoA-1 IgG levels were associated with a 16-fold increased risk of displaying low CD4 + levels, independent of HIV RNA levels and treatment (adjusted Odds ratio [OR]:16.1, 95% Confidence Interval [95%CI]:1.80–143.6; p = 0.01), and a 6-fold increased risk of having a detectable viremia, independent of antiretroviral treatment (OR:5.47; 95% CI:1.63–18.36; p = 0.006). In vitro , anti-apoA-1 IgG induced dose and time-dependent CD4 + apoptosis that was increased by exposure to HIV RNA. Conclusions In HIV patients, anti-apoA-1 IgG levels are associated with low CD4+ counts, high viremia and a pro-inflammatory systemic profile. Anti-apoA-1 IgG can promote CD4+ lymphocyte apoptosis via undefined pathways.

BACKGROUND Drug resistance is a major barrier to successful antiretroviral treatment (ART). Therefore, it is important to monitor time trends at a population level. METHODS We included 11 084 ART-experienced patients from the Swiss HIV Cohort Study (SHCS) between 1999 and 2013. The SHCS is highly representative and includes 72% of patients receiving ART in Switzerland. Drug resistance was defined as the presence of ≥1 major mutation in a genotypic resistance test. To estimate the prevalence of drug resistance, data for patients with no resistance test was imputed based on the patient's risk of harboring drug-resistant viruses. RESULTS The emergence of new drug resistance mutations declined dramatically from 401 to 23 patients between 1999 and 2013. The upper estimated prevalence limit of drug resistance among ART-experienced patients decreased from 57.0% in 1999 to 37.1% in 2013. The prevalence of 3-class resistance decreased from 9.0% to 4.4% and was always

Currently, management of antibody deficient patients differs significantly among caregivers. Evidence and consensus based (S3) guidelines for the treatment of primary antibody deficiencies were developed to improve the management of these patients.

Toll-like receptors (TLRs) are key receptors of the innate immune system and show cell subset-specific expression. We investigated the messenger RNA (mRNA) expression of TLR genes in human haematopoietic stem cells (HSC), in naive B cells, in memory B cells, in plasma cells from palatine tonsils and in plasma cells from peripheral blood. HSC and plasma cells showed unrestricted expression of TLR1-TLR9, in contrast to B cells which lacked TLR3, TLR4 and TLR8 but expressed mRNA of all other TLRs. We demonstrated, for the first time, that TLR triggering of terminally differentiated plasma cells augments immunoglobulin production. Thus, boosting the immediate antibody response by plasma cells upon pathogen recognition may point to a novel role of TLRs.

Switzerland has a complex human immunodeficiency virus (HIV) epidemic involving several populations. We examined transmission of HIV type 1 (HIV 1) in a national cohort study. Latent class analysis was used to identify socioeconomic and behavioral groups among 6027 patients enrolled in the Swiss HIV Cohort Study between 2000 and 2011. Phylogenetic analysis of sequence data available for 4013 patients was used to identify transmission clusters. Concordance between sociobehavioral groups and transmission clusters was assessed in correlation and multiple correspondence analyses. A total of 2696 patients were infected with subtype B 203 with subtype C 196 with subtype A and 733 with recombinant subtypes (mainly CRF02\_AG and CRF01\_AE). Latent class analysis identified 8 patient groups. Most transmission clusters of subtype B were shared between groups of gay men (groups 1 3) or between the heterosexual groups ``heterosexual people of lower socioeconomic position{''} (group 4) and ``injection drug users{''} (group 8). Clusters linking homosexual and heterosexual groups were associated with ``older heterosexual and gay people on welfare{''} (group 5). ``Migrant women in heterosexual partnerships{''} (group 6) and ``heterosexual migrants on welfare{''} (group 7) shared non B clusters with groups 4 and 5. Combining approaches from social and molecular epidemiology can provide insights into HIV 1 transmission and inform the design of prevention strategies.}}}}}

This paper evaluates the strength of the balance sheet channel in the U.S. monetary policy transmission mechanism over the past three decades. Using a Factor-Augmented Vector Autoregression model on an expanded data set, including sectoral balance sheet variables, we show that the balance sheets of various economic agents act as important links in the monetary policy transmission mechanism. Balance sheets of financial intermediaries, such as commercial banks, asset-backed-security issuers and, to a lesser extent, security brokers and dealers, shrink in response to monetary tightening, while money market fund assets grow. The balance sheet effects are comparable in magnitude to the traditional interest rate channel. However, their economic significance in the run-up to the recent financial crisis was small. Large increases in interest rates would have been needed to avert a rapid rise of house prices and an unsustainable expansion of mortgage credit, suggesting an important role for macroprudential policies.

