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Objectives Echinocandins represent the first-line treatment of candidaemia. Acquired echinocandin resistance is mainly observed among Candida albicans and Candida glabrata and is associated with FKS hotspot mutations. The commercial Sensititre YeastOne™ (SYO) kit is widely used for antifungal susceptibility testing, but interpretive clinical breakpoints are not well defined. We determined echinocandins epidemiological cut-off values (ECV) for C. albicans/glabrata tested by SYO and assessed their ability to identify FKS mutants in a national survey of candidaemia. Methods Bloodstream isolates of C. albicans and C. glabrata were collected in 25 Swiss hospitals from 2004 to 2013 and tested by SYO. FKS hotspot sequencing was performed for isolates with an MIC≥ECV for any echinocandin. Results In all, 1277 C. albicans and 347 C. glabrata were included. ECV 97.5% of caspofungin, anidulafungin and micafungin were 0.12, 0.06 and 0.03 μg/mL for C. albicans, and 0.25, 0.12 and 0.03 μg/mL for C. glabrata, respectively. FKS hotspot sequencing was performed for 70 isolates. No mutation was found in the 52 ‘limit wild-type' isolates (MIC=ECV for at least one echinocandin). Among the 18 ‘non-wild-type' isolates (MIC>ECV for at least one echinocandin), FKS mutations were recovered in the only two isolates with MIC>ECV for all three echinocandins, but not in those exhibiting a ‘non-wild-type' phenotype for only one or two echinocandins. Conclusion This 10-year nationwide survey showed that the rate of echinocandin resistance among C. albicans and C. glabrata remains low in Switzerland despite increased echinocandin use. SYO-ECV could discriminate FKS mutants from wild-type isolates tested by SYO in this population.

Spinal epidural abscess (SEA) is a rare but severe infection requiring prompt recognition. The major prognostic factor for a favourable outcome is early diagnosis, leading to appropriate treatment. In clinical practice, a diagnosis of SEA is often not considered, particularly in the early stages of the disease when neurological symptoms are not apparent. Knowledge of persons at risk, clinical features and the required diagnostic procedures may decrease the number of initially misdiagnosed cases. Clinical signs, duration of symptoms and the rate of neurological deterioration show a high inter-individual variability, and the classic triad (spinal pain, fever and neurological deficit) is often not found, especially not at first presentation to a physician. However, most patients complain of severe localized back pain. Inflammatory parameters in the blood are generally elevated, but not specific. Gadolinium-enhanced magnetic resonance imaging is the most sensitive, specific and accurate imaging method. Although neurosurgical decompression is still the treatment of choice in the majority of cases, less invasive procedures (e.g. computed tomography-guided needle aspiration) or antimicrobial treatment alone can be applied in selected cases. The choice of the most appropriate therapy should be discussed immediately after a confirmed diagnosis in consultation with infectious disease, radiology and spinal surgery specialists. The outcome of SEA is largely influenced by the severity and duration of neurological deficits prior to surgery, stressing the importance of early recognition.

Background: Epidermodysplasia verruciformis (EV) is a rare autosomal-recessive disorder characterized by widespread and persistent infection with human papilloma virus (HPV) and a risk of malignant degeneration. Most cases of EV are caused by mutations in the two EV genes, EVER1/TMC6 and EVER2/TMC8. The clinical presentation of EV takes two different forms, which coexist in most cases. Over a period of years, patients develop plane warts and pityriasis versicolor-like lesions. Sixteen cases of EV in HIV-positive patients have been clinically investigated and reported in the literature. However, different inherited susceptibilities towards HPV infection in immunodeficient patients, like HIV-positive patients, have only rarely been addressed. Observation: We describe a 22-year-old female patient with a congenital HIV infection, who presented with slowly progressing and confluent erythematous papules on her hands and hypopigmented macules on her extremities. The histopathology was typical for EV, and HPV5 was detected by PCR and reverse hybridization. The 44-year-old HIV-positive mother has no typical EV lesions. The patient is homozygous for an A to T single nucleotide polymorphism (SNP) at position 917 of the TMC8/EVER2 gene. The mother of the patient is heterozygous for this SNP. Conclusion: These results support the hypothesis that the combination of immunodeficiency and a susceptibility allele may contribute to the differences in occurrence of EV in HIV-positive patients.

Atypische Mykobakterien sind Umweltsaphrophyten. Hautverletzungen konnen die Eintrittspforte fur lokalisierte Hautinfekte sein. Klinisch finden sich entzundliche Knoten, Plaques, Ulzera oder pannikulitisartige Lasionen. Disseminierte Hautinfekte treten vorwiegend bei Immunsupprimierten auf. Der Nachweis atypischer Mykobakterien erfolgt uber eine Gewebeprobe. Wichtig ist der kulturelle Nachweis, der haufig nur bei geausertem klinischem Verdacht gelingt, weil das Anzuchten einiger atypischer Mykobakterien spezielle Nahrboden und Anzuchttemperaturen erfordert. Das Buruli-Ulkus, durch M. ulcerans verursacht, ist die weltweit haufigste atypische Mykobakteriose und tritt in tropischen Regionen auf. In Europa ist das Schwimmbadgranulom, verursacht durch M. marinum, haufig. M.-avium-Komplex, M. kansasii und schnell wachsende Mykobakterien des M.-fortuitum-Komplexes sind weitere Verursacher kutaner Mykobakteriosen. Die Therapie ist schwierig, weil viele Keime resistent gegen gangige Antituberkulotika und Antibiotika sind.

