Miracle-dz/UniFAR-FTUs huggingface dataset:
[The association of TGF beta1 and AT1R gene polymorphisms with hereditary susceptibility and clinical phenotype of HBV-induced liver cirrhosis].

OBJECTIVE To investigate the association of TGF beta1 and AT1R gene polymorphisms with hereditary susceptibility and clinical phenotype of HBV-induced liver cirrhosis. METHODS Peripheral blood samples were collected from 102 patients with HBV-induced liver cirrhosis and 106 healthy blood donors. The polymorphisms of the promoter site -509C/T of TGF beta1 and 1166A/C of AT1R gene were determined by PCR-RFLP. RESULTS The frequency of the homozygote CC of -509C/T of TGF beta1 gene in the group of liver cirrhosis was higher than that the control group (P<0.05); and the frequency rate of homozygote CC was higher in group C than in group A and group B of liver cirrhosis (P<0.05), but there was no significant difference in allele frequency among these group (P>0.05). There was no significant difference in genotypes and allele frequency of AT1R gene 1166A/C between the liver cirrhosis group and the control group (P>0.05). CONCLUSION The polymorphism of the promoter site -509C/T of TGF beta1 gene is associated with hereditary susceptibility to liver cirrhosis and severity of HBV-induced liver cirrhosis; the polymorphism of AT1R gene 1166A/C is not associated with hereditary susceptibility to HBV-induced liver cirrhosis.
Coronary heart disease in women: Less extensive disease and improved long-term survival compared to men

Objectives. The aim of the study was to compare extent of coronary disease and subsequent long-term survival in women compared to men adjusted for baseline differences in demographics and morbidity. Design. In the database at Feiring Heart Clinic 18 767 patients had a coronary angiographic examination in the period from March 1999 to December 31, 2006. Their survival status as of May 31, 2007 was ascertained through the Norwegian National Registry. Survival was compared using age stratified analyses and Cox regression adjusting for baseline differences. Results. Significantly more women than men had no coronary disease (28.7 vs. 10.5%, p <0.001), while three vessel disease was more frequently present in men (38.7 vs. 21.8%, p <0.001), as judged by coronary angiography. Covariate adjusted survival was significantly better in women compared to men with an overall hazard ratio of 1.29 (p <0.001), but with no significant difference in the subgroup with high left ventricular end diastolic pressure. Conclusions. At the time of referral to invasive examination women had less extensive coronary artery disease than men as judged by coronary angiography and improved long-term survival when baseline differences were accounted for.
Effect of propranolol, alprenolol, pindolol, and bopindolol on beta 2-adrenoceptor density in human lymphocytes.

Abrupt withdrawal of beta-adrenoceptor antagonists may lead to "rebound effects. " To investigate the position of the new nonselective beta-adrenoceptor antagonist bopindolol [with moderate intrinsic sympathomimetic activity (ISA)], this drug was compared with propranolol (no ISA), alprenolol (weak ISA), and pindolol (marked ISA). The effects on lymphocyte beta 2-adrenoceptor density--assessed by (+/-)-[125I]iodocyanopindolol (ICYP) binding--were investigated in healthy volunteers aged 23-35 years. None of the test drugs changed the affinity of ICYP for beta 2 adrenoceptors. Propranolol treatment (4 X 40 mg/day) increased the density of beta 2-adrenoceptors by 25% after 2 days; during treatment beta 2-adrenoceptor density remained elevated. After withdrawal of propranolol, beta 2-adrenoceptor density declined slowly, being still significantly increased after 3 days, although propranolol was not detectable in plasma after 24 h, though heart rate was significantly increased. Alprenolol treatment (4 X 100 mg/day) did not significantly affect beta 2-adrenoceptor density. Pindolol treatment (2 X 5 mg/day) caused a 50% decrease of beta 2-adrenoceptor density after 2 days, which remained reduced during treatment. After withdrawal, beta 2-adrenoceptor density was still significantly diminished after 4 days. During and after treatment heart rate was not affected. Bopindolol treatment (2 mg/day) caused a 40% decrease of beta 2-adrenoceptor density after 2 days, which remained reduced during treatment. After withdrawal, beta 2-adrenoceptor density was still significantly diminished after 4 days. During and after treatment heart rate was not affected. It is concluded that the ISA may play an important role in modulating beta 2-adrenoceptor density and hence tissue responsiveness to beta-adrenoceptor stimulation. (ABSTRACT TRUNCATED AT 250 WORDS)
ADAPTIVE COLORATION AND GENE FLOW AS A CONSTRAINT TO LOCAL ADAPTATION IN THE STREAMSIDE SALAMANDER, AMBYSTOMA BARBOURI