Immigrants from high-burden countries and HIV-coinfected individuals are risk groups for tuberculosis (TB) in countries with low TB incidence. Therefore, we studied their role in transmission of Mycobacterium tuberculosis in Switzerland. We included all TB patients from the Swiss HIV Cohort and a sample of patients from the national TB registry. We identified molecular clusters by spoligotyping and mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) analysis and used weighted logistic regression adjusted for age and sex to identify risk factors for clustering, taking sampling proportions into account. In total, we analyzed 520 TB cases diagnosed between 2000 and 2008; 401 were foreign born, and 113 were HIV coinfected. The Euro-American M. tuberculosis lineage dominated throughout the study period (378 strains; 72.7%), with no evidence for another lineage, such as the Beijing genotype, emerging. We identified 35 molecular clusters with 90 patients, indicating recent transmission; 31 clusters involved foreign-born patients, and 15 involved HIV-infected patients. Birth origin was not associated with clustering (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 0.73 to 3.43; P = 0.25, comparing Swiss-born with foreign-born patients), but clustering was reduced in HIV-infected patients (aOR, 0.49; 95% CI, 0.26 to 0.93; P = 0.030). Cavitary disease, male sex, and younger age were all associated with molecular clustering. In conclusion, most TB patients in Switzerland were foreign born, but transmission of M. tuberculosis was not more common among immigrants and was reduced in HIV-infected patients followed up in the national HIV cohort study. Continued access to health services and clinical follow-up will be essential to control TB in this population.

HIV-infected children have impaired antibody responses after exposure to certain antigens. Our aim was to determine whether HIV-infected children had lower varicella zoster virus (VZV) antibody levels compared with HIV-infected adults or healthy children and, if so, whether this was attributable to an impaired primary response, accelerated antibody loss, or failure to reactivate the memory VZV response.In a prospective, cross-sectional and retrospective longitudinal study, we compared antibody responses, measured by enzyme-linked immunosorbent assay (ELISA), elicited by VZV infection in 97 HIV-infected children and 78 HIV-infected adults treated with antiretroviral therapy, followed over 10 years, and 97 age-matched healthy children. We also tested antibody avidity in HIV-infected and healthy children.Median anti-VZV immunoglobulin G (IgG) levels were lower in HIV-infected children than in adults (264 vs. 1535 IU/L; P0.001) and levels became more frequently unprotective over time in the children [odds ratio (OR) 17.74; 95% confidence interval (CI) 4.36-72.25; P0.001]. High HIV viral load was predictive of VZV antibody waning in HIV-infected children. Anti-VZV antibodies did not decline more rapidly in HIV-infected children than in adults. Antibody levels increased with age in healthy (P=0.004) but not in HIV-infected children. Thus, antibody levels were lower in HIV-infected than in healthy children (median 1151 IU/L; P0.001). Antibody avidity was lower in HIV-infected than healthy children (P0.001). A direct correlation between anti-VZV IgG level and avidity was present in HIV-infected children (P=0.001), but not in healthy children.Failure to maintain anti-VZV IgG levels in HIV-infected children results from failure to reactivate memory responses. Further studies are required to investigate long-term protection and the potential benefits of immunization.

We examine the characteristics and comovement of cycles in house prices, credit, real activity and interest rates in advanced economies during the past 25 years, using a dynamic generalized factor model. House price cycles generally lead credit and business cycles over the long term, while in the short to medium term the relationship varies across countries. Interest rates tend to lag other cycles at all time horizons. While global factors are important, the U.S. business cycle, house price cycle and interest rate cycle generally lead the respective cycles in other countries over all time horizons, while the U.S. credit cycle leads mainly over the long term.

