Driving and emergency braking may be impaired after tibiotalar joint arthrodesis: conclusions after a case series.

PURPOSE To assess whether reaction time (RT) and movement time (MT), as the two components of the total brake response time (TBRT) and brake force (BF) are different in patients with a foot joint arthrodesis in comparison to controls. METHODS The study was a comparative case series in a driving simulator under realistic driving conditions. Mobile patients without a walker, ≥6 months after surgery who were driving a car and had no neurological co-morbidity, knee or hip joint prosthesis were included in the study. The selection criteria resulted in 12 patients with right tibiotalar joint arthrodesis (TTJA) and 12 patients with another right foot joint arthrodesis (OFJA), who were compared to 17 individuals without any ankle-joint pathology. For TBRT, an empirical safe driving threshold of 700 ms was used. The outcome measures were RT, MT, TBRT, BF and McGuire score. RESULTS MT (p = 0.034) and TBRT (p = 0.026) were longer in TTJA patients in comparison with the controls. Also, more patients with TTJA than patients with OFJA and controls exceeded the safe driving threshold (p = 0.028). The outcomes in OFJA patients and in controls were comparable. The McGuire score was similar between the TTJA and OFJA patients (p = 0.26). CONCLUSIONS Significantly slower MT and TBRT, and significantly more patients exceeding the safe driving threshold, were observed after a tibiotalar-joint arthrodesis in comparison to the controls. Patients with OFJAs were not significantly different from the controls. Driving and emergency braking may be impaired after tibiotalar-joint arthrodesis.

Patent foramen ovale may be causal for the first stroke but unrelated to subsequent ischemic events

Studies with very long follow-up are scarce in patients with cryptogenic stroke and patent foramen ovale (PFO). Little is known about the etiology of recurrent cerebrovascular events (CVE) in PFO patients.

Antegrade perfusion with bacillus Calmette-Guérin in patients with non-muscle-invasive urothelial carcinoma of the upper urinary tract: who may benefit?

There is paucity of data on bacillus Calmette-Guérin (BCG) perfusion in patients with non-muscle-invasive urothelial carcinoma (NMIUC) of the upper urinary tract (UUT).

Ignoring non-specific abdominal pain in emergency department patients may be related to decreased quality of life. A follow up of an underestimated problem

Patients suffering from chronic pain have a high prevalence of depression, resulting in a significant impact on overall quality of life. Our aim was to investigate how long term acute non-specific abdominal pain (NSAP) affected overall physical and mental well-being in patients admitted to our emergency department (ED).

The Rapid TEG α-Angle may be a sensitive predictor of transfusion in moderately injured blunt trauma patients

Background. To guide the administration of blood products, coagulation screening of trauma patients should be fast and accurate. The purpose of this study was to identify the correlation between CCT and TEG in trauma, to determine which CCT or TEG parameter is most sensitive in predicting transfusion in trauma, and to define TEG cut-off points for trauma care. Methods. A six-month, prospective observational study of 76 adult patients with suspected multiple injuries was conducted at a Level 1 trauma centre of a university hospital. Physicians blinded to TEG results made the decision to transfuse based on clinical evaluation. Results. The study results showed that conventional coagulation tests correlate moderately with Rapid TEG parameters (R: 0.44–0.61). Kaolin and Rapid TEG were more sensitive than CCTs, and the Rapid TEG α-Angle was identified as the single parameter with the greatest sensitivity (84%) and validity (77%) at a cut-off of 74.7 degrees. When the Rapid TEG α-Angle was combined with heart rate >75 bpm, or haematocrit < 41%, sensitivity (84%, 88%) and specificity (75%, 73%) were improved. Conclusion. Cutoff points for transfusion can be determined with the Rapid TEG α-Angle and can provide better sensitivity than CCTs, but a larger study population is needed to reproduce this finding.

