Toll-like receptor signalling associated with immunomodulation of umbilical cord-derived mesenchymal stem cells in mice with systemic lupus erythematosus.

With potent immunomodulatory activities, mesenchymal stem cells (MSCs) have the potential to be a beneficial treatment option for diseases with aberrant immune responses such as systemic lupus erythematosus (SLE). However, the underlying mechanisms remain largely unknown. Here, we used NZBWF1 mice as a SLE animal model to examine immunomodulation of MSCs as well as to assess the role of Toll-like receptor signalling in this circumstance. We found that mice receiving MSCs had a significant decrease in severity of proteinuria at 20 and 22 weeks of age (p = 0.009 and p = 0.022, respectively). Serum anti-dsDNA levels were significantly lower compared with the control group (p = 0.016 and p = 0.036, respectively). C3 and C4 levels were significantly higher at 22 weeks of age (p = 0.046 and p = 0.016, respectively). Altered expression of inflammation-associated cytokine profiles in the serum was also noted in mice receiving MSCs. Down-regulation of myeloid differentiation factor 88 (MyD88)-nuclear factor-κB (NF-κB) signalling in the liver was demonstrated by quantitative polymerase chain reaction, ELISA and Western blotting. In addition to demonstrating the beneficial effects of MSC treatment in NZBWF1 mice, our study provided the first evidence for the association of MyD88-NF-κB signalling and MSC-mediated immunomodulation in this disease.

Concurrent hypopituitarism and leukemic retinopathy in a child with B-precursor acute lymphoblastic leukemia and isolated central nervous system relapse.

Hypopituitarism in leukemia is very rare. In addition, central nervous system (cns) relapse and leukemic retinopathy in childhood acute lymphoblastic leukemia (all) have declined with the use of modern systemic chemotherapy that includes cns prophylaxis. Here, we report the case of a 4-year-old girl who received chemotherapy and intrathecal therapy without cns radiation after a diagnosis of B-precursor all without cns involvement. Three months after chemotherapy completion, she presented with lower-extremity weakness and was diagnosed with an isolated cns relapse. Concurrent hypopituitarism and leukemic retinopathy were also found. After receiving craniospinal radiotherapy and systemic chemotherapy, her retinopathy and vision improved. She is now in complete remission, and she is still on chemotherapy according to the guideline from the Pediatric Oncology Group. Although rare, hypopituitarism and leukemic retinopathy should be taken into consideration in patients with cns involvement by leukemia.

Dasatinib for a child with Philadelphia chromosome-positive acute lymphoblastic leukemia and persistently elevated minimal residual disease during imatinib therapy.

Imatinib has improved outcomes in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (all). Minimal residual disease (mrd) is a useful tool for predicting leukemia relapse. However, there is no consensus on how to treat children with elevation of BCR-ABL transcripts but no evidence of hematologic relapse during chemotherapy combined with imatinib. Here, we report the case of a child with Ph+ all who had persistent elevation of mrd, but no evidence of hematologic relapse while receiving imatinib plus intensive chemotherapy. Dasatinib was substituted for imatinib because no suitable donor for allogeneic hematopoietic stem-cell transplantation (hsct) was available. Less-intensive chemotherapy with methotrexate and 6-mercaptopurine was administered concomitantly. No serious adverse events were encountered. With continuous dasatinib combined with chemotherapy, but no allogeneic hsct, our patient reached complete molecular remission and has been in complete molecular remission for more than 13 months. This report is the first about the long-term use of dasatinib in patients with Ph+ all and mrd elevation but hematologic remission during imatinib chemotherapy. In a similar situation, chemotherapy combined with dasatinib instead of allogeneic hsct could be considered to avoid hsct-related mortality and morbidity. Clinical trials are needed.

Long-term results of Taiwan Pediatric Oncology Group studies 1997 and 2002 for childhood acute lymphoblastic leukemia.

