27 These previous studies differed in sample size, technology use

27 These previous studies differed in sample size, technology used, and the major etiologic cause (i.e., hepatitis B virus [HBV], hepatitis C virus [HCV], and alcohol). The current study is the largest to date and is comprised of Taiwanese cases who are predominantly HBV positive. 5-HT, 5-hydroxytryptamine; AFB1, aflatoxin B1; bp, base pairs; HBC, hepatitis B virus; HBsAg, hepatitis B surface antigen; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NTU, National Taiwan University; PCR, polymerase chain

reaction; QC, quality control; SD, standard deviation; TSS, transcription start site. This study was approved by the institutional review boards of Columbia University (New York, Selleck LY2606368 NY) and National Taiwan University (NTU; Taipei, Taiwan). Written informed consent was obtained. Sixty-six frozen liver tissues collected in the Department of Surgery at selleck NTU Hospital were assayed. Demographic data and clinicopathologic characteristics were obtained from hospital charts; HBV (hepatitis B surface

antigen; HBsAg) and HCV (anti-HCV) status were determined by immunoassay. For 39 subjects missing HCV status, liver tissues were stained with monoclonal antibody nonstructural protein 3 (Novocastra Laboratories Ltd., Newcastle upon Tyne, UK). Specimens were kept at −70°C until shipment to Columbia University, where pathologic analysis confirmed HCC status and indicated that adjacent tissues were primarily cirrhotic. Blood specimens were collected at the time of diagnosis for 30 patients and were plasma-frozen. Plasma from 8 additional cases from the same hospital was included in the analysis. DNA was extracted by standard proteinase K/RNase treatment and phenol/chloroform extraction. Plasma DNAs were extracted using DNeasy Blood and Tissue Kits (Qiagen, Valencia, CA). Bisulfite modification of 1 μg of DNA was conducted using an EZ DNA Methylation Kit (Zymo Research, Irvine, CA). The HumanMethylation27 DNA Analysis BeadChips (Illumina) were used to interrogate 27,578 highly informative CpG sites covering 14,495 genes, following their standard protocol. Paired samples

(e.g., HCC tumor and adjacent nontumor tissues) 上海皓元医药股份有限公司 were processed on the same chip to avoid chip-to-chip variation; four pairs of tissues were repeat-assayed as a quality control (QC). Information on location of CpG sites in the promoter regions was provided by Dr. Kim.28 Pyrosequencing was carried out with primers designed with Pyromark Assay Design software (version 2.0; Qiagen). The region selected for interrogation included the CpG sites identified to be differentially methylated based on the array data, as well as surrounding sites. Polymerase chain reaction (PCR) was performed in a 25-uL reaction mix containing 50 ng of bisulfite-converted DNA, 1× Pyromark PCR Master Mix (Qiagen), 1× Coral Load Concentrate (Qiagen), and 0.

27 These previous studies differed in sample size, technology use

27 These previous studies differed in sample size, technology used, and the major etiologic cause (i.e., hepatitis B virus [HBV], hepatitis C virus [HCV], and alcohol). The current study is the largest to date and is comprised of Taiwanese cases who are predominantly HBV positive. 5-HT, 5-hydroxytryptamine; AFB1, aflatoxin B1; bp, base pairs; HBC, hepatitis B virus; HBsAg, hepatitis B surface antigen; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NTU, National Taiwan University; PCR, polymerase chain

reaction; QC, quality control; SD, standard deviation; TSS, transcription start site. This study was approved by the institutional review boards of Columbia University (New York, Autophagy Compound Library chemical structure NY) and National Taiwan University (NTU; Taipei, Taiwan). Written informed consent was obtained. Sixty-six frozen liver tissues collected in the Department of Surgery at Akt inhibitor NTU Hospital were assayed. Demographic data and clinicopathologic characteristics were obtained from hospital charts; HBV (hepatitis B surface

