Susceptibility of patients receiving chemotherapy for haematological malignancies to scabies.

BACKGROUND: Scabies is a contagious dermatosis. The risk factors for its transmission remain unclear. A scabies outbreak, involving patients who were receiving chemotherapy for haematological malignancies, occurred at our hospital. METHODS: The outbreak population was analysed to determine whether the incidence of scabies was higher among contact patients receiving chemotherapy for haematological malignancies. RESULTS: A patient with crusted scabies was the index case, and 18 of 78 contact healthcare workers (HCWs) and 22 of 135 contact patients were diagnosed with classical scabies. Ten of 17 contact patients with haematological malignancies and 12 of 118 contact patients with other diseases were infected with scabies. The incidence rate was significantly higher among the patients with haematological malignancies (P<0.001). The patients with haematological malignancies had a significantly lower mean minimum neutrophil count than those with other diseases (1159/µL vs 3761/µL, P=0.0012). Most haematological patients did not require special nursing assistance, suggesting that the higher incidence of scabies among these patients resulted from their immunodeficiency rather than greater skin-to-skin contact with infected HCWs. CONCLUSION: Our study suggests that patients receiving chemotherapy for haematological malignancies are more susceptible to scabies than patients with other diseases, and require stricter protection.

Structural Transformation and Melting in Gold Shock Compressed to 355 GPa.

Gold is believed to retain its ambient crystal structure at very high pressures under static and shock compression, enabling its wide use as a pressure marker. Our in situ x-ray diffraction measurements on shock-compressed gold show that it transforms to the body-centered-cubic (bcc) phase, with an onset pressure between 150 and 176 GPa. A liquid-bcc coexistence was observed between 220 and 302 GPa and complete melting occurs by 355 GPa. Our observation of the lower coordination bcc structure in shocked gold is in marked contrast to theoretical predictions and the reported observation of the hexagonal-close-packed structure under static compression.

Identification of ABCG2 as an Exporter of Uremic Toxin Indoxyl Sulfate in Mice and as a Crucial Factor Influencing CKD Progression.

Chronic kidney disease (CKD) patients accumulate uremic toxins in the body, potentially require dialysis, and can eventually develop cardiovascular disease. CKD incidence has increased worldwide, and preventing CKD progression is one of the most important goals in clinical treatment. In this study, we conducted a series of in vitro and in vivo experiments and employed a metabolomics approach to investigate CKD. Our results demonstrated that ATP-binding cassette transporter subfamily G member 2 (ABCG2) is a major transporter of the uremic toxin indoxyl sulfate. ABCG2 regulates the pathophysiological excretion of indoxyl sulfate and strongly affects CKD survival rates. Our study is the first to report ABCG2 as a physiological exporter of indoxyl sulfate and identify ABCG2 as a crucial factor influencing CKD progression, consistent with the observed association between ABCG2 function and age of dialysis onset in humans. The above findings provided valuable knowledge on the complex regulatory mechanisms that regulate the transport of uremic toxins in our body and serve as a basis for preventive and individualized treatment of CKD.

The Impact of Alemtuzumab and Basiliximab Induction on Patient Survival and Time to Bronchiolitis Obliterans Syndrome in Double Lung Transplantation Recipients.

We examined the effect of alemtuzumab and basiliximab induction therapy on patient survival and freedom from bronchiolitis obliterans syndrome (BOS) in double lung transplantation. The United Network for Organ Sharing database was reviewed for adult double lung transplant recipients from 2006 to 2013. The primary outcome was risk-adjusted all-cause mortality. Secondary outcomes included time to BOS. There were 6117 patients were identified, of whom 738 received alemtuzumab, 2804 received basiliximab, and 2575 received no induction. Alemtuzumab recipients had higher lung allocation scores compared with basiliximab and no-induction recipients (41.4 versus 37.9 versus 40.7, p < 0.001) and were more likely to require mechanical ventilation before to transplantation (21.7% versus 6.5% versus 6.2%, p < 0.001). Median survival was longer for alemtuzumab and basiliximab recipients compared with patients who received no induction (2321 versus 2352 versus 1967 days, p = 0.001). Alemtuzumab (hazard ratio 0.80, 95% confidence interval 0.67-0.95, p = 0.009) and basiliximab induction (0.88, 0.80-0.98, p = 0.015) were independently associated with survival on multivariate analysis. At 5 years, alemtuzumab recipients had a lower incidence of BOS (22.7% versus 55.4 versus 55.9%), and its use was independently associated with lower risk of developing BOS on multivariate analysis. While both induction therapies were associated with improved survival, patients who received alemtuzumab had greater median freedom from BOS.

