Objective To explore the changes of CD40 and CD40 ligand(CD40L) levels and investigate their significances in children with graft-versus-host disease(GVHD)after related-donor human leukocyte antigen(HLA) matching allogeneic hematopoietic stem cell transplantation(HSCT).Methods Nineteen patients with ?-thalassemia major and 1 patient with congenital inherent hemolytic anemia accepted umbilical cord blood transplantation(UCBT) and allogeneic peripheral blood stem cell transplantation(allo-PBSCT),respectively,and all cases were received successfully related-donor human leukocyte antigen matching allogeneic HSCT.Peripheral blood samples were obtained before and after transplantation,the time when GVHD happened,the expressions of CD40 and CD40L were measured by using immunofluresence asssy.Results Four UCBT children and 3 allo-PBSCT children had no acute GVHD.Thirteen children had acute GVHD(degreeⅠ-Ⅳ),the expressions of CD40L on CD4+ and CD8+ T cells in the patients with acute GVHD increased,especially in allo-PBSCT.Five cases of UCBT and 12 cases of allo-PBSCT patients had chronic GVHD,the expressions of CD40L+,CD25+ and CD69+ on CD4+ and CD8+ T cells in patients with chronic GVHD increased obviously.The expression of CD19+CD40+ was lower than normal within 3 months after transplantation.Conclusions The high expression of CD40L+T cells in periferal blood after HSCT was related to the activation and proliferation of T cells in the development of GVHD in HSCT.

Objective:To know the effect of counseling on personality feature and self-conscious symptom of college students with internet addiction disorder (IAD).Methods:Before and after counseling,38 students with IAD in Guangdong Medical College (GDMC)were measured by Sixteen Personality Factor Questionnaire (16PF)and Symptom Check List 90 (SCL-90).Results:After counseling,these students with IAD had higher scores of 4 factors in 16PF(sociability,intelligence,perseverance,autonomy),had lowerer scores of 5 factors in 16PF (daring,suspicion,illusion,anxiety,tensity),and had lower scores of 6 factors in SCL-90 (force,interpersonal sensitivity,depression,anxiety,hostility,terror)(P＜0.05 or P＜0.01).Conclusion:To college students with IAD, counseling could enhance their positive personality features,weaken their negative personality feature and mitigate their self- conscious symptom.

The genome of Epstein-Barr virus (EBV) encodes proteins essential for malignant transformation, for example, latent membrane protein 1 (LMP1). Whereas, LMP1 up-regulates anti-apoptotic proteins to support viral replication, it also potentiates apoptosis, suggesting that a viral protein contributes to the survival of the virus, and it also elicit host defense leading to the destruction of the infected cells. The antitumor immunity is exerted by infiltrated CD8+ T cells elaborating cytotoxic effectors, like Fas ligand (FasL,CD95L or CD178). As a nuclear factor-κB (NF-κB)-dependent molecule,Fas is induced by LMP1, and LMP1 enhances Fas-mediated apoptosis,according to our finding of stimulus-dependent apoptosis regulation by LMP1.Data has shown that FasL-mediated cytotoxicity has significant therapeutic effect on EBV-associated nasopharyngeal carcinoma (NPC). Recent reports suggest that mutations affecting the Fas-mediated apoptotic pathway reduce individuals' susceptibility to cancers, but cytokine-targeting therapy which precisely regulates the Fas level on tumor cells could still contribute to enhancement of antitumor immunity in cancer patients.

