Objective To study the efficacy of late course accelerated fractionation(LCAF) radio- therapy in the treatment of nasopharyngeal carcinoma(NPC).The end-po s were local control,radiation-in- duced complications,factors influencing survival.Methods From December 1995 to April 1998,178 NPC patients were admitted for radiation treatment.The radiation beam used was ~(60)Co?or 6 MV X-ray.For the first two-thirds of the treatment,two daily fractions of 1.2 Gy were given to the primary lesion ,with an interval of≥6 hours,5 days per week to a total dose of 48 Gy/40 fractions,over a period of 4 weeks.For the last one third of the treatment,i.e.beginning from the 5th week,an accelerated hyperfractionation schedule was carried out.The dose per fraction was increased to 1.5 Gy,2 fractions per day with an interval of≥6 hours,the total dose for this part of the protocol was 30 Gy/20 fractions over 2 weeks.Thus the total dose was 78 Gy in 60 fractions in 6 weeks.Results All patients completed the treatment.Acute mucosi- tis:none in 2 patients,Grade 1 in 43,Grade 2 in 78,Grade 3 in 52,and Grade 4 in 3 patients.Local control rate:the 5-year nasopharyngeal local control rate was 87.7%,and the cervical lymph node local control rate was 85.7%.The 5-year distant metastasis rate was 26.1%,and 5-year survivals was 67.9%. Sixteen patients had radiation-induced cranial nerve palsy.Conclusions With this treatment schedule, patient's tolerance is good,local control and 5 year survivals are better than control groups of conventional fractionation and hyperfractionation radiotherapy.Radiation-related late complication does not increase.Ran- domized clinical trials are being carried out to further confirm the efficacy of LCAF for nasopharyngeal carci- noma.

BACKGROUND AND OBJECTIVEPrecursor T lymphoblastic lymphoma (T-LBL) is a highly aggressive lymphoma. Myeloid antigen expression was found in some of the patients, and its clinical significance is worth studying. This study was to compare the clinical features, short-term efficacy and survival of T-LBL patients with or without myeloid antigen expression so as to evaluate its prognostic significance.

METHODSForty-five T-LBL patients, with a median age of 14 years, were treated at Sun Yet-sen University Cancer Center between January 2000 and July 2008. These patients were divided into myeloid antigen-positive group (My(+) group) and myeloid antigen-negative group (My(-) group) based on the flow cytometric (FCM) analysis in bone marrow or pleural fluid. Myeloid antigen expression and its correlation with the short-term efficacy and overall survival were assessed in the two groups.

RESULTSThere were 18 patients (40.0%) in the My(+) group and 27 (60.0%) in the My(-) group. The myeloid antigen expression was negatively correlated with the initial level of lactate dehydrogenase (LDH), but not with other clinical features. The remission rate was lower in the My(+) group than in the My(-) group (38.8% vs. 70.3%, P = 0.028). The 2-year overall survival rate was lower in the My(+) group than in the My(-) group (51.9% vs. 78.7%, P = 0.036). By age subgroup analysis, there were no differences in response and survival rate among children and adolescents with or without myeloid antigen expression. But the remission rate and the 2-year overall survival rate were significantly lower in adult patients with myeloid antigen expression than in patients without it. Univariate and multivariate analysis demonstrated that age and myeloid antigen expression were adverse prognostic factors.

CONCLUSIONMyeloid antigen expression is a predictor of a poor response to chemotherapy, and adverse prognostic factor in adult T-LBL, but not in children with T-LBL.

Adolescent ; Adult ; Age Factors ; Aged ; Antigens, CD7 ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Asparaginase ; therapeutic use ; Child ; Cyclin D3 ; metabolism ; Cyclophosphamide ; therapeutic use ; Cytarabine ; therapeutic use ; Daunorubicin ; therapeutic use ; Doxorubicin ; therapeutic use ; Etoposide ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Male ; Mercaptopurine ; therapeutic use ; Methotrexate ; therapeutic use ; Middle Aged ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; immunology ; Prednisone ; therapeutic use ; Proportional Hazards Models ; Remission Induction ; Survival Rate ; Transcription Factors ; metabolism ; Vincristine ; therapeutic use ; Young Adult

