[A medical biography of Ludwig van Beethoven]. / Ludwig van Beethoven, el genio de Bonn atormentado por sus enfermedades: su historia médica.

Much emphasis has been given to the deafness of Ludwig van Beethoven and its potential causes. However, when analyzing several symptoms reported by himself throughout his life in many letters and his final illness, a common etiology emerges. This article reports the medical history of this artist, based on authoritative scientific sources.

[IMMUNOREHABILITOLOGY: A LOOK FROM THE SOURCES TO THE FUTURE. FROM IMMUNOTHERAPY TO PERSONALIZED TARGETED IMMUNOREHABLITATION].

Development and introduction of modern clinical diagnostic tests (that allow to evaluate the functional system of immune homeostasis) into medical practice, a huge body of evidence on the leading role of the immune system in pathogenesis most acute and chronic diseases and even identification of specific nosological forms of immune-mediated diseases forced the scientists to search and develop new tools and techniques that have therapeutic effects on the impaired immune homeostasis and restore it to the normal state. The introduction of a new concept - immunorehabilitation - was an impetus for the accumulation of new knowledge and a catalyst for research in clinical immunology. It was Revaz Sepiashvili who breathed life into the concept of immunorehabilitation. He was lucky to be at its origi. He became not only the founder of the brand new scientific field - immunorehabilitation, but also the founder of a new medical science - immunorehablitology. In this paper, the author returns to the roots and recalls the way that medical science has gone before coming to understand immunorehablitology and tells readers about current successes and its development prospects.

The Historical Development of Immunoendocrine Concepts of Psychiatric Disorders and Their Therapy.

Relationships between the central nervous, immune and endocrine systems are a focus of psychiatric research, particularly in depression and schizophrenia. The field has long antecedents. Observed phenomena attributable to these relationships date back to the Neolithic era. Immunoendocrine theories in the broadest sense are recorded in antiquity. In the 19th century, Kraepelin and Wagner-Jauregg reported pioneering clinical observations in psychiatric patients. Von Basedow, Addison and Cushing described psychiatric symptoms in patients suffering from endocrine diseases. The 20th century opened with the identification of hormones, the first, adrenaline, chemically isolated independently by Aldrich und Takamine in 1901. Berson and Yalow developed the radioimmunoassay (RIA) technique in 1959 making it possible to measure levels of hormones and cytokines. These developments have enabled great strides in psychoimmunoendocrinology. Contemporary research is investigating diagnostic and therapeutic applications of these concepts, for example by identifying biomarkers within the endocrine and immune systems and by synthesizing and testing drugs that modulate these systems and show antidepressant or antipsychotic properties.

The deafness of Ludwig van Beethoven: an immunopathy.

OBJECTIVE: To analyze and discuss the deafness of Ludwig van Beethoven (1770-1827) and to offer a logical theory for its etiology. METHOD: The study will carefully review the composer's symptoms as described in his letters to friends and acquaintances and also will review a large body of source material, particularly publications by his contemporaries, some of which were generously loaned by Beethoven-Haus, Bonn, Germany, where necessary translations were made directly from the original German. We will also study publications on Inflammatory Bowel Disease (IBD) and its associated extraintestinal manifestations and personal discussions with experienced gastroenterologists. RESULTS: Beethoven's abdominal symptoms that began in his teens are highly suggestive of IBD, which we believe to be a correct diagnosis. IBD is an umbrella term that includes a number of named entities such as ulcerative colitis and Crohn's Disease. IBD is now considered to be a problem of immune regulation with extra intestinal manifestations that include sensorineural hearing loss and primary sclerosing cholangitis (PSC). PSC eventually causes cirrhosis and failure of the liver. A diagnosis of IBD therefore provides a single entity that explains most of the composer's symptoms and was finally the cause of his death. Our conclusion is that Beethoven's sensorineural hearing loss was an immunopathy associated with IBD.

[Immunology in the 20th century--progress made in research on infectious and immunological diseases].

The new era of the modern medicine was opened 100 years ago by Robert Koch and Louis Pasteur who demonstrated that various infectious diseases were caused by their respective microbes. Koch discovered Mycobacterium tuberculosis, the causative agent of tuberculosis. The first breakthrough in the modern medicine to combat against infectious diseases was the discovery of anti-diphtheria toxin antibody by E.A. von Behring and S. Kitasato. The concept of immunity--immune from disease--has thus been established. The immune response between antigen and antibody sometimes provides the host with a harmful effect. The concept of allergy was introduced by Richet and later by Prausnitz and Küstner. Why the same immune response leads to the different outcome, immunity or allergy had not been made clear until the discovery of IgE by Drs. Kimishige and Teruko Ishizaka in 1968: The IgG antibody plays a role in immunity whereas IgE antibody is involved in allergy. Tuberculin skin reaction which is well known as the diagnostic tool for mycobacterial infection was studied by M. Chase in 1945 demonstrating that it was able to be transferred to the healthy individual by immune cells but not by antibody. The immune response is now categorized into two; soluble immunity--immediate type allergy and cell-mediated immunity--delayed type allergy. The rapid progress in the molecular biology in the past decades has also accelerated the progress in immunology, several of which include discovery of two types of lymphocytes; T and B cells; concept of two T cells; Th1 and Th2 cells; and the discovery of cytokines which regulate immune cell responses. The mechanism of the immune response is now understood at the gene level. Several immunological diseases can now be successfully treated by controlling the levels of cytokines involved. For example, refractory rheumatoid arthritis is now under control by the administration of recombinant soluble TNF receptor molecules to the patients. The complete human genome sequence is currently under investigation. We can now envisage the advent of the days when every disease can be diagnosed and intervened at the gene level.

