Short- and long-term therapeutic effects of thermal mineral waters in knee osteoarthritis: a systematic review of randomized controlled trials

The objective of the study was to evaluate short- and long-term therapeutic effectiveness of natural thermal mineral waters in patients with knee osteoarthritis (OA). We performed a systematic review of randomized controlled trials (RCTs) testing efficacy of thermal mineral water for treating patients with knee OA. Trials were identified by systematic searches of PubMed, Cochrane Central Register of Controlled trials, and Amed. We used the MeSH terms balneotherapy, balneology, and mineral water in combination with knee and osteoarthritis. Literature screening and data extraction were performed in duplicate. Nine RCTs satisfied the inclusion criteria, all published as full journal articles. Trial duration ranged from 10 to 24 weeks (median 15.33 ± 5.56 weeks). The final sample included 493 patients who provided data at the ends of the studies. All interventions that were used in these trials found out an improvement in pain and functional capacity, which were sustained until week 24. No serious adverse events were reported to be associated with thermal mineral waters treatment. This work provide the most current and comprehensive review of the existing evidence of short- and long-term therapeutic effects of thermal mineral waters in knee OA. Additional RCTs with similar intervention comparisons and outcome measures, bigger sample size, and longer follow-up are required to confirm these results and to assess the biological effect of thermal mineral waters in patients with knee OA.     

Cyclin D1 overexpression in a model of human breast premalignancy: preferential stimulation of anchorage-independent but not anchorage-dependent growth is associated with increased cdk2 activity

Cyclin Dl is frequently overexpressed in human breast ductal carcinoma in situ (DCIS) specimens, which confer a high risk for the development of infiltrating ductal carcinoma. If causally involved in the genesis of human breast malignancy, cyclin D1 may represent an interesting target for chemopreventive approaches, as it sits at the junction of many growth factor and hormonal pathways. We have used the MCF-10A human breast cell line, derived from a mastectomy containing a low risk premalignant lesion, as a model system. Three cyclin D1 transfectants exhibited physiologically relevant levels of transgene overexpression, but no coordinate overexpression of other cell cycle related genes. Proliferation assays, flow cytometry, and cdk enzymatic assays of anchorage-dependent proliferation indicated only a minimal and transient effect of cyclin D1. In contrast, cyclin D1 overexpression significantly stimulated anchorage-independent colonization in soft agar or methylcellulose, accompanied by greater Gl-S progression. The cdk4 activity of the control- and cyclin D1 transfectants in colonization assays was comparable, but the cdk2 activity was higher in the latter. Injection of control- and cyclin D1 transfected MCF-10A cells in matrigel into nude mice failed to produce tumors within 1.5 years. The data suggest that cyclin D1 overexpression is an early feature of breast neoplastic progression, and can contribute to cancer development through the promotion of colonization.     

Survival response to B-cell receptor ligation is restricted to progressive chronic lymphocytic leukemia cells irrespective of Zap70 expression

Despite very similar gene expression profiles, the clinical course of B-cell chronic lymphocytic leukemia (B-CLL) is heterogeneous. Immunoglobulin VH (IgVH) mutational status and expression of B-cell receptor (BCR) signaling mediators have been associated with disease progression. However, the consequences of BCR engagement on cell survival and evolution of the disease remain unclear. We show here that B-CLL cell survival is dependent on the threshold of BCR stimulation induced by immobilized antibody, in contrast to soluble anti-mu F(ab)'2 antibody, which leads to apoptosis. Measurement of metabolic activity and apoptotic response discriminated two subgroups. "Nonresponders" showed low metabolic activity and unmodified apoptotic response upon BCR stimulation. In contrast, "responders" exhibited increased metabolic activity and inhibition of spontaneous apoptosis. This survival advantage was associated to a BCR-dependent activation profile leading to induction of cyclin D2/cyclin-dependent kinase 4 (cdk4) expression and G1 cell cycle progression. The ability to respond to BCR ligation correlated with an unfavorable clinical course and allowed to define an additional group of patients among IgVH-mutated cases exhibiting a risk of progression. Remarkably, we show that Zap70 expression was neither mandatory nor sufficient to generate downstream survival signals and cyclin D2/cdk4 up-regulation. In conclusion, BCR engagement has a significant effect on B-CLL cell survival, activation, and G1 progression. Furthermore, our results provide new insights in the physiopathology of progressive IgVH-mutated cases.     