Einleitung. Die Behandlung schwersterkrankter Patienten stellt eine grose medizinische und menschliche Herausforderung dar. Ziel der Studie war die Ermittlung der Mortalitat von Patienten mit langdauerndem intensivmedizinischem Aufenthalt sowie die Bestimmung des somatischen, psychischen und sozialen Status der Uberlebenden. Methoden. Die Daten aller Patienten, die mindestens 30 Tage auf einer chirurgischen Intensivstation behandelt waren, wurden retrospektiv nach Alter, Geschlecht, Art der Grunderkrankung, APACHE-II-Score, ISS, Vorerkrankungen, Behandlungsmasnahmen, Komplikationen, Art und Ausmas der Storungen von Organsystemen und Mortalitat analysiert. Die Uberlebenden wurden nach 35±14 Monaten nachuntersucht. Von ihnen wurden somatische, psychische und soziale Parameter erhoben. Ergebnisse. Es wurden die Daten von 101 Patienten analysiert (m/w: 78/23, mittleres Alter: 49,9±18,2 Jahre, mittlere Liegedauer: 57±37 Tage, Anteil Traumapatienten: 46%). 31 Patienten verstarben auf der Intensivstation. Bis zur Nachuntersuchung verstarben weitere 24 Patienten. Damit fand sich eine Gesamtmortalitat von 55%. Alter, Art der Grunderkrankung und Ausmas des Multiorganversagens beeinflussten das Versterben auf der Intensivstation. Die Mortalitat nach Entlassung zeigte eine Abhangigkeit von Alter, Anzahl der Vorerkrankungen und der Grunderkrankung. Von den uberlebenden 46 Patienten konnten 41 (89%) nachuntersucht werden. Knapp die Halfte wiesen in allen Funktionsbereichen keine oder nur geringe Einschrankungen auf, bei einem Drittel fanden sich schwerste Beeintrachtigungen. Traumapatienten zeigten die geringste Mortalitat aber schlechtere Rehabilitationsergebnisse. Schlussfolgerungen. Einerseits besteht nach Langzeitintensivtherapie eine deutlich erhohte Mortalitat im Vergleich zu einer durchschnittlichen intensivmedizinischen Behandlung. Andererseits konnen die uberlebenden Patienten nach uberstandener Akutphase in der Mehrheit erfolgreich somatisch, psychisch und sozial rehabilitiert werden. Deren Langzeitergebnis ist mit dem nach durchschnittlicher intensivmedizinischer Behandlung vergleichbar. Die Behandlungsergebnisse ermutigen zum konsequenten Einsatz aller medizinischen Moglichkeiten.

Untersuchungen zur Haufigkeit, Relevanz und Versorgung praklinischer psychiatrischer Notfalle beschreiben bislang lediglich Teilaspekte. Ziel der Untersuchung war die umfassende Darstellung psychiatrischer Notfalle nach Haufigkeit, Diagnose und Therapie. Hierzu wurden die Notarztprotokolle eines norddeutschen Landkreises ausgewertet und parallel Notarzte und Rettungsdienstmitarbeiter hinsichtlich Haufigkeit, Wertigkeit und Umgang mit psychiatrischen Notfallsituationen mittels eines validierten Fragebogens befragt. Danach stellen psychiatrische Notfalle mit 9,2% die dritthaufigste Einsatzursache dar, den grosten Anteil nahmen dabei Suchterkrankungen (70%) ein. Suizidalitat lag bei ca. 33% vor. Eine spezifische Therapie psychiatrischer Erkrankungen findet so gut wie nie statt. Bei der Befragung hielten sowohl Notarzte wie Rettungssanitater psychiatrische Kenntnisse fur wichtig, schatzten die eigenen Kenntnisse aber als nur gering ein. Bei der Beantwortung 5 typischer Notfallsituationen wurde von den Notarzten in 71% die richtige Diagnose (Rettungsdienstmitarbeiter: 39%) und in 32% die richtige Therapie (Rettungsdienstmitarbeiter: 14%) angegeben. Die Fortbildungsbereitschaft war hoch und wurde signifikant wichtiger von Notarzten mit langerer Diensterfahrung beurteilt. Praklinische psychiatrische Notfalle sind haufig und stellen das behandelnde Personal vor grose Anforderungen. Eine ausreichende Ausbildung findet bislang nicht statt. Gefordert sind Fortbildungsprogramme zu Diagnostik und Therapie psychiatrischer Notfalle. Die Motivation zur Teilnahme ist hoch.

OBJECTIVES To investigate the influence of interferon (IFN) beta-1b on the serum levels of sTNF-R1, sTNF-R2 and TNF-beta in patients with multiple sclerosis (MS) in correlation with clinical and MRI activity. MATERIALS AND METHODS Serum samples were obtained every 3 months from 24 patients treated with 8 x 10(6) U of IFN beta-lb every other day (treatment group) and from 21 patients without any immunomodulatory therapy (control group) over a 15-month observation period. The cytokine levels were measured by ELISA. Cranial MRI was performed every 6 months to determine the burden of disease of every patient. RESULTS In the treatment group we found an obvious increase of sTNFR1 and sTNF-R2 (P < 0.001) and relatively stable serum levels of TNFbeta with no statistical significance (P = 0.56). In the control group, sTNF-R1 showed a significant decrease (P < 0.001) during the same observation period of 15 months. During the 15-month observation period, the MRI-responders group had significant larger mean AUC (area under the concentration-time curve) values of sTNF-R1 (P = 0.04) and sTNF-R2 (P = 0.01) when compared to the group of MRInonresponders. CONCLUSION The present data suggest that IFN beta-1b induces the expression and shedding of TNF-R1 and TNF-R2. The magnitude of an increase of sTNF-Rs may be a marker for the effectiveness of treatment with IFN beta-1b.