Ludwig van Beethoven, el genio de Bonn atormentado por sus enfermedades: su historia médica / A medical biography of Ludwig van Beethoven

Much emphasis has been given to the deafness of Ludwig van Beethoven and its potential causes. However, when analyzing several symptoms reported by himself throughout his life in many letters and his final illness, a common etiology emerges. This article reports the medical history of this artist, based on authoritative scientific sources.

Immune-Mediated Diseases II Congress: summary.

The remarkable progress in basic immunological research during the past 50 years can account for the emerging of medical or clinical immunology as a novel discipline, which may be defined as the application of basic immunology rules to the diagnosis, treatment, and prophylactics of patients with diseases in which immunological pathways may play an important etiological and/or pathogenetic role. The immune system has a central role not only in fighting infections, but also in many other diseases and disorders including cancer, AIDS, and organ transplantation. In addition, the immune system imbalance is responsible for primary and secondary immunodeficiencies, hypersensitive illnesses, such as asthma, dermatitis, and other allergies, as well as systemic and organ-specific autoimmune disorders, such as multiple sclerosis, lupus, rheumatoid arthritis and diabetes. Immune-mediated diseases such as autoimmune diseases and allergic diseases are important health problems in many countries. For instance, autoimmune diseases afflict up to 8% of the United States population; allergic diseases represent the sixth leading cause of chronic illness and disability in the United States, and the leading cause among children. Thus, immune-mediated diseases represent an enormous medical, social, and economical problem and require serious and instant attention from clinicians, scientists, pharmacists, and biotech professionals. The goal of the Second International Immune-Mediated Diseases (IMD) Congress was to advance medical and biomedical immunological sciences and clinical practice via the organization of multiple sessions and training courses as well as providing an environment for stimulating scientific discussions, the exchange of ideas, and consideration of novel clinical diagnostic and therapeutic approaches. Selected contributions from the participants of this Congress who are eager to share some of the academic and clinical enthusiasm are presented in this issue (and the subsequent issue) of the Journal of Immunotoxicology.

Immunological disorders--the evolution of an hypothesis.

In honouring the memory of Dr Alwyn Zoutendyk, a respected member of the staff of the South African Institute for Medical Research, attention is called to the studies of the immunological disorders. While investigating serum hepatitis affecting soldiers of the US army following the administration of yellow fever vaccine, an antigen similar to that later called the Australia antigen, now hepatitis B surface antigen, was found in the acute phase serum and the corresponding antibody was found in convalescence. This finding and subsequent studies suggested there was a group of disease, which we called the hyperreactive auto-allergic disorders, of which examples were to be found in every system. The obverse of these we called the hyporeactive immunologically deficient disorders resulting from defects of the cell or serum components of the immunological reactions, of which many examples have also been found.

[From Bogomoletz anti-reticular cytotoxic serum to monoclonal antibodies]. / Vid antyretykuliarnoï tsytotoksychnoï cyrovatky Bohmol'tsia do monoklonal'nykh antytil.

The paper devoted to the 120th anniversary of A.A. Bogomoletz birth deals with the developmental stages of the cytotoxin (xenogenic antibody) doctrine from creating the anti-reticular cytotoxic serum (ACS) of Bogomoletz to the use of monoclonal antibodies both in biological investigations and in medicine. The use of ACS for treating various diseases and the mechanisms of its effect; obtaining other anti-organ and anti-tissue cytotoxic sera and establishing their experimental effects; the use of a set of cytotoxic sera, taken in both inhibitory and stimulating doses, in medicine and agriculture, as well as the drawbacks of cytotoxic sere (polyclonal xenogenic antibodies) are described. The experience of using monoclonal antibodies to identify the structures of protein antigenic determinants and to establish their role in different diseases are analysed. The use of monoclonal antibodies for treating various diseases is reviewed. The advances in the techniques of obtaining monoclonal antibodies are noted.

Cellular immunology in a historical perspective.

Bruton's XLA and DiGeorge syndrome patients show that two basic immune systems are distinct from each other in humans - thymus-dependent cell-mediated immunodeficiencies vs. antibody-based immunodeficiencies. The appendix-sacculus lymphoid organ of rabbits, like the bursa of Fabricius, represents a central lymphoid organ. Chronic granulomatous disease of childhood (CGD) revealed that phagocytosis killing of catalase-positive microorganisms employ oxidative burst. Bone marrow transplantation (BMT) proved life saving in severe combined immunodeficiency (SCID). The first BMT cured XSCID and the second BMT cured a complicating aplastic anemia launching BMT as a treatment of many diseases. Now 75 fatal diseases have been cured by myeloablative BMT. BMT also cured experimental autoimmune diseases. BMT alone did not cure lupus with polyarthritis in MRL/lpr mice or polyarthritis in NZB/KN mice, but BMT plus bone (stromal cell) transplants cured these diseases. Autoimmune diseases and lethal glomerulonephritis were prevented or cured in BXSB mice by mixed allogeneic plus syngeneic BMT. X-linked Hyper IgM syndrome (XHIM) was also cured by BMT from a 2-year-old MHC-matched sibling donor. Nonmyeloablative BMT plus mesenchymal stem cells (stromal cells) was effective treatment for a form of collagen-vascular disease and also a lethal form of hypophosphatasia. Mannan-binding lectin, an opsonin that activates the complement system when mutated and at low levels in blood, opens a door to frequent infections throughout childhood and adult life. This new immunodeficiency is based on genetic mutations that involve a native defense system.