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Although Internal Medicine (IM) has played for many years a crucial role in the medical education and in the diagnostic framing of the most common diseases, starting from the beginning of the 70's the knowledge explosion, the recognition of the multidisciplinary nature of IM and the consequent impossibility for the Internist to master an ever growing array of notions have resulted in the development of specialized disciplines restricted to pathologies of single organs or apparatus. The parcelling out of medical knowledge has thus induced the onset of a number of specializations stemmed from IM and, as a direct consequence, an identity crisis of the same IM. Social transformations and variations in the epidemiology of several diseases have contributed to such crisis, including aging, frailty and disability, polypathology and chronicity. In the last few years, however, IM has regained a central role in medicine, in that the Internist is an expert of "medicine of complexity" and the only specialist able to envisage an holistic approach to the patient. The development of biotechnologies, characterized on one side by nanotechnologies and on the other by the instruments of diagnostic imaging, has provided an important contribution to make clinical medicine more and more precise and reliable. The genomic analysis of novel pharmacological targets has opened new therapeutic horizons, especially in the oncology field. A striking aspect of modern medicine, again based on unreasonable expectations of improvement and recovery, is the progressive increment of malpractice claims leading to an indemnity payment. Defensive medicine has been the answer to face this growing problem: physicians are in fact induced to prescribe a much higher number of often unnecessary examinations and laboratory tests, that result in a wasting rise of health costs. In view of the rapidly changing reality, it seems fair to ask the question as to whether in our country the medical education is abreast of the times. And the answer can only be diversified to reflect a leopard skin image. Indeed, familism, nepotism, unfairness, inefficiency and comparative evaluations marked by an excess of local factors have inevitably caused merciless and often deserved criticism that has been extensively debated in several monographs.

In tumors characterized by a high osteotropism, such as multiple myeloma, the measurement of bone metabolism markers is helpful in monitoring both severity and prognosis of the skeletal disease. Here, we review the pathophysiology of these markers including tartrate resistant acid phosphatase (TRAcP), which appears highly specific and closely related to the extent of myeloma bone lesions.

Mesenchymal stem cells (MSC) are a cell population present not only in the bone marrow, but also in a number of adult and fetal tissues. Their multilineage differentiation in vitro emphasizes their potential usefulness in the field of the regenerative medicine. New techniques of molecular biology and genetic manipulation of MSC are under investigation for cell therapy of several bone diseases.

The structure and organization of post-graduate training in Internal Medicine in the United States is described as compared to the Italian situation. The main differences are highlighted and discussed, with particular emphasis on the central role that education in Internal Medicine has in the United States for medical subspecialties as well.

Chemokines are cytokines which induce chemotaxis on many cell types, thus regulating cell migration within inflammatory and allergic sites, and leucocyte homing. Also, they play a crucial role in inflammatory and tumor-associated angiogenesis, as well as in tumor progression. Chemokines are grouped into: 1) alpha or CXC; 2) beta or CC; 3) gamma or C; 4) delta or CX3C molecules. Each of them recognizes one or more cell surface receptors, named CXCR, CCR, XCR, CX3CR respectively, according to the corresponding subfamily. Many chemokines have been identified within tumor tissues, as a secretory product of tumor cells and/or inflammatory cells. The CXC chemokines (such as IL-8, IP10, Mig, SDF-1 alpha) or CC chemokines (such as MCP-1, MIP-1 alpha, eotaxin, RANTES) have been frequently harvested from tumor tissues or the biological fluids of patients. Some chemokines inhibit tumor growth and progression by activating immunocompetent cytolytic cells or inhibiting tumor-associated angiogenesis. In contrast, other chemokines induce tumor progression by interacting with the specific receptor expressed on the tumor cells and hence by activating chemotaxis and secretion of proteolytic enzymes, or by inducing angiogenesis and metastatic spreading. Sometimes neoplastic cells express chemokine receptors which are not expressed on their normal counterpart. Data from this lab show the CXCR3 expression by cells from lymphoproliferative diseases, such as multiple myeloma and lymphoma, and the stimulation of an invasive phenotype following interaction with specific chemokines.