Testicular Dislocation After Pelvic Ring Injury: A Report of 2 Cases.

CASES: We present 2 cases of traumatic testicular dislocation associated with a pelvic ring injury after a motorcycle collision. Case 1 describes bilateral testicular dislocation discovered intraoperatively. Urology was consulted, and the testicles were manually reduced under general anesthesia. Case 2 describes unilateral testicular dislocation discovered at the 1-month follow-up after pelvic ring fixation. Concern for infarction prompted urology to take the patient for surgical reduction. Both cases resolved uneventfully without genitourinary complaints at the follow-up. CONCLUSIONS: Testicular dislocation is rare but should be considered in the setting of pelvic injury due to a motorcycle collision. Detection warrants urgent urologic consultation.

Covalent self-assembly of the specific RSSR isomer of 14-membered tetrakisphosphine.

The first representative of the specific RSSR isomer of 14-membered tetrakisphosphine has been obtained instead of the RRRR/SSSS isomer predicted according to the empirical rule formulated recently. The geometry of the obtained 14-P4N2 is preorganized for the dicopper complex formation with the unique coordination mode in the row of P4N2 corands.

Next Generation Driver for Attosecond and Laser-plasma Physics.

The observation and manipulation of electron dynamics in matter call for attosecond light pulses, routinely available from high-order harmonic generation driven by few-femtosecond lasers. However, the energy limitation of these lasers supports only weak sources and correspondingly linear attosecond studies. Here we report on an optical parametric synthesizer designed for nonlinear attosecond optics and relativistic laser-plasma physics. This synthesizer uniquely combines ultra-relativistic focused intensities of about 1020 W/cm2 with a pulse duration of sub-two carrier-wave cycles. The coherent combination of two sequentially amplified and complementary spectral ranges yields sub-5-fs pulses with multi-TW peak power. The application of this source allows the generation of a broad spectral continuum at 100-eV photon energy in gases as well as high-order harmonics in relativistic plasmas. Unprecedented spatio-temporal confinement of light now permits the investigation of electric-field-driven electron phenomena in the relativistic regime and ultimately the rise of next-generation intense isolated attosecond sources.

JC polyomavirus reactivation is common following allogeneic stem cell transplantation and its preemptive detection may prevent lethal complications.

Extended application of allogeneic stem cell transplantation (alloSCT) is expected to increase the frequency of JC polyomavirus (JCPyV)-related progressive multifocal leukoencephalopathy (PML). The aim of this study was to assess frequency, risk factors and course of JCPyV reactivation in allografted hematology patients. This retrospective study included consecutive adult patients, treated with alloSCT between January 2008 and December 2011. Quantitative JCPyV-PCR analysis was performed on whole blood DNA samples, originally drawn for cytomegalovirus detection since transplant date. The study included 164 patients diagnosed with hematological malignancies. Patients received reduced-intensity conditioning (n=74) or myeloablative conditioning (n=90), followed by alloSCT. Twenty patients developed transient and 20 had persistent JCPyV reactivation. Two of the patients with persistent reactivation showed a gradual increase in JCPyV levels, preceding PML development by 96 and 127 days. Cessation of immunosuppression resulted in complete resolution of neurological symptoms in one patient, while the other died of PML. Seventy percent of the 'persistently reactivating' patients died. Multivariate analysis confirmed age to be the only significant predictive factor for JCPyV reactivation. In conclusion, JCPyV reactivation occurs in a quarter of allografted patients. Preemptive detection of JCPyV reactivation in high-risk subjects and early discontinuation of immunosuppressive therapy may prevent development of lethal PML.

Bile acids inhibit Na⁺/H⁺ exchanger and Cl⁻/HCO3⁻ exchanger activities via cellular energy breakdown and Ca²âº overload in human colonic crypts.

