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Background The diagnosis of epilepsy is at times elusive for both neurologists and nonneurologists, resulting in delays in diagnosis and therapy. The development of screening methods has been identified as a priority in response to this diagnostic and therapeutic gap. EpiFinder is a novel clinical decision support tool designed to enhance the process of information gathering and integration of patient/proxy respondent data. It is designed specifically to take key terms from a patient's history and incorporate them into a heuristic algorithm that dynamically produces differential diagnoses of epilepsy syndromes. Objective The objective of this study was to test the usability and diagnostic accuracy of the clinical decision support application EpiFinder in an adult population. Methods Fifty-seven patients were prospectively identified upon admission to the Epilepsy Monitoring Unit (EMU) for episode classification from January through June of 2017. Based on semiologic input, the application generates a list of epilepsy syndromes. The EpiFinder-generated diagnosis for each subject was compared to the final diagnosis obtained via continuous video electroencephalogram (cVEEG) monitoring. Results Fifty-three patients had habitual events recorded during their EMU stay. A diagnosis of epilepsy was confirmed (with cVEEG monitoring) in 26 patients while 27 patients were found to have a diagnosis other than epilepsy. The algorithm appropriately predicted differentiation between the presence of an epilepsy syndrome and an alternative diagnosis with 86.8% (46/53 participants) accuracy. EpiFinder correctly identified the presence of epilepsy with a sensitivity of 86.4% (95% confidence interval [CI]: 65.0–97.1) and specificity of 85.1% (95% CI: 70.2–96.4). Conclusion The initial testing of the EpiFinder algorithm suggests possible utility in differentiating between an epilepsy syndrome and an alternative diagnosis in adult patients.

This study evaluates the outcome of axillary nerve injuries treated with nerve grafting. Thirty-six patients were retrospectively reviewed after a mean of 53 months (minimum 12 months). The mean interval from injury to surgery was 6.5 months. Recovery of deltoid function was assessed by the power of both abduction and retropulsion, the deltoid bulk and extension lag. The deltoid bulk was almost symmetrical in nine of 34 cases, good in 22 and wasted in three. Grade M4 or M5* was achieved in 30 of 35 for abduction and in 32 of 35 for retropulsion. There was an extension lag in four patients. Deltoid bulk continued to improve with a longer follow-up following surgery. Nerve grafting to the axillary nerve is a reliable method of regaining deltoid function when the lesion is distal to its origin from the posterior cord.

Objective The aim of this study was to evaluate right and left ventricular functions in patients with pulmonary arterial hypertension after living-donor lobar lung transplantation compared with those without hypertension. Methods Thirty-three recipients of living-donor lobar lung transplantation were divided into two groups: those with pulmonary arterial hypertension (PAH group; n=12) and those without (non-PAH group; n=21). Their systolic pulmonary artery pressure was 93.1 ± 6.7 mm Hg versus 31.4 ± 2.9 mm Hg, respectively. Right and left ventricular ejection fractions, systolic pulmonary artery pressure, and cardiac index were serially measured by radionuclide ventriculography and right heart catheterization, respectively. Results Pretransplant right and left ventricular ejection fractions were lower in the PAH group (29.8% ± 7.0%, 49.9% ± 6.6%) than in the non-PAH group (49.7% ± 3.3%, 65.2% ± 1.9%) ( P = .010, .068). Two months after living-donor lobar lung transplantation, right ventricular ejection fraction and systolic pulmonary artery pressure in the PAH group (57.3% ± 5.1%, 25.7 ± 1.8 mm Hg) improved dramatically, equal to those in the non-PAH group. In contrast, left ventricular ejection fraction and cardiac index in the PAH group (50.9% ± 3.7%, 2.66 ± 0.12 L · min −1 · m −2 ) were still significantly lower than in the non-PAH group (65.4% ± 2.8%, 3.13 ± 0.15 L · min −1 · m −2 ) ( P = .0038, .037). At 6 to 12 months, the PAH group demonstrated a significant rise in left ventricular ejection fraction and cardiac index that reached similar values in the non-PAH group measured at 2 months. These values were stable for up to 3 years. Conclusions Right ventricular function recovered early after living-donor lobar lung transplantation in the PAH group. In contrast, recovery of left ventricular function required 6 to 12 months. Improved cardiac function was sustained for up to 3 years, suggesting long-term durability of cardiac function recovery after living-donor lobar lung transplantation.

For the purpose of a nationwide surveillance of the antimicrobial susceptibility of bacterial respiratory pathogens in patients in Japan, the Japanese Society of Chemotherapy conducted their second year survey, during the period from January to August, 2007. A total of 1178 strains were collected from clinical specimens obtained from adult patients with well-diagnosed respiratory tract infections. Susceptibility testing was evaluable for 1108 strains (226 Staphylococcus aureus, 257 Streptococcus pneumoniae, 6 Streptococcus pyogenes, 206 Haemophilus influenzae, 120 Moraxella catarrhalis, 122 Klebsiella pneumoniae, and 171 Pseudomonas aeruginosa). A total of 44 antibacterial agents, including 26 beta-lactams (four penicillins, three penicillins in combination with beta-lactamase inhibitors, four oral cephems, eight parenteral cephems, one monobactam, five carbapenems, and one penem), three aminoglycosides, four macrolides (including ketolide), one lincosamide, one tetracycline, two glycopeptides, six fluoroquinolones, and one oxazolidinone were used for the study. Analysis was conducted at the central reference laboratory according to the method recommended by the Clinical and Laboratory Standards Institute (CLSI). The incidence of methicillinresistant Staphylococcus aureus (MRSA) was high, at 59.7%, and the incidences of penicillin-intermediateresistant and -resistant Streptococcus pneumoniae (PISP and PRSP) were 30.4% and 5.1%, respectively. Among Haemophilus influenzae strains, 19.9% of them were found to be beta-lactamase-non-producing ampicillin (ABPC)-intermediately-resistant (BLNAI), 29.1% to be beta-lactamasenon-producing ABPC-resistant (BLNAR), and 6.7% to be beta-lactamase-producing ABPC-resistant (BLPAR) strains. Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae was not isolated. Two isolates (1.2%) of Pseudomonas aeruginosa were found to be metallo-beta-lactamase-producing strains, including one (0.6%) suspected multidrug-resistant strain showing resistance to imipenem, amikacin, and ciprofloxacin. These data will be a useful reference for future periodic surveillance studies and for investigations to control resistant infections as well. Continued surveillance is required to prevent the further spread of these antimicrobial resistances.

