To develop estradiol transdermal film-forming spray (TFS), various polymers were screened using solvent appearance, spray ability, film-forming rate and appearance as indices. The influence of polymer type, plasticizer and penetration enhancer on the transdermal flux were investigated by selecting porcine skin as model, and transdermal flux of TFS was compared with commercial patch and gel. The drug existing state in the formed film was investigated by differential scanning calorimetry (DSC). The solvent appearances, spray abilities, film-forming rates and appearances of eudragit E PO, RL PO, hydroxypropyl cellulose EF, polyvinylpyrrolidone K30, Plasdone S630 and Agrimer VA64 were suitable for the preparation of TFS. TFS prepared by Eudragit RL PO had the biggest transdermal flux of estradiol among all the polymers investigated. Triethyl citrate, the plasticizer, decreased the transdermal flux. Azone increased the transdermal flux, while oleic acid, isopropyl myristate and menthol had opposite effects. TFS had a higher transdermal rate and a higher accumulative penetrated estradiol of 24 h than commercial patch and gel. The DSC result showed that estradiol was spread as molecule in the formed film of TFS. It was indicated that TFS could be expected to be an effective transdermal drug delivery system.
Administration, Cutaneous ; Aerosols ; Animals ; Azepines ; chemistry ; Calorimetry, Differential Scanning ; Cellulose ; analogs & derivatives ; chemistry ; Citrates ; chemistry ; Drug Delivery Systems ; Estradiol ; administration & dosage ; pharmacokinetics ; Plasticizers ; chemistry ; Polymers ; chemistry ; Skin Absorption ; Swine

Our objective is to report a female carrier of Duchenne muscular dystrophy (DMD) presented with remarkable asymmetric limb weakness and atrophy caused by a heterozygous point mutation in DMD gene. The patient was born in a non-consanguineous marriage. She experienced slowly progressive weakness and atrophy of her right limbs for approximately 20 years. The thigh muscle magnetic resonance imaging (MRI) showed obvious atrophy with fatty replacement on the right thigh compared with the left, and the ‘trefoil with single fruit sign’ was observed. Muscle pathology revealed decreased dystrophin protein expression in scattered fibers. The multiplex ligation-dependent probe analysis (MLPA) analysis did not detect any large rearrangements. Subsequent whole exome sequencing (WES) identified a heterozygous nonsense mutation, c.1471C>T (p. Q491* ) of dystrophin (DMD) gene in the patient. This report highlights that marked hemiatrophy can occur in a female manifesting carriers of DMD and WES should be considered in MLPA-negative patients. Muscle MRI can serve as an adjunct to diagnose dystrophinopathies.

OBJECTIVETo investigate the role of 99mTc-TRODAT-1 SPECT in diagnosis and assessing severity of idiopathic Parkinson's disease (PD).

METHODSThirty-eight patients with primary, tentative diagnosis of PD and eighteen age-matched normal controls were studied with 99mTc-TRODAT-1 SPECT imaging. The regions of interests (ROIs) were drawn manually on cerebellum (CB), occipital cortex (OC) and three transverse plane slice-views of striatums, the semiquantitative BG (background)/[(OC+CB)/2] were then calculated.

RESULTSA lower uptake of 99mTc-TRODAT-1 in striatums were displayed in thirty-six out of thirty-eight PD patients by visual inspection, compared to controls. In twenty-four PD cases with (Hoehn and Yahr scale) HYS stage I, a greater loss of DAT uptake was found in striatum and its subregions contralateral striatum to the affected limbs than in the same regions of the controls, although the striatal uptake was bilaterally reduced. Using Spearman correlation analysis showed that the reduction of the uptake ratios significantly correlated with the UPDRS in striatum and all its subregions in the PD group (P<0.05), a similar change was also found in the putamen by using the rating scale of Hoehn and Yahr (P<0.05). However, analysis of variance (ANOVA) did not show any relationship between the decreasing uptake of 99mTc-TRODAT-1 and increasing severity of PD patients, although the specific uptake of 99mTc-TRODAT-1 was continuously decreased in the striatum by visual inspection with the progress of PD from HYS stage I to III.

CONCLUSION99mTc-TRODAT-1 SPECT imaging may serve as a useful method for improving the correct diagnosis of PD. In assessing the role of 99mTc-TRODAT-1 SPECT in disease severity of PD, UPDRS can offer a comprehensive index, although the Hoehn and Yahr assessment may be available in part.

