Techniques to Address Humeral Bone Insufficiency During Total Shoulder Arthroplasty With a Nonspherical Humeral Head and Inlay Glenoid.

Total shoulder arthroplasty with a humeral head resurfacing (HHR) component and an inlay glenoid (OVOMotion; Arthrosurface) is a successful treatment option for patients with advanced glenohumeral arthritis, an intact rotator cuff, and adequate proximal humeral bone stock. In patients with poor proximal humeral bone, historically stemmed humeral components have been used instead of HHR. However, strategies can be used to successfully optimize HHR implant fixation in suboptimal bone without converting to stemmed implants or in surgical centers where stemmed prostheses are not available. This Technical Note describes 3 techniques-upsizing the humeral taper post, using humeral autograft, and cementation-to improve humeral implant fixation in patients with suboptimal bone stock when using the Arthrosurface OVOMotion implant.

Anatomic total shoulder arthroplasty with a nonspherical humeral head and inlay glenoid: 90-day complication profile in the inpatient versus outpatient setting.

BACKGROUND: Total shoulder arthroplasty (TSA) with a nonspherical humeral head component and inlay glenoid is a successful bone-preserving treatment for glenohumeral arthritis. This study aimed to describe the 90-day complication profile of TSA with this prosthesis and compare major and minor complication and readmission rates between inpatient- and outpatient-procedure patients. METHODS: A retrospective review was performed of a consecutive cohort of patients undergoing TSA with a nonspherical humeral head and inlay glenoid in the inpatient and outpatient settings by a single surgeon between 2017 and 2022. Age, sex, body mass index, American Society of Anesthesiologists (ASA) score, Charlson Comorbidity Index (CCI), and 90-day complication and readmission rates were compared between inpatient and outpatient groups. RESULTS: One hundred eighteen TSAs in 111 patients were identified. Mean age was 64.9 years (range, 39-90) and 65% of patients were male. Ninety-four (80%) and 24 (20%) patients underwent outpatient and inpatient procedures, respectively. Four complications (3.4%) were recorded: axillary nerve stretch injury, isolated ipsilateral arm deep venous thrombosis (DVT), ipsilateral arm DVT with pulmonary embolism requiring readmission, and gastrointestinal bleed requiring readmission. There were no reoperations or other complications. Outpatients were younger with lower ASA and CCI scores than inpatients; however, there was no difference in complications (1/24 vs. 3/94, P=1.00) or readmissions (1/24 vs. 1/94, P=0.37) between these two groups. CONCLUSIONS: TSA with a nonspherical humeral head and inlay glenoid can be performed safely in both inpatient and outpatient settings. Rates of early complications and readmissions were low with no difference according to surgical setting. Level of evidence: IV.

Structure-Functional Selectivity Relationship Studies on A-86929 Analogs and Small Aryl Fragments toward the Discovery of Biased Dopamine D1 Receptor Agonists.

Dopamine regulates normal functions such as movement, reinforcement learning, and cognition, and its dysfunction has been implicated in multiple psychiatric and neurological disorders. Dopamine acts through D1- (D1R and D5R) and D2-class (D2R, D3R, and D4R) receptors and activates both G protein- and ß-arrestin-dependent signaling pathways. Current dopamine receptor-based therapies are used to ameliorate motor deficits in Parkinson's disease or as antipsychotic medications for schizophrenia. These drugs show efficacy for ameliorating only some symptoms caused by dopamine dysfunction and are plagued by debilitating side effects. Studies in primates and rodents have shown that shifting the balance of dopamine receptor signaling toward the arrestin pathway can be beneficial for inducing normal movement, while reducing motor side effects such as dyskinesias, and can be efficacious at enhancing cognitive function compared to balanced agonists. Several structure-activity relationship (SAR) studies have embarked on discovering ß-arrestin-biased dopamine agonists, focused on D2 partial agonists, noncatechol D1 agonists, and mixed D1/D2R dopamine receptor agonists. Here, we describe an SAR study to identify novel D1R ß-arrestin-biased ligands using A-86929, a high-affinity D1R catechol agonist, as a core scaffold to identify chemical motifs responsible for ß-arrestin-biased activity at both D1 and D2Rs. Most of the A-86929 analogs screened were G protein-biased, but none of them were exclusively arrestin-biased. Additionally, various small-fragment molecular probes displayed weak bias toward the ß-arrestin pathway. Continued in-depth SFSR (structure-functional selectivity relationship) studies informed by structure determination, molecular modeling, and mutagenesis studies will facilitate the discovery of potent and efficacious arrestin-biased dopamine receptor ligands.