The objective of this study was to investigate the effect of interferon (IFN) beta-1b on the serum levels of soluble tumor necrosis factor receptor 1 (sTNF-R1) and sTNF-R2 in patients with multiple sclerosis (MS) in correlation with clinical and magnetic resonance image (MRI) activity. Serum samples were obtained every 3 months from 24 patients treated with 8 × 106 U of IFN beta-1b every other day (treatment group) and from 21 patients without any immunomodulatory therapy (control group) over a 15-month observation period. The cytokine receptor levels were assessed by ELISA. Cranial MRI was performed every 6 months to determine the burden of disease. In the treatment group, the MRI responders had significantly larger mean values for the area under the concentration-time curve of sTNF-R1 (p = 0.04) and sTNF-R2 (p = 0.01) when compared to the MRI nonresponders during the 15-month observation period. With regard to an increase in sTNF-R1 and -2 of more than 20% during the first 3 months of treatment, we observed a sensitivity of 33 and 58%, respectively, a specificity of 90 and 60%, respectively, and a positive predictive value of 80 and 64%, respectively, for MRI response during the 15-month observation period. A decrease in sTNF-R1 and -2 of more than 20% during the first 3 months of treatment had a sensitivity of 40 and 20%, respectively, a specificity of 100 and 100%, respectively, and a positive predictive value of 100 and 100%, respectively, for further MRI nonresponse (during the 15-month observation period). The present data suggest that assessment of sTNF-Rs may contribute to the identification of subgroups of patients who are likely to respond better than others to treatment with IFN beta-1b. This could help to establish a cost-effective prescription pattern for this expensive treatment, which is of importance for the future management of patients with MS.

Fragestellung. Die Langzeitbehandlung auf Intensivstationen (ICU) bedeutet eine erhebliche somatische, psychische und soziale Belastung fur die Patienten. Um die Ergebnisse im Langzeitverlauf beurteilen zu konnen, wurden nach der Entlassung Lebensqualitat und Gesundheitszustand von Uberlebenden untersucht. Methodik. Alle Patienten, die wahrend eines 4 Jahres Zeitraumes auf einer operativen ICU mindestens 30 Tage in Behandlung gewesen waren, wurden in die Untersuchung eingeschlossen. Die Uberlebenden wurden 35±14 Monate nach der Entlassung korperlich untersucht und ausfuhrlich befragt. Zur Anwendung kamen auserdem Selbst- und Fremdbeurteilungsskalen (Munchner Inventar fur Lebensqualitat und Gesundheit, POMS, Spitzer Quality-of-life-Index). Ergebnisse. 101 Patienten wurden mindestens 30 Tage behandelt. Die Mortalitat bis zur Nachuntersuchung betrug 55%. Von den 46 verbleibenden Patienten konnten 41 (89%) untersucht werden (m/w=31/10; Alter 41,6±17,2 Jahre; Liegedauer 51±19 Tage; Diagnosen: Trauma n=32, andere n=9). Je ein Drittel der Patienten zeigten keine, mittlere oder schwere korperliche Beeintrachtigungen. Lebensqualitat und Gesundheit wurden von ca. der Halfte, unabhangig vom Testverfahren, als zufriedenstellend beurteilt. Traumapatienten waren in allen Bereichen starker belastet. Es zeigte sich keine Abhangigkeit von Alter, Geschlecht und Zeitraum bis zur Nachuntersuchung. Schlussfolgerungen. Patienten nach Langzeitintensivbehandlung weisen etwa zur Halfte deutliche Einschrankungen ihrer Lebensqualitat auch als Folge der Erkrankung oder Behandlung auf. Besonders Traumapatienten geben trotz somatisch zufriedenstellender Behandlungsergebnisse erhebliche Probleme im psychosozialen Bereich an, die rehabilitativen Masnahmen zuganglich sind.

Objective The aim of this study was to investigate clinical and sonographic parameters, in particular Doppler blood flow measurements, in severe second-trimester twin–twin transfusion syndrome before and after endoscopic laser coagulation of the placental vascular anastomoses, to correlate these data with fetal outcome and to determine whether fetal blood flow measurements could help to estimate the probability of fetal survival. Methods In 121 cases of severe twin–twin transfusion syndrome examined between 17 and 26 weeks of gestation, the following investigations were performed: fetal biometry, placental location, deepest pool of amniotic fluid, echocardiography and Doppler sonography of the umbilical arteries and the ductus venosus of both twins before and after fetoscopic laser ablation of the placental anastomoses. Results The overall survival rate was 64% (156/242). Both fetuses survived in 48% (58/121) and one fetus survived in 33% (40/121), resulting in 81% (98/121) of pregnancies with at least one survivor. Gestational age at the time of the procedure and placental location had no significant influence on fetal survival. The amniotic fluid volume drained after laser coagulation correlated significantly (p = 0.038) with the risk of miscarriage or extremely premature delivery within 4 weeks of the procedure. Intertwin discrepancy in abdominal circumference showed a significant negative correlation (p = 0.004) with the probability for survival of donor fetuses. Before the procedure, 19% (23/121) of donor twins and 5% (6/121) of recipient twins showed absent or reversed end-diastolic flow in the umbilical artery (p = 0.001). This finding had no significant influence on the survival rate of donors. An increase of waveform indices in the umbilical artery 1 day after the procedure compared to immediately after the procedure correlated significantly with a lower probability for survival of donors (p = 0.042) and recipients (p = 0.018). Before the procedure, 37% (45/121) of recipient twins and 9% (10/113) of donor twins showed absent or reversed flow during atrial contraction in the ductus venosus (p < 0.0001). This finding had a significant negative influence on the survival rate of recipient fetuses (p = 0.02). Furthermore, an increase of waveform indices in the ductus venosus 1 day after the procedure compared to immediately after the procedure correlated significantly with a lower probability of survival in recipients (p = 0.005). Conclusions Fetoscopic laser coagulation of the placental vascular anastomoses in severe mid-trimester twin–twin transfusion is a potentially corrective and effective, minimally invasive procedure. Doppler investigation of the umbilical and fetal circulations provides important information on the fetal condition, prognosis and therapeutic effects of the intervention. Signs of congestive heart failure in the recipient may reduce the probability of survival, whereas increased placental resistance in the donor before the procedure is not necessarily associated with a reduction in the probability of survival after laser coagulation. Copyright © 1999 International Society of Ultrasound in Obstetrics and Gynecology

