Editor's Choice - Subsequent Results for Arch Aneurysm Repair with Inner Branched Endografts.

OBJECTIVES: The aim was to evaluate the current results of aortic arch aneurysm repair using inner branched endografts performed in three high volume aortic endovascular centers and to compare them to the pioneering global experience with this technology. METHODS: Included patients underwent repair of aortic arch aneurysms >55 mm in diameter using inner branched endograft technology between April 2013 and November 2014. All patients were deemed unfit for open surgery. Inner branches were designed to perfuse the brachiocephalic trunk and the left common carotid artery in all cases. A left subclavian artery (LSA) revascularization was performed prior to the arch endovascular repair. Data were collected retrospectively in an electronic database. Parameters included length of procedure, fluoroscopy time, contrast volume, technical success, presence of endoleaks, early and late complications, and mortality. RESULTS: Twenty-seven patients were included in the study. Technical success was achieved in all cases. No patients died during the 30 day post-operative period. Early neurologic events included two major strokes (7.4%) and one minor stroke (3.7%). Transient spinal cord ischemia with full recovery was observed in two patients (7.4%). Four patients (14.8%) underwent early (<30 day) re-interventions; these were for an access complication, an ischemic limb and exploration of the left ventricle through a sternotomy in two patients. During follow up (median 12 months), one patient (3.7%) died from a remote thoraco-abdominal aneurysm rupture. There were three Type 2 endoleaks (11.1%). Two re-interventions (7.4%) were performed, one to treat a Type 2 endoleak and one to treat a septic false aneurysm. A significant decrease in overall mortality was observed when comparing patients from the early experience with patients from the current report. CONCLUSIONS: The early outcomes associated with this technology are favorable. Branched endografting of aortic arch aneurysms should be considered in patients unfit for open surgery.

Influence of anti-HBc seropositivity on the risk of hepatocellular carcinoma in HCV-infected patients after adjusting for confounding factors.

It is controversial whether past hepatitis B virus infection constitutes an additional risk of hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV). The incidence of HCC between 1994 and 2004 was analysed among 1262 patients who were only positive for HCV. The cumulative incidence of HCC was assessed by Kaplan-Meier analysis and the difference between two groups was assessed by the log-rank test. The effect of anti-HBc positivity on the risk of HCC was assessed with multivariate Cox proportional analysis. Anti-HBc was positive in 522 (41.4%) patients. The proportion of male patients (56.7 vs 46.8%, P < 0.001) and mean age (60.8 vs 56.9 years, P < 0.001) were significantly higher in the anti-HBc positive group. HCC developed in 339 patients (mean follow-up 7.0 years), with cumulative incidence rates at 3, 5 and 10 years of 12.7, 24.5 and 41.9% in the anti-HBc positive group and 10.6, 17.7 and 33.4% in the negative group, respectively (P = 0.005). However, anti-HBc seropositivity did not reach statistical significance in multivariate analysis including age and gender (hazard ratio, 1.06; 95% CI, 0.85-1.31; P = 0.63). Anti-HBc positivity and HCC incidence were confounded by male gender and older age.

Visceral fat accumulation is an independent risk factor for hepatocellular carcinoma recurrence after curative treatment in patients with suspected NASH.

BACKGROUND AND AIMS: Visceral fat accumulation reportedly increases the risk of hepatocellular carcinoma (HCC) development in patients with chronic liver disease. However, it has not been fully elucidated whether visceral fat accumulation increases the risk of HCC recurrence after curative treatment in patients with suspected non-alcoholic steatohepatitis (NASH). Therefore this was investigated in the current study. METHODS: 62 patients with naive HCC with suspected NASH were enrolled. All were curatively treated with percutaneous radiofrequency ablation between 1999 and 2006. The visceral fat area (VFA) was determined in each patient from CT images, taken at the time of HCC diagnosis. Patients were divided into two groups based on VFA: the high VFA group (>130 cm(2) in males, >90 cm(2) in females, n = 27) and the others (n = 35). The effects of VFA on HCC recurrence were analysed together with other factors including patients' background, tumour-related factors and liver function-related factors. RESULTS: The cumulative recurrence rates differed significantly between the two groups; 15.9, 56.5 and 75.1% at 1, 2 and 3 years, respectively, in the high VFA group, and 9.7, 31.1 and 43.1%, respectively, in the controls (p = 0.018). Multivariate analysis indicated visceral fat accumulation (risk ratio 1.08, per 10 cm(2), p = 0.046) and older age (risk ratio 1.06 per 1 year, p = 0.04) as independent risk factors of HCC recurrence. CONCLUSIONS: Visceral fat accumulation is an independent risk factor of HCC recurrence after curative treatment in patients with suspected NASH.