Background The indication of lung transplantation for patients with pulmonary complications of hematopoietic stem cell transplantation (HSCT) remains controversial, and only few such cases have been reported. We reviewed our experiences regarding living-donor lobar lung transplantation (LDLLT) in patients with pulmonary complications of HSCT. Methods We reviewed and assessed seven patients (age, 6-45 yr) who underwent LDLLT at Okayama University Hospital for pulmonary complications of HSCT (HSCT group). Their characteristics and postoperative results were compared with those of 41 LDLLT without HSCT patients (non-HSCT group). In the HSCT group, indications for LDLLT included bronchiolitis obliterans (n=6) and pulmonary fibrosis (n=1) that had developed after treatments involving HSCT. Preexisting hematologic diseases included acute lymphocyte leukemia (n=4), acute promyelocystic leukemia (n=1), myelodysplastic syndrome (n=1), and aplastic anemia (n=1). Results In the HSCT group, two patients died due to infectious complications, whereas five are currently alive (an overall survival of 71.4%) without any recurrence of the hematologic diseases (mean follow-up period, 35.7 months). The mean of acute rejection episodes was 1.1 per patient in the HSCT group and 1.8 in the non-HSCT group. One of the seven HSCT (14.4%) and 10 non-HSCT (24.4%) patients have currently developed bronchiolitis obliterans syndrome. Conclusion Our results showed that LDLLT for patients with respiratory failure because of pulmonary complications of HSCT could be an effective approach with less rejection episodes; however, it has a possibly higher risk of the development of infectious complications.

Living-donor lobar lung transplantation (LDLLT) is performed in critically ill patients, although the outcome is generally expected to be poor for those who are ventilator dependent. The aim of this study was to compare the outcomes of LDLLT in ventilator-dependent patients compared with those in ventilator-independent patients.We reviewed 31 consecutive patients who received LDLLT between October 1998 and May 2004.Five patients were ventilator dependent and 26 were ventilator independent. All five ventilator-dependent patients were female, with a mean age of 29.6 years. The duration of preoperative ventilation was 23.4 +/- 5.7 days. The underlying diagnoses in the ventilator-dependent patients included only obstructive (n = 3) and infectious lung diseases (n = 2), whereas those in the ventilator-independent patients included hypertensive and restrictive diseases (P = 0.004). There were no significant differences between the groups in early postoperative clinical values. The incidences of acute rejection and bronchiolitis obliterans syndrome (BOS) were comparable. The 5-year survival rates were 100% for the ventilator-dependent patients and 92.3% for the ventilator-independent patients (P = 0.45).Our findings suggest that LDLLT can have a favorable outcome in selected ventilator-dependent patients.

The living-donor lobar lung transplantation procedure has been developed clinically as an alternative approach for patients considered too ill to await cadaveric transplantation. With this procedure, 2 lobes are implanted in the recipient in place of whole right and left lungs, respectively. However, the shortage of graft volume can be a problem when compared with full-sized cadaveric grafts. In an attempt to solve this problem, we have developed a native lobe-preserving lobar transplant technique using a large animal model. We report a first successful case of a patient undergoing native lobe-preserving lobar lung transplantation for severe pulmonary emphysema.

In this study we report the case of a 28-year-old female patient with recurrent lymphangioleiomyomatosis (LAM) in the allografts after bilateral living-donor lobar lung transplantation. Although her post-operative course under immunosuppression with tacrolimus and prednisolone had been uneventful without rejection episodes, she had developed shortness of breath and a progressive chylous effusion with diffuse cystic changes in both lungs 5 years after transplantation. In spite of a diagnosis of having a recurrence of LAM based on radiologic findings and deteriorating pulmonary function, her clinical symptoms, which included dyspnea and chylothorax, were significantly improved after treatment with sirolimus. Although a beneficial effect of sirolimus in the treatment of LAM has not been definitively determined, this report may provide useful information for management of recurrent LAM after lung transplantation.

Behçet’s disease is a chronic, relapsing, inflammatory disorder. This case report describes how use of an improvised topical negative pressure (TNP) device in a patient with a non-healing para-ileostomal ulcer with Behçet’s disease

The Japanese Society of Chemotherapy (JSC) conducted the first nationwide surveillance of bacterial respiratory pathogens during the period from January to August 2006. With the cooperation of 32 medical institutions throughout Japan, a total of 924 strains belonging to seven clinically relevant bacterial species were collected from adult patients with well-diagnosed respiratory tract infections (RTIs). Antimicrobial susceptibility testing of the 887 evaluable strains (205 Staphylococcus aureus, 200 Streptococcus pneumoniae, 9 Streptococcus pyogenes, 165 Haemophilus influenzae, 91 Moraxella catarrhalis, 74 Klebsiella pneumoniae, and 143 Pseudomonas aeruginosa) to 42 antibacterial agents was conducted at the Central Laboratory of the Research Center for Anti-infective Drugs of the Kitasato Institute, according to recommendations issued by the Clinical and Laboratory Standards Institute (CLSI). The antibacterial agents employed were 25 beta-lactams, three aminoglycosides, four macrolides (including one azalide and one ketolide), one lincosamide, one tetracycline, two glycopeptides, five fluoroquinolones, and one oxazolidinone. The incidence of methicillin-resistant S. aureus (MRSA) was 63.4%, and the incidences of penicillin-intermediately resistant S. pneumoniae (PISP) and penicillin-resistant S. pneumoniae (PRSP) were 35.0% and 4.0%, respectively. Among H. influenzae, 21.2% of the strains were found to be beta-lactamase-nonproducing ampicillin (ABPC)-intermediately resistant (BLNAI), 29.1% to be beta-lactamase-nonproducing ABPC-resistant (BLNAR), and 4.8% to be beta-lactamaseproducing ABPC-resistant (BLPAR) strains. The incidence of extended-spectrum beta-lactamase-producing K. pneumoniae was 2.7% (2 of 74 strains). Three (2.1%) of the 143 P. aeruginosa strains were found to be metallo-beta-lactamaseproducing, including 1 (0.7%) multidrug-resistant strain. Through the nationwide surveillance, we obtained fundamental antimicrobial susceptibility data of clinically relevant bacterial pathogens in adult RTI to various antibacterial agents. These data will be a useful reference for future periodic surveillance studies, as well as for investigations to control antimicrobial-resistant pathogens.

