Indicative factors for surgical or angiographic intervention in hemodynamically stable patients with blunt abdominal trauma: A retrospective cohort study.

INTRODUCTION: The standard of care for intraperitoneal injury in hemodynamically stable patients after blunt abdominal trauma has been replaced by non-operative management (NOM). However, selective NOM, depending on the situation, seems necessary in determining the treatment plan. In this study, we attempted to identify risk factors for surgical or angiographic intervention (SAI) in hemodynamically stable blunt abdominal trauma patients. METHODS: This retrospective study which included adult patients who were brought to a regional trauma center was conducted from March 2015 to October 2019. We evaluated the characteristics of blunt abdominal trauma patients and analyzed factors that were related to the requirement of SAI in these patients. Patients were divided into SAI and conservative management (CM) groups. RESULTS: We reviewed 1,176 patients, and after exclusions, of whom 248 blunt abdominal trauma and free fluid observed on CT were identified. The mean pulse rate was higher in the SAI than in the CM (P=0.025). Laboratory findings showed that lactate and delta neutrophil index (DNI) levels were higher in the SAI than in the CM (P=0.002 and 0.026 respectively). Additionally, the mean free fluid size in the SAI (85.69mm) was significantly larger than that in the CM (68.12mm; P=0.001), and blush was more frequently observed in the SAI (P<0.001). In multivariate analysis, only blush was an independent prognostic factor for SAI (OR 11.7, 95% CI, 5.1-30.8, P<0.001). CONCLUSION: In hemodynamically stable patients with blunt abdominal trauma, blush but also high lactate and DNI are associated with the requirement of interventional radiology and/or surgery.

Empowerment of nurses in antibiotic stewardship: a social ecological qualitative analysis.

BACKGROUND: Inappropriate antibiotics use and antimicrobial resistance (AMR) are increasingly becoming global health issues of great concern. Despite the established antibiotic stewardship programmes (ASPs) in many countries, limited efforts have been made to engage nurses and clearly define their roles in ASPs. AIM: An exploratory qualitative study was conducted to understand the facilitators and barriers that impact nurses' involvement and empowerment in antibiotic stewardship. METHODS: Focus group discussions (FGDs) were conducted with purposively sampled nurses from three major public hospitals in Singapore. FGDs were audio-recorded and transcribed verbatim. Data were analysed using Applied Thematic Analysis and interpreted using the Social Ecological Model. FINDINGS: At the intrapersonal level, nurses felt empowered in carrying out their roles in antibiotic administration. They saw themselves as gatekeepers to ensure that the prescribed antibiotics were administered appropriately. However, nurses felt they lacked the knowledge and expertise in antibiotic use and AMR prevention. At the interpersonal level, this deficit in knowledge and expertise in antibiotic use impacted how they were perceived by patients and caregivers as well as their interactions with the primary care team when voicing outpatient safety concerns and antibiotic administration suggestions. At the organizational level, nurses relied on drug administration guidelines to ensure appropriate antibiotic administration and as a safety net when physicians questioned their clinical practice. At the community level, nurses felt there was a lack of awareness and knowledge on antibiotic use among the general population. CONCLUSION: These findings provide important insights to harness the contributions of nurses, and to formally acknowledge and enlarge their roles in ASPs.

An electronic patient-reported outcomes measurement system in paediatric orthopaedics.