Cysteine amide adduct formation from carboxylic acid drugs via UGT-mediated bioactivation in human liver microsomes.

Although chemical trapping has been widely used to evaluate cytochrome P450-mediated drug bioactivation, thus far, only a few in vitro-trapping studies have been performed on UDP-glucuronosyltransferase (UGT)-mediated drug bioactivation. In this study, we used cysteine (Cys) as trapping agent to gain new insights into the UGT-mediated bioactivation involving acyl glucuronides of carboxylic acid drugs. Diclofenac, ketoprofen and ibuprofen were incubated in human liver microsomes with UDPGA and Cys, followed by analysis using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The N-acyl-Cys amide adduct of diclofenac was characterized by mass analysis and was detectable even in photodiode array analysis. Our data indicated that the formation of such adducts reflects the reactivity of the corresponding acyl glucuronides. In addition, it was suggested that the adduct formation requires an N-terminal Cys moiety with both a free amine and a free thiol group, from the results using various cysteine derivatives. We propose that the S-acyl-Cys thioester adduct can form via transacylation of an acyl glucuronide and can then form to an N-acyl-Cys amide adduct through intramolecular S- to N-acyl rearrangement. This series of the reactions has important implications as a possible bioactivation mechanism for covalent binding of carboxylic acid drugs to macromolecules.

Temporal models for mitotic phase labelling.

With the widespread use of time-lapse data to understand cellular function, there is a need for tools which facilitate high-throughput analysis of data. Fluorescence microscopy of genetically engineered cell lines in culture can be used to visualise the progression of these cells through the cell cycle, including distinctly identifiable sequential stages of cell division (mitotic phases). We present a system for automated segmentation and mitotic phase labelling using temporal models. This work takes the novel approach of using temporal features evaluated over the whole of the mitotic phases rather than over single frames, thereby capturing the distinctive behaviour over the phases. We compare and contrast three different temporal models: Dynamic Time Warping, Hidden Markov Models, and Semi Markov Models. A new loss function is proposed for the Semi Markov model to make it more robust to inconsistencies in data annotation near transition boundaries. The models are tested under two different experimental conditions to explore robustness to changes in biological conditions.

Single donor-derived strongyloidiasis in three solid organ transplant recipients: case series and review of the literature.

Donor-derived Strongyloides stercoralis infections in transplant recipients are a rare but recognized complication. In this case series, we report donor-derived allograft transmission of Strongyloides in three solid organ transplant recipients. Following detection of infection in heart and kidney-pancreas recipients at two different transplant centers, a third recipient from the same donor was identified and diagnosed. S. stercoralis larvae were detected in duodenal aspirates, bronchial washings, cerebrospinal fluid, urine and stool specimens. Treatment with ivermectin and albendazole was successful in two of the three patients identified. The Centers for Disease Control and Prevention was contacted and performed an epidemiologic investigation. Donor serology was strongly positive for S. stercoralis antibodies on retrospective testing while all pretransplant recipient serum was negative. There should be a high index of suspicion for parasitic infection in transplant recipients and donors from endemic regions of the world. This case series underscores the need for expanded transplant screening protocols for Strongyloides. Positive serologic or stool tests should prompt early treatment or prophylaxis in donors and recipients as well as timely notification of organ procurement organizations and transplant centers.

Epidemiology and outcomes of deep surgical site infections following lung transplantation.