Human pegivirus type 1 infection in Asia-A review of the literature.

The human pegivirus type 1 (HPgV-1)-as known as hepatitis G virus and GB virus C-is a common single-stranded RNA flavivirus. Because few studies have demonstrated an association between HPgV-1 infection and disease, screening for HPgV-1 is not performed routinely. Nonetheless, a beneficial impact of HPgV-1 infection on HIV disease progression has been reported in multiple studies. Given the burden of HIV in Asia and the complex interactions between viral co-infections and the host, we provide a comprehensive overview of the existing data from Asia on HPgV-1 infection, including the prevalence and circulating genotypes in all Asian countries with data reported. This review highlights the research conducted thus far and emphasizes the need for additional studies on HPgV-1 across the Asian continent.

Physiologic Effects of Instilled and Aerosolized Surfactant Using a Breath-Synchronized Nebulizer on Surfactant-Deficient Rabbits.

Surfactant administration incorporates liquid bolus instillation via endotracheal tube catheter and use of a mechanical ventilator. Aerosolized surfactant has generated interest and conflicting data related to dose requirements and efficacy. We hypothesized that aerosolized surfactant with a novel breath-actuated vibrating mesh nebulizer would have similar efficacy and safety as instilled surfactant. Juvenile rabbits (1.50 ± 0.20 kg, n = 17) were sedated, anesthetized, intubated, and surfactant was depleted via lung lavage on mechanical ventilation. Subjects were randomized to receive standard dose liquid instillation via catheter (n = 5); low dose surfactant (n = 5) and standard dose surfactant (n = 5) via aerosol; and descriptive controls (no treatment, n = 2). Peridosing events, disease severity and gas exchange, were recorded every 30 min for 3 h following surfactant administration. Direct-Instillation group had higher incidence for peridosing events than aerosol. Standard dose liquid and aerosol groups had greater PaO2 from pre-treatment baseline following surfactant (p < 0.05) with greater ventilation efficiency with aerosol (p < 0.05). Our study showed similar improvement in oxygenation response with greater ventilation efficiency with aerosol than liquid bolus administration at the same dose with fewer peridosing events. Breath-synchronized aerosol via nebulizer has potential as a safe, effective, and economical alternative to bolus liquid surfactant instillation.

Patellar Fracture Fixation With Cannulated Compression Screws and FiberTape Cerclage.

Transverse patella fractures with loss of knee extensor mechanism function are a common orthopaedic injury requiring operative fixation. Current accepted surgical options for noncomminuted transverse fractures include open reduction with tension band wiring. Although these procedures result in good clinical outcomes and fracture healing, symptomatic hardware from the historically used metal implants is very common. The purpose of this Technical Note is to describe a technique for treatment of transverse patellar fractures using cannulated compression screws with tensioned high-resistance suture tape functioning as the tension band. This technique provides effective, reproducible fracture fixation while minimizing symptomatic hardware, failure, and reoperation.

Breath-Synchronized Nebulized Surfactant in a Porcine Model of Acute Respiratory Distress Syndrome.

