Efficacy of prophylactic antibiotics for the prevention of neutropenic fever in patients with multiple myeloma receiving high-dose cyclophosphamide for stem cell mobilization.

High-dose cyclophosphamide (HD-Cy) (3 g/m2) plus granulocyte colony-stimulating factor (G-CSF) is a very effective regimen for peripheral blood stem cell (PBSC) mobilization. Unfortunately, it is associated with an increased risk of neutropenic fever (NF). We analyzed the effect of NF on PBSC apheresis results and the efficacy of prophylactic antibiotics for the prevention of NF associated with HD-Cy plus G-CSF for PBSC mobilization in patients with newly diagnosed multiple myeloma (MM). First, patients were divided into NF ( +) and NF ( -) groups according to whether they suffered from NF during mobilization. Second, we divided patients into an antibiotic prophylaxis group and a nonantibiotic prophylaxis group according to whether antibiotic prophylaxis was used during the mobilization period. Our study showed that NF( +) patients (n = 44) had lower CD34 + cell dose collection (median 2.60 versus 5.34 × 106/kg, P < 0.001) and slower neutrophil engraftment and platelet engraftment (median 11 versus 10 days, P = 0.002, and median 13 versus 11 days, P = 0.043, respectively) than NF( -) patients (n = 234). Of note, the nonantibiotic prophylaxis group patients (n = 30) had a 26.7% incidence of NF. In the patients receiving antibiotic prophylaxis (n = 227), the incidence was reduced to 9.3% (P = 0.01). The antibiotic prophylaxis patients had higher CD34 + cell collection (median 5.41 versus 2.27 × 106/kg, P < 0.001) and lower hospitalization cost of mobilization ($ median 3108.02 versus 3702.39, p = 0.012). Thus, our results demonstrate that NF is associated with lower CD34 + cell collection and that antibiotic prophylaxis can reduce the incidence of NF and improve stem cell mobilization and collection outcomes, which reduces the hospitalization cost of mobilization.

On-demand plerixafor added to high-dose cyclophosphamide and pegylated recombinant human granulocyte colony-stimulating factor in the mobilization of patients with multiple myeloma: a treatment with high effectiveness, convenient, and affordable cost.

Objective: The combination of high-dose cyclophosphamide (HD-Cy) (3g/m2) plus granulocyte colony-stimulating factor (G-CSF) and on-demand plerixafor (PXF) has been considered an effective mobilization regimen of patients with multiple myeloma(MM). However, the daily multi-injection regimen of G-CSF poses challenges. This study delves into the efficiency and cost implications of a novel approach, using HD-Cy alongside pegylated G-CSF (PEG G-CSF) and on-demand PXF. Unlike G-CSF, which necessitates daily injections, the half-life of PEG G-CSF extended allows for a single injection. Methods: A retrospective analysis was conducted on 350 MM patients, which were categorized based on their mobilization regimens: Cy+PEG G-CSF+/-PXF (n=66), Cy+PEG G-CSF (n=91), Cy+ G-CSF (n=169), and G-CSF+PXF (n=24). Results: Mobilization with Cy+PEG G-CSF+/-PXF(8.79)yielded a notably higher median CD34+ cell count compared to the other regimens: Cy+PEG G-CSF(4.96), Cy+G-CSF (4.65), and G-CSF+PXF (2.99) (P<0.001). The percentage of patients who achieved >6×106/kg CD34+ cells was significantly higher in the Cy+PEG G-CSF+/-PXF group (77.3%) than in the other mobilization regimens: Cy+PEG G-CSF (41.8%), Cy+ G-CSF (37.3%), and G-CSF+PXF (8.3%) (P<0.001). From a cost perspective, the Cy+PEG G-CSF+/-PXF approach was more economical than the G-CSF+PXF strategy but was marginally costlier than the other two methods. A multivariate assessment highlighted that the combination of Cy+PEG G-CSF with on-demand PXF had a superior potential to achieve the desired harvest (6×106/kg) compared to the Cy+PEG G-CSF protocol without PXF. The incremental cost-effectiveness ratio for each 1% increase in the probability of achieving a successful optimal harvest was $ 97.02 per patient. The incidence of neutropenic fever was 3.0% in the Cy+PEG G-CSF+/-PXF group. Conclusion: The combination of on-demand PXF with HD-Cy and PEG G-CSF offers a cost-effective approach with a high mobilization success rate, manageable side effects, and the convenience of fewer injections. It stands as a promising mobilization strategy for MM patients.