We conducted a retrospective study of deep surgical site infections (SSIs) among consecutive patients who underwent lung transplantation (LTx) at a single center from 2006 through 2010. Thirty-one patients (5%) developed SSIs at median 25 days after LTx. Empyema was most common (42%), followed by surgical wound infections (29%), mediastinitis (16%), sternal osteomyelitis (6%), and pericarditis (6%). Pathogens included Gram-positive bacteria (41%), Gram-negative bacteria (41%), fungi (10%) and Mycobacterium abscessus, Mycoplasma hominis and Lactobacillus sp. (one each). Twenty-three percent of SSIs were due to pathogens colonizing recipients' native lungs at time of LTx, suggesting surgical seeding as a source. Patient-related independent risk factors for SSIs were diabetes and prior cardiothoracic surgery; procedure-related independent risk factors were LTx from a female donor, prolonged ischemic time and number of perioperative red blood cell transfusions. Mediastinitis and sternal infections were not observed among patients undergoing minimally invasive LTx. SSIs were associated with 35% mortality at 1 year post-LTx. Lengths of stay and mortality in-hospital and at 6 months and 1 year were significantly greater for patients with SSIs other than empyema. In conclusion, deep SSIs were uncommon, but important complications in LTx recipients because of their diverse microbiology and association with increased mortality.

A method of reducing background radiance for emissivity-compensated radiation thermometry of silicon wafers.

We studied the spectral and directional emissivities of silicon wafers using an optical polarization technique. Based on simulation and experimental results, we developed two radiation thermometry methods for silicon wafers: one is based on the polarized emissivity-invariant condition and the other is based on the relationship between the ratio of the p- and s-polarized radiance and the polarized emissivity. These methods can be performed at temperatures above 600 °C and over a wide wavelength range (0.9-4.8 µm), irrespective of the dielectric film thickness and the substrate resistivity, which depends on the dopant concentration. The temperature measurements were estimated to have expanded uncertainties (k = 2) of less than 5 °C. With a view to practically applying these methods, we investigated a method to reduce the intense background radiance produced by high-intensity heating lamps. We found that the background radiance can be greatly reduced by using a radiometer that is sensitive to wavelengths of 4.5 or 4.8 µm and suitable geometrical arrangements of a quartz plate. This opens up the possibility of using the two proposed radiation thermometry methods in practical applications.

Predictors and outcomes of health-related quality of life in caregivers of cardiothoracic transplant recipients.

Cardiothoracic transplant programs generally require that transplant recipients have family caregivers to assist them posttransplant. The burden of caregiving on the family members remains poorly understood. If caregivers' well-being is compromised by caregiving, it may bode poorly for transplant recipients' own health in the long-term posttransplant. We examined caregiver health-related quality of life (HRQOL) during the first year after their family member's transplant, its predictors and its relationship to subsequent patient survival. Adult (aged 18+) caregivers of 242 cardiothoracic transplant recipients (lung = 134; heart = 108) completed assessments of demographics, psychosocial characteristics and caregiver burden at 2 months posttransplant, and HRQOL at 2, 7 and 12 months posttransplant. Recipients' survival time was obtained from medical records. Caregiver HRQOL was generally high across the first-year posttransplant in emotional and social functioning; caregiver physical functioning significantly worsened. There were no differences by type of recipient transplant. Greater caregiver burden predicted poorer caregiver HRQOL in several physical domains at 12 months posttransplant. Transplant recipients whose caregivers had lower perceived general health at 12 months posttransplant showed poorer survival rates during the subsequent 7 years of follow up. Transplant teams should identify those caregivers at risk for poorer general health posttransplant to maximize positive outcomes for the entire family.

Lung transplantation in patients with prior cardiothoracic surgical procedures.

The full spectrum of prior cardiothoracic procedures in lung transplant candidates and the impact of prior procedures on outcomes after lung transplantation (LTx) remain unknown, though the impact is considered to be large. Patients transplanted at our institution from 2004 to 2009 were identified (n = 554) and divided into two groups: patients who had undergone cardiothoracic surgical (CTS) procedures prior to LTx (n = 238) and patients who had not (non-CTS: n = 316). Our primary endpoint was survival. Secondary endpoints included allograft function and the incidence of major complications including reexploration due to bleeding, prolonged ventilation, renal insufficiency and primary graft dysfunction. Long-term survival was not significantly different between the groups whereas postoperative bleeding, nerve injury, respiratory and renal complications were higher in the CTS group. Posttransplant peak FEV1 was lower in the CTS group (73.4% vs. 86.9%, p < 0.05). In multivariate analysis, performance of a chemical pleurodesis procedure and prolonged cardiopulmonary bypass were significantly associated with mortality (OR, 1.7; CI, 1.5-2.0; p < 0.005). Our results suggest that patients with LTx and prior CTS remain technically challenging and experience worse outcomes than patients without prior CTS. A surgical strategy to minimize cardiopulmonary bypass time is critical for these challenging LTx patients.

