Health and quality of life among a cohort of patients having lateral internal sphincterotomy for anal fissures.

AIM: The aim of this study is to report changes in health-related quality of life attributable to lateral internal sphincterotomy for treatment of anal fissure. There is very little evidence on whether the overall health-related quality of life of patients is detrimentally affected by the condition, or which aspects of self-perceived health status improve after lateral internal sphincterotomy. This study will articulate which aspects of health tend to improve and guide postoperative expectations appropriately. Knowledge gained from this study may also identify gaps in an individual patient's episode of care. METHOD: Patients were prospectively identified when they consented to surgical treatment of their anal fissure and were contacted by phone to participate. Participants completed a number of patient-reported outcomes preoperatively and 6 months postoperatively. Faecal incontinence-related quality of life, pain and depression were measured at both time points. The severity of faecal incontinence was measured at both times. RESULTS: Participants reported high levels of pain preoperatively. Postoperatively, improvement in pain exceeded the threshold of clinical relevance (P < 0.01). Thirty-five per cent of participants reported significant effects of faecal incontinence preoperatively, while 26% did so postoperatively. Participants with multiple comorbidities were more likely to report faecal incontinence postoperatively than preoperatively. CONCLUSION: This study reports that lateral internal sphincterotomy improved pain symptoms without adverse effects on continence. Not all domains of health-related quality of life were similarly positively affected by anal fissure repair.

Seroprevalence of Toxoplasma gondii in South Asian countries.

Toxoplasmosis, a cosmopolitan zoonosis, is caused by an apicomplexan, obligate, intracellular protozoan parasite, Toxoplasma gondii. Nearly all animals, including humans, are at risk owing to its broad geographical distribution. The authors searched published data related to T. gondii in databases, including Google Scholar, PubMed and Science Direct for South Asian countries, and retrieved a total of 113 articles fulfilling the criterion of seroprevalence investigation. Toxoplasma gondii infection in livestock and humans was investigated using various serological tests. In these studies, a total of 14,431 samples from domestic animals and 53,899 samples from humans were screened for anti-T. gondii antibodies in all South Asian countries. Among the animals, cattle (n = 1,981), goats (n = 3,285), buffaloes (n = 1,695), sheep (n = 1,747), cats (n = 1,480), camels (n = 435), elephants (n = 45), pigs (n = 920), dogs (n = 1,604) and poultry (n = 1,206) were tested. This comprehensive review will be useful to biologists, public health workers, physicians and veterinarians and provides a better understanding of the distribution of T. gondii in this region. Furthermore, this knowledge will support efforts to find and apply effective prevention measures to better manage this zoonosis in South Asian countries.

La toxoplasmose est une maladie cosmopolite causée par Toxoplasma gondii, un protozoaire unicellulaire obligatoire appartenant au phylum des Apicomplexa. Du fait de sa distribution géographique, pratiquement toutes les espèces animales sont exposées, ainsi que l'homme. Les auteurs ont fait une recherche dans plusieurs bases de données, dont Google Scholar, PubMed et Science Direct, sur les articles consacrés à T. gondii dans les pays d'Asie du Sud, qui a permis d'extraire un total de 113 articles présentant toutes les caractéristiques d'une enquête sérologique. L'infection par Toxoplasma gondii chez l'homme et chez les animaux d'élevage a fait l'objet de plusieurs enquêtes recourant à divers tests sérologiques. Ces études font état d'un total de 14 431 échantillons prélevés d'animaux domestiques et de 53 899 échantillons prélevés chez l'homme, qui ont été soumis à une épreuve de détection d'anticorps dirigés contre T. gondii dans les pays d'Asie du Sud. Les études ont couvert les espèces suivantes : bovins (n = 1 981), chèvres (n = 3 285), buffles (n = 1 695), moutons (n = 1 747), chats (n = 1 480), chameaux (n = 435), éléphants (n = 45), porcs (n = 920), chiens (n = 1 604) et volailles (n = 1 206). Ce panorama exhaustif sera utile aux biologistes, aux intervenants en santé publique, aux médecins et aux vétérinaires et permettra de mieux appréhender la distribution de T. gondii dans la région. Ces connaissances contribueront à concevoir et à appliquer des mesures de prévention efficaces afin de mieux gérer cette zoonose dans les pays d'Asie du Sud.