Histopathological study of gastric polyps. A report of 65 cases

In a retrospective study of the specimens of gastric polypectomy, carried out between January 1992 and December 2002, we analysed the demographic and histological aspects of 65 polyps. This study revealed hyperplastic polyps in 66%, adenomatous lesions in 9.2%, Peutz-Jeghers polyps in 7.7%, inflammatory fibroid polyps in 6.15%, two cases of focal foveolar hyperplasia (3%), two cases of Brunner's gland heterotopia (3%), 1 pancreatic heterotopia (1.5%), 1 fundic gland polyp (1.5%) and 1 carcinoid tumor (1.5%). All adenomas and two Peutz-Jeghers polyps include intraepithelial neoplasia. Moreover, we identified a case of Brunner's gland heterotopia, which contain a focus of plane tubular adenoma with high-grade intraepithelial neoplasia. Other lesions were found within the polyps or into the surrounding gastric mucosa, such as intestinal metaplasia and Helicobacter Pylori gastritis. This work allowed us to recommend complete removal of gastric polyps and the realization of biopsies of the nonpolypoid gastric mucosa in the search of intraepithelial neoplasia or other lesions with malignant potential.     

Phase I, randomized, controlled trial to study the reactogenicity and immunogenicity of a nasal, inactivated trivalent influenza virus vaccine in healthy adults

We performed a randomized, placebo-controlled, dose-escalating clinical trial to evaluate the safety and immunogenicity of an inactivated, split virion, trivalent, nasal influenza vaccine using lipid/polysaccharide molecules as carriers. A total of 64 adults (mean age 29; range 19-69 years) were randomly allocated to receive a mixture of lipid/polysaccharide carrier molecules and 7.5, 15, or 30 microg hemagglutinin antigen of each of the three influenza strains (A/Johannesburg/82/96 [H1N1], A/Nanchang/933/95 [H3N2], B/Harbin/07/94) or placebo via nasal spray on two occasions separated by 28 days. Adverse events were assessed immediately after immunization and for 14 days after each dose. Nasal and serum antibodies were measured before and two weeks after each dose. All but three participants completed the study; no withdrawals were because of adverse events. Adverse events were similar immediately after immunization except for anterior nasal dripping after the first dose which was more common in the combined vaccine groups (64.4%) than in the placebo group (31.3%; p < 0.05). A similar trend was observed after the second dose. Nasal dripping was also more common in the first two days after immunization in the vaccine groups than the placebo group (31.3%-50% vs. 0%) with no difference with increasing vaccine dose. The vaccine elicited a modest serum antibody response against all three viruses, with the highest dose eliciting the highest serum antibody levels. In contrast, significant nasal antibody rises were observed for all three viruses; again, the 30 microg group achieved the highest mucosal antibody levels at the earliest time points. We conclude that this trivalent, split virion, inactivated nasal influenza vaccine formulated with lipid/polysaccharide molecule carriers is well tolerated and modestly immunogenic in healthy adults.     

Inhibition of signal transduction by the nm23 metastasis suppressor: possible mechanisms

The first metastasis suppressor gene identified was nm23. Transfection of nm23 into metastatic cell lines resulted in the inhibition of metastasis, but not primary tumor size in vivo. Using in vitro assays, nm23 overexpression resulted in reduced anchorage-independent colonization in response to TGF-β, reduced invasion and motility in response to multiple factors, and increased differentiation. We hypothesize that the mechanism of action of Nm23 in metastasis suppression involves diminished signal transduction downstream of a particular receptor. Candidate biochemical mechanisms are identified and discussed herein.     

AIDS in Tunisian women. Study of 92 cases

The authors report a retrospective study about 92 cases of HIV-1 infections among adult tunisian women hospitalised or consulting in the department of infectious diseases at Rabta hospital over a period of 15 years and 6 months. The middle age is 33.2 years. 64.1% of patients are married, and the conjoint is HIV-1 positive in 84.1% of cases. The route of transmission is sexual in 75%, parenteral in 22.8% and unknown in 2.2%. According to CD4 level and clinical symptoms, patients are at AIDS stage in 75.5%. The main clinical symptoms are: oral candidiasis in 92.4%, diarrhea in 54.3%, pneumocystis carinii pneumoniae in 11.9%, cerebral toxoplasmosis in 10.9%, septicemia caused particularly by salmonella in 9.7%, tuberculosis in 6.7%, cryptococcal meningitis in 4.3% an Kaposi's sarcoma in 3.2%. Mother to child HIV transmission is found in 33.3%, and the mortality is noted in 43.5% of cases.     

Stratification of cardiac risk in unstable angina: value of troponin measurements

Recent studies have identified patients with unstable angina and increased troponin I or T as a high risk population gaining benefit from adjunctive treatment with glycoprotein IIb/IIIa receptor antagonists and early reperfusion by coronary interventions.