The acute toxic effects of platinum nanoparticles on ion channels, transmembrane potentials of cardiomyocytes in vitro and heart rhythm in vivo in mice.

BACKGROUND: Platinum nanoparticles (PtNPs) have been considered a nontoxic nanomaterial and been clinically used in cancer chemotherapy. PtNPs can also be vehicle exhausts and environmental pollutants. These situations increase the possibility of human exposure to PtNPs. However, the potential biotoxicities of PtNPs including that on cardiac electrophysiology have been poorly understood. METHODS: Ion channel currents of cardiomyocytes were recorded by patch clamp. Heart rhythm was monitored by electrocardiogram recording. Morphology and characteristics of PtNPs were examined by transmission electron microscopy, dynamic light scattering and electrophoretic light scattering analyses. RESULTS: In cultured neonatal mice ventricular cardiomyocytes, PtNPs with diameters 5 nm (PtNP-5) and 70 nm (PtNP-70) concentration-dependently (10-9 - 10-5 g/mL) depolarized the resting potentials, suppressed the depolarization of action potentials and delayed the repolarization of action potentials. At the ion channel level, PtNPs decreased the current densities of INa, IK1 and Ito channels, but did not affect the channel activity kinetics. In vivo, PtNP-5 and PtNP-70 dose-dependently (3-10 mg/kg, i.v.) decreased the heart rate and induced complete atrioventricular conduction block (AVB) at higher doses. Both PtNP-5 and PtNP-70 (10-9 - 10-5 g/mL) did not significantly increase the generation of ROS and leak of lactate dehydrogenase (LDH) from cardiomyocytes within 5 mins after exposure except that only very high PtNP-5 (10-5 g/mL) slightly increased LDH leak. The internalization of PtNP-5 and PtNP-70 did not occur within 5 mins but occurred 1 hr after exposure. CONCLUSION: PtNP-5 and PtNP-70 have similar acute toxic effects on cardiac electrophysiology and can induce threatening cardiac conduction block. These acute electrophysiological toxicities of PtNPs are most likely caused by a nanoscale interference of PtNPs on ion channels at the extracellular side, rather than by oxidative damage or other slower biological processes.

The acute toxic effects of silver nanoparticles on myocardial transmembrane potential, INa and IK1 channels and heart rhythm in mice.

This study focused on the potential toxicity of silver nanoparticles (AgNPs) on cardiac electrophysiology which is rarely investigated. We found that AgNPs (10-9-10-6 g/ml) concentration-dependently depolarized the resting potential, diminished the action potential, and finally led to loss of excitability in mice cardiac papillary muscle cells in vitro. In cultured neonatal mice cardiomyocytes, AgNPs (10-9-10-7 g/ml) concentration-dependently decreased the Na+ currents (INa), accelerated the activation, and delayed the inactivation and recovery of Na+ channels from inactivation within 5 min. AgNPs at 10-8 g/ml also rapidly decreased the inwardly rectifying K+ currents (IK1) and delayed the activation of IK1 channels. Intravenous injection of AgNPs at 3 mg/kg only decreased the heart rate, while at ≥4 mg/kg sequentially induced sinus bradycardia, complete atrio-ventricular conduction block, and cardiac asystole. AgNPs at 10-10-10-6 g/ml did not increase reactive oxygen species (ROS) generation and only at 10-6 g/ml mildly induced lactate dehydrogenase (LDH) release in the cardiomyocytes within 5 min. Endocytosis of AgNPs by cardiomyocytes was not observed within 5 min, but was observed 1 h after exposing to AgNPs. Comparative Ag+ (≤0.02% of the AgNPs) could not induce above toxicities. We conclude that AgNPs exert rapid toxic effects on myocardial electrophysiology and induce lethal bradyarrhythmias. These acute toxicities are likely due to direct effects of AgNPs on ion channels at the nano-scale level, but not caused by Ag+, ROS, and membrane injury. These findings provide warning to the nanomedical practice using AgNPs.

Degeneration and energy shortage in the suprachiasmatic nucleus underlies the circadian rhythm disturbance in ApoE-/- mice: implications for Alzheimer's disease.

