Predictors of failure to detect early hepatocellular carcinoma in patients with chronic hepatitis B who received regular surveillance.

BACKGROUND: A proportion of chronic hepatitis B (CHB) patients are diagnosed with advanced hepatocellular carcinoma (HCC) despite regular surveillance. AIMS: To determine predictors for HCC detection failure in CHB patients who underwent regular surveillance. METHODS: CHB patients with well-preserved liver function, who underwent ultrasonography and alpha-foetoprotein (AFP) analysis every 6 months, were enrolled. Cox regression analysis was used to identify predictors for detection failure, defined as HCC initially diagnosed at Barcelona Clinic Liver Cancer (BCLC) stage B or C. RESULTS: Of the 4590 CHB patients (mean age, 52.1 years; men, 61.6%), 169 patients were diagnosed with HCC (3.68%) and 35 (20.7%) HCC patients were initially diagnosed with HCC BCLC stage B or C. The cumulative incidence of HCC detection failure was 0.2% at year 1 and 1.3% at year 5. Multivariate analyses indicated that cirrhosis (hazard ratio [HR], 3.078; 95% CI, 1.389-6.821; P = 0.006), AFP levels ≥9 ng/mL (HR, 5.235; 95% CI, 2.307-11.957; P = 0.010), and diabetes mellitus (HR, 3.336; 95% CI, 1.341-8.296; P = 0.010) were independent predictors of HCC detection failure. Another model that incorporated liver stiffness (LS) values identified LS values ≥11.7 kPa (HR, 11.045; 95% CI, 2.066-59.037; P = 0.005) and AFP levels ≥9 ng/mL (HR, 4.802; 95% CI, 1.613-14.297; P = 0.005) as predictors of detection failure. CONCLUSIONS: In CHB patients undergoing regular surveillance with ultrasonography and alpha-foetoprotein (AFP) analysis every 6 months, the HCC detection failure rate was not high (0.8% per person; 0.1% per test). However, careful attention should be paid in patients with advanced liver fibrosis (clinical cirrhosis or LS value >11.7 kPa), high AFP levels, or diabetes mellitus, who are prone to surveillance failure.

Exposure to fine particulate matter associated with senile lentigo in Chinese women: a cross-sectional study.

BACKGROUND: Skin ageing especially senile lentigo directly affects self-esteem. For decades, senile lentigo has been associated with chronic exposure to solar radiation. However, a study conducted recently in Caucasian subjects suggested that exposure to air pollution was significantly correlated with extrinsic skin ageing, in particular senile lentigines. OBJECTIVE: To investigate the association between fine particulate matter (PM2.5 ) and skin ageing, particularly senile lentigo and seborrheic keratosis. METHODS: The study enrolled 400 Chinese women aged 40-90 years including 210 from the Yanqing county in Beijing (low PM2.5 exposure group) and 190 from the Xuanwumen in Beijing (high PM2.5 exposure group). Skin ageing symptoms, particularly senile lentigines and seborrheic keratoses, were clinically assessed using scores of intrinsic and extrinsic skin ageing. An ordinal logistic regression model was used to analyse the effect of PM2.5 on skin ageing adjusted for factors underlying skin ageing. RESULTS: In the study population of Xuanwumen, we found that senile lentigo on cheeks and back of hands was 1.48 times and 2.8 times higher, respectively, compared with those from Yanqing county. However, no association was found between PM2.5 and seborrheic keratosis. We found that other variables such as smoking, second-hand smoking, contact with fossil fuels and skin types were significantly associated with skin ageing. CONCLUSION: These results indicate that PM2.5 was another extrinsic factor promoting skin ageing.

Effects of guar gum ingestion on postprandial blood pressure in older adults.