Bombesin receptor antagonists may be preferable to agonists for tumor targeting

Two bombesin analogs, Demobesin 4 and Demobesin 1, were characterized in vitro as gastrin-releasing peptide (GRP) receptor agonist and antagonist, respectively, and were compared as (99m)Tc-labeled ligands for their in vitro and in vivo tumor-targeting properties. METHODS: N(4)-[Pro(1),Tyr(4),Nle(14)]Bombesin (Demobesin 4) and N(4)-[d-Phe(6),Leu-NHEt(13),des-Met(14)]bombesin(6-14) (Demobesin 1) were characterized in vitro for their binding properties with GRP receptor autoradiography using GRP receptor-transfected HEK293 cells, PC3 cells, and human prostate cancer specimens. Their ability to modulate calcium mobilization in PC3 and transfected HEK293 cells was analyzed as well as their ability to trigger internalization of the GRP receptor in transfected HEK293 cells, as determined qualitatively by immunofluorescence microscopy and quantitatively by enzyme-linked immunosorbent assay (ELISA). Further, their internalization properties as (99m)Tc-labeled radioligands were tested in vitro in both cell lines. Finally, their biodistribution was analyzed in PC3 tumor-bearing mice. RESULTS: A comparable binding affinity with the 50% inhibitory concentration (IC(50)) in the nanomolar range was measured for Demobesin 4 and Demobesin 1 in all tested tissues. Demobesin 4 behaved as an agonist by strongly stimulating calcium mobilization and by triggering GRP receptor internalization. Demobesin 1 was ineffective in stimulating calcium mobilization and in triggering GRP receptor internalization. However, in these assays, it behaved as a competitive antagonist as it reversed completely the agonist-induced effects in both systems. (99m)Tc-Labeled Demobesin 1 was only weakly taken up by PC3 cells or GRP receptor-transfected HEK293 cells (10% and 5%, respectively, of total added radioactivity) compared with (99m)Tc-labeled Demobesin 4 (45% of total added radioactivity in both cell lines). Remarkably, the biodistribution study revealed a much more pronounced uptake at 1, 4, and 24 h after injection of (99m)Tc-labeled Demobesin 1 in vivo into PC3 tumors than (99m)Tc-labeled Demobesin 4. In vivo competition experiments demonstrated a specific uptake in PC3 tumors and in physiologic GRP receptor-expressing tissues. The tumor-to-kidney ratios were 0.7 for Demobesin 4 and 5.2 for Demobesin 1 at 4 h. CONCLUSION: This comparative in vitro/in vivo study with Demobesin 1 and Demobesin 4 indicates that GRP receptor antagonists may be superior targeting agents to GRP receptor agonists, suggesting a change of paradigm in the field of bombesin radiopharmaceuticals.

Reduction in rat phosphatidylethanolamine binding protein-1 (PEBP1) after chronic corticosterone treatment may be paralleled by cognitive impairment: a first study

Chronic stress is associated with hippocampal atrophy and cognitive dysfunction. This study investigates how long-lasting administration of corticosterone as a mimic of experimentally induced stress affects psychometric performance and the expression of the phosphatidylethanolamine binding protein (PEBP1) in the adult hippocampus of one-year-old male rats. Psychometric investigations were conducted in rats before and after corticosterone treatment using a holeboard test system. Rats were randomly attributed to 2 groups (n = 7) for daily subcutaneous injection of either 26.8 mg/kg body weight corticosterone or sesame oil (vehicle control). Treatment was continued for 60 days, followed by cognitive retesting in the holeboard system. For protein analysis, the hippocampal proteome was separated by 2D electrophoresis (2DE) followed by image processing, statistical analysis, protein identification via peptide mass fingerprinting and gel matching and subsequent functional network mapping and molecular pathway analysis. Differential expression of PEBP1 was additionally quantified by Western blot analysis. Results show that chronic corticosterone significantly decreased rat hippocampal PEBP1 expression and induced a working and reference memory dysfunction. From this, we derive the preliminary hypothesis that PEBP1 may be a novel molecular mediator influencing cognitive integrity during chronic corticosterone exposure in rat hippocampus.

Symptoms with acid and nonacid reflux may be produced by different mechanisms

Twenty-four-hour multichannel intraluminal impedance and pH (MII-pH) esophageal monitoring detects both acid and nonacid gastroesophageal reflux episodes. The MII-pH catheter contains six impedance segments placed 3, 5, 7, 9, 15, and 17 cm above the lower esophageal sphincter (LES). A pH electrode at 5 cm above the LES identifies the type of reflux, i.e. acid or nonacid. Patients with acid and nonacid reflux exhibit typical and atypical symptoms often within 5 min following a reflux episode. The aim of this study is to compare the timing of symptoms after reflux episodes in patients with acid and nonacid reflux. Methods include a review of 70 MII-pH tracings (42 females, mean age 40, range 18-85 years) either on (50 points) or off (20 points) acid suppression therapy. Typical (heartburn, regurgitation) and atypical (cough) symptoms with acid or nonacid reflux episodes detected by impedance were analyzed. Symptoms were considered positive with acid reflux if there was a pH drop to <4, plus an MII detected a reflux episode and with nonacid reflux if pH remained >4 and MII detected a reflux episode. The timing of the symptom after each reflux episode was recorded. Symptom perception occurred significantly sooner after acid versus nonacid reflux (P < 0.05). Acid reflux episodes are more likely to be perceived in the first 2 min following the reflux episode. Patients with acid reflux are likely to perceive symptoms earlier, and symptoms with acid and nonacid reflux may be produced by different mechanisms.

