Prediction of common bile duct stones by noninvasive tests

OBJECTIVE: To define accurate and useful predictors of common bile duct stones (CBDS). SUMMARY BACKGROUND DATA: The ability to predict CBDS with noninvasive tests can avoid unnecessary, costly, or risky procedures. METHODS: All patients referred for examination for CBDS by endoscopic ultrasonography (EUS) from 1993-1996 were prospectively entered in a database. In a first sample selected randomly from the whole population, predictors of CBDS were determined by univariate analysis and logistic regression. Predictors were subsequently tested in that sample and in the rest of the population. A separate analysis was done for patients planned for cholecystectomy. RESULTS: Eight hundred and eighty patients (328 men, 552 women), aged 57.8 +/- 17 years (range 16-94), were included. The prevalence of CBDS was 18.8%. Age, serum levels of bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase (GGT), and alkaline phosphatase, and the existence of jaundice and fever, a dilated bile duct, and a pathologic gallbladder were found to be associated with CBDS. Logistic regression was undertaken separately for patients younger than 70 years (predictors: GGT >7 x normal; pathologic gallbladder; dilated bile duct) and older than 70 years (predictors: GGT >7 x normal; fever > 38 degrees C; dilated bile duct). Odds ratios were 3 to 6.7. The model was satisfactorily applicable to the second sample; age <70 years: chi2 = 3.3 (NS); age >70 years: chi2 = 3.8 (NS). In patients younger than age 70 and planned for cholecystectomy, the combination of the level of GGT and dilated bile duct predicted CBDS accurately. CONCLUSIONS: A simple screening of patients at risk for CBDS can be achieved with three predictive criteria adapted for the patient's age.     

Peptidic complex mixtures as therapeutic agents in CNS autoimmunity

Limited success with antigen-specific immunotherapies has led to the identification of novel approaches which consider the degeneracy of the T cell response, i.e. their ability to respond to multiple antigenic peptides. Random complex mixtures of polypeptides such as glatiramer acetate (GA) were among the first to be applied as immunodulators that take into account T cell degeneracy. While the mechanisms of action are not completely understood, the immunogenicity of GA, its strong major histocompatability complex (MHC) binding, immune deviation and bystander suppression all appear to be important. In the present study we have designed peptidic complex mixtures (CM) of varied lengths and compositions to test their potential as immunomodulating agents. CM were synthesized that had defined lengths and contained aa corresponding to binding motifs of MHC class II molecules relevant in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), specifically HLA-DRB1*1501 and HLA-DRB5*0101, which are related to MS, and H2-IA(s) associated with EAE in SJL mice. Additional CM were designed based on specificity profiles derived from positional scanning synthetic combinatorial library (PS-SCL) testing of a GA-specific T cell clone (TCC). Several mixtures were strongly stimulatory for peripheral blood mononuclear cells (PBMC) from MS patients and healthy donors suggesting a high degree of cross-reactivity with other peptide antigens. A subset of these mixtures exhibited cross-reactivity to myelin antigens and prophylactic efficacy in reducing the severity of EAE. Based on these observations we envision mixture-based peptidic compounds can be developed not only for immunotherapeutic purposes in autoimmune diseases and cancer, but also in vaccine development.     

Expression of the ret proto-oncogene in phaeochromocytoma. An in situ hybridization and northern blot study

The expression and distribution of ret proto-oncogene mRNA were investigated in five phaeochromocytomas of both familial and sporadic types by in situ hybridization (ISH) using digoxigenin-labelled cRNA probes and Northern blot (NB) analysis with random priming labelled cDNA probes. The probes corresponded to the tyrosine kinase domain of the gene. An excellent correlation was found between the ISH and NB results. By both techniques, the expression of the ret proto-oncogene was detected in three of the five cases, two of four familial tumours, and the only sporadic tumour that was studied. The results confirm that ret is frequently expressed in phaeochromocytomas and suggest that it might be an important event in their development and/or progression.     

Immunohistochemical study of sarcoma-like mural nodules in a mucinous cystadenocarcinoma of the ovary

Summary We describe an ovarian mucinous cystadenocarcinoma with several sarcoma-like mural nodules (SLMN). The distinction between these lesions and foci of anaplastic carcinoma is important because of the poor prognosis of the latter. We have studied the potential value of immunohistochemistry in the differential diagnosis of these two lesions. In contrast to an anaplastic carcinoma, which was largely composed of keratin-positive cells, SLMN were negative or only focally positive. Therefore, in distinguishing SLMN from foci of anaplastic carcinoma, keratin stains may be added to other gross and microscopical differential features, such as size, demarcation, and presence or lack of obvious carcinomatous elements.     