Bile acids play important physiological role in the solubilisation and absorption of dietary lipids. However, under pathophysiological conditions, such as short bowel syndrome, they can reach the colon in high concentrations inducing diarrhoea. In this study, our aim was to characterise the cellular pathomechanism of bile-induced diarrhoea using human samples. Colonic crypts were isolated from biopsies of patients (controls with negative colonoscopic findings) and of cholecystectomised/ileum-resected patients with or without diarrhoea. In vitro measurement of the transporter activities revealed impaired Na⁺/H⁺ exchanger (NHE) and Cl⁻/HCO3⁻ exchanger (CBE) activities in cholecystectomised/ileum-resected patients suffering from diarrhoea, compared to control patients. Acute treatment of colonic crypts with 0.3 mM chenodeoxycholate caused dose-dependent intracellular acidosis; moreover, the activities of acid/base transporters (NHE and CBE) were strongly impaired. This concentration of chenodeoxycholate did not cause morphological changes in colonic epithelial cells, although significantly reduced the intracellular ATP level, decreased mitochondrial transmembrane potential and caused sustained intracellular Ca²âº elevation. We also showed that chenodeoxycholate induced Ca²âº release from the endoplasmic reticulum and extracellular Ca²âº influx contributing to the Ca²âº elevation. Importantly, our results suggest that the chenodeoxycholate-induced inhibition of NHE activities was ATP-dependent, whereas the inhibition of CBE activity was mediated by the sustained Ca²âº elevation. We suggest that bile acids inhibit the function of ion transporters via cellular energy breakdown and Ca²âº overload in human colonic epithelial cells, which can reduce fluid and electrolyte absorption in the colon and promote the development of diarrhea.

Predictors of relapse in patients with Crohn's disease in remission after 1 year of biological therapy.

BACKGROUND: Some of the most important questions relating to the use of biological therapy in inflammatory bowel diseases concern the duration of maintenance therapy. AIM: To assess the disease course and frequency of relapse of Crohn's disease (CD) following discontinuation of biological therapy, and to determine predictive factors for relapse. METHODS: One hundred twenty-one CD patients who had achieved clinical remission following 1 year of biological therapy and for whom biological therapy was then discontinued participated in this prospective observational study. Eighty-seven CD patients had received infliximab and 34 adalimumab. The definition of relapse was an increase of >100 points in CDAI to at least a CDAI of 150 points. RESULTS: Biological therapy was restarted within 1 year of treatment cessation in 45% of patients. Logistic regression analysis revealed that previous biological therapy (P = 0.011) and dose intensification during the 1-year course of biological therapy (P = 0.024) were associated with the need for and the time to the restarting of biological therapy. Smoking was observed to have an effect that was not statistically significant (P = 0.053). CONCLUSIONS: Biological therapy was restarted a median of 6 months after discontinuation in almost half of Crohn's disease patients in who had been in clinical remission following 1 year of biological therapy. These results suggest that, in the event of the presence of certain predictive factors, biological therapy should probably be continued for more than 1 year by most patients.

Proteinase-activated receptor-4 evoked colorectal analgesia in mice: an endogenously activated feed-back loop in visceral inflammatory pain.

BACKGROUND: Activation of proteinase-activated receptor-4 (PAR-4) from the colonic lumen has an antinociceptive effect to colorectal distension (CRD) in mice in basal conditions. We aimed to determine the functional localization of the responsible receptors and to test their role in two different hyperalgesia models. METHODS: Mice received PAR-4 activating peptide (PAR-4-AP, AYPGKF-NH(2)) or vehicle intraperitoneally (IP), and abdominal EMG response to CRD was measured. The next group received PAR-4-AP intracolonically (IC) with or without 2,4,6-triaminopyrimidine, a chemical tight junction blocker, before CRD. The SCID mice were used to test the role of lymphocytes in the antihyperalgesic effect. The effects of PAR-4-AP and PAR-4-antagonist (P4pal-10) were evaluated in water avoidance stress (WAS) model and low grade 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis. Spinal Fos protein expression was visualized by immunohistochemistry. KEY RESULTS: The antinociceptive effect of PAR-4-AP disappeared when was administrered IP, or with the blockade of colonic epithelial tight junctions, suggesting that PAR-4-AP needs to reach directly the nerve terminals in the colon. The CRD-induced spinal Fos overexpression was reduced by 43% by PAR-4-AP. The PAR-4-AP was antihyperalgesic in both hyperalgesia models and in mice with impaired lymphocytes. The PAR-4-antagonist significantly increased the TNBS, but not the WAS-induced colonic hyperalgesia. CONCLUSIONS & INFERENCES: The antinociceptive effect of PAR-4-AP depends on its penetration to the colonic mucosa. The PAR-4 activation is endogenously involved as a feedback loop to attenuate inflammatory colonic hyperalgesia to CRD.