ObjectivesThe aim of this study was to evaluate the long-term effects of living-donor lobar lung transplantation (LDLLT) for critically ill patients with pulmonary arterial hypertension (PAH) who failed in epoprostenol treatment.BackgroundAlthough continuous epoprostenol infusion has markedly improved survival in patients with PAH, some patients do not benefit from this therapy.MethodsFrom July 1998 to December 2003, 28 consecutive PAH patients who were treated with epoprostenol and accepted as candidates for lung transplantation were enrolled. All data were prospectively collected. As of July 2006, LDLLT was performed in 11 of those patients whose condition was deteriorating. Cadaveric lung transplantation (CLT) was performed in 2 patients. Medical treatment was continued in 15 patients.ResultsThere was no mortality in patients receiving LDLLT during a follow-up period of 11 to 66 months (average 48 months), and all patients returned to World Health Organization functional class I. Mean pulmonary artery pressure decreased from 62 ± 4 mm Hg to 15 ± 2 mm Hg (p < 0.001) at discharge and remained normal at 3 years. One CLT patient died of primary graft failure. Among medically treated patients, 6 patients died of disease progression. The survival rate was 100% at 5 years for patients receiving LDLLT, and 80% at 1 year, 67% at 3 years, and 53% at 5 years for patients medically treated (p = 0.028). All living donors have returned to their previous lifestyles.ConclusionsThese follow-up data support the option of LDLLT in patients with PAH who would die soon otherwise.

As an alternative to cadaveric transplantation, living donor lobar lung transplantation (LDLLT) has been applied in critical patients with end-stage pulmonary disease because of the mismatch between the supply and demand of lungs for transplantation. However, it is unclear whether two pulmonary lobes can provide adequate long-term pulmonary function and satisfactory clinical outcome in recipients.Between October 1998 and September 2004, 28 females and 3 males, including 5 children, underwent LDLLT at Okayama University Hospital. Their mean age was 31.8 years, and the mean observation period was 53.8 months. One patient who underwent single-lung transplantation and another who died peri-operatively were excluded from further analyses.The most common indication for transplantation was pulmonary arterial hypertension (32.3%). The overall survival rate was 93.6%. Seven recipients (22.6%) developed bronchiolitis obliterans syndrome after LDLLT. The mean percent predicted forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) improved between 12 and 24 months after transplantation (71.8 +/- 12.9% and 65.8 +/- 17.2% at 12 months vs 77.4 +/- 16.6% and 72.8 +/- 14.6% at 24 months; p0.005 and p0.05, respectively). The actual recipient FVC ultimately reached 123.0% of the estimated graft FVC of two donor lobes (calculated based on the donor FVC and number of segments implanted) at 36 months after LDLLT.Although LDLLT may be associated with the limitation of size mismatch, it holds promise for providing well-functioning pulmonary lobar grafts to critically ill patients with poor life expectancy.

We experienced three cases of nocardiosis by Nocardia farcinica in the same ward within a six-month period. The result of gene analysis by randomly amplified polymorphic DNA gave the same pattern. Thus, these three cases were considered to be caused by the same strain of N. farcinica, implying the presence of nosocomial infection.

A 38-year-old woman with Eisenmenger's syndrome underwent bilateral living-donor lobar lung transplantation and simultaneous closure of atrial septal defect. The grafts were a right lower lobe from her husband and a left lower lobe from her brother. Although only 2 lobes were implanted, the dramatic improvement in pulmonary hemodynamics has been well maintained for more than 5 years. Living-donor lobar lung transplantation and simultaneous cardiac repair may be one of the therapeutic options for patients with adult Eisenmenger's syndrome with simple congenital heart disease.

Extracellular products of group A streptococci isolated from patients with streptococcal toxic shock syndrome (STSS) were examined. The outline of the discussion of the 3 products are as follows; streptolysin O (SLO), proteinase and erythrogenic toxin. SLO and proteinase showed a relatively large amount of products more than erythrogenic toxin. SLO produced by group A streptococci isolated from the patient with STSS had an isoelectric point (pI) of 6.0 and a molecular weight of 64,000 and showed hemolytic activity in the presence of 2-mercaptoethanol (2-ME). Furthermore, the hemolytic activities of all components were inhibited by gamma-globulin and cholesterol. Proteinase had pIs of 8.7 and 8.9, and a molecular weight of 21,000. These data suggest that STSS clinical criteria probably reflects a characteristic of a large amount of products of individual S. pyogenes isolates.

The capacity of various growth factors to induce c-fos expression is diminished with senescence. Because adenosine 3',5'-cyclic monophosphate (cAMP)-mediated responses are also blunted with aging, we wondered whether cAMP-induced c-fos gene expression might be impaired with senescence. Using IMR fibroblasts, we found that prostaglandin E1 (PGE1) and forskolin, stimulators of cAMP accumulation in young and senescent cells, increased abundance of c-fos and junB mRNA more in young than senescent cells. The abundance of the cAMP response element binding protein (CREB), a transcription factor which enhances gene expression when phosphorylated by protein kinase A, was markedly decreased in both whole cell and nuclear extracts of senescent cells, in both Western blotting and in gel retardation assays. Also, PGE1-induced phosphorylation of CREB by protein kinase A was markedly attenuated in senescent cells. There is a marked decrement in expression of CREB with senescence, and the results suggest the possibility that the diminished expression of CREB may contribute to altered cAMP-mediated regulation of gene expression with senescence.

