[Bilateral pneumothorax during awake fiberoptic intubation : A rare complication of bronchoscopy]. / Beidseitiger Pneumothorax bei fiberoptischer Wachintubation : Eine seltene Komplikation der Bronchoskopie.

An 86-year-old woman was scheduled for surgical treatment of a periprosthetic femoral fracture after a fall. Because of a known difficult airway due to multiple surgeries and radiation for cancer in the orofacial area, awake fiberoptic intubation was planned. During the fiberoptic maneuver the patient experienced a massive bout of coughing which resulted in large soft tissue emphysema and double-sided pneumothorax. This case reports a rare complication of fiberoptic intubation and airway management.

Evaluation of a Novel System for Linear Conformation, Gait, and Personality Trait Scoring and Automatic Ranking of Horses at Breed Shows: A Pilot Study in American Quarter Horses.

The study compared results of the traditional horse judging system (T) using subjective grades with those of a novel system of linear scoring (LS) using an application ("Breed Show App"). The horse's quality in relation to the total breeding aim was evaluated based on weighting factors for 57 individual traits commonly regarded in T, thus allowing immediate ranking of the horses. Results were stated as total grade in percent for both systems. One thousand nine hundred nine American Quarter horses were judged at regular breed shows with either T (n = 883), LS (n = 1,026), or both systems (n = 17). In addition, suitable traits for personality evaluation using LS were selected (n = 559 horses). Mixed-model analysis (F-test throughout) and Pearson correlations were used to assess agreement between systems and to identify highly correlated personality traits. Mean total grade was slightly greater in T (83.3 ± 0.2%) than LS (81.7 ± 0.3, P < .0001). Overall grades showed a wider range with LS, thus likely better reflecting phenotypic variance and improving comparability between horses without affecting overall horse ranking (r = 0.95, P < .00001) and thresholds for licensing minimum standards. Most personality traits deviated from a normal distribution (Kolmogorov-Smirnov: P < .01), potentially indicating that genetic or phenotypic preselection took place in the participating horses. Foals that were perceived as more "bright" by the observers kept a larger distance from their dam (r = 0.4) and showed more exploration of the environment (r = 0.2, all P < .01). Especially with more complex traits, including personality traits, variation of results and thus possibilities for differentiating between horses seem to be increased in horse judging using LS.

Prevalence of different head-neck positions in horses shown at dressage competitions and their relation to conflict behaviour and performance marks.

Much controversy exists among riders, and in particular among those practicing dressage, regarding what can be considered an "appropriate" Head-Neck-Position (HNP). The objective was to assess the prevalence of different HNPs in the field, the behavioural reactions of horses during warm-up and competition rides in relation to HNP and the relation between HNP and marks achieved in the competition. Horses (n = 171) were selected during dressage competitions according to their HNP (3 categories based on the degree of flexion), and their behaviour was recorded during 3 minutes each of riding in the warm-up area and in the competition. Scans were carried out on an additional 355 horses every 15 minutes to determine the proportion of each HNP in the warm-up area. Sixty-nine percent of the 355 horses were ridden with their nasal planes behind the vertical in the warm-up area, 19% were ridden at or behind the vertical and only 12% were ridden with their nasal plane in front of the vertical. Horses carrying their nasal plane behind the vertical exhibited significantly (P<0.0001) more conflict behaviours than horses with their nose held in front of the vertical. Horses were commonly presented with a less flexed HNP during competition compared to warm-up (P<0.05). A HNP behind the vertical was penalised with lower marks in the lower (P = 0.0434) but not in the higher (P = 0.9629) competition levels. Horses in higher classes showed more (P = 0.0015) conflict behaviour than those in lower classes. In conclusion, dressage horses are commonly ridden during warm-up for competitions with their nasal plane behind the vertical, and this posture seems to cause significantly more conflict behaviour than HNPs in front of the vertical.

Strategy for the simulation and analysis of longitudinal phenotypic and genomic data in the context of a temperature × humidity-dependent covariate.