PURPOSE: The purpose of the study was to evaluate the reliability, review differences and assess patient satisfaction of electronic patient-reported outcome measures (PROMs) compared with paper PROMs. METHODS: Participants between 12 and 19 years of age with a knee-related primary complaint were randomized into two groups. Group 1 completed paper PROMs followed by electronic, while Group 2 received the electronic followed by paper. PROMs included the Pediatric International Knee Documentation Committee (Pedi-IKDC), Hospital for Special Surgery (HSS) Pediatric Functional Activity Brief Scale (HSS Pedi-FABS), Tegner Activity Level Scale, Visual Analogue Scale (VAS), PedsQL Teen and a satisfaction survey. RESULTS: In all, 87 participants were enrolled with one excluded due to incomplete PROMs. Of the 86 participants, 54 were female and 32 were male with an average age of 14.3 years (12 to 18). A high degree of reliability was found when comparing the paper and electronic versions of the Pedi-IKDC (0.946; p < 0.001), HSS Pedi-FABS (0.923; p < 0.001), PedsQL Teen (0.894; p < 0.001), Tegner Activity Level Scale before injury (0.848; p < 0.001) and the Tegner Activity Level Scale after (0.930; p < 0.001). Differences were noted between the VAS scores, with paper scores being significantly higher than electronic (5.3 versus 4.6; p < 0.001). While not significant, a trend was noted in which electronic PROMs took, overall, less time than paper (10.0 mins versus 11.2 mins; p = 0.096).Of all participants, 69.8% preferred the electronic PROMs, 67.4% felt they were faster, 93.0% stated they would complete forms at home prior to appointments and 91.8% were not concerned about the safety/privacy of electronic forms. CONCLUSION: PROMs captured electronically were reliable when compared with paper. Electronic PROMs may be quicker, will not require manual scoring and are preferred by patients. LEVEL OF EVIDENCE: II.

Combined Heart and Kidney Transplantation: A 23-Year Experience.

BACKGROUND: We report clinical experience with combined heart and kidney transplantation (HKTx) over a 23-year time period. METHODS: From June 1992 to August 2015, we performed 83 combined HKTx procedures at our institution. We compared the more recent cohort of 53 HKTx recipients (group 2, March 2009 to August 2015) with the initial 30 previously reported HKTx recipients (group 1, June 1992 to February 2009). Pre-operative patient characteristics, peri-operative factors, and post-operative outcomes including survival were examined. RESULTS: The baseline characteristics of the two groups were similar, except for a lower incidence of ethanol use and higher pre-operative left-ventricular ejection fraction, cardiac output, and cardiac index in group 2 when compared with group 1 (P = .007, .046, .037, respectively). The pump time was longer in group 2 compared with group 1 (153.30 ± 38.68 vs 129.60 ± 37.60 minutes; P = .007), whereas the graft ischemic time was not significantly different between the groups, with a trend to a longer graft ischemic time in group 2 versus group 1 (195.17 ± 45.06 vs 178.07 ± 52.77 minutes; P = .056, respectively). The lengths of intensive care unit (ICU) and hospital stay were similar between the groups (P = .083 and .39, respectively). In addition, pre-operative and post-operative creatinine levels at peak, discharge, 1 year, and 5 years and the number of people on post-operative dialysis were similar between the groups (P = .37, .75, .54, .87, .56, and P = .139, respectively). Overall survival was not significantly different between groups 2 and 1 for the first 5 years after transplant, with a trend toward higher survival in group 2 (P = .054). CONCLUSIONS: The most recent cohort of combined heart and kidney transplant recipients had similar ICU and hospital lengths of stay and post-operative creatinine levels at peak, discharge, and 1 and 5 years and a similar number of patients on post-operative dialysis when compared with the initial cohort. Overall survival was not significantly different between the later and earlier groups, with a trend toward higher overall survival at 5 years in the more recent cohort of patients. In selected patients with co-existing heart and kidney failure, combined heart and kidney transplantation is safe to perform and has excellent outcomes.

Single monosomy as a relatively better survival factor in acute myeloid leukemia patients with monosomal karyotype.