The technique of endoscopic excision of large capsulated lipomas is presented and the versatility of this method is discussed based on our clinical experience. We have applied this new technique in 6 cases. In all cases the lipoma was completely removed in one piece through a single incision, up to 1.5 cm in length. The endoscope made it possible to view the lipoma through a narrow space with a wide range of vision on a TV monitor. We stress that this method is not only appropriate as treatment for benign lipomas but also effective from a cosmetic point of view. The applications of the endoscope should widen in plastic surgery when the advantages of it are recognized and new operative approaches for using it are developed.

Cell-mediated immunity was examined in 45 patients with bronchial asthma by observing the delayed cutaneous reaction to purified protein derivative (PPD) and Candida albicans (C. albicans). The delayed skin reaction to PPD showed a decrease with age starting between 50 and 59 years old. The delayed reaction to PPD decreased more prominently with aging, being significantly depressed in the patients aged over 70 years than in those aged between 30 and 49 years (induration, p < 0.02; flare, p < 0.01). The C. albicans-induced skin reaction was significantly lower in the patients aged over 70 years than in those between 60 and 69 years old (induration, p < 0.01; flare, p < 0.05). The delayed skin reaction to PPD and C. albicans was significantly depressed in the patients with a serum IgE level over 1001 IU/ml. Delayed skin reaction to PPD and C. albicans was more depressed with aging and an elevated serum IgE, and the age (50-59 years) at the initiation of depression in the PPD-induced delayed skin reaction was younger than that (over 70 years) in the C. albicans-induced reaction.

The improvement of ventilatory function by spa therapy was examined in 37 patients with steroid-dependent intractable asthma (SDIA) in relation to clinical asthma types. All subjects had been on long-term corticosteroid therapy before spa therapy. Spa therapy was found to improve the values of ventilatory parameters. The percent improvement in all subjects was +4.1% in %FVC, +8.9% in FEV1.0%, +9.8% in %PEFR, +22.0% in %MMF, +19.7% in %V50 and +28.2% in %V25, respectively. Relating to clinical asthma types, moderate improvement in %MMF and %V25 from 16.7% to 16.9% was observed in type Ia cases, and marked increase in %MMF, %V50 and %V25 was observed from 42.2% to 43.2% in type Ib cases. However, no significant increase was found in these parameters of types Ia or Ib after spa therapy. In patients with type II, a significant increase was shown in %V50 (p less than 0.05) and %V25 (p less than 0.01) after spa therapy. The results show that spa therapy improves the condition of small airways disorder in patients with SDIA.

A 77-year-old female with abdominal pain and ascites was admitted to our hospital. She had a past history of the postoperative pelvic irradiation for uterine cancer and subsequently suffered from neurogenic bladder. On admission, serum creatinine (s-Cr) and blood urea nitrogen (BUN) were elevated to 9.9 mg/dl and 131 mg/dl, respectively. However, both the ratio of BUN/s-Cr and creatinine in ascites/s-Cr were significantly elevated. The clinical manifestations of the present case were not typical for acute kidney injury. Furthermore, 2 days after urethral catheterization, both s-Cr and BUN were normalized (0.69 mg/dl and 10 mg/dl, respectively) and her symptoms had improved immediately. Therefore, we diagnosed her disease as spontaneous bladder rupture. We report a case with spontaneous bladder rupture mimicking acute kidney injury forty years after postoperative pelvic irradiation for uterine cancer.

Patients with atopic dermatitis (AD) are susceptible to cutaneous bacterial infection. When such patients develop infection, some have extensive impetiginized dermatitis with high fever. To clarify the risk factors for severe impetiginized AD and its microbiological features, we reviewed clinical and microbiological data of 14 patients with impetiginized AD who were admitted to our hospital between the years 1999 and 2006. All patients had poorly controlled AD with eczematous lesions on the extensive body surface. The mean age was 28.2 years (range 18-35). Cultures of the lesional skin yielded both Streptococcus pyogenes and Staphylococcus aureus in 12 patients. S. pyogenes alone was isolated in two cases. These observations suggest that poorly controlled AD in adults is a risk factor for severe impetiginized AD and that S. pyogenes might play an important role in the development of severe clinical symptoms.

Serum levels of total IgE, specific IgE, IgG and IgG4 against house dust mite were measured in mite-sensitive asthma patients receiving immunotherapy with house dust. Serum levels of total IgE, mite specific IgE and IgG did not significantly change during the course of hyposensitization. Increased levels of mite specific IgG4 were observed in patients during immunotherapy. The increase in specific IgG4 was dependent on the total dose of house dust administered in both children (r = 0.636, p less than 0.001) and adults (r = 0.629, p less than 0.01). However, the increase of specific IgG4 in adults was not as apparent as in children. These results might suggest that mite specific IgG4 is a useful immunological marker in the immunotherapy for allergic asthma, and that IgG4 antibody acts as a blocking antibody in atopic bronchial asthma.

Based on results from the kindling model of epilepsy, we hypothesized that enhanced binding of radioligands to the NMDA receptor and decreased binding to the alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionate (AMPA)-sensitive quisqualate (ASQ) receptor would be found within epileptic hippocampi of humans with complex partial epilepsy (CPE). To test these hypotheses, we used tissue that was surgically removed from patients with intractable CPE, and control tissue that was obtained at autopsy. We used autoradiographic techniques to measure ASQ receptor binding (with 3H-AMPA as the radioligand) and binding to 2 sites on the NMDA receptor/channel complex: the agonist recognition site (with 3H-glutamate) and the phencyclidine (PCP) binding site that resides within the NMDA channel [with 3H-N-(1-[thienyl]cyclohexyl) piperidine (TCP) in the presence of saturating concentrations of NMDA and glycine]. Measurements of receptor binding were corrected for pathologic alterations in neuronal density. Contrary to our expectations, ASQ receptor binding was significantly increased (100%; p less than 0.02) in the dentate gyrus stratum moleculare in patients with CPE (n = 8), and it was unchanged in other hippocampal regions. In nearby sections from the same specimens, binding was significantly decreased to the agonist recognition site of the NMDA receptor in the stratum oriens of area CA3 (46%; p less than 0.05) and was also decreased to the PCP site in the stratum radiatum and stratum oriens of CA3 (44% and 74%, respectively; p less than 0.05). The increase in ASQ receptor binding may contribute to hyperexcitability in these epileptic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

