Cyclosporin as initial treatment for Crohn's disease

Childhood Crohn's disease may cause significant morbidity. T cell activation is considered to be central to Crohn's disease pathology, and as cyclosporin is a powerful inhibitor of T cell activation, and has been used in adult Crohn's disease with encouraging results, it may offer the prospect of remission if given early in the course of disease. Children with newly diagnosed Crohn's disease or those relapsing off treatment were therefore given cyclosporin or conventional treatment (enteral nutrition or corticosteroids) by random allocation. Evaluation was performed initially and at two months. Twenty four children were studied (10 on cyclosporin and 14 on conventional treatment; one child on cyclosporin withdrew). Significant clinical improvement occurred in the group on conventional treatment, but not in the cyclosporin group. Colonoscopic improvement was noted in 5/9 on cyclosporin and 8/14 on conventional treatment, but neither group produced a significant fall in median colonoscopic index. Histological improvement was seen in 7/8 on cyclosporin and 8/13 on conventional treatment, but cyclosporin was not significantly better. Cyclosporin produced improved clinical and histological appearance without matched improvement in blood disease indices. It was not better than conventional treatment, and simple oral administration is probably not suitable for newly diagnosed patients with Crohn's disease.     

Insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations in fluid from human stimulated follicles

Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP- 3) play an important role in regulating follicle growth and maturation. We have evaluated whether responsiveness to gonadotrophins during an in- vitro fertilization (IVF) treatment is related to follicular fluid IGF- I and IGFBP-3 concentrations. We also investigated if a difference is present in IGF-I and IGFBP-3 concentrations between patients treated with human menopausal gonadotrophin (HMG) and patients treated with highly purified follicle stimulating hormone (FSH). We have measured IGF-I and IGFBP-3 in follicular fluid from pre-ovulatory follicles in an IVF programme. All 70 patients were stimulated after being down- regulated with a gonadotrophin-releasing hormone (GnRH) analogue. IGF-I concentrations in follicular fluid were significantly inversely correlated with the number of ampoules FSH administered and number of days of FSH administration, and significantly correlated with the number of follicles aspirated. IGFBP-3 concentrations were not correlated with any other parameter measured nor were IGF-I and IGFBP-3 concentrations correlated. IGFBP-3 concentrations were significantly higher in patients receiving highly purified FSH compared with patients receiving HMG (P < 0.005). These results are new evidence that IGF-I concentration in follicular fluid is higher in women who respond better to follicular stimulation, i.e. women who grow many follicles, women who need a shorter duration of stimulation and women who need fewer ampoules FSH before oocyte retrieval.      

Altered metabolism of familial Alzheimer's disease-linked amyloid precursor protein variants in yeast artificial chromosome transgenic mice

Missense mutations in the beta-amyloid precursor protein gene (APP) co- segregate with a small subset of autosomal dominant familial Alzheimer's disease (FAD) cases wherein deposition of the 39-43 amino acid beta-amyloid (A beta) peptide and neurodegeneration are principal neuropathological hallmarks. To accurately examine the effect of missense mutations on APP metabolism and A beta production in vivo, we have introduced yeast artificial chromosomes (YACs) containing the entire approximately 400 kbp human APP gene encoding APP harboring either the asparagine for lysine and leucine for methionine FAD substitution at codons 670 and 671 (APP(K670N/M671L)), the isoleucine for valine FAD substitution at codon 717 (APP(V7171)) or a combination of both substitutions into transgenic mice. We demonstrate that, relative to YAC transgenic mice expressing wild-type APP, high levels of A beta peptides are detected in the brains of YAC transgenic mice expressing human APP(K670N/M671L) that is associated with a concomitant diminution in the levels of apha-secretase-generated soluble APP derivatives. Moreover, the levels of longer A beta peptides (species terminating at amino acids 42/43) are elevated in YAC transgenic mice expressing human APP(V7171). These mice should prove valuable for detailed analysis of the in vivo effects of the APP FAD mutations in a variety of tissues and throughout aging and for testing therapeutic agents that specifically alter APP metabolism and A beta production.      