La toxoplasmosis es una zoonosis cosmopolita causada por un protozoo, parásito intracelular obligado, del grupo de los apicomplejos: Toxoplasma gondii. Por su amplia distribución geográfica, constituye una amenaza para casi todos los animales, incluido el ser humano. Tras indagar en bases de datos de publicaciones (Google Scholar, PubMed y Science Direct) en busca de información relacionada con la presencia de T. gondii en los países del meridión asiático, los autores encontraron un total de 113 artículos que cumplían el criterio de dar cuenta de investigaciones sobre la seroprevalencia. Para estudiar la infección por Toxoplasma gondii en el ganado y el ser humano se habían empleado diversas pruebas serológicas. En el conjunto de esos estudios, que cubrían todos los países de Asia meridional, se habían analizado un total de 14.431 muestras de animales domésticos y 53.899 muestras humanas para detectar anticuerpos contra T. gondii. Los animales analizados eran: ganado vacuno (n = 1.981), cabras (n = 3.285), búfalos (n = 1.695), ovejas (n = 1.747), gatos (n = 1.480), camellos (n = 435), elefantes (n = 45), cerdos (n = 920), perros (n = 1.604) y aves de corral (n = 1.206). Este repaso general, que resultará útil a biólogos, agentes de salud pública, médicos y veterinarios, permite conocer mejor la distribución de T. gondii en la región, lo que además será de ayuda a la hora de determinar y aplicar medidas eficaces de prevención con objeto de controlar más eficazmente esta zoonosis en los países de Asia meridional.

The effect of calving in the summer on the hepatic transcriptome of Holstein cows during the peripartal period.

The liver is the main metabolic organ coordinating the adaptations that take place during the peripartal period of dairy cows. A successful transition into lactation, rather than management practices alone, depends on environmental factors such as temperature, season of parturition, and photoperiod. Therefore, we analyzed the effect of calving season on the hepatic transcriptome of dairy cows during the transition period. A total of 12 Holstein dairy cows were assigned into 2 groups based on calving season (6 cows March-April, spring; 6 cows June-July, summer, SU). The RNA was extracted from liver samples obtained at -30, 3, and 35 DIM via percutaneous biopsy and hybridized to the Agilent 44K Bovine (V2) Gene Expression Microarray (Agilent Technologies Inc., Santa Clara, CA). A quantitative PCR on 22 target genes was performed to verify and expand the analyses. A total of 4,307 differentially expressed genes were detected (false discovery rate ≤0.05) in SU compared with spring. Furthermore, 73 unique differentially expressed genes were detected in SU compared with spring cows after applying a fold-change threshold ≥3 and ≤-3. For Kyoto Encyclopedia of Genes and Genomes pathways analysis of differentially expressed genes, we used the dynamic impact approach. Ingenuity Pathway Analysis software was used to analyze upstream transcription regulators and perform gene network analysis. Among metabolic pathways, energy metabolism from lipids, carbohydrates, and amino acids was strongly affected by calving in SU, with a reduced level of fatty acid synthesis, oxidation, re-esterification, and synthesis of lipoproteins, leading to hepatic lipidosis. Glycan-synthesis was downregulated in SU cows probably as a mechanism to counteract the progression of this lipidosis. In contrast, calving in the SU resulted in upregulation of gluconeogenesis but also greater use of glucose as an energy source. Among nonmetabolic pathways, the heat-shock response was obviously activated in SU cows but was also associated with inflammatory and intracellular stress response. Furthermore, data support a recent finding that cows experience endoplasmic reticulum stress around parturition. Transcription regulator analysis revealed how metabolic changes are related to important regulatory mechanisms, including epigenetic modification. The holistic analyses of the liver transcriptome response to calving in the summer at high environmental temperatures underscore how transition cows should be carefully managed during this period, as they experience alterations in liver energy metabolism and inflammatory state increasing susceptibility to health disorders in early postpartum.