antigen; HBsAg) and HCV (anti-HCV) status were determined by immunoassay. For 39 subjects missing HCV status, liver tissues were stained with monoclonal antibody nonstructural protein 3 (Novocastra Laboratories Ltd., Newcastle upon Tyne, UK). Specimens were kept at −70°C until shipment to Columbia University, where pathologic analysis confirmed HCC status and indicated that adjacent tissues were primarily cirrhotic. Blood specimens were collected at the time of diagnosis for 30 patients and were plasma-frozen. Plasma from 8 additional cases from the same hospital was included in the analysis. DNA was extracted by standard proteinase K/RNase treatment and phenol/chloroform extraction. Plasma DNAs were extracted using DNeasy Blood and Tissue Kits (Qiagen, Valencia, CA). Bisulfite modification of 1 μg of DNA was conducted using an EZ DNA Methylation Kit (Zymo Research, Irvine, CA). The HumanMethylation27 DNA Analysis BeadChips (Illumina) were used to interrogate 27,578 highly informative CpG sites covering 14,495 genes, following their standard protocol. Paired samples

(e.g., HCC tumor and adjacent nontumor tissues) MCE公司 were processed on the same chip to avoid chip-to-chip variation; four pairs of tissues were repeat-assayed as a quality control (QC). Information on location of CpG sites in the promoter regions was provided by Dr. Kim.28 Pyrosequencing was carried out with primers designed with Pyromark Assay Design software (version 2.0; Qiagen). The region selected for interrogation included the CpG sites identified to be differentially methylated based on the array data, as well as surrounding sites. Polymerase chain reaction (PCR) was performed in a 25-uL reaction mix containing 50 ng of bisulfite-converted DNA, 1× Pyromark PCR Master Mix (Qiagen), 1× Coral Load Concentrate (Qiagen), and 0.

Recombinant wild-type GPIb has been coupled to uniform beads maki

Recombinant wild-type GPIb has been coupled to uniform beads making the assay completely platelet free. The assay is available in two versions, one based on turbidimetric detection and the other on chemiluminescence. Recent evaluations showed that the new assay protocols were precise and suitable for diagnosis of VWD [17-19]. With

specific amino acid substitutions in the GPIb receptor it is possible to obtain constructs that bind AZD0530 concentration VWF without requiring ristocetin. With these gain-of-function GPIb peptides, novel assays, based on the ELISA format or particle-based automated assays, have been successfully developed [20, 21]. It appears, also, that activity is unaffected by a common VWF gene polymorphism known to result in false low VWF:RCo activity results [20]. An automated version of this assay type was recently commercialized and has gained popularity in regions where it has been released. According to the European external quality assessment (EQA) organization, ECAT, the number of laboratories that use a VWF:RCo assay protocol is steadily declining whereas the number using alternative activity assays is increasing. The method group for assays determining GPIb binding capacity in the ECAT programme is now divided into two activity groups: classical VWF:RCo and novel ‘VWF activity’. The current number

of participants in the two groups check details is almost equal. The majority use the latex VWF activity assay, from Instrumentation Laboratory, or the Innovance VWFAc, from Siemens. 上海皓元 The former is not a ‘true’ activity assay as it relies on a monoclonal antibody that recognizes the functional GPIb binding epitope on VWF. However, the Innovance VWFAc assay is based on the gain-of-function GPIb construct that binds VWF without ristocetin. Despite their apparent success, based on the number of users

in various EQAs, surprisingly few independent evaluations of the novel assays have been published [22]. Compared with the VWF:RCo assay, the novel assays have several practical advantages that probably explain the rapid transition from the VWF:RCo to the novel activity assays. Moreover, the total number of users in the ECAT VWF module has increased recently and it is likely that the simplicity of the novel assays encourages less experienced laboratories to include them as the activity assay in their test repertoire. With the increased diversity of VWF activity assays, other problems arise. First, the diagnostic industry provides assays that have been developed for specific instruments that may not be available in all countries. Second, the assays themselves may not be approved for clinical use in large parts of the world. This is currently the case for the Siemens Innovance VWFAc assay, not yet approved by the US FDA. As a consequence, it is difficult to suggest general recommendations on VWD testing that include the novel activity assays.