Predation is an important selective force that influences animal color patterns. Some larval populations of the streamside salamander, Ambystoma barbouri, inhabit streams with fish predators. Other larval salamanders are found in shallow, ephemeral streams that are predator‐free. Quantitative melanophore cell counts and estimates of percent body area pigmented indicated that larval coloration is strongly correlated with stream type. Larvae that coexist with fish tend to be lighter than larvae from streams that are Ashless and ephemeral. Two approaches demonstrated that lightly pigmented salamander larvae better match the common background in relatively permanent streams and are less conspicuous to fish than dark larvae. First, using a model based on the spectral sensitivity of the fish and reflectance properties of salamanders and natural stream backgrounds, we showed that light larvae are three times more cryptic than dark larvae on rocks. Second, lighter larvae had higher survival than darker salamanders on rocks in a predator‐ choice experiment. It is not clear why larvae in ephemeral streams are darker. Larvae in ephemeral streams should be active to feed and develop rapidly and reach sufficient size to metamorphose before seasonal drying. Several hypotheses may explain why larvae tend to be darker in ephemeral streams, such as increased thermoregulatory ability, better screening of ultraviolet radiation (in these shallower streams), or better background matching to terrestrial predators. Among populations where salamander larvae coexist with fish, there are differences in relative crypsis. Larvae from populations with fish and relatively high gene flow from ephemeral populations (where larvae are dark) tend to be darker (with more melanophores) and more conspicuous to predators than those from more genetically isolated populations, where larvae are lighter and more cryptic. These differences illustrate the role of gene flow as a constraint to adaptive evolution.
Schizophrenia and the HLA-DRB1 gene in the Japanese population.

OBJECTIVE Small Japanese studies have suggested that patients with schizophrenia have higher rates of the HLA-DR1 gene than normal subjects. The authors' goal in the present study was to confirm this finding in a larger number of Japanese subjects. They also investigated the rate of DR4 in Japanese patients with schizophrenia because it has been reported that Caucasian patients with schizophrenia have higher rates of DR4. METHOD They studied the occurrence of the HLA-DRB1 gene in 233 unrelated Japanese patients with schizophrenia compared with the occurrence of the gene in a group of 493 healthy Japanese volunteers. RESULTS A larger proportion of the patients with schizophrenia (15.9%) than the comparison subjects (10.5%) were found to have DR1 (DRB1*0101). The proportion of patients (36.9%) and comparison subjects (40.6%) with DR4 did not differ significantly. CONCLUSIONS Consistent with the findings of three other Japanese studies, the findings of the present study suggest that the rate of HLA-DR1 may be higher in Japanese patients with schizophrenia than in normal Japanese subjects. No evidence for an association between schizophrenia and the rate of DR4 was obtained in this study, although the combined data from the present study and other Japanese studies support the finding of lower rates of DR4 among patients with schizophrenia.
A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma

A trial of autologous T cells redirected to a specific mutation in glioblastoma patients illustrates mechanisms of resistance. Speeding toward CAR T cell therapy for glioblastoma Chimeric antigen receptor (CAR) T cells have been successfully implemented for treating leukemia and are now being investigated for solid tumors. O’Rourke et al. conducted a phase 1 safety study of autologous CAR T cells targeted to EGFR variant III in glioblastoma patients. Treatment seemed to be well tolerated, which is critical because other CAR T cell products have been implicated in devastating central nervous system complications. Of the 10 patients enrolled, 7 had surgical intervention, allowing for some analysis of the tumors and T cells in patients’ brains. The results of this trial indicate that CAR T cell therapy is a viable option for treating glioblastoma. We conducted a first-in-human study of intravenous delivery of a single dose of autologous T cells redirected to the epidermal growth factor receptor variant III (EGFRvIII) mutation by a chimeric antigen receptor (CAR). We report our findings on the first 10 recurrent glioblastoma (GBM) patients treated. We found that manufacturing and infusion of CAR-modified T cell (CART)–EGFRvIII cells are feasible and safe, without evidence of off-tumor toxicity or cytokine release syndrome. One patient has had residual stable disease for over 18 months of follow-up. All patients demonstrated detectable transient expansion of CART-EGFRvIII cells in peripheral blood. Seven patients had post–CART-EGFRvIII surgical intervention, which allowed for tissue-specific analysis of CART-EGFRvIII trafficking to the tumor, phenotyping of tumor-infiltrating T cells and the tumor microenvironment in situ, and analysis of post-therapy EGFRvIII target antigen expression. Imaging findings after CART immunotherapy were complex to interpret, further reinforcing the need for pathologic sampling in infused patients. We found trafficking of CART-EGFRvIII cells to regions of active GBM, with antigen decrease in five of these seven patients. In situ evaluation of the tumor environment demonstrated increased and robust expression of inhibitory molecules and infiltration by regulatory T cells after CART-EGFRvIII infusion, compared to pre–CART-EGFRvIII infusion tumor specimens. Our initial experience with CAR T cells in recurrent GBM suggests that although intravenous infusion results in on-target activity in the brain, overcoming the adaptive changes in the local tumor microenvironment and addressing the antigen heterogeneity may improve the efficacy of EGFRvIII-directed strategies in GBM.
Perception of Bleeding as a Danger Sign During Pregnancy, Delivery, and the Postpartum Period in Rural Nepal

Many developing countries implement safe motherhood programs to tackle high maternal mortality rates. The approach requires recognition of the signs of emergency obstetric cases in order to facilitate immediate care seeking, followed by immediate medical care. Whether such signs are recognized in a timely manner at the community level is determined by how the community perceives health problems. We explore the local understanding of one danger sign—bleeding during pregnancy and at delivery—and the meaning attached to it. The study was conducted in the Kavrepalanchowk district of Nepal. Different qualitative methods were applied. The findings indicate that the community's perception of bleeding might be quite different from that of health professionals and that perceptions and meanings attached to bleeding vary depending on the actors in the family. They all have significant implications for what should be the focus of health education and who should be involved in promoting maternal health.
Intraoperative pancreatoscopy with the ultrathin pancreatoscope for mucin-producing tumors of the pancreas.

OBJECTIVE To evaluate the diagnostic accuracy of intraoperative pancreatoscopy with the ultrathin pancreatoscope for the main pancreatic lesions of mucin-producing tumors of the pancreas (MPT). DESIGN Prospective diagnostic test study with a criterion standard of pathologic examination and masked comparison. SETTING A university hospital. PATIENTS Twenty-four consecutive patients with MPT referred for surgery in whom endoscopic retrograde pancreatography, endoscopic ultrasonography, and computed tomography had been performed as a diagnostic examination. All patients underwent surgery and the diagnosis was confirmed by pathologic examination. INTERVENTION Intraoperative pancreatoscopy was performed with the ultrathin pancreatoscope. MAIN OUTCOME MEASURES Findings of intraoperative pancreatoscopy, endoscopic retrograde pancreatography, and endoscopic ultrasonography were confirmed by pathologic examination of resected specimens. The diagnostic accuracy of these 3 modalities in detection of MPT lesions in the main pancreatic duct was compared. RESULTS The diagnostic criterion of MPT lesions in the main pancreatic duct by intraoperative pancreatoscopy was a granular and papillary mural nodule. An MPT lesion in the main pancreatic duct was found in 17 of 24 cases. Intraoperative pancreatoscopy detected 10 cases of intraductal MPT lesions that could not be detected by endoscopic ultrasonography or endoscopic retrograde pancreatography. Five of 10 cases were intraductal multicentric lesions. In 3 of these 5, additional pancreatic resection was performed. For diagnosis of MPT lesions, the sensitivity, specificity, and overall accuracy of intraoperative pancreatoscopy were all 100%; respective values were 43.8%, 100%, and 60.9% for endoscopic retrograde pancreatography and 47%, 100%, and 62.5% for endoscopic ultrasonography. CONCLUSIONS Intraoperative pancreatoscopy is safe and effective in diagnosing the intrapancreatic duct extension and multicentric lesions of MPT. It provides important information for operative strategy and contributes to successful pancreatic surgery.
Biodiversity of Endophytic Fungi Associated with Uncaria gambier Roxb. (Rubiaceae) from West Sumatra