Alzheimer's disease (AD) patients suffer sleep disorders and circadian rhythm disturbances (CRDs). The underlying mechanisms are incompletely understood, and treatments are lacking. In this study, we characterized the locomotor activity, clock gene expression, morphological degeneration and energy metabolism of suprachiasmatic nucleus (SCN), together with retinal light sensing, in ApoE-/- mice, a model for AD. Compared with the control C57BL/6J mice, ApoE-/- mice exhibited disordered circadian locomotor activity under dim light and constant darkness, with impaired re-entrainment to phase change schedules. Decreased retinal melanopsin expression, together with amyloidosis and tau deposition, was evident in ApoE-/- mice. Mitochondrial and synaptic deterioration, altered SIRT1-mediated energy metabolism and clock gene expression were also observed in ApoE-/- SCN. Supplementation with fat or ketone bodies but not glucose, or intraperitoneal administration of nicotinamide, restored the locomotor rhythmicity and circadian expression of SIRT1 and clock genes, as well as reducing neurodegeneration. Taken together, ApoE deficiency induced degeneration and a significant disturbance in the SCN rhythmicity. Decline of retinal light sensing and SCN structural and metabolic deteriorations represented the major pathologies accounting for the CRDs in ApoE-/- mice. Our curative experiments may help develop future therapies to treat the CRDs and sleep disorders in AD patients.

Tanshinone II-A sodium sulfonate (DS-201) enhances human BKCa channel activity by selectively targeting the pore-forming α subunit.

AIM: Tanshinone II-A sodium sulfonate (DS-201), a water-soluble derivative of Tanshinone II-A, has been found to induce vascular relaxation and activate BKCa channels. The aim of this study was to explore the mechanisms underlying the action of DS-201 on BKCa channels. METHODS: Human BKCa channels containing α subunit alone or α plus ß1 subunits were expressed in HEK293 cells. BKCa currents were recorded from the cells using patch-clamp technique. The expression and trafficking of BKCa subunits in HEK293 cells or vascular smooth muscle cells (VSMCs) were detected by Western blotting, flow cytometry and confocal microscopy. RESULTS: DS-201 (40-160 µmol/L) concentration-dependently increased the total open probability of BKCa channels in HEK293 cells, associated with enhancements of Ca(2+) and voltage dependence as well as a delay in deactivation. Coexpression of ß1 subunit did not affect the action of DS-201: the values of EC50 for BKCa channels containing α subunit alone and α plus ß1 subunit were 66.6±1.5 and 62.0±1.1 µmol/L, respectively. In both HEK293 cells and VSMCs, DS-201 (80 µmol/L) markedly increased the expression of α subunit without affecting ß1 subunit. In HEK293 cells, DS-201 enriched the membranous level of α subunit, likely by accelerating the trafficking and suppressing the internalization of α subunit. In both HEK293 cells and VSMCs, DS-201 (≥320 µmol/L) induced significant cytotoxicity. CONCLUSION: DS-201 selectively targets the pore-forming α subunit of human BKCa channels, thus enhancing the channel activities and increasing the subunit expression and trafficking, whereas the ß1 subunit does not contribute to the action of DS-201.

[Observation of humoral immunity reconstitution and its relationship with infection after autologous hematopoietic stem cell transplantation for patients with multiple myeloma].

OBJECTIVE: To study the humoral immunity reconstitution and its relationship with infection in patients with multiple myeloma (MM) after undergoing autologous hematopoietic stem cell transplantation (auto-HSCT). METHODS: Forty-two MM patients undergoing auto-HSCT were included in this study. Peripheral blood were obtained for immunoglobulin detection, including IgG, IgA and IgM before transplantation and 1, 3, 6, 12, 18 and 24 months after transplantation. The time, type, pathogen of infection between 1 and 24 month after transplantation were analyzed. RESULTS: The level of IgA at 6 month [(0.75±0.59) g/L] after auto-HSCT was lower than that of pre-auto-HSCT [(1.04±0.70) g/L], and reached the level of pre-auto-HSCT at 9 months [(0.99±0.52) g/L] after auto-HSCT. The level of IgM reached the level of pre-auto-HSCT [(0.45±0.26) g/L] at 3 months after auto-ASCT [(0.50±0.26) g/L]. The level of IgG reached the level of pre-auto-HSCT [(9.80±2.98) g/L] at 1 month after auto-HSCT [(11.09±2.69) g/L], and higher than that of pre-auto-HSCT at 9 months after auto-HSCT [(12.07±3.57) g/L]. The level of IgG with IgG-type MM was higher than that of patients with light-chain type and IgD-type MM at 6, 9 and 12 months after auto-HSCT. The IgA level of patients who obtained complete remission (CR) is much higher than that of patients who obtained nCR in IgG-type patients. The incidence of infection in 6 month after auto-HSCT was higher than that of (6-12) month and >12 month after auto-HSCT. The incidence of infection was strongly negative correlated with IgA (r =-0.943, P=0.005) and IgG (r=-0.943, P=0.005) level. The frequency of viral infection was also negatively correlated with IgA and IgG. CONCLUSION: The reconstitution time of IgG, IgA and IgM was different in MM patients after auto-HSCT. IgG recovered first, then IgM, and IgM the last. The incidence of infection was negatively correlated with IgA and IgG. With the recovery of IgG and IgA, the incidence of infection was decreased accordingly.