Monosomal karyotype (MK) defined by either ⩾2 autosomal monosomies or single monosomy with at least one additional structural chromosomal abnormality is associated with a dismal prognosis in patients with acute myeloid leukemia (AML). It was detected in 174 of 3041 AML patients in South Korean Registry. A total of 119 patients who had received induction therapy were finally analyzed to evaluate the predictive factors for a positive prognosis. On multivariate analysis, single monosomy, the absence of abn(17p), ⩾10% of cells with normal metaphase and the achievement of a complete remission (CR) after induction therapy were significant factors for more favorable outcomes. Especially, single monosomy remained as a significantly independent prognostic factor for superior survival in both patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR and who did not. Allo-HSCT in CR improved overall survival significantly only in patients with a single monosomy. Our results suggest that MK-AML may be biologically different according to the karyotypic subtype and that allo-HSCT in CR should be strongly recommended to patients with a single monosomy. For other patients, more prudent treatment strategies should be examined. Furthermore, the biological mechanism by which a single monosomy influences survival should be investigated.

Attitudinal concordance toward uptake and disclosure of genetic testing for cancer susceptibility in patient-family member dyads.

Decisions for cancer susceptibility genetic testing (CSGT) uptake and dissemination of results occur within the family context. A national survey was performed with 990 patient-family member dyads (participation rate:76.2%), with paired questionnaires examining attitudes toward CSGT uptake and disclosure of results in response to a hypothetical scenario in which a reliable CSGT was available for the specific cancer a patient was being treated. While most patients and family members responded they would uptake or recommend CSGT if available, concordance between the dyads was poor for both patient's testing (agreement rate 77.5%, weighted κ=0.09) and first-degree relatives' testing(agreement rate 78.0%, weighted κ=0.09). Most patients (93.2%) and family members (92.9%) indicated that patients should disclose positive CSGT results to family members, with dyadic agreement of 89.1% (κ=0.15). However, there were substantial disagreement regarding when disclosure should take place, who should make the disclosure (the patient or the health care professionals), and to whom the results should be disclosed. Patients and family members may hold different attitudes toward CSGT uptake of and disclosure of results within the family. Our findings reinforce the need for a family system approach to incorporate perspectives of patients as well as their family members.

Influence of enzyme and transporter polymorphisms on trough imatinib concentration and clinical response in chronic myeloid leukemia patients.

BACKGROUND: This study explored the impact of genetic polymorphisms in cytochrome P450 (CYP) enzymes and transporters on the plasma trough concentration of imatinib mesylate (IM) and clinical response in chronic myeloid leukemia (CML). PATIENTS AND METHODS: In total, 82 patients with CML who had been administered 400 mg IM daily for over 6 months were genotyped for 11 single-nucleotide polymorphisms in nine genes (CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC22A1, SLC22A2 and ABCG2) using blood samples. The trough imatinib concentration and clinical responses were assessed 6 months after the initiation of IM therapy. RESULTS: The CC, CA and AA genotypes in ABCG2 421C>A gave significantly different frequencies for the major molecular response (MMR) (P = 0.02). However, no significant differences were found between the genotypes of the CYP enzymes and transporters identified in this study and the imatinib plasma trough concentrations and clinical response frequencies, except for the correlation of ABCG2 with MMR. CONCLUSIONS: The results of the present study may indicate that the ABCG 421C>A genetic polymorphism influences the MMR of imatinib in patients with CML.

Giant flexoelectric effect in ferroelectric epitaxial thin films.

We report on nanoscale strain gradients in ferroelectric HoMnO(3) epitaxial thin films, resulting in a giant flexoelectric effect. Using grazing-incidence in-plane x-ray diffraction, we measured strain gradients in the films, which were 6 or 7 orders of magnitude larger than typical values reported for bulk oxides. The combination of transmission electron microscopy, electrical measurements, and electrostatic calculations showed that flexoelectricity provides a means of tuning the physical properties of ferroelectric epitaxial thin films, such as domain configurations and hysteresis curves.

Hepatic artery resistance index at doppler ultrasonography is a useful parameter of hepatic graft-vs-host disease after allogeneic stem cell transplantation.