Expression of Hepatocyte Growth Factor (HGF) and its Receptor (MET) in Medullary Carcinoma of the Thyroid

The tyrosine kinase receptor encoded by the MET oncogene has the unusual property of mediating the invasive growth of epithelial cells upon binding with the hepatocyte growth factor (HGF). The MET/HGF receptor is known to be overexpressed in thyroid carcinomas originated from follicular cells, but has not been reported in C cell tumors. To investigate the role of HGF and of its receptor (encoded by MET oncogene) in medullary carcinoma of the thyroid (MCT), we studied the expression of HGF and MET in 20 cases by means of different techniques. By RT-PCR, HGF mRNA was found in 10/20 cases, while MET mRNA presence was demonstrated in 8/20, of which 7 also expressed HGF. Northern blot analysis and in situ hybridization were performed in selected cases and confirmed RT-PCR data in some cases, although the lower sensitivity of these procedures did not allow the identification of all RT-PCR positive cases. By immunohistochemistry (using specific monoclonal antibodies) HGF was demonstrated in 8/9 RT-PCR positive cases ald a monoclonal to MET immunostained 5/6 RT-PCR positive cases. All receptor positive cases also expressed the ligand in the same tumor cell population. These findings demonstrate MET and HGF co-expression in a subset of MCT, in which autocrine/paracrine circuits may be active. No correlation was found between HGF/MET expression and clinico-pathological parameters, except for the more common multifocality of HGF/MET positive MCT. Whether the potential activation of MET in MCT is responsible for local invasion and malignant evolution is to be further investigated, especially in multifocal and aggressive tumors.     

Hepatocyte growth factor (HGF) stimulates tumour invasiveness in papillary carcinoma of the thyroid

The present study has investigated the functional role of the Met receptor in primary cultures of 20 papillary carcinomas and of normal thyroid cells obtained from the same patients. Normal and tumour cells grew as adherent cells, formed a confluent monolayer after 10-20 days, had epithelial morphology, and were immunoreactive for cytokeratin, vimentin, and thyroglobulin. The potential effect of hepatocyte growth factor (HGF) on cell invasiveness was investigated in Boyden chambers, using a nucleopore filter coated with Matrigel as the barrier and HGF as the chemoattractant. Tumour cells of five out of seven cases of papillary carcinoma were more responsive to HGF than the corresponding normal cells in terms of the number of migrated cells per mm(2). Involvement of the Met receptor in the HGF-induced migratory response was suggested by the observation that the agonistic anti-Met monoclonal antibody (MAb) DO-24 was equally effective. HGF did not affect the proliferative activity of thyroid cells. Under the same experimental conditions, 10 per cent fetal bovine serum (FBS) induced a two-fold increase in [(3)H]thymidine incorporation into normal cells and tumour cells. These findings are consistent with the possibility that HGF plays a crucial role in determining the invasiveness of tumour cells in papillary carcinoma of the thyroid.     

The usefulness of a difference in the transmucosal potential in the functional evaluation of ileoanal reservoirs]

A patient with carcinoid syndrome was treated with the somatostatin analogue (SMS 201-995). The drug significantly improved the symptoms of the patient, flushing and diarrhea, and reduced urinary excretion of 5-hydroxyindole acetic acid. However, hepatic metastases remained unchanged. Clinical or biochemical adverse effects were not present during the treatment period.     

Positive predictive values of peripheral arterial and venous thrombosis codes in French hospital database

French hospital database, called Programme de Médicalisation des Systèmes d'Information (PMSI), covers all hospital stays in France (>66 million inhabitants). The aim of this study was to estimate the positive predictive values (PPVs) of primary diagnosis codes of peripheral arterial and venous thrombosis codes in the PMSI, encoded with the International Classification of Diseases, 10th revision. Data were extracted from the PMSI database of Toulouse University Hospital, south of France. We identified all the hospital stays in 2015 with a code of peripheral arterial or venous thrombosis as primary diagnosis. We randomly selected 100 stays for each category of thrombosis and reviewed the corresponding medical charts. The PPV of peripheral arterial thrombosis codes was 83.0%, 95% confidence interval (CI): 73.9–89.1, and the PPV of correct location of thrombosis was 81.0%, 95% CI: 72.2–87.5. The PPV of pulmonary embolism was 99.0%, 95% CI: 93.8–99.9. The PPV of peripheral venous thrombosis was 95.0%, 95% CI: 88.2–98.1, and the PPV of correct location of thrombosis was 85.0%, 95% CI: 76.7–90.7. Primary diagnoses of peripheral arterial and venous thrombosis demonstrated good PPVs in the PMSI.