Body condition score at calving affects systemic and hepatic transcriptome indicators of inflammation and nutrient metabolism in grazing dairy cows.

Calving body condition score (BCS) is an important determinant of early-lactation dry matter intake, milk yield, and disease incidence. The current study investigated the metabolic and molecular changes induced by the change in BCS. A group of cows of mixed age and breed were managed from the second half of the previous lactation to achieve mean group BCS (10-point scale) that were high (HBCS, 5.5; n=20), medium (MBCS, 4.5; n=18), or low (LBCS, 3.5; n=19). Blood was sampled at wk -4, -3, -2, 1, 3, 5, and 6 relative to parturition to measure biomarkers of energy balance, inflammation, and liver function. Liver was biopsied on wk 1, 3, and 5 relative to parturition, and 10 cows per BCS group were used for transcript profiling via quantitative PCR. Cows in HBCS and MBCS produced more milk and had greater concentrations of nonesterified fatty acids and ß-hydroxybutyrate postpartum than LBCS. Peak concentrations of nonesterified fatty acids and ß-hydroxybutyrate and greater hepatic triacylglycerol concentrations were recorded in HBCS at wk 3. Consistent with blood biomarkers, HBCS and MBCS had greater expression of genes associated with fatty acid oxidation (CPT1A, ACOX1), ketogenesis (HMGCS2), and hepatokines (FGF21, ANGPTL4), whereas HBCS had the lowest expression of APOB (lipoprotein transport). Greater expression during early lactation of BBOX1 in MBCS and LBCS suggested greater de novo carnitine synthesis. The greater BCS was associated with lower expression of growth hormone/insulin-like growth factor-1 signaling axis genes (GHR1A, IGF1, and IGFALS) and greater expression of gluconeogenic genes. These likely contributed to the higher milk production and greater gluconeogenesis. Despite greater serum haptoglobin around calving, cows in HBCS and MBCS had greater blood albumin. Cows in MBCS, however, had a higher albumin:globulin ratio, probably indicating a less pronounced inflammatory status and better liver function. The marked decrease in expression of NFKB1, STAT3, HP, and SAA3 coupled with the increase in ALB on wk 3 in MBCS cows were consistent with blood measures. Overall, results suggest that the greater milk production of cows with higher calving BCS is associated with a proinflammatory response without negatively affecting expression of genes related to metabolism and the growth hormone/insulin-like growth factor-1 axis. Results highlight the sensitivity of indicators of metabolic health and inflammatory state to subtle changes in calving BCS and, collectively, indicate a suboptimal health status in cows calving at either BCS 3.5 or 5.5 relative to BCS 4.5.

Feed restriction, but not l-carnitine infusion, alters the liver transcriptome by inhibiting sterol synthesis and mitochondrial oxidative phosphorylation and increasing gluconeogenesis in mid-lactation dairy cows.