Adult ; Aged ; Corpus Striatum ; diagnostic imaging ; metabolism ; Dopamine Plasma Membrane Transport Proteins ; Feasibility Studies ; Female ; Humans ; Male ; Membrane Glycoproteins ; metabolism ; Membrane Transport Proteins ; metabolism ; Middle Aged ; Nerve Tissue Proteins ; metabolism ; Organotechnetium Compounds ; pharmacokinetics ; Parkinson Disease ; diagnostic imaging ; metabolism ; Radiopharmaceuticals ; pharmacokinetics ; Reproducibility of Results ; Sensitivity and Specificity ; Severity of Illness Index ; Tomography, Emission-Computed, Single-Photon ; methods ; Tropanes ; pharmacokinetics

OBJECTIVETo measure the serum level of secretory type II phospholipase A2 (sPLA2) in patients with coronary heart disease and investigate the possible relationship with IL-8 and LPA.

METHODSA total of 110 patients with acute coronary syndrome (ACS), 63 patients with stable coronary heart disease (SCHD) group and 89 non-CHD control patients were studied. Serum levels of sPLA2, IL-8, LPA and hs-CRP were measured and the correlation among these parameters was observed.

RESULTSThe levels of serum sPLA2 [(68 +/- 17) U/ml], IL-8 [(182 +/- 80) pg/ml] and LPA [(2.85 +/- 0.36) micromol/L] were significantly higher in CHD patients than those in controls [sPLA2: (55 +/- 12) U/ml; IL-8: (119 +/- 33) pg/ml; LPA: (2.34 +/- 0.36) micromol/L, all P < 0.01], and sPLA2 and IL-8 were also significantly higher in ACS patients [sPLA2: (71 +/- 18) U/ml; IL-8: (195 +/- 78) pg/ml] than those in SCHD patients [sPLA2: (63 +/- 12) U/ml; IL-8: (159 +/- 79) pg/ml, both P < 0.01]. Serum sPLA2 level was positively correlated with hs-CRP, IL-8 and LPA (r = 0.203, P = 0.007; r = 0.658, P < 0.01; r = 0.231, P = 0.005, respectively). The relative risk of having CHD is 6.248 (P < 0.01) with the sPLA2 level above 63.75 U/ml.

CONCLUSIONElevated serum sPLA2 level is a risk factor for CHD.

Adult ; Aged ; Aged, 80 and over ; C-Reactive Protein ; metabolism ; Coronary Angiography ; Coronary Disease ; blood ; diagnostic imaging ; Female ; Group II Phospholipases A2 ; Humans ; Interleukin-8 ; blood ; Lysophospholipids ; blood ; Male ; Middle Aged ; Phospholipases A ; blood ; Phospholipases A2

OBJECTIVETo explore the molecular mechanisms involved in the patient with congenital FV deficiency.

METHODSActivity of FV was determined by biochemical method. The PCR products of FV gene was analysed by directly sequencing or sequencing after cloned into T-vector. The mutative FV gene was analysed by restriction enzyme analysis in the proband and her family members.

RESULTSA homozygous missense mutation G5729T resulting in Gly1880Val was revealed in the proband and confirmed in the family screening. Structure-function studies of the factor V mutants (Gly1880Val) demonstrated the importance of Gly1880 for structural stability of the Factor V.

CONCLUSIONG5729T mutation of FV gene is related to the pathogenesis of congenital FV deficiency.

Adult ; DNA Mutational Analysis ; Factor V ; genetics ; metabolism ; Factor V Deficiency ; blood ; congenital ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; Polymerase Chain Reaction

OBJECTIVETo evaluate the therapeutic effects of a combined immunotherapy, high-dose immunoglobulin (HDIG) plus cyclosporine A (CsA) plus prednisone (P), in children with aplastic anemia (AA) and to explore the association of peripheral blood lymphocyte subsets, peripheral blood cells and marrow CD34+ cells with therapeutic effects in AA.

METHODSThe clinical data of 46 children with AA and who received the combined immunotherapy of HDIG + CsA + P were retrospectively studied.

RESULTSOf the 46 children with AA, 31 (67.4%) were responded to the combined immunotherapy. The binary logistic regression analysis showed low absolute neutrophil count (B=4.703, p<0.05), low percentage of peripheral blood CD4+ cells (B=0.142, p<0.05) and low ratio of peripheral blood CD4+/CD8+ (B=2.945, p<0.05)were associated with poor therapeutic effects. The ratio of CD34+/karyocytes of bone marrow in children with AA was lower than that in normal individuals, but it was not significantly related to the therapeutic effect.

CONCLUSIONSThe combined immunotherapy (HDIG+CsA+P) was effective in children with AA. The absolute neutrophilcount, the percentage of peripheral blood CD4+ and the ratio of peripheral blood CD4+/CD8+ were important prognostic factors in AA.