OBJECTIVES: The aim of this study was to investigate the effects of guar gum on postprandial blood pressure in older people. DESIGN: A randomized, double-blind, placebo-controlled, cross-over design. SETTING: Community senior centers in B city, South Korea. PARTICIPANTS: Twenty-two older female adults aged 67 to 88 with postprandial hypotension. INTERVENTION: The participants were randomly assigned to guar gum (semi-fluid food with 9 gram) or placebo intervention during the first treatment phase. After a washout period of 1 week, the two interventions were switched to the other in the second treatment phase. MEASUREMENTS: Blood pressure was measured during both phases before having a meal and every 15 minutes during 120 minutes after a meal with automated sphygmomanometer. RESULTS: Change in systolic blood pressure (SBP) over time was significantly different between guar gum and placebo groups (F=4.07, p=0.001). Compared with placebo group, guar gum group had significantly low prevalence of postprandial hypotension (PPH) (guar gum group=18.2% vs. placebo group=72.7%; χ² =13.20, p<0.001). It also had significant difference in change of diastolic blood pressure (DBP) over time between guar gum and placebo groups (F=2.49, p=0.027). CONCLUSION: This findings show that guar gum could be effective on postprandial drops in blood pressure in older female adults.

The frequency and impact of ROS1 rearrangement on clinical outcomes in never smokers with lung adenocarcinoma.

BACKGROUND: To determine the frequency and predictive impact of ROS1 rearrangements on treatment outcomes in never-smoking patients with lung adenocarcinoma. PATIENTS AND METHODS: We concurrently analyzed ROS1 and ALK rearrangements and mutations in the epidermal growth factor receptor (EGFR), and KRAS in 208 never smokers with lung adenocarcinoma. ROS1 and ALK rearrangements were identified by fluorescent in situ hybridization. RESULTS: Of 208 tumors screened, 7 (3.4%) were ROS1 rearranged, and 15 (7.2%) were ALK-rearranged. CD74-ROS1 fusions were identified in two patients using reverse transcriptase-polymerase chain reaction. The frequency of ROS1 rearrangement was 5.7% (6 of 105) among EGFR/KRAS/ALK-negative patients. Patients with ROS1 rearrangement had a higher objective response rate (ORR; 60.0% versus 8.5%; P = 0.01) and a longer median progression-free survival (PFS; not reached versus 3.3 months; P = 0.008) to pemetrexed than those without ROS1/ALK rearrangement. The PFS to EGFR-tyrosine kinase inhibitors in patients harboring ROS1 rearrangement was shorter than those without ROS1/ALK rearrangement (2.5 versus 7.8 months; P = 0.01). CONCLUSIONS: The frequency of ROS1 rearrangements in clinically selected patients is higher than that reported for unselected patients, suggesting that ROS1 rearrangement is a druggable target in East-Asian never smokers with lung adenocarcinoma. Given the different treatment outcomes to conventional therapies and availability of ROS1 inhibitors, identification of ROS1 rearrangement can lead to successful treatment in ROS1-rearranged lung adenocarcinomas.

Endovascular treatment for unruptured intracranial aneurysms in elderly patients: single-center report.

BACKGROUND AND PURPOSE: The optimal management of patients with unruptured intracranial aneurysms remains controversial in elderly populations. The aim of this study was to evaluate technical results and clinical outcomes in a single center of consecutive elderly patients with unruptured intracranial aneurysms treated with endovascular embolization. MATERIALS AND METHODS: Between May 2003 and February 2010, 96 patients older than 70 years (men, 16 patients; women, 80 patients; mean age, 73 years) with 122 saccular unruptured intracranial aneurysms were treated in our hospital with an endovascular approach. The endovascular procedures and technique, angiographic follow-up, and complications were evaluated. RESULTS: Successful embolizations without complications were completed in 95.9%. Five patients had procedure-related events, including thromboembolism in 1 patient, aneurysm perforation during the procedure in 1, and 3 postoperative transient minor symptoms (headache, otalgia, and trigeminal pain) in 3. The degree of occlusion of the treated aneurysm was complete in 46.7%; there was a small neck remnant in 40.9% and residual filling in 12.2%. Imaging (MR angiography) follow-up was performed in 68.7% of the patients. The mean follow-up duration was 19.4 months (range, 5-57 months). Fifty-five patients (93.9%) showed no interval change of the residual neck. Four (6%) demonstrated recanalizations, all of which were successfully recoiled. CONCLUSIONS: Endovascular treatment of unruptured intracranial aneurysms in patients older than 70 years of age appears to be safe. Favorable outcomes with low morbidities may replace surgery or conservative treatment as an active management alternative.