To review the outcome of bronchial healing after living-donor lobar lung transplantation (LDLLT).We retrospectively analyzed 87 anastomoses in 45 consecutive patients who underwent LDLLT, and 14 anastomoses in 10 consecutive patients who underwent cadaveric lung transplantation (CLT), between October 1998 and September 2007. Bronchial anastomosis complications that required intervention were defined as "airway complications" (ACs).There were no significant differences in the background characteristics of the LDLLT and CLT recipients. Airway complications developed in 2 (2.2%) of the 87 anastomoses in the LDLLT group and in 3 (21.4%) of the 14 anastomoses in the CLT group (P = 0.018). The donors of the LDLLT grafts were significantly younger than the donors of the CLT grafts (38.3 years vs 46.1 years, respectively; P = 0.013). The ischemic graft times in the LDLLT and CLT groups were 136.9 min and 413.7 min, respectively (P0.0001). The periods of pretransplant ventilation in the LDLLT and CLT groups were 0 days and 4.5 days, respectively (P = 0.0083).Our study suggests that bronchial healing after LDLLT is acceptable.

We report a successful case of sirolimus treatment for chylous pleural and peritoneal effusions of lymphangioleiomyomatosis after lung transplantation. A 32-year-old woman underwent living donor lung transplantation. Persistent chylous pleural and peritoneal effusions were seen postoperatively. Pleurodesis by intrathoracic injection of OK-432, minomycin, and somatostatine analog failed to control chylous effusions. However, sirolimus treatment reduced the amount of chylous drainage and improved both chylous pleural and peritoneal effusions.

Although cadaveric lung transplantation (CLT) offers acceptable prospects for 5-year survival, chronic rejection and donor shortages remain major problems. In an effort to address the donor shortage issue, living-donor lobar lung transplantations (LDLLT) have been performed in some institutions. As of 2006, LDLLT has been performed in approximately 300 patients worldwide. The survival appears to be similar to or better than International Society for Heart and Lung Transplantation registry data on CLT. Because of the possible serious complications after donor lobectomy, LDLLT should be performed only for very sick patients by a well-prepared program. This type of procedure can be applied to restrictive, obstructive, infectious, and hypertensive lung diseases for both pediatric and adult patients who would die soon otherwise.

Many drugs associated with acquired long QT syndrome (LQTS) directly block human ether-a-go-go-related gene (hERG) K(+) channels. Recently, disrupted trafficking of the hERG channel protein was proposed as a new mechanism underlying LQTS, but whether this defect coexists with the hERG current block remains unclear. This study investigated how ketoconazole, a direct hERG current inhibitor, affects the trafficking of hERG channel protein.Wild-type hERG and SCN5A/hNa(v) 1.5 Na(+) channels or the Y652A and F656C mutated forms of the hERG were stably expressed in HEK293 cells. The K(+) and Na(+) currents were recorded in these cells by using the whole-cell patch-clamp technique (23 degrees C). Protein trafficking of the hERG was evaluated by Western blot analysis and flow cytometry.Ketoconazole directly blocked the hERG channel current and reduced the amount of hERG channel protein trafficked to the cell surface in a concentration-dependent manner. Current density of the hERG channels but not of the hNa(v) 1.5 channels was reduced after 48 h of incubation with ketoconazole, with preservation of the acute direct effect on hERG current. Mutations in drug-binding sites (F656C or Y652A) of the hERG channel significantly attenuated the hERG current blockade by ketoconazole, but did not affect the disruption of trafficking.Our findings indicate that ketoconazole might cause acquired LQTS via a direct inhibition of current through the hERG channel and by disrupting hERG protein trafficking within therapeutic concentrations. These findings should be considered when evaluating new drugs.

The control of the postoperative infectious disease is one of the important elements in transplantation. Among them, the control of the cytomegalovirus (CMV) infection may be said the most important in the management of the transplant recipient who is under the immunosuppression. This time, we review the status of the pre-transplant CMV infection in the donors and recipients of both brain-death and living-related lung transplantation that we performed, and report our prophylactic treatment for CMV infection and its results. The CMV positive rate of the recipients and donors of the lung transplantation that we experienced in Okayama University was 87%. We experienced 4 cases that developed CMV infection after lung transplantation. However, there is no case that died of a CMV-related infectious disease after lung transplantation to date. By the CMV mismatch transplant, it seemed that the frequency of the postoperative CMV disease was high in comparison with the transplant of recipient CMV (+). But, the control of the CMV infection after lung transplantation is thought to be possible if we give a proper prophylactic treatment even in CMV mismatch transplantation.

Phrenic nerve paralysis is a well-documented complication of cardiac operation, but there is less commonly reported after lung transplantation. A retrospective study of 49 lung transplantation was done at Okayama University Hospital. Phrenic nerve paralysis (unilateral in 3 patients and bilateral in 1) was found in 4 patients (8.2%). All of these paralyses were transiently recovered. The average length of ventilation, intensive care unit stay and hospitalization for recipients with phrenic nerve paralysis was not significantly longer than the other (no diaphragmatic paralysis) recipients, but there was a tendency to be longer. Diaphragmatic paralysis is most likely related to difficulty in detecting the phrenic nerve caused by adhesions, injury due to dissection, thermal injury by electrocartery, or local topical hypothermia using ice-slush. Therefore, it is important to take care of avoiding the injury of the nerve during the operation.

The rate of infection among lung transplant recipients is several times higher than that among recipients of other organs and is most likely related to the exposure of the allograft to the external environment. Meticulous peri-operative management is mandatory in performing living-donor lobar lung transplantation for patients with infectious lung diseases. All 5 patients with end-stage infectious lung diseases are currently alive for 17-104 months after receiving living-donor lobar lung transplantation at Okayama University Hospital.