Abomasal carnitine infusion during acute feed restriction increases hepatic fatty acid oxidation and decreases liver lipid in dairy cows. Eight mid-lactation Holstein cows were used in a replicated 4×4 Latin square design with 14-d periods. A 2×2 factorial arrangement was used to determine the effects of water infusion+ad libitum dry matter intake (DMI), water infusion+restricted DMI (50% of previous 5-d average), l-carnitine infusion (20 g/d)+ad libitum DMI, or l-carnitine infusion+restricted DMI. Liver RNA from 7 healthy cows was used for transcriptome profiling using a bovine microarray. An ANOVA with a false discovery rate was used to identify treatment and interaction effects. A substantial transcriptome change was observed only with DMI restriction, resulting in 312 (155 downregulated, 157 upregulated) differentially expressed genes. Quantitative PCR was performed to verify microarray data and measure expression of additional genes not present on the microarray. The quantitative PCR data confirmed the effect of feed restriction but not of l-carnitine treatment. Feed restriction increased expression of GPX3 and of genes associated with gluconeogenesis (PC, PDK4), inflammation (SAA3), and signaling (ADIPOR2). In contrast, feed restriction downregulated BBOX, a key for l-carnitine biosynthesis, and the transcription factor HNF4A. The bioinformatics functional analysis of genes affected by DMI restriction uncovered biosynthesis of cholesterol and energy generation by mitochondrial respiration as the most relevant and inhibited functions. The data also indicated an increase of flux toward gluconeogenesis. We interpreted those results as a likely response of the liver to spare energy and provide glucose for the lactating mammary gland during feed deprivation.

Gas extrusion in natural products total synthesis.

The thermodynamic driving force from the release of a gaseous molecule drives a broad range of synthetic transformations. This review focuses on gas expulsion in key reactions within natural products total syntheses, selected from the past two decades. The highlighted examples survey transformations that generate sulfur dioxide, carbon dioxide, carbonyl sulfide, or nitrogen through polar, radical, pericyclic, photochemical, or organometallic mechanisms. Of particular interest are applications wherein the gas extrusion enables formation of a synthetically challenging motif, such as an unusually hindered or strained bond.

Effect of silymarin on sodium fluoride-induced toxicity and oxidative stress in rat cardiac tissues.

This study aim to evaluate the protective effect of silymarin on sodium fluoride-induced oxidative stress in rat cardiac tissues. Animals were pretreated with silymarin at 20 and 10 mg/kg prior to sodium fluoride consumption (600 ppm through drinking water). Vitamin C at 10 mg/kg was used as standard antioxidant. There was a significant increase in thiobarbituric acid reactive substances level (59.36 ± 2.19 nmol MDA eq/g tissue) along with a decrease in antioxidant enzymes activity (64.27 ± 1.98 U/g tissue for superoxide dismutase activity and 29.17 ± 1.01 µmol/min/mg protein for catalase activity) and reduced glutathione level (3.8 ± 0.15 µg/mg protein) in the tissues homogenates of the sodium fluoride-intoxicated rats. Silymarin administration to animals before sodium fluoride consumption modified the levels of biochemical parameters.

Morphological and molecular evidences of Ascaridia galli in migratory quail Coturnix coturnix japonica from Baluchistan Pakistan.

The current study was conducted to examine the point prevalence of gastrointestinal parasites of migratory quails. Due to its economic importance, the control of ascaridiosis is critical. Migration of birds is considered to enhance the global spread and cross-species transmission of pathogens. The current study was aimed to detect A.galli in migratory quails, a potential contributory risk factor for transmission of this parasite to local birds. A total of 230 migratory quails were trapped using nets from migratory routes in Balochistan and examined under the compound microscope for the presence of A. galli. Conventionally, A. galli was identified by its morphology with the presence of three large lips and absence of posterior esophageal bulb. Results revealed that out of 230, 120 (52.17%) quails were positive for A. galli by targeting COX1 gene (533 bp) by using conventional PCR. Further, the amplicon was sequenced which showed 99% similarity with A. galli publically available in NCBI Gen Bank. Phylogenetic analysis of sequences of our isolated parasite indicated the close relationship with A.galli isolated from chickens. In conclusion migratory quails and other migratory birds may play a key role in spreading and transmission of these parasites and other pathogens to domestic chicken. Therefore, strict biosecurity measures should be adopted especially for commercial poultry farms.

Change in hepatitis C virus clades: a cross-sectional study of chronic HCV patients in Pakistan from 2000-2010.

The changing pattern in hepatitis C virus (HCV) clades overtime is not well known in Pakistan. To find out the changing pattern of different HCV clades over time in this country 22,125 patients were genotyped and tracked for a period of 11 years (2000-2010). A changing pattern in HCV clades was seen in this region during the study period. Sub-clade 3a remained the dominant sub-clade circulating in different areas of the country in the study era. HCV sub-clade 3a demonstrated significantly high correlation with time (p < 0.05) whereas undetermined clades were seen with statistically non-significant correlation with time (years). All the other clades showed negative correlation with time. In general a significant decline was observed in the percentages of HCV clades 2, 4, 5 and 6 (p < 0.001). Among sub-clades, HCV 1a, 2c, 2b and 3b significantly decreased overtime (p < 0.05), while an increase has been observed for HCV 3a sub-clade and mixed clades (p <0.001). The ratio of undetermined clades remained constant over the study period. In conclusion, a changing pattern of HCV clades was observed over the 11-year study period, and this changed pattern might have direct impact on HCV disease outcome.

Comparison of conventional methods with commercially available topical hemostat surgical snow (oxidized cellulose) for achieving hemostasis in canine model of partial splenectomy.

Spleen is highly vascularized organ and bleeding control during partial splenectomy is a big challenge. In this study conventional methods of electrocautery, absorbable suturing and advance methods of topical hemostat Surgicel® were compared to control bleeding during partial splenec- tomy. Twelve healthy dogs (n=4) were divided in A, B and C groups. After partial splenectomy Surgicel®, electrocautery and absorbable horizontal mattress sutures were used to control hemor- rhages in group A, B and C respectively. Bleeding time and loss of blood volume was evaluated during surgery. In addition, blood samples were taken on day 0 pre-surgery and on days 3, 10 and 17 post-surgery to evaluate changes in biochemical parameters after the application of dif- ferent hemostatic techniques. Ultrasonography was also performed at alternative days to check any gross changes in the spleen. Dogs in group A showed minimum bleeding time and loss of blood volume as compared to group B and C. Drop in red blood cells count was compared be- tween group A, B and C showing significant change (p≤0.05) at day 3, 10 and 17, while a sig- nificant decline in hemoglobin was found in group C followed by groups B and A at 3rd and 10th day. There was no difference between platelet counts in various groups. Ultrasonography showed no significant changes in the spleen parenchyma. It was concluded that Surgicel® was an effective material for controlling hemorrhage in veterinary patients.

Pneumocystis diversity as a phylogeographic tool.

Parasites are increasingly used to complement the evolutionary and ecological adaptation history of their hosts. Pneumocystis pathogenic fungi, which are transmitted from host-to-host via an airborne route, have been shown to constitute genuine host markers of evolution. These parasites can also provide valuable information about their host ecology. Here, we suggest that parasites can be used as phylogeographic markers to understand the geographical distribution of intra-specific host genetic variants. To test our hypothesis, we characterised Pneumocystis isolates from wild bats living in different areas. Bats comprise a wide variety of species; some of them are able to migrate. Thus, bat chorology and migration behaviour can be approached using Pneumocystis as phylogeographic markers. In the present work, we find that the genetic polymorphisms of bat-derived Pneumocystis are structured by host chorology. Therefore, Pneumocystis intra-specific genetic diversity may constitute a useful and relevant phylogeographic tool.

Cardiac complications after smallpox vaccination.

In 2002, the US Federal government initiated a campaign to vaccinate military personnel and members of the civilian population against smallpox to counter a possible bioterrorism attack. More than 1,200,000 military personnel and approximately 40,000 civilians have been vaccinated since that time. The incidence of myopericarditis in these vaccinees has clearly exceeded calculated background rates and has prompted discussion about cardiac inflammation and other potential vaccine-associated cardiac complications such as dilated cardiomyopathy (DCM) and myocardial ischemia. Although it seems reasonable to predict that some cases of smallpox-associated myopericarditis will progress to DCM, only small numbers have been documented so far, and a causal relationship is difficult to ascertain. With regard to myocardial ischemia, both historical and current data do not suggest a causal association with the vaccine. We describe a case report of myopericarditis following smallpox immunization and provide a review of all cardiac complications associated with vaccination.

