Positive end-expiratory pressure aggravates left ventricular diastolic relaxation further in patients with pre-existing relaxation abnormality.

BACKGROUND: Positive end-expiratory pressure (PEEP) has been known to adversely influence cardiac output. Even though left ventricular (LV) diastolic function significantly contributes to LV performance, the effects of PEEP on LV diastolic function remains controversial. We, therefore, aimed to examine the effects of PEEP on LV diastolic function by use of pulsed wave Doppler tissue imaging in patients with pre-existing LV relaxation abnormality. METHODS: Seventeen patients with peak early diastolic velocity of lateral mitral annulus (E') <8.5 cm s(-1) among patients who underwent coronary artery bypass graft surgery were evaluated. Echocardiographic and haemodynamic variables were measured with 0, 5, and 10 cmH2O of PEEP. E' and deceleration time (DT) of peak early transmitral filling velocity (E) were used as echocardiographic indicators of LV diastolic function. RESULTS: Mean arterial blood pressure decreased during 10 cmH2O PEEP, compared with that during 0 cmH2O PEEP. E' showed a gradual and significant decrease with an incremental increase in PEEP (6.9 ± 0.9, 5.8 ± 0.9, and 5.2 ± 1.2 cm s(-1) during 0, 5, and 10 cmH2O PEEP, respectively), and DT of E was prolonged during 10 cmH2O PEEP, compared with that during 0 cmH2O PEEP. CONCLUSIONS: Increasing PEEP led to a progressive decline in LV relaxation in patients with pre-existing LV relaxation abnormality.

Impact of intravenous lidocaine on myocardial injury after off-pump coronary artery surgery.

BACKGROUND: Lidocaine has been demonstrated to exert cardioprotective effects against myocardial ischaemia and reperfusion injury. We evaluated whether a continuous i.v. infusion of lidocaine reduced myocardial injury in patients undergoing off-pump coronary artery bypass graft surgery (OPCAB). METHODS: In this randomized, double-blinded trial, 99 patients received i.v. lidocaine 2% (i.e. a 1.5 mg kg(-1) bolus at induction of anaesthesia followed by a 2.0 mg kg(-1) h(-1) infusion intraoperatively) or an equal volume of saline. Serum creatine kinase-myocardial band (CK-MB) and troponin I (TnI) concentrations were measured before surgery, upon arrival in the intensive care unit, and at 6, 24, 48, and 72 h after surgery. Cardiac enzymes, other biological markers, and rate of postoperative adverse events were compared between the groups. RESULTS: The median (25-75% inter-quartile range) TnI [0.90 (0.43-1.81) vs 1.71 (0.88-3.02) ng ml(-1), P=0.027] and CK-MB [6.5 (3.9-12.3) vs 9.8 (6.0-18.6) ng ml(-1), P=0.005] concentrations 24 h after surgery were significantly lower in the lidocaine group than in the control group. Moreover, lidocaine infusion reduced the total area under the curve of TnI and CK-MB release after surgery by 42% and 27%, respectively, compared with control. CONCLUSIONS: Continuous i.v. infusion of lidocaine during surgery reduces myocardial injury in patients undergoing OPCAB.

Prophylactic control of post-operative nausea and vomiting using ondansetron and ramosetron after cardiac surgery.

BACKGROUND: The aim of this study was to evaluate the efficacy of ondansetron and ramosetron in the reduction of post-operative nausea and vomiting (PONV) associated with patient-controlled analgesia (PCA) after cardiac surgery. METHODS: A total of 320 patients scheduled for elective cardiac surgery were enrolled. Patients were randomly assigned to one of four treatment regimens (n=80 in each group): no prophylactic antiemetics (group P); intravenous (i.v.) ondansetron 4 mg at the end of surgery and 12 mg added to PCA (group O); i.v. ramosetron 0.3 mg at the end of surgery and no antiemetics added to PCA (group R1); and i.v. ramosetron 0.3 mg at the end of surgery and 0.6 mg added to PCA (group R2). RESULTS: The incidence of PONV during the 48-h post-operative period was lower in groups O (46%), R1 (54%), and R2 (35%) compared with group P (71%, P<0.001). The incidence and severity of nausea were lower in groups O, R1, and R2 than in group P during the 24-h post-operative period, whereas the incidence and severity of nausea during 24-48 h after surgery were lower in groups O and R2, but not in group R1, than in group P. Compared with group P (53%), the frequency of rescue antiemetic usage was significantly lower in groups O (34%) and R2 (29%), but not in group R1 (43%). CONCLUSION: The addition of either ondansetron or ramosetron to PCA can reduce the incidence of PONV during 48 h after cardiac surgery.

Arctic terrestrial biota: paleomagnetic evidence of age disparity with mid-northern latitudes during the late cretaceous and early tertiary.