Objective To study the pharmacokinetic and pharmacody-namic characteristics of febuxostat tablets after single and mutiple oral dose in hyperuricemia patients with chronic kidney disease .Methods A total of 18 hyperuricemia patients with chronic kidney disease were ran-domly divided into three groups , each group containing 6 patients as fol-lows: those in group A were administrated with a single oral dose of febuxostat tablet 40 mg, those in group B were administrated with a single oral dose of febuxostat tablet 80 mg, and followed by multiple oral doses of febuxostat 80 mg, qd for 28 days and those in group C were treated with a single oral dose of febuxostat tablet 120 mg.The serum uric acid was determined by clinical chemistry testing , and the plasma drug levels were determined by HPLS -MS/MS method.Results The main febuxostat pharmacokinetic parameters of a single oral administra-tion of 40, 80 and 120 mg division were as follows: t1/2 were (3.98 ±1.45), ( 4.63 ±1.37 ) and ( 4.27 ±1.33 ) h; tmax were (0.97 ±0.39), ( 1.22 ±0.46 ), ( 1.35 ±0.37 ) h; Cmax were (1626.33 ± 342.97 ) , ( 2669.27 ± 384.91 ) , ( 3904.83 ± 835.98 ) ng ? mL-1; AUC0-24 h were (4324.32 ±976.87), (8415.4 ±1965.9), (12979.6 ±3788.5) ng? h? mL -1.Drug accumulation was not detec-ted following multiple oral doses .After 4 weeks treatment (80 mg, qd) , febuxostat lowered the serum uric acid levels of hyperuricemia patients with chronic kidney disease significantly , and the target serum uric acid level (6.0 mg? dL -1 ) was achieved in 5 patients.Conclusion Febuxostat displayed a linear pharmacokinetic profile in single oral doses of 40 to 120 mg.Continuous oral therapic dose of febuxostat tablets can significantly reduce the uric acid levels in hyperu -ricemia patients with chronic kidney disease .

This study was aimed to investigate the therapeutic efficacy of rabbit anti-thymocyte globulin (r-ATG) combined with cyclosporine A (CsA) and to analyse the efficacy-related factors in children with aplastic anemia (AA). Twenty five AA children treated with r-ATG [3.5 mg/(kg·d)×5 days] combined with CsA were analyzed retrospectively. The lymphocyte subgroups, CD4(+)/CD8 ratio and expression of CD55, CD59 on surface of neutrophils and erythrocytes in peripheral blood were detected by direct immunofluorescence method and flow cytometry; the responsive time, effective rate, adverse effects and infections after immunosuppressive therapy (IST) were analyzed; the distribution of T-lymphocyte subgroups in IST-effective and IST-uneffective groups was compared, and therapeutic efficacy-related factors were evaluated. The results showed that the response to treatments was found in 21 out of 25 cases, the total responsive rate was 84.0%; the response time was 3 - 6 months, average of 4 months; the effective rates in month 3, 6, 9, 12 after treatment were 56.0%, 72.0%, 80.0% and 84.0% respectively. The AA children with age ≥ 5 years old, course of disease < 6 months and absolute neutrophil value ≥ 1.5 ×10(9)/L on 30 days after IST had good curative effect; the effective rate in AA children with age ≥ 5 years old, course of disease < 6 months, high or reverse ratio of CD4(+)/CD8(+) and absolute neutrophil value ≥ 1.5×10(9)/L after IST was higher than that in AA children with age < 5 years old, course of disease ≥ 6 months, normal ratio of CD4(+)/CD8(+) and absolute neutrophil value after IST < 1.5×10(9)/L (94.4% vs 57.1%, 90.4% vs 50.0%, 94.1% vs 62.5%, 94.1% vs 62.5%) (P < 0.05). The high effective rate was observed in AA children with decrease of CD55 and CD59 expression, but there was no significant difference (P > 0.05) as compared with normal expression of CD55, CD59. It is concluded that the treatment using r-ATG (3.5 mg/kg·d × 5 d) combined with CsA is a safe and effective for children with AA. Age, course of disease and absolute neutrophil value on 30 days after IST are the main factors affecting curative affect.
Adolescent ; Anemia, Aplastic ; drug therapy ; Antilymphocyte Serum ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Cyclosporine ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Female ; Humans ; Lymphocyte Count ; Lymphocyte Subsets ; Male ; Retrospective Studies ; Treatment Outcome