Salivary anti-Helicobacter pylori positivity among endoscopy patients with chronic liver disease.

In this study, endoscopy patients with and without chronic liver disease (CLD) were examined and tested for Helicobacter pylori infection by detecting the presence of serum and salivary anti-H. pylori antibody. The validity of these measures was compared with Campylobacter-like organism analysis (gold standard) performed on patients requiring gastric biopsy. Among 114 patients with CLD and 50 without, the commonest endoscopy diagnosis was gastritis (27.2%). Salivary H. pylori positivity was significantly associated with older age. Salivary anti-H. pylori antibody positivity showed low sensitivity (36.6%) and high specificity (75.8%) in CLD patients.

Infective endocarditis complicating permanent pacemaker and implantable cardioverter-defibrillator infection.

OBJECTIVE: To describe management of patients with permanent pacemaker (PPM)- and implantable cardioverter-defibrillator (ICD)-related endocarditis. PATIENTS AND METHODS: We retrospectively reviewed all cases of infection involving PPMs and ICDs among patients presenting to Mayo Clinic's site in Rochester, MN, between January 1, 1991, and December 31, 2003. Cardiac device-related infective endocarditis (CDIE) was defined as the presence of both vegetation on a device lead or valve and clinical or microbiological evidence of CDIE. Of 189 patients with PPM or ICD infection who were admitted during the study period, 44 met the case definition for CDIE (33 PPM, 11 ICD). RESULTS: The mean +/- SD age of patients was 67 +/- 14 years. Staphylococci (36 [82%]) were the most commonly isolated pathogens. Nearly all patients (43 [98%]) were treated with a combined approach of complete hardware removal and parenteral antibiotics. The median duration of antibiotic treatment after infected device explantation was 28 days (interquartile range, 19-42 days). Device leads were removed percutaneously in 34 cases (77%); only 7 cases (16%) required surgical lead extraction. Percutaneous extraction was uncomplicated in 15 patients with lead vegetation greater than 10 mm in diameter. Six patients (14%) died during hospitalization. Twenty-seven (96%) of 28 patients remained infection free at their last visit (median follow-up, 183 days; intraquartile range, 36-628 days). CONCLUSION: Prompt hardware removal and prolonged parenteral antibiotic administration decrease mortality among patients with CDIE. The presence of a large (> 10 mm in diameter) vegetation on a lead is not a contraindication for percutaneous lead extraction.

Small molecule targeting the Rac1-NOX2 interaction prevents collagen-related peptide and thrombin-induced reactive oxygen species generation and platelet activation.

Essentials Reactive oxygen species (ROS) generation by NOX2 plays a critical role in platelet activation. Rac1 regulation of NOX2 is important for ROS generation. Small molecule inhibitor of the Rac1-p67phox interaction prevents platelet activation. Pharmacologic targeting of Rac1-NOX2 axis can be a viable approach for antithrombotic therapy. SUMMARY: Background Platelets from patients with X-linked chronic granulomatous disease or mice deficient in nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidase isoform NOX2 exhibit diminished reactive oxygen species (ROS) generation and platelet activation. Binding of Rac1 GTPase to p67phox plays a critical role in NOX2 activation by facilitating the assembly of the NOX2 enzyme complex. Objective We tested the hypothesis that Phox-I, a rationally designed small molecule inhibitor of Rac-p67phox interaction, may serve as an antithrombosis agent by suppressing ROS production and platelet activation. Results Collagen-related peptide (CRP) induced ROS generation in a time-dependent manner. Platelets from Rac1-/- mice or human platelets treated with NSC23766, a specific Rac inhibitor, produced significantly less ROS in response to CRP. Treatment of platelets with Phox-I inhibited diverse CRP-induced responses, including: (i) ROS generation; (ii) release of P-selectin; (iii) secretion of ATP; (iv) platelet aggregation; and (v) phosphorylation of Akt. Similarly, incubation of platelets with Phox-I inhibited thrombin-induced: (i) secretion of ATP; (ii) platelet aggregation; (iii) rise in cytosolic calcium; and (iv) phosphorylation of Akt. In mouse models, intraperitoneal administration of Phox-I inhibited: (i) collagen-induced platelet aggregation without affecting the tail bleeding time and (ii) in vivo platelet adhesion/accumulation at the laser injury sites on the saphenous vein without affecting the time for complete cessation of blood loss. Conclusions Small molecule targeting of the Rac1-p67phox interaction may present an antithrombosis regimen by preventing GPVI- and non-GPVI-mediated NOX2 activation, ROS generation and platelet function without affecting the bleeding time.