A cryogenic spin-torque memory element with precessional magnetization dynamics.

We present a study of precessional magnetization switching in orthogonal spin-torque spin-valve devices at low temperatures. The samples consist of a spin-polarizing layer that is magnetized out-of-the film plane and an in-plane magnetized free and reference magnetic layer separated by non-magnetic metallic layers. We find coherent oscillations in the switching probability, characterized by high speed switching (~200 ps), error rates as low as 10-5 and decoherence effects at longer timescales (~1 ns). Our study, which is conducted over a wide range of parameter space (pulse amplitude and duration) with deep statistics, demonstrates that the switching dynamics are likely dominated by the action of the out-of-plane spin polarization, in contrast to in-plane spin-torque from the reference layer, as has been the case in most previous studies. Our results demonstrate that precessional spin-torque devices are well suited to a cryogenic environment, while at room temperature they have so far not exhibited coherent or reliable switching.

Increased uptake of oxLDL does not exert lipotoxic effects in insulin-secreting cells.

Modified lipoproteins can negatively affect beta cell function and survival. However, the mechanisms behind interactions of modified lipoproteins with beta cells - and in particular, relationships to increased uptake - are only partly clarified. By over-expressing the scavenger receptor CD36 (Tet-on), we increased the uptake of fluorescent low-density modified lipoprotein (oxLDL) into insulin-secreting INS-1 cells. The magnitude of uptake followed the degree of CD36 over-expression. CD36 over-expression increased concomitant efflux of 3H-cholesterol in proportion to the cellular contents of 3H-cholesterol. Exposure to concentrations of oxLDL from 20 to 100 µg/mL dose-dependently increased toxicity (evaluated by MTT) as well as apoptosis. However, the increased uptake of oxLDL due to CD36 over-expression did not exert additive effects on oxLDL toxicity - neither on viability, nor on glucose-induced insulin release and cellular content. Reciprocally, blocking CD36 receptors by Sulfo-N-Succinimidyl Oleate decreased the uptake of oxLDL but did not diminish the toxicity. Pancreatic islets of CD36-/- mice displayed reduced uptake of 3H-cholesterol-labeled oxLDL vs wild type but similar toxicity to oxLDL. OxLDL was found to increase the expression of CD36 in islets and INS-1 cells. In summary, given the experimental conditions, our results indicate that (1) increased uptake of oxLDL is not responsible for toxicity of oxLDL, (2) increased efflux of the cholesterol moiety of oxLDL counterbalances, at least in part, increased uptake and (3) oxLDL participates in the regulation of CD36 in pancreatic islets and in INS-1 cells.

High temperatures activate local viral multiplication and cell-to-cell movement of Melon necrotic spot virus but restrict expression of systemic symptoms.

The infection of melon plants by Melon necrotic spot virus (MNSV) and the development of necrotic disease symptoms are a seasonal occurrence in Japan, which take place between winter and early summer, but not during mid-summer. In this paper we investigate the effect of three different temperatures (15, 20, and 25 degrees C) on the local and systemic expression of MNSV in melon plants. Previously, the incidence of plants expressing systemic symptoms caused by MNSV and other viruses was found to be greater at temperatures less than 20 degrees C. In this study, our temperature-shift experiments support previous studies that found the expression of systemic symptoms increases as temperature falls from 25 to 20 degrees C and decreases as temperature rises from 20 to 25 degrees C. However, MNSV replication in melon cells and local viral movement within leaves following the inoculation of melon protoplasts or cotyledons were more frequent at 25 degrees C than at 15 or 20 degrees C.