Endophytic fungi are specific microbes that live at a specific ecosystem in nature. Various endophytic fungi have been known posses an ability to produce a broad range of biologically active substances. Totally 53 endophytic filamentous fungi were isolated from leaves, stems, fruits and roots of the two plant varieties of Uncaria gambier Roxb. (Rubiaceae), i.e. gambir udang and gambir nasi. Morphological observation of 53 isolated endophytic filamentous fungi was further divide into two classes, Coelomycetes and Hypomycetes. Fifteen fungi isolates are unidentified due to lack of specific morphological characters. Morphologically identified fungi at genera level are: Aspergillus, Cladosporium, Diaporthe, Fusarium, Penicillium, Pestalotiopsis, Phoma and Phomopsis. Chemotaxonomic analysis base on their TLC chromatogram patterns of the ethyl acetate extract are in agreement to morphological grouping.Key words: endophytic fungi, Uncaria gambier Roxb. , morphological character, chemotaxonomy.
Islet generation from intra islet precursor cells of diabetic pancreas: in vitro studies depicting in vivo differentiation.

CONTEXT Beta-cells have a limited replicative capacity; hence, there is always a quest for sources of islet regeneration to compensate for the loss of functional beta-cells in diabetes. OBJECTIVE To test the hypothesis of whether intra islet precursor cells of islets isolated from a diabetic pancreas and in vitro streptozotocin treated islets are capable of giving rise to neoislets. INTERVENTIONS Streptozotocin treatment was given to mice and to islets isolated from normal mice. Islets were isolated from diabetic mice, cultured on matrigel coated plates with a well-defined serum free medium containing mitotic (nicotinamide) and differentiating (keratinocyte growth factor) agents. Initially, islets gave rise to an epithelial-like cell monolayer and, later on, differentiated into islet-like clusters. These were characterized for the ductal epithelial cell specific markers cytokeratin-19 and cytokeratin-7 and for the islet specific markers-insulin and PDX1. Insulin secretion in response to glucose and L-arginine was estimated by ELISA. RESULTS A cytokeratin-19 and cytokeratin-7 positive precursor cell population was found scattered throughout the epithelial monolayer. Upon addition of the keratinocyte growth factor, these precursor cells gave rise to islet-like clusters which were confirmed to be islets by marker studies. Though streptozotocin treatment on islets of normal mice allowed proliferation of the epithelial monolayer, it did not give rise to neoislets under similar growth conditions. CONCLUSION The present study reveals that streptozotocin treatment of normal islets in vitro leads to the loss of the potential of intra islet precursor cells to form neoislets; however, in streptozotocin-induced experimental diabetes, they retain their potential to generate new islets opening a novel putative way of treating diabetes.
Robot-Assisted Partial Cystectomy of a Bladder Pheochromocytoma

Pheochromocytoma of the urinary bladder is an unusual tumor that typically presents with hypertensive crises related to micturition. We report here an unusual case of bladder pheochromocytoma that was treated by robotic-assisted laparoscopic partial cystectomy. A 35-year-old male patient presented with headache and hypertension related to micturition. The patient, who had a 3.5 × 4 cm solitary bladder tumor in the bladder dome, underwent robot-assisted partial cystectomy. The whole procedure was successfully performed using the robot without conversion to open surgery. The total operative time was 120 min and the estimated blood loss was 30 ml.
Concentration-resistance relationships with Pseudomonas aeruginosa exposed to doripenem and ciprofloxacin in an in vitro model.

OBJECTIVES To compare the abilities of doripenem and ciprofloxacin to restrict the enrichment of resistant Pseudomonas aeruginosa, multiple antibiotic dosing regimens were simulated in an in vitro model at comparable ratios of the 24 h AUC (AUC24) to the MIC. METHODS Three clinical isolates of ciprofloxacin-resistant P. aeruginosa (MIC of doripenem 1 mg/L, MIC of ciprofloxacin 4 mg/L) were exposed to thrice-daily doripenem or twice-daily ciprofloxacin for 3 days at AUC24/MIC ratios from 50 to 170 h (doripenem) and from 55 to 180 h (ciprofloxacin). RESULTS Doripenem- and ciprofloxacin-resistant mutants were enriched at antibiotic concentrations that fell into the mutant selection window for ≥ 45% and ≥ 60% of the dosing interval, respectively. The anti-mutant effects of doripenem and ciprofloxacin expressed by the area under the bacterial mutant concentration-time curve (AUBCM) depended on the AUC24/MIC ratio, and the AUBCM-log AUC24/MIC relationships were antibiotic specific. CONCLUSION Based on AUC24/MIC relationships with AUBCM, a greater anti-mutant potential was predicted for doripenem compared with ciprofloxacin.
Understanding non-adherence in chronic heart failure: a mixed-method case study