Lead Extraction Imaging.

Lead extraction procedures have a low but real risk of major complications, such as superior vena cava tear and cardiac tamponade. Complications during lead removal are commonly related to lead binding sites, lead malposition, and lead perforation. Lead extraction imaging may indicate lead vascular binding sites, lead position, and perforation. Several imaging modalities are available, including chest radiograph, cardiac computed tomography, and echocardiography. The information provided by various imaging modalities will help assess the challenges of each lead extraction procedure and allows for better preprocedure planning.

Molecular Adsorbent Recirculating System Support Followed by Liver Transplantation for Multiorgan Failure From Heatstroke.

BACKGROUND: Exertional heatstroke is an extremely rare cause of fulminant hepatic failure. Maximal supportive care has failed to provide adequate survival in earlier studies. This is particularly true in cases accompanied by multiorgan failure. METHODS AND MATERIALS: Our prospectively collected transplant database was retrospectively reviewed to identify patients undergoing liver transplantation for heatstroke between January 1, 2012, and December 31, 2016. We report 3 consecutive cases of male patients with fulminant hepatic failure from exertional heatstroke. RESULTS: All patients developed multiorgan failure and required intubation, vasopressor support, and renal replacement therapy. All patients were listed urgently for liver transplantation and were supported with the molecular adsorbent recirculating system while awaiting transplantation. All patients underwent liver transplantation alone and are alive and well, with recovered renal function, normal liver allograft function, and no chronic sequelae of their multiorgan failure at more than one year. CONCLUSION: Extreme heatstroke leading to whole-body organ dysfunction and fulminant liver failure is a complex entity that may benefit from therapy using the Molecular Adsorbent Recirculating System while waiting for liver transplantation as a component of a multidisciplinary, multiorgan system approach.

Twelve-Lead ECG Optimization of Cardiac Resynchronization Therapy in Patients With and Without Delayed Enhancement on Cardiac Magnetic Resonance Imaging.

Background Delayed enhancement ( DE ) on magnetic resonance imaging is associated with ventricular arrhythmias, adverse events, and worse left ventricular mechanics. We investigated the impact of DE on cardiac resynchronization therapy ( CRT ) outcomes and the effect of CRT optimization. Methods and Results We studied 130 patients with ejection fraction ( EF ) ≤40% and QRS ≥120 ms, contrast cardiac magnetic resonance imaging, and both pre- and 1-year post- CRT echocardiograms. Sixty-three (48%) patients did not have routine optimization of CRT . The remaining patients were optimized for wavefront fusion by 12-lead ECG . The primary end point in this study was change in EF following CRT . To investigate the association between electrical dyssynchrony and EF outcomes, the standard deviation of activation times from body-surface mapping was calculated during native conduction and selected device settings in 52 of the optimized patients. Patients had no DE (n=45), midwall septal stripe (n=30), or scar (n=55). Patients without DE had better ∆ EF (13±10 versus 4±10 units; P<0.01). Optimized patients had greater ∆ EF in midwall stripe (2±9 versus 12±12 units; P=0.01) and scar (0±7 versus 5±10; P=0.04) groups, but not in the no- DE group. Patients without DE had greater native standard deviation of activation times ( P=0.03) and greater ∆standard deviation of activation times with standard programming ( P=0.01). Device optimization reduced standard deviation of activation times only in patients with DE ( P<0.01). Conclusions DE on magnetic resonance imaging is associated with worse EF outcomes following CRT . Device optimization is associated with improved EF and reduced electrical dyssynchrony in patients with DE .