Magnetostratigraphic correlation of the Eureka Sound Formation in the Canadian high Arctic reveals profound difference between the time of appearance of fossil land plants and vertebrates in the Arctic and in mid-northern latitudes. Latest Cretaceous plant fossils in the Arctic predate mid-latitude occurrences by as much as 18 million years, while typical Eocene vertebrate fossils appear some 2 to 4 million years early.

Cutaneous lymphangiectasia associated with photoageing and topical corticosteroid application.

We report the case of a 69-year-old man with a history of multiple erythematous bullae on both forearms, which had been present for about 1 month. The lesions appeared after several years of topical corticosteroid application and photoageing. A biopsy revealed lymphangiectasia with solar elastosis and increase in the ratio of elastic to collagen fibres in the dermis. We suggest that this patient's lymphangiectasia resulted from abnormal structure and function of the dermis due to photoageing and steroid-related atrophy.

Clinical and economic analyses of antimicrobial therapy in fever wards of a Hong Kong teaching hospital.

OBJECTIVE: The aims of this study were to evaluate the use of antimicrobial agents in the fever wards of a Hong Kong teaching hospital and to identify those factors associated with treatment failure and having an influence on the total direct medical costs of antimicrobial therapy. METHODS: This was a retrospective observational study. Demographic and clinical data were collected on 123 patients admitted to the fever wards in a local teaching hospital between July 2004 and August 2004. Multivariate analyses were performed to identify factors associated with treatment failure and the total direct medical treatment cost. RESULTS: The rate of treatment failure was 30.1% (37 out of 123 patients). The mean total direct medical cost was HK$ 26,442 +/- 17,153 (US$ 1 = HK$ 7.8). The empirical therapy in 90 (73.2%) patients complied with the institutional guidelines. 25 (20.3%) patients were eligible for renal dosage adjustment and in 7 (28%) of these patients the dosage of antimicrobial agents was renally adjusted. Of the 27 patients in whom pathogens were identified, 9 (33.3%) patients were eligible for antimicrobial streamlining (changing to an antibiotic with a narrower spectrum) but streamlining was only done in 2 (22.2%) patients. Multivariate analysis showed that the history of malignant diseases (RR = 5.07; 95% CI = 1.06 - 24.22) and non-compliance with the institutional treatment guidelines for selection of empirical antimicrobial therapy (RR = 3.58; 95% CI = 1.35 - 9.54) were risk factors associated with treatment failure. Duration of intravenous antimicrobial therapy was associated with the total cost of treatment (RR = 1.60; 95% CI = 1.35 - 2.10). CONCLUSION: Non-compliance with treatment guidelines in empirical antimicrobial treatment and the duration of intravenous antimicrobial therapy were modifiable risk factors for treatment failure and total treatment cost, respectively.

A novel gene, DSCR5, from the distal Down syndrome critical region on chromosome 21q22.2.

Based on a detailed sequence of the distal Down syndrome critical region (DSCR), we predicted and molecularly cloned a novel gene, designated DSCR5. We determined the sequences of expressed sequence tags (ESTs) that almost matched the predicted cDNA sequence of DSCR5. Northern blot analysis showed that DSCR5 is expressed in several tissues including the liver, skeletal muscle, heart, pancreas and testis. To determine the 5'-end of DSCR5, the oligo-capping method was employed. Combining the EST sequence data and that from the oligo-capping experiments, we obtained the full-length cDNA sequence of DSCR5. DSCR5 had at least four types of alternatively spliced variants. According to the number of exons, they could be classified into two subtypes: DSCR5alpha and DSCR5beta. DSCR5alpha includes three splice variant subtypes, DSCR5alpha1, alpha2 and alpha3, which each has different first non-coding exon. In addition, the most abundantly isolated form, DSCR5alpha1, shows microheterogeneity of the mRNA start site. Comparison of the sequences between the predicted cDNA and the molecularly cloned cDNA revealed that the computer programs had limited validity to correctly predict the terminal exons. Thus, molecular cloning should always be required to complement the inadequacy of the computer predictions.

Developmentally-regulated expression of mNapor encoding an apoptosis-induced ELAV-type RNA binding protein.

Proteins with RNA recognition motifs (RRMs) participate in many aspects of RNA metabolism, and some of them are required for the accomplishment of normal development. The neuroblastoma apoptosis-related RNA binding protein (NAPOR) is an ELAV-type RNA-binding protein with three characteristic RNP2/RNP1-type RRMs, which we identified as a gene induced during apoptosis of neuroblastoma cells. Here we isolated and characterized the cDNA for mNapor, the mouse homolog of NAPOR. The mNapor encodes mRNA sharing striking homology with that of NAPOR, not only in its open reading frame (98.5%) but also in the 3'-untranslated region (80.1%), and is mapped to chromosome 2 A2-A3, a region syntenic to the human NAPOR locus. In situ hybridization analysis revealed that the expression pattern of mNapor is spatially and temporally coincident with the occurrence of programmed cell death, suggesting its involvement in the development of the central nervous system in which apoptosis plays a crucial role.

