Enhanced influenza A H1N1 T cell epitope recognition and cross-reactivity to protein-O-mannosyltransferase 1 in Pandemrix-associated narcolepsy type 1.

Narcolepsy type 1 (NT1) is a chronic neurological disorder having a strong association with HLA-DQB1*0602, thereby suggesting an immunological origin. Increased risk of NT1 has been reported among children or adolescents vaccinated with AS03 adjuvant-supplemented pandemic H1N1 influenza A vaccine, Pandemrix. Here we show that pediatric Pandemrix-associated NT1 patients have enhanced T-cell immunity against the viral epitopes, neuraminidase 175-189 (NA175-189) and nucleoprotein 214-228 (NP214-228), but also respond to a NA175-189-mimic, brain self-epitope, protein-O-mannosyltransferase 1 (POMT1675-689). A pathogenic role of influenza virus-specific T-cells and T-cell cross-reactivity in NT1 are supported by the up-regulation of IFN-γ, perforin 1 and granzyme B, and by the converging selection of T-cell receptor TRAV10/TRAJ17 and TRAV10/TRAJ24 clonotypes, in response to stimulation either with peptide NA175-189 or POMT1675-689. Moreover, anti-POMT1 serum autoantibodies are increased in Pandemrix-vaccinated children or adolescents. These results thus identify POMT1 as a potential autoantigen recognized by T- and B-cells in NT1.

Difficult to treat: are there organism-dependent differences and overall risk factors in success rates for two-stage knee revision?

OBJECTIVES: Failure after two-stage procedure for periprosthetic joint infection (PJI) is a rare, but devastating complication. Some authors assume a correlation of underlying organisms and recurrence rate. Methicillin-resistant Staphylococci (MRS) and other organisms (quinolone-resistant Gram-negative bacteria, rifampicin-resistant Staphylococcus, Enterococcus, and Candida) are meant to be "difficult to treat" (DTT) with an inferior outcome for two-stage revision. In addition to the type of bacteria, some more risk factors seem to be present. The aim of this study was (1) to detect a difference of reinfection rates between reinfection-causing groups of bacteria ["difficult to treat" (DTT), "easy to treat" (ETT) and methicillin-resistant staphylococci (MRS)] after a two-stage procedure, and (2) find overall risk factors for reinfection in a standardized long (spacer insertion for at least 6 weeks) two-stage procedure for periprosthetic knee infection. METHODS: One hundred and thirty-seven two-stage revisions for periprosthetic knee infection were performed at one tertiary referral center. Finally, 96 patients could be included for analyses. Possible risk factors (comorbidities, prior surgery, etc.) and the types of organisms were documented. Quinolone-resistant Gram-negative bacteria, rifampicin-resistant Staphylococcus, Enterococcus, and Candida were classified as "difficult to treat" (DTT). Methicillin-resistant Staphylococci were summarized as "MRS", all other organism are summarized as "easy to treat" (ETT). Statistical analyses included univariate analysis (t test, Fisher's exact test, Chi square test) and logistic regression analysis. RESULTS: There were no statistical significant differences in recurrent infection rates between organism groups (DTT vs. ETT, p = 0.674; DTT vs. MRS, p = 0.705; ETT vs. MRS, p = 0.537). Risk factors seem to be "need of revision after first stage" (p = 0.019, OR 5.62) or completed second stage (p = 0.000, OR 29.07), numbers of surgeries (p = 0.028) and alcohol abuse (p = 0.019, OR 5.62). CONCLUSIONS: Revision needed during or after a two-stage exchange, numbers of surgeries and alcohol abuse are risk factors for recurrence, a different recurrence rates between organism-groups cannot be shown. The absence of significant differences in recurrence rates points to the importance of the individuality of each periprosthetic infection case: a reduction of necessary surgeries (with a thorough debridement, appropriate antibiotic addition to spacers) and the control of comorbidities (alcohol abuse) appear to be essential components of a two-stage exchange.

[Measurement of acetabular cup inclination in anteroposterior pelvic radiogram : An indicator of quality after primary total hip arthroplasty?] / Die Pfanneninklinationsmessung in der Beckenübersichtsaufnahme : Ein Qualitätsindikator nach Hüft-TEP-Primärimplantation?