OBJECTIVEChronic graft versus host disease (cGVHD) is the most common late complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and it represents the major cause of mortality in long-term survivors. Over the past decade, although conventional therapy has achieved complete responses in approximately 50% of patients, the prophylaxis and treatment of cGVHD are still not satisfactory. In the late years, utilization of new immunosuppressant such as tacrolimus (FK506), mycophenolate mofetil (MMF) on cGVHD improved the curative effects. This study tried to analyze the results of combination of methylprednisolone (MP), MMF and FK506 or cyclosporine A (CSA) as immunosuppressive therapies for cGVHD and to explore the effective regimen for children.

METHODSForty-five patients received allo-HSCT. Among them 32 received UCBT and 13 received PBSCT. The conditional regimen mainly consisted of busalphan, cyclophosphamide, antihuman thymocyte globulin, fludarabin, melphalan, thiotepa and total lymph node irradiation. Prophylaxis of GVHD consisted of CSA, MP and MMF. Patients with cGVHD received a regimen with combination of MP, MMF and FK506 or CSA.

RESULTSSeventeen out of 32 patients who received UCBT were engrafted. while 9 out of 13 patients who received PBSCT were engrafted. Nine cases of the 30 engrafted patients developed cGVHD (morbidity 30%). Among the 17 patients who received UCBT, 3 developed cGVHD (18%). Among the 13 patients who received PBSCT, 6 developed cGVHD (46%). Six cGVHD continued from aGVHD (6/9). One patient was given CSA plus MMF, and 8 were given three-drug regimen with MP, MMF and FK506. The overall response rate was 100%. Two patients died of CMV-IP or septicemia (mortality 20%). Seven (78%) patients survived (event free survival, EFS) longer than 3 years. The side effects included hepatotoxicity, nephrotoxicity, hypertension, articular capsulitis and arrhythmia. The main complication and the major causes of death were infection.

CONCLUSIONThe incidence of cGVHD is low in children. The incidence of cGVHD after PBSCT is higher than that after UCBT. aGVHD is a highly dangerous factor. Combined therapy of MP plus MMF and FK506 or CSA is safe and effective for the treatment of cGVHD in children.

Child ; Child, Preschool ; Chronic Disease ; Drug Therapy, Combination ; Female ; Graft vs Host Disease ; drug therapy ; epidemiology ; prevention & control ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Incidence ; Male ; Methylprednisolone ; administration & dosage ; Mycophenolic Acid ; administration & dosage ; analogs & derivatives ; Tacrolimus ; administration & dosage

OBJECTIVETo evaluate the clinical effect and side-effect of interferon-alpha (IFN-a) and ribavirin (RBV) combination therapy for Chinese patients with co-infection of hepatitis C virus (HCV) and human immunodeficiency virus (HIV), and to compare them with only HIV infection patients.

METHODS10 patients with HCV-HIV and 17 patients with only HCV infection received 5 million units of IFNalpha-2b every other day intramuscularly, and 300 mg RBV orally three times a day. Dynamic observations were done for HCV RNA and HIV RNA loads, CD4+ and CD8+ T lymphocyte counts, liver function and blood cell measures, and the side-effects of the medicines.

RESULTSAfter 12 weeks and 24 weeks of IFNalpha and RBV combination therapy, mean HCV RNA levels reduced 1.14 log (t = 3.843, P < 0.01) and 2.08 log (t =6.564, P < 0.01) from the baseline at week 0 in the HCV-HIV co-infection group, and reduced 1.48 log (t = 6.438, P less than 0.01) and 2.33 log (t = 7.343, P < 0.01) in the HCV infection group. Meanwhile, the HIV RNA levels decreased 1.22 log (t = 3.662, P < 0.01) and 1.73 log (t = 6.119, P < 0.01) from the base line. However, there were no obvious different changes among T lymphocyte counts of HCV-HIV and HCV patients at week 0, week 12 and week 24. All 27 patients showed satisfactory biochemical response to therapy. There were some mild or moderate influenza-like symptoms, intestinal discomfort and decreased blood cell counts in the early stages of the treatments. No neuropsychic and auto-immune disorders were found.