Recently, the export performance of France relative to its own past and relative to a major trading partner, Germany, deteriorated. That deterioration seems related to the geographical destination and product composition of trend exports. Faced with an increase in unit labor costs or in its terms of trade, France adjusts relatively less via price and wage changes, and more via employment changes. Given that SMIC convergence resulted in a significant increase in unit labor costs, foreign sector difficulties might be structural. Trade flows relevance and euro area policy constraints highlight the importance of structural reforms that increase markets flexibility.

BACKGROUND: Plasma HIV-1 RNA levels are high in vertically infected infants. Information in older children is limited, particularly in those who have not received antiretroviral therapy. OBJECTIVES: To describe the relationships between HIV-1 RNA, age and CD4 cell count in untreated vertically infected children. DESIGN: HIV-1 RNA was measured in 70 children [median age, 3.5 years (range, 0.4-11.9 years); median CD4 cell count, 881 x 10(6)/l (interquartile range, 576-1347 x 10(6) cells/l)] enrolled in a randomized placebo-controlled trial comparing immediate with deferred zidovudine in asymptomatic or mildly symptomatic vertically infected children (PENTA-1 trial). Short-term variability was assessed by comparing HIV-1 RNA at -2 and 0 weeks (prior to randomization). The relationship between age and HIV-1 RNA, and CD4 cell count was analysed using data from all children prior to randomization and sequential samples from 35 remaining on placebo for up to 105 weeks, by fitting mixed linear models. RESULTS: The within-individual SD in viral load was 0.26 log10 copies/ml. The median plasma HIV-1 RNA at enrollment was 4.61 log10 (range, 2.3-6.56 log10 copies/ml), significantly higher in children aged < or = 2 years (median, 5.23 log10 copies/ml) than in those aged > 2 years (4.51 log10 copies/ml; P < 0.0001). Mean HIV-1 RNA fell by 0.38 log10 copies/ml per year up to 2 years of age, by 0.21 log10 copies/ml per year from 2 to 4 years of age, and by 0.03 log10 copies/ml per year from 4 to 6 years of age reaching a nadir of 4.25 log10 copies/ml at 6 years. Mean log10 CD4 cell count declined steadily with age and was not significantly correlated with HIV-1 RNA, although there was some evidence that the rate of log10 CD4 cell decline was negatively correlated with the initial rate of HIV-1 RNA decline. No mutations associated with resistance to zidovudine were observed. CONCLUSIONS: Age is a key factor in the interpretation of both viral load and CD4 cell count in vertically infected children

Infections with varicella zoster virus (VZV) are common viral infections associated with significant morbidity. Diagnosis and management are complex, particularly in immunocompromised patients and during pregnancy. The present recommendations have been established by a multidisciplinary panel of specialists and endorsed by numerous Swiss medical societies involved in the medical care of such patients (Appendix). The aim is to improve the care of affected patients and to reduce complications.

Infections with varicella zoster virus (VZV) are common viral infections associated with significant morbidity. Diagnosis and management are complex, particularly in immunocompromised patients and during pregnancy. The present recommendations have been established by a multidisciplinary panel of specialists and endorsed by numerous Swiss medical societies involved in the medical care of such patients (Appendix). The aim was to improve the care of affected patients and to reduce complications.

This study identifies the main shocks that cause fluctuations in French output and their channels of transmission. It uses a large-dimensional structural approximate dynamic factor model. There are three main findings. First, common shocks, especially demand shocks, which seem to originate from the U.S., play an important role in explaining French economic activity. While international trade, relative prices, and FDI flows are the main channels of transmission, the stock market, consumer confidence, and interest rates also matter. Second, France's integration with the rest of the world has increased over time. Third, there is some tentative evidence of regional components in explaining French output fluctuations; countryspecific components also contribute. The predominance of exogenous factors affecting French output, the asymmetry in the transmission of shocks, and France's participation in a currency area, argue for making French goods, services, and labor markets as flexible as possible.

Definition. Unter Enzephalitis versteht man eine Entzundung des Hirnparenchyms. Sie kann durch eine virale Infektion bedingt sein und lasst sich dann in 4 Gruppen unterteilen (Tab. 205.1).