Urocanic acid-modified chitosan-mediated PTEN delivery via aerosol suppressed lung tumorigenesis in K-ras(LA1) mice.

The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. Revisiting of aerosol gene delivery may provide an alternative for safe and effective treatment for lung cancer. In this study, imidazole ring-containing urocanic acid-modified chitosan (UAC) designed in the previous study was used as a gene carrier. The potential effects of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) on Akt-related signals and cell cycle regulation were evaluated. Aerosols of UAC-PTEN were delivered into K-ras(LA1) lung cancer model mice through the nose-only inhalation system twice a week for total 4 weeks. Delivered PTEN suppressed lung tumor development significantly through nuclear complex formation between PTEN and p53, suppressing Akt-related signals as well as cell cycle regulation. Together, our results suggest that aerosol delivery of UAC-PTEN may be compatible with noninvasive in vivo gene therapy.

Thrombolytic evacuation of post-craniotomy epidural haematomas using closed suction drains: a pilot study.

BACKGROUND: As an effective treatment for post-craniotomy epidural haematomas (EDHs), a novel method of urokinase instillation using a closed suction drain is presented and the procedure feasibility and outcomes assessed. METHOD: A closed system, comprising a closed suction drain with a three-spring 200 mL evacuator, fluid bag with urokinase, and syringe, was constructed to instill urokinase and evacuate a postoperative EDH. Nine patients with a symptomatic, localised EDH under a bone flap after a craniotomy underwent successive urokinase instillation following the proposed protocol. Measurement of the EDH volume and clinical evaluation were performed. FINDINGS: An improvement of computerised tomography findings and clinical state after urokinase instillation was observed in all patients. Six urokinase instillations lasting 12 h in 6 patients with an EDH (18.2 +/- 2.4 mL) and 12 urokinase instillations lasting 24 h in the other 3 patients with an EDH (33.0 +/- 7.9 mL) succeeded in achieving a minimal residual EDH (6.1 +/- 2.8 mL). The EDH volume decreased at a rate of 13.0 +/- 2.3 mL/12 h. The GCS scores increased immediately after thrombolytic evacuation of the EDHs in 6 out of the 9 patients. For the other three patients who did not show a change of GCS score, the severe headaches were improved. All the patients were successfully treated using the proposed technique with no procedural complications such as haemorrhage or infection in the operative wound. CONCLUSIONS: This pilot study demonstrated that thrombolytic evacuation of a post-craniotomy EDH using a closed suction drain is feasible without complications and may be associated with better outcomes.

Lentivirus-mediated carboxyl-terminal modulator protein gene transfection via aerosol in lungs of K-ras null mice.

The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. Aerosol gene delivery may provide the alternative for safe and effective treatment for lung cancer. Therefore, current study was performed to elucidate the potential effects of C-terminal modulator protein (CTMP) via aerosol on lung tumorigenesis. Lentiviral vector-CTMP was delivered into K-ras null lung cancer mice through the nose-only inhalation system for 30 min. After 48 h, the potential effects of CTMP on Akt1-related signals and cell cycle regulation in the lungs were evaluated by western blot, immunohistochemistry and zymography. Lentivirus-based CTMP delivery inhibited the Akt1 activity through selective suppression of Akt1 phosphorylation at Ser473. Aerosol delivery of CTMP inhibited proteins important for Akt1 signals, cell cycle and tumor metastasis in lungs of K-ras null mice. Together, our results suggest that lentivirus-mediated aerosol delivery of CTMP may be compatible with noninvasive in vivo gene therapy. Our results emphasize the importance of noninvasive-targeted delivery of CTMP for lung cancer therapy in the future. While the studies are conducted in mice, it is envisioned that noninvasive targeting the specific genes responsible for cancer progression is an attractive strategy for effective anticancer therapeutics.

Aerosol-delivered programmed cell death 4 enhanced apoptosis, controlled cell cycle and suppressed AP-1 activity in the lungs of AP-1 luciferase reporter mice.