CONCLUSIONSIFNalpha-2b and RBV combination therapy showed similar anti-HCV effects during the 24 week treatment for HCV-HIV and HCV infected patients, and some anti-HIV effect was also observed. No obvious different biochemical responses and side-effects were found between the above two groups.

Adult ; Antiviral Agents ; administration & dosage ; Drug Therapy, Combination ; Female ; HIV Infections ; complications ; drug therapy ; Hepatitis C, Chronic ; complications ; drug therapy ; Humans ; Interferon-alpha ; administration & dosage ; Male ; Ribavirin ; administration & dosage

BACKGROUNDIt is internationally accepted that in drug-naïve individuals with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection, chronic hepatitis C should be treated first if the CD4 cell count does not require the initiation of anti-retroviral therapy. Present paper evaluated the clinical effect and side-effect of interferon-alpha (IFN-alpha) and ribavirin (RBV) combination therapy for Chinese patients with HCV-HIV co-infection, and compared with them for HIV infection alone.

METHODSTen patients with HCV-HIV and 17 patients with HCV received 5 million unit IFNalpha-2b every other day intramuscularly, and 300 mg RBV triple daily by oral. Dynamic observations were made for HCV RNA and HIV RNA loads, CD4+ and CD8+ T lymphocyte counts, liver function and blood cell measurement, and the medicine side-effects.

RESULTSAfter 12-week and 24-week treatments of IFN-alpha and RBV combination therapy, mean HCV RNA levels reduced 1.14 logs and 1.56 logs from the baseline at week 0 in HCV-HIV co-infection, and reduced 1.48 logs and 1.75 logs in HCV infection, respectively. The HIV RNA levels decreased 1.22 logs and 1.32 logs from the base line; however, there were no obvious different changes at T lymphocyte counts of HCV-HIV and HCV patients through 24-week treatments. Whole 27 patients showed satisfactory biochemical response to therapy. There were some mild or mediate influence-like symptoms, intestinal uncomfortable and depressed blood cell counts in early stage of the treatments. No neuropsychiatric and auto-immune disorders were found.

CONCLUSIONSIFN-alpha and RBV combination therapy had similar anti-HCV effects during 24-week treatment for HCV-HIV and HCV infected Chinese patients, and some anti-HIV effect. There were no obvious different biochemical responses and side-effects between two groups above.

Adult ; Antiretroviral Therapy, Highly Active ; CD4 Lymphocyte Count ; Drug Therapy, Combination ; Female ; HIV Infections ; drug therapy ; immunology ; virology ; Hepatitis C, Chronic ; drug therapy ; immunology ; virology ; Humans ; Interferon-alpha ; administration & dosage ; Male ; Middle Aged ; RNA, Viral ; analysis ; Recombinant Proteins ; Ribavirin ; administration & dosage

OBJECTIVETo investigate the clinical features of severe acute respiratory syndrome (SARS).

METHODSForty-one medical care workers (aged 23 - 55 years, with a average of 32 years; men/women = 8/32) who were admitted to our hospital and diagnosed with SARS during March and April, 2003 were retrospectively analyzed.