Hemophilia B (HB) is a recessive X-linked inherited disorder, the pathogenesis of HB is deficiency or functional abnormalities of coagulation factor IX, which is caused by F9 gene mutations. To explore the mechanism of its molecular pathology, 40 patients with HB were studied with polymerase chain reaction (PCR) and direct sequencing. The diagnosis of HB patients were based on clinical manifestation and deficient factor IX activity in plasma. DNA was routinely extracted from peripheral blood cells of the patients and their relatives, all the 8 exons and their flanking boundaries were amplified by PCR, and the PCR products were screened by direct sequencing. Mutations which were found in study need to exclude polymorphism. The results showed that 34 mutations were confirmed in 40 HB patients, including 6 nonsense mutations, 24 missense mutations, 2 splice site mutations and 2 frame mutations for 1 or 2 nucleotide insertion. After retrieved, 4 missense mutations and 1 frameshift mutation were found for the first time. Among the 34 mutations, 2 mutations in signal peptide, 7 mutations in propeptide and gla domain, 7 mutations in epidermal growth factor-like domain, 3 mutations in activation domain, 15 mutations in serine protease or catalytic domain. It is concluded that gene analysis can directly explain molecular mechanism of hemophilia B and also provides the foundation for further studies to the function of coagulation factor IX. There is obvious heterogeneity in F9 gene mutation and missense mutation is still the main way of mutation, which are closely related to clinical features. DNA sequencing and linkage analysis are efficient methods for HB carriers and prenatal gene diagnosis.
Base Sequence ; DNA Mutational Analysis ; Factor IX ; genetics ; Hemophilia B ; diagnosis ; genetics ; Humans ; Male

OBJECTIVETo identify gene mutations involved in five cases of inherited factor V (FV) deficiency.

METHODSActivity of FV was determined by one-stage clotting assay using FV-deficiency plasma, and FV antigen by an ELISA assay. All the exons and exon-intron boundaries of FV gene were amplified by PCR and then DNA sequencing. Restriction enzyme analysis was used to analyze the probands, their family members and healthy volunteers.

RESULTSBoth activity and antigen of FV in the 5 patients were extremely lower compared with that of normal mixed plasma. Six mutations were identified in these 5 patients, G69969T (G2079V), C45533T (R712Ter), C46796T (R1133Ter), G45366A (C656Y), C46253T (R952C) and G16088C (D68H), the latter three were novel mutations reported for the first time and the C46253T (R952C) was the first missense mutation reported in B domain. The result of sequencing or restriction enzyme analysis showed that the three novel missense mutations were not caused by single nucleotide polymorphisms.

CONCLUSIONGene mutations in 5 type I inherited FV deficiency of patients including 2 nonsense mutations and 4 missense mutations identified which led to the instability of FV protein and the reducing of FV: Ag in the plasma.

Adolescent ; Adult ; Child ; DNA Mutational Analysis ; Exons ; genetics ; Factor V ; genetics ; metabolism ; Factor V Deficiency ; blood ; genetics ; Female ; Humans ; Male ; Mutation ; Pedigree ; Phenotype ; Young Adult

OBJECTIVETo evaluate the clinical application value of oocyte vitrification in failed testicular sperm extraction cycles in non-obstructive azoospermia (NOA) patients.

METHODSWe retrospectively analyzed the clinical data of 8 women undergoing oocyte frozen-thawing cycles by vitrification because of failed testicular sperm extraction from their NOA husbands and no banked donor sperm on the day of oocyte retrieval. The oocytes were cryopreserved by vitrification with cryotop and thawed 2 months later. The surviving metaphase II (MII) oocytes were injected with the banked donor sperm of the same blood type as the husbands by intracytoplasmic sperm injection (ICSI) for fertilization. The rates of oocyte survival, fertilization, cleavage, good embryos and pregnancy were evaluated.

RESULTSSixty oocytes were vitrified and 47 (78.3%) survived after thawing, of which 41 MII oocytes underwent ICSI and 33 (80.5%) of them were fertilized. The rates of cleavage and good embryos were 81.8% (27/33) and 59.3% (16/27) respectively. Fifteen of the embryos were transferred to the 8 patients, with 1.9 +/- 0.8 per cycle, of which 5 (33.3%) were confirmed by ultrasound to have been implanted and 5 resulted in clinical pregnancy (62.5%), all singleton without miscarriage. Three normal boys and 1 normal girl were already born, with the pregnancy time of (39 + 4 +/- 0.4) wk and newborn body weight of (3787.5 +/- 513.7) g, respectively.

CONCLUSIONVitrification of oocytes in failed testicular sperm extraction cycles is a promising technique for preserving female fertility, which, with ICSI of banked donor sperm, may result in satisfactory clinical outcomes.

Adult ; Azoospermia ; Cryopreservation ; methods ; Female ; Humans ; Male ; Oocytes ; Pregnancy ; Pregnancy Rate ; Retrospective Studies ; Sperm Banks ; Sperm Injections, Intracytoplasmic ; Testis ; Treatment Failure

OBJECTIVETo investigate the potential association between factor VIII inhibitor development and polymorphisms of tumor necrosis factor-α (TNF-α)-308 and cytotoxic T-lymphocyte associated protein-4 gene in Chinese Han patients with hemophilia A (HA).