Structure of the gene encoding human alpha 2-HS glycoprotein (AHSG).

Alpha 2-HS glycoprotein (AHSG) is a human plasma glycoprotein and fetuin is the homologue in the calf. In this report, we present the structure and organization of the AHSG gene. Introns and the 5' and 3'-flanking regions were obtained by polymerase chain reaction (PCR) and the inverted PCR, respectively, from genomic DNA using AHSG cDNA-specific oligonucleotide primers. The sequence of the PCR products shows that the coding region spans approximately 8.2 kb and is composed of seven exons interrupted by six introns. The exon-intron splice junctions agree with the consensus sequence, and the positions interrupted by introns are precisely identical to those of the rat insulin receptor tyrosine kinase inhibitor (fetuin) gene. The 5'-promoter region contains several characteristic sequences such as an A + T-rich sequence of TAAATAA, C/EBP-binding site, and hepatocyte nuclear factor-5 (HNF-5) and serum response factor (SRF) sites.

Conformational changes at the highly reactive cystein and lysine regions of skeletal muscle myosin induced by formation of transition state analogues.

Myosin forms stable ternary complexes with Mg2+-ADP and phosphate analogues of aluminum fluoride (AlF4-), beryllium fluoride (BeFn), and scandium fluoride (ScFn). These complexes are distinct from each other and may mimic different transient states in the ATPase cycle [Maruta et al. (1993) J. Biol. Chem. 268, 7093-7100]. Regions of skeletal muscle myosin containing the highly reactive residues Cys 707 (SH1), Cys 697 (SH2), and lysine 83 (RLR) dramatically alter their local conformation when myosin hydrolyzes ATP, and these changes may reflect formation of a series of transient intermediates during ATP hydrolysis. We used the fluorescent probes 4-fluoro-7-sulfamoylbezofurazan, 2-(4'-maleimidylanilino)naphthalene-6-sulfonic acid, and trinitrobenzene-sulfonate, which bind to SH1, SH2, and RLR, respectively, to examine differences in local conformations within myosin.ADP.phosphate analogue (BeFn, Vi, AlF4-, and ScFn) complexes. It was observed that the ternary complexes had SH1 conformations similar to those seen on S-1 in the presence of ATP. In contrast, local conformations in the SH2 and RLR regions of S-1.ADP.BeFn were different from those in corresponding regions of S-1.ADP.AlF4- or ScFn. These results suggest that SH1 and SH2 move distinctly during ATP hydrolysis and that the local conformations of the SH2 and RLR regions more sensitively reflect different transient states.

Secondary exposure of medical staff to sarin vapor in the emergency room.

OBJECTIVE: To clarify the risk of secondary exposure of medical staff to sarin vapor in the emergency room, and to warn emergency room staffs of the hazard. DESIGN: Retrospective observational survey. SETTING: Emergency department of a university hospital in a metropolitan area of Japan. PARTICIPANTS: Fifteen doctors treating victims of a terrorist attack with sarin in the Tokyo subways on the day of the attack. MEASUREMENTS AND RESULTS: Of the 15 doctors who worked in the emergency room treating the victims, 13 became simultaneously aware of symptoms during the resuscitation of two victims who were exposed to sarin. Among 11 doctors (73%) who complained of dim vision, the pupils were severely miotic (<2 mm) in 8 (73%). Other symptoms included rhinorrhea in eight (53%), dyspnea or tightness of the chest in four (27%), and cough in two (13%). Atropine sulfate was given to six, and pralidoxime was given to one of these six doctors. To decontaminate the emergency room of sarin vapor, ventilation was facilitated and all belongings of the patients were sealed up. None of the doctors noticed worsening of their symptoms thereafter. CONCLUSIONS: Careful attention to the risks of secondary exposure to toxic gas in the emergency room and prompt decontamination if such exposure should occur are necessary in the case of large-scale disasters caused by sarin.

Preoperative use of erythropoietin for cardiovascular operations in anemia.

