[One century of the cholesterol model of atherosclerosis].

2012 sees the centennial of the development of the cholesterol model of atherosclerosis by N.N. Anitchkov and S.S. Khalatov. Its appearance became an important stage in the development of atherosclerosis pathogenesis and determined the further directions by Anitchkov's investigations direction as well as others Russian and world researchers. The Anitchkov biography and the history of experimental cholesterol atherosclerosis model creation described in details. This article considers the history of the development of the cholesterol model, some modern concepts on the nature of hypercholesterolemia (Watanabe's genetic model), demonstrating importance of the cell receptors in the homeostasis maintenance.

["Item as Kaiser Friedrich's foot was amputated". The leg amputation of Kaiser Friedrich III on 8 June 1493 in Linz]. / "Item als man dem kayser Fridrichen sin funss abschnitt". Die Beinamputation an Kaiser Friedrich III. am 8. Juni 1493 in Linz.

The article deals with the amputation of emperor Friedrich III's left leg, which took place in Linz (Upper Austria) on June 8th 1493. This is one of the most famous and best documented surgical operations of the whole Middle Ages. The article offers a study about the two most important sources, i.e., the description of the amputation by the doctor Hans Seyff (Stuttgart, Württembergische Landesbibliothek, Cod. med. et phys. 20 8, fol. 71V-72V) and an anonymous painting (Wien, Graphische Sammlung Albertina, Min. 22475), followed by a detailed analysis of the amputation and an overview about the different types of doctors working at Friedrich's court.

Breve historia de la relación entre el colesterol y las enfermedades cardiovasculares / Brief history of the relationship between cholesterol and cardiovascular diseases

The association of plasma levels of cholesterol and atherogenesis was not an easy task. During the 18th century the first evidences about the discovery of cholesterol appeared. However, in the 19th century, from the work of Anichkov, was possible to establish that atheromas originate from cholesterol deposition. The discovery and the isolation of lipoproteins by John Goffman was another landmark in cholesterol history. The observation of Laurence Kinsell that diets rich in polyunsaturated fatty acids produce a reduction of plasma cholesterol was another important landmark. The discovery of the LDL-receptor by Goldstein and Brown was one of the most important discoveries about the relationship of cholesterol with cardiovascular diseases. This work reviews the main events of the history of cholesterol.

No fue fácil asociar lo niveles plasmáticos de colesterol con la aterogénesis. En el siglo XVIII se produjeron las primeras evidencias del descubrimiento del colesterol, pero fue en el siglo XIX, con los trabajos de Anichkov, cuando fue posible establecer que los depósitos de colesterol originan los ateromas. El descubrimiento y el aislamiento de las lipoproteínas por John Gofman fue otro hito importante en la historia del colesterol. También lo fue la observación de Laurence Kinsell, quien describió que las dietas ricas en ácidos grasos poliinsaturados producen disminución del colesterol plasmático. El descubrimiento de Goldstein y Brown del receptor de LDL, ha sido quizás uno de los descubrimientos más importantes sobre la relación del colesterol y las enfermedades cardiovasculares. Este trabajo revisa los principales acontecimientos de la historia del colesterol.

Hyperhomocysteinemia and arteriosclerosis: historical perspectives.

Early concepts of the origin of arteriosclerosis were introduced in the 19th century by Rokitansky and Virchow, who described mural thrombosis, inflammatory damage to arterial intima, increased intimal permeability to plasma, mucoid degeneration of arterial wall, deposition of plasma lipids in plaques, and fibrosis and calcification of plaques. Experimental production of arteriosclerosis by feeding animal foods to rabbits was attributed to protein intoxication by Ignatowsky in 1908 and to dietary cholesterol by Anitschkow in 1913. Newburgh confirmed the protein hypothesis in 1915-1925 but failed to identify which amino acid produced plaques because methionine (1922) and homocysteine (1932) had not yet been discovered. Cases of homocystinuria from inherited deficiency of cystathionine synthase were found to be associated with thrombosis and vascular disease in 1964. The index case of methionine synthase deficiency (cobalamin C disease) was found by McCully in 1969 to be associated with arteriosclerosis, leading to the homocysteine theory of arteriosclerosis. The theory explains experimental arteriosclerosis by deficiency of vitamin B6 in monkeys, choline deficiency in rats, thyroid deficiency in rats, and methionine deficiency in monkeys. The thrombogenic and atherogenic effects of homocysteine were demonstrated in rabbits, baboons and other species, reproducing the pathological findings found in homocystinuria. Clinical and epidemiological studies in the past two decades have demonstrated that elevated plasma homocysteine is a potent independent risk factor for arteriosclerosis in the general population, supporting the validity of the theory.

The Lexington physicians of General Robert E. Lee.

