Predicting outcomes in older patients undergoing vascular surgery using the Hospital Frailty Risk Score.

BACKGROUND: Frailty may explain why some older patients having vascular surgery are at high risk of adverse outcomes. The Hospital Frailty Risk Score (HFRS) has been designed specifically for use with administrative data and has three categories of frailty risk (low, intermediate and high). The aim of this study was to evaluate the HFRS in predicting mortality, and hospital use in older patients undergoing vascular surgery. METHODS: Routinely collected hospital data linked to death records were analysed for all patients aged 75 years or older who had undergone either endovascular or open vascular surgery between 2010 and 2012 in New South Wales, Australia. Multilevel logistic regression models were used to compare outcomes adjusted for patient and procedural factors, with and without frailty. RESULTS: Some 9752 patients were identified, of whom 1719 (17·6 per cent) had a high-risk HFRS. Patients in the high-risk frailty category had an adjusted odds ratio for death by 30 days after surgery of 4·15 (95 per cent c.i. 2·99 to 5·76) compared with those in the low-risk frailty category, and a similarly increased odds of death by 2 years (odds ratio 4·27, 3·69 to 4·95). Adding the HFRS to a model adjusted for age, sex, co-morbidity score, socioeconomic status, previous hospitalization and vascular procedure type improved the prediction of 2-year mortality and prolonged hospital stay, but there was minimal improvement for 30-day mortality and readmission. CONCLUSION: Adjusting for the HFRS in addition to other patient and procedural risk factors provided greater discrimination of outcomes in this cohort of older patients undergoing vascular surgery.

Educational effects using a robot patient simulation system for development of clinical attitude.

INTRODUCTION: The aim of this study was to assess the effectiveness of improving the attitude of dental students towards the use of a full-body patient simulation system (SIMROID) compared to the traditional mannequin (CLINSIM) for dental clinical education. MATERIALS AND METHODS: The participants were 10 male undergraduate dental students who had finished clinical training in the university hospital 1 year before this study started. They performed a crown preparation on an upper pre-molar tooth using SIMROID and CLINSIM as the practical clinical trials. The elapsed time for preparation was recorded. The taper of the abutment teeth was measured using a 3-dimensional shape-measuring device after this trial. In addition, a self-reported questionnaire was collected that included physical pain, treatment safety and maintaining a clean area for each simulator. Qualitative data analysis of a free format report about SIMROID was performed using text mining analysis. This trial was performed twice at 1-month intervals. RESULTS: The students considered physical pain, treatment safety and a clean area for SIMROID significantly better than that for CLINSIM (P < .01). The elapsed time of preparation in the second practical clinical trial was significantly lower than in the first for SIMROID and CLINSIM (P < .01). However, there were no significant differences between the abutment tapers for both systems. For the text mining analysis, most of the students wrote that SIMROID was similar to real patients. CONCLUSION: The use of SIMROID was proven to be effective in improving the attitude of students towards patients, thereby giving importance to considerations for actual patients during dental treatment.

Surgical strategies for hepatocellular carcinoma with special reference to anatomical hepatic resection and intraoperative contrast-enhanced ultrasonography.

Here we described our strategies to attain a better prognosis for hepatocellular carcinoma (HCC) patients by surgery. Among a variety of attempts conducted to date, we focused on anatomical resection and intraoperative contrast-enhanced ultrasonography. There are still controversies with respect to the significance of anatomical resection. We analyzed the significance of this surgical procedure in 207 patients without macrovascular invasion. These patients underwent either anatomical resection or non-anatomical resection. We found that the patients with anatomical resection had higher recurrence-free survival rate than those with non-anatomical resection. Univariable analysis showed that liver damage, the serum level of alpha-fetoprotein, tumor number, surgical margin, and type of surgery (anatomical or non-anatomical resection) were significant predictive factors for intrahepatic recurrence. Multivariable analysis revealed that multiple tumors, alpha-fetoprotein, and non-anatomical resection were independent risk factors for recurrence. We conclude that anatomical resection is a recommendable surgical procedure in patients without macrovascular invasion. A recent innovation is the development of contrast-enhanced ultrasonography. Then we have applied this to liver surgery intraoperatively. We confirm that vascular images contribute to a precise diagnosis and the detection of small portal tumor thrombi, and that Kupffer images are useful to discover the minute tumors. In addition, by clarifying the relationship between tumors and the vascular architecture, real-time 3-dimensional images using Kupffer imaging are a promising guide during the surgical procedures, although further development is needed.

Dissemination of Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus USA300 clone in multiple hospitals in Tokyo, Japan.