[Clinical significance of abnormal protein bands in multiple myeloma treated with bortezomib-based induction regimen and autologous stem cell transplantation].

OBJECTIVE: To study the clinical significance of abnormal protein bands (APB) in multiple myeloma (MM) patients treated with bortezomib-based induction regimen and autologous stem cell transplantation (ASCT). METHODS: Sixty-eight MM patients submitted to bortezomib-based induction therapy and ASCT from January 2007 to July 2012 were retrospectively studied. Monoclonal protein was detected by immunofixation electrophoresis (IFE). RESULTS: Of all 68 patients, 33 (48.5%) patients had APB. At the first emergence of an APB, two patients with light chain type achieved CR and before transplantation, and thirty-one patients were after transplantation with median time of 104 (ranged 33-404) days. The median duration of APB appearance was 105 (ranged 35-801) days. Patients who developed APB compared with those without APB, had a significantly higher CR plus very good partial response (VGPR) rates (100.0% vs 85.7%%, P=0.017) and CR rates (87.9% vs 62.9%) (P=0.03). There were no significant differences in gender, age, HGB, ALB, ß2-microglobulin, M protein type, Durie-Salmon and ISS stages, the case number of first line or second line treatment, induction courses of bortezomib-based regimen, and the mode of ASCT. With a median follow-up of 33.4 (ranged 7.0-71.7) months, patients with APB tended to have a longer overall survival (OS) versus non-APB patients, although no significant difference obtained (P＞0.05). Among APB patients, OS was longer in patients whose appearance of APB occurred ＜6 months after transplantation than those ≥ 6 months, but the significant difference was not obtained yet (P＞0.05). CONCLUSIONS: Patients who developed APB had a significantly better response to bortezomib-based induction regimen followed ASCT. APB emergence has a good prognostic significance.

Defective T wave combined with incomplete right bundle branch block: a new electrocardiographic index for diagnosing atrial septal defect.

BACKGROUND: Incomplete right bundle branch block (ICRBBB) is commonly associated with atrial septal defect (ASD), but lacks sufficient diagnostic test characteristics. An abnormal T wave is also often observed in ASD, with horizontal or inverted displacement of the proximal T wave limb in the right precordial leads, termed "defective T wave" (DTW). METHODS: We examined the diagnostic test characteristics of combining ICRBBB with DTW as a new index to diagnose ASD. A total of 132 consecutive patients with ASD and 132 cases of age/gender-matched controls without ASD were enrolled. RESULTS: Sensitivities of DTW, ICRBBB, and both were 87.1% - 87.9%. Specificities were 97.0%, 96.2%, and 100%, respectively. Positive predictive values were 1.3%, 1.1%, and 100.0% respectively, while negative predictive values were 99.9% for each. CONCLUSION: Combining ICRBBB with DTW in electrocardiogram (ECG) as a new index significantly increased the specificity and positive predictive values while maintaining a high sensitivity in diagnosing ASD.

Differentiation induction enhances bortezomib efficacy and overcomes drug resistance in multiple myeloma.