Fluorescent differential display analysis of gene expression in apoptotic neuroblastoma cells.

Identification of differentially expressed genes will provide leads in the elucidation of the molecular mechanisms underlying neuronal cell death associated with neurodegenerative disorders. Using a high-throughput fluorescent differential display (FDD) system based on an automated DNA sequencer, we analyzed global patterns of gene expression during the apoptosis of neuroblastoma SH-SY5Y cells induced by a neurotoxin, colchicine. Initial screening of approximately 24000 cDNA bands displayed with 320 primer combinations has revealed 263 fragments showing differential expression patterns, suggesting that approximately 1% of transcripts are modulated in their expression level. Of these differentially displayed bands, we cloned 18 fragments composed of 17 distinct species and confirmed differential expression of each species by reverse transcription-PCR or Northern blot hybridization, thereby proving the reliability of the approach. These include eight derived from seven known genes, five homologous to expressed sequence tags (ESTs), and five totally lacking any homology to those deposited in the database. Among these, a novel transcript SAI1 induced prominently was characterized further and revealed to encode a putative RNA-binding protein NAPOR (neuroblastoma apoptosis-related RNA-binding protein), containing three copies of evolutionarily conserved RNA recognition motif. Since several RNA-binding proteins have been known to play crucial roles in other apoptosis systems, it is conceivable that NAPOR is also involved in the process of neuronal cell death.

COX-2 and neurodegeneration in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Recent observations link cyclooxygenase type-2 (COX-2) to the progression of the disease. Consistent with this notion, studies with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) show that inhibition and ablation of COX-2 markedly reduce the deleterious effects of this toxin on the nigrostriatal pathway. The similarity between this experimental model and PD strongly supports the possibility that COX-2 expression is also pathogenic in PD.

Discovery of a novel compound: insight into mechanisms for acrylamide-induced axonopathy and colchicine-induced apoptotic neuronal cell death.

The exposure of humans and experimental animals to certain industrial toxins such as acrylamide is known to cause nerve damage classified as axonopathy, but the mechanisms involved are poorly understood. Here we show that acrylamide induces morphological changes and tyrosine phosphorylation of focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2), a member of the FAK subfamily, in human differentiating neuroblastoma SH-SY5Y cells. Furthermore, we identified a novel molecule designated 'compound-1' that inhibits the morphological and biochemical events. Daily oral administrations of the compound also effectively alleviated behavioral deficits in animals elicited by acrylamide in inclined plane testing, landing foot spread testing and rota-rod performance testing. The compound also effectively inhibited the biological and biochemical responses caused by another axonopathy inducer, colchicine, including tyrosine phosphorylation of Pyk2, formation of an 85-kDa poly(ADP-ribose)polymerase (PARP) fragment and apoptosis-associated induction of the NAPOR gene as well as neuronal cell death. Our findings not only provide insight into FAK and Pyk2 functions in neuronal cells, but may also be important in the development of therapeutic agents for peripheral neuropathy and neurodegeneration.

A negative regulatory factor for the dark repression of Arabidopsis thaliana cab1 gene.

A protein factor and its binding site involved in light-responsive gene expression of Arabidopsis thaliana cab1 were investigated. Mobility shift assays were performed to identify a nuclear protein factor and its binding sites on the cab1 promoter. For the binding assay, the Arabidopsis cab1 promoter was cleaved with endonucleases into small fragments (65-200 bp) and end-labeled with Klenow fragments. Nuclei were prepared from the light-grown plants and nuclear proteins were prepared by extracting the purified nuclei with 0.5 M ammonium sulfate. The binding site of the nuclear protein factor was scattered throughout the whole promoter region from the transcription start site to the far upstream region of the promoter. To identify the binding sites that are involved in the light responsiveness, mobility shift assays were performed between the cab1 promoter fragments and the nuclear extracts prepared from the 2 day dark-adapted sample. The mobility shift assay of the 65 bp (-318/ -254) fragment with nuclear extract from the dark-adapted sample showed an additional band, not seen with the light-grown sample. Because the new band was present only in the dark-adapted sample that repressed cab1 expression, it may represent a negative regulatory factor (NRF). The NRF was separable on a heparin-Sepharose column from the other factor present in both the light-grown and dark-adapted samples. The implications of the presence of the NRF have been discussed with respect to gene products of the photosignal transduction Arabidopsis mutants.

Only the chemical state of Indium changes in Mn-doped In3Sb1Te2 (Mn: 10 at.%) during multi-level resistance changes.