A renewed insight into Barrett's esophagus: comparative histopathological analysis of esophageal columnar metaplasia.

Specialized intestinal metaplasia (SIM) is considered as a premalignant condition of the esophagus, but other types of esophageal metaplasia are commonly neglected. A standardized histopathological analysis was focused not only on SIM but also on the presence of metaplastic processes typical of additional glands. A morphological study using standardized histopathological tests was carried out between 2004 and 2007, with biopsies taken from esophageal mucosa of 826 consecutive patients. Mean age and male : female ratio of patients were 55.6 ± 14.7 and 1.1 : 1, respectively. Only 4.1% (n = 34) of all cases proved to have SIM. The remainder of the cases (n = 615; 74.4%) contained cardiac-fundic mucosa without SIM. Some samples exhibited superficial mucous glands, pancreatic acinar metaplasia (PAM), and ciliated metaplasia accounting for 24% (n = 198), 14.9% (n = 123), and 0.2% (n = 2), respectively. SIM was colocalized with superficial mucous glands (103/198 superficial mucous gland cases; P < 0.001). Low-grade dysplasia (n = 51; 6.2%) and high-grade dysplasia (n = 9; 1.1%) were found mainly in SIM (37/51; 9/9; P = 0.071) with male preponderance (3 : 1 at low-grade and 2 : 1 at high-grade dysplasia). PAM was found mainly in cases without dysplasia (103 of 123 pancreatic metaplasias; P < 0.001). SIM alone in the esophagus is rare, and its frequent association with cardiac mucosa-type metaplasia testifies to transition of mucinous-goblet cell through pseudogoblet cells. PAM rather indicates absence of dysplasia, but superficial mucous glands predicts that SIM follows dysplasia.

Detailed esophageal function and morphological analysis shows high prevalence of gastroesophageal reflux disease and Barrett's esophagus in patients with cervical inlet patch.

Although the pathogenesis of cervical inlet patch (CIP) is not fully understood, most authors consider it as a congenital abnormality, whereas others surmise it to be related to gastroesophageal reflux disease (GERD). We aimed to evaluate esophageal function and the prevalence of GERD and Barrett's esophagus in patients with CIP. GERD is defined by the presence of erosive esophagitis or an abnormal pH monitoring. Seventy-one consecutive patients with endoscopic and histological evidence of CIP were prospectively evaluated. Esophageal symptom analysis, 24-hour simultaneous biliary reflux and double-channel pH-monitoring, and esophageal manometry were carried out in 65/71 (92%) patients and in 25 matched controls. Six patients were not suitable for testing and were, therefore, excluded. The histological evaluation of the heterotopic islands showed cardia and/or oxyntic mucosa in 64/65 (98%) patients and specialized intestinal metaplasia (SIM) in one patient (2%). The cardia and/or oxyntic mucosa was accompanied by focally appearing pancreatic acinar metaplasia and pancreatic ductal metaplasia in 7/64 (11%) and in 1/64 (2%), superficial mucous glands in 6/64 (9%), and SIM in 2/64 (3%) cases. In total, SIM was present in three patients (5%), and one of them had low-grade dysplasia. At the gastroesophageal junction, 28 (43%) patients had columnar metaplasia, including nine (14%) patients with SIM. Erosive esophagitis was present in 37 (57%) cases. Thirty-two patients (49%) had abnormal acid reflux in the distal and 25 (38%) in the proximal esophagus. Abnormal biliary reflux was present in 25 (38%) cases. On the basis of endoscopic and pH studies, GERD was established in 44/65 (68%) patients. Typical reflux symptoms were common (33/65, 51%). The combined 24-hour biliary and double-channel pH-monitoring detected significantly more significant acidic reflux at both measurement points and significantly longer bile exposure time in the distal esophagus in patients with CIP. Acid secretion in the CIP was detected in three (5%) cases. Esophageal manometry revealed decreased LES pressure and prolonged relaxation with decreased peristaltic wave amplitude, and an increased number of simultaneous contractions in the esophageal body. The detailed evaluation of the esophageal morphology and function in subjects with CIP showed a high prevalence of GERD and Barrett's esophagus. Further studies are needed to evaluate whether combined acidic and biliary reflux is able to promote similar histomorphological changes in the CIP, as it is shown distally in patients with Barrett's esophagus.