The hepatic artery resistance index (HARI) reflects portal venous blood pressure and resistance in several diseases of the liver. This study investigated whether preconditioning HARI values would predict hepatic complications such as hepatic graft-vs-host disease (GvHD), veno-occlusive disease, and drug- and sepsis-related hepatotoxicity after allogeneic stem cell transplantation (SCT). Fifty-nine patients who underwent allogeneic SCT were studied to determine whether pre-SCT HARI would predict post-SCT hepatic complications. Twenty-six patients (44.1%) had high HARI values (≥0.74) before allogeneic SCT. At univariate analysis, a high HARI value correlated with incidence of hepatic GvHD. Multivariate analysis revealed that a nonmyeloablative regimen (P = .009; hazard ratio [HR], 4.05), infused CD34-positive cell dosage (P = .01; HR, 3.32), and high HARI (P = .02; HR, 2.82) were independent predictors. However, a high HARI did not correlate with nonrelapsed mortality and overall survival. In conclusion, it seems that a high HARI before SCT might be an important predictor of significant hepatic GvHD in patients after allogeneic SCT.

Early onset of acute GVHD indicates worse outcome in terms of severity of chronic GVHD compared with late onset.

Acute GVHD (aGVHD) is an important risk factor for predicting the incidence or severity of chronic GVHD (cGVHD). Transplant outcome can be influenced by the onset time of aGVHD in patients who have received allogeneic PBSC transplants (PBSCTs). The medical records of 134 patients who survived more than 3 months after myeloablative allogeneic PBSCT were retrospectively reviewed. In all, 38 patients (28.4%) developed grade II-IV aGVHD before day +28 (early aGVHD) and 25 patients (18.7%) after day +28 (late aGVHD). The 5-year cumulative incidence of cGVHD was 78.9% in the early-aGVHD group and 56.6% in the late-aGVHD group (P=0.034). The 5-year OS was 51.0% for the early-aGVHD and 80.8% for the late-aGVHD group (P=0.406). Infection was the primary cause of death for the early-aGVHD group (51.4 vs 16.7%, P=0.017), whereas relapse of the primary disease was higher among the patients with late aGVHD, although this was statistically insignificant (58.3 vs 25.7%, P=0.309). In a multivariate analysis, early aGVHD was identified as a risk factor for developing cGVHD (hazard ratio (HR) 2.278, P=0.004). The development of aGVHD early after allogeneic PBSCT increased the risk of cGVHD and infection-related death rate when compared with the late onset of aGVHD.

Effects of cadmium exposure and intermittent anoxia on nitric oxide metabolism in eastern oysters, Crassostrea virginica.

Nitric oxide (NO) is an intracellular signaling molecule synthesized by a group of enzymes called nitric oxide synthases (NOS) and involved in regulation of many cellular functions including mitochondrial metabolism and bioenergetics. In invertebrates, the involvement of NO in bioenergetics and metabolic responses to environmental stress is poorly understood. We determined sensitivity of mitochondrial and cellular respiration to NO and the effects of cadmium (Cd) and intermittent anoxia on NO metabolism in eastern oysters, Crassostrea virginica. NOS activity was strongly suppressed by exposure to 50 microg l(-1) Cd for 30 days (4.76 vs 1.19 pmol NO min(-1) mg(-1) protein in control and Cd-exposed oysters, respectively) and further decreased during anoxic exposure in Cd-exposed oysters but not in their control counterparts. Nitrate/nitrite content (indicative of NO levels) decreased during anoxic exposure to less than 10% of the normoxic values and recovered within 1 h of re-oxygenation in control oysters. In Cd-exposed oysters, the recovery of the normoxic NO levels lagged behind, reflecting their lower NOS activity. Oyster mitochondrial respiration was inhibited by exogenous NO, with sensitivity on a par with that of mammalian mitochondria, and ADP-stimulated mitochondrial respiration was significantly more sensitive to NO than resting respiration. In isolated gill cells, manipulations of endogenous NOS activity either with a specific NOS inhibitor (aminoguanidine) or a NOS substrate (L-arginine) had no effect on respiration, likely due to the fact that mitochondria in the resting state are relatively NO insensitive. Likewise, Cd-induced stimulation of cellular respiration did not correlate with decreased NOS activity in isolated gill cells. High sensitivity of phosphorylating (ADP-stimulated) oyster mitochondria to NO suggests that regulation of bioenergetics is an evolutionarily conserved function of NO and that NO-dependent regulation of metabolism may be most prominent under the conditions of high metabolic flux when the ADP-to-ATP ratio is high.