The long-term outcome of 1390 children with acute lymphoblastic leukemia (ALL), treated in two successive clinical trials (Taiwan Pediatric Oncology Group (TPOG)-ALL-97 and TPOG-ALL-2002) between 1997 and 2007, is reported. The event-free survival improved significantly (P=0.0004) over this period, 69.3+/-1.9% in 1997-2001 to 77.4+/-1.7% in 2002-2007. A randomized trial in TPOG-97 testing L-asparaginase versus epidoxorubicin in combination with vincristine and prednisolone for remission induction in standard-risk (SR; low-risk) patients yielded similar outcomes. Another randomized trial, in TPOG-2002, showed that for SR patients, two reinduction courses did not improve long-term outcome over one course. Decreasing use of prophylactic cranial irradiation in the period 1997-2008 was not associated with increased rates of CNS relapse, prompting complete omission of prophylactic cranial irradiation from TPOG protocols, beginning in 2009. Decreased use of etoposide and cranial irradiation likely contributed to the low incidence of second cancers. High-risk B-lineage ALL, T-cell, CD10 negativity, t(9;22), infant, and higher leukocyte count were consistently adverse factors, whereas hyperdiploidy >50 was a consistently favorable factor. Higher leukocyte count and t(9;22) retained prognostic significance in both TPOG-97 and TPOG-2002 by multivariate analysis. Although long-term outcome in TPOG clinical trials is comparable with results being reported worldwide, the persistent strength of certain prognostic variables and the lower frequencies of favorable outcome predictors, such as ETV6-RUNX1 and hyperdiploidy >50, in Taiwanese children warrant renewed effort to cure a higher proportion of patients while preserving their quality of life.

Therapeutic potential of human umbilical cord-derived stem cells in ischemic diseases.

Recent advances suggest human umbilical cord is a new source for stem cells. Our laboratory has established a method to readily isolate and expand stem cells from human umbilical cord tissues. The aim of this study was to investigate the therapeutic potential of human umbilical cord-derived stem (UCDS) cells in ischemic diseases. The UCDS cells were characterized by flow cytometry and differentiation into osteogenic and adipogenic cells. Unilateral hind limb ischemia was surgically induced by femoral artery ligation in nude mice. The animals were intramuscularly injected with 10(6) UCDS cells or control phosphate-buffered saline. Blood perfusion of ischemic limbs was detected by laser Doppler perfusion imaging. Transplantation of UCDS cells to the ischemic limbs of nude mice significantly improved the blood flow to the affected limbs. Thus, transplantation of UCDS cells may potentially be a promising treatment for human ischemic diseases.

Mathematical model for carbon dioxide evolution from the thermophilic composting of synthetic food wastes made of dog food.

The impacts of the aeration and the agitation on the composting process of synthetic food wastes made of dog food were studied in a laboratory-scale reactor. Two major peaks of CO(2) evolution rate were observed. Each peak represented an independent stage of composting associated with the activities of thermophilic bacteria. CO(2) evolutions known to correlate well with microbial activities and reactor temperatures were fitted successfully to a modified Gompertz equation, which incorporated three biokinetic parameters, namely, CO(2) evolution potential, specific CO(2) evolution rate, and lag phase time. No parameters that describe the impact of operating variables are involved. The model is only valid for the specified experimental conditions and may look different with others. The effects of operating parameters such as aeration and agitation were studied statistically with multivariate regression technique. Contour plots were constructed using regression equations for the examination of the dependence of CO(2) evolution potentials on aeration and agitation. In the first stage, a maximum CO(2) evolution potential was found when the aeration rate and the agitation parameter were set at 1.75 l/kg solids-min and 0.35, respectively. In the second stage, a maximum existed when the aeration rate and the agitation parameter were set at 1.8 l/kg solids-min and 0.5, respectively. The methods presented here can also be applied for the optimization of large-scale composting facilities that are operated differently and take longer time.

Amino acid concentrations in cerebrospinal fluid in children with acute lymphoblastic leukemia undergoing chemotherapy.