The long-term survival of lung cancer patients treated with conventional therapies remains poor and therefore the need for novel approaches remains high. This has led to the re-emergence of aerosol delivery as a therapeutic intervention. In this study, glucosylated polyethylenimine (GPEI) was used as carrier to investigate programmed cell death 4 (PDCD4) and PDCD4 mutant (D418A), an eIF4A-binding mutant, on PDCD4-related signaling and activator protein-1 (AP-1) activity in the lungs of AP-1 luciferase reporter mice. After confirming the efficiency of GPEI as a carrier in lungs, the effects of aerosol-delivered PDCD4 were investigated in AP-1 luciferase reporter mice. Aerosol delivery of GPEI/PDCD4 through a nose-only inhalation facilitated the apoptosis of lungs whereas aerosol PDCD4 mutant did not. Also, such aerosol delivery regulated proteins relevant to cell-cycle control and suppressed AP-1 activity. Results obtained by western blot analysis, immunohistochemistry, luciferase assay and deoxynucleotidyl-transferase-mediated nick end labeling study suggest that combined actions such as facilitating apoptosis, controlling cell cycle and suppression of AP-1 activity by PDCD4 may provide useful tool for designing lung tumor prevention and treatment by which PDCD4 functions as a transformation suppressor in the future.

Aerosol delivery of Akt controls protein translation in the lungs of dual luciferase reporter mice.

Lung cancer has emerged as a leading cause of cancer death in the world; however, most of the current conventional therapies are not sufficiently effective in altering the progression of disease. Therefore, development of novel treatment approaches is needed. Although several genes and methods have been used for cancer gene therapy, a number of problems such as specificity, efficacy and toxicity reduce their application. This has led to re-emergence of aerosol gene delivery as a noninvasive method for lung cancer treatment. In this study, nano-sized glucosylated polyethyleneimine (GPEI) was used as a gene delivery carrier to investigate the effects of Akt wild type (WT) and kinase deficient (KD) on Akt-related signaling pathways and protein translation in the lungs of CMV- LucR-cMyc-IRES-LucF dual reporter mice. These mice are a powerful tool for the discrimination between cap-dependent/-independent protein translation. Aerosols containing self-assembled nano-sized GPEI/Akt WT or GPEI/Akt KD were delivered into the lungs of reporter mice through nose-only-inhalation-chamber with the aid of nebulizer. Aerosol delivery of Akt WT caused the increase of protein expression levels of Akt-related signals, whereas aerosol delivery of Akt KD did not. Furthermore, dual luciferase activity assay showed that aerosol delivery of Akt WT enhanced cap-dependent protein translation, whereas a reduction in cap-dependent protein translation by Akt KD was observed. Our results clearly showed that targeting Akt may be a good strategy for prevention as well as treatment of lung cancer. These studies suggest that our aerosol delivery is compatible for in vivo gene delivery which could be used as a noninvasive gene therapy in the future.

Intramedullary clear cell meningioma.

Intramedullary clear cell meningioma (CCM), which is more aggressive than other meningioma variants, is extremely rare. To date, only one case of such a spinal tumour has been documented. We report the first case of an intramedullary CCM originating in the thoracic region of the spinal cord.

Molecular cloning and expression analysis of 3-ketoacyl-ACP synthases in the immature seeds of Perilla frutescens.

We report the isolation and expression analysis of two cDNAs encoding 3-ketoacyl-acyl carrier protein synthases (KAS) that are involved in the de novo synthesis of fatty acids in plastids of perilla (Perilla frutescens L.). The cDNAs, designated PfFAB1 and PfFAB24, encoded polypeptides with high sequence identities to those of KAS I and KAS II/IV, respectively, of various plants. Genomic Southern blots revealed that there was a single PfFAB1 gene but two PfFAB24 genes in the perilla genome. Of interest is that the expression of both genes was developmentally regulated in seeds. Their mRNA expression patterns in seeds were also discussed in comparison with the profile of fatty acid accumulation.

Infantile head injury, with special reference to the development of chronic subdural hematoma.