A simulation study was conducted to evaluate the performance of genomic random regression models for the continuous environmental descriptor temperature-humidity index (THI). Statistically innovative aspects of the study included the combined simulation of both longitudinal phenotypic data representing the same trait in the course of THI and genomic data. The longitudinal trait was simulated (phenotypically expressed) at 5 different values of THI. For a moderate heritability trait, heritabilities were 0.30, 0.35, 0.40, 0.40, and 0.35 for THI of 15, 30, 45, 60 and 75, respectively. In a consecutive run, low heritabilities of 0.05, 0.1, 0.15, 0.15, and 0.10 were simulated, respectively. On the genomic level, simulation combined high and low linkage disequilibrium with 5,000-, 15,000-, and 50,000-SNP chip applications to simulate different scenarios of genomic architecture. With regard to data analyses, 2 strategies were applied to evaluate the accuracy of genomic predictions across THI, with special focus on the extreme ends of the environmental scale. In the first strategy, 100, 80, 50, or 20% of phenotypes at THI 75 were deleted randomly and the remaining data set was used to predict the breeding value at THI 75 for non-phenotyped, but genotyped cows. In the second strategy, 1,600 cows had complete information (genotypes and phenotypes) and 400 cows were genotyped, but with missing phenotypes for all THI. For the first strategy and without phenotypic observations at THI 75, accuracies of genomic predictions were lower than 0.34. When only 20% of cows had phenotypic records at THI 75, accuracies increased (~0.60). Such a small proportion of phenotyped cows was sufficient to predict reliable genomic breeding values for cows without phenotypes for extreme THI. For the second strategy, also for low linkage disequilibrium combined with a low density 5,000-SNP chip, the average accuracy of genomic predictions was 0.52, which is substantially higher than accuracies based on pedigree relationships. From a practical perspective, genomic random regression models can be used to predict genomic breeding values for scarce phenotypes (e.g., novel traits) traits measured in extreme environments, or traits measured late in life, such as longevity.

Human leucocyte antigen class I and class II antigen expression in malignant fibrous histiocytoma, fibrosarcoma and dermatofibrosarcoma protuberans is significantly downregulated.

BACKGROUND: Abnormalities in the expression of human leucocyte antigens (HLA) by tumour cells impair cellular immune responses promoting immune evasion and tumour survival. To date, studies analysing HLA class I and class II expression levels in malignant fibrous histiocytomas, fibrosarcomas and dermatofibrosarcoma protuberans are limited. AIMS: Therefore, we investigated the in vivo expression profile of HLA class I and class II antigens in 99 malignant fibrous histiocytomas, 20 fibrosarcomas and 34 dermatofibrosarcoma protuberans from different anatomical sites. MATERIAL AND METHODS: Immunohistochemistry using monoclonal antibodies to HLA class I and class II antigens was used to define the expression levels of these antigens on respective tumour samples. RESULTS: Frequent loss or downregulation of HLA class I and class II expression in malignant fibrous tumours was observed for the different types of tumours examined. DISCUSSION: The data presented suggest for the first time a high frequency of HLA class I and class II abnormalities in malignant fibrous histiocytomas, fibrosarcomas and dermatofibrosarcoma protuberans in vivo. CONCLUSION: This information might be useful in the practical and clinical design of tumour vaccination strategies.

Hepatocyte growth factor/scatter factor (HGF/SF) induces vascular permeability factor (VPF/VEGF) expression by cultured keratinocytes.

Skin expression of the endothelial cell-specific vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) as an outstanding mediator of physiologic and pathologic angiogenesis has been previously demonstrated to be subject to regulation by distinct stimuli. We explored whether the multifunctional hepatocyte growth factor/scatter factor (HGF/SF) may mediate its angiogenic properties in part through paracrine induction of cutaneous VPF/VEGF synthesis. In these studies, we demonstrate that HGF/SF functions as a potent inducer of VPF/VEGF expression by human epidermal keratinocytes and by different epithelial-derived cells in vitro. VPF/VEGF mRNA and protein expression are regulated by HGF/SF in both a concentration- and a time-dependent fashion. Examination of mRNA half-lives does not reveal an increase in VPF/VEGF mRNA stability after HGF/SF stimulation. Thus, HGF/SF-induced VPF/VEGF mRNA expression appears to be largely dependent on enhanced gene transcription. In analyses of transiently transfected 5'-deletional reporter gene constructs, we identified a GC-rich VPF/VEGF promoter element that conveys transcriptional activation in response to HGF/SF. This sequence, located between nucleotides -88 and -70, is critical for both constitutive and HGF/SF-induced transcriptional activity. Together, our observations support a model in which HGF/SF mediates angiogenic properties in part through paracrine induction of VPF/VEGF synthesis by keratinocytes. In addition to cutaneous inflammation and wound healing, our findings have potential significance for vascular hyperpermeability and angiogenesis in tumor growth.

Calibration of a reflectance pulse oximeter in fetal lambs for arterial oxygen saturations below 70%.