AIM: It is of clinical importance to find methods to overcome bortezomib resistance. In the current study, we clarified the relationship between resistance to bortezomib and the differentiation status of myeloma cells, and explored the feasibility of induction of differentiation in overcoming bortezomib resistance in myeloma. METHODS: Cell morphology, immunoglobulin light-chain protein secretion levels, and XBP-1 expression were used to evaluate the differentiation status of myeloma cells. Low dose 2-ME2 alone or in combination with ATRA was used to induce differentiation in myeloma cells. RESULTS: The differentiation status of myeloma cells was related to myeloma sensitivity to bortezomib. After successful induction of differentiation, the myeloma cells were more sensitive to bortezomib with decreased growth and an increased rate of apoptosis. Induction of differentiation increased the proteasome workload in myeloma cells by increasing immunoglobulin secretion, while reducing proteasome capacity by decreasing proteasome activity. The imbalance between increased proteasome workload and decreased proteasome capacity is a possible mechanism by which induction of differentiation overcomes myeloma resistance to bortezomib. CONCLUSION: The current study demonstrated, for the first time, that myeloma differentiation status is associated with myeloma sensitivity to bortezomib and that induction of differentiation can overcome myeloma resistance to bortezomib.

[In vitro study of human multiple myeloma cell transfected with soluble vascular endothelial growth factor receptor-1 gene].

BACKGROUND AND OBJECTIVE: Vascular endothelial growth factor (VEGF) is the most important angiogenic factor of multiple myeloma (MM). This study was to investigate the effect of transfection of human soluble vascular endothelial growth factor receptor-1 (sFlt-1) gene on the proliferation of human MM cell line RPMI8226. METHODS: The recombinant plasmid pcDNA3-sFlt-1 was constructed and transfected into RPMI8226 cells. The expression of sFlt-1 was identified by reverse transcription-polymerase chain reaction (RT-PCR) and ELISA. The effects of sFlt-1 protein on the proliferation and VEGF expression of RPMI8226 cells were investigated by MTT assay and ELISA, respectively. RESULTS: The recombinant plasmid pcDNA3-sFlt-1 was successfully transfected into RPMI8226 cells. sFlt-1 protein expression was identified by ELISA, which inhibited the proliferation of RPMI8226 cells and reduced VEGF concentration in the culture supernatant. CONCLUSION: RPMI8226 cells can express sFlt-1 protein with high biological activity when transfected with the sFlt-1 gene, which inhibits the proliferation of RPMI8226 cells.

[The clinical features and risk factors for invasive fungal infection in multiple myeloma.].

OBJECTIVE: To study the clinical features and risk factors of invasive fungal infection (IFI) in multiple myeloma (MM). METHODS: Three hundred and fifty-seven cases of MM were retrospectively analyzed for IFI, clinical features, complicating diseases, treatment of fungus and side effect of anti-fungal drugs. RESULTS: Forty-four cases (12.3%) of IFI were diagnosed. Three of them were diagnosed definitely, 8 clinically and 33 probably. Ten cases incurred IFI in the induction therapy, 4 in platform, 27 in progress and 3 in the treatment with autologous stem cell transplantation. The lung was the commonest site of infection (50.0%). The total effective rates of amphotericin B liposome, voriconazole, itraconazole, caspofungin and fluconazol were 83.3%, 75.0%, 78.9%, 75.0% and 57.1% respectively (P = 0.493). In a multivariate analysis, independent factors significantly associated with IFI were diabetes (P = 0.035, OR 2.527, 95%CI 1.005 - 6.052), dialysis (P = 0.022, OR 2.768, 95%CI 1.161 - 6.600), persistent agranulocytosis (P = 0.019, OR 3.215, 95%CI 1.200 - 7.407), broad-spectrum antibiotic therapy (P = 0.009, OR 3.350, 95%CI 1.353 - 8.295) and fludarabine treatment (P = 0.001, OR 4.669, 95%CI 1.813 - 12.023). CONCLUSIONS: Patients with MM are in high risk of IFI. The lung is the commonest site of infection. The therapeutic effect was similar with itraconazole, voriconazole, caspofungin and amphotericin B liposome in MM patients with complicating IFI. The risk factors for IFI in MM were diabetes, dialysis, persistent agranulocytosis and the use of broad-spectrum antibiotics and fludarabine.

[The clinical features, chemotherapy responses and survival of 223 patients with newly diagnosed multiple myeloma].