OBJECTIVES: Effective treatment options for surfactant therapy in acute respiratory distress syndrome and coronavirus disease 2019 have not been established. To conduct preclinical studies in vitro and in vivo to evaluate efficiency, particle size, dosing, safety, and efficacy of inhaled surfactant using a breath-synchronized, nebulized delivery system in an established acute respiratory distress syndrome model. DESIGN: Preclinical study. SETTING: Research laboratory. SUBJECTS: Anesthetized pigs. INTERVENTION: In vitro analysis included particle size distribution and inhaled dose during simulated ventilation using a novel breath-synchronized nebulizer. Physiologic effects of inhaled aerosolized surfactant (treatment) were compared with aerosolized normal saline (control) in an adult porcine model (weight of 34.3 ± 0.6 kg) of severe acute respiratory distress syndrome (Pao2/Fio2 <100) with lung lavages and ventilator-induced lung injury during invasive ventilation. MEASUREMENTS AND MAIN RESULTS: Mass median aerosol diameter was 2.8 µm. In vitro dose delivered distal to the endotracheal tube during mechanical ventilation was 85% ± 5%. Nebulizers were functional up to 20 doses of 108 mg of surfactant. Surfactant-treated animals (n = 4) exhibited rapid improvement in oxygenation with nearly full recovery of Pao2/Fio2 (~300) and end-expiratory lung volumes with nominal dose less than 30 mg/kg of surfactant, whereas control subjects (n = 3) maintained Pao2/Fio2 less than 100 over 4.5 hours with reduced end-expiratory lung volume. There was notably greater surfactant phospholipid content and lower indicators of lung inflammation and pathologic lung injury in surfactant-treated pigs than controls. There were no peridosing complications associated with nebulized surfactant, but surfactant-treated animals had progressively higher airway resistance post treatment than controls with no differences in ventilation effects between the two groups. CONCLUSIONS: Breath-synchronized, nebulized bovine surfactant appears to be a safe and feasible treatment option for use in coronavirus disease 2019 and other severe forms of acute respiratory distress syndrome.

Retrograde Labeling Illuminates Distinct Topographical Organization of D1 and D2 Receptor-Positive Pyramidal Neurons in the Prefrontal Cortex of Mice.

The cortex plays an important role in regulating motivation and cognition, and does so by regulating multiple subcortical brain circuits. Glutamatergic pyramidal neurons in the prefrontal cortex (PFC) are topographically organized in different subregions such as the prelimbic, infralimbic (IL), and orbitofrontal and project to topographically-organized subcortical target regions. Dopamine D1 and D2 receptors are expressed on glutamatergic pyramidal neurons in the PFC. However, it is unclear whether D1 and D2 receptor-expressing pyramidal neurons in the PFC are also topographically organized. We used a retrograde adeno-associated virus (AAVRG)-based approach to illuminate the topographical organization of D1 and D2 receptor-expressing neurons, projecting to distinct striatal and midbrain subregions. Our experiments reveal that AAVRG injection in the nucleus accumbens (NAcc) or dorsal striatum (dSTR) of D1Cre mice labeled distinct neuronal subpopulations in medial orbitofrontal or prelimbic PFC, respectively. However, AAVRG injection in NAcc or dSTR of D2Cre mice labeled medial orbitofrontal, but not medial prelimbic PFC, respectively. Additionally, D2R+ but not D1R+ PFC neurons were labeled on injection of AAVRG in substantia nigra pars compacta (SNpc). Thus, our data are the first to highlight a unique dopamine receptor-specific topographical pattern in the PFC, which could have profound implications for corticostriatal signaling in the basal ganglia.

Structure-Functional-Selectivity Relationship Studies of Novel Apomorphine Analogs to Develop D1R/D2R Biased Ligands.

Loss of dopamine neurons is central to the manifestation of Parkinson's disease motor symptoms. The dopamine precursor L-DOPA, the most commonly used therapeutic agent for Parkinson's disease, can restore normal movement yet cause side-effects such as dyskinesias upon prolonged administration. Dopamine D1 and D2 receptors activate G-protein- and arrestin-dependent signaling pathways that regulate various dopamine-dependent functions including locomotion. Studies have shown that shifting the balance of dopamine receptor signaling toward the arrestin pathway can be beneficial for inducing normal movement, while reducing dyskinesias. However, simultaneous activation of both D1 and D2Rs is required for robust locomotor activity. Thus, it is desirable to develop ligands targeting both D1 and D2Rs and their functional selectivity. Here, we report structure-functional-selectivity relationship (SFSR) studies of novel apomorphine analogs to identify structural motifs responsible for biased activity at both D1 and D2Rs.

A biomechanical comparison of new techniques for distal clavicular fracture repair versus locked plating.