An infantile head injury has unique features in that infants are totally helpless and dependent on their parents, and biomechanical characteristics of the skull and brain are very different from those of other age groups. The authors reviewed a total of 16 infant head injury patients under 12 months of age who were treated in our hospital from 1989 to 1997. Birth head injury was excluded. The most common age group was 3-5 months. Early seizures were noted in 7 cases, and motor weakness in 6. Three patients with acute intracranial hematoma and another 3 with depressed skull fracture were operated on soon after admission. Chronic subdural hematomas (SDHs) developed in 3 infants. Initial CT scans showed a small amount of SDH that needed no emergency operation. Resolution of the acute SDH and development of subdural hygroma appeared on follow-up CT scans within 2 weeks of injury. Two of these infants developed early seizures. Chronic SDH was diagnosed on the 68th and 111th days after the injuries were sustained, respectively. The third patient was the subject of close follow-up with special attention to the evolution of chronic SDH in view of our experience in the previous 2 cases, and was found to have developed chronic SDH on the 90th day after injury. All chronic SDH patients were successively treated by subduro-peritoneal shunting. In conclusion, the evolution of chronic SDH from acute SDH is relatively common following infantile head injury. Infants with head injuries, especially if they are associated with acute SDH and early development of subdural hygroma, should be carefully followed up with special attention to the possible development of chronic SDH

Molecular cloning and functional expression of Perilla frutescens 3-ketoacyl-(acyl carrier protein) synthase III.

The 3-ketoacyl-acyl carrier protein synthase III (KAS III) is a condensing enzyme catalyzing the initial step of fatty acid biosynthesis. We isolated two KAS III cDNA isoforms (PfKAS3a and PfKAS3b) from a cDNA library specific to Perilla frutescens immature seeds. Two cDNAs coded for 401 and 400 amino acids, respectively, which showed high degree of sequence similarity to corresponding enzymes from various sources. Results of Southern hybridization indicated that the PfKAS3a gene is present as two copies, whereas the PJKAS3b gene is a single copy. While both genes were equally expressed in high levels during early stages of seed maturation in a development-specific manner, the PfKAS3b transcript showed more prolonged appearance. Expression of the functional recombinant perilla KAS III increased the myristate level in E. coli but it exerted no appreciable effect on cell growth.

Soft drugs. 12. Design, synthesis, and evaluation of soft bufuralol analogues.

In the search for more potent but still short-acting beta-blockers (BB), the methyl, ethyl, isopropyl, tert-butyl, cyclohexyl, 2-(1-adamantyl)ethyl, and methylthiomethyl esters of the acidic inactive metabolite of bufuralol were synthesized based on the "inactive metabolite" approach. The cleavage of the ester bond by blood and tissue esterases rapidly deactivates these compounds, resulting in an ultrashort duration of action. The beta-antagonist potencies and time courses of actions of the new "soft" BBs were characterized by recording ECG and intra-arterial blood pressure (BP) in rats. In the isoproterenol-induced tachycardia model, while bufuralol at an iv dose of 1 mg/kg (3.8 micromol/kg) diminished heart rate (HR) for at least 2 h, the effects of the soft drugs lasted for only 10-30 min at equimolar dose. The inactive metabolite did not decrease HR significantly. The first four members of this series of compounds showed the highest beta-blocking potencies, ranging between 25% and 50% of that of bufuralol. Next, the effects of these most active compounds on resting HR and BP were evaluated in comparison to esmolol. Infused for 10 min at a rate of 20 micromol/kg/min, esmolol decreased HR and mean arterial pressure (MAP) by 40% and 60%, respectively. The soft drugs at doses ranging only between 2 and 4 micromol/kg/min resulted in a 20-40% decrease in HR and a 30-50% reduction in MAP. However, the time courses of both the bradycardic and hypotensive effects of the soft drugs were superimposable to that of esmolol, diminishing within 60 min after the discontinuation of the infusions.

Secondary structural and phylogenetic implications of nuclear large subunit ribosomal RNA in the ectomycorrhizal fungus Tricholoma matsutake.

The sequence of large subunit (LSU) and 5.8S rRNA genes has been determined for Tricholoma matsutake. A secondary structure model was predicted for both LSU and 5.8S rRNAs, showing most of the structural features consistent with those of the consensus secondary structure model proposed for the eukaryotic cytoplasmic LSU rRNAs. With a reconstructed eukaryotic phylogeny based on full-length LSU rDNA sequences, T. matsutake was placed on the same branch with Cryptococcus neoformans as its closest neighbor. We proposed that T. matsutake be considered as one of the representative members of the division Basidiomycota. Here we report for the first time the complete LSU rRNA gene sequence in T. matsutake, a member of Homobasidiomycetes.