OBJECTIVE: To explore the proportion, clinical and laboratory features, chemotherapy responses and long term survival of different kinds of newly diagnosed multiple myeloma (MM) in China. METHODS: The clinical data of 223 cases of newly diagnosed MM patients were gathered in the First Affiliated Hospital of Sun Yat-sen University from Jan, 2000 to Seb, 2007 were retrospectively analyzed. RESULTS: The proportions of each kind of MM including IgG, IgA, light chain, IgD, IgM and biclonal MM were 48.0%, 20.6%, 25.6%, 4.0%, 0.9% and 0.9% respectively. No IgE and nonsecretory myeloma was found. The median age of onset was 58 years, of which that of the IgA type was the oldest one and the light chain type was the youngest (P = 0.004). Bone pain, renal insufficiency, and anemia were the most common symptoms which accounted for 67.7%, 61.0% and 45.3% respectively. The incidences of renal inadequacy, hypercalcemia and pathological fracture in light chain type were higher than those in IgG and IgA types. Besides, no M protein were found in serum protein electrophoresis and no elevation of total globulin. The clinical features of IgD type were similar to that of the light-chain type. The total chemotherapy efficacy rate of 89 patients who were treated with more than 3 cycles in our hospital is 61.8%, which has no difference in all types. Median overall survival of the 89 patients was 33.0 months. CONCLUSION: IgG is the most common type in MM. Bone pain, anemia, hypercalcemia and renal insufficiency are common symptoms. Immunofixation electrophoresis should be performed routinely to avoid missed diagnosis of light-chain and IgD types of MM.

Reinvestigation of the effect of orexin A on catecholamine release from adrenal chromaffin cells.

Orexins have been shown to be implicated in the regulation of adrenal medulla functions. However, there are still inconsistent investigations on the effects of orexins on catecholamine release from chromaffin cells in varying species. In the present study, using the carbon-fiber amperometry, we investigated whether orexin A would stimulate catecholamine release from rat and mouse adrenal chromffin cells. Puff application of orexin A dose-dependently induced amperometric currents in the cultured rat chromaffin cells, which was completely blocked by the selective OX1R antagonist SB-334867 or by the removal of extracellular calcium. Likewise, in the mouse adrenal medulla slices, orexin A also induced catecholamine release mainly through the activation of OX1R. These results gain insight into our understanding of the pharmacological relevance of orexin system in modulating neuroendocrine functions.

[Real-time measurement of noradrenaline release in central nervous system].

In order to investigate the central nervous mechanism and the diseases involved in catecholamine transmitter secretion, the dynamics of catecholamine release is studied in single cell, brain slice or in vivo. Noradrenaline is an important neurotransmitter and modulator in the central nervous system (CNS) and the peripheral nervous system (PNS). In the present paper, we first compared three real-time methods used to measure noradrenaline secretion in single cells (membrane capacitance, amperometry and confocal fluorescence microscopy imaging). Compared to the electrophysiological method and fluorescence microscopy, the basic usage of the carbon fiber electrode (CFE) in neuroscience research was presented as an example. Then, we presented a primary description of ion channels, including voltage-gated Na(+), K(+) and Ca(2+) channels in locus coeruleus (LC) neurons in rat brain slices. Finally, we presented example recordings of combined patch-clamp and amperometry measurements in LC neurons, indicating Ca(2+)-dependent quantal noradrenaline release following Ca(2+) influx through Ca(2+) channels.

[Expression and clinical significance of beta-catenin in multiple myeloma].

BACKGROUND & OBJECTIVE: beta-catenin is the pivotal regulator in Wnt pathway and in charge of cellular adhesion and signal conduction. Overexpression of beta-catenin has been observed in various human tumors. This study was to investigate the expression and clinical significance of beta-catenin in multiple myeloma (MM). METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect mRNA and protein expression of beta-catenin in bone marrow samples from 12 newly diagnosed MM patients, 14 relapsed/refractory MM patients, and 11 healthy donors. The clinical data and treatment outcomes of the MM patient were also analyzed. RESULTS: The positive rate and the expression level of beta-catenin mRNA were significantly lower in healthy donors than in newly diagnosed patients and relapsed/refractory patients (27.3% vs. 75.0% and 100%, P=5.01e(-4); 0.35+/-0.17 vs. 0.72+/-0.11 and 0.85+/-0.16, P=5.88e(-5)); the mRNA level of beta-catenin was significantly lower in newly diagnosed patients than in relapsed/refractory patients (P=0.045). beta-catenin protein was not detected in healthy donors; while the positive rate and the expression level of beta-catenin protein were significantly lower in newly diagnosed patients than in relapsed/refractory patients (50.0% vs. 85.7%, 0.32+/-0.11 vs. 0.21+/-0.08, P=0.039). In the 10 newly diagnosed MM patients with evaluable treatment outcomes, the positive rate of beta-catenin protein was significant lower in the 7 patients without response than in the 3 patients showed response (14.3% vs. 100%, P=0.033). The positive rate of beta-catenin protein was significant higher in the 16 Durie/Salmon stage III patients than in the 10 stage II patients (87.5% vs. 40.0%, P=0.026), and significant higher in ISS stage III patients than in stage I and II patients (100% vs. 45.5% and 33.3%, P=0.006, P=0.032). The protein level of beta-catenin was positively correlated to serum levels of beta2-MG (r=0.688, P=0.002) and lactate dehydrogenase (LDH) (r=0.502, P=0.034). CONCLUSION: The expression of beta-catenin is related with treatment outcome, Durin-Salmon stage and ISS stage of MM, and is positively correlated to serum levels of LDH and beta2-MG.