Erythropoietin was used in 10 patients undergoing elective cardiovascular operations who were compromised with anemia. Initially, their blood hemoglobin levels were less than 10 g/dL (range, 7.5 to 9.9 g/dL). Erythropoietin (600 to 700 units/kg per week) was administered intravenously or subcutaneously for about 2 to 12 weeks. Blood hemoglobin levels increased in each patient (11.0 to 14.5 g/dL) until the day operation, and during this course autologous blood donations (400 to 1,200 mL) were obtained from 8 patients. As a result, homologous blood transfusions were needed in only 1 patient in whom erythropoietin treatment was interrupted for other reasons. All these patients were discharged without event, and no adverse effects due to erythropoietin were found. Although the causes of anemia were not specified in some of these patients, it was noteworthy that erythropoietin was effective even in a patient with hypoplastic bone marrow. Subcutaneous use was assumed to be especially favorable in managing anemic patients, in whom preoperative erythropoietin treatment could be continued for up to 82 days. We conclude that erythropoietin would be beneficial for the anemic population to secure homologous-blood-free operations.

Antiandrogen withdrawal syndrome in prostate cancer after treatment with steroidal antiandrogen chlormadinone acetate.

OBJECTIVES: A case report is presented of 2 patients whose levels of serum prostate-specific antigen (PSA) improved after the withdrawal of a steroidal antiandrogen. METHODS: Two cases with prostate cancer had been treated with surgical castration and the steroidal antiandrogen chlormadinone acetate (CMA), and, on disease progression, the administration of CMA was terminated. RESULTS: Following withdrawal of CMA, a fall in PSA levels and remarkable clinical improvement were observed in both cases. One patient revealed a decrease and the other an increase in serum prostate acid phosphatase after the discontinuation of CMA. Serum levels of testosterone, prolactin, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione were not significantly elevated after CMA withdrawal. CONCLUSIONS: Withdrawal of the steroidal antiandrogen CMA resulted in a decline in PSA levels and clinical improvement in prostate cancer patients with disease progression. Changes in testosterone, prolactin, or adrenal androgens were not a cause of the antiandrogen withdrawal syndrome.

Chemotherapy for endocrine-therapy-refractory prostate cancer.

The effects of various chemotherapy regimens on endocrine-therapy-refractory prostate cancer were examined in 64 patients. Chemotherapy was started from the first evidence of relapse. The regimens of the initial chemotherapy were as follows: cisplatin (CDDP, 4 cases) and ifosfamide (4 cases) were given as single agents and vincristine, ifosfamide, and peplomycin (VIP, 8 cases); cyclophosphamide, doxorubicin, and CDDP (CAP, 14 cases); ifosfamide, doxorubicin, and CDDP (IAP, 24 cases); and etoposide, doxorubicin, and CDDP (EAP, 10 cases) were given as combinations. On the basis of the results, the patients were divided into two groups: single agents plus VIP and other combinations. In the CAP, IAP, and EAP groups, the cause-specific survival was similar, and the survival of these groups was longer than that of the single agents plus VIP group. Since patients with a long duration between the start of endocrine therapy and the start of chemotherapy were contained in the CAP, IAP, and EAP groups, comparison was performed without these cases. No difference was found between the two groups, suggesting that no superior regimen was found. The short-term effect was evaluated on the basis of the changes observed in prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) levels at 3 months after the start of chemotherapy, and patients showing a complete response, partial response, or no change on any of the regimens exhibited longer survival than did those with progressive disease. Since the PSA doubling time estimated before the chemotherapy correlated with the change in the PSA values due to the chemotherapy, the rate of proliferation of the tumor influenced the effect of the chemotherapy. Thus, this finding suggests that slowly growing cancers show a better response to chemotherapy than do rapidly proliferating ones.

Identification of the novel developmentally regulated gene, Bdm2, which is highly expressed in fetal rat brain.