Syntheses and cytotoxicities of four stereoisomers of muricatacin from D-glucose.

Four stereoisomers of muricatacin 1a-d were prepared by the reaction of corresponding aldehydes 4a-d, which in turn were prepared from D-glucose, with the anion of triethylphosphonoacetate followed by reduction and cyclization under acidic conditions. Cytotoxicities of four stereoisomers were tested against in vitro A-549 cell line as well as MCF-7 cell line. Stereochemistry at C4 and C5 position of muricatacin did not affect the cytotoxicities significantly.

Small-subunit ribosomal DNA of an ectomycorrhizal fungus tricholoma matsutake: sequence, structure and phylogenetic analysis.

A 2861 bp nucleotide sequence containing Tricholoma matsutake SSU rRNA gene and its flanking regions was determined and analyzed. Comparison with known SSU rDNA sequences and primer extension analysis revealed that the SSU rRNA coding region and intergenic spacer 2 (IGS2) are 1805 bp and 1043 bp in length, respectively. The IGS2 has an imperfect direct repeat (type 1) homologous to the region downstream to the 5S rRNA gene and the three imperfect tandem direct repeats (type 2) upstream to the SSU rRNA-encoding sequence. Structural analysis by a comparative method showed that the overall secondary structure of the SSU rRNA is generally similar to that of S. cerevisiae, whereas the secondary structures of the V4 regions predicted by the thermodynamics-based method showed different configurations between distantly related taxa, implying that these structural differences can provide phylogenetically informative features. Phylogenetic trees based on both the aligned SSU rRNA sequences with almost full-length sequences and V4 sequences revealed that T. matsutake is very closely related to other basidiomycetes belonging to Agaricales. Thus we propose that the V4 region is also a good source for the inference of phylogeny to support the SSU rRNA phylogeny.

Prolonged ethanol intake increases D2 dopamine receptor expression in the rat brain.

Dopamine via interaction with its receptor is known to be involved in the behavioral and endocrine actions in the mammalian brain. Behavioral effects produced by ethanol appear to be due to its actions on the dopaminergic system. In the present study using in situ hybridization histochemistry and RNase protection assay, the effect of prolonged ethanol intake on the expression of D2 dopamine receptor mRNA was examined in the rat brain. Specific D1 and D2 receptor mRNA signals were detected in the caudate putamen, nucleus accumbens, olfactory tubercle, hippocampus, dentate gyrus, and amygdaloid complex of the rat brain. Within the hypothalamus, the level of receptor mRNA was low in most nuclei with a somewhat higher level in the arcuate nucleus. Only the supurachiasmatic nucleus showed moderate to dense dopamine receptor mRNAs. Prefrontal cortex showed hybridization signals but their intensity was very low. A considerable amount of D2 mRNA was localized in the substantia nigra but D1 mRNA was not. Ethanol (10%) intake for 5 weeks increased both the density of hybridization signal and number of cells expressing D2 dopamine receptor mRNA in the caudate putamen, and nucleus accumbens, but not in the olfactory tubercle. RNase protection assay revealed about a 1.5-fold increase in the D2 dopamine receptor mRNA level in the corpus striatum. These results provide a basis for the involvement of dopamine D2 receptor expression in alcoholism.

Cementless total hip arthroplasty with AML, PCA and HGP prostheses.

Two hundred and fourteen patients who had 270 cementless hip prostheses were followed for 2 to 8 years. PCA (Porous-Coated Monatomic), AML (Monatomic Medullary Locking) and HGP (Harris-Galante-Porous) femoral stems and acetabular cups were used without any preference for the prostheses. The overall clinical results were similar for the three prostheses with average Harris hip scores of 93, 93 and 91 respectively. Four PCA prostheses had radiological aseptic loosening and one was revised because of polyethylene wear. There was no loosening in the AML and HGP prostheses. Pain in the thigh, usually slight, occurred in 17% of AML, 21% of PCA and 19% of HGP prostheses. Five years after operation, radiological changes such as migration, calcar remodelling and radiolucent lines were the same for the 3 prostheses, but bony ingrowth was greater with the AML femoral stems.