Clinical application of wireless capsule endoscopy in pediatric patients for suspected small bowel diseases.

Capsule endoscopy (CE) has been demonstrated to be safe and well tolerated in adults with suspicion of small intestinal diseases with negative results of gastroscopy and colonoscopy. However, its value in pediatric patients has not yet been well studied. This study aimed to evaluate the results and safety of CE in pediatric patients with suspicion of small bowel disorders. There were 16 consecutive children and adolescents (12 boys, 4 girls) and 15 adults (9 men, 6 women) referred to us for suspected small bowel diseases from August 2002 to September 2005. Among the pediatrics, six patients were less than 10 years old. Technique for capsule placement, gastric transit time, small bowel transit time, excretion time of capsule endoscopy, capsule findings, and complications were recorded. All 16 pediatric patients described that the capsule was easy to swallow except for three children. Finally we delivered the capsule under gastroscopy with overtube for these three children. No capsule retention occurred during our study. Median recording time was 7 h 44 min (range 6 h 51 min-9 h 11 min). Median gastric transit time was 83.5 min (range 4-296 min). Median small bowel transit time was 270 min (range 142-484 min). Median excretion time of capsule was 33.9 h (range 12-96 h). There was no significant difference in excretion time of capsule, gastric transit time and small bowel transit time between pediatric patients and adult patients (P > 0.05). CE was positive in 12 patients, including Crohn's disease (4), hemangioma (2), angiodysplasia (2), Meckel diverticulum (1), polyp (1), aphthous ulcer in ascending colon (1), and cobblestone appearance of ileal mucosa. CE has been performed safely in a small series of pediatric patients after ingestion or endoscopic placement of the capsule. The high yield of abnormal findings was comparable to those of adult patients.

[Clinical application of wireless capsule endoscopy in pediatric and adolescent patients].

OBJECTIVE: Capsule endoscopy (CE) has been demonstrated to be safe and well tolerated in adults. However, its value in pediatric patients has not been well studied. The present study aimed to evaluate the safety and effectiveness of CE in pediatric patients with suspicious small bowel disorders. METHODS: Fifteen children and adolescents (less than 18 years) were referred to our study for suspected small bowel diseases from Aug. 2002 to May 2005. They aged from 3 to 18 years. Among them, 5 patients were less than 10 years old. The range of weight was from 17 to 83 kg and height was from 49 to 176 cm. Clinical indications included obscure gastrointestinal bleeding (n = 12) and abdominal pain (n = 3). All the patients had normal results on upper and lower gastrointestinal examinations before they underwent CE. The procedures for capsule placement, gastric transit time, small bowel transit time, the average time of the elimination of the capsule, capsule findings, and complications were recorded. RESULTS: All the patients described that the capsule was easy to swallow except 3 youngest children. Finally the capsule was delivered via gastroscopy with overtube for these three children under intravenous anesthesia. No capsule retention occurred during the study. Median recording time was (464 +/- 40) min. In 5 patients, the capsule did not pass the ileal valve by the end of the recording time. Median gastric transit time was (85 +/- 90) min. Median small bowel transit time was (283 +/- 106) min. The average time of the elimination of the capsule was (34.3 +/- 21.8) h. The detective yield of CE was 80%. These positive findings included Crohn's disease (5), hemangioma (2), angiodysplasia (2), Meckel diverticulum (1), polyp (1), and granulomatous lesions (1). CONCLUSION: CE was performed safely in pediatric patients after ingestion or endoscopic placement of the capsule. The high yield of abnormal findings was comparable to those of adult patients.