Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer: a multicentric phase II study.

We have recently reported high clinical activity against advanced colorectal cancer of a regimen-alternating bolus FUra, modulated by methotrexate (MTX), and continuous infusion FUra, modulated by 6-s-leucovorin (6-s-LV). Considering the low toxicity of the bolus part of this regimen and our recent in vitro finding of a strong synergism between bolus FUra and natural-beta-IFN (n-beta-IFN), this cytokine was incorporated in the bolus part of our treatment programme. Fifty-six patients with untreated, advanced, measurable colorectal cancer were treated with two biweekly cycles of FUra bolus (600 mg m(-2)), modulated by MTX (24 h earlier, 200 mg m(-2)), and n-beta-IFN (3 x 10(6) IU i.m. every 12 h, starting at the time of FUra administration for four doses), alternating with a 3-week continuous infusion of FUra (200 mg m(-2) daily), modulated by 6-s-LV (20 mg m(-2) weekly bolus). After a 1-week rest, the whole cycle (8 weeks) was repeated if indicated. A total of 5 complete and 17 partial responses were obtained (response rate, 41%; 95% confidence limits, 28-55%) in 54 assessable patients. After a median follow-up time of 36 months, five patients are still alive. Overall, the median time to treatment failure was 6.4 months. The median duration of survival was 15.0 months. There was one treatment-related death after a course of MTX --> bolus FUra/n-beta-IFN and grade III-IV toxicity occurred in 18% of the patients. As the addition of n-beta-IFN results in high toxicity, whereas the efficacy seems to be similar to that of the same regimen without the cytokine, our groups are currently randomizing the original regimen, without IFN, against standard modulated bolus FUra.     

Immunophenotyping to Detect and Characterize Acute Lymphocytic Leukemia in Testicular Biopsies

This study establishes the utility of immunophenotyping testicular biopsy specimens in patients with acute lymphoid leukemia. The value of immunophenotyping in detecting or excluding leukemic testicular infiltration is demonstrated in six children with acute lymphocytic leukemia. A panel of monoclonal antibodies was employed on snap-frozen testicular biopsies, allowing both detection and immunologic characterization of four neoplastic lymphocytic infiltrates. Two samples were proven both histologically and phenotypically negative for leukemic infiltration. One of the four leukemic cases was clinically silent and might have escaped detection except for phenotyping. One leukemic infiltrate was also suspected to possess a multidrug-resistant phenotype (-glycoprotein +); the latter possibility was excluded by an absence of reactivity with anti-p-glycoprotein monoclonal antibody. Thus, three clinically useful applications are demonstrated: (1) confirmation of testicular leukemic relapse, gaining assertion in histologically uncertain cases; (2) exclusion of clinically suspected disease relevant to cessation of therapy, and (3) detection/exclusion of drug-resistant phenotypes. Unexpectedly, we found expression of plasma cell-associated antigen in testicular germ cells, which may prove to be diagnostically useful in the future evaluation of germ cell tumors.     

Keeping up appearances: using qualitative research to enhance knowledge of dental practice

Current issues in dentistry including a focus on patients' wishes for outcomes and dentists' role in that process raise important questions that cannot be addressed by quantitative, statistical study alone. The intriguing complexities and ambiguities that are emerging with ever-improving techniques and materials in dentistry, as well as competing demands for attention in dental health, require a range of research methodologies to address important existing and future research questions. Qualitative research, much like what a dentist does in an office visit, can seem intuitive and almost common sense in nature. Yet behind that research, when it is done well, lie years of training and practice, rules of evidence, guidelines for rigor, and various subspecializations in its pursuit. Qualitative research begins with a clearly defined problem; identifies the appropriate strategy to gather data from people, existing documents, and other sources of information that will help address the problem; uses a multifaceted tool kit of analytic methods to work with those data; and proceeds to investigate the data for their insight into the research problem and interpretation of the findings. This article provides an overview of common approaches to qualitative methods and resources to explore their potential for dental research.     

Correlation of myeloid-derived suppressor cells with C-reactive protein,ferritin and lactate dehydrogenase levels in patients with severe COVID-19

The novel coronavirus disease 2019 (COVID-19) remains a global health emergency, and understanding the interactions between the virus and host immune responses is crucial to preventing its lethal effects. The expansion of myeloid-derived suppressor cells (MDSCs) in COVID-19, thereby suppressing immune responses, has been described as responsible for the severity of the disease, but the correlation between MDSC subsets and COVID-19 severity remains elusive. Therefore, we classified patients according to clinical and laboratory findings—aiming to investigate the relationship between MDSC subsets and laboratory findings such as high C-reactive protein, ferritin and lactate dehydrogenase levels, which indicate the severity of the disease. Forty-one patients with COVID-19 (26 mild and 15 severe; mean age of 49.7 ± 15 years) and 26 healthy controls were included in this study. MDSCs were grouped into two major subsets—polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs—by flow cytometric immunophenotyping, and PMN-MDSCs were defined as mature and immature, according to CD16 expressions, for the first time in COVID-19. Total MDSCs, PMN-MDSCs, mature PMN-MDSCs and monocytic MDSCs were significantly higher in patients with COVID-19 compared with the healthy controls (P < .05). Only PMN-MDSCs and their immature PMN-MDSC subsets were higher in the severe subgroup than in the mild subgroup. In addition, a significant correlation was found between C-reactive protein, ferritin and lactate dehydrogenase levels and MDSCs in patients with COVID-19. These findings suggest that MDSCs play a role in the pathogenesis of COVID-19, while PMN-MDSCs, especially immature PMN-MDSCs, are associated with the severity of the disease.     

Total hip replacement with an uncemented Wagner cone stem for patients with congenital hip dysplasia

Purpose  

The purpose of this study was to review retrospectively the cases operated upon in our department in recent years with a Wagner stem and a small socket in cases of Crowe I or II dysplastic hips.     

Curcumin: footprints on cardiac tissue engineering

ABSTRACT

Introduction: Curcumin-based products are extensively used as therapeutics in the treatment of cardiac disorders; however, there is no significant report on the curcumin potentials in cardiac tissue engineering applications. Due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties, curcumin has been demonstrated to be a promising candidate for tissue engineering (TE) applications.

Areas covered: Various curcumin-containing tissue-engineered constructs have been developed for the management of soft tissue damages (such as wound injuries); hence, there are hopes for the use of this natural product in cardiac tissue engineering (CTE). However, some crucial issues should primarily be addressed before curcumin could be widely used in CTE.

Expert opinion: The challenges regarding the use of curcumin in CTE include the optimum dosages of curcumin for promoting cardiac regeneration, the type of carrier used (e.g., polymeric matrices), the preferable release profile, as well as the short- and long-term toxicity in the human body.