BACKGROUND AND OBJECTIVE: Acetabular cup orientation, consisting of pelvic positioning, version and inclination, can influence short-term and long-term results after total hip arthroplasty (THA). The radiographic measurement of acetabular cup inclination represents an indicator of quality for the EndoCert certification in Germany. The purpose of this study was to determine the intrarater and interrater reliability of radiographic measurements of acetabular cup inclination after THA. MATERIAL AND METHODS: In this study four independent investigators with different levels of expertise retrospectively performed measurements on radiograms (anteroposterior pelvic radiogram) from 99 patients. The intraclass correlation coefficient (ICC) and Pearson's correlation coefficient were determined and were considered statistically significant with r > 0.8 and p < 0.05. RESULTS AND CONCLUSION: A high correlation was found for both intrarater and interrater reliability based on determination of Pearson's correlation coefficient and the ICC with r > 0.9 and p < 0.001 for all measurements. Based on these results the radiographic measurement of acetabular cup inclination can be considered as a simple measuring tool with high intrarater and interrater reliability. As cup orientation consists of inclination, version and positioning, the exclusive measurement of cup inclination for radiological quality assessment needs to be discussed critically.

[The economic solution for integrating radiology and surgery: hybrid OR]. / Die wirtschaftliche Lösung für die Integration von Bildgebung und Chirurgie - Hybrid-OP.

Currently, interventional (angiographically-guided) therapies have become more and more important in cardiovascular medicine. Hybrid procedures in hybrid operating rooms (ORs) have now become major topics at national and international meetings. A few hospitals have already implemented the project "hybrid OR", in some institutions the system is still in the planning stage. The aim of our article is to present the hospital management point of view, and thus, to focus on the economic and logistic issues from planning through to implementation.

Gliadin-primed CD4+CD45RBlowCD25- T cells drive gluten-dependent small intestinal damage after adoptive transfer into lymphopenic mice.

BACKGROUND AND AIMS: Coeliac disease is a common small intestinal inflammatory disorder that results from a breach of intestinal tolerance to dietary gluten proteins, driven by gluten-reactive effector T cells. We aimed to assess the pathogenic role of gluten-reactive T cells and to generate a model of gluten-induced enteropathy. METHODS: CD4+CD25- T cell fractions were adoptively transferred into lymphopenic mice, leading to "baseline" small intestinal inflammation. RESULTS: Rag1-/- recipients of gliadin-presensitised CD4+CD45RBlowCD25- T cells, but not CD4+CD45RBhigh naive T cells, gained less weight and suffered from more severe duodenitis when challenged with oral gluten than recipients on gluten-free diet, or recipients of control (ovalbumin)-presensitised T cells. This was accompanied by deterioration of mucosal histological features characteristic of coeliac disease, and increased Th1/Th17 cell polarisation in the duodenum and the periphery. Interestingly, reintroduction of a gluten-free diet led to weight gain, improvement of histological duodenitis, and a decrease in duodenal interferon gamma and interleukin 17 transcripts. Moreover, B cell-competent nude recipients of gliadin-presensitised CD4+CD45RBlowCD25- T cells produced high levels of serum anti-gliadin immunoglobulin A (IgA) and IgG1/IgG2c only when challenged with oral gluten. CONCLUSIONS: CD4+ T cell immunity to gluten leads to a breach of oral gluten tolerance and small intestinal pathology in lymphopenic mice, similar to human coeliac disease. This model will be useful for the study of coeliac disease pathogenesis, and also for testing novel non-dietary therapies for coeliac disease.

Naturally occurring bacteriophages lyse a large proportion of canine and feline uropathogenic Escherichia coli isolates in vitro.

We investigated the feasibility of bacteriophage therapy to combat canine and feline Escherichia coli urinary tract infections (UTIs) by testing the in vitro lytic ability of 40 naturally occurring bacteriophages on 53 uropathogenic E. coli (UPEC). The mean number of UPEC strains lysed by an individual bacteriophage was 21/53 (40%, range 17-72%). In total, 50/53 (94%) of the UPEC strains were killed by one or more of the bacteriophages. Ten bacteriophages lysed 51% of UPEC strains individually and 92% of UPEC strains as a group. Electron microscopy and DNA sequencing of 5 'promising' bacteriophages revealed that 4 bacteriophages belonged to the lytic T4-like genus, while one displayed morphologic similarity to temperate P2-like bacteriophages. Overall, these results indicate that the majority of UPEC are susceptible to lysis by naturally occurring bacteriophages. Thus, bacteriophages show promise as therapeutic agents for treatment of canine and feline E. coli UTIs.

Feline uropathogenic Escherichia coli from Great Britain and New Zealand have dissimilar virulence factor genotypes.