Thus, a higher PPV suggests more accuracy of a test in identifyin

Thus, a higher PPV suggests more accuracy of a test in identifying patients with good prognosis; a higher NPV suggests more accuracy of a test in identifying patients with poor prognosis; and a lower NLR suggests more accuracy of a test in identifying patients with

poor prognosis. The performance of biochemical response after 3, 6, and 12 months of UDCA therapy for prediction of long-term outcome was assessed (Table 4). We found that biochemical responses at the sixth month may identify patients with good or poor prognosis with no less accuracy than evaluation at 1 year. The former showed higher or the same PPV and NPV and lower NLR than the latter by all definitions tested. In contrast, biochemical responses at the third month demonstrated higher PPV, lower NPV, and increased NLR by all definitions compared with biochemical responses at 1 year. selleck It can be inferred that biochemical responses at the third month were superior in identifying patients with good prognosis, yet were less potent in selecting high-risk patients for therapeutic trials. Our findings are in accordance with and provide more direct evidence to the statement that

therapeutic trials should target patients with incomplete biochemical response after 3 to 6 months of UDCA treatment.11 Our study was limited by small sample size and relatively Raf inhibitor short duration of follow-up. Another limitation is that a considerable proportion of patients did not strictly follow the regular 3-month examination interval, making biochemical data available for 128 (68.4%) patients for the third month after UDCA treatment, 145 (77.5%) patients for the sixth month, and 157 (84.0%) patients for 1 year. MCE公司 To make full use of the available data, we used all data for the statistical analyses. To avoid bias, we compared the baseline characteristics of patients with or without recorded biochemical data. They did not differ statistically in age, sex, baseline biochemical data, and long-term outcomes

(data not shown). Thus, the influence of missing data would mostly likely not effect the results. The strict criteria for selecting patients at entry, the careful follow-up of patients, and the prospective nature of the collected data can partly compensate for these limitations. The evolution of laboratory liver parameters within the first year of UDCA therapy, the compatibility of biochemical response at 3, 6, and 12 months in discriminating patients with good or poor outcome, and similar prognostic impact of biochemical responses at 6 and 12 months together contributed to our conclusion that an early biochemical response at 6 months would as efficiently identify patients at risk of poor outcome as evaluation at 1 year.

Thus, a higher PPV suggests more accuracy of a test in identifyin

Thus, a higher PPV suggests more accuracy of a test in identifying patients with good prognosis; a higher NPV suggests more accuracy of a test in identifying patients with poor prognosis; and a lower NLR suggests more accuracy of a test in identifying patients with

poor prognosis. The performance of biochemical response after 3, 6, and 12 months of UDCA therapy for prediction of long-term outcome was assessed (Table 4). We found that biochemical responses at the sixth month may identify patients with good or poor prognosis with no less accuracy than evaluation at 1 year. The former showed higher or the same PPV and NPV and lower NLR than the latter by all definitions tested. In contrast, biochemical responses at the third month demonstrated higher PPV, lower NPV, and increased NLR by all definitions compared with biochemical responses at 1 year. XL765 chemical structure It can be inferred that biochemical responses at the third month were superior in identifying patients with good prognosis, yet were less potent in selecting high-risk patients for therapeutic trials. Our findings are in accordance with and provide more direct evidence to the statement that

therapeutic trials should target patients with incomplete biochemical response after 3 to 6 months of UDCA treatment.11 Our study was limited by small sample size and relatively Roxadustat supplier short duration of follow-up. Another limitation is that a considerable proportion of patients did not strictly follow the regular 3-month examination interval, making biochemical data available for 128 (68.4%) patients for the third month after UDCA treatment, 145 (77.5%) patients for the sixth month, and 157 (84.0%) patients for 1 year. 上海皓元医药股份有限公司 To make full use of the available data, we used all data for the statistical analyses. To avoid bias, we compared the baseline characteristics of patients with or without recorded biochemical data. They did not differ statistically in age, sex, baseline biochemical data, and long-term outcomes

(data not shown). Thus, the influence of missing data would mostly likely not effect the results. The strict criteria for selecting patients at entry, the careful follow-up of patients, and the prospective nature of the collected data can partly compensate for these limitations. The evolution of laboratory liver parameters within the first year of UDCA therapy, the compatibility of biochemical response at 3, 6, and 12 months in discriminating patients with good or poor outcome, and similar prognostic impact of biochemical responses at 6 and 12 months together contributed to our conclusion that an early biochemical response at 6 months would as efficiently identify patients at risk of poor outcome as evaluation at 1 year.