Das Auftreten von Aortendissektionen nach primar erfolgreich durchgefuhrtem Aortenklappenersatz ist in seinen Entstehungsmechanismen nicht geklart. Auch ist unklar, ob sich Patienten mit Risiko fur eine spatere Dissektion bereits zum Zeitpunkt des elektiven Aortenklappenersatzes identifizieren lassen.

Es wurden Tumorgewebsproben von 110 Patienten mit Plattenepithelkarzinomen der Kopf-Hals-Region (KHPEK) untersucht. Mit Hilfe der Polymerasekettenreaktion (PCR) und anschliesender Temperaturgradientengelelektrophorese (TGGE) konnten in 48/110 Tumoren (44%) Mutationen in den Exons 5–8 des p53-Gens nachgewiesen werden. Die Sequenzierung der PCR-Produkte ergab in den meisten Fallen Missense-Mutationen. Die Mutationshaufigkeit korrelierte nicht mit dem Tumorstadium, dem Differenzierungsgrad der Tumoren, dem Lymphknotenstatus oder dem Tabakkonsum der Patienten. Infektionen mit den High-Risk-HPV-Typen 16 und 18 zeigten 39/92 Tumoren (42%). Die Gesamtuberlebensrate der Patienten korrelierte nicht mit der p53-Mutationsfrequenz und der HPV-Infektionsrate. Das Fehlen einer statistisch signifikanten Korrelation mindert jedoch nicht die mogliche Bedeutung dieser Faktoren fur die fruhen Phasen der Tumorentstehung.

Patients not having a general practitioner will more likely use the emergency departments (ED) of hospitals for primary care. Crowding of the ED due to patients with minor health problems is a growing burden. The present work was aimed to analyze data of ED consultations at a Swiss regional hospital. Leading diagnoses of ED consultations covered a broad spectrum of internal medicine. The majority of patients seen in the ED are «walk-in» patients with minor problems that after initial evaluation and treatment in the ED could be managed as outpatients. Pediatric patients made a considerable part of the workload. Elderly patients (65 years) were hospitalized more often.

Epidermodysplasia verruciformis (EV) is a rare autosomal-recessive disorder characterized by widespread and persistent infection with human papilloma virus (HPV) and a risk of malignant degeneration. Most cases of EV are caused by mutations in the two EV genes, EVER1/TMC6 and EVER2/TMC8. The clinical presentation of EV takes two different forms, which coexist in most cases. Over a period of years, patients develop plane warts and pityriasis versicolor-like lesions. Sixteen cases of EV in HIV-positive patients have been clinically investigated and reported in the literature. However, different inherited susceptibilities towards HPV infection in immunodeficient patients, like HIV-positive patients, have only rarely been addressed.We describe a 22-year-old female patient with a congenital HIV infection, who presented with slowly progressing and confluent erythematous papules on her hands and hypopigmented macules on her extremities. The histopathology was typical for EV, and HPV5 was detected by PCR and reverse hybridization. The 44-year-old HIV-positive mother has no typical EV lesions. The patient is homozygous for an A to T single nucleotide polymorphism (SNP) at position 917 of the TMC8/EVER2 gene. The mother of the patient is heterozygous for this SNP.These results support the hypothesis that the combination of immunodeficiency and a susceptibility allele may contribute to the differences in occurrence of EV in HIV-positive patients.

Objective To assess outcome after fetoscopic laser coagulation (FLC) of placental vascular anastomoses with the 30° fetoscope in mid-trimester severe twin-to-twin transfusion syndrome (TTTS) with completely anterior placenta compared with the regular 0° fetoscope in TTTS with other placental locations. Methods This was a prospective study of 176 consecutive monochorionic twin pregnancies undergoing FLC for severe TTTS. Of these, 51 patients required use of the 30° fetoscope (study group) and 125 placental locations permitted use of the 0° fetoscope (controls). Results The two groups had very similar outcomes. The median gestational age at FLC in the study group vs. control group was 21.0 (range, 17.4–24.6) weeks vs. 20.6 (range, 15.9–24.6) weeks. Both fetuses survived in 58.8% (30/51) of study patients vs. 66.4% (83/125) of controls. At least one fetus survived in 84.3% (43/51) of study patients and 88.8% (111/125) of controls (P = 0.45). Study patients delivered at a median of 34.1 (range, 25.0–38.4) weeks and controls at 34.0 (range, 25.0–40.3) weeks' gestation. Conclusions Use of a 30° fetoscope for FLC in cases of technically challenging extensive anterior placentation is associated with an outcome that is very similar to that achieved when a 0° fetoscope is used in cases of more favorable placental location. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.