OBJECTIVE: To calibrate a reflectance pulse oximeter developed at the Division of Perinatal Physiology, University Hospital of Zurich, for monitoring of oxygen saturations below 70%. METHODS: Oxygen saturation measured noninvasively with the reflectance pulse oximeter in fetal sheep was compared with oxygen saturation of arterial blood samples measured by a conventional two-wavelength oximeter. Oxygen saturation was varied by stepwise reduction of the inspired oxygen concentration of the ewe. RESULTS: A total of 58 data pairs was obtained from five fetuses, with a range of 10.9-73.5% for the reference method and 6.8-69.2% for the pulse oximetry oxygen saturation values. There was good correlation between the results obtained by the two methods (r2 = .89, P < .0001), with a 95% confidence interval of +/- 12.5%. The pulse oximeter showed a precision of 6.2% oxygen saturation. CONCLUSION: The Zurich reflectance pulse oximeter offers valid measurements of oxygen saturation levels down to 10% oxygen saturation, and is therefore suitable for monitoring the fetus during delivery.

Reflectance pulse oximetry--principles and obstetric application in the Zurich system.

Transmission and reflectance are the two main modes of pulse oximetry. In obstetrics, due to the absence of a transilluminable fetal part for transmission oximetry, the only feasible option is the reflectance mode, in which sensor and detector are located on the same surface of the body part. However, none of the reflectance pulse oximeters developed for intrapartum use are fully satisfactory, as indicated by the fact that none have entered routine use. We have designed, developed, constructed and tested a reflectance pulse oximeter with the possibility to adjust the electronic circuits and signal processing in order to determine the effects of various parameters on signal amplitude and wave-form and to optimize the sensitivity and spatial arrangement of the optical elements. Following an explanation of the principles of reflectance pulse oximetry, we report our experience with the design, development, construction and field-testing of an in-house reflectance pulse oximetry system for obstetric application.

Intrapartum reflectance pulse oximetry: effects of sensor location and fixation duration on oxygen saturation readings.

OBJECTIVE: To determine the effects of sensor location and suction fixation duration on measurements of intrapartum fetal oxygen saturation (SpO2) with a new reflectance pulse oximetry system. DESIGN: Fetal SpO2 values (n = 18) were determined in the first stage of labor before and after moving the sensor to another part of the fetal head. RESULTS: Mean fetal SpO2 values did not differ with sensor location (95% CI: -3.59 to 1.48). The duration of measurement period 1, before moving the sensor, was 104 +/- 44 (range 30-240) min. No time-dependent changes in SpO2 values were seen (r = 0.17). CONCLUSION: Suction is an effective and noninvasive method of securing the reflectance pulse oximetry sensor to the fetal head in the first stage of labor and does not interfere with reproducible SpO2 values over several hours.

Pre-core mutants of hepatitis B virus in patients receiving immunosuppressive treatment after orthotopic liver transplantation.

Orthotopic liver transplantation (OLT) is a possible treatment for acute or chronic liver failure due to hepatitis B virus (HBV) infection, but reinfection of the graft can be a serious complication. The aim of this study was to monitor HBV markers, to analyse pre-core-/core-mutations as well as to identify the viral population causing reinfection after OLT, and to investigate the emergence or disappearance of these mutants in patients receiving immunosuppressive treatment. Fifty-four pre-and posttransplant serum samples of 17 patients were analysed. All patients underwent OLT for HBV-related liver disease and had HBV-DNA before and after OLT. Total DNA was extracted from all sera and a 240 bp fragment comprising the pre-core region of HBV was amplified by polymerase chain reaction (PCR). Pre-core mutants of HBV were determined by direct sequencing of these PCR products and by sequencing of PCR clones. Eight of 17 patients were infected with pre-core wildtype HBV before OLT (group A). Seven of eight patients of group A were reinfected by pre-core wildtype HBV after OLT. In one of eight patients in addition to wildtype HBV a mutant strain (nt. 1899 G-->A) was detected. Nine of 17 patients were infected with pre-core mutant HBV before OLT (group B). Six of nine patients of group B were reinfected with the same mutant population; in one, an additional pre-core mutation emerged; two patients lost pre-core mutant HBV (nt. 1896 and 1899 G-->A). In one of the latter two, a pre-core start-codon mutant (nt. 1816 G-->T), not detectable before OLT, emerged, in the other a nt. 1897 G-->A stop-codon mutant persisted. Five patients of each group were followed-up for more than 24 (25 to 58) months on immunosuppressive therapy. In all five patients of group A, pre-core wildtype of HBV persisted during long-term follow up. Two of five patients of group B were infected stably with a stop-codon HBV-mutant nt. 1896. In three patients, the nt. 1896 stop-codon mutant disappeared during immunosuppressive therapy. However, in one of the latter three, an HBV stop-codon mutant nt. 1897 persisted. In conclusion, most patients who underwent OLT for HBV-related disease were reinfected with the same virus population that existed before OLT. In rare cases, new mutants emerged after OLT or preexisting mutants were lost. During long-term follow-up on immunosuppressive therapy, in the majority of patients pre-core mutants disappeared and wildtype HBV became the predominant virus strain.

