Long-term follow-up of a phase III study of recombinant human granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid malignancies

One hundred and twenty-eight patients with non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), and acute lymphoblastic leukemia (ALL) previously reported from a phase III trial of rhGM-CSF or placebo following autologous bone marrow transplantation (ABMT) were investigated for the development of late toxicities. Median follow-up is 36 months. No apparent long-term deleterious effects on BM function were observed. Moreover, disease-free survival and overall survival were similar for patients on both treatment arms, arguing for the long- term safety of recombinant human granulocyte macrophage-colony- stimulating factor (rhGM-CSF). The only factors predictive for both a high risk of relapse over time and mortality were having the diagnosis of ALL and/or undergoing ABMT in resistant relapse. We attempted to identify clinical variables before BM harvest, at the time of marrow infusion, or events within the first 100 days posttransplant, which might predict speed of neutrophil recovery in the setting of placebo or rhGM-CSF administration after ABMT. Only previous exposure to agents that deplete stem cells led to a significant delay in neutrophil recovery, suggesting their avoidance in patients who may undergo ABMT. Nevertheless, even those patients benefited from rhGM-CSF. For all patients, rhGM-CSF and agents that deplete stem cells were the strongest independent predictors for neutrophil engraftment. With the increasing use of newer hematopoietic growth factors both alone and in combination, long-term follow-up is essential to confirm the same safety that we report with rhGM-CSF.     

Children into DSM don't go: a comparison of classification systems for eating disorders in childhood and early adolescence

OBJECTIVE: To evaluate the reliability of diagnostic classification systems for eating disorders when applied to children and young adolescents. METHOD: Eighty-one patients were randomly selected from a population of 226 children (age 7-16) presenting with eating difficulties to a specialist clinic. Diagnoses were assigned according to three classification systems: the 10th edition of the International Classification of Diseases (ICD 10), the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), and Great Ormond Street (GOS) criteria. Ratings were performed by two clinicians blind to the diagnosis of the other. RESULTS: Interrater reliability values (kappa) for the three systems were 0.357 (ICD 10), 0.636 (DSM-IV), and 0.879 (GOS). Using DSM criteria, more than 50% of children were classified as eating disorder not otherwise classified (EDNOS) or could not be classified. DISCUSSION: DSM-IV and ICD 10 criteria are of little value in the classification of the eating difficulties of children. The GOS criteria, which were developed for this age range, are more reliable. The classification of eating disorders in childhood needs reevaluation.     

先天性无肛直肠舟状窝瘘手术186例

1临床资料1988-06/2003-12我院共186例,均为女性,无肛门,其中0～6月龄21例,0.5～1岁96例,1～3岁53例,3～8岁15例,13岁1例.以大便从会阴部舟状窝瘘口处排出而就诊,患儿有不同程度的排便困难,严重时伴腹胀呕吐,多数患儿有营养不良性贫血.瘘口直径0.3～0.6 cm,直肠盲端到肛穴皮肤之间的距离1.0～2.5 cm,属于中、低位肛门直肠畸形.本组有3例合并先天性心脏病-室间隔缺损,2例合并骶前囊肿,1例合并脐疝.     

PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor geosmin

Streptomycetes are high G+C Gram-positive, antibiotic-producing, mycelial soil bacteria. The 8.7-Mb Streptomyces coelicolor genome was previously sequenced by using an ordered library of Supercos-1 clones. Here, we describe an efficient procedure for creating precise gene replacements in the cosmid clones by using PCR targeting and lambda-Red-mediated recombination. The cloned Streptomyces genes are replaced with a cassette containing a selectable antibiotic resistance and oriT(RK2) for efficient transfer to Streptomyces by RP4-mediated intergeneric conjugation. Supercos-1 does not replicate in Streptomyces, but the clones readily undergo double-crossover recombination, thus creating gene replacements. The antibiotic resistance cassettes are flanked by yeast FLP recombinase target sequences for removal of the antibiotic resistance and oriT(RK2) to generate unmarked, nonpolar mutations. The technique has been used successfully by >20 researchers to mutate around 100 Streptomyces genes. As an example, we describe its application to the discovery of a gene involved in the production of geosmin, the ubiquitous odor of soil. The gene, Sco6073 (cyc2), codes for a protein with two sesquiterpene synthase domains, only one of which is required for geosmin biosynthesis, probably via a germacra-1 (10) E,5E-dien-11-ol intermediate generated by the sesquiterpene synthase from farnesyl pyrophosphate.     

WHITHER RURAL HEALTH? REVIEWING A DECADE OF PROGRESS IN RURAL HEALTH

ABSTRACT: The problems associated with rural and remote health have been widely recognised by health workers, rural communities and health professions for some time. Yet it has only been in the past decade that any concerted effort has been made to address rural health issues. Today the state of health in rural Australia remains less than optimal. The tenth anniversary of the Australian Journal of Rural Health provides the opportunity to reflect on what progress has been achieved over the past decade, to recognise those factors that have contributed most to the implementation of policies designed to address the health needs of rural and remote Australians, and to discuss outstanding impediments and barriers to resolving rural health issues.     

Radiation‐induced brain disorders in patients with pituitary tumours

Radiation‐induced brain disorders (RIBD) are uncommon and they are grave sequelae of conventional radiotherapy. In the present report, we describe the clinical spectrum of RIBD in 11 patients who received post‐surgery conventional megavoltage irradiation for residual pituitary tumours. Of these 11 patients (nine men, two women), seven had been treated for non‐functioning pituitary tumours and four for somatotropinomas. At the time of irradiation the age of these patients ranged from 30 to 59 years (mean, 39.4 ± 8.3; median, 36) with a follow‐up period of 6?96 months (mean, 18.3 ± 26.4; median, 11). The dose of radiation ranged from 45 to 90 Gy (mean, 51.3 ± 13.4; median, 45), which was given in 15?30 fractions (mean, 18.6 ± 5.0; median, 15) with 2.8 ± 0.3 Gy (median, 3) per fraction. The biological effective dose calculated for late complications in these patients ranged from 78.7 to 180 Gy (mean, 99.1 ± 27.5; median, 90). The lag time between tumour irradiation and the onset of symptoms ranged from 6 to 168 months (mean, 46.3 ± 57.0; median, 57). The clinical spectrum of RIBD included new‐onset visual abnormalities in five, cerebral radionecrosis in the form of altered sensorium in four, generalized seizures in four, cognitive dysfunction in five, dementia in three and motor deficits in two patients. Magnetic resonance imaging (MRI)/CT of the brain was suggestive of radionecrosis in eight, cerebral oedema in three, cerebral atrophy in two and second neoplasia in one patient. Associated hormone deficiencies at presentation were hypogonadism in eight, hypoadrenalism in six, hypothyroidism in four and diabetes insipidus in one patient. Autopsy in two patients showed primitive neuroectodermal tumour (PNET) and brainstem radionecrosis in one, and a cystic lesion in the left frontal lobe following radionecrosis in the other. We conclude that RIBD have distinctive but varying clinical and radiological presentations. Diabetes insipidus and PNET as a second neoplastic disorder in adults following pituitary irradiation have not been reported previously.