OBJECTIVE: Particularly for therapy-experienced patients, resistance assessment by genotypic or phenotypic methods produces discordances. This study seeks proof that differences may arise from the fact that genotyping produces a single summary sequence whereas replicative phenotyping (rPhenotyping) functionally detects and assigns resistances in mixed HIV populations. METHODS: For validation, defined mixes of wild-type and M184V mutant were analysed by rPhenotyping or standard genotyping. Allele-specific and quantitative polymerase chain reaction (PCR) set detection and quantification limits for minor virus populations in vitro and in authentic clinical samples showing geno-/pheno-discrepant lamivudine resistance. RESULTS: Allele-specific and real-time PCR methods detected down to 0.3% of mutant M184V. The functional assessment was sensitive enough to reveal >1% of mutant M184V in mixed samples. Also in discordant samples from the diagnostic routine, in which rPhenotyping had identified drug resistance, real-time PCR confirmed minute amounts of mutant M184V. CONCLUSION: By utilizing the replication dynamics of HIV under drug pressure, a rPhenotyping format potently reveals relevant therapy-resistant minority species, even of HIV known to possess reduced replicative fitness. With its rapid turnaround of 8 days and its high sensitivity, our rPhenotyping system may be a valuable diagnostic tool for detecting the early emergence of therapy-threatening HIV minorities or the persistence of residual resistant virus.

Atypical mycobacteria are environmental saprophytes. Occasionally they may enter human skin through injuries and cause localized infection. Papules, nodules, plaques, ulcers and panniculitis-like lesions are common manifestations. Disseminated infection occurs in immunocompromised patients. Evidence of mycobacterial infection can be obtained by tissue specimens, culture being most important for diagnosis. Because many mycobacteria only grow on special media and at special temperatures it is crucial that clinical suspicion is raised so correct testing is performed. Buruli ulcer caused by M. ulcerans is the most prevalent atypical mycobacteriosis worldwide; its occurrence is restricted to tropical areas. In European countries fish tank granuloma caused by M. marinum is most commonly observed. M. avium-complex, M. kansasii und rapidly growing mycobacteria of M. fortuitum-complex are other atypical mycobacteria that can cause cutaneous infection. Treatment is difficult because many atypical mycobacteria are resistant to common antibiotics.

Objectives To assess the natural history and perinatal outcome in monochorionic diamniotic twin pregnancies with discordant amniotic fluid volume without signs of severe twin–twin transfusion syndrome (TTTS). Methods This was an observational study of 84 consecutive monochorionic twin pregnancies which did not meet the criteria for severe TTTS and endoscopic laser coagulation of placental anastomoses at initial presentation. The population was subdivided into two groups. Group 1 consisted of 64 pregnancies (median gestational age, 20.1 (range, 15.6–24.7) weeks) with amniotic fluid discordance and no signs of congestive heart failure in the twin with the larger amniotic fluid volume (Twin 1) and positive end-diastolic flow in the umbilical artery of the twin with the smaller amniotic fluid volume (Twin 2). Group 2 (median gestational age, 19.1 (range, 16.0–24.4) weeks) consisted of 20 pregnancies with amniotic fluid discordance and intrauterine growth restriction (IUGR) (abdominal circumference < 5th percentile) in combination with absent or reversed end-diastolic (ARED) flow in the umbilical artery of Twin 2. After exclusion of one patient from Group 1, who opted for termination of pregnancy, nine patients in Group 1 and one in Group 2 developed severe TTTS, and laser coagulation was offered. The remaining 54 pregnancies of Group 1 were compared with the remaining 19 pregnancies of Group 2. Results Fetuses in Group 1 showed significantly higher survival rates (overall survival, 100/108 (92.6%) vs. 23/38 (60%), P < 0.0001; survival of both fetuses, 49/54 (90.7%) vs. 9/19 (47.4%), P = 0.0002) and median gestational age at delivery (33.6, (range, 27.6–37.8) weeks vs. 32.0 (range, 26.9–36.3) weeks, P = 0.0457). Overall, there was a significantly higher incidence of complications, defined as necessity for intrauterine intervention, fetal or neonatal death or delivery prior to 32 weeks, in Group 2 (Group 1: 30/63 (47.6%); Group 2: 16/20 (80%), P = 0.0188). Conclusions Our data suggest that amniotic fluid discordance in monochorionic diamniotic twin pregnancies in combination with IUGR and umbilical artery ARED flow in one fetus represents an extremely high-risk constellation for adverse pregnancy outcome. Copyright © 2005 ISUOG. Published by John Wiley & Sons, Ltd.

An immunocompetent patient recovering from gallstone-induced pancreatitis had to be readmitted due to abdominal pain, fever, and rapid deterioration. Computed tomography guided needle aspiration established the diagnosis of pancreatic necrosis infection; microbiological investigations revealed monoinfection with Lactobacillus paracasei subspecies tolerans. To our knowledge, this is the first description of a pancreatic necrosis infection due to L. paracasei in an immunocompetent patient without any known risk factors for Lactobacillus infections.

When to start or change antiretroviral treatment against HIV infection is of major importance. Patients’ readiness is considered a major factor influencing such treatment decisions, in particular because no objective, absolute time point when to start antiretroviral therapy exists. We aimed at evaluating patients’ readiness to start or change antiretroviral therapy (ART). HIV–infected patients starting or changing ART between July 2002 and February 2003, treating physicians and nurses participated in this prospective, observational multicenter study. We assessed shared decision–making including qualitative aspects, expected treatment decisions and treatment status after 3 months. 75 patients were included. Of 34 patients for whom starting ART was considered, 27 (79%) indicated that they were willing to start treatment. After 3 months, 21 of 27 (78%) actually started therapy, six did not. Patients with depression were less likely to be ready for ART (p < 0.05). Of 41 patients for whom changing ART was considered, 35 (85%) indicated that they were willing to change treatment. Of the latter 35 patients, 33 (94%) finally changed ART within 3 months. Physicians and nurses were too optimistic in predicting the start or change of ART. The main reason to start or change ART was the sole recommendation of the physician (52% in those starting, 61% in those changing ART). Patients mainly judged the decision as shared and were very satisfied (71%) with the process. Qualitative findings revealed the importance of a dialectic decisionmaking, described with two categories: “dealing with oneself and others”‚ and “understanding and being understood.” Patients mainly shared the decision made during consultation. Although physicians have an essential role concerning ART, patients, physicians, and nurses all contribute to the decision. Qualitative findings indicate the importance for health–care providers to include patients’ expertise and contributions.