Coordinated interactions between the embryo/fetus and its environment are critical for proper development. In addition to acting as metabolic substrates for cellular homeostasis, basic physiological factors, such as oxygen tension, have a profound influence on developmental outcomes. Since the mammalian embryo resides in a physiologically hypoxic environment during gestation, understanding its responses to oxygen deprivation on a cellular level is critical. In this review, we analyze interactions between the hypoxia-inducible factor family of transcriptional regulators and epigenetic mechanisms governing chromatin structure. The ability of hypoxia-inducible factors to interact physically with histone deacetylase (HDAC) enzymes and modulate nuclear HDAC activities places them in the pivotal position of integrating physiological and epigenetic effectors. Multiple embryonic and extra-embryonic stem cell populations in mice and humans rely on this interaction – an important determinant of stem cell fate. Dissection of the pathways involved will provide novel insights into the metabolic as well as molecular determinants of the stem cell niches that allow self-renewal of progenitors in an undifferentiated state.

We studied the vascular effects of invasive human cytotrophoblasts in vivo by transplanting placental villi to the fifth mammary fat pads or beneath the kidney capsules of Scid mice. Over 3 weeks, robust cytotrophoblast invasion was observed in both locations. The architecture of the mammary fat pad allowed for detailed analysis of the cells' interactions with resident murine blood vessels, which revealed specific induction of apoptosis in the endothelial cells and smooth muscle walls of the arterioles. This finding, and confirmation of the results in an in vitro coculture model, suggests that a parallel process is important for enabling cytotrophoblast endovascular invasion during human pregnancy. Cytotrophoblast invasion of the kidney parenchyma was accompanied by a robust lymphangiogenic response, while in vitro, the cells stimulated lymphatic endothelial cell migration via the actions of VEGF family members, FGF, and TNF-alpha. Immunolocalization analyses revealed that human pregnancy is associated with lymphangiogenesis in the decidua since lymphatic vessels were not a prominent feature of the nonpregnant endometrium. Thus, the placenta triggers the development of a decidual lymphatic circulation, which we theorize plays an important role in maintaining fluid balance during pregnancy, with possible implications for maternal-fetal immune cell trafficking.

¶Background. The role of intraoperative angiography in the surgical treatment of cerebrovascular malformations remains controversial. The authors report on their experiences with intraoperative angiography in a series of 20 cases with cerebrovascular malformation to determine whether the use of intraoperative angiography has a favorable impact on the surgical treatment of cerebrovascular malformations. Methods. Intraoperative angiography was performed in the surgical resection of arteriovenous malformation in 18 patients and in the surgical obliteration of arteriovenous fistula in 2 patients. The incidence of unexpected findings, such as residual nidus, demonstrated by intraoperative angiography was determined. Findings. High-quality subtraction images were obtained by intraoperative angiography in every case and the findings prompted an additional procedure in 1 case that displayed an unexpected residual nidus (5.6%). There were no complications from the intraoperative angiography procedure. Interpretation. Intraoperative assessment of technical results prior to wound closure offers the neurosurgeon the opportunity to resect or obliterate a vascular malformation completely, obviating a second operation.

We report a case of advanced gastric cancer producing Alpha Fetoprotein (AFP) with multiple liver metastases in which TS-1 is effective. Prognosis of gastric cancer producing AFP is well known to poor. A 74-year-old female was admitted complaining of anemia. She was diagnosed as having advanced gastric cancer with multiple liver metastases producing AFP by endoscopy, computed tomography and angiography. Her serum AFP level was 17,666 ng/ml and her serum CEA level was 5-2 ng/ml. After transarterial embolization (TAE), her family rejected her operation because it would not be curative. So, she was treated with TS-1, 40 mg, administered orally every day, followed by 14 days rest, as the first course. The next was TS-1, 80 mg orally administered for 6 courses. Her serum AFP level was down from 17,666 ng/ml to 94 ng/ml after 6 courses of TS-1. CT revealed that liver metastases did not change and endoscopy showed the primary lesion has diminished. Our report is the first to demonstrate that TS-1 is effective for patients with advanced gastric cancer producing AFP with multiple liver metastases.

This study examined the relationship between Chlamydia pneumoniae (C. pneumoniae) infection and the accelerated development of coronary artery disease (CAD) in patients with chronic renal failure (CRF).Two-hundred and fourteen patients undergoing coronary angiography, including 67 controls and 147 patients with CAD (97 without CRF and 50 with CRF), were enrolled in this study. Anti-C. pneumoniae specific IgG and IgA antibodies were measured using an enzyme-linked immunosorbent assay (ELISA).Coronary artery disease (expressed as CAD score) was more severe in patients with than without CRF (14.9 +/- 6.0 vs. 11.3 +/- 6.0, p0.01). Seropositive rates of IgG and IgA antibodies against C. pneumoniae were higher in all CAD patients than in the controls (76.2% vs. 44.8%, p0.001 for IgG; 59.9% vs. 40.3%, p0.01 for IgA). In both CAD subgroups, IgG seropositive rates were similarly elevated (82.0% and 73.2% vs. 44.8% for control, p0.001, respectively), whereas those of IgA were significantly elevated only in CAD with CRF (68.0% vs. 55.7% for control, p0.01). The mean antibody index of IgG was elevated in all CAD patients compared with the controls (1.9 +/- 1.0 vs. 1.3 +/- 0.9, p0.0001), but that of IgA was not (1.5 +/- 1.0 vs. 1.2 +/- 0.9). Levels of IgG were elevated in all patients with CAD compared with the control (2.4 +/- 1.1 and 1.8 +/- 1.0 vs. 1.3 +/- 0.9, p0.001 and p0.001, respectively), whereas those of IgA were elevated only in CAD with CRF (1.8 +/- 1.1 vs. 1.2 +/- 0.9, p0.05). Stepwise logistic regression analysis revealed that the elevated IgG antibody index was an independent risk factor for CAD regardless of CRF (odds ratios 1.9, 1.8, and 2.3), whereas the IgA index was a risk factor only in CAD with CRF (odds ratio 1.7).Chlamydia pneumoniae infection may be related to the accelerated CAD in patients with CRF, which was specifically suggested by an elevated IgA level. In other words, the prevalence of active C. pneumoniae infection is higher in patients with CAD and CRF than that in those with CAD without CRF.

