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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.

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.

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

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.

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.

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.

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.