OBJECTIVES: Panton-Valentine leukocidin (PVL) gene (lukS/F-PV)-positive community-acquired methicillin-resistant Staphylococcus aureus (MRSA), particularly the USA300 clone, is a health concern worldwide. Recently, community-acquired MRSA clones have been found to spread and persist in hospital settings. We aimed to investigate the prevalence and molecular epidemiologic features of lukS/F-PV-positive MRSA in Japanese hospitals. METHODS: A total of 3433 MRSA isolated from nine hospitals in 2011-2015 were assessed. Molecular epidemiologic analysis performed by staphylococcal cassette chromosome mec typing, PVL typing, arginine catabolic mobile element typing, detection of virulence determinants, multilocus sequence typing, pulsed-field gel electrophoresis and antimicrobial susceptibility testing. RESULTS: The detection rate of lukS/F-PV was increased annually from 0.6% (5/817) in 2011 to 3.1% (17/544) in 2015. Molecular epidemiologic analysis for 64 lukS/F-PV-positive MRSA isolates revealed that 42 isolates (65.6%) were the USA300 clone. Resistance rates of levofloxacin and gentamicin among lukS/F-PV-positive isolates increased annually as a result of increased prevalence of the multidrug-resistant USA300 clone. CONCLUSIONS: This is the first report on dissemination of the USA300 clone and PVL-positive MRSA in multiple Japanese hospitals. Our data strongly suggest that the USA300 clone may become epidemic in Japanese hospitals.

An orthognathic simulation system integrating teeth, jaw and face data using 3D cephalometry.

A method for simulating the movement of teeth, jaw and face caused by orthognathic surgery is proposed, characterized by the use of 3D cephalometric data for 3D simulation. Computed tomography data are not required. The teeth and facial data are obtained by a laser scanner and the data for the patient's mandible are reconstructed and integrated according to 3D cephalometry using a projection-matching technique. The mandibular form is simulated by transforming a generic model to match the patient's cephalometric data. This system permits analysis of bone movement at each individual part, while also helping in the choice of optimal osteotomy design considering the influences on facial soft-tissue form.

Recurrent multinodular neurilemmoma of the female upper lip.

Neurilemmoma is the most commonly encountered nerve sheath tumour of the oral cavity. It generally appears as a single encapsulated nodule. The tongue is involved most frequently and the lip rarely. The tumour is usually uninodular. Multinodular neurilemmoma of the upper lip is very rare and has been reported in only one patient. This is the first reported case of multinodular neurilemmoma in the upper lip of a female.

A new navigation system based on cephalograms and dental casts for oral and maxillofacial surgery.

Intraoperative navigation systems help surgeons to accurately carry out preoperative plans without injuring anatomically important structures. A system is evaluated that uses cephalograms instead of computed tomographic (CT) scans to create images. Three-dimensional (3D) dental casts provide registration between imaging data and the patient. Cephalograms are widely employed in orthognathic and oral and maxillofacial surgery and expose patients to lower doses of radiation than CT. The system uses a dental cast to register the operation field to a pair of frontal and lateral cephalograms. The cast is transformed to 3D data with a laser scanner and a programme that runs on a personal computer. 3D data describing the dental cast, cephalograms and the oral and maxillofacial region of the patient are integrated with specialized software. The optical tracking system for navigation uses charged-coupled-device (CCD) video cameras and light-emitting diodes (LEDs). Two CCD video cameras follow the 3D coordinates of LED assemblies attached to the head, lower jaw and a handpiece. Errors occurring when a dental cast was transformed to 3D data ranged from 0.08 to 0.21 mm. Mean errors were 0.71 mm (0.21-1.09 mm) for the right maxillary central incisor, 0.62 mm (0.04-1.69 mm) for the right maxillary 2nd molar and 1.02 mm (0.23-1.47 mm) for the left maxillary 2nd molar. This surgical navigation system is sufficiently accurate for use in oral and maxillofacial surgery.

Correlation of enzyme-induced cleavage sites on negatively superhelical DNA between prokaryotic topoisomerase I and S1 nuclease.

Negatively superhelical pNS1 DNA with a molecular weight of 2.55 MDa (4 kbp) was found to contain 13 specific, unbasepaired sites that are sensitive to a single-strand-specific S1 nuclease cleavage. The S1-cleavage occurred once at these sites. In the absence of added Mg2+, the topoisomerase I purified from Haemophilus gallinarum formed a complex with the superhelical pNS1 DNA which has a hidden strand cleavage. Extensive proteinase K digestion of the complex led to cleavage of the DNA chain. Then the proteinase K-cleaved product was digested with S1, which can cut the opposite strand at the preexisting strand cleavage to generate unit-length linear DNA. Restriction endonuclease analysis of the linear DNA shows that the topoisomerase-induced cleavage occurred once at ten specific sites on the DNA. The topoisomerase caused mainly single-strand cleavage at these sites, but infrequently also caused double-strand cleavage at the same sites. Of interest is the fact that these sites considerably coincide with the S1-cleavable, unbasepaired sites.