BACKGROUND: Unstable distal clavicular fractures treated surgically are associated with high failure rates and hardware-related complications. Newer techniques have shown promising early clinical results with fewer hardware complications; however, their biomechanical performance has not been assessed. This study biomechanically compared a distal-third locking plate with 3 newer techniques that incorporate coracoid fixation into the construct. METHODS: The study randomized 36 adult fresh frozen cadaveric shoulders to 4 groups: (1) distal-third locking plate (P); (2) distal-third locking plate with a coracoid button augmentation (P + CB); (3) coracoclavicular button (CB); and (4) coracoclavicular button with coracoclavicular ligament reconstruction using semitendinosus allograft (CB + CC). After fixation, each specimen was stressed in the coronal plane. Cyclic displacement, load at 10-mm displacement, and ultimate load to failure were measured. RESULTS: All 3 experimental groups biomechanically outperformed the locking plate. Mean load to failure was significantly higher in the CB (343 ± 76 N) and CB + CC (349 ± 94 N) groups compared with the P group (193 ± 52 N). There was also significantly less cyclic displacement in the CB (4.3 ± 1.9 mm) and CB + CC (4.4 ± 1.9 mm) groups compared with the P group (8.2 ± 2.9 mm). With respect to load at 10 mm of displacement, which essentially measures a clinical failure, the P + CB (235 ± 112 N), CB (253 ± 111 N), and CB+CC (238 ± 76 N) experimental groups significantly outperformed the P group (96 ± 29 N). CONCLUSIONS: CB and CB + CC techniques demonstrated more than 75% greater strength than the traditional locking plate alone. Coupled with greater overall construct strength and lower-profile hardware, these newer techniques may result in improved clinical outcome and fewer hardware-related complications.

Diagnosis, characterization, and 3-month outcome after detoxification of 39 patients with narcotic bowel syndrome.

UNLABELLED: OBFECTIVES: Narcotic bowel syndrome (NBS) is characterized by a paradoxical increase in abdominal pain associated with continued or escalating dosages of narcotics. This study evaluated the clinical and psychosocial features of patients with NBS and the response to detoxification treatment. METHODS: For 2 years, 39 patients seen by the GI consult service at the University of North Carolina at Chapel Hill (UNC) with presumed NBS were placed on a detoxification program. Clinical, psychosocial, health status, and outcome data were obtained before and after detoxification. Our aims were to: (i) clinically characterize patients with presumed NBS, (ii) assess the clinical response and adverse effects to detoxification, (iii) identify clinical and psychosocial predictors of treatment response, and (iv) determine the clinical outcome at 3 months after detoxification and the time frame for patients who revert back to narcotics. RESULTS: Of the 39 patients detoxified, 89.7% met predefined criteria. Patients were mostly well educated (14.5 ± 2.3 years of school), female (92.3%), and with a variety of diagnoses (21% irritable bowel syndrome IBS/functional, 37% inflammatory bowel disease and other structural, 29% fibromyalgia and other functional somatic, or orthopedic, and 13% postoperative or other). They reported high health-care use (15.3 ± 10.1 MD visits/6 months; 6.5 ± 6.1 hospitalizations/2 years, 6.4 ± 2.0 surgeries/lifetime), and 82.1% were jobless. Despite high dosages of narcotics (total intravenous (IV) morphine equivalent 75.3 ± 78.0 mg/day), pain scores were rated severe (52.9 ± 28.8 visual analog scale (VAS); 257.1 ± 139.6 functional bowel disorder severity index (FBDSI); 17.2 ± 10.2 (McGill Pain and greater than labor or postoperative pain). Multiple symptoms were reported (n = 17.8 ± 9.2) and rated as moderate to severe. Psychosocial scores showed high catastrophizing (19.9 ± 8.6); poor daily function (Short Form-36 (SF-36) physical 28.3 ± 7.7, mental 34.3 ± 11.0; worse than tetraplegia); 28.2% were clinically depressed and 33.3% anxious (Hospital Anxiety and Depression Scale (HADS)). Detoxification was successfully completed by 89.7%; after detoxification, abdominal pain was reduced by 35% (P < 0.03) and nonabdominal pain by 42% (P < 0.01) on VAS, and catastrophizing significantly improved (P < 0.01). Responder status was met in 56.4% with 48.7% achieving a ≥ 30% reduction in pain. By 3 months after detoxification, 45.8% had returned to using narcotics. For those who remained off narcotics at 3 months, the VAS abdominal pain score was 75% lower than pretreatment when compared with those who went back on narcotics (24% lower). Successful detoxification and a good clinical response was associated with low abuse potential (Current Opioid Misuse Measure (COMM) score < 9). CONCLUSIONS: Despite severe pain, poor coping, and poor health status, almost all patients with NBS undergoing detoxification were able to stop using narcotics and have significant improvement in pain and coping. However, almost ½ reverted to narcotic use at 3 months. Those who stayed off narcotics showed greater improvement in pain scores. This study provides a rationale for treating patients with NBS by detoxification in order to improve their clinical status. Further work is needed to understand the reasons for the high recidivism rate.