[Efficacy of alverina citrate and simethicone combination in abdominal pain and discomfort of irritable bowel syndrome].

UNLABELLED: The alverina citrate and simethicone combination (ACS-Meteospazmil) is used for irritable bowel syndrome (IBS) for almost 20 years, but the supporting scientific evidence for efficacy is limited. OBJECTIVE: to evaluate the effectiveness of ACS in patients with abdominal pain and discomfort at IBS. METHODS: In a double-blind, randomized, placebo-controlled study enrolled 412 patients with IBS conform to Rome criteria III. Selection criterion in the study was to evaluate the intensity of abdominal pain or discomfort during the 2-week run-in period without medication, which according to analog scale (VAS) was to be 60-100 mm. With the help of an interactive voice communication system (IVCS), patients were randomized to treatment with either alverin citrate 60 mg with Simethicone 300 mg three times daily or corresponding placebo for 4 weeks. RESULTS: For analyze of the results of the study were selected 409 patients. After 4 weeks, patients treated with ACS, was observed lower scores in the VAS assessment of abdominal pain or discomfort compared to placebo (mean--40 and 50 mm, p = 0.047) and a higher level of response to treatment (46.8% and 34.3%, respectively). Recorded side effects were similar in both groups. CONCLUSION: The combination of ACS was significantly more effective in patients with IBS compared to placebo in reducing abdominal pain or discomfort.

Clinical trial: the efficacy of alverine citrate/simeticone combination on abdominal pain/discomfort in irritable bowel syndrome--a randomized, double-blind, placebo-controlled study.

BACKGROUND: Alverine citrate and simeticone combination has been used for almost 20 years in irritable bowel syndrome (IBS), but supportive scientific evidence of efficacy was limited. AIM: To evaluate the efficacy of alverine citrate and simeticone combination in patients with IBS-related abdominal pain/discomfort. METHODS: A total of 412 IBS patients meeting ROME III criteria were included in this double-blind randomized placebo-controlled study if their abdominal pain/discomfort intensity was at least 60 mm on a 0-100 mm visual analogue scale (VAS) during a 2-week run-in treatment-free period. Patients were randomly assigned through the use of Interactive Voice Response System to receive either alverine citrate 60 mg with simeticone 300 mg three times daily or matching placebo for 4 weeks. RESULTS: The full analysis set included 409 patients (71.4% female: mean age: 46.2 +/- 13.9 years). At week 4, alverine citrate and simeticone group had lower VAS scores of abdominal pain/discomfort (median: 40 mm vs. 50 mm, P = 0.047) and higher responder rate (46.8% vs. 34.3%, OR = 1.3; P = 0.01) as compared with placebo group. Patient receiving alverine citrate and simeticone reported greater global symptom improvement compared with those receiving placebo (P = 0.0001). Reported adverse events were similar in both groups. CONCLUSION: Alverine citrate/simeticone combination was significantly more effective than placebo in relieving abdominal pain/discomfort in patients with IBS.