We experienced 2 cases of septic children after open heart surgery. Both of them recovered by using exchange blood transfusion technique. We use irradiated and dialysed fresh blood for exchange blood transfusion. After this procedure, they recovered from sepsis, as the datas improving, white blood cell reduced from 19,700 +/- 3,710 to 8,200 +/- 2,360, CRP reduced from 5.46 +/- 1.65 to 1.89 +/- 0.70, T-Bil reduced from 7.61 +/- 2.66 to 3.02 +/- 0.89, and BUN reduced from 525.92 +/- 6.64 to 19.76 +/- 5.34. Furthermore, blood pressure and urine volume were stable between exchange blood transfusion, although after open heart surgery. Therefore this procedure has benefits for the compromised, septic patients, performed open heart surgery, because of its stability of the circulating circumstances. And using the irradiated and dialysed fresh blood provides stable condition eventhough under high dose catecholamine use.

A 67-year-old man, in whom a linear ulcer running from the duodenal bulb to the descending part had been noted 3 years previously, was admitted to our hospital because of abdominal pain and melena. Duodenoscopy revealed a bleeding giant longitudinal ulcer, which was more extensive than before. Tests for Helicobacter pylori (Hp) were negative. The ulcer was cured by endoscopic hemostasis and repeated blood transfusions. Attention must be paid to Hp-negative post-bulbar duodenal ulcers because of the frequent complications including hemorrhage.

We reviewed the records of outpatient chemotherapy for advanced lung cancer in our institution. Thirty-two patients received 122 courses of cisplatin-free chemotherapy as outpatient treatments. Before outpatient treatment, every patient received the first chemotherapy as an inpatient treatment and the dose of cytotoxic drugs was reduced accordingly when side effects were judged to be untolerable. Only 1 patient needed hospitalization because of pneumonia with grade IV neutropenia. The overall response included partial responses (PR) 18%, no change (NC) 55%, progressive disease (PR) 11% and the median survival from the start of outpatient chemotherapy was 384 days. The monthly average cost of medical care per inpatient was more than three times as high as that of outpatients. Cisplatin-free chemotherapy for advanced lung cancer should be given as outpatient treatment not only to maintain the quality of life of patients, but also to restrain the total cost of medical care and to use hospital beds efficiently.

Extracellular superoxide dismutase (EC-SOD) concentration was measured in sera from 141 patients with 20 forms of infantile diseases including IDDM, SLE and epilepsy, 31 healthy children (controls), and 21 healthy young men by an enzyme-linked immunosorbent assay using a polyclonal antibody against human lung EC-SOD. Serum from patients with IDDM and fever of unknown origin had a significantly (p0.05) lower concentration of EC-SOD than control serum. Part of sera from patients with the seven forms of diseases (SLE, viral infections, epilepsy, nephrosis, hyperthyroidism, hepatic disease, and Reye syndrome), on the other hand, had a greatly high concentration of EC-SOD, albeit not statistically significant. This SOD isoenzyme profile appears to be specific to each pediatric disease.

In July, 1999, an outbreak of vancomycin-resistant Enterococcus faecalis (VREF) with the vanB genotype occurred for the first time in Japan at Hokushin General Hospital, Nakano City, Nagano Prefecture. Four VREF strains were isolated from the clinical specimens of four inpatients, and 16 VREF strains were isolated by the screening of asymptomatic carriers and by surveillance of the hospital environment. All of the isolates possessed vanB genes. In a pulsed-field gel electrophoresis analysis, 19 out of 20 VREF isolates exhibited the indistinguishable restriction endonuclease digestion patterns of the chromosomal DNA. Additional investigation by Southern hybridization using the vanB probe implied that the vanB gene of these 19 isolates was encoded on a 110-kb plasmid. These findings indicate that the outbreak was principally caused by a single clone. The restriction endonuclease digestion patterns of the remaining single isolate was different from those of the other isolates. The vanB gene was encoded on the chromosome.

To evaluate radiation exposure to patients and radiologists during transcatheter arterial embolization(TAE) for hepatocellular carcinoma.In 39 TAE procedures performed at eight institutes, skin doses were evaluated with thermoluminescence dosimeters at the patient's back(entrance surface) and lower abdomen, and at the radiologist's forehead and abdomen. Real-time dosimeters were also used to evaluate patient skin dose.The patients' mean entrance surface dose was 973 +/- 681 mGy(range, 185 to 3543 mGy) with the mean fluoroscopic time of 21 minutes and 6 digital subtraction angiography(DSA) acquisitions. The dose at the patients' lower abdomen was 0.98 +/- 0.77 mGy. Doses for the radiologists were 0.04 +/- 0.04 mGy at the forehead and 0.15 +/- 0.19 mGy and 0.005 +/- 0.01 mGy at the abdomen over and under the apron, respectively. Fifty-six percent of the patients' skin dose was from DSA and 44% from fluoroscopy.Patient skin dose may occasionally exceed the dose for transient erythema. Because a patient may have repeated TAEs, skin doses or X-ray conditions should be recorded. The exposed doses of radiologists were considered to be acceptable with proper techniques. Further efforts to reduce radiation should be directed toward both DSA and fluoroscopy.

We conducted a prospective study to examine the influence of discontinuing peak flow monitoring (PFM) in stable asthmatics who had already been properly educated and were monitoring their own peak expiratory flows (PEF). All subjects had been performing PFM for at least 3 months prior to their entry into the study, and PFM was then stopped for a period of 3 months. Comparisons of endpoints were made between a period of 3 months prior to, and after discontinuing PFM. Forty patients with a mean age of 52 were studied. Only one patient experienced a single emergency room visit either before or after discontinuing PFM. Short courses of oral steroids were administered in 6 patients (15%), both before and after discontinuing PFM. There was no significant change in pulmonary function, beta 2-agonist use and asthma symptoms during a 3-month period before and after discontinuing PFM. These results suggest that simply continuing PFM in stable, educated asthmatics may have little impact on asthma control, although its long term influence should be carefully examined.