Non-esophageal symptoms cannot differentiate between erosive reflux esophagitis and non-erosive reflux disease in a referred population.

BACKGROUND: Non-esophageal symptoms are highly prevalent in non-erosive reflux disease (NERD). However, their prevalence in erosive esophagitis (ErE) is unclear. The aims of this study were to compare patients with pH-positive NERD and ErE in terms of non-esophageal symptoms and to investigate whether such symptoms can differentiate between these two conditions. MATERIAL AND METHODS: A prospective observational study of ErE and pH-positive NERD patients matched for age and gender with a nested case-control analysis. Symptoms were scored on validated scales. The association between the scale scores and diagnosis was evaluated in a random group comprising 67% of the total (group A) and was validated on the rest (group B). RESULTS: 124 ErE and 248 pH-positive NERD patients were studied. In group A, pH-positive NERD patients scored higher than ErE patients on all symptom scales. Scores on chest, constipation, sleep and urinary symptoms scales were significantly associated with diagnosis. A composite weighted score on these scales was 41.5% sensitive and 86.0% specificity in the differentiation of ErE from pH-positive NERD patients. When applied to group B, the sensitivity and specificity of this score were 48.8% and 70.3%, respectively. CONCLUSIONS: Digestive and non-digestive symptoms occurred with a significant higher prevalence in pH-positive NERD compared with ErE patients. However a composite score on scales of constipation, chest, sleep and urinary symptoms was not enough sensitive and specific to differentiate these two conditions.

Evidence of intestinal inflammation in patients with cystic fibrosis.

OBJECTIVES: Treatment with pancreatic enzymes fails to completely correct malabsorption and gastrointestinal symptoms in patients with cystic fibrosis (CF). The aim of the present study was to examine the small intestine of patients with CF without overt evidence of gastrointestinal disease using capsule endoscopy (CE). METHODS: Patients with CF received the agile patency capsule and, depending on the result of that procedure, then underwent standard CE using the PillCam SB capsule (Given Imaging, Yokneam, Israel). A stool specimen was taken on the same day as the CE for determination of the calprotectin level. RESULTS: Forty-two patients with CF ages 10 to 36 years were included; 29 had pancreatic insufficiency. One patient failed to excrete the patency capsule after 36 hours and was withdrawn from the study. Pulmonary function was mild to moderate with FEV1 68.5% +/- 16% predicted. Review of the CE videos showed that most of the patients had varying degrees of diffuse areas of inflammatory findings in the small bowel including edema, erythema, mucosal breaks, and frank ulcerations. There were no adverse events. Fecal calprotectin levels were markedly high in patients with pancreatic insufficiency, 258 microg/g (normal <50). CONCLUSIONS: Small bowel mucosal pathology may be detected using CE in most of the patients with CF. The high fecal calprotectin levels found are suggestive of mucosal inflammation, which may correlate with the CE findings. Additional study is required to examine the possible relation of these mucosal lesions, which may be part of a newly identified enteropathy associated with CF, with persistent intestinal malabsorption in many of these patients.

Enhancement of electric oxygen-iodine laser performance using larger mode volume resonators.

Herein the authors report on the demonstration of an 87% enhancement in cw laser power on the 1315 nm transition of atomic iodine via a 100% increase in the resonator mode volume. O(2)(a1Delta) is produced by a single rf-excited electric discharge sustained in an O(2)-He-NO gas mixture flowing through a rectangular geometry, and I(P2(1/2)) is then pumped using energy transferred from O(2)(a1Delta). A total laser output power of 102.5 W was obtained using a Z-pass resonator configuration.

Screening for drug-resistant Candida yeasts with chromogenic agar.