Cerebrospinal fluid (CSF) amino acid concentrations were measured in 45 children with acute lymphoblastic leukemia (ALL). Central nervous system (CNS) disease was absent in 34 and present in 11 (Groups L and M, respectively) at diagnosis. Thirty-two otherwise healthy children with febrile convulsions were studied for comparison. Results from this study show that glutamine levels at Day 0 were significantly higher in patients than in controls. Patients in Group M had elevated glutamine levels compared to Group L. In comparison, at Day 14, concentrations of glutamine and asparagine decreased, while glutamic acid amounts increased significantly in Group L. Glutamine levels fell at Day 42 in Group M, which may have resulted from more intensive treatment. From this study we hypothesise that higher baseline glutamine levels are indicative of a greater risk for CNS leukemia. Large-scale prospective trials are required to confirm increased baseline CSF glutamine levels in ALL patients, to identify glutamine as a marker for CNS disease and to clarify underlying mechanisms regulating glutamine in ALL.

Estrogen and laryngeal synaptic strength in Xenopus laevis: opposite effects of acute and chronic exposure.

Synaptic transmission at the vocal synapse, the laryngeal neuromuscular junction, of Xenopus laevis has been shown to be regulated by long-term changes in circulating estrogen. In females, high levels of circulating estrogen also accompany gonadotropin-induced ovulation and oviposition and the switch from sexually unreceptive to receptive states, including changes in vocal behaviors (ticking to rapping). Here we examine the effects of gonadotropin injection on laryngeal synaptic strength and call type. Gonadotropin acutely reduced quantal content values of laryngeal synapses in intact, adult females; the lowest values were attained by 12 h post-injection. Estrogen and progesterone levels increased following human chorionic gonadotropin (hCG) injection; the time course was similar to, but negatively correlated with, changes in synaptic strength. In ovariectomized frogs, exogenous estrogen, but not progesterone or hCG, mimicked the acute effects of hCG in weakening laryngeal synapses of intact frogs. hCG injection suppressed ticking and sometimes induced rapping. Females could tick with either strong or weakened laryngeal synapses while rapping was only produced during the weakening action of hCG. The normally strong synapses of females may enable vocal production even when laryngeal synapses are weakened by hormones that induce ovulation. In contrast to the acute effect of estrogen on weakening laryngeal synapses, juveniles required more than 2 weeks of estrogen treatment to strengthen laryngeal synapses while at least 4 weeks postovariectomy were required to weaken synapses in adult females. We conclude that acute (hours) increases in circulating levels of estrogen weaken synapses while chronic (weeks) increases strengthen laryngeal synapses.

Lichen sclerosus et atrophicus, bullous morphea, and systemic lupus erythematosus: a case report.

Lichen sclerosus et atrophicus (LSA) rarely coexists with morphea, especially when bullae occur in lesions of morphea. Here we report the case of a 15-year-old girl with this condition, who also fulfilled four out of 11 diagnostic criteria for systemic lupus erythematosus (SLE). Tissue biopsy of different skin lesions showed LSA in the regions of bullous morphea, that has rarely been reported in the literature.

Age-related changes in blood lymphocyte subsets of Chinese children.

BACKGROUND: Flow cytometric analysis of major lymphocyte populations and their subsets reveals age-related changes in the human cellular immune system. SUBJECTS AND METHODS: Immunophenotypic markers were evaluated in 136 healthy pediatric subjects divided into groups of newborn infants (cord blood), children aged 1 to 2 years, 2 to 5 years, and 6 to 15 years. RESULTS: The percentage of T cells increased gradually with age and the evolution of the percentage of B and NK cells was found to be variable. The percentage of CD4+ cells remains relatively unchanged from infancy to adolescence, but the percentage of CD8+ T cells was lowest at birth and reached maximal levels in the one to two year-old period. The percentage of naive T cells declined with time, but the percentage of memory T cells increased with age. Similar trends were seen in T-cell receptor alphabeta- and gammadelta-bearing T cells. The percentage of CD 11b+CD8+ T cells increased gradually from birth and reached maximal levels from 6 to 15 years old. The expression of the activation markers CD25 and HLA-DR on CD4+ T cells increased with age. The percentage of CD16+CD56- NK cells declined with age, but the evolution of the percentage of CD 16-CD56+ NK cells was variable. The fraction of B cells that expressed CD5 was high at birth (72.9%) and was highest in one to two year olds (73.1%), then declined steadily over time. The CD23 antigen was expressed on 41.9% of B cells at birth and 68.6% during the first to second year, then declined steadily with age. CONCLUSION: These data may serve as a reference range for studies of Chinese pediatric subjects.

