[The role of biology in the diagnosis of cerebrospinal fluid leaks]. / Place de la biologie dans la prise en charge des brèches ostéoméningées.

Cerebrospinal fluid leakage is a rare but critical condition with a substantial risk of intracranial infection, therefore its diagnosis and treatment is of major importance. CSF leakage diagnostic can be a challenging problem. Nephelometric measurement of beta-trace protein in the liquorrhoea is a non-invasive and fast method that can be used for CSF leakage diagnosis. It should kept in mind, however, that the cut-off of 1.1 mg/L is not suitable for patients with bacterial meningitis and those with a reduced glomerular filtration rate. Complementary use of beta-trace protein assay and beta2-transferrin detection is therefore recommended.

Accidental caustic ingestion in children: is endoscopy always mandatory?

BACKGROUND: Patients who have experienced severe caustic injury to the gastrointestinal tract are at high risk of esophageal strictures. Early endoscopy is usually recommended systematically in children after caustic ingestion to assess the severity of the initial digestive lesions. The aim of this study was to determine the predictive value of clinical symptoms and ingested-substance types as markers of severe esophagogastric lesions and to define indications for endoscopy. METHODS: Ingested-product types, clinical symptoms, endoscopic data and outcome were prospectively recorded in 85 children admitted after accidental caustic ingestion. RESULTS: Forty-eight children (57%) had no symptoms; the others presented with vomiting, hematemesis, drooling, respiratory distress, and/or oropharyngeal lesions. Endoscopy showed no or minimal lesions in 63 cases (74%). None of the children developed digestive sequelae. Severe esophagogastric lesions were present in 22 cases (26%), mostly caused by lye ingestion (14 of 22) but also by strong acids (4 of 22); 9 of the 22 children (41%) developed esophageal stenosis. Vomiting, drooling, and oropharyngeal lesions did not predict severe endoscopic lesions. Hematemesis, respiratory distress, or presence of at least three of the symptoms was associated with severe lesions (positive predictive value = 1). The absence of symptoms was always associated with no or minimal lesions (negative predictive value = 1). CONCLUSIONS: In conclusion, endoscopy is not recommended for children living in developed countries who are asymptomatic after accidental caustic ingestion.

Telomerase activity as a potential marker in preneoplastic bladder lesions.

OBJECTIVE: To assess telomerase activity (involved in cell immortalization and detectable in most malignant tumours but not in normal somatic tissues) as a marker in cancer diagnosis. PATIENTS AND METHODS: Tissue telomerase activity was assayed by two different techniques, the telomeric repeat amplification protocol-polymerase chain reaction (TRAP-PCR) and a telomerase PCR-enzyme linked immunosorbent assay. Malignant and inflammatory bladder lesions and their adjacent normal tissues were assessed for telomerase activity in a group of 18 patients, 14 of whom had urothelial carcinoma and four a nonspecific inflammatory lesion of the bladder. RESULTS: Eleven of the 14 tumour samples analysed were telomerase-positive and two of the three telomerase-negative tumour samples had a detectable 'telomerase inhibitor'. In the apparently normal tissues next to bladder tumours, four of the 14 specimens were telomerase-positive. Interestingly, these lesions were always next to high-grade muscle-invasive bladder tumours (pT2G3). Two of the four nonspecific inflammatory lesions (one of cystitis glandularis and one of severe dysplasia), known to be preneoplastic lesions, were also telomerase-positive. CONCLUSION: These results strongly suggest that the reactivation of telomerase may be an early event in bladder carcinogenesis, preceding morphological changes related to malignant transformation. Telomerase activity may therefore be useful both as an indicator of malignant potential in preneoplastic lesions, e.g. cystitis glandularis and severe dysplasia, and as a prognostic marker of bladder tumour relapse or progression.

Multiple myeloma in two brothers. An immunochemical and immunogenetic familial study.

When multiple myeloma was diagnosed within 6 months in two brothers a family study was carried out in 34 relatives to assess the genetic factors involved. The monoclonal immunoglobulin isotype identified was identical for the two brothers (IgG kappa) as well as their genotype (a = A2B12BfSDR4 GIo2/d:A9B27BfSDR2GIol). Blood protein electrophoresis and the major histocompatibility complex markers (HLA A, B, DR, Bf, glyoxalase phenotypes) were also determined in the other family members. The immunochemical study revealed no other case of monoclonal gammapathy, but 12 cases of low gamma-globulin and three cases of polyclonal hypergammapathy were found. The immunogenetic study showed that no other family member had the a/d genotype of the two brothers, whereas nine family members were semi-identical for haplotype a and five for haplotype d. It is unlikely that a double immunochemical and immunogenetic identity in two siblings with multiple myeloma would be due only to random encounter, rather this finding suggests that, besides environmental factors, genetic factors may be involved in the pathogenesis. Systematic immunochemical and immunogenetic studies in familial multiple myeloma are proposed as a method to further elucidate an eventual genetic background in multiple myeloma.

RPR112378 and RPR115781: two representatives of a new family of microtubule assembly inhibitors.

A screening program aimed at the discovery of new antimicrotubule agents yielded RPR112378 and RPR115781, two natural compounds extracted from the Indian plant Ottelia alismoides. We report their isolation, structural determination, and mechanisms of action. RPR112378 is an efficient inhibitor of tubulin polymerization (IC(50) = 1.2 microM) and is able to disassemble preformed microtubules. Regarding tubulin activity, RPR115781 is 5-fold less active than RPR112378. Tubulin-RPR112378 complexes, when isolated by gel filtration, were able to block further tubulin addition to growing microtubules, a mechanism that accounts for the substoichiometric effect of the drug. RPR112378 was found to prevent colchicine binding but not vinblastine binding to tubulin. Although colchicine binding is known to induce an increase of tubulin GTPase activity, no such increase was observed with RPR112378. We show that RPR112378 is a highly cytotoxic compound and that RPR115781 is 10, 000-fold less active as an inhibitor of KB cell growth. Part of the cytotoxicity of RPR112378 is probably caused by a reaction of addition with sulfhydryl groups, an observation that has not been made with RPR115781. In conclusion, these molecules represent a new class of inhibitors of microtubule assembly with potential therapeutic value.