Influence of low absolute lymphocyte count of patients with nongerminal center type diffuse large B-cell lymphoma with R-CHOP therapy.

BACKGROUND: Rituximab has dramatic impact on outcome of patients with diffuse large B-cell lymphoma (DLBCL), especially nongerminal center (non-GC) type. A low absolute lymphocyte count (ALC) before rituximab, cyclophosphamide, vincristine, adriamycin, and prednisone (R-CHOP) therapy as a surrogate marker of immune status is associated with poor clinical outcome in DLBCL. Therefore, we hypothesized that low ALC before R-CHOP would have effect on the survival in non-GC type. PATIENTS AND METHODS: One hundred and thirty-six DLBCL patients who were treated with R-CHOP from 2003 to 2007 were analyzed in the present study. RESULTS: ALC > or = 1.0 x 10(9)/l predicted a longer 3-year progression-free survival (PFS) and 3-year overall survival (OS) versus ALC <1.0 x 10(9)/l (82.6% versus 60.0%, P = 0.005 and 87.2% versus 62.0%, P < 0.001, respectively). Non-GC type had similar PFS and OS to germinal center type (68.2% versus 80.0%, P = 0.074 and 72.7% versus 82.9%, P = 0.111, respectively). However, considering clinical influence of the ALC according to immunophenotype, low ALC in non-GC type DLBCL was associated with lower PFS and OS compared with others (PFS, P = 0.002; OS, P < 0.001). Multivariate analysis revealed that low ALC in non-GC type had lower PFS [hazard ratio (HR) = 3.324, P = 0.001] and OS (HR = 4.318, P < 0.001), independent of international prognostic index. CONCLUSION: A low ALC in non-GC type DLBCL counteracted the beneficial effect of rituximab on survival.

Quantitation of whole blood Epstein-Barr virus DNA is useful for assessing treatment response in patients with non-Hodgkin's lymphoma.

INTRODUCTION: Epstein-Barr virus (EBV) is a well-known tumorigenic virus and is associated with lymphoproliferative disorders. Quantitations of EBV viral loads in plasma and peripheral blood mononuclear cells have been reported to be useful biomarkers for monitoring Hodgkin's lymphoma and EBV-associated non-Hodgkin lymphoma (NHL). METHODS: In the present study, whole blood specimens were used to determine quantitatively EBV viral loads, which were then compared with clinical data. Using real-time quantitative polymerase chain reaction (RQ-PCR), EBV-DNA was monitored in whole blood samples from patients with NHL (n = 61) at the time of diagnosis, relapse, and follow-up. RESULTS: A statistically significant correlation was observed between positive EBV viral load and extranodal involvement in diffuse large B-cell lymphoma at the time of diagnosis or relapse (n = 29, P = 0.009). In patients who were serially checked for EBV-DNA levels (n = 16), viral load was found to fall to undetectable levels during complete remission. On the contrary, progressive disease and relapse were found to be associated with sustained or elevated EBV-DNA levels. CONCLUSION: These results suggest that whole blood EBV-DNA quantitation might be of value as a convenient biomarker for therapeutic responsiveness of NHL.

Induction chemotherapy with S-1 plus cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck.

