John Paul Jones: An Overlooked Autopsy Finding that May Explain His Terminal Illness.

A finding in the autopsy of John Paul Jones, the American Revolutionary War naval hero, may explain his terminal illness. During his last 2 years, he had a persistent productive cough and dyspnea. Ten days before death, he developed rapidly progressive dependent edema and ascites. He died in France in 1792. His body, preserved in alcohol in a lead coffin, was, in 1905, removed to the United States. Glomerulonephritis was noted on an autopsy, performed in France, but there was no comment then or since about ventricular wall thickness being the same in both ventricles at 5-6 mm. Hypertrophy and dilatation with biventricular failure followed by tissue shrinkage during 113 years in alcohol could have resulted in these ventricular wall findings. Systemic hypertension and left ventricular failure are consistent with his respiratory symptoms complicated perhaps by pulmonary emboli, right ventricular failure with tricuspid regurgitation, peripheral congestion, and jaundice.

Twenty-five years of RENHIS: a history of histopathological studies within EUVAS.

In the early 1990s, an international working group of experienced renal pathologists, the Renal Histology group, set up a scoring system for biopsies with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis. This scoring system subdivided glomerular, interstitial and vascular lesions and served as a tool for the evaluation of all renal biopsies from studies of the European Vasculitis Study Group (EUVAS). Histopathological studies gave new insights into the prediction of renal outcome in patients with ANCA-associated glomerulonephritis. Percentage of normal glomeruli and a selected number of interstitial parameters were reliable predictors of long-term follow-up glomerular filtration rate in all studies. Out of these results, a histopathological classification distinguishing focal, crescentic, mixed and sclerotic classes of ANCA-associated glomerulonephritis was developed. Until today, 13 studies have validated this classification system. Future studies will try to determine if and how renal histology could be helpful in guiding treatment of ANCA-associated glomerulonephritis.

[Bright's disease is mentioned in an official Hungarian medical document in the 19th century]. / A Bright-féle vesebetegség említése egy XIX. századi magyar nyelvu, hivatalos orvosi dokumentumban.

The World Kidney Day was announced for the fifth time in 2011, that calls attention to chronic renal failure as it attains the title of endemic. Richard Bright (1789-1858), a British doctor was the first to recognize and describe the uremic state and the kidney diseases leading to it. There are many aspects that the readers should remember him about especially in connection with the World Kidney Day. During his European study tour's stage in Hungary, he was not so much interested in the country's medical and health conditions, rather in its economic and cultural life, natural history and geography. He travelled to Hungary on two occasions and recorded his experiences in a personal travel documentation illustrated with his own drawings. He finally established himself in London in 1820 and together with Thomas Addison and Thomas Hodgkin they formed the Guy's Hospital's world-famous "scientist trio". Bright described the nephritis's classical image, nowadays known as Bright's disease for the first time at the age of 38 years in 1827. A presently turned up Hungarian medical certificate from 1870 contains the Bright's disease described by Richard Bright as a written diagnosis. This 140-year-old document also confirms that we can be proud of our predecessors concerning our knowledge of kidney diseases and their application in daily use in Hungary, because in the past they were the ones who used the most advanced knowledge in their practices. One of today's greatest challenges for us is to be able to inform healthy and ill people alike properly about kidney diseases and their prevention or management. Place this in order to stem the epidemic of chronic renal failure and still pay homage to this disease's greatest scientist, Richard Bright.

Patient-based continuum of care in nephrology: why read Thomas Addis' "Glomerular Nephritis" in 2010?

The name of Thomas Addis (1881-1949) is linked to several aspects of nephrological practice: from the "Addis count" