Miracle-dz/UniFAR-FTUs huggingface dataset:
The effect of angiotensin-converting enzyme polymorphism on hemodynamic response to endotracheal intubation in hypertensive patients

Abstract Endotracheal intubation elicits a hemodynamic response associated with increased heart rate and blood pressure that is influenced by the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) genetic polymorphism which may be of importance also for the pressure response to anesthesia. A total of 337 patients underwent abdominal surgery in general anesthesia and 16% were D/D-homozygotes, 45% were I/D heterozygotes and 39% of the patients were I/I homozygotes. Before surgery most patients were in treatment for arterial hypertension. Systolic and diastolic pressure, heart rate and concentrations of catecholamines in blood were determined before and after induction of anesthesia and for up to 10 minutes following endotracheal intubation. Anesthesia decreased blood pressure and for patients presenting ID and DD, blood pressure and heart rate reached similar levels but compared to II-homozygotes, D-carriers demonstrated significantly higher levels for systolic pressure and heart rate before and after intubation (p < 0.05). The blood levels of catercholamines were similar in the three genotype groups. The incidence of ECG-determined myocardial ischemia was higher in D-allele carriers compared to I-allele homozygotes (DD 22%, ID 25% vs. II 5%). In response to anesthesia and intubation and independent of sympathetic nervous activity, D-allele carriers for ACE polymorphism increased blood pressure response and higher risk for development of cardiovascular complications compared to patients homozygous for the I-allele.
Increased capsaicin receptor TRPV1 nerve fibres in the inflamed human oesophagus

Background Gastro-oesophageal reflux disease (GORD) patients commonly describe symptoms of heartburn and chest pain. The capsaicin receptor vanilloid receptor 1 (TRPV1) (VR1) is a cation channel expressed by sensory neurones and activated by heat, acid pH and ethanol, which may trigger burning pain. Aim To study the distribution of TRPV1-expressing nerve fibres in oesophageal mucosal biopsies from patients with symptomatic oesophagitis and in control subjects. Methods Biopsies were taken at gastroscopy from the distal oesophagus of seven symptomatic oesophagitis patients and seven asymptomatic patients undergoing investigation for iron-deficiency anaemia. These biopsies were studied by immunohistochemistry using affinity-purified antibodies to TRPV1 and to the neuronal marker peripherin. The density of oesophageal epithelial TRPV1 innervation was assessed by calculating the proportion of papillae in each oesophageal epithelium biopsy specimen containing TRPV1-immunoreactive fibres. Results TRPV1-immunoreactive nerves were distributed within the lamina propria in healthy subjects and in oesophagitis patients. The percentage of papillae positive for TRPV1 was elevated in oesophagitis patients compared with controls. Peripherin fibre density was not significantly different between the groups. Conclusions TRPV1-immunoreactive sensory nerve fibres are expressed in human oesophageal mucosa both in health and in disease. Increased TRPV1 expression in the inflamed oesophagus may mediate the heartburn in oesophagitis, and TRPV1 blockers may provide novel treatment.
Surgery for appendicitis: is it necessary?

BACKGROUND Appendectomy for acute appendicitis is an effective, universally accepted procedure performed more than 300,000 times annually in the United States. It is generally believed that appendicitis progresses invariably from early inflammation to later gangrene and perforation, and that appendectomy is required for surgical source control. Although non-operative management with antibiotics of uncomplicated diverticulitis, salpingitis, and neonatal enterocolitis is now established, the non-operative management of appendicitis remains largely unexplored. METHODS Systematic review of published literature and derived expert opinion. RESULTS Clinical, epidemiologic, radiologic, and pathologic evidence is presented for spontaneous resolution of uncomplicated acute appendicitis. The pathogenesis of appendicitis is reviewed with specific consideration of the role of bacterial infection in the pathogenesis. Evidence is also provided documenting the clinical success of non-operative management. CONCLUSIONS Appendectomy may not be necessary for the majority of patients with acute uncomplicated appendicitis, as many patients resolve spontaneously and others may be treatable with antibiotics alone. However, the supporting documentation is scant and of poor quality. A randomized, prospective trial of non-operative management versus early appendectomy of acute uncomplicated appendicitis corroborated by radiologic imaging is called for.
Competition, estimated, and test maximum heart rate.

AIM The aim of the present study was to compare the highest heart rate (HR) of soccer players recorded during competition matches with the maximum HR (HR(max)) estimated from age and the highest HR recorded in effort tests within a single category (intracategory) and between categories (intercategories). METHODS The sample was made up of 19 under-17 athletes, 12 under-20 athletes and 14 professional athletes of a Brazilian first division soccer team. Players' HR was monitored during official competition matches and maximum effort test with a set of HR monitors. The highest HR recorded during competitive matches (MHR1) was considered as the highest HR value attained by each player during matches. HR(max) estimated from age (MHR2) was estimated by using the equation HR(max)= (220-age). The highest HR recorded in effort tests (MHR3) was determined as being the highest HR value recorded during a maximum effort test (1 000-m run). The Wilcoxon test was used in intracategory statistical analysis. The Kruskal Wallis test was used in intercategory statistical analysis. The significance level adopted was P<0.05. RESULTS In all categories, MHR3 was lower than MHR1. Concerning intercategory analysis, the three categories did not exhibit a difference in MHR1 RESULTS Relative to MHR3, the under-17 and under-20 categories were not different from each other. These two categories exhibited larger MHR3 values than the professional one did. CONCLUSION HR(max) measured during field tests can be underestimated in relation to that measured during competition activities, maybe because the tests represent an artificial situation for athletes, who do not feel as motivated as during competitions.
Reversible shear-mediated platelet dysfunction during cardiac surgery as assessed by the PFA-100® platelet function analyzer

We undertook this investigation to assess alterations in shear-mediated platelet function during cardiac surgery and to determine the potential for the PFA-100® to predict post-operative bleeding. Platelet aggregation and PFA-100® closure times were determined in 18 adult patients at five intervals during cardiac surgery. Associations between post-operative bleeding and closure times were examined in an additional 58 patients. Statistical analysis consisted of Student's t, Wilcoxon signed rank, and Spearman correlation tests. All results are reported as mean ± SEM. Collagen/epinephrine closure times were prolonged prior to and throughout surgery. Collagen/adenosine-5′-diphosphate (ADP) closure times were significantly prolonged by heparin administration, 141 ± 15 s versus 115 ± 10 s (P= 0.01), and subsequent initiation of cardiopulmonary bypass (CPB), 203 ± 12 s (P= 0.0001); however, 15 min after protamine administration, closure times returned to near pre-operative values, 138 ± 12 s (P= not significant). In contrast, platelet aggregation in response to ADP remained impaired in 17 of 19 patients after CPB. Neither ex vivo correction of sample hematocrits nor supplementation with Humate P1 affected closure times. Positive and negative predictive values for post-CPB collagen/ADP closure times to predict bleeding were 18 and 96%, respectively. These results suggest that factors both intrinsic and extrinsic to the platelet contribute to reversible shear-mediated platelet dysfunction during CPB, and that the PFA-100® may prove useful after CPB to identify patients unlikely to benefit from platelet transfusions.
Minimally Invasive Sacroiliac Arthrodesis: Outcomes of a New Technique

Study Design Prospective cohort. Objective Comparing efficacy and outcomes of a new technique for sacroiliac arthrodesis. Background The sacroiliac joint has been described as a possible source of chronic low back pain. However, surgical treatment of sacroiliac pain and dysfunction is controversial. Arthrodesis is normally reserved as a salvage procedure when all others have failed to relieve pain and involves an extensive surgical exposure. We have developed a novel technique of sacroiliac arthrodesis using percutaneously inserted fusion cages filled with bone morphogenic protein. This study describes the radiographic and clinical outcomes of this procedure. Methods Thirteen consecutive patients underwent minimally invasive sacroiliac arthrodesis between February and December 2004 at a single teaching hospital and were prospectively followed. Six patients had bilateral fusions for a total of 19 joints. The average age was 53.1 (range 45 to 62). Average body mass index was 31.2 (range 21.9 to 46.9). Mean follow-up was 29.5 months (range 24 to 35). Diagnosis was confirmed using fluoroscopically guided intra-articular injections of local anesthetic and corticosteroid when their pain was relieved 2 or more hours. Arthrodesis was only performed on patients with positive injections who subsequently had their symptoms recur. Outcome measurements included radiographic assessment for fusion and improvement in visual analog pain scale for low back pain, leg pain, and dyspareunia. Computed tomography scan to evaluate implant placement was performed postoperatively and again at 6 months to assess fusion. Results The overall fusion rate was 89% (17/19 joints). Significant improvements were seen in final low back pain score on a visual analog scale (0 to 10) (average improvement 4.9, P≤0.001). Leg pain improved an average of 2.4 (P=0.013). Dyspareunia improved an average of 2.6 (P=0.0028). One patient was revised to an open arthrodesis secondary to nonunion and persistent pain. There were no infections or neurovascular complications. Conclusions Minimally invasive sacroiliac arthrodesis via a percutaneous posterior approach is a safe and efficacious procedure, leading to a high fusion rate and significant improvement in low back, leg pain, and dyspareunia.
Emerging drugs for prevention of graft failure after allogeneic hematopoietic stem cell transplantation

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the treatment of choice for many patients suffering from hematological malignancies, severe hemoglobinopathies, bone marrow failures or severe primary immunodeficiencies. Graft rejection/failure (GF) is a life-threatening complication following allo-HSCT that is most commonly caused by the reactivity of recipient T cells, natural killer (NK) cells or antibodies against donor grafted hematopoietic cells. The increasing use of allo-HSCT following reduced-intensity conditioning (RIC) and the increasing use of alternative donors (unrelated cord blood and human leukocyte antigen (HLA)-mismatched donor) have resulted in higher frequency of GF. Areas covered: This review describes the pathogenesis and current prevention and treatment of GF as well as agents in development for GF prevention or treatment. Expert opinion: The risk of GF may be reduced in the future by optimizing the conditioning regimens and post-grafting immunosuppression, increasing the number of hematopoietic stem cells (HSCs) and/or immune cells transplanted, optimizing HSC homing and better detecting patients at high risk of GF by searching for pre-transplant donor-specific anti-HLA antibodies in patients given grafts from HLA-mismatched donors, or by closely monitoring donor T- and/or NK-cell chimerism after allo-HSCT following RIC.
The relationship between visceral obesity and hepatic steatosis measured by controlled attenuation parameter

Background Nonalcoholic fatty liver disease (NAFLD) is closely related with obesity. However, obese subjects, generally represented by high BMI, do not always develop NAFLD. A number of possible causes of NAFLD have been studied, but the exact mechanism has not yet been elucidated. Methods A total of 304 consecutive subjects who underwent general health examinations including abdominal ultrasonography, transient elastography and abdominal fat computed tomography were prospectively enrolled. Significant steatosis was diagnosed by ultrasonography and controlled attenuation parameter (CAP) assessed by transient elastography. Results Visceral fat area (VFA) was significantly related to hepatic steatosis assessed by CAP, whereas body mass index (BMI) was related to CAP only in univariate analysis. In multiple logistic regression analysis, VFA (odds ratio [OR], 1.010; 95% confidence interval [CI], 1.001–1.019; P = 0.028) and triglycerides (TG) (OR, 1.006; 95% CI, 1.001–1.011; P = 0.022) were independent risk factors for significant hepatic steatosis. The risk of significant hepatic steatosis was higher in patients with higher VFA: the OR was 4.838 (P<0.001; 95% CI, 2.912–8.039) for 100200 cm2, compared to patients with a VFA ≤100 cm2. Conclusions Our data demonstrated that VFA and TG is significantly related to hepatic steatosis assessed by CAP not BMI. This finding suggests that surveillance for subjects with NAFLD should incorporate an indicator of visceral obesity, and not simply rely on BMI.
p300-mediated acetylation facilitates the transfer of histone H2A-H2B dimers from nucleosomes to a histone chaperone.

We have used a purified recombinant chromatin assembly system, including ACF (Acf-1 + ISWI) and NAP-1, to examine the role of histone acetylation in ATP-dependent chromatin remodeling. The binding of a transcriptional activator (Gal4-VP16) to chromatin assembled using this recombinant assembly system dramatically enhances the acetylation of nucleosomal core histones by the histone acetyltransferase p300. This effect requires both the presence of Gal4-binding sites in the template and the VP16-activation domain. Order-of-addition experiments indicate that prior activator-meditated, ATP-dependent chromatin remodeling by ACF is required for the acetylation of nucleosomal histones by p300. Thus, chromatin remodeling, which requires a transcriptional activator, ACF and ATP, is an early step in the transcriptional process that regulates subsequent core histone acetylation. Glycerol gradient sedimentation and immunoprecipitation assays demonstrate that the acetylation of histones by p300 facilitates the transfer of H2A-H2B from nucleosomes to NAP-1. The results from these biochemical experiments suggest that (1) transcriptional activators (e.g., Gal4-VP16) and chromatin remodeling complexes (e.g., ACF) induce chromatin remodeling in the absence of histone acetylation; (2) transcriptional activators recruit histone acetyltransferases (e.g., p300) to promoters after chromatin remodeling has occurred; and (3) histone acetylation is important for a step subsequent to chromatin remodeling and results in the transfer of histone H2A-H2B dimers from nucleosomes to a histone chaperone such as NAP-1. Our results indicate a precise role for histone acetylation, namely to alter the structure of nucleosomes (e.g., facilitate the loss of H2A-H2B dimers) that have been remodeled previously by the action of ATP-dependent chromatin remodeling complexes. Thus, transcription from chromatin templates is ordered and sequential, with precise timing and roles for ATP-dependent chromatin remodeling, subsequent histone acetylation, and alterations in nucleosome structure.
Intradiscal thermal annuloplasty versus intradiscal radiofrequency ablation for the treatment of discogenic pain: a prospective matched control trial.

OBJECTIVE Two minimally invasive techniques have been used more recently as a possible treatment for painful internal disk disruption (IDD). Intradiscal thermal annuloplasty (IDTA), known as IDET, has already shown promising results in pain reduction and functional restoration. The second technique, radiofrequency posterior annuloplasty (RFA), is used in many interventional pain practices, although studies on the technique's efficacy are lacking. This study compares the effectiveness of those two methods. DESIGN AND PATIENTS We matched 42 patients (21 had IDTA and 21 radiofrequency annuloplasty) for age, sex, weight, smoking history, manual labor, and number of intervertebral disks treated. Enrolled patients completed pain disability index (PDI) questionnaires before receiving either IDTA or RFA; at 2 weeks; and 2, 3, 6, 9, and 12 months following either treatment. RESULTS From the third to the twelfth month after the procedure, the IDTA group had significantly lower mean pain scores than the RFA group. Visual analog scale (VAS) pain scores decreased from 6.6 +/- 2.0 before to 4.4 +/- 2.4 at 1 year after radiofrequency annuloplasty (P = 0.001), while in the IDTA group the average VAS pain score decreased from 7.4 +/- 1.9 before IDTA to 1.4 +/- 1.9 at 1 year follow-up. Similarly, PDI scores in the IDTA group had a significantly larger improvement than those for patients who received radiofrequency annuloplasty. CONCLUSIONS This study shows significant improvement in pain scores and patients' PDI following IDTA but not after RFA of the intervertebral disks. IDTA appears to be more efficacious than RFA based on PDI and VAS scores measured at 1 year following procedure.
Progressive Dopamine Neuron Loss in Parkinson's Disease: The Multiple Hit Hypothesis

Animal models have been an essential tool for researchers and clinicians in their efforts to study and treat Parkinson's disease (PD). Thus, the various ways 6-hydroxydopamine is employed, the use of MPTP in rodents and nonhuman primates, the prenatal exposure to bacterial endotoxin, the postnatal exposure to environmental toxins such as paraquat and rotenone, the assessment of dopamine (DA) neurons in genetic knockout mouse, and even the behavioral analysis of fruit flies and worms have added significantly to our knowledge base of PD—or have they? Are these animal models manifesting a true model of PD? Have the 7786 published studies (to date) on PD with animal models led to a clearer understanding of its etiology, treatment, or progression? In this review we critically assess this question. We begin with a succinct history of the major contributions, which have led to the current animal models of PD. We then evaluate the primary issue of the progressive loss of DA neurons, which, except for a few studies, has not been addressed in animal models of PD, even though this is the major pathological characteristic of the disease. Lastly, we discuss the possibility that more than one risk factor for PD may be necessary to develop an animal model that shows synergy—the progressive loss of DA neurons. Thus, the multiple hit hypothesis of PD—that is, the effect of more then one risk factor—may be the start of new era in animal models of PD that is one step closer to mimicking the pathology of PD in humans.
Elective endovascular stent-grafting of abdominal aortic aneurysms