Objectives– Multiple sclerosis (MS) is believed to be an autoimmune disease of the human central nervous system mediated by autoreactive T cells. Interferon-β1b (IFN-β1b) has been shown to be effective in reducing disease activity defined by clinical and magnetic resonance imaging (MRI) criteria in relapsing–remitting MS (RRMS). Yet, the exact mechanisms by which these benefits are achieved remain unknown. CD45RA is a marker for naive T lymphocytes and intercellular adhesion molecule-3 (ICAM-3) is expressed on resting lymphocytes. Material and methods– Forty-eight patients with RRMS, 24 of them treated with recombinant IFN-β1b and 24 untreated, were enrolled in this prospective study over 18 months. We investigated the percentage of CD45RA+ ICAM-3+ cells within the total lymphocyte subset in the peripheral blood serially every 3 months and in CSF once at baseline. Detailed clinical examination including Expanded Disability Status Scale (EDSS) score was performed every 3 months and cranial MRI scans were assessed every 6 months. Results– We found a temporary increase in the CD45RA+ ICAM-3+ lymphocyte ratio in peripheral blood of both untreated and IFN-β1b-treated RRMS patients. Moreover, we determined a significant negative correlation (r = −0.5874; P

The treatment of severely ill patients remains a medical and human challenge. The aim of the study was to determine the survival rate of patients with prolonged intensive care unit (ICU) treatment. Additionally, the somatic, psychological, and social sequelae of the survivors should be determined.Data of all patients who stayed for at least 30 consecutive days on a surgical ICU were evaluated with respect to age, sex, diagnosis on admission, APACHE II-Score, ISS, pre-existing diseases, therapeutic procedures, complications, organ dysfunctions, and mortality. The survivors passed a follow-up examination after 35 +/- 14 months. This included somatic, psychological, and social parameters.Data of 101 patients were analysed (m/f: 78/23, mean age: 49.9 +/- 18.2 years, mean stay on ICU: 57 +/- 37 days, trauma patients: 46%). 31 subjects died on the ICU. Until the follow-up, another 24 patients deceased. Thus, the total mortality rose to 55%. Age, diagnosis on admission and severity of organ failure influenced the ICU mortality. Concerning the mortality after discharge, age, pre-existing morbidity and diagnosis on admission affected the outcome. 41 of the remaining 46 patients (89%) underwent the follow-up. Nearly half of them showed no or minor signs of impairment in any of the investigated areas. One third had severe handicaps. Trauma patients had the lowest mortality rates but showed worse results in rehabilitation.The mortality after prolonged ICU-treatment is substantially higher compared to average ICU patients. However, having survived the acute phase of the illness, successful rehabilitation in somatic, psychic as well as social terms could be performed to a considerable extent. This outcome is comparable to the one of other ICU populations. The results encourage to a consequent use of all medical options.

Patients with myelodysplasia are susceptible to infections due to their compromised immunity. If presenting with a cervical lymphadenopathy patients must, in addition to other causes, be evaluated for tuberculosis, especially if they show a concurrent erythema nodosum.

We present a patient who was hospitalized due to a purulent skin lesion with a surrounding erythematous area in the region of the right paranasal crease accompanied by a swelling of the right eyelid. Initially the diagnosis of a carbuncle caused by an infection with Staphylococcus aureus was supposed. A surgical debridement was performed and an antibiotic therapy was started. Only special microbial investigations requested by the clinician led to the diagnosis of a cutaneous infection with Nocardia brasiliensis. The presented case is remarkable because the nocardia infection was in an immune-competent patient and the patient showed a primary cutaneous nocardiosis without dissemination.

Preclinical psychiatric emergency situations (PES) rank third in frequency of calls in the German emergency medical system (EMS). However, few data exist concerning relevance and treatment of PES. The aim of this study was to investigate this relevance in preclinical EMS and its appraisal by emergency physicians and paramedics. The protocols filled in by EMS physicians on emergency duty in a German district were evaluated concerning PES. In addition, the emergency physicians and paramedics of the district were asked to complete a validated questionnaire concerning the importance, their own understanding of PES, and interest in training programs. With 9.2%, preclinical PES ranked third in frequency of all EMS calls. The most frequent case was substance abuse disorder (70%), followed by suicide attempts or ideation (33%). Specific therapy for psychiatric disorders is hardly ever performed. Emergency physicians and paramedics estimated the importance of knowledge about PES as high but rated their own knowledge as poor. Assessing five typical PES, emergency physicians gave the correct diagnoses in 71% of cases (paramedics 39%) and the correct therapy in 32% (paramedics 14%). The interest in training programs was significantly higher in experienced EMS physicians. Preclinical PES is a relevant diagnosis within EMS and correct treatment is hampered by limited knowledge. Sufficient training is not yet available, although programs are necessary and the willingness to participate in them is high.