The body temperature is influenced among other things by time of day or age and exhibits a Gaussian inter-individual distribution. If measured orally, normal values vary between 35.6 degrees C and 38.2 degrees C. Temperature exceeding the 99th percentile (37.7 degrees C) can therefore be interpreted as fever. Nevertheless, an universally accepted definition of fever does not exist. Viral infection is the most frequent cause of acute fever in infants, even in the absence of a source. Bacterial infections are by far a rarer reason. Nevertheless, below the age of 3 years, acute fever is a ticklish issue because of the higher risk for rapidly evolving life-threatening invasive bacterial infections. Following introduction of vaccination against Haemophilus influenzae type b (Hib), Streptococcus pneumoniae has advanced to the most frequent cause of invasive bacterial infections in infants. Fever is rarely seen in newborns (age 1-28 days), but when present, it is more frequently serious. Around 12% of these newborns show an invasive bacterial infection. Therefore, a full workup for sepsis is strongly indicated. This includes cultures of blood,urine and cerebrospinal fluid plus a chest radiography. In addition, immediate start of an empirical intravenous antibiotic therapy and monitoring in a hospital setting are necessary. Apart from this exception, primary antibiotic therapy is rarely necessary in fever without a detectable focus and source. Also, routine prescription of antipyretics is not indicated. Though paracetamol may improve well-being and drinking behavior of infants, it does neither shorten the duration of fever duration, nor prevent febrile seizures.

Es werden Infekte der oberen und Infekte der unteren Atemwege unterschieden. Bezuglich der Infektionserreger stellen aber die Atemwege von der Nase bis zu den Alveolen ein Kontinuum dar. Gewisse Erreger zeigen Vorliebe fur bestimmte Abschnitte der Atemwege (Abb. 8.1).

Data on the weekly operating time of capital improve the measurement of effective capital input in production. The production function of the French business sector is found to be consistent with a Cobb-Douglas technology under constant returns to scale. Total factor productivity growth, estimated as an unobservable variable, has declined steadily since the late 1970s, but more slowly since 1994. During the 1990s, a secular increase in shift work raised the operating time of capital and began to contribute positively to growth, albeit only slightly.

This paper uses the classical (level) definition of business cycles to analyze the characteristics-duration, amplitude, steepness, and cumulative output movements-of the real GDP series of France, Germany, Italy, the rest of the euro area, and the United States. An index of concordance and its test statistic suggest a great deal of comovement/synchronization between output cycles. Following that result, a dynamic factor model is estimated. Output fluctuations are mostly explained by a global common component and an euro area common component. However, idiosyncratic components also matter, especially for France, the rest of the euro area, and the United States.

Introduction Treatment options for children with HIV-1 are limited. We aimed to compare activity and safety of three dualnucleoside analogue reverse-transcriptase inhibitor (NRTI) regimens with or without a protease inhibitor in previously untreated children with HIV-1. Methods In our multicentre trial, we randomly assigned 36 children to zidovudine and lamivudine, 45 to zidovudine and abacavir, and 47 to lamivudine and abacavir. Children who were symptomfree (n=55) were also randomly assigned to receive nelfinavir or placebo. Children with more advanced disease received open-label nelfinavir (73). Primary endpoints were change in plasma HIV-1 RNA at 24 and 48 weeks for the NRTI comparison and occurrence of serious adverse events for both randomised comparisons. Analyses were by intention to treat. Findings Children had a median CD4 percentage of 22% (IQR 15–29) and a mean HIV-1 RNA concentration of 5·0 log copies/mL (SD 0·8). One child was lost to follow-up and one died of sepsis. At 48 weeks, in the zidovudine/lamivudine, zidovudine/abacavir, and lamivudine/abacavir groups, mean HIV-1 RNA had decreased by 1·71, 2·19, and 2·63 log copies/mL, respectively (estimated in absence of nelfinavir) (p=0·02 after adjustment for baseline factors). One child had a hypersensitivity reaction to abacavir; and three with possible reactions stopped abacavir. There were 24 serious adverse events—six in the symptom-free children (all on nelfinavir), but none were attributed to nelfinavir. Interpretation Regimens containing abacavir were more effective than zidovudine/lamivudine. Such regimens could be combined with protease inhibitors and non-nucleoside reverse transcriptase inhibitors for safe and effective treatment of previously untreated children with HIV-1.