Risk factor analysis of permanent pacemaker infection.

Background. Several host- and procedure-related factors have been reported to increase the risk of permanent pacemaker (PPM) infection on the basis of descriptive analyses of case series. The purpose of this study is to assess the risk factors for PPM infection using case-control study methods.Methods. All patients who had a PPM implanted at our institution from January 1991 to December 2003 were retrospectively reviewed. Each patient who experienced a PPM infection was matched with 2 control subjects by age, sex, year of implantation, and duration of follow-up. Univariate and multivariable analyses were performed to identify significant risk factors for PPM infection.Results. Twenty-nine case patients and 58 control subjects met inclusion criteria. The majority (83%) of case patients presented with a pocket infection; a minority (10%) had PPM-related endocarditis. Staphylococcus species (69%) were the most common pathogens. On univariate analysis, previous PPM infection, malignancy, long-term corticosteroid use, multiple device revisions, a permanent central venous catheter, the presence of >2 pacing leads, and a lack of antibiotic prophylaxis at the time of PPM placement were associated with an increased risk of PPM infection. A multivariable logistic regression model identified long-term corticosteroid use (odds ratio [OR], 13.90; 95% confidence interval [CI], 1.27-151.7; P=.03) and the presence of >2 pacing leads versus 2 leads (OR, 5.41; 95% CI, 1.44-20.29; P=.01) as independent risk factors for PPM infection. In contrast, use of antibiotic prophylaxis prior to PPM implantation had a protective effect (OR, 0.087; 95% CI, 0.016-0.48; P=.005).Conclusions. These findings should assist clinicians in identifying patients who are at increased risk of PPM infection, as well as in developing strategies to minimize the modifiable risks.

Genetic and pharmacologic evidence that Rac1 GTPase is involved in regulation of platelet secretion and aggregation.

BACKGROUND: Rac1 GTPase, a member of the Ras-related Rho GTPase family, is the major Rac isoform present in platelets and has been shown to be involved in cell actin cytoskeleton reorganization and adhesion. Agonists that induce platelet secretion and aggregation also activate Rac1 GTPase, raising the possibility that Rac1 GTPase may be involved in regulation of platelet function. OBJECTIVES: To rigorously define the role of Rac1 in platelet regulation. METHODS: We have used a dual approach of gene targeting in mice and pharmacologic inhibition of Rac1 by NSC23766, a rationally designed specific small molecule inhibitor, to study the role of Rac1 in platelet function. RESULTS: Platelets from mice as well as human platelets treated with NSC23766 exhibited a significant decrease in: (i) active Rac1 species and phosphorylation of the Rac effector, p21-activated kinase; (ii) expression of P-selectin and secretion of adenosine triphosphate induced by thrombin or U46619; and (iii) aggregation induced by adenosine 5'-diphosphate, collagen, thrombin and U46619, a stable analog of thromboxane A(2). NSC23766 did not alter the cAMP or cGMP levels in platelets. Consistent with the requirement of Rac1 for normal platelet function, the bleeding times in Rac1(-/-) mice or mice given NSC23766 were significantly prolonged. CONCLUSIONS: Our data show that deficiency or inhibition of Rac1 GTPase blocks platelet secretion. The inhibition of secretion, at least in part, is responsible for diminished platelet aggregation and prolonged bleeding times observed in Rac1 knockout or Rac1 inhibitor-treated mice.