We examined the utility of agar dilution to screen yeasts for reduced susceptibility to several newer antifungal drugs including echinocandins and azoles. We compared agar dilution susceptibility screening with the Clinical and Laboratory Standards Institute (CLSI) method for Candida isolates. We added echinocandins and azoles to CHROMagar Candida medium prior to its solidification. Assessment of resistance was based on growth characteristics, wherein decreased colony size in the presence of antifungal drugs was used as an indicator of susceptibility. Clinical Candida isolates of C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. guilliermondii, C. lusitaniae, C. rugosa and C. dubliniensis were screened for drug susceptibility. Overall, antifungal susceptibility of the yeasts to anidulafungin, caspofungin, micafungin, posaconazole and voriconazole, determined using CHROMagar agar dilution, were shown to be 96, 80, 94, 90 and 97% as accurate, respectively, as those determined by the CLSI method, i.e., within one tube dilution of CLSI MICs. Categorical errors by percentage had a broader range. Major errors noted with anidulafungin, caspofungin and micafungin were 3, 6 and 0%, respectively, while very major errors were 15, 55 and 38%, respectively. Major errors with posaconazole and voriconazole were 12 and 0%, respectively, while very major errors were 0 and 22%, respectively, compared to CLSI standards. Most of the assessment errors were found with C. glabrata and C. parapsilosis. Agar dilution screening for drug susceptibility with the current panel of antifungal drugs is rapid, accurate and effective. However, the determination of resistance or non-susceptibility in yeasts may be more problematic, and may be species dependent.

Trends in acute non-variceal bleeding in Israel in 1996-2007: a significant decrease in the rates of bleeding peptic ulcers.

BACKGROUND: A decrease in the incidence of hospital admissions for acute non-variceal upper GI bleeding (AUGIB) has been reported in regions with a low prevalence of Helicobacter pylori (HP) infection. AIM: To investigate trends in hospital admissions for AUGIB in Israel, where the prevalence of HP infection is intermediate. METHODS: We have searched the National Hospital Discharge Database of the Israeli Ministry of Health, where all admissions to acute care hospitals for the period January 1, 1996 through December 31, 2007 are compiled. Using a validated strategy, we identified all admissions for AUGIB according to ICD-9-CM codes. Incidence rates were calculated and adjusted to reflect the age and gender distribution of the Israeli population. RESULTS: The overall rates of hospital admissions for AUGIB decreased significantly from 29.3 to 16.8 cases/10(5)population/year (p<0.0001). The decreases were similar in both genders. This decrease was due to decreased rates of bleeding from duodenal ulcers (from 13.6 to 5 cases/10(5)population/year) and gastric ulcers (from 4.3 to 2.4 cases/10(5)population/year). The rates of bleeding from other causes remained unchanged. The rates of surgical interventions bleeding control decreased significantly (overall from 11 to 4%). The in-hospital mortality rate varied between 7.6 and 7%, did not change significantly in both genders but increased significantly with age during the study period. CONCLUSIONS: A decline in the overall incidence of AUGIB during the study period was due to a significant decrease in the rate of bleeding peptic ulcers.

Bowel symptoms in nonerosive gastroesophageal reflux disease: nature, prevalence, and relation to acid reflux.

BACKGROUND: Nonerosive gastroesophageal reflux disease (NERD) patients frequently show features of the irritable bowel syndrome (IBS). AIMS: To investigate the prevalence and intensity of bowel symptoms and their relationship to esophageal acid exposure in NERD patients. METHODS: Bowel and reflux symptoms and IBS status were assessed in NERD patients (normal upper endoscopy; esophageal pH <4 for >or= 5% of the time on 24-h pH monitoring; n=326), in relation to nonpatient controls. Bowel symptoms were scored on the 3 scales: diarrhea, constipation, and pain/gas symptoms. RESULTS: NERD and age were independently associated with bowel symptoms. NERD patients scored significantly higher than controls on all bowel scales. In a multivariate analysis, the scores on the pain/gas scale were independently associated with NERD. In NERD patients, reflux symptoms independently predicted the bowel symptoms while acid exposure did not. Forty-nine percent of the NERD patients and 18% of the controls met the criteria for IBS [IBS(+)NERD]. IBS(+)NERD patients scored significantly higher than those not meeting IBS criteria [IBS(-)] on all bowel scales. Yet IBS(-) patients scored significantly higher than controls on the scales of constipation and pain/gas. IBS(+)NERD patients scored higher than IBS(-) also on the GERD symptoms scale. CONCLUSIONS: (1) NERD patients scored significantly higher than controls on all the bowel scales; (2) Bowel symptoms were associated with reflux symptom scores, but not with acid exposure. (3) The presence of IBS features in a large proportion of NERD patients reflects a high prevalence of visceral hypersensitivity that may aggravate acid reflux symptoms.

Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer.

Many genes associated with CpG islands undergo de novo methylation in cancer. Studies have suggested that the pattern of this modification may be partially determined by an instructive mechanism that recognizes specifically marked regions of the genome. Using chromatin immunoprecipitation analysis, here we show that genes methylated in cancer cells are specifically packaged with nucleosomes containing histone H3 trimethylated on Lys27. This chromatin mark is established on these unmethylated CpG island genes early in development and then maintained in differentiated cell types by the presence of an EZH2-containing Polycomb complex. In cancer cells, as opposed to normal cells, the presence of this complex brings about the recruitment of DNA methyl transferases, leading to de novo methylation. These results suggest that tumor-specific targeting of de novo methylation is pre-programmed by an established epigenetic system that normally has a role in marking embryonic genes for repression.

Electromagnetic interference with implantable cardiac pacemakers by video capsule.

BACKGROUND: Electromagnetic fields, such as those generated by cellular phones and metal detectors, may interfere with normal pacemaker function. However, it remains unclear whether the wireless capsule endoscope interacts with implanted pacemakers. This prospective study evaluated potential interactions between the M2A video capsule (Given Imaging, Yoknam, Israel) and implanted pacemakers. METHODS: A total of 100 consecutive patients (70 men, 30 women) with an implanted pacemaker (95 on bipolar mode) were studied. The testing was performed with a functional testing device (Test Cap) for the Given Diagnostic System that reproduces the effect of the video capsule by transmitting at exactly the same frequency. During continuous electrocardiographic monitoring and recording, 100 tests were carried out without changing the pacemaker settings. Those with a positive result were retested 1 week later. RESULTS: The 100 pacemakers evaluated in the study population included the following: 70 dual chamber (11 DDD, 56 DDDR, 3 VDD) and 30 ventricular inhibited (12 VVI, 18 VVIR). In 4 of the 100 patients, pacemaker interference (noise-mode function forcing a synchronous mode) was registered during the Test Cap operation. Three patients had a dual-chamber pacemaker, and one had a single-chamber pacemaker. The interference was reproducible in all cases 1 week later. None of the implanted pacemakers tested was affected by oversensing. CONCLUSIONS: Electromagnetic interferences with pacemakers from the M2A video capsule can occur, but this is without clinical significance. No potentially dangerous pacemaker inhibition was observed.

Extraintestinal symptoms in irritable bowel syndrome and inflammatory bowel diseases: nature, severity, and relationship to gastrointestinal symptoms.

Patients suffering from the irritable bowel syndrome (IBS) tend to have extraintestinal symptoms. The purposes of this study were to compare the nature and severity of these symptoms in IBS patients in relation to patients with inflammatory bowel disease (IBD) and to nonpatients and to clarify the relationship between intestinal and extraintestinal symptoms. A consecutive group of male patients and a control group of age-matched male subjects were studied. Symptoms were graded for severity using a validated, self-administered inventory. There were 53 IBS patients, 55 IBD patients (32 Crohn's disease), and 56 controls. IBS patients scored significantly higher than IBD patients on constipation, dyspepsia, and reflux scales. Musculoskeletal symptoms, neurasthenia, and sleep scores were similar in IBS and IBD patients, and both groups scored significantly higher than the controls. The scores of urinary, thoracic, and oral symptoms were similar in IBD patients and in controls. However, IBS patients scored significantly higher than both groups on all these scales. Reflux symptoms were the most powerful predictors of extraintestinal symptoms, both in IBS and in IBD. Diarrhea was predictive of extraintestinal symptoms only in IBD. In conclusion, IBS patients experienced extraintestinal symptoms to the same extent, or even more than patients with IBD. However, the relationship between intestinal and extraintestinal symptoms differed in the two conditions.