Recognition memory (RM), familiarity, and recollection were exami

Recognition memory (RM), familiarity, and recollection were examined in 21 patients with

mild-to-moderate PD (Hoehn and Yahr mean: 2.67). Patients were subdivided into two subgroups according to dopamine agonist (pramipexole [PPX] or ropinirole [RPR]), and completed matched versions of an RM test in a medicated and unmedicated condition (termed ON and OFF, respectively). Ten demographically matched healthy volunteers (HVs) also completed both RM tasks in two separate sessions. The PD group (PPX and RPR subgroups combined) Idasanutlin ic50 showed impairments in RM and recollection, but spared familiarity. When subdivided by dopamine agonist, the PPX subgroup’s ON-medication recollection performance was significantly lower than that of both the HVs and RPR subgroup. There was no evidence of decline in OFF-medication recollection or familiarity in either the PPX or RPR subgroups. Recollection in both PD subgroups correlated positively with a composite measure

of recall, but not prefrontally dependent measures of cognitive control. These findings suggest that mild-to-moderate PD patients may show relatively preserved recollection and familiarity, but that recollection is selectively disrupted by PPX, but not RPR and that this effect may depend on disrupted hippocampal function Selleck BIBW2992 rather than impaired pre-frontally dependent executive functions. “
“The ability to recognize and label emotional facial expressions is an important aspect of social cognition. However, existing paradigms to examine this ability present only static facial expressions, suffer from ceiling effects or have limited or no norms. A computerized test, the Emotion Recognition Task (ERT), was developed

to overcome these difficulties. In this study, we examined the effects of age, sex, and intellectual ability on emotion perception using the ERT. In this test, emotional facial expressions are presented as morphs gradually expressing one of the six basic emotions from neutral to four levels of intensity (40%, 60%, 80%, and 100%). The task MCE was administered in 373 healthy participants aged 8–75. In children aged 8–17, only small developmental effects were found for the emotions anger and happiness, in contrast to adults who showed age-related decline on anger, fear, happiness, and sadness. Sex differences were present predominantly in the adult participants. IQ only minimally affected the perception of disgust in the children, while years of education were correlated with all emotions but surprise and disgust in the adult participants. A regression-based approach was adopted to present age- and education- or IQ-adjusted normative data for use in clinical practice. Previous studies using the ERT have demonstrated selective impairments on specific emotions in a variety of psychiatric, neurologic, or neurodegenerative patient groups, making the ERT a valuable addition to existing paradigms for the assessment of emotion perception.

Recognition memory (RM), familiarity, and recollection were exami

Recognition memory (RM), familiarity, and recollection were examined in 21 patients with

mild-to-moderate PD (Hoehn and Yahr mean: 2.67). Patients were subdivided into two subgroups according to dopamine agonist (pramipexole [PPX] or ropinirole [RPR]), and completed matched versions of an RM test in a medicated and unmedicated condition (termed ON and OFF, respectively). Ten demographically matched healthy volunteers (HVs) also completed both RM tasks in two separate sessions. The PD group (PPX and RPR subgroups combined) DAPT in vitro showed impairments in RM and recollection, but spared familiarity. When subdivided by dopamine agonist, the PPX subgroup’s ON-medication recollection performance was significantly lower than that of both the HVs and RPR subgroup. There was no evidence of decline in OFF-medication recollection or familiarity in either the PPX or RPR subgroups. Recollection in both PD subgroups correlated positively with a composite measure

of recall, but not prefrontally dependent measures of cognitive control. These findings suggest that mild-to-moderate PD patients may show relatively preserved recollection and familiarity, but that recollection is selectively disrupted by PPX, but not RPR and that this effect may depend on disrupted hippocampal function HDAC inhibitor mechanism rather than impaired pre-frontally dependent executive functions. “
“The ability to recognize and label emotional facial expressions is an important aspect of social cognition. However, existing paradigms to examine this ability present only static facial expressions, suffer from ceiling effects or have limited or no norms. A computerized test, the Emotion Recognition Task (ERT), was developed

to overcome these difficulties. In this study, we examined the effects of age, sex, and intellectual ability on emotion perception using the ERT. In this test, emotional facial expressions are presented as morphs gradually expressing one of the six basic emotions from neutral to four levels of intensity (40%, 60%, 80%, and 100%). The task MCE公司 was administered in 373 healthy participants aged 8–75. In children aged 8–17, only small developmental effects were found for the emotions anger and happiness, in contrast to adults who showed age-related decline on anger, fear, happiness, and sadness. Sex differences were present predominantly in the adult participants. IQ only minimally affected the perception of disgust in the children, while years of education were correlated with all emotions but surprise and disgust in the adult participants. A regression-based approach was adopted to present age- and education- or IQ-adjusted normative data for use in clinical practice. Previous studies using the ERT have demonstrated selective impairments on specific emotions in a variety of psychiatric, neurologic, or neurodegenerative patient groups, making the ERT a valuable addition to existing paradigms for the assessment of emotion perception.