Objectives Understanding non-adherence to guidelines in patients with co-morbidities by supplementing quantitative data through patient-centred qualitative research. It is hypothesised that clinical constraints and patient-related factors explain the vast proportion of non-adherence. Design Mixed-method case study. Setting Primary and secondary acute care hospital, Department for Internal Medicine. Participants All consecutive patients having chronic heart failure (CHF) being hospitalised within a 2-year period. Results Quantitative drug prescribing analysis in 348 patients with CHF confirms moderate guideline adherence: the guideline adherence index (GAI) corresponds to 0.7 for the three most important drug classes indicated for CHF and to 0.6 for all five recommended drug classes. Corrections with regard to the most important clinical contraindication (renal insufficiency) for these drugs raise the GAI to 0.8 in both categories. Semistructured interviews in 50 consecutive patients show relevant reasons for non-adherence in half of the remaining patients with non-adherence to guidelines and raise the adjusted GAI to 0.9. Up to 75% of de jure non-adherence can thus be explained by clinical constraints. Conclusion Quantitative data analysis of treatment regimens in patients with CHF is an inaccurate method for measuring guideline adherence. Combining quantitative prescribing data with semistructured interviews shows a 90% match concerning guideline adherence compared to an only 60% match based on quantitative data alone. Thus, neither quality nor economical assessments of the treatment strategy in patients with chronic diseases should be solely based on quantitative analysis. Understanding non-adherence is crucial for defining and improving quality of care.
Remission of chemotherapy‐induced emesis with concurrent olanzapine treatment: a case report

Chemotherapy-related nausea and vomiting affect at least half of the patients receiving chemotherapy (Morrow and Dobkin, 1988; Morrow et al., 1998). They can be severe and lead to conditioned responses that linger even years later. Although newer antiemetic medications, such as ondansetron and granisetron, have been developed over the last decade, chemotherapyinduced nausea and vomiting still remain a difficult problem. Sometimes nausea and vomiting may persist in patients after all current antiemetic treatments have been exhausted (Gawande, 1999). Psychiatric medications have played a prominent role in the battle against nausea. In recent years, benzodiazopines, such as lorazopam and alprazolam, have been used to ease chemotherapy-induced nausea, particularly anticipatory or conditioned nausea. There has also been some suggestion that nefazadone, an atypical antidepressant, may have antiemetic effect (Khouzam et al., 1998). However, many medications used to treat nausea fall into the antipsychotic class. Typical antipsychotics, particularly phenothiazines (prochlorperazine) and butyrophenones (droperidol and haloperidol), and other medications with antipsychotic-like structures, such as metoclopramide, are widely used in cancer treatment as antiemetics. These medications work by blocking brain dopamine receptors in the chemotrigger zone (CTZ) of the medulla (Veyrat-Follet et al., 1997). However, the antiemetic effect is thought to be mainly from antagonism of the D2 receptor, which can also commonly cause unwanted extrapyramidal side effects, such as akasthisia, dystonia, and even tardive dyskinesia (Stefanini and ClementCormier, 1981; Breitbart, 1986; Leslie et al., 1990). Newer atypical antipsychotic medications, such as clozapine, respiradone and olanzapine, are less likely to produce extrapyramidal side effects because of their weaker affinity for the D2 receptor, but have not been used as antiemetics. Clozapine requires close monitoring because of its risk for agranulocytosis, an unacceptable additional risk in cancer patients already receiving marrow-suppressing chemotherapy. Risperidone and olanzapine have much safer side effect profiles and do not require close monitoring. Although risperidone has been shown to have antiemetic effect in animals, there have not been any reports of risperidone or other atypical antipsychotics acting as antiemetics in humans (Physicians’ Desk Reference, 1999). We report a case of a woman with leukemia and chemotherapy-induced emesis, seen recently at Memorial Sloan-Kettering Cancer Center, who was treated with olanzapine for psychiatric reasons that may suggest some antiemetic effect from this drug. * Correspondence to: Erich Lindeman Mental Health Center, 25 Staniford Street, Boston, MA 02114, USA. Tel. : +1 617 626 8525; e-mail: wpirl@partners.org