The aim of this study was to compare the detectability and image contrast of metastatic brain tumors depicted by T1-weighted MR imaging (T1WI) with the magnetization transfer (MT) technique after the administration of a standard dose(MT-SD-T1WI) or T1WI without MT after the administration of a double dose of gadoteridol(DD-T1WI). We also assessed the usefulness of enhanced fluid attenuated inversion recovery (FLAIR) for depicting very small metastatic tumors.Forty-six MRI procedures were performed in 31 patients with metastatic brain tumors that had been diagnosed clinically and radiologically. An incremental dose technique was used with intravenous injections of 0.1 and 0.1 mmol/kg of gadoteridol. In 28 MRI procedures, enhanced FLAIR was carried out after an MT-SD-T1WI study.Detectability was significantly greater with both MT-SD-T1WI and DD-T1WI than with SD-T1WI. However, there was no significant difference between MT-SD- and DD-T1WI. Although an MT pulse increased the contrast between the enhanced tumor and white matter, the contrast between edema and white matter was decreased. Both MT-SD- and DD-T1WI showed small but conspicuous enhanced foci, but we could not determine whether these were vessels or small metastases on the brain surface. However, enhanced FLAIR only demonstrated foci that were thought to be small metastases.MT-SD- and DD-T1WI had equal ability to detect metastatic brain tumors. Enhanced FLAIR was useful for assessing very small metastases on the brain surface.

We administered neoadjuvant chemotherapy by a selective intra-arterial infusion method using a trans-radial approach in patients with advanced breast cancer (stage III and stage IV). The trans-radial approach uses the arterial flow, based on the Seldinger technique. In this method, the radial artery is cannulated, and epirubucin is infused into the artery that carries blood from the subclavical artery to the breast. We have used this method in 4 cases thus far. Two of the patients received a single intra-arterial infusion of epirubicin. The other 2 patients were catheterized before they received chemotherapy by intra-arterial infusion. This technique decreased the pain or discomfort caused by the catheterizations during chemotherapy in all 4 cases. However, the currently available catheters are not always able to approach the artery flowing into the breast, thus the protocol will need to be refined.

Transbronchial needle aspiration (TBNA) is a bronchoscopic technique to obtain cytologic and histologic specimen from deep site of bronchial wall. We investigated the utility and safety of TBNA in 200 patients who had mass lesions in the lung or in the mediastinum. 101 patients had submucosal or peribronchial malignant lesions (central malignancy) and TBNA was the only diagnostic method in 28 patients (28%). 39 patients had peripheral malignant lesions (peripheral malignancy) and TBNA was the only diagnostic method in 12 patients (31%). The other 60 patients had benign lesions and TBNA was diagnostic in only 5 patients (8%); bronchogenic cyst in 2, tuberculous lymph adenitis in 1, parathyroid adenoma in 1 and lung abscess in 1. In central malignancy, the yield of TBNA as exclusive means of diagnosis was higher for mediastinal tumor than for lung cancer. In peripheral malignancy it was higher for metastatic lung tumor than for primary lung tumor. In order to stage patients of lung cancer, we sampled 39 lymph nodes and 21 of them were proved to be positive. TBNA was thought to be of greatest value in the diagnosis of peritracheal mediastinal tumor and peribronchial metastatic lung tumor and in the staging of lung cancer. We used 19-gauge transbronchial histology needle in 8 patients and 2 cases were diagnostic. Low diagnostic yields were probably due to the lack of our experience and it was expected that training on this technique would increase diagnostic utility of the histology needle. No significant complications occurred and all patients tolerated TBNA well.

We have recently observed a rare case of pheochromocytoma associated with meningioma. To determine the mechanism of such a coexistence in this particular case, we compared the constitutional and pheochromocytoma genotypes of the patient using polymorphic four DNA markers, and we found a loss of heterozygosity at the D1S7 locus. A loss of heterozygosity at this locus has previously been reported by Mathew et al. in pheochromocytoma patients, and our results were in agreement with that study. Therefore the allelic deletion at the D1S7 locus may be an important step in the tumorigenesis of pheochromocytoma in this case.

Standard reference ranges for all laboratory test values are mandatory. This study was designed to establish a reference range for blood vitamin B1 levels, since the normal range has not been determined in the Japanese population. We founded the Japan Committee for Vitamin Laboratory Standards, which was incorporated with the Vitamin Society of Japan and the Japanese Society of Nutrition and Food Science. We standardized whole blood vitamin B1 levels using three HPLC techniques (post-column reverse-phase HPLC, pre-column reverse-phase HPLC, and precolumn GP-HPLC). The reference range was obtained in 54 volunteers administered a 1,800 kcal diet with 2 mg of vitamin B1 (1.74 mg measured) daily to avoid marginal vitamin B1 deficiency in the population. The range for each assay was 26-47, 28-51, and 28-56 ng/ml, respectively. Our data suggest that 26-28 ng/ml is the lower limit of normal for whole blood vitamin B1, but further studies in a larger population are needed in order to obtain more definitive results.

We genetically analyzed a case of hypofibrinogenemia that showed no bleeding or thrombotic tendency. Direct sequencing of a polymerase chain reaction-amplified gamma-chain gene segment showed a novel nucleotide substitution. This heterozygous mutation encodes both Cys (TGT) and Arg (CGT) at residue 153. To examine the basis for the fibrinogen deficiency, we prepared expression vectors containing mutant gamma-chain DNAs encoding gamma153R and gamma153A for in vitro expression in Chinese hamster ovary (CHO) cells. Enzyme-linked immunosorbent assay and immunoblot analysis of the culture media and cell lysates showed that CHO cells transfected with gamma153R or gamma153A synthesized the variant gamma-chain, but did not secrete variant fibrinogen into the culture medium. Metabolic pulse-chase experiments showed that fibrinogen assembly was impaired when either variant gamma-chain was expressed. In cells expressing normal fibrinogen, assem- bly intermediates and intact fibrinogen were seen in cell lysates prepared after short (3 minutes) or long (1 hour) incubation with (35)S-methionine. Neither intermediates nor intact fibrinogen was seen with the variant gamma-chains. These data suggest that gamma-chains have an important early role in fibrinogen assembly. Thus, our results support the model for fibrinogen assembly proposed by Huang et al (J Biol Chem 268:8919, 1993), in which the first step in assembly is the formation of alphagamma or betagamma dimers, or both. This model implies that gammaCys153 has a critical role in the formation of these early assembly intermediates. We concluded that the gamma153Cys--Arg substitution does not allow fibrinogen assembly and secretion, and this is manifest in vivo as a fibrinogen deficiency. We designated this variant as fibrinogen Matsumoto IV.