We fabricated and characterized the material with Mn (10 at.%: atomic percent) doped In3Sb1Te2 (MIST) using co-sputtering and synchrotron radiation, respectively. The MIST thin film showed phase-changes at 97 and 320 °C, with sheet resistances of ~10 kΩ(sq) (amorphous), ~0.2 kΩ(sq) (first phase-change), and ~10 Ω(sq) (second phase-change). MIST did not exhibit any chemical separation or increased structural instability during either phase-change, as determined with high-resolution x-ray photoelectron spectroscopy. Chemical state changes were only depended for In without concomitant changes of Sb and Te. Apparently, doped Mn atoms can be induced with movement of only In atoms.

A modification of the trans-oesophageal echocardiography protocol can reduce post-operative dysphagia following cardiac surgery.

Use of intra-operative trans-oesophageal echocardiography (TEE) is an independent risk factor for post-operative dysphagia. This study investigated whether modifying the TEE probe-placement protocol could reduce the incidence of post-operative dysphagia. In group I (n = 100), the TEE probe was inserted after anaesthetic induction and remained in place until the completion of surgery. In group II (n = 100), the TEE probe was inserted after anaesthetic induction, the heart was examined, then the probe was removed. The probe was inserted again before weaning from cardiopulmonary bypass and then immediately removed after examination. The incidence of dysphagia was significantly higher in group I than in group II patients (51.1% versus 28.6%). Multivariate regression analysis showed that the length of time that the TEE probe was in the oesophagus was an independent predictor of dysphagia. Modification of the TEE protocol in this way can reduce the incidence of post-operative dysphagia in cardiac surgery patients.

Aggravation of mitral regurgitation by calcium administration in a patient with hypertrophic cardiomyopathy during liver transplantation: a case report.

Aggravation of mitral regurgitation (MR) due to left ventricular outflow tract obstruction (LVOTO) is likely to occur during liver transplantation in cirrhotic patients with hypertrophic cardiomyopathy (HCMP). Moreover, calcium administration following severe hypocalcemia due to inadequate citrate metabolism and massive transfusion may induce MR aggravation with LVOTO in such patients. Herein we have described a cirrhotic patient with HCMP in whom MR was aggravated due to LVOTO resulting from inadvertent rapid administration of calcium during liver transplantation.

Expression profiling of radiation-induced genes in radiodermatitis of hairless mice.

BACKGROUND: Radiation induces many cellular events leading to radiodermatitis. OBJECTIVES: The aim of this study was to establish a radiodermatitis model using experimental animals, and to examine the expression profile of radiation-induced genes. METHODS: Hairless mice were irradiated on the dorsal skin; then total RNAs were isolated and microarray hybridizations were performed. RESULTS: Irradiation with a total of 40 Gy (10 Gy day-1 for four consecutive days) provokes radiodermatitis in the hairless mouse. After microarray analysis, 130 genes that showed upregulation by radiation were selected and organized into four different clusters, depending on the time-kinetic pattern. Classification of these genes into several functional categories revealed that various biological processes were globally affected by radiation. These include transcription regulation, signal transduction, cell communication, cell death regulation and metabolism. CONCLUSIONS: These results demonstrate the complexity of the transcriptional profile of the radiation response, providing important clues on which to base further investigations of the molecular events underlying radiodermatitis.

A modified Coomassie blue staining of proteins in polyacrylamide gels with Bismark brown R.

A rapid and sensitive protein staining method employing a mixed dye technique has been developed. Solutions of Coomassie brilliant blue R-250 (CB, 0.2%) and Bismark brown R (BBR, 0.05%) were mixed in the volume ratio of 1:0.75 for staining (final molar ratio, 4.5:1). In this staining, BBR inhibits the binding of CB to gel matrix by forming ion-pairing complex with excess CB; therefore, it reduces staining/destaining times and also enhances the staining effect of CB on protein band. As a result, the mixed dye staining enables complete staining/destaining within 20/25 min and detection of up to 25 ng of bovine serum albumin.

Characterization of murine monoclonal antibodies against serogroup B salmonellae and application as serotyping reagents.

Six murine hybridoma monoclonal antibodies reactive with lipopolysaccharide antigens of Salmonella typhimurium were obtained from a fusion of immune spleen cells from mice immunized with S. typhimurium and NS1 myeloma cells. Four antibodies appeared to be specific for serogroup B salmonellae, while the remaining two antibodies were found to be cross-reactive with Salmonella paratyphi A. The exquisite specificities of the Salmonella serogroup B monoclonal antibodies were demonstrated by their unique reactivities with different serotypes of group B salmonellae but with neither other O serogroups of salmonellae nor a wide spectrum of standard strains of other bacterial species. Serotyping of salmonella strains by the slide agglutination method with two of the serogroup B-specific monoclonal antibodies demonstrated their usefulness as serotyping reagents for the identification of serogroup B salmonellae in a routine diagnostic bacteriology laboratory.