Adolescent ; Anemia, Aplastic ; drug therapy ; immunology ; CD4-CD8 Ratio ; Child ; Child, Preschool ; Cyclosporine ; administration & dosage ; Female ; Humans ; Immunoglobulins ; administration & dosage ; Infant ; Logistic Models ; Male ; Retrospective Studies

BACKGROUNDThe gender difference on long-term outcome in unselected patients after percutaneous coronary intervention (PCI) has not yet been fully investigated. This study aimed to evaluate the gender difference on five-year outcomes following EXCEL biodegradable polymer-coated sirolimus-eluting stenting in patients with coronary disease.

METHODSA total of 2077 "all comers", consisting of 1528 (73.6%) men and 549 (26.4%) women, who were exclusively treated with EXCEL coronary stents were enrolled in the prospective CREATE study at 59 centers from four countries. After propensity score matching, the baseline characteristics of the two groups were well matched. Recommended antiplatelet regimen was clopidogrel and aspirin for six months followed by chronic aspirin therapy. The primary outcome that was the rate of major adverse cardiac events (MACE), defined as a composite of cardiac mortality, non-fatal myocardial infarction (MI) and target lesion revascularization (TLR), and stent thrombosis (ST) at five years were compared between the two gender groups.

RESULTSIn the two groups, women had higher proportions of clinical risk factors, such as being elderly, diabetes mellitus, hypertension and hyperlipidemia, compared to men. Besides, the mean target vessel number per patient was higher and the mean reference vessel diameter smaller for women. Men had higher risks of cardiac death (3.7% vs. 1.6%, P = 0.021) and MACE (8.4% vs. 4.7%, P = 0.004) at five years compared with women. However, the cumulative hazards of non-fatal MI and TLR were similar between men and women. The incidence of Academic Research Consortium (ARC) definite or probable stent thrombosis was similar between the two groups (1.3% vs. 1.0%, P = 0.639). Prolonged clopidogrel therapy (>6 months) did not reduce the cumulative hazards of ST from six months to five years in both men (χ(2) = 0.098, log rank P = 0.754) and women (χ(2) = 2.043, log rank P = 0.153) patients.

CONCLUSIONSWomen had a lower MACE and cardiac death rate than men after biodegradable polymer-coated sirolimus-eluting stenting in long term follow-up. Effects of prolonged dual antiplatelet therapy (DAPT) in preventing stent thrombosis was similar with six-month DAPT after EXCEL stent implantation in both men and women groups.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Coronary Angiography ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Polymers ; chemistry ; Prospective Studies ; Sex Factors ; Sirolimus ; therapeutic use ; Treatment Outcome

OBJECTIVETo study the clinical characteristics of ecotopic viral integration site-1 (EVI1) and BCR/ABL positive childhood leukemia.

METHODSClinical data of four children with EVI1 and BCR/ABL positive leukemia and eight children with BCR/ABL positive but EVI1 negative chronic myeloid leukemia (CML) were retrospectively analyzed.

RESULTSIn the four children with EVI1 and BCR/ABL positive leukemia, two were initially diagnosed with chronic phase of CML, one with accelerated phase of CML and one with high-risk acute lymphoblastic leukemia (ALL). There were no significant differences in clinical characteristics at diagnosis between the patients with EVI1 and BCR/ABL positive leukemia and BCR/ABL positive but EVI1 negative leukemia. CD33 and CD38 were highly expressed and t(9;22) abnormality was present in all patients with EVI1 and BCR/ABL positive leukemia. Two of the 3 children with EVI1 and BCR/ABL positive CML achieved complete remission one or three months after treatment. Acquired negative status conversion occurred for EVI1 but not BCR/ABL in one CML case. The 3 children with EVI1 and BCR/ABL positive CML survived 20, 13 and 14 months, respectively, without recurrence. The child with EVI1 and BCR/ABL positive ALL failed to achieve complete remission after the first course of treatment and discontinued further treatment.

CONCLUSIONSCo-expression of EVI1 and BCR/ABL fusion gene can be found in childhood CML and ALL. The relatively rare leukemia has not significant difference respect to clinical characteristics. Prognosis of the disease needs to be determined by clinical studies with a larger sample size.

Child ; DNA-Binding Proteins ; genetics ; Female ; Genes, abl ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; MDS1 and EVI1 Complex Locus Protein ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Prognosis ; Proto-Oncogenes ; genetics ; Retrospective Studies ; Transcription Factors ; genetics

OBJECTIVETo study the expression of ecotropic viral integration site (EVI1) gene in childhood acute myeloid leukemia (AML) and the clinical features of EVI1-positive children with AML.