General Robert E. Lee has been interpreted by history as one of the most intriguing personalities of the American Civil War era. In more recent years, there has been much speculation regarding General Lee's health during the war and the possible influence this had on his decision making and performance. Lee's personal letters during and after the war provide some documentation about his health condition, albeit through the eyes of a lay person. The history that was recorded by his personal physicians in Lexington, Virginia provides invaluable insights into his medical history. This manuscript focuses on the lives of these two physicians, Drs. Howard Barton and Robert Madison, and their interactions with their famous patient.

Thematic review series: the pathogenesis of atherosclerosis: an interpretive history of the cholesterol controversy, part III: mechanistically defining the role of hyperlipidemia.

In this third installment of the series, we point out that the absence of an explicit, detailed and plausible hypothesis linking hypercholesterolemia to the events in the artery wall was probably an important reason for continuing skepticism and for failure to treat elevated blood cholesterol levels. The rapid advances in understanding of lipoprotein metabolism in the 1950s and 1960s and the application of modern cellular biology in the 1970s provided the context for a modern consensus on pathogenetic mechanisms of atherogenesis.

[Some historical considerations on the inflammatory theory of atherosclerosis]. / Una breve riflessione storica sulla teoria infiammatoria dell'aterosclerosi.

In the past 20 years several clinical and experimental observations have led to the hypothesis that an inflammatory response can trigger some key processes during the development of atherosclerosis. Here we briefly review, from the historical viewpoint, the inflammatory theory of atherosclerosis, as proposed by the Berliner pathologist Rudolf Virchow in the XIX century. Contrary to this hypothesis, in the same period the Viennese Karl von Rokitansky recognized blood dyscrasia (particularly fibrin-induced alterations) as the promoting factor in the process of atherogenesis. Moreover, we outline the relationship between atherosclerosis and arthritis, by reporting some passages from two scientific works published in the late XIX century, the former by the Italian Achille De Giovanni ("Sull'arterite. Sue forme cliniche e sua patogenesi", 1882) and the latter by the French Theophile Guyot ("L'arthritis. Maladie Constitutionnelle", 1890).

Síndrome metabólica: aspectos históricos, prevalência, e morbidade e mortalidade / The metabolic syndrome: historic aspects, prevalence, morbity, and mortality

A associação de fatores de risco cardiovascular causa hoje grande preocupação nos órgãos de saúde pública nos vários países do mundo. A síndrome metabólica,caracterizada pela associação de vários fatores de risco para doença cardiovascular, resulta provavelmente de fatores genéticos e ambientais. Os primeiros relatos relacionados com a síndrome ocorreram na década de 20, embora tenha sido maisbem descrita a partir da década de 80. A prevalência da síndrome metabólica é alta nos Estados Unidos, porém são poucos os dados em relação à prevalência da síndrome em outros países do mundo. Dispomos hoje de três critérios propostos para classificar a síndrome metabólica: o da Organização Mundial da Saúde, o do "National Cholesterol Evaluation Program" -ATP III e o da "American Association of Clinical Endocrinologists". Como os índices de morbidade e de mortalidade em pacientes com síndrome metabólica são muito altos, essa síndrome deve ser vista hoje como uma das principais metas do ponto de vista terapêutico em termos de prevenção cardiovascular.

Novas perspectivas no tratamento das dislipidemias / New perspectives on dislipidemia therapy

As projeções da Organização Mundial de Saúde indicam que a morbidade e a mortalidade causadas pela doença cardiovascular, nas próximas décadas, se constituirão na primeira causa de morte em todo o mundo. No Brasil, a doença aterosclerótica coronariana e cerebrovascular já são a primeira causa de incapacidade e morte, correspondendo a 32,1 por cento de todas as causas, enquanto em outros países essas taxas vêm aumentando, particularmente no leste da Europa, no sudoeste da Ásia e na América do Sul. As dislipidemias desempenham um importante papel neste cenário porque participam ativamente da fisiopatologia do processo aterosclerótico, sendo reconhecidas na atualidade como um dos maiores fatores de risco modificáveis para o desenvolvimento da doença arterial coronariana. Conseqüentemente, reduzir o LDL-colesterol tornou-se o alvo terapêutico a ser atingido na busca do tratamento e da prevenção desta doença. Diversos estudos de intervenção com as vastatinas e com os fibratos, entre outras drogas hipolipemiantes, demonstraram redução de eventos cardiovasculares em pacientes de alto, médio e baixo riscos, tornando essas medicações a primeira escolha para o tratamento dessas anormalidades...

Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy: part I.

This is the first of a series of reviews of the controversy that swirled around the "lipid hypothesis" of atherosclerosis for so many years. Today, in the era of the statins, there is no longer any doubt about the value of decreasing blood cholesterol levels. In fact, "the lower the better" is the position of many clinicians. However, getting to this point has been a long uphill battle marked by heated debate and sometimes violent disagreement. The history of this controversy is worth telling for its own sake and because remembering it may help us avoid similar mistakes in the future. The history of this controversy is worth telling for its own sake and because remembering it may help us avoid similar mistakes in the future.