Successful lung retransplantation after extended use of extracorporeal membrane oxygenation as a bridge.

Redo lung transplantation remains a major clinical challenge and its indication for patients with early allograft dysfunction is difficult to determine. We report a case of potentially fatal early allograft dysfunction owing to possible acute cellular rejection after single lung transplantation in a patient who underwent redo double lung transplantation after successful use of extracorporeal membrane oxygenation as a bridge, which resulted in a successful outcome.

Successful double lung transplantation in a patient with bilateral pulmonary and sinus aspergillomas.

The outcome of patients with aspergilloma undergoing lung transplantation is not completely known, but anecdotal reports of poor outcome after transplant have discouraged this practice. We present a 45-year-old female with pulmonary sarcoidosis complicated by bilateral pulmonary and sinus aspergillomas who underwent successful double lung transplantation. Patients with aspergillomas can receive lung transplantation, provided that there is sufficient technical expertise to explant the infected lungs with minimal chance of chest wall contamination, and aggressive antifungal therapy is used post transplantation.

Lactobacillus probiotic use in cardiothoracic transplant recipients: a link to invasive Lactobacillus infection?

Organisms contained in probiotics are generally regarded as non-pathogenic and safe to administer. However, increasing reports of probiotic-associated infection raise concern over the safety of these products. We report a case of Lactobacillus empyema in a human immunodeficiency virus-infected lung transplant recipient receiving a probiotic containing Lactobacillus rhamnosus GG. We compare the epidemiology of Lactobacillus infections in heart and lung transplant recipients at our institution before and after the introduction of this probiotic, and discuss the potential mechanism for Lactobacillus within the probiotic to cause infections and disseminate.

Mycoplasma hominis pericarditis in a lung transplant recipient: review of the literature about an uncommon but important cardiothoracic pathogen.

Purulent pericarditis due to Mycoplasma hominis is rare, and is usually associated with mediastinitis or pleuritis following cardiothoracic surgery. We report the first case to our knowledge of isolated purulent pericarditis caused by M. hominis in a lung transplant recipient and review previously reported cases of this disease.

Alemtuzumab induction prior to cardiac transplantation with lower intensity maintenance immunosuppression: one-year outcomes.

Induction therapy with alemtuzumab (C-1H) prior to cardiac transplantation (CTX) may allow for lower intensity maintenance immunosuppression. This is a retrospective study of patients who underwent CTX at a single institution from January 2001 until April 2009 and received no induction versus induction with C-1H on a background of tacrolimus and mycophenolate. Those with C-1H received dose-reduced calcineurin inhibitor and no steroids. A total of 220 patients were included, 110 received C-1H and 110 received no induction. Recipient baseline characteristics, donor age and gender were not different between the two groups. Mean tacrolimus levels (ng/mL) for C-1H versus no induction: months 1-3 (8.5 vs. 12.9), month 4-6 (10.2 vs. 13.0), month 7-9 (10.2 vs. 11.9) and month 10-12 (9.9 vs. 11.3) were all significantly lower for the C-1H group, p < 0.001. There were no differences between the C-1H and no induction groups at 12 months for overall survival 85.1% versus 93.6% p = 0.09, but freedom from significant rejection was significantly higher for the C-1H group, 84.5% versus 51.6%, p < 0.0001. In conclusion, induction therapy after CTX with C-1H results in a similar 12 month survival, but a greater freedom from rejection despite lower calcineurin levels and without the use of steroids.

Correlation of axillary osmidrosis to a SNP in the ABCC11 gene determined by the Smart Amplification Process (SmartAmp) method.