RESULTSThirteen of all the patients were physicians and the rest were nurses. The disease was mainly transmitted through air droplet in a short distance, and overwork induced tiredness was involved in disease stimulation. Seventy-three percent of the patients presented fever as their first symptom. Ten patients complained inertia and myalgia. One patient showed no clinical symptoms, and bilateral infiltrates was found in his chest X-ray. Among the 41 cases, 6 (15%) were diagnosed as severe type. At the first week, the counts of white blood cells (WBCs), lymphocyte and platelets were (4.4 +/- 1.5) x 10(9)/L, 0.22 +/- 0.12 and (143 +/- 37) x 10(9)/L, which were significantly lower when compared with those at the 2nd to 4th week. Abnormal liver function was found in 27 cases (mostly with elevated serum ALT), with 70% occurred at the 3rd or 4th week. In terms of CT, 30 patients (73%) showed pathological changes in lungs, and bilateral lung involvement was found in 35.59%. Of 36 cases treated with steroids, 86% received middle or low dosage (80 - 240 mg/d). Artificial ventilation was used for twenty-seven patients, and air pipe mechanical ventilation was used for 1 case. Mortality in this study was 5%.

CONCLUSIONSInertia and myalgia may be the earlier symptoms of health care workers with SARS include, which are parallel to CT manifestations. There is no objective index for the assessment of the severity of the disease at early stage. The medicine associated toxicities may be the main reason of liver lesions. damages. Middle or low dosage of steroid was reasonable to be used as early as possible.

Adult ; Female ; Humans ; Infectious Disease Transmission, Patient-to-Professional ; Male ; Methylprednisolone ; therapeutic use ; Middle Aged ; Nurses ; Physicians ; Respiration, Artificial ; Retrospective Studies ; Severe Acute Respiratory Syndrome ; diagnosis ; therapy ; transmission

OBJECTIVEAplastic anemia is characterized by bone marrow failure and marked reduction of white blood cells, red blood cells and platelets in peripheral blood. Clinical studies have shown that immunosuppressive therapy greatly prolonged the long-term survival of some patients with aplastic anemia. But in severe aplastic anemia (SAA) patients whose ANC was < 0.5 x 10(9)/L, platelets were < 20 x 10(9)/L, very low bone marrow proliferation and high death rate were observed. The present study aimed to evaluate the efficacy of immunosuppressive treatments with cyclosporine A (CSA) alone or CSA combined with antithymocyte globin (ATG) in children with acquired SAA.

METHODSFifty-four cases with SAA were treated with immunosuppressive agents mentioned above in our department from Jan. 1997 to June 2003, 31 of the cases had treated with CSA combined with ATG. There were 18 cases with SAA type I and 13 cases with SAA type II in CSA combined with ATG group, and 13 cases had very severe aplastic anemia. The other 23 cases were treated with CSA alone (CSA group), 10 of these cases had SAA-I and 13 had SAA-II, and 5 cases had very severe aplastic anemia. The responsive rate, relapse, adverse reactions and event free survival (EFS) were compared between CSA combined with ATG group and CSA group.

RESULTSThe proportions of patients with different types of the disease and severity were comparable between the two groups. The responsive time of the CSA combined with ATG group and CSA group was 2.5 months and 3.5 months, respectively (P < 0.05), the responsive rate in two groups was 81% (25/31) and 52% (12/23), respectively (chi(2) = 4.962, P < 0.05). In 37 cases who were responsive to therapy, the relapse rate was 8% (2/25) and 50% (6/12) respectively (chi(C)(2) = 6.143, P < 0.05). There were no significant differences in adverse reactions to the immunosuppressive agents. All cases were followed-up for more than 1 year, and the event-free survival over one year in these two groups was 81% (25/31) and 52% (12/23), respectively. Forty-seven cases were followed-up for more than two years, and the event-free survival was 74% (20/27) and 50% (10/20), respectively (P < 0.01). Twelve cases were followed-up for over 5 years. There were no secondary tumor, myelodysplastic syndrome and other colony diseases.

CONCLUSIONThe immunosuppressive therapies for acquired severe aplastic anemia in childhood were effective. The effect of CSA combined with ATG was better than that of CSA alone, and the relapse rate was lower with the combined treatment. However, the long-term effect needs longer follow-up studies to evaluate.

Adolescent ; Anemia, Aplastic ; drug therapy ; Antilymphocyte Serum ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Cyclosporine ; administration & dosage ; therapeutic use ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Male