To investigate the influence of interferon (IFN) beta-1b on the serum levels of sTNF-R1, sTNF-R2 and TNF-beta in patients with multiple sclerosis (MS) in correlation with clinical and MRI activity.Serum samples were obtained every 3 months from 24 patients treated with 8 x 10(6) U of IFN beta-lb every other day (treatment group) and from 21 patients without any immunomodulatory therapy (control group) over a 15-month observation period. The cytokine levels were measured by ELISA. Cranial MRI was performed every 6 months to determine the burden of disease of every patient.In the treatment group we found an obvious increase of sTNFR1 and sTNF-R2 (P0.001) and relatively stable serum levels of TNFbeta with no statistical significance (P = 0.56). In the control group, sTNF-R1 showed a significant decrease (P0.001) during the same observation period of 15 months. During the 15-month observation period, the MRI-responders group had significant larger mean AUC (area under the concentration-time curve) values of sTNF-R1 (P = 0.04) and sTNF-R2 (P = 0.01) when compared to the group of MRInonresponders.The present data suggest that IFN beta-1b induces the expression and shedding of TNF-R1 and TNF-R2. The magnitude of an increase of sTNF-Rs may be a marker for the effectiveness of treatment with IFN beta-1b.

Long-term treatment in surgical intensive care units (SICU) subjects the patient to a high degree of somatic, psychological, and social stress. The aim of this study was to determine their outcome in terms of quality of life and health status.All patients from a 4-year period in a SICU with a length of stay (LOS) of 30 days or more were included. All survivors were interviewed and examined after 35 +/- 14 months; they also completed several questionnaires (Munich Inventory for Quality of Life and Health Status, POMS, and Spitzer Quality of Life Index).One hundred one patients fulfilled the inclusion criteria, and 46 survived until follow-up. Forty-one (89%) could be traced and examined. Male:female ratio was 31:10, age 42 +/- 17 years, and LOS 51 +/- 19 days, Diagnoses on admittance were multiple trauma (n = 32) and other (n = 9). When classifying patients according to physical impairment, one third each showed no, mediocre, or severe limitations. Subjective appraisal of quality of life and well-being was sufficient for about half the patients in every test. Trauma victims experienced more severe impairment of quality of life. There were no differences between sex, age, or time until follow-up.After prolonged SICU treatment, about half of the patients report limitations in their quality of life as a result of their illness and the subsequent treatment. Some patients, in particular after trauma, exhibit striking psychosocial problems despite satisfactory somatic treatment results. These problems can be positively addressed in rehabilitative efforts.

The aim of this study was to investigate clinical and sonographic parameters, in particular Doppler blood flow measurements, in severe second-trimester twin-twin transfusion syndrome before and after endoscopic laser coagulation of the placental vascular anastomoses, to correlate these data with fetal outcome and to determine whether fetal blood flow measurements could help to estimate the probability of fetal survival.In 121 cases of severe twin-twin transfusion syndrome examined between 17 and 26 weeks of gestation, the following investigations were performed: fetal biometry, placental location, deepest pool of amniotic fluid, echocardiography and Doppler sonography of the umbilical arteries and the ductus venosus of both twins before and after fetoscopic laser ablation of the placental anastomoses.The overall survival rate was 64% (156/242). Both fetuses survived in 48% (58/121) and one fetus survived in 33% (40/121), resulting in 81% (98/121) of pregnancies with at least one survivor. Gestational age at the time of the procedure and placental location had no significant influence on fetal survival. The amniotic fluid volume drained after laser coagulation correlated significantly (p = 0.038) with the risk of miscarriage or extremely premature delivery within 4 weeks of the procedure. Intertwin discrepancy in abdominal circumference showed a significant negative correlation (p = 0.004) with the probability for survival of donor fetuses. Before the procedure, 19% (23/121) of donor twins and 5% (6/121) of recipient twins showed absent or reversed end-diastolic flow in the umbilical artery (p = 0.001). This finding had no significant influence on the survival rate of donors. An increase of waveform indices in the umbilical artery 1 day after the procedure compared to immediately after the procedure correlated significantly with a lower probability for survival of donors (p = 0.042) and recipients (p = 0.018). Before the procedure, 37% (45/121) of recipient twins and 9% (10/113) of donor twins showed absent or reversed flow during atrial contraction in the ductus venosus (p0.0001). This finding had a significant negative influence on the survival rate of recipient fetuses (p = 0.02). Furthermore, an increase of waveform indices in the ductus venosus 1 day after the procedure compared to immediately after the procedure correlated significantly with a lower probability of survival in recipients (p = 0.005).Fetoscopic laser coagulation of the placental vascular anastomoses in severe mid-trimester twin-twin transfusion is a potentially corrective and effective, minimally invasive procedure. Doppler investigation of the umbilical and fetal circulations provides important information on the fetal condition, prognosis and therapeutic effects of the intervention. Signs of congestive heart failure in the recipient may reduce the probability of survival, whereas increased placental resistance in the donor before the procedure is not necessarily associated with a reduction in the probability of survival after laser coagulation.

Dissection of the ascending aorta (type A) following later after aortic valve replacement has been described with increasing frequency. This study analyzes the role of aortic valve replacement for the evolution of late dissection. In a series of 80 consecutive patients with type A dissection, a previous aortic valve replacement had been performed in 12 cases (15%). In addition to arterial hypertension (p0.001) and Marfan syndrome (p0.01), multivariate analysis identified previous aortic valve replacement (p0.01) as an independent predisposing factor for type A dissection. Dissection occurred 3 +/- 4 years after aortic valve replacement with a clinical and anatomical profile similar to classic dissection as proven by comparison to a group of 62 patients with classic dissection associated with arterial hypertension or Marfan syndrome. With 75% and 66%, respectively, 30 day and 1 year survival of patients with dissection following later after aortic valve replacement was similar to patients with classic type A dissection. Extensive thinning and/or fragility (p0.05) of the aortic wall in the presence of a mildly dilated aorta (45 +/- 5 mm) at the time of aortic valve replacement was associated with a high risk for late dissection; this finding was substantiated by comparison to a control group of 10 consecutive patients with a similarly dilated aortic root but no dissection. Type and diameter of valve prostheses, cross-clamp time, NYHA functional class, and left ventricular ejection fraction were unrelated to late dissection. Previous aortic valve replacement is an independent predisposing factor for a dissection of the ascending aorta later. At the time of aortic valve replacement, prophylactic replacement or wrapping of the ascending aorta should be considered in patients with a thinned/fragile aortic wall even without a markedly dilated aortic root.