Treatment of chronic hepatitis C with interferon alpha: long-term follow-up and prognostic relevance of HCV genotypes.

To evaluate the importance of hepatitis C virus (HCV) genotypes for the long-term response to interferon alpha (IFN alpha) therapy, we retrospectively investigated 81 patients with chronic hepatitis C treated within two randomized multicenter studies with comparable inclusion criteria. Forty patients received recombinant IFN alpha 3 MU three times a week for 12 months and 41 patients lymphoblastoid IFN alpha 3 or 5 MU three times a week for 6 or 12 months (total dosage 216-720 MU). The patients were followed up for up to 4 yr (2-4 yr, mean 3.2 yr). A sustained remission defined as normalization of aminotransferases and negative PCR for HCV-RNA was achieved in 23% of patients treated with recombinant IFN alpha and in 25% of the group with lymphoblastoid IFN alpha therapy. All patients with sustained remission showed a normalization of aminotransferases during the first 3 months of therapy. Determination of HCV genotypes revealed a major prevalence of type 1 (77%) versus type 2 (5%) and type 3 (18%). The response rate was significantly higher in patients with type 2 and 3 infections (75 and 73%) than in patients infected with genotype 1 (37%) (p = 0.005). Sustained remission was observed in 13% for genotype 1, in 75% for genotype 2, and in 33% for genotype 3 (differences between type 2/3 versus type 1, p = 0.03). There were no significant differences between responders and non-responders concerning age, level of aminotransferases before therapy or the dosage and type of IFN alpha administered. The data indicate that the determination of HCV genotypes may have prognostic relevance in the responsiveness to IFN alpha therapy.

Reflectance pulse oximetry in neonates.

OBJECTIVE: To test the feasibility and reliability in neonates of an in-house reflectance pulse oximetry (RPOX) system as an alternative method of non-invasive oxygen saturation monitoring when transmission pulse oximetry (TPOX) cannot be used, as in fetal scalp oxygen saturation monitoring during delivery. STUDY DESIGN: The study population consisted of 31 intensive care neonates. The RPOX sensor was attached by suction to the forehead, cheek, occiput and back; recordings were under simultaneous TPOX control. RESULTS: There was close agreement between RPOX and TPOX oxygen saturation and heart rate values, even in periodic breathing. RPOX signals from the back were unreliable because of breathing artifacts. Differences in mean absolute RPOX and TPOX oxygen saturation values were due to different calibrations. Both systems were equally sensitive to motion artifacts. CONCLUSION: As a feasible and reliable method of non-invasive oxygen saturation monitoring in neonates, RPOX has potential applications in fetal scalp monitoring.

[Prognostic relevance of hepatitis C virus genotype for responsiveness to interferon-alpha]. / Prognostische Relevanz der Hepatitis-C-Virus-Genotypen für das Ansprechen auf Interferon-alpha.

The influence of hepatitis C virus (HCV)-genotypes on the responsiveness to interferon- (IFN-alpha) was studied in 116 patients with proven chronic hepatitis C. 88 of 116 (76%) patients were infected with HCV-genotype 1, 7 (6%) with HCV-genotype 2, and 21 patients (18%) with HCV-genotype 3. All patients received at least 3 MU recombinant IFN-alpha-2a, 2b or lymphoblastoid IFN-alpha tiw for at least 6 month (total IFN-alpha dose per patient 216-720 MU, mean 360; treatment duration 6-12 month, mean 8). The follow-up after cessation of therapy was 9-48 months (mean 25). Sustained normalization of the aminotransferase levels was observed in 20 (17%) of the 116 patients. 10 of the 88 (11%) patients with HCV-genotype 1, 7 of the 21 (33%) patients with HCV-genotype 3 (p < 0.02), and 3 out of the 7 patients with HCV-genotype-2- infection achieved a sustained remission. No response was observed in 58 (66%) and 3 (14%) patients with HCV-genotype 1 and 3 infections, respectively (p < 0.002). All but one of the sustained responders remained HCV-RNA negative during the entire follow-up. There were no significant differences between the sustained responders and the group of non-responders and responders with relapse in relation to age, pretreatment aminotransferase levels, histological activity index, or given IFN-alpha dosage. HCV-genotyping is helpful in evaluating the responsiveness to IFN-alpha and will be of importance considering the indication of therapy.