Axillary osmidrosis (AO) is caused by apocrine glands secretions that are converted to odouriferous compounds by bacteria. A potential link between AO and wet earwax type has been implicated by phenotype-based analysis. Recently, a non-synonymous single nucleotide polymorphism (SNP) 538G> A (Gly180Arg) in the human adenosine triphosphate (ATP)-binding cassette (ABC) transporter ABCC11 gene was found to determine the type of earwax. In this context, we examined a relationship between the degree of AO and the ABCC11 genotype. We have genotyped the SNP 538G> A in a total of 82 Japanese individuals (68 volunteers and 14 AO patients) by both DNA sequencing and the recently developed Smart Amplification Process (SmartAmp). The degree of AO in Japanese subjects was associated with the genotype of the ABCC11 gene as well as wet earwax type. In most AO patients investigated in this study, the G/G and G/A genotypes well correlated with the degree of AO, whereas A/A did not. The specific SmartAmp assays developed for this study provided genotypes within 30 min directly from blood samples. In East Asian countries, AO is rather infrequent. Although the judgement of the degree of AO prevalence is subjective, the SNP 538G> A in ABCC11 is a good genetic biomarker for screening for AO. The SmartAmp method-based genotyping of the ABCC11 gene would provide an accurate and practical tool for guidance of appropriate treatment and psychological management for patients.

Orbital magnetic moment in Ir doped CaMnO(3).

The magnetism of CaMn(0.55)Ir(0.45)O(3) has been studied using the magnetic Compton scattering technique. The analysis of the magnetic Compton profile shows that the spin moments of Mn and Ir form an antiparallel configuration, establishing ferrimagnetism. Moreover, the experimental results indicate the existence of an orbital moment 0.2  µ(B)/f.u.. The possible model for these results has been discussed under the framework of the localized electron model by taking account of the electronic states of the Ir(4+) ion.

MRP class of human ATP binding cassette (ABC) transporters: historical background and new research directions.

1. The adenosine triphosphate (ATP) binding cassette (ABC) transporters form one of the largest protein families encoded in the human genome, and more than 48 genes encoding human ABC transporters have been identified and sequenced. It has been reported that mutations of ABC protein genes are causative in several genetic disorders in humans. 2. Many human ABC transporters are involved in membrane transport of drugs, xenobiotics, endogenous substances or ions, thereby exhibiting a wide spectrum of biological functions. According to the new nomenclature of human ABC transporter genes, the 'ABCC' gene sub-family comprises three classes involving multidrug resistance-associated proteins (MRPs), sulfonylurea receptors (SURs), and a cystic fibrosis transmembrane conductance regulator (CFTR). 3. Molecular cloning studies have identified a total of ten members of the human MRP class including ABCC11, ABCC12, and ABCC13 (pseudo-gene) that have recently been characterized. 4. This review addresses the historical background and discovery of the ATP-driven xenobiotic export pumps (GS-X pumps) encoded by MRP genes, biological functions of ABC transporters belonging to the MRP class, and regulation of gene expression of MRPs by oxidative stress.

Sensitivity and specificity of lung cancer screening using chest low-dose computed tomography.

Lung cancer screening programmes using chest X-ray and sputum cytology are routinely performed in Japan; however, the efficacy is insufficient. Screening using low-dose computed tomography (CT) is a more effective approach and has the potential to detect the disease more accurately. A total of 7183 low-dose CT screening tests for 4689 participants and 36 085 chest X-ray screening tests for 13 381 participants were conducted between August 1998 and May 2002. Sensitivity and specificity of lung cancer screening were calculated by both the detection method and the incidence method by linkage of the screening database and the Cancer Registry database. The preclinical detectable phase was assumed to be 1 year. Sensitivity and specificity by the detection method were 88.9 and 92.6% for low-dose CT and 78.3 and 97.0% for chest X-ray, respectively. Sensitivity of low-dose CT by the incidence method was 79.5%, whereas that of chest X-ray was 86.5%. Lung cancer screening using low-dose CT resulted in higher sensitivity and lower specificity than traditional screening according to the detection method. However, sensitivity by the incidence method was not as high as this. These findings demonstrate the potential for overdiagnosis in CT screening-detected cases.