METHODSThe clinical data of EVI1-positive children with AML were collected and analyzed. RT-PCR and real-time quantitative PCR were used for qualitative and quantitative analysis of expression of EVI1. Flow cytometry (FCM) was used for determining the immunophenotypes of bone marrow cells. Multiparameter FCM was used for monitoring minimal residual disease. The karyotypes were determined.

RESULTSOf 241 children with AML, 33 (13.7%) were positive for EVI1 expression. There were no significant differences in age at first visit as well as the white blood cell count, hemoglobin level, and platelet count in peripheral blood between EVI1-positive and EVI1-negative children with AML (P>0.05), but EVI1-positive children had a significantly increased proportion of females compared with EVI1-negative children (P<0.05). The change in EVI1 expression was not synchronous with clinical remission and the change of MRD: some children had clinical remission or negative conversion of MRD before negative conversion of EVI1, while some had negative conversion of EVI1 before clinical remission or while MRD showed positive. EVI1 gene was usually co-expressed with other fusion genes. CD33 (100%), CD38 (88%), and HLADR (76%) were highly expressed in EVI1-positive children with AML. Abnormal chromosome structure or number was found in 15 patients. Compared with EVI1-negative children, EVI1-positive children had significantly lower complete remission rates after the first course of treatment (P<0.05).

CONCLUSIONSEVI1-positive children with AML have a poor short-term prognosis. In the development of AML, the activation of EVI1 gene is not isolated, but the result of interactions with other genes or chromosome abnormalities, and the mechanism of activation and its function need further study.

Adolescent ; Child ; Child, Preschool ; Chromosome Aberrations ; DNA-Binding Proteins ; genetics ; Female ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; Humans ; Immunophenotyping ; Infant ; Leukemia, Myeloid, Acute ; genetics ; immunology ; MDS1 and EVI1 Complex Locus Protein ; Male ; Neoplasm, Residual ; Prognosis ; Proto-Oncogenes ; genetics ; Transcription Factors ; genetics

OBJECTIVETo investigate viral relapse and the associated risk factors during a long-term follow-up study of chronic hepatitis C (CHC) patients who achieved end-of-treatment response (ETR) after interferon and ribavirin therapy.

METHODSThis retrospective study was conducted on 146 CHC patients treated with a combination of ribavirin and pegylated (PEG) interferon-alpha (IFNa) (n=126) or conventional IFNa (n=20) for 24 (hepatitis C virus (HCV) non-genotype 1b) or 48 (HCV genotype 1b) weeks. The main outcome measure was serum HCV RNA load. The risk factors analyzed included age, sex, HCV genotype, baseline HCV RNA load, and IFN type.

RESULTSThe mean follow-up time for all patients was 33.45+/-16.41 months (range: 12-85 months). The cumulative relapse rate during follow-up was 14.80%. The relapse rate within six months (8.90%) was significantly higher than other periods during two years of follow-up, and no relapse occurred after 30 months. Of all relapsers (n=20), 65% occurred within six months, followed by 35% within 7-24 months after antiviral therapy. The relapse rates in patients with HCV genotype 1b and non-1b were not significantly different (20.37% vs. 12.12%, X2 =1.517, P=0.315). The mean baseline HCV RNA load was significantly higher in the relapsers than that in the non-relapsers (t=0.915, P=0.362). Relapse rates were similar in patients treated with PEG-IFNa-2b, PEG-IFNa-2a and IFNa (12.12% vs. 13.97% vs. 15.00%, respectively; X2=0.104, p=0.949). The mean age of relapsers was significantly higher than that of non-relapsers (P less than 0.005).

CONCLUSIONThe maximum probability of relapse for CHC patients exists within six months from when ETR is achieved by interferon and ribavirin therapy. A lower risk for relapse persists past this period. Thus, ETR CHC patients, especially older patients, should be carefully monitored during the two years after cessation of antiviral therapy. Standard antiviral therapy based on HCV genotype eliminates the influence of viral factors on treatment-response.

Adolescent ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; Drug Therapy, Combination ; Female ; Genotype ; Hepatitis C, Chronic ; drug therapy ; pathology ; virology ; Humans ; Interferon-alpha ; therapeutic use ; Middle Aged ; Polyethylene Glycols ; therapeutic use ; RNA, Viral ; Recurrence ; Retrospective Studies ; Ribavirin ; therapeutic use ; Treatment Outcome ; Young Adult