Effects of ebselen and probucol on oxidative modifications of lipid and protein of low density lipoprotein induced by free radicals.

The oxidative modification of low density lipoprotein (LDL) is accepted to be an important early event of atherosclerosis, but it has not yet been well understood. The preventive effects of two antioxidants with different functions, ebselen and probucol, against the oxidative modification of LDL induced by copper or a water-soluble radical initiator, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) were studied in order to elucidate the mechanism of modification of apolipoprotein B-100 (apoB). Ebselen inhibited the copper-induced oxidation completely by reducing the hydroperoxides in LDL, since the initiation of copper-dependent oxidation requires the presence of a trace amount of hydroperoxides in LDL. On the other hand, ebselen did not suppress the oxidations of LDL induced by AAPH which generated free radicals by its thermal decomposition. The AAPH-induced oxidation of LDL in the absence of ebselen gave phosphatidylcholine hydroperoxide and cholesteryl ester hydroperoxide as major products, while in its presence, the hydroperoxides were reduced to corresponding alcohols. Interestingly, ebselen had little effect on the increase of relative electrophoretic mobility and fragmentation of intact apoB in the AAPH-induced oxidation. Probucol inhibited the oxidation of lipids in LDL effectively induced by either copper or AAPH, but the protein modifications were observed even in the presence of probucol. It was suggested that (1) lipid hydroperoxides do not play an important role in the modification of apoB such as increase in negative charge and fragmentation, (2) the direct attack of free radicals upon apoB and its modification by lipid oxidation products derived from hydroperoxides increase the negative charge of apoB, and (3) its fragmentation is caused primarily by an attack of free radicals.

Dynamics of the oxidation of low density lipoprotein induced by free radicals.

Although the oxidation of low density lipoprotein (LDL) has been studied extensively, its dynamics have received much less attention. The present study was carried out aiming to elucidate the rates and products of the oxidation of LDL induced by free radicals generated in three different ways by hydrophilic and lipophilic azo radical initiators and copper. The oxidations were followed by measuring the formation of lipid oxidation products, the uptake of oxygen, consumption of vitamin E, and the fragmentation and acquisition of negative charge by apolipoprotein B within a single oxidation reaction. LDL was oxidized by a free radical chain mechanism independent of the manner of initiating free radical generation to give phosphatidylcholine hydroperoxide (PCOOH) and cholesteryl ester hydroperoxide (CEOOH) as major primary products. When the radicals were generated within the LDL compartment, CEOOH was formed almost exclusively and quantitatively at the initial stage. The kinetic chain length for the oxidation of cholesteryl ester was larger than that for phosphatidylcholine in the presence and absence of vitamin E even when the radicals were generated initially in the aqueous phase. PCOOH and CEOOH accumulated with increasing extent of oxidation, but then decreased at the later stage of oxidation. The decrease in hydroperoxides was more significant in copper-induced oxidations. The thiobarbituric acid reactive substances also increased with time, but they accounted for less than 10% of total oxygen uptake. Oxidative modification of apo B was also observed. The modification of apo B, that is, fragmentation and increase in negative charge correlated well with the oxidation of lipids independent of the manner of chain initiation. It was also suggested that some radicals formed in the aqueous phase attacked apo B directly. These results suggest the importance of chain propagation in the oxidative modification of LDL and also the lipophilic, chain-breaking antioxidants within LDL in its inhibition.

Antioxidant activities of probucol against lipid peroxidations.

The antioxidant activities of probucol were measured in the oxidations of methyl linoleate in homogeneous solution and soybean phosphatidylcholine liposomal membranes and also of low-density lipoproteins. When an excess amount of probucol was reacted with galvinoxyl, the EPR spectrum of galvinoxyl disappeared and a new triplet EPR signal was found: g = 2.0058 and aH(2H) = 0.14 mT. The identical EPR spectrum was observed when probucol was reacted with tert-butoxyl radical generated from di-tert-butylperoxy oxalate. This EPR signal disappeared rapidly when reacted with either alpha-tocopherol or 6-O-palmitoyl-ascorbic acid. Probucol suppressed the free-radical-mediated oxidations of methyl linoleate in hexane and in acetonitrile, in a dose-dependent manner. Its antioxidant activity was 17.5-fold less than that of alpha-tocopherol in hexane. Probucol incorporated into soybean phosphatidylcholine liposomes suppressed its oxidation. The antioxidant activity of probucol was less than that of alpha-tocopherol, but the difference between the two antioxidant activities was smaller in the membranes than in homogeneous solution. Probucol also suppressed the oxidation of low-density lipoprotein. Interestingly, probucol suppressed the oxidation of LDL as efficiently as alpha-tocopherol, implying that physical factors as well as chemical reactivity are important in determining the overall activity of antioxidant in low-density lipoprotein.