92 In NAFLD/NASH the picture is less clear, as reviewed93 While

92 In NAFLD/NASH the picture is less clear, as reviewed.93 While it is clear that caloric excess is associated with obesity, it does not discriminate between those with NASH, simple steatosis or normal liver histology; when matched for body weight, most studies report similar calorie intake. In a Japanese study, where patients with NASH and SS were compared to a large, healthy population, increased energy intake was observed, particularly in younger patients,

but failed to distinguish steatohepatitis from steatosis.94 Differences in total fat content have been noted in a single study.95 Another, in non-obese individuals with NASH found significant differences only in saturated fatty acid intake,96 but this has not been a consistent finding, with others finding differences in simple carbohydrate content (substrate for lipogenesis), not fat.97,98 In the Vismodegib latter study in morbidly obese individuals, carbohydrate content correlated with hepatic inflammatory response, and fat content appeared to have a protective effect.98

In agreement http://www.selleckchem.com/products/XL184.html with this, the potential importance of fructose intake is highlighted by the association of sugar-sweetened beverages and NAFLD.99 Studies of polyunsaturated fatty acid (PUFA) content have also produced divergent results; some have shown lower n-3 PUFA content,94,97 others comparable n-3 PUFA but higher intake of n-6 PUFA in subjects with NAFLD.95,99 Re-analysis of data derived from a population-based survey identified a significant association between dietary cholesterol and cirrhosis, irrespective of cause.100

Finally, lower intake of anti-oxidant vitamins A, C and E have been variably reported in patients with NASH, as have decreased zinc and iron intake.93–99 Clearly, more extensive investigation is required to 上海皓元 determine if certain dietary factors do predispose to NASH, or whether more subtle diet/genotype interactions alter an individual’s susceptibility to development of liver injury and inflammation. The latter has been suggested for metabolic syndrome, in respect of adiponectin promoter polymorphisms.101 Several studies have shown that increasing aerobic exercise on a regular basis improves the metabolic indices strongly associated with NASH (waist circumference, serum insulin, hyperglycemia, serum lipids); this is associated with correction of liver test abnormalities.102–104 Histological studies have confirmed improvement of NASH following institution of an organized lifestyle program that combines physical activity with dietary advice.102 Few studies have compared a combined lifestyle approach delivered in a motivating (behavior changing) context with caloric restriction alone.

Results: Aortic

thrombi may have devastating complication

Results: Aortic

thrombi may have devastating complications like peripheral embolism and may cause angina and ischemia, so it requires prompt recognition and treatment. Conclusion: We report a case of a descending aorta thrombus in a patient with CRC and liver metastases, which arised without any surgical intervention or chemotherapy and has not been reported previously in literature. Key Word(s): 1. Aortic thrombus; 2. Ca Rectum; 3. Metastasis; Presenting Author: TONGMING FU Additional Authors: CAICHANG CHUN Corresponding Author: CAICHANG CHUN Affiliations: jiujiang university; university of jiujiang Objective: Summary clinical features of ischemic colitis, and test the fluctuation of plasma D-dimer, to evaluate the value of plasma D-dimer in diagnosing ischemic colitis. learn more Methods: Analysis RXDX-106 supplier the date of 31 cases with ischemic colitis, admitted in our hospital from December 2007 to December 2011. Dignosised mainly by endoscopy, Histological pathology, ultrasound and CTA. plasma D-dimer level need to tested for every patient at the first day after admitted. colonoscopy should done after 48 hours, two weeks later, do colonoscopy again. Results: All patients are above the age of 55, average age is 58.6. Typical endoscopic

features include ischemia, erythema, crisp, gangrene, ulceration, exudation and bleeding lie in submucosa, all of these features are no specifical. Pathological features include epithelial degeneration, necrosis, regeneration, hemorrhage, edema, exudation of protein-rich ingredients.