We investigated the prevalence of 30 known virulence factor genes (VFGs) in uropathogenic E. coli (UPEC) from two geographically distinct feline populations, using a PCR-based approach. E. coli isolates were also subjected to macrorestriction analysis to assess their phylogenetic relationships. VFG profiles differed considerably according to the geographic origin of the isolates, enabling discriminant analysis to correctly predict population membership for 15/15 NZ isolates and 18/22 UK isolates. The prevalence of gene markers for P-fimbriae (PapA, PapC, PapEF, and PapG III), colicin V (CvaC), increased serum survival factor (Iss), complement resistance factor (TraT), pathogenicity-associated island (MalX), iron-regulated siderophore receptor (IreA) and haemolysin (HlyD) differed significantly between UK and NZ isolates. Significant phylogenetic differences between the two populations were also identified, but VFG profiles could not be predicted on the basis of phylogenetic relationships. Consequently, a geographically uneven distribution of certain virulence genes, independent of phylogeny, is the likely cause of VFG differences between populations. We cannot rule out that subtle differences in patient disease status may have contributed to the dissimilarity of VFG profiles.

[Age and sex distribution of primary thyroid cancer in relation to histological type]. / Alters- und Geschlechtsverteilung beim primären Schilddrüsenmalignom in Abhängigkeit vom Tumortyp.

METHOD: Data of all (239) patients suffering from thyroid carcinoma and operated on between January 1st, 1982, and December, 31st, 1997 in our center, were analyzed retrospectively with respect to age- and sex-distribution in relation to the histological type of cancer. The change of frequency in the histological groups was observed over a 16 years period. RESULTS: From all 239 cases, 202 (84.5%) were females and 37 (15.5%) males. The most common histological type with 70.3% in both male and female was the papillary carcinoma, followed by follicular carcinoma with 21.6% of male and 17.8% of female patients. A medullary carcinoma was seen in 8.1% and 5.9%, respectively and an anaplastic carcinoma in only 5.9% of female patients. There was no significant gender difference regarding the histological type. In male patients there was also no influence of age on histological groups. Females with papillary and medullary cancer were significantly younger than those suffering from follicular and anaplastic cancer. Beside, we observed an increase in papillary and a decrease in anaplastic carcinoma during the examination period. CONCLUSIONS: Although the relation of 1 male to 5 females with thyroid carcinoma shows a clear dependence on sex, the histological type distribution is identical in both male and female. Therefore, several different factors seem to influence the development of thyroid carcinoma. One of these factors depends on sex and supports an increased development of carcinoma in female patients. Another factor doesn't depend on sex and causes different histological types. Causes for that could be as well hormonal and reproductive ones as regional differences in iodine availability.

[Pathogenesis of hypotrophic and eutrophic preterm deliveries --a morphologic study of 212 cases]. / Zur Genese hypotroph-prätermer und eutroph-prätermer Geburten--eine morphologische Untersuchung von 212 Fällen.

The exact pathogenesis of prematurity and intrauterine growth retardation (IUGR) is still obscure in detail. Histological examination of placental tissue may be helpful. In a retro- and prospective study we examined 212 placentas including eutroph-term (n = 80 as controls), hypotroph-term (n = 68), eutroph-preterm (n = 53) and hypotroph-preterm (n = 11) deliveries, respectively. Placentas of the control group showed a significant higher weight, a higher utero-placental diameter and a smaller thickness. We observed villous dysmaturity in a significant higher frequency in risk groups, compared with controls (70-80% vs. 15%). Retarded villous maturity occurred in 38.2% in the hypotroph-term group and in 36.4% in the hypotroph-preterm group, respectively. Placentas of eutroph-preterm deliveries showed a prematurity of the villous tree in 47.2% Our own results and data from literature suggest, that the majority of prematurity and IUGR is not caused by placental dysmaturity itself. Fetal hypotrophy is sometimes caused by inadequate adaptation of the placental tissue due to a virtual slowly appeared disturbance, probably in the uterine maternal blood flow. After the adaptation of placental tissue the organ is able to secure the fetal nutrition supply. A second "hit", e.g. inflammation of the chorion may lead to prematurity. If the compensation of the dysbalance between fetal nutrition-supply and placental capacity is impossible the birth of a premature fetus, mostly dysmature, takes place.

Effect of amphotericin B on hepatic cytochrome P-450 and glucose-6-phosphatase in the rat.