Since Taylor estimated a trade-off between inflation and output variance, it has been widely accepted that efforts to keep the inflation rate “too low and stable” will likely result in relatively larger output fluctuations. Following the generalized reduction in inflation variance in the 1990s, that concern was rekindled. This study estimates whether conditional output variance has changed in a sample of 12 countries. With the possible exception of Canada, there is no evidence of an increase in output variance. Either output variance has not changed (i.e., in Korea and Singapore) or has fallen (i.e., in Australia and New Zealand).

Fehlbildungen (Misbildungen, Anomalien) sind pranatal durch Anlagefehler entstandene Formabweichungen von Organen oder Korperteilen bei sonst normalen Geweben. Als Dysplasien werden morphologische Anomalien bezeichnet, die durch fehlerhafte Organisation und/oder Funktion von Gewebe oder Gewebekomponenten zustande kommen Von primaren Fehlbildungen sind sekundare Formabweichungen zu unterscheiden: Disruptionen (Defekte eines ursprunglich sich normal entwickelnden Organs, Organ- oder Korperteils), Deformitaten (durch mechanische Einflusse hervorgerufene Form- oder Lageanomalien eines Organs, Organ- oder Korperteils), Degeneration oder Deterioration. Kombinierte Anomalien (multiple Defekte) treten auf, wenn ein Entwicklungsfeld betroffen ist (polytope Felddefekte) oder pathogenetische Sequenzen entstehen (z.B. Potter-Sequenz bei Oligohydramnion). Fehlbildungssyndrome sind Muster angeborener Anomalien, die in ihrer Pathogenese sicher oder vermutlich zusammenhangen und nicht auf einen einzelnen morphologischen Defekt zuruckgefuhrt werden konnen, auch nicht Teil eines embryonalen Entwicklungsfeldes sind. Sie konnen Ausdruck pleiotroper Wirkung von Genmutationen sein und durch Chromosomenanomalien oder Teratogene hervorgerufen werden. Man unterscheidet sie von Assoziationen, die durch eine Storung in der fruhen Blastogenese entstehen, sowie von einem zufalligen Zusammentreffen verschiedener Anomalien, die sich in ihrer Pathogenese (noch) nicht verbinden lassen (Syntropie).

Knowledge concerning the long-term antiretroviral and immunological efficacy of protease inhibitors in children is limited.An open-label, prospective, multicenter clinical trial was conducted over a period of 72 weeks in Switzerland. 60 HIV-1 infected children (aged 0.3-16.9 years) naive to protease inhibitors were enrolled. Ritonavir or nelfinavir and at least one new nucleoside reverse transcriptase inhibitor were introduced into the current treatment regimen. HIV-1 RNA levels and CD4 cell counts were monitored after introducing the protease inhibitor, and the tolerability and safety of the drugs were assessed.Dictated by chronological availability, 37 children received ritonavir and 23 nelfinavir. At baseline, children given ritonavir had higher mean plasma HIV-1 RNA levels (5.03 vs 4.63 log10 copies/ml; p = 0.001) and lower mean CD4 cell counts (277 vs 555 cells/microl; p = 0.009) than children given nelfinavir. Antiretroviral treatment (ART) naive children showed higher mean plasma HIV-1 RNA levels than non-naive (5.18 vs 4.64 log10 copies/ml; p = 0.02). The decline in plasma HIV-1 RNA levels 72 weeks after treatment with ritonavir and nelfinavir was -2.17 and -1.30 log10 copies/ml, respectively (p = 0.006) and in ART-naive vs non-naive patients -2.70 vs -1.39 log10 copies/ml (por = 0.01). 69% of ART-naive patients and 32% of non-naive patients achieved sustained plasma HIV-1 RNA levels400 copies/ml. Increases in CD4 cells were higher in ART-naive compared to non-naive patients (p0.04).The antiretroviral and immunologic benefits of protease inhibitors are more profound in ART-naive than in non-naive children.

The paper estimates two time-varying parameter models of Chilean inflation: a Phillips curve model and a small open economy model. Their out-of-sample forecasts are compared with those of simple Box-Jenkins models. The main findings are; forecasts that include the pre-announced inflation target as a regressor are relatively better; the Phillips curve model outperforms the small open economy model in out-of-sample forecasts; and although Box-Jenkins models outperform the two models for short-term out-of-sample forecasts, their superiority deteriorates in longer forecasts. Adding a Markov-switching process to the models does not explain much of the conditional variance of the forecast errors.