Altered stoichiometry of FKBP12.6 versus ryanodine receptor as a cause of abnormal Ca(2+) leak through ryanodine receptor in heart failure.

BACKGROUND: In the pathogenesis of cardiac dysfunction in heart failure, a decrease in the activity of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase is believed to be a major determinant. Here, we report a novel mechanism of cardiac dysfunction revealed by assessing the functional interaction of FK506-binding protein (FKBP12.6) with the cardiac ryanodine receptor (RyR) in a canine model of pacing-induced heart failure. METHODS AND RESULTS: SR vesicles were isolated from left ventricular muscles (normal and heart failure). The stoichiometry of FKBP12.6 per RyR was significantly decreased in failing SR, as assessed by the ratio of the B(max) values for [(3)H]dihydro-FK506 to those for [(3)H]ryanodine binding. In normal SR, the molar ratio was 3.6 ( approximately 1 FKBP12.6 for each RyR monomer), whereas it was 1.6 in failing SR. In normal SR, FK506 caused a dose-dependent Ca(2+) leak that showed a close parallelism with the conformational change in RyR. In failing SR, a prominent Ca(2+) leak was observed even in the absence of FK506, and FK506 produced little or no further increase in Ca(2+) leak and only a slight conformational change in RyR. The level of protein expression of FKBP12.6 was indeed found to be significantly decreased in failing SR. CONCLUSIONS: An abnormal Ca(2+) leak through the RyR is present in heart failure, and this leak is presumably caused by a partial loss of RyR-bound FKBP12.6 and the resultant conformational change in RyR. This abnormal Ca(2+) leak might possibly cause Ca(2+) overload and consequent diastolic dysfunction, as well as systolic dysfunction.

Susceptibilities to clarithromycin, amoxycillin and metronidazole of Helicobacter pylori isolates from the antrum and corpus in Tokyo, Japan, 1995-2001.

The aim of this study was to determine the susceptibilities to clarithromycin, amoxycillin and metronidazole of Helicobacter pylori isolates from the antrum and corpus of Japanese patients examined during the period 1995-2001. There was an increase, from 6.2% in 1995 to 22.1% in 2000-2001, in the proportion of patients infected with clarithromycin-resistant H. pylori. Of patients infected with clarithromycin-resistant H. pylori, 39.1% were infected with both clarithromycin-susceptible and -resistant H. pylori. Furthermore, the MIC90 of clarithromycin for H. pylori rose from < 1 mg/L in 1995-1998 to 8 mg/L in 1999. In contrast, the MIC90s of amoxycillin and metronidazole were < or = 0.125 and 4 mg/L, respectively, throughout the study period. The results showed that, while most H. pylori isolates were susceptible to amoxycillin and metronidazole, resistance to clarithromycin among H. pylori isolates increased markedly in Japan during 1995-2001. The results also indicated a need to test the susceptibility of H. pylori isolates from more than two samples obtained from two different sites in the stomach of a single patient in order to diagnose the presence of clarithromycin-resistant H. pylori correctly.

In vivo complex formation of oxidized alpha(1)-antitrypsin and LDL.

An inactivated form of alpha(1)-antitrypsin (AT) and LDL coelutes in gel permeation chromatography. To characterize and to quantify the amount of this fraction of AT, a monoclonal antibody was established against chloramine T-oxidized AT and named OxAT-4. OxAT-4 recognized the oxidatively modified AT, including hexylaldehyde- or 4-hydroxy-2-nonenal-modified AT, but neither normal active AT nor trypsin/AT complex. Comigration of apoB and oxidized AT was demonstrated by Western blotting analysis of AT-LDL by means of anti-apoB monoclonal antibody and OxAT-4. A complex of oxidized AT and LDL (AT-LDL) was isolated from human plasma LDL by affinity column with an OxAT-4 antibody-coated carrier. AT-LDL was degraded 4 times more effectively by mouse peritoneal macrophages, but this was not mediated by scavenger receptor class A type I. Localization of AT-LDL was detected in human atherosclerotic lesions of the coronary artery, but distribution of it was not completely identical to that of macrophages. In situ hybridization revealed AT expression by macrophages, which were present in intimal layers of the coronary artery. From these findings, we concluded that AT is produced and oxidized by macrophages, then attached to LDL in the intimal layer of the arterial wall. Although AT-LDL that escapes into the blood stream can be cleared by hepatocytes, the remaining AT-LDL may be taken up by macrophages and contribute to the lipid accumulation in arterial wall cells as the early stage of atherogenesis.