The effect of amphotericin B on hepatic microsomal cytochrome P-450 (P-450) concentration was measured in vitro, in vivo and ex vivo in the rat. In vitro, both amphotericin B (0-500 micrograms/ml) and its vehicle, sodium deoxycholate (0-410 micrograms/ml), caused similar dose-dependent decreases of P-450 concentrations and glucose-6-phosphatase activity. Intravenous amphotericin B (3 mg/kg) given daily for 3 days decreased antipyrine clearance from control values of 1.24 +/- 0.24 ml/min to 0.67 +/- 0.12 ml/min (p less than 0.001); whereas antipyrine clearance was unchanged by sodium deoxycholate. The P-450 concentration on the third day was reduced from 0.74 +/- 0.14 nmol/mg protein in control rats to 0.33 +/- 0.09 nmol/mg protein in rats treated with amphotericin B (p less than 0.001). Sodium deoxycholate had no effect on P-450 concentration. In contrast, amphotericin B had no effect on either antipyrine clearance or P-450 concentration following enzyme induction by phenobarbital. Amphotericin B had no effect on microsomal glucose-6-phosphatase activity in vivo. Neither amphotericin B nor sodium deoxycholate induced lipid peroxidation, measured as malondialdehyde production. These results show that amphotericin B decreases hepatic cytochrome P-450 content and function in the rat. These effects can not be observed in the enzyme induced state. Amphotericin B has no effect on glucose-6-phosphatase in vivo, the key enzyme of the gluconeogenesis, indicating selective effects on hepatic microsomal function.

Studies on the role of sodium- and potassium-activated adenosine triphosphatase inhibition in the pathogenesis of human hypertension. Changes in vascular and cardiac function following inhibition of the sodium pump in normotensive subjects and effects of calcium entry blockade.

An endogenous humoral factor which inhibits the sodium- and potassium-activated adenosine triphosphatase (Na-K-ATPase) enzyme in vitro has been incriminated recently of playing a pathogenetic role in experimental and human hypertension. The present study was therefore performed in six healthy volunteers to investigate the hemodynamic consequences of an inhibition of this enzyme by ouabain, a potent and specific inhibitor of Na-K-ATPase. In addition, the role of intracellular calcium as a potential mediator was studied indirectly by the administration of nifedipine, a potent calcium entry blocker with predominant vasodilator properties. Intravenous administration of 8.5 micrograms ouabain/kg body weight inhibited red blood cell (RBC) - Na-K-ATPase by 49% which was accompanied by a significant increase in RBC - ATP and a decrease in intracellular potassium concentrations. This enzyme inhibition resulted in a 24% increase in peripheral vascular resistance. The parallel decrease in cardiac output and heart rate, however, prevented a rise in arterial pressure. This increase in vascular resistance was completely abolished by pretreatment with nifedipine (10 mg orally). In the absence of an effect of nifedipine on Na-K-ATPase, its attenuation of the vasoconstrictor effect of ouabain suggests that the effects of ouabain on the vascular smooth muscle cell are mediated by intracellular calcium. These results demonstrate that inhibition of the Na-K-ATPase enzyme in vivo causes a marked peripheral vasoconstriction. They are also compatible with the concept that an endogenous inhibitor of Na-K-ATPase - in the presence of decreased baroreceptor reflex sensitivity due to blood volume expansion - may play a role in the pathogenesis of human arterial hypertension.

The changing role of the hospital chief financial officer.

Things are changing. That statement is obviously true of things political, economic and scientific. Not surprisingly, therefore, the statement applies to the activities, responsibilities, qualifications and, ultimately, status of the hospital chief financial officer (CFO).

Fracture characteristics of acrylic bone cements. I. Fracture toughness.

The vital first phase of the overall materials study to protract the life of the total joint replacements is the identification of the fracture toughness and fatigue properties of bone cements. Information gained from fatigue testing, performed in a manner which simmulates in vivo conditions, and fracture toughness, which is a measure of the propensity of a crack to propagate, is the first step towards the prediction of the life of the total joint replacement. This study is concerned with the fracture toughness of Zimmer and Simplex-P cold-curing bone cements. Following cement fabrication conditions which closely approximate clinical procedures, fracture toughness testing was conducted on cement specimens which were immersed in bovine serum at 37 degrees C in order to simulate in vivo conditions. In addition, a similar study was completed on specimens, tested in air at ambient temperature for purposes of comparison. Results of this procedure, when analyzed by a Student's t-test at the 95% confidence level with eight degrees of freedom, indicate that both Zimmer and Simplex-P exhibit a higher fracture toughness in the simulated physiological environment. In order to determine whether the addition of barium sulfate to these cements compromises the fracture toughness, the above described testing rationale was repeated, indicating the existence of a complicated relationship between the different testing environments and barium sulfate. The importance of these results lies in the fact that an increased fracture toughness indicates that a cement will inherently exhibit a greater degree of resistance to the propagation of cracks, which could contribute to the ultimate failure of the total joint replacement.