METHODSThe single base change polymorphism in TNF-α and CTLA-4 gene was analyzed in 140 Chinese Han patients with hemophilia A who have been treated with plasma-derived FVIII concentrates and 108 normal controls by using PCR-restrictive fragment length polymorphism (RFLP). All of the HA patients' plasma samples were measured by modified-Nijmegen assay simultaneously.

RESULTSIn HA patients, G/G genotype, G/A genotype and A/A genotype were detected in 118 (84.3%), 18 (12.8%) and 4 cases (2.9%) respectively; C/C genotype, C/T genotype and T/T genotype were detected in 108 (77.2%), 30 (21.4%) and 2 cases (1.4%) respectively. The difference in the genotype frequencies between HA patients and controls was nonsignificant (P > 0.05). Patients who were carriers of homozygotes for A allele had a higher risk of inhibitor development compared with those who were not (OR = 7.519, 95% CI = 3.168 - 17.844). Severe HA patients who were carriers of homozygotes for A allele had a higher risk of inhibitor development compared with those who were not (OR = 8.163, 95% CI = 2.521 - 26.434). There was no statistical difference in the risk of inhibitor development between the patients who were carriers or not (OR = 1.586, 95% CI = 0.729 - 3.450).

CONCLUSIONTNF-α-308 gene polymorphism is significantly associated with inhibitor development in Chinese Han patients with severe hemophilia A. TNF-α gene may be a useful marker and potential modulator of the immune response to replacement therapy for hemophilia A patients.

Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; CTLA-4 Antigen ; genetics ; Child ; Child, Preschool ; Genotype ; Hemophilia A ; genetics ; Humans ; Infant ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Tumor Necrosis Factor-alpha ; genetics ; Young Adult

OBJECTIVEThis study was to identify the post-traumatic stress disorder (PTSD) changes and the relative risk factors within one year after Wenchuan earthquake among middle school students in the disaster area.

METHODSA total of 1966 students from 3 schools in Wenchuan earthquake region were selected as the target population. For each student, personal basic information and standard psychological scale (PCL-C, PSSS) were investigated by a self-administrated questionnaire in the 3rd, the 6th, the 9th and the 12th month after the earthquake, respectively. PTSD trends over the time and the associated risk factors were analyzed through the establishment of multi-level random coefficient model.

RESULTSThere were 1677 middle school students fully participated in the PTSD follow-up study by turning in the valid questionnaires. The averaged scores of PTSD at the time of the 3rd, the 6th, the 9th and the 12th month after the earthquake were 35.14 ± 11.08, 32.90 ± 11.03, 30.67 ± 11.28 and 29.75 ± 11.22, respectively. Meanwhile, the general incidences of PTSD were 36.6% (613/1677), 30.7% (515/1677), 24.8% (416/1677)and 22.2% (373/1677), respectively. The median score of perceived social support system was 60.00 and the general incidences of PSS was 17.20% (289/1677). The PTSD scores for the students had a decreasing trend during the period of our observation (β(time) = -1.879, χ(2) = 47.03, P < 0.05). The averaged scores for boys for the 4 follow-up studies were 33.71, 31.61, 29.66, 28.83; for girls were 36.33, 33.98, 31.51, 30.52; for junior school students were 35.46, 33.28, 30.18, 29.22; for senior school students were 34.89, 32.62, 31.04, 30.15. Moreover, two factors, gender and grade, were related with the decreasing trend (the trend for girls and senior school students was sharper than that for boys and junior school students) (β(gender-time) = -0.354, χ(2) = 4.83, P < 0.05; β(grade-time) = 0.622, χ(2) = 11.30, P < 0.05).

CONCLUSIONSThe prevalence of PTSD was high. Meanwhile, there was a trend of self-recovery for adolescent's PTSD during the first year of post-earthquake, but boys and junior school students recovered more slowly.

Adolescent ; Child ; China ; epidemiology ; Disasters ; Earthquakes ; Female ; Follow-Up Studies ; Humans ; Incidence ; Life Change Events ; Male ; Stress Disorders, Post-Traumatic ; epidemiology ; psychology ; Students ; psychology ; Surveys and Questionnaires ; Young Adult

Child ; Cord Blood Stem Cell Transplantation ; methods ; Histocompatibility Testing ; standards ; Humans ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; therapy ; Transplantation, Homologous ; methods ; Treatment Outcome