Comparison of the cuffed oropharyngeal airway and laryngeal mask airway in spontaneous breathing anesthesia.

BACKGROUND: The cuffed oropharyngeal airway (COPA) is a modified Guedel airway with a cuff at its distal end and a standard 15 mm connector at its proximal end. This study was performed to determine if the COPA would offer any advantage over the laryngeal mask airway (LMA). METHODS: Eighty ASA class I to II adult patients scheduled for short elective procedures (less than 1 h) were randomly allocated into two groups. All patients were given atropine 0.01 mg/kg, fentanyl 2 micrograms/kg and propofol 2 mg/kg intravenously for induction of anesthesia. The COPA or LMA was inserted following the loss of eyelash reflex. If the jaw was not relaxed enough for insertion of a COPA or LMA, succinylcholine 1 mg/kg was given to facilitate the insertion. When correctly positioned, the cuff was immediately inflated with an appropriate volume. Gentle positive pressure ventilation was applied before spontaneous breathing resumed. Capnography was used to assess the patency of the airway. Anesthesia was maintained with isoflurane-N2O-O2 until the end of surgery. The success rate, vital signs, and adverse events were evaluated and compared. RESULTS: The success rate in the LMA group (95%) was higher than the COPA group (85%). The increase in circulatory response after the LMA insertion was greater than that after the COPA insertion (P < 0.05). Nine patients (22.5%) in the LMA group needed succinylcholine to facilitate insertion compared with only two patients (5%) in the COPA group. Additional manipulation was frequently (57.5%) needed after inserting the COPA to maintain the patency of the airways, but none needed so in the LMA group. Two patients had laryngospasms upon removal of the LMA, but none had laryngospasm in the COPA group. The incidence of sore throat in the LMA group was higher than in the COPA group (18% vs. 10%). CONCLUSIONS: We demonstrated that the COPA could be easily inserted without the need of muscle relaxants in most patients. But the COPA needed airway intervention to provide an effective airway in most patients. Compared with the LMA, the COPA caused less stimulation than the LMA.

Cardiac arrest during anesthesia in a teaching hospital. A 4 years survey.

METHODS: During the past 4 years, 48 cases of cardiac arrest occurred during anesthesia among a total of 104,600 cases of anesthesia at Mackay Memorial Hospital in Taipei. RESULTS: The incidence of cardiac arrest was thus about 0.046% (48/104,600), with the causative factors being anesthetic related in 21% (10/48) of cases, surgical factors in 19% (9/48) of cases and patient's pathological factors in 60% (29/48) of cases. Of these 48 patients, 34 died and 14 survived after cardiopulmonary resuscitation (CPR). Anesthesia contributed to death in 3 cases of a total of 104,600 cases of anesthesia giving an approximate incidence of 3/100,000. Two of these 3 cases were avoidable.

Differential cytotoxicity of cadmium to rat embryonic fibroblasts and human skin fibroblasts.