levels of plasma D-dimer in all patients are 1450 ± 242 ng/ml, much higher than nomal level. Conclusion: ① Ischemic colitis always accompanied with other basic diseases; ② colonoscoy is a very Sensitive method for dignosis at early stage. ③ plasma D-dimer increasing much at early stage for ischemin colitis, which inply plasma D-dimer can play a importment role in diagnosing ischemic colitis. Key Word(s): 1. clinical features; 2. ischemic colitis; 3. plasma D-dimer; 4. diagnosis; Presenting Author: ZHANGYU JIE Additional Authors: medchemexpress LI YANI, LIANG SHUHUI, HONG LIU, WANG BIAOLUO, WU KAICHUN Corresponding Author: ZHANGYU JIE Affiliations: Fourth Military Medical University Objective: A 18-year-old man presented to the emergency department with intermittent abdominal pain for two week, severe constipation for 48 hours. The patient had otherwise unremarkable medical history. On clinical examination, there were scarce bowel sounds and the abdomen was diffusely tender. There were no palpable masses and no feces in the rectum. Clinically, there was voluntary guarding, but no signs of peritonitis. Methods: Blood tests were within normal limits. Abdominal radiographs showed a distended large bowel with a remarkable distention of the left colon without small bowel involvement. Results: During the next 24 hours, the patient’s clinical and radiologic picture deteriorated.

Results: Aortic

thrombi may have devastating complication

Results: Aortic

thrombi may have devastating complications like peripheral embolism and may cause angina and ischemia, so it requires prompt recognition and treatment. Conclusion: We report a case of a descending aorta thrombus in a patient with CRC and liver metastases, which arised without any surgical intervention or chemotherapy and has not been reported previously in literature. Key Word(s): 1. Aortic thrombus; 2. Ca Rectum; 3. Metastasis; Presenting Author: TONGMING FU Additional Authors: CAICHANG CHUN Corresponding Author: CAICHANG CHUN Affiliations: jiujiang university; university of jiujiang Objective: Summary clinical features of ischemic colitis, and test the fluctuation of plasma D-dimer, to evaluate the value of plasma D-dimer in diagnosing ischemic colitis. RG7204 Methods: Analysis CAL-101 price the date of 31 cases with ischemic colitis, admitted in our hospital from December 2007 to December 2011. Dignosised mainly by endoscopy, Histological pathology, ultrasound and CTA. plasma D-dimer level need to tested for every patient at the first day after admitted. colonoscopy should done after 48 hours, two weeks later, do colonoscopy again. Results: All patients are above the age of 55, average age is 58.6. Typical endoscopic

features include ischemia, erythema, crisp, gangrene, ulceration, exudation and bleeding lie in submucosa, all of these features are no specifical. Pathological features include epithelial degeneration, necrosis, regeneration, hemorrhage, edema, exudation of protein-rich ingredients.

levels of plasma D-dimer in all patients are 1450 ± 242 ng/ml, much higher than nomal level. Conclusion: ① Ischemic colitis always accompanied with other basic diseases; ② colonoscoy is a very Sensitive method for dignosis at early stage. ③ plasma D-dimer increasing much at early stage for ischemin colitis, which inply plasma D-dimer can play a importment role in diagnosing ischemic colitis. Key Word(s): 1. clinical features; 2. ischemic colitis; 3. plasma D-dimer; 4. diagnosis; Presenting Author: ZHANGYU JIE Additional Authors: 上海皓元医药股份有限公司 LI YANI, LIANG SHUHUI, HONG LIU, WANG BIAOLUO, WU KAICHUN Corresponding Author: ZHANGYU JIE Affiliations: Fourth Military Medical University Objective: A 18-year-old man presented to the emergency department with intermittent abdominal pain for two week, severe constipation for 48 hours. The patient had otherwise unremarkable medical history. On clinical examination, there were scarce bowel sounds and the abdomen was diffusely tender. There were no palpable masses and no feces in the rectum. Clinically, there was voluntary guarding, but no signs of peritonitis. Methods: Blood tests were within normal limits. Abdominal radiographs showed a distended large bowel with a remarkable distention of the left colon without small bowel involvement. Results: During the next 24 hours, the patient’s clinical and radiologic picture deteriorated.