Vitamin E protects against polymorphonuclear leukocyte-dependent adhesion to endothelial cells.

We evaluated the effects of alpha-Toc on surface expression of CD11b/CD18 on polymorphonuclear leukocytes (PMN) stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) and oxidized low-density lipoprotein (oxLDL). Incubation of PMN with fMLP (1 microM) or oxLDL (100 microg/mL) increased CD11b/CD18 expression; pretreatment with alpha-Toc reduced in a dose-dependent manner. PMN obtained from healthy adults ingesting 600 mg alpha-Toc per day for 10 days were similarly incubated with fMLP or oxLDL; the surface level of CD11b/CD18 was inversely correlated with serum alpha-Toc concentrations. Adherence of PMN to human umbilical vein endothelial cells was increased by fMLP or oxLDL stimulation but reduced by alpha-Toc pretreatment or anti-CD18 monoclonal antibodies. cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) activity in PMN was also assayed. A PKC inhibitor, but not a PKA inhibitor, suppressed CD11b/CD18 up-regulation, and alpha-Toc slightly decreased fMLP- and oxLDL-induced activation of PKC. These results suggest that alpha-Toc may prevent inflammation by both reducing CD11b/ CD18 up-regulation and decreasing PMN-dependent adherence to EC.

Intraoral drainage under surgical microscopy with tonsillectomy for parapharyngeal abscesses.

BACKGROUND: An intraoral approach combined with tonsillectomy has been used to access the parapharyngeal space. However, the utility of this technique for parapharyngeal abscesses in paediatric patients has not been investigated. This paper describes an intraoral drainage technique combined with tonsillectomy for treating children with a parapharyngeal abscess that obviates the need for skin incision. METHODS: Clinical case records are presented, along with a description of the surgical procedure accompanied by a video clip. RESULTS: Both cases encountered involved paediatric parapharyngeal space abscesses that extended to the skull base. The patients underwent an intraoral approach combined with tonsillectomy performed under surgical microscopy; this resulted in a good post-operative course without complications. CONCLUSION: To our knowledge, no previous reports have addressed the use of surgical microscopy to help access the parapharyngeal space. The procedure described herein, performed under surgical microscopy, was specifically helpful in enabling access to these challenging spaces; it also meant that surgical procedures could be recorded clearly and findings shared with other medical staff.

Complete nucleotide sequence of pTZ12, a chloramphenicol-resistance plasmid of Bacillus subtilis.

The complete nucleotide sequence of pTZ12, a chloramphenicol-resistance (CmR) plasmid (2517 bp) derived from Corynebacterium xerosis plasmid pTZ10, has been determined after propagation in Bacillus subtilis. The nucleotide sequence of pTZ12 suggests that a recombination event may have occurred naturally within the open reading frames for the Rep protein of pT181 (or a pT181-like plasmid) and pC221 (or a pC221-like plasmid).

Construction and propagation of deletion derivatives of staphylococcal tetracycline-resistance plasmid pTP-5 in Bacillus subtilis.

Tetracycline-resistance (TCr) plasmid pTP-5 (4.46 kb) from Staphylococcus aureus was cleaved with HindIII into three fragments: A (2.35 kb), B (1.57 kb) and C (0.54 kb). A deletion plasmid (3.92 kb) lacking HindIII-C fragment was obtained, and was designated pNS1. This plasmid retained the TCr phenotype and the ability to replicate autonomously in Bacillus subtilis. A restriction endonuclease cleavage map of pNS1 was constructed. Attempts to construct smaller plasmids by digesting pNS1 with BAL31 nuclease led to production of a set of deletion derivatives whose molecular sizes range from 3.75 to 2.77 kb. Through analyses of these derivatives, the regions essential for autonomous replication and expression of TCr were deduced.

Nucleotide sequence of the chromosomal gene coding for the aminoglycoside 6-adenylyltransferase from Bacillus subtilis Marburg 168.

Gene aadK of Bacillus subtilis is 855 bp long and codes for aminoglycoside 6-adenylyltransferase.