Mutations of the p53 gene are the most commonly observed genetic alterations in malignant tumors and are often associated with a loss of the tumor suppressor function of the p53 protein. We have analyzed specimens of head and neck squamous cell carcinomas (HNSCC) from 110 patients for p53 gene mutations and 92 of them additionally for human papillomavirus (HPV) infection in order to evaluate the prognostic significance of these factors by comparison with clinical follow-up data. Using the method of polymerase chain reaction (PCR)/temperature gradient gel electrophoresis (TGGE), mutations within the exons 5 to 8 of the p53 gene were found in 48 tumors (44%). Sequencing revealed missense mutations in most cases (15/20). Frequency of p53 gene mutations was not related to the tumor stage, the grade of differentiation, the presence of lymph node metastases, or the smoking history of the patients. With the help of a highly sensitive PCR/hybridization assay, an infection with the high-risk HPV types 16 and 18 could be detected in 39/92 tumor specimens (42%). Follow-up data were obtained from 99 patients with a range of 2-112 months. No correlation of overall survival on the presence of p53 gene mutations or HPV infection could be observed. The absence of statistically significant correlations between p53 gene mutations and progressive disease, however, does not exclude its putative relevance in early phases of tumor development.

We analyzed specimens of head and neck squamous cell carcinomas (HNSCC) from 110 patients for p53 gene mutations, and 92 of them for human papillomavirus (HPV) infection, in order to evaluate the prognostic significance of these factors by comparison with clinical follow-up data. Mutations within the exons 5 to 8 of the p53 gene were found in 48 tumors (44%). Sequencing revealed in most cases mis-sense mutations (16/21). Frequency of p53 gene mutations was not related to the tumor stage or the presence of lymph node metastases. Of the 46 tumors that were analyzed by immunohistochemistry, 26 stained positively (56%). The number of positively stained nuclei increased slightly with decreasing differentiation of the tumors, whereas no correlation was found between tumor stage and immunoreactivity. An infection with the high-risk HPV types 16 and 18 could be detected in 39/92 tumor specimens (42%). Follow-up data were obtained from 99 patients within a range of 2 to 112 months. No dependence of overall survival on the presence of p53 gene mutations or HPV infection could be observed. The absence of statistically significant correlations between p53 gene mutation and progressive disease, however, does not deny its putative relevance in early phases of tumor development.

In recent decades an increase in the incidence of fungal infection has been reported. We retrospectively analyzed 41 patients with candidemia seen at Basel University Hospital over a six-year period. 1.2-6.7 candidemias per 10000 admissions were observed. In contrast to other studies, there was no increase during the study period. Out of 41 patients, 19 were hospitalized in ICUs. All patients had risk factors such as intravascular catheters (92.7%), antibiotic therapy (88%), immunosuppressive therapy (31%), indwelling Foley catheters (54%) and previous surgery (63%). The most frequent symptoms were fever with rigor, tachycardia and hypotension. The isolates were Candida albicans (n = 28), Torulopsis glabrata (n = 5), C. krusei (n = 3), C. parapsilosis (n = 2), C. guilliermondii, C. kefyr and C. lusitaniae (n = 1 each). In 22 patients, candida colonization had been documented and 5 patients had superficial mucocutaneous candidiasis before candidemia. The initial foci were the gastrointestinal tract (n = 13), an intravascular catheter (n = 8), the urinary tract (n = 5), the respiratory tract, or intravenous drug use (n = 3 each). Out of 32 patients who were treated either with amphotericin B or fluconazole, 13 died. 5 of the untreated patients died, in 3 instances before microbiological diagnosis. The mortality was similar for treatment with amphotericin B and with fluconazole (50% vs. 33%) (p = 0.3).

The changes that have taken place in asthma therapy during the past ten years and their consequences regarding costs were studied analyzing retrospectively 285 clinical histories of asthmatics treated at the University Hospital Zurich in 1977, 1982 and 1987. The following changes in the use of the five basic antiasthmatic drugs i.e. beta-adrenoceptor agonists, anticholinergic drugs, xanthines, glucocorticosteroids and antiallergic drugs were observed: In 1977 80% of asthmatics received beta-agonists, in 1987 90%. Conversely, parasympatholytics were rarely used: In 1977 in only 2%, in 1982 in 16% and in 1987 in 27% of patients. In 1987 xanthines were prescribed in only 50% of asthmatics whereas in 1982 after the introduction of retarded preparations, these drugs were given to 86% of patients. In 1977 only one-third of asthmatics received glucocorticosteroids; in 1987, however, three-quarters of them. Antiallergic drugs were prescribed in 1977 and 1987 in about 25% of the asthmatics, in 1982 in only 13%. Considering the form of application there was a significant trend towards metered aerosols. This was true for betamimetics, parasympatholytics and glucocorticosteroids. Fixed combinations and rectal applications of xanthines were substituted for retarded formulations. In 1977 one or two antiasthmatic drugs accounted for 75% of asthma therapy. In contrast, in 1987 60% of asthmatics received more than two antiasthmatic drugs. The dosages of salbutamol and beclomethasone increased significantly from 1977 to 1987. Other changes in dosages were not significant. The change in costs of antiasthmatic therapy revealed significant savings in regard of xanthines and antiallergic drugs. During the past ten years the overall costs of antiasthmatic drugs therapy remained the same despite more complex therapy.