Most of the neurogenesis take place during the embryonic stage; the genes expressed predominantly in this stage may play important roles in the control of development of the central nervous system. Using a differential display method, we identified the novel rat gene, brain development-related molecule 2 (Bdm2), that is expressed more abundantly in the embryonic brain than in the adult brain. Full-length Bdm2 cDNA consists of 1842 base pairs (bp) and contains an open reading frame of 1260 bp. Northern blot analysis demonstrated that Bdm2 was strongly expressed in the late embryonic brain and was still detected at lower levels in an early postnatal period; in adults, Bdm2 mRNA was decreased to an undetectable level in brain, though the expression of this mRNA was revealed in other tissues. Level of Bdm2 mRNA was maintained during neuronal differentiation of mouse embryonal carcinoma cell P19, but decreased during the differentiation to glial and unidentified non-neuronal cells. In situ hybridization study demonstrated the wide distribution of Bdm2 mRNA in the embryonic brain; in the adult brain, the hybridization signals became more restricted to the hippocampus, olfactory bulb, cerebellum, and neocortex, almost coinciding with the regions where nascent and immature neurons are present. Thus, it appears likely that Bdm2 encodes a protein that is involved in both the regulation of growth of undifferentiated neural cells and the terminal differentiation of neuronal cells.

Endovascular graft repair of ruptured aortoiliac aneurysms.

BACKGROUND: The feasibility of endovascular graft (EVG) repair of ruptured aortoiliac aneurysms (AIAs) has yet to be demonstrated. There are inherent limitations in EVG repair, including the need for preoperative measurements of the aneurysmal and adjacent arterial anatomy to determine the appropriate size and type of graft and the inherent delay to obtain proximal occlusion. We developed an EVG system with broad versatility that largely eliminates these problems. STUDY DESIGN: Between 1993 and 1998, within an experience of 134 endovascular AIA repairs, 12 ruptured AIAs were treated using EVGs that facilitated intraoperative customization and eliminated the need for preoperative measurements. The EVGs consisted of either a Palmaz stent and a PTFE graft deployed by a compliant balloon (n = 9) or a self-expanding covered stent graft (n = 3). Both grafts were cut to the appropriate length intraoperatively. The mean age of the patients was 72 years (range 40 to 86 years). The mean size of the aneurysms was 7.6 cm (range 3 to 16 cm). Preoperative symptoms were present in all patients and included abdominal or back pain (n = 9), syncope (n = 4), and external bleeding (n = 2). All patients were high surgical risks because of comorbid disease (n = 10) or previous abdominal operations (n = 6), and nine experienced hypotension. RESULTS: All EVGs were inserted successfully and excluded the aneurysms from the circulation. The mean operating time was 263 minutes, the mean blood loss was 715 mL, and the mean length of hospital stay was 6.5 days. There were two deaths (16%), one from the preexisting acute myocardial infarction and one from multiple organ failure. There were three minor complications (25%). Two patients required evacuation of an intraabdominal hematoma from the initial rupture. All but one of the grafts was functioning at a mean followup of 18 months. CONCLUSIONS: This study demonstrates the feasibility of EVG repair for ruptured AIAs using a graft that can be customized intraoperatively for each patient. Such repairs currently are valuable in patients with ruptured AIAs and serious comorbidities and may be applicable in other circumstances as well.

Pattern of aliphatic dicarboxylic acids in uremic serum including a new organic acid, 2,4-dimethyladipic acid.

(1) 2,4-Dimethyladipic acid was first identified in normal human urine using gas chromatography-mass spectrometry. Urinary excretion of 2,4-dimethyladipic acid in 7 healthy adults ranged from 4.9 mumol to 14 mumol per 24 h. (2) Succinic acid, adipic acid, 3-methyladipic acid, 2,4-dimethyladipic acid, pimelic acid and azelaic acid were identified in the ultrafiltrate of the blood obtained from a chronic uremic patient using a hemodialyzer. (3) Levels of succinic acid, adipic acid, 3-methyladipic acid, 2,4-dimethyladipic acid, pimelic acid and azelaic acid in uremic serum were determined using a mass fragmentographic technique. Concentration of succinic acid in uremic serum was comparable to that in normal serum, whereas concentrations of adipic acid, 3-methyladipic acid, 2,4-dimethyladipic acid, pimelic acid and azelaic acid were highly elevated in uremic serum.

A gas chromatographic-mass spectrometric analysis for phenols in uremic serum.

