Transforming growth factor-beta(1) in the kidney and urine of patients with glomerular disease and proteinuria.

BACKGROUND: Transforming growth factor-beta(1) (TGF-beta(1)) is the major fibrogenic growth factor implicated in the pathogenesis of renal scarring. Proteinuria is a poor prognostic feature for various types of glomerular disease and its toxic action may be related to the activation of tubular epithelial cells towards increased production of cytokines and chemoattractant peptides. In this work we studied the site of synthesis and expression profile of TGF-beta(1) in the renal tissue of patients with heavy proteinuria and examined the relation of this expression with the urinary excretion of TGF-beta(1). METHODS: Twenty-five patients with heavy proteinuria (8.4+/-3.0 g/24 h) were included in the study. All patients underwent a diagnostic kidney biopsy and were commenced on immunosuppressive therapy with corticosteroids and cyclosporin. The sites of synthesis and expression profile of TGF-beta(1) mRNA and protein in the kidney were examined by in situ hybridization and immunohistochemistry. Urinary and plasma TGF-beta(1) levels were determined by ELISA before the initiation of treatment and 6 months later and compared with those of normal subjects and of patients with IgA nephropathy and normal urinary protein excretion. RESULTS: The site of synthesis and expression of TGF-beta(1) in the renal tissue of patients with heavy proteinuria was mainly localized within the cytoplasm of tubular epithelial cells. Interstitial expression was also present but glomerular TGF-beta(1) expression was found only in patients with mesangial proliferation. Urinary TGF-beta(1) excretion was significantly higher in nephrotic patients compared with normal subjects and with patients with IgA nephropathy and normal urinary protein excretion (783+/-280 vs 310+/-140 and 375+/-90 ng/24 h, respectively; P<0.01). In patients with remission of proteinuria after immunosuppressive therapy, urinary TGF-beta(1) excretion was significantly reduced (from 749+/-290 to 495+/-130 ng/24 h; P<0.01), while in patients with persistent nephrotic syndrome, it remained elevated. CONCLUSIONS: The localization of TGF-beta(1) mRNA and protein within tubular epithelial cells, along with its increased urinary excretion in patients with nephrotic syndrome, suggest the activation of these cells by filtered protein towards increased TGF-beta(1) production.     

Neonatal gallbladder enlargement and alpha 1-antitrypsin deficiency

Patients with clinical signs of alpha 1-antitrypsin deficiency in the neonatal period usually present with prolonged obstructive jaundice. We report a patient with alpha 1-antitrypsin deficiency who presented with gallbladder enlargement in the neonatal period. This gallbladder enlargement may be due to cystic duct hypoplasia or atresia, which has been reported in association with alpha 1-antitrypsin deficiency. The diagnosis of alpha 1-antitrypsin deficiency should be considered in neonates with gallbladder enlargement and prolonged obstructive jaundice.     

The pros and cons of fecal occult blood testing for colorectal neoplasms

Testing feces for occult blood is widely recommended as a means of detecting subclinical colorectal tumors. Guaiac tests such as Hemoccult^® are the most widely used, but chemical sensitivity is relatively low and the tests are affected by dietary peroxidases, the state of fecal hydration, and certain drugs. The newly devised HemoQuant^® and immunologic techniques appear more sensitive and specific, but they require further evaluation before widespread clinical usage can be recommended.Occult blood screening has both merits and weaknesses. Testing does uncover subclinical colorectal cancer, often at a relatively early stage, but whether this actually improves the prognosis remains to be proven. Benign neoplastic polyps are also detected, although it is debatable whether this is a valid rationale for screening. Test sensitivity for malignancy varies from good to moderate, but is poor for benign polyps. Specificity is usually around 97%–98%, yet the predictive value of a positive test for cancer is only about 10%: hence most test-positive individuals are needlessly subjected to invasive colonic investigations. Reported figures on public compliance with occult blood testing vary widely from excellent to poor. Published costs of screening are usually quite low, but these overlook important indirect and hidden expenses and are therefore misleading.On balance, the problems of occult blood testing currently appear to outweight the merits. This could change, however, with the newer testing techniques and with awaited mortality data from controlled clinical trials now underway.     

Épidémiologie et facteurs de risque psychosociaux dans l’anorexie mentale

The prevalence for anorexia nervosa is estimated at 0.5% in the young girls and the highest incidence was found between ten to 19 years. Among women, the prevalence for anorexia nervosa is estimated between 0 to 1.5%. The lifetime prevalence varies between 0.6 and 4%. The methodological limitations relate to the variety of the instruments to diagnose an eating disorder and the lack of definition approved for eating disorders not otherwise specified. The empirical models of the pathogenesis of eating disorders continue to stress the role of social pressure to thinness, this one being transmitted by the media, the family environment and the peers. The methodological limitations continue to pose a challenge in the interpretation of the modulation by the sociocultural factors of the etiologic ways for anorexia nervosa. A complex multifactor aetiology is considered, implying the interaction of genetic predisposition and certain specific environmental risk factors, in particular social factors.     

Proficiency tests for radionuclide laboratories supporting the network of IMS stations.

A tailored proficiency test programme in high-resolution gamma-spectrometric analysis has been established for the radionuclide laboratories designated to support the verification of the Comprehensive Nuclear-Test-Ban Treaty (CTBT). It entails certified reference samples that contain fission products relevant to the CTBT. The sample geometries and materials correspond to aerosol filter samples from the high-volume samplers of the radionuclide stations of the International Monitoring System (IMS) and the related calibration sources are matrix and geometry matched to the reference samples.     

L-Dopa-responsive Parkinson's syndrome in association with phenylketonuria: In vivo dopamine transporter and D2 receptor findings.

Reports of parkinsonism in phenylketonuria are exceedingly rare. We report on a patient who had received a delayed diagnosis of phenylketonuria as an infant and subsequently developed levodopa-responsive parkinsonism at the age of 33. Single-photon emission computed tomography (SPECT) using (123)I-FP-CIT ([(123))I]-2 beta-carbomethoxy-3beta-(-4-iodophenyl)-N-(3-fluoropropyl)-nortropane) used to measure dopamine transporter levels on two occasions, 7 and 9 years after the onset of neurological symptoms, were normal. Iodine-123-iodo-lisuride SPECT (IBZM) imaging, however, showed reduced caudate over putamen binding. This combination of imaging findings indicates a possible upregulation of postsynaptic D2 receptors in the context of intact presynaptic dopamine nerve terminal density.     

Germline mutations in the neurofibromatosis type 2 tumour suppressor gene

The recent identification of the NF2 tumour suppressor genehas enabled large scale screening for pathological mutationsin the gene. We have sought germline mutations In the NF2 geneby SSCP and heteroduplex analysis of cDNA and genomic DNA samplesfollowed by cloning and sequencing of mutant alleles. In thepresent report we describe 11 putative pathological mutations,including five nonsense mutations, three short insertions ordeletions cauing frameshifts and three missense mutations. Moststop mutations and frameshift mutations were found In Individualsexpressing a severe phenotype while one of the three missensemutations was associated with a mild phenotype. Four unrelatedNF2 patients of the 93 tested were found to have identical nonsensemutations caused by a C to T transition (C169) in a CpG dinucleotide,which is a potential mutational hotspot in the NF2 tumour suppressorgene.