Bacillus Calmette-Guérin Failure in Patients with Non-Muscle-invasive Urothelial Carcinoma of the Bladder May Be Due to the Urologist's Failure to Detect Urothelial Carcinoma of the Upper Urinary Tract and Urethra

BACKGROUND: Various reasons exist for so-called bacillus Calmette-Guérin (BCG) failure in patients with non-muscle-invasive urothelial bladder carcinoma (NMIBC). OBJECTIVE: To explore whether urothelial carcinoma of the upper urinary tract (UUT) and/or prostatic urethra may be a cause for BCG failure. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of 110 patients with high-risk NMIBC repeatedly treated with intravesical BCG, diagnosed with disease recurrence, and followed for a median time of 9.1 yr. INTERVENTION: Two or more intravesical BCG induction courses without maintenance. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome was pattern of disease recurrence (BCG failure) within the urinary tract categorised into UUT and/or urethral carcinoma (with or without intravesical recurrence), and intravesical recurrence alone. Secondary outcome was survival. Predictors of UUT and/or urethral carcinoma and the effect of pattern of disease recurrence on cancer-specific survival were assessed with multivariable Cox regression analysis adjusting for multiple clinical and tumour characteristics. RESULTS AND LIMITATIONS: Of the 110 patients, 57 (52%) had UUT and/or urethral carcinoma (with or without intravesical recurrence), and 53 (48%) had intravesical recurrence alone. In patients with UUT and/or urethral carcinoma, bladder carcinoma in situ (Tis) before the first and second BCG course was present in 42 of 57 (74%) and 47 of 57 (82%) patients, respectively. On multivariable analysis, bladder Tis before the first and/or second BCG course was the only independent predictor of UUT and/or urethral carcinoma. Of the 110 patients, 69 (63%) were alive at last follow-up visit, 18 (16%) had died due to metastatic urothelial carcinoma, and 23 (21%) had died of other causes. Pattern of disease recurrence within the urinary tract was not an independent predictor of cancer-specific survival. Main study limitations were retrospective design and limited power for survival analysis. CONCLUSIONS: In our patients with high-risk NMIBC failing after two or more courses of intravesical BCG, UUT and/or urethral carcinoma was detected in >50% of the cases during follow-up. The vast majority of these patients had bladder Tis before the first and/or second BCG course. In patients experiencing the so-called BCG failure, a diagnostic work-up of UUT and prostatic urethra should always be performed to exclude urothelial carcinoma before additional intravesical therapy or even a radical cystectomy is considered.

Anti-Alpha-2-Macroglobulin-Like-1 Autoantibodies Are Detected Frequently and May Be Pathogenic in Paraneoplastic Pemphigus

Paraneoplastic pemphigus (PNP) shows autoantibodies mainly to plakin and desmosomal cadherin family proteins. We have recently identified alpha-2-macroglobulin-like-1 (A2ML1), a broad range protease inhibitor, as a unique PNP antigen. In this study, we tested a large number of PNP sera by various methods. Forty (69.0%) of 58 PNP sera recognized A2ML1 recombinant protein expressed in COS7 cells by immunofluorescence (IF) and/or immunoprecipitation (IP)/immunoblotting (IB). IP/IB showed higher sensitivity than IF. In addition, 22 (37.9%) PNP sera reacted with A2ML1 by IB of cultured normal human keratinocytes (NHKs) under non-reducing conditions. Statistical analyses using various clinical and immunological data showed that the presence of anti-A2ML1 autoantibodies was associated with early disease onset and absence of ocular lesions. Next, to investigate the pathogenic role of anti-A2ML1 antibody, we performed additional functional studies. Addition of anti-A2ML1 polyclonal antibody to culture media decreased NHK cell adhesion examined by dissociation assay, and increased plasmin activity detected by casein zymography, suggesting that anti-A2ML1 antibody may decrease NHK cell adhesion through plasmin activation by inhibition of A2ML1. This study demonstrates that autoantibodies to A2ML1 are frequently and specifically detected and may have a pathogenic role in PNP.

Bovine prion protein gene (PRNP) promoter polymorphisms modulate PRNP expression and may be responsible for differences in bovine spongiform encephalopathy susceptibility

The susceptibility of humans to the variant Creutzfeldt-Jakob disease is greatly influenced by polymorphisms within the human prion protein gene (PRNP). Similar genetic differences exist in sheep, in which PRNP polymorphisms modify the susceptibility to scrapie. However, the known coding polymorphisms within the bovine PRNP gene have little or no effect on bovine spongiform encephalopathy (BSE) susceptibility in cattle. We have recently found a tentative association between PRNP promoter polymorphisms and BSE susceptibility in German cattle (Sander, P., Hamann, H., Pfeiffer, I., Wemheuer, W., Brenig, B., Groschup, M., Ziegler, U., Distl, O., and Leeb, T. (2004) Neurogenetics 5, 19-25). A plausible hypothesis explaining this observation could be that the bovine PRNP promoter polymorphisms cause changes in PRNP expression that might be responsible for differences in BSE incubation time and/or BSE susceptibility. To test this hypothesis, we performed a functional promoter analysis of the different bovine PRNP promoter alleles by reporter gene assays in vitro and by measuring PRNP mRNA levels in calves with different PRNP genotypes in vivo. Two variable sites, a 23-bp insertion/deletion (indel) polymorphism containing a RP58-binding site and a 12-bp indel polymorphism containing an SP1-binding site, were investigated. Band shift assays indicated differences in transcription factor binding to the different alleles at the two polymorphisms. Reporter gene assays demonstrated an interaction between the two postulated transcription factors and lower expression levels of the ins/ins allele compared with the del/del allele. The in vivo data revealed substantial individual variation of PRNP expression in different tissues. In intestinal lymph nodes, expression levels differed between the different PRNP genotypes.