(1) The concentrations of unconjugated and conjugated phenol, p-cresol, benzyl alcohol, catechol, hydroquinone, homocatechol, and 2-methoxyresorcinol in uremic serum were determined using a mass fragmentographic method. Concentrations of all phenols in uremic serum were higher than in normal serum. Conjugated phenols existed mainly as sulfate esters. (2) The concentration of unconjugated phenol in uremic serum correlated with those of serum creatinine and urea, but not with the hematocrit value. Patients with the highest concentration of unconjugated phenol suffered from cerebral disorders, coma or lethargy, and hemorrhagic tendencies. Unconjugated phenol was detected in normal serum at a concentration of 0.86 +/- 0.63 mumol/l (mean +/- S.D., n = 10). (3) The concentration of unconjugated p-cresol in uremic serum did not correlate with those of serum creatinine, urea and the hematocrit value. (4) The concentrations of unconjugated and conjugated hydroquinone in uremic serum correlated with those of serum creatinine and urea. (5) 2-Methoxyresorcinol was first detected mainly as sulfate ester in uremic serum at a concentration of 19 +/- 9.0 mumol/l (mean +/- S.D,. n = 17). (6) The daily excretion of eight unconjugated phenols into normal urine was determined.

A gas chromatographic-mass spectrometric assay for nine hydroxyphenolic acids in uremic serum.

A mass fragmentographic method for the determination of m-hydroxybenzoic acid, p-hydroxybenzoic acid, o-hydroxyphenylacetic acid, m-hydroxyphenylacetic acid, p-hydroxyphenylacetic acid, vanillic acid, p-hydroxymandelic acid, homovanillic acid and vanilmandelic acid in uremic serum is described. The hydroxyphenolic acids were extracted from one ml of serum ultrafiltrate. After trimethylsilylation, the extract was analyzed by a gas chromatograph-mass spectrometer. Concentrations of nine hydroxyphenolic acids are higher in uremic serum. In particular, p-hydroxybenzoic acid and p-hydroxyphenylacetic acid are markedly increased in uremic serum. The influence of hemodialysis on the hydroxyphenolic acids was studied by quantitating the acids before and after hemodialysis.

Profiling of uremic ultrafiltrate using high resolution gas chromatography-mass spectrometry - identification of 6 polyphenols.

An analytical method for separation and identification of compounds in uremic ultrafiltrate has been developed using a glass capillary column gas chromatography-mass spectrometry-computer system. The ultrafiltrate samples of blood were obtained during hemodialysis treatment of chronic uremic patients and non-uremic patients using the extracorporeal ultrafiltration method. Sample preparation consisted of acidification, extraction, evaporation, and trimethylsilylation. Many compounds were newly identified in the uremic ultrafiltrate by electron impact ionization, chemical ionization, and high resolution mass spectrometry. Six toxic polyphenols, namely, catechol, resorcinol, hydroquinone, 2-methoxyresorcinol, 3-methoxycatechol, and methoxyhydroquinone were first detected in the uremic ultrafiltrate.

alpha-glucosidase activity in human leucocytes: choice of lymphocytes for the diagnosis of Pompe's disease and the carrier state.

alpha-Glucosidase activity was assayed in polymorphonuclear cells and lymphocytes from human peripheral blood with 4-methylumbelliferyl-alpha-D-glucopyranoside as substrate in the presence of sodium taurocholate. The pH vs. activity curve of the alpha-glucosidase indicated that differential estimation between acid and neutral alpha-glucosidases was difficult to perform with polymorphonuclear cells, but easily accessible with lymphocytes. The use of peripheral blood lymphocytes for the enzymatic diagnosis of Pompe's disease seemed to be more reliable than the use of whole leucocytes; this also the case with a classical Pompe's patient. The lymphocytes from the parents had normal or low normal activity of acid alpha-glucosidase in the freshly isolated state, but when cultured with phytohaemagglutinin for 72 h, the stimulated lymphocytes of both parents showed about half the enzyme activity of the cultured controls. It was deemed possible in all probability to identify the carrier state by assay of the enzyme activity in phytohaemagglutinin-stimulated lymphocytes.