In order to identify why cadmium is differentially toxic to humans and rats, we compared cadmium-induced cytotoxic responses in rat embryonic fibroblasts (REF) and human skin fibroblasts (HFW). According to the values of the lethal concentration 50% for cadmium, REF were about 13-fold more sensitive than HFW to cadmium acetate (1.5 vs 25 microM). Furthermore, progression of S phase cells was more severely delayed by cadmium in REF than in HFW. At doses that killed 90% of REF or HFW (5 or 50 microM, respectively), 50% of DNA synthesis was inhibited in REF, whereas DNA synthesis was not apparently inhibited in HFW. The differential sensitivity to cadmium could not be simply due to different basal levels of metallothionein, since the cellular metallothionein content in HFW was only 1.6 times that in REF, and metallothionein was apparently induced by cadmium in both cells with similar synthesis rates. Furthermore, elevation of cellular metallothionein levels by zinc sulfate pretreatment decreased cadmium toxicity in both cell types, but did not alter their relative sensitivity to cadmium. The differential sensitivity was also not due to differences in cadmium accumulation, since HFW accumulated more cadmium than REF after a 24-hr exposure to 1 or 5 microM cadmium acetate. Although most of the cadmium remained in the cytoplasm, the nuclei of REF contained 12-fold more cadmium than nuclei of HFW (1.31 vs 0.11 micrograms Cd/mg nuclear protein). Therefore, our results indicate that a high level of cadmium accumulation in nuclei of REF may be responsible for cell killing through breakdown of nuclear functions.

[4P- syndrome (Wolf-Hirschhorn syndrome) complicated with delay onset of malignant hyperthermia: a case report].

One 8-month-old female patient, weighted 5 kg, with congenital abnormality (4P- syndrome) underwent elective cheiloplasty for cleft lip and palate. Two hours later, with smooth anesthesia and operation, a life-threatening anesthetic complication of malignant hyperthermia occurred at pediatric intensive care unit. The immediate treatments were initially hyperventilating the patient with 100% O2 and cooling the patient with ice bags. Subsequently, intravenous dantrolene 2.5 mg/kg and symptomatic supportive care were administered successfully to treat the event. Upon reviewing the articles, we found that a congenital chromosome 4P deletion abnormality complicated with a delay onset of malignant hyperthermia has not been described previously.

Arthrogryposis multiplex congenita: report of a case of amyoplasia.

Arthrogryposis multiplex congenita is a congenital syndrome characterized by multiple congenital joint contractures; and refers to a large heterogeneous group of disorders. We present a 40 days old male baby who has had multiple fixed contractures of joints since birth. Midline capillary hemangioma, internal rotation of bilateral shoulders, extension contracture of elbows, flexed wrists with pronation deformity, flexion and internal rotation of hips, equinovarus of feet were noted. A series of examinations for differential diagnosis including brain sonogram, echocardiogram, muscle echogram, muscle biopsy, chromosome study were performed and all showed normal findings. Amyoplasia was impressed. Early rehabilitation was arranged. Normal intelligence and a normal life span are expected.

[Surgical and anesthetic mortality in Mackay Memorial Hospital 1988-1989].

The mortality associated with 52128 anesthetics administered over two years (1988-1989) at Mackay Memorial Hospital, Taipei, was reported. The frequency of death to which anesthesia contributed was 0.4/10000 (2 cases in 52128 anesthetics). The total mortality rate from surgery within one week was 0.2% (105 cases in 52128 anesthetics). Anesthetic deaths were responsible for 1.9% of the total mortality. There were 25 cases of cardiac arrest with 18 fatal cases (7 cases were recovered after cardiopulmonary resuscitation). The causes of cardiac arrest during anesthesia included anesthetic factors (24%), surgical factors (24%) and patients' pathological factors (52%).

Treatment of malignant trophoblastic tumors. An analysis of 209 cases.

From 1948 to 1985, a total of 630 cases of choriocarcinoma and invasive mole were treated in our hospital. The methods of treatment varied in different periods of time. In the third period (1972-1985), 5 Fu and/or KSM were the main therapeutic agents used in the treatment of 110 cases of choriocarcinoma and 99 cases of invasive mole. Metastases were observed in more than 90% of cases of choriocarcinoma and nearly 1/4 belonged to stage IV. The mortality of choriocarcinoma decreased from 84.3% to 32.7% after treatment and that of invasive mole from 32.4% to 8.1%. 43 of 80 patients treated with chemotherapy alone conceived after recovery, resulting in a total of 50 pregnancies including 31 term deliveries by 28 women. All the children are normal and healthy, the eldest being 11 years old now.