Limitations of forehead pulse oximetry.

During initial clinical tests to calibrate our reflectance pulse oximetry system, we observed serious physiologic limitations to the use of pulse oximetry in the forehead region. We present a case of simultaneous reflectance and transmission mode pulse oximetry monitoring in a child undergoing cardiac surgery for congenital cyanotic heart disease with a large intracardiac shunt. During general anesthesia, when the patient was endotracheally intubated and mechanically ventilated, the transmission mode saturation agreed well with arterial oxygen saturation measurements; but, our reflectance pulse oximeter, with the sensor applied to the forehead, displayed spuriously lower (-18%) oxygen saturations. Before and after anesthesia and surgery, there was fine agreement between reflectance and transmission mode saturation values. We suggest that the difference was caused by vasodilatation and pooling of venous blood due to compromised venous return to the heart, and a combination of arterial and venous pulsations in the forehead region. This means that the reflectance pulse oximeter measured a mixed arterial-venous oxygen saturation.

Long-term follow-up of hepatitis B virus-infected recipients after orthotopic liver transplantation.

The outcome after OLT was studied in 53 patients with chronic hepatitis B virus (HBV)* infection, 15 of whom had, in addition, evidence of hepatitis delta virus (HDV) superinfection. Nine of 53 patients received short-term immunoprophylaxis with anti-hepatitis B surface (HBs) hyperimmunoglobulin up to 1 week after OLT and 44 of 53 patients received long-term unlimited immunoprophylaxis. Eight of 9 (89%) patients with short-term immunoprophylaxis showed reactivation of replication with HBV DNA in serum > 10 pg/ml independently of the preoperative HBV DNA level and HBsAg reappeared in all cases. Four (44%) patients in this group lost their graft because of fulminant hepatitis or cirrhosis and required retransplantation, and 2 patients (22%) died after reinfection in the second graft. Nineteen of 44 (43%) patients with long-term immunoprophylaxis developed HBV values > 10 pg/ml after transplant and 12 of 44 (27%) became HBsAg+ again. Most of them had quantifiable HBV DNA levels before OLT. Retransplantation was required in 5 of 44 (11%) patients and 4 of them died after HBV recurrence. The frequency of HBV reactivation and the development of viral hepatitis after OLT were associated with the preoperative presence of HBV, as determined by the molecular hybridization assay. With nested polymerase chain reaction, all 53 patients were HBV-DNA+ in the serum before and after OLT. with just one exception, none of the patients with HDV superinfection died, in spite of increased HDV replication after OLT. The data indicate that long-term immunoprophylaxis with anti-HBs hyperimmunoglobulin after OLT improves the prognosis in HBV-infected patients. The preoperative detection of HBV DNA in serum by molecular hybridization assay is correlated with graft infection and represents a prognostic parameter. The presence of HDV may have a protective effect after OLT.

[Long-term follow-up of chronic hepatitis C after treatment with recombinant interferon alpha-2a]. / Langzeitbeobachtung der chronischen Hepatitis C nach Behandlung mit rekombinantem Interferon alpha-2a.

As part of a multicenter randomized study 40 patients with chronic hepatitis C (HCV)-infection, 28 kryptogenic and 12 posttransfusional, were treated with recombinant interferon alfa (IFN alpha-2a) for 1 year in a dosage of 3 x 3 Mio. units per week versus dosis escalation after 8 and 16 weeks in serological non-responders. 36 of the 40 patients were followed over 3 years. The rate of patients with normalization of aminotransferases was 42% after two months of therapy, 28% at the end of treatment, 28% after 1 year and 23% after 3 years of follow-up. The polymerase chain reaction (PCR) for detection of HCV-RNA became negative after two months of treatment in 73%, at the end of therapy in 63%, after 1 year follow-up in 63% and after 3 years in 35%. All patients with persisting remission maintained HCV-RNA negative. Dosis escalation was realized in 8 patients without increase of responder rate. Antibodies against IFN alpha-2a developed in 4 (10%) patients without remarkable influence on the IFN-effect. Histological improvement at the end of treatment was observed in 61% including all patients with serological remission. The data support the prognostic relevance of the course of aminotransferases. If aminotransferases are not normalized during the first two months the treatment can be terminated. Persisting normalization of aminotransferases during 1 year after therapy and negative HCV-PCR result indicate maintaining remission.