OBJECTIVE: This study was performed to assess the efficacy and safety profile of combination treatment with S-1 and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck. DESIGN: Eligibility criteria comprised: histologically confirmed squamous cell carcinoma of the head and neck; stage three or four disease with no evidence of distant metastasis; evaluable lesions; adequate organ function; age 20-80 years; and a performance status of two or less. Cisplatin was infused over one hour on day one (75 mg/m2) and S-1 was administered orally for 14 consecutive days (days two to 15). The dosages of S-1 were calculated according to the patients' body surface area: 50 mg twice a day (body surface area 1.5 m2). Each course was repeated every three weeks. After two courses, tumour response was evaluated by computed tomography and laryngoscopy. If a response was evident (either complete or partial), the patient received one more course of chemotherapy, before undergoing radical treatment such as radiotherapy or surgery. RESULTS: All 30 patients were assessable for toxicity, and 29 patients for treatment response. The overall response was 89.7 per cent (complete response: nine; partial response: 17). The two-year estimated overall survival rate was 79.2 per cent. Adverse reactions occurred 128 times during 81 courses in the 30 cases. The most common grade three to four adverse event was neutropenia, which occurred in eight patients. Cases of non-haematological grade three or four toxicity included nausea and vomiting in four patients, stomatitis in two and diarrhoea in one. CONCLUSION: S-1 plus cisplatin combination chemotherapy is effective against locally advanced squamous cell carcinoma of the head and neck, with only mild toxicity.

Neoadjuvant docetaxel and cisplatin chemotherapy followed by local irradiation is highly active on locoregionally advanced squamous cell carcinoma of the head and neck.

The purpose of this study was to determine the treatment outcome of neoadjuvant docetaxel and cisplatin chemotherapy followed by local radiotherapy for chemotherapy-naïve patients with locoregionally advanced squamous cell carcinoma of the head and neck. Thirty-seven patients with stage III or IV squamous cell carcinoma of the head and neck who received docetaxel and cisplatin regimen for a maximum of three cycles followed by radiation therapy were enrolled in this study. The overall response rate to the regimen was 91.9 per cent (34 of 37) (the complete remission rate was 48.6 per cent). The median time to treatment failure was 38 months (95 per cent confidence interval, 15-61 months). The four year estimated overall survival rates were 85.1 per cent. The most frequent moderate-to-severe toxicity was grade 3-4 neutropenia. The most common acute non-haematologic toxicities included anorexia, nausea and asthenia. Neoadjuvant docetaxel and cisplatin chemotherapy followed by radiotherapy is a feasible treatment strategy for patients with locoregionally advanced squamous cell carcinoma of the head and neck.

Increased serum pigment epithelium-derived factor is associated with microvascular complications, vascular stiffness and inflammation in Type 1 diabetes.

AIMS: To determine in Type 1 diabetes patients if levels of pigment epithelium-derived factor (PEDF), an anti-angiogenic, anti-inflammatory and antioxidant factor, are increased in individuals with complications and positively related to vascular and renal dysfunction, body mass index, glycated haemoglobin, lipids, inflammation and oxidative stress. METHODS: Serum PEDF levels were measured by ELISA in a cross-sectional study of 123 Type 1 diabetic patients (71 without and 52 with microvascular complications) and 31 non-diabetic control subjects. PEDF associations with complication status, pulse-wave analysis and biochemical results were explored. RESULTS: PEDF levels [geometric mean (95% CI)] were increased in patients with complications 8.2 (7.0-9.6) microg/ml, vs. complication-free patients [5.3 (4.7-6.0) microg/ml, P < 0.001] and control subjects [5.3 (4.6-6.1) microg/ml, P < 0.001; anova between three groups, P < 0.001], but did not differ significantly between control subjects and complication-free patients (P > 0.05). In diabetes, PEDF levels correlated (all P < 0.001) with systolic blood pressure (r = 0.317), pulse pressure (r = 0.337), small artery elasticity (r = -0.269), glycated haemoglobin (r = 0.245), body mass index (r = 0.362), renal dysfunction [including serum creatinine (r = 0.491), cystatin C (r = 0.500)], triglycerides (r = 0.367), and inflammation [including log(e)C-reactive protein (CRP; r = 0.329), and soluble vascular cell adhesion molecule-1 (r = 0.363)]. Age, blood urea nitrogen, systolic blood pressure, pulse pressure and log(e)CRP correlated with PEDF levels in control subjects (all P < 0.04). PEDF levels were not significantly correlated with measures of oxidative stress: isoprostanes, oxidized low-density lipoprotein or paraoxonase-1 activity. On stepwise linear regression analysis (all subjects), independent determinants of PEDF levels were renal function, triglycerides, inflammation, small artery elasticity and age (r(2) = 0.427). CONCLUSIONS: In Type 1 diabetes, serum PEDF levels are associated with microvascular complications, poor vascular health, hyperglycaemia, adiposity and inflammation.