Objectives: To investigate the results following endovascular treatment of patients with inflammatory abdominal aortic aneurysms (IAAA). Design: Retrospective study based on the EUROSTAR registry. Material and methods: Patients included in the EUROSTAR registry with IAAA (n=52, 1.4%) were compared with those having aneurysms without aortic fibrosis (n=3613, 98.6%). The mean follow-up period in patients with IAAA was 23 months (range 1-60). In 11 of the patients detailed information on the effect of endovascular repair and perianeurysmal fibrosis and ureteral entrapment was obtained by a dedicated questionnaire. Results: Twelve patients (23%) with IAAA had preoperative impairment of renal function and five had known hydronephrosis. Variables that were significantly associated with IAAA included younger age (p<0.0001, mean difference 5.9, CI 3.7-7.9) and lower pulmonary risks score (OR 0.38, CI 0.19-0.74). At completion of the endovascular procedure, device stenosis was more frequently observed in patients with IAAA (OR 18.1, CI 3.5293.0). There were no differences with regard to the rates of mortality, rupture or conversion in patients with IAAA and controls. In the majority, the aneurysm size regressed irrespective of nature of aneurysm. Of the 11 patients with a detailed assessment three had deterioration of renal function and three still had ureteral entrapment during follow-up. Conclusion: Despite persistence of perianeurysmal inflammation in a proportion of patients operative and midterm results of endovascular repair were comparable in the patients with inflammatory and standard AAA.
Matrix metalloproteinases 2 and 9 in central nervous system and their modification after vanadium inhalation

Vanadium (V) derivatives are well‐known environmental pollutants and its toxicity has been related with oxidative stress. Toxicity after vanadium inhalation on the substantia nigra, corpus striatum, hippocampus and ependymal epithelium was reported previously. The purpose of this study was to analyse the role of matrix metalloproteinases 2 (MMP‐2) and 9 (MMP‐9) in the changes observed in brain tissue after chronic V inhalation. Mice were exposed to vaporized, vanadium pentoxide 0.02 m in deionized water for 1 h twice a week, and killed at 1 h, 1, 2 and 4 weeks after exposure. The brain was removed and the olfactory bulb, prefrontal cortex, striatum and hippocampus were dissected and the MMP content was obtained by zymography. The results showed that MMP‐9 increased in all the structures at the end of the exposure, although in the hippocampus this increment was evident after 1 week of exposure. When MMP‐2 was analysed in the olfactory bulb and prefrontal cortex it remained unchanged throughout the whole exposure, while in the hippocampus it increased at week 4, while in the striatum MMP‐2 increased from the second week only, through the whole experiment. These results demonstrate that V increased MMPs in different structures of the CNS and this change might be associated with the previously reported modifications, such as dendritic spine loss and neuronal cell death. The modifications in MMPs could be related with blood–brain barrier (BBB) disruption which was reported previously. Oxidative stress might also be involved in the activation of these gelatinases as part of the different mechanisms which take place in V toxicity in the CNS. Copyright © 2007 John Wiley & Sons, Ltd.
Data reduction for prediction: A case study on robust coding of age and family history for the risk of having a genetic mutation

Data reduction is often desired in the development of a prediction model, for example for effects of age and family history in the identification of subjects having a genetic mutation. We aimed to evaluate a strategy for model simplification by robust coding of related predictors. We considered 898 patients suspected of having Lynch syndrome, which is caused primarily by mutations in the mismatch repair genes, MLH1 or MSH2. The presence of colorectal cancer (CRC) and endometrial cancer in patients and their relatives was related to mutation prevalence with logistic regression analysis. The performances of simplified and more complex models were quantified with a concordance statistic (c), which was corrected for optimism by cross‐validation and bootstrapping. External validation was performed in 1016 patients.