Autosomal recessive retinitis pigmentosa and cone-rod dystrophy caused by splice site mutations in the Stargardt's disease gene ABCR

Ophthalmological and molecular genetic studies were performed in a consanguineous family with individuals showing either retinitis pigmentosa (RP) or cone-rod dystrophy (CRD). Assuming pseudodominant (recessive) inheritance of allelic defects, linkage analysis positioned the causal gene at 1p21-p13 (lod score 4.22), a genomic segment known to harbor the ABCR gene involved in Stargardt's disease (STGD) and age- related macular degeneration (AMD). We completed the exon-intron structure of the ABCR gene and detected a severe homozygous 5[prime] splice site mutation, IVS30+1G->T, in the four RP patients. The five CRD patients in this family are compound heterozygotes for the IVS30+1G- >T mutation and a 5[prime] splice site mutation in intron 40 (IVS40+5G- >A). Both splice site mutations were found heterozygously in two unrelated STGD patients, but not in 100 control individuals. In these patients the second mutation was either a missense mutation or unknown. Since thus far no STGD patients have been reported to carry two ABCR null alleles and taking into account that the RP phenotype is more severe than the STGD phenotype, we hypothesize that the intron 30 splice site mutation represents a true null allele. Since the intron 30 mutation is found heterozygously in the CRD patients, the IVS40+5G->A mutation probably renders the exon 40 5[prime] splice site partially functional. These results show that mutations in the ABCR gene not only result in STGD and AMD, but can also cause autosomal recessive RP and CRD. Since the heterozygote frequency for ABCR mutations is estimated at 0.02, mutations in ABCR might be an important cause of autosomal recessive and sporadic forms of RP and CRD.      

阿霉素羧甲基葡聚糖微球犬肝动脉栓塞后阿霉素的体内过程

研究了阿霉素羧甲基葡聚糖微球经肝动脉栓塞后的体内动力学过程、靶向特征和微球在体内的肝动脉栓塞效果。对犬进行肝动脉栓塞实验,并与肝动脉阿霉素(ADM)溶液灌注组进行对照。用HPLC荧光检测外周静脉和组织中药物浓度。结果表明:微球组峰浓度为0.558μg/ml,溶液组为1.013μg/ml;微球组的T_1/2(α),T_1/2(β)和MRT分别为溶液组的2.82,3.19和1.28倍。栓塞不同部位组织中ADM浓度,微球组分别是溶液组的8.0和9.1倍。动态血管造影表明:肝内外未见侧枝循环形成,栓塞作用持久,16周后微球仍未见完全降解。     

Coarctation of the aorta: MR imaging

Thirteen patients, aged 3-31 years, with coarctation of the thoracic aorta were examined by magnetic resonance (MR) imaging (total of 14 studies). Eight studies were performed preoperatively and six postoperatively. Catheterization data were available on 12 patients for verification of MR imaging findings. Electrocardiographically gated sagittal and left anterior oblique images best depicted the coarctations; however, involvement of arch vessels was best evaluated on transaxial images. MR imaging readily identified all coarctations but one, their site and extent, and involvement of the arch vessels. In addition, MR images depicted poststenotic dilatation and dilated collateral vessels. In patients studied postoperatively, restenosis could be evaluated, and complications such as postoperative aneurysm and perianastomotic hematoma were identified. MR imaging provides excellent anatomic detail of coarctation of the aorta, potentially obviating the need for angiography.     

Pulmonary edema: an MR study of permeability and hydrostatic types in animals

Permeability pulmonary edema was induced in ten rats by intravenous injection of oleic acid. Hydrostatic pulmonary edema was induced in another ten rats by continuous infusion of saline. Permeability pulmonary edema was detected as increased signal intensity in all animals on images obtained with repetition times (TR) of 2.0 sec and echo times (TE) of 28 and 56 msec. Hydrostatic pulmonary edema was perceivable only in seven of ten rats. It was best seen on spin-echo TR = 2.0 sec, TE = 28 msec images as increased intensity either throughout the whole lung or in a predominant central distribution. The slopes of the relationships between the mean signal intensity and water content of both lungs were lower for hydrostatic pulmonary edema than for permeability pulmonary edema. Hydrostatic pulmonary edema demonstrated similar T1 but markedly shorter T2 relaxation times than permeability edema. Magnetic resonance imaging can be used to estimate severity of hydrostatic and permeability pulmonary edemas.     

Delayed rupture of renal artery after renal percutaneous transluminal angioplasty

Two cases are reported in which rupture of the renal artery occurred many hours after renal percutaneous transluminal angioplasty. Delayed rupture can be recognized by the angiographic appearance and by the presence of persistent flank pain. The typical angiographic finding is a poorly defined zone of contrast medium at the site of perforation.