Medical practices and cancer care networks: examples in oncology

Understanding medical practices or the whys and wherefores of care decision-making is among the major objectives of medical, economic and sociological research in the current political environment. Although variations of medical practice have long been known to exist, causes and deciding factors remain obscure. This is one of the reasons why medical auditing became widely used in the past years. Using methods similar to those of clinical research, we will explore existing medical practices and their implications, with the aim to propose possible improvements. Elaborating clinical practice guidelines and promoting cancer network activities might prove promising and have a significant impact on clinical practice. This article provides a state-of-the-art overview of the subject, notably in the domain of oncology where substantial advances are being made.     

Cancer networks

The complexity of legislation and the obstacle race run by all promoters in search of approval and funding for their projects could have greatly hindered the development of healthcare networks in France, or at least discouraged many promoter. Yet social and health professionals, along with certain healthcare service staff, considered these networks highly useful for decompartmentalising the French healthcare system. They would favour patient-oriented projects. It is not a surprise that the number of networks in the field of oncology is expanding rapidly, with more than 60 projects registered by public authorities by the end of 1999. Cancers are chronic diseases which often bring into play the patient's vital prognosis, as well as psychological and social consequences - sometimes dreadful - for patients and their relatives. Cancer patient management calls for a multidisciplinary approach in elaborating the therapeutic project and providing psychological support. Continuity and consistency of care require a partnership between different care providers from different specialities, with different medical practice and environments - hospital or home care, public or private practice. Though so much information has become available in the medical literature, quality of care demands that each healthcare professional keeps fully aware of the latest diagnostic or therapeutic findings and techniques in his/her field. Certain cancer networks have become a place where care providers and establishments can share methods and medical practice. Network promoters and members have thus been able to regain control over the functioning and the future of their profession. Patients have also obtained a place in decisions concerning their own health. Setting up healthcare networks will certainly shake up the tranquil system which the WHO has reported as the world's best health care system at the dawn of this century. However, this will also probably contribute to maintaining this excellence.     

The effect of local deep microwave hyperthermia on experimental zymosan-induced arthritis in rabbits

The effect of local deep microwave hyperthermia (LDMWH) on normal and Zymosan-induced arthritis has been evaluated in 12 rabbits (24 joints). LDMWH, four treatments to each joint (twice weekly for a period of 2 wk), was generated by an antenna operating at 915 MHz for 60 min, reaching an intraarticular temperature of 42.5 +/- 0.5 degrees C. A surface cooling system was used with the microwave apparatus. Two weeks after the last treatment, all animals were sacrificed. The application of LDMWH on normal joints induced a limited proliferation of the synovial lining cells with a minimal perivascular infiltration of mononuclear and neutrophil cells. However, no histologic damage to the skin, muscles, bone, cartilage or bone marrow adjacent to the heated joints could be noted. Induction of Zymosan arthritis (2 wk before LDMWH) was characterized by pannus formation and granulomatous reaction accompanied by fibrinoid deposits and disseminated necrotic foci in the synovial intima. The LDMWH treatment on the examined arthritic joints brought about a reduction in the degree of granulomatous reaction concomitant with the appearance of some fibrocytes and fine collagen fibrils. These findings suggest that LDMWH can be safely applied, even repeatedly, without morphologic evidence of damage to any normal mesenchymal tissue. Moreover, it reduces the inflammatory process in experimentally induced synovitis.     

Lack of association between 5HT2A receptor gene haplotype, bipolar disorder and its clinical subtypes in a West European sample.

Bipolar affective disorder (BPAD) is a complex psychiatric disorder with a major genetic contribution. Abnormalities in serotonergic function have been implicated in its aetiology. The 5HT2A receptor (5HT2AR) gene is a strong candidate gene for involvement in BPAD, but previous association studies have reported conflicting results. These data are difficult to interpret because most negative results were obtained with small samples. The aim of this study was to test the association between the 5HT2AR gene and BPAD in a large West European sample. We studied the -1438G/A and the His452Tyr polymorphisms, for haplotype analysis to increase both informativity and the likelihood of detecting an association between BPAD and the 5HT2AR gene. We analysed the genotype, allele and haplotype distributions of two 5HT2AR gene variants in a population of 356 BPAD patients, which we compared with 208 healthy controls. We also carried out exploratory analysis in clinical subgroups of patients defined according to personal history of mood disorders, suicidal behaviour, comorbid psychiatric disorders and family history of affective disorders. We found no difference between BPAD patients and controls for allele, genotype and haplotype distributions. Exploratory analysis in subgroups of BPAD patients showed only a marginal difference in haplotype distribution between controls and BPAD patients with antidepressant-induced mania (P = 0.018). This difference was not significant after correction for multiple testing. Our study suggests that the 5HT2AR gene is unlikely to be involved in genetic susceptibility to BPAD but should be further investigated in a pharmacogenetic study.     

PTEN has tumor-promoting properties in the setting of gain-of-function p53 mutations

We show, for the first time, that the tumor suppressor PTEN can have tumor-promoting properties. We show that PTEN acquires these unexpected properties by enhancing gain-of-function mutant p53 (mut-p53) protein levels. We find that PTEN restoration to cells harboring mut-p53 leads to induction of G(1)-S cell cycle progression and cell proliferation and to inhibition of cell death. Conversely, PTEN inhibition in cells expressing wild-type PTEN and mut-p53 leads to inhibition of cell proliferation and inhibition of in vivo tumor growth. We show the dependency of the tumor-promoting effects of PTEN on mut-p53 by showing that knockdown of mut-p53 expression inhibits or reverses the tumor-promoting effects of PTEN. Mechanistically, we show that PTEN expression enhances mut-p53 protein levels via inhibition of mut-p53 degradation by Mdm2 and possibly also via direct protein binding. These findings describe a novel function of PTEN and have important implications for experimental and therapeutic strategies that aim at manipulating PTEN or p53 in human tumors. They suggest that the mutational status of PTEN and p53 should be considered to achieve favorable therapeutic outcomes. The findings also provide an explanation for the low frequency of simultaneous mutations of PTEN and p53 in human cancer.     

Worldwide emergence of extensively drug-resistant tuberculosis

Mycobacterium tuberculosis strains that are resistant to an increasing number of second-line drugs used to treat multidrug-resistant tuberculosis (MDR TB) are becoming a threat to public health worldwide. We surveyed the Network of Supranational Reference Laboratories for M. tuberculosis isolates that were resistant to second-line anti-TB drugs during 2000-2004. We defined extensively drug-resistant TB (XDR TB) as MDR TB with further resistance to > or = 3 of the 6 classes of second-line drugs. Of 23 eligible laboratories, 14 (61%) contributed data on 17,690 isolates, which reflected drug susceptibility results from 48 countries. Of 3,520 (19.9%) MDR TB isolates, 347 (9.9%) met criteria for XDR TB. Further investigation of population-based trends and expanded efforts to prevent drug resistance and effectively treat patients with MDR TB are crucial for protection of public health and control of TB.