Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand

Benign intracranial hypertension (BIH) is reported in three children from Australia and one from New Zealand, who were being treated with recombinant human growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y, developed intracranial hypertension within 2 weeks to 3 months of starting treatment. A national database, OZGROW, has been prospectively collecting data on all 3332 children treated with rhGH in Australia and New Zealand from January 1986 to 1996. The incidence of BIH in children treated with growth hormone (GH) is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical GHD (<10IUml ^-1), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95% confidence interval 1.9-176.1, than in all other children on the database. The incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No cases in patients with partial GHD (10–20 IUml ^-1) or chronic renal failure were identified. Possible causative mechanisms are discussed. The authors'practice is now to start GH replacement at less than the usual recommended dose of 14IUm-² week^-1 in those children considered to be at high risk of developing BIH. Ophthalmological evaluation is recommended for children before and during the first few months following commencement of rhGH therapy and is mandatory in the event of peripheral or facial oedema, persistent headaches, vomiting or visual symptoms. The absence of papilledema does not exclude the diagnosis.     

O,O′-二烷基-O″-(5-取代-3-苯并噻吩乙腈肟)磷酸酯及硫代磷酸酯的合成

合成了18个O,O′-二烷基-O″-(5-取代-3-苯并噻吩乙腈肟)磷酸酯及硫代磷酸酯类化合物(Ⅰ_1～18)。初步杀螺试验结果表明,其中5个化合物,即Ⅰ_2,3,7,11,12有明显的杀螺增效作用。     

Growth of Hodgkin cell lines in severely combined immunodeficient mice.

No animal model exists for the in vivo growth of Hodgkin's-lymphoma-derived cells. Neither unmanipulated Hodgkin's-disease(HD)-derived cell lines nor primary biopsy tissue could be grown in nude mice. Since the severe combined immunodeficient (SCID) mouse has been reported to be a better recipient for transplanted human lymphatic tissue than the nude mouse, we tested whether SCID mice provide suitable conditions for the in vivo growth of HD cell lines. Tumorigenicity of HD cells was tested in untreated and pre-treated SCID mice and in another combined immunodeficient mouse strain, beige/nude/X-linked immunodeficient (BNX) mouse. SCID mice supported in vivo growth of the 6 HD cell lines tested (L428, L540, L591, DEV, HD-LM2, KM-H2). Only one of the 6 lines (DEV) was tumorigenic in BNX mice. No HD cell line proliferated in T-cell-deficient nude mice. Thus, in vivo growth of HD cell lines appeared to be related to the degree of host immunodeficiency. Additional growth supportive treatments such as fibrosarcoma co-transplantation, intraperitoneal mineral oil injection or immunosuppressive pre-treatment (anti-asialo-GMI-antibody injection) permitted growth of 3 additional HD cell lines in BNX mice. The immunophenotype and karyotype of explanted graft cells were identical to the original cell lines. Our experiments describe an effective and reproducible xenograft model for growth of Hodgkin's-disease-derived cell lines. This may be of value for elucidating the growth characteristics of Hodgkin's-lymphoma-derived cells as well as for testing new therapeutic regimens.     

Stimulation of tumor growthin vitro andin vivo by suramin on the VX2 model

Suramin is an antitrypanosomal compound with confirmed efficacy against several human malignancies. It is generally assumed that its mechanism of action includes the interaction with different growth factors, unlike most of the anticancer drugs. Its anticancer activity has not been testedin vivo against squamous cell carcinoma. The purpose of this study was to assess the efficacy and toxicity of suraminin vivo andin vitro on the VX2 tumor model at therapeutic monitored plasma concentrations. We determined the pharmacokinetics of suramin in rabbits, and modelized its administration in order to obtain plasma concentrations between 150 and 300 μg/ml throughout the treatment course of 3 weeks. Under these conditions, antitumor effects of suramin were evaluatedin vivo by comparing liver tumor involvement in suramin-treated and control rabbits. Liver involvement was quantified by image analysis andin vitro effects were also determined at the same concentrations.In vivo, suramin promoted liver tumor growth significantly (p<0.05), compared to untreated controls.In vitro, suramin significantly stimulated tumor cell growth at concentrations above 200 μg/ml (p<0.01). Suramin may have stimulatory effects on tumor growth in squamous cell carcinoma at relevant plasma drug concentrations. Caution should be taken in further trials in patients with squamous cell carcinomas.     

A survey of newborn screening for cystic fibrosis in Europe.

BACKGROUND: Cystic fibrosis (CF) is a recessively inherited condition caused by mutation of the CFTR gene. Newborn infants with CF have raised levels of immuno-reactive trypsinogen (IRT) in their serum. Measurement of IRT in the first week of life has enabled CF to be incorporated into existing newborn screening (NBS) blood spot protocols. However, IRT is not a specific test for CF and NBS therefore requires a further tier of tests to avoid unnecessary referral for diagnostic testing. Following identification of the CFTR gene, DNA analysis for common CF-associated mutations has been increasingly used as a second tier test. The aim of this study was to survey the current practice of CF NBS programmes in Europe. METHOD: A questionnaire was sent to 26 regional and national CF NBS programmes in Europe. RESULTS: All programmes responded. The programmes varied in number of infants screened and in the protocols employed, ranging from sweat testing all infants with a raised first IRT to protocols with up to four tiers of testing. Three different assays for IRT were used; in the majority (24) this was a commercially available kit (Delfia). A number of programmes employed a second IRT measurement in the 4th week of life (as the IRT is more specific at this point). Nineteen programmes used DNA analysis for common CFTR mutations on samples with a raised first IRT. Three programmes used a second IRT measurement on infants with just one recognised mutation to reduce the number of infants referred for sweat testing. Referral to clinical services was prompt and diagnosis was confirmed by sweat testing, even in infants with two recognised mutations in most programmes. Subsequent clinical pathways were less uniform. Multivariate analysis demonstrated a relationship between the age of diagnosis and the timing of the first IRT. More sweat tests were undertaken if the first IRT was earlier and the diagnosis was later. CONCLUSIONS: Annually these programmes screen approximately 1,600,000 newborns for CF and over 400 affected infants are recognised. The findings of this survey will guide the development of European evidence based guidelines and may help new regions or nations in the development and implementation of NBS for cystic fibrosis.     

Histopathological grading of soft tissue tumours. Prognostic significance in a prospective study of 278 consecutive cases

A consecutive 10-year series of 278 soft tissue sarcomas was prospectively graded, using a system based on the number of mitoses and taking into account parameters such as cellularity, anaplasia, necrosis, and histogenetic type and subtype of tumour. Prognostic factors in relation to metastasis-free survival were studied by uni- and multivariate analysis. Fifty-seven (20.5 per cent) were low-grade tumours, 43 (15.5 per cent) were intermediate, and 178 (64 per cent) were high grade. High-grade tumours were divided into two groups; 80 (29 per cent) grade 3A (= 5-20 mitoses per 10 high power fields (HPF)) and 78 grade 3B (28 per cent) (= more than 20 mitoses/10 HPF); 10 HPF corresponds to 2.5 mm2. Twenty (7.2 per cent) high-grade tumours could not be further subdivided. Grading was found to be the prognostic factor associated with the strongest predictive value. Five-year survival in low-grade and intermediate tumours (95 and 86 percent, respectively) differed significantly (P less than 0.0001) from high grade (50 per cent) and (p = 0.0018) between grade 3A (64 per cent) and grade 3B (41 per cent). Other prognostic indicators of importance in high-grade tumours were age, local recurrence at presentation (primary operation outside the Centre), and localization (superficial vs. deep).