New myeloablative conditioning regimen with fludarabine and busulfan for allogeneic stem cell transplantation: comparison with BuCy2.

A regimen of busulfan and cyclophosphamide (BuCy2) is regarded as the standard myeloablative regimen for SCT. This study evaluated the hypothesis that fludarabine can replace cyclophosphamide for myeloablative allogeneic SCT. Ninety-five patients underwent allogeneic SCT from HLA-identical donors, following BuCy2 (n=55) or busulfan+fludarabine (BF, n=40). The efficacy of fludarabine compared to cyclophosphamide was retrospectively evaluated. The BF group exhibited a shorter duration until engraftment (P=0.001), lower incidence of acute and chronic GVHD (P<0.001 and P=0.003, respectively), and non-relapse mortality (NRM) (P=0.039). Furthermore, the event-free survival and overall survival were significantly higher for the BF group compared to the BuCy2 group (P=0.004 and 0.002, respectively). After adjusting for age, the risk status of disease, GVHD prophylaxis and donor type, the BF regimen was found to be an independent favorable risk factor for event-free survival (hazard ratio (HR), 0.181; 95% confidence interval, 0.045-0.720; P=0.016) and overall survival (HR, 0.168; 0.035-0.807; P=0.026). The replacement of cyclophosphamide with fludarabine for myeloablative conditioning seems to be more effective in terms of short-term NRM, and GVHD compared to BuCy2 regimen in allogeneic transplantation.

Identification and developmental expression of mRNAs encoding crustacean cardioactive peptide (CCAP) in decapod crustaceans.

Full-length cDNAs encoding crustacean cardioactive peptide (CCAP) were isolated from several decapod (brachyuran and astacuran) crustaceans: the blue crab Callinectes sapidus, green shore crab Carcinus maenas, European lobster Homarus gamarus and calico crayfish Orconectes immunis. The cDNAs encode open reading frames of 143 (brachyurans) and 139-140 (astacurans) amino acids. Apart from the predicted signal peptides (30-32 amino acids), the conceptually translated precursor codes for a single copy of CCAP and four other peptides that are extremely similar in terms of amino acid sequence within these species, but which clearly show divergence into brachyuran and astacuran groups. Expression patterns of CCAP mRNA and peptide were determined during embryonic development in Carcinus using quantitative RT-PCR and immunohistochemistry with whole-mount confocal microscopy, and showed that significant mRNA expression (at 50% embryonic development) preceded detectable levels of CCAP in the developing central nervous system (CNS; at 70% development). Subsequent CCAP gene expression dramatically increased during the late stages of embryogenesis (80-100%), coincident with developing immunopositive structures. In adult crabs, CCAP gene expression was detected exclusively in the eyestalk, brain and in particular the thoracic ganglia, in accord with the predominance of CCAP-containing cells in this tissue. Measurement of expression patterns of CCAP mRNA in Carcinus and Callinectes thoracic ganglia throughout the moult cycle revealed only modest changes, indicating that previously observed increases in CCAP peptide levels during premoult were not transcriptionally coupled. Severe hypoxic conditions resulted in rapid downregulation of CCAP transcription in the eyestalk, but not the thoracic ganglia in Callinectes, and thermal challenge did not change CCAP mRNA levels. These results offer the first tantalising glimpses of involvement of CCAP in environmental adaptation to extreme, yet biologically relevant stressors, and perhaps suggest that the CCAP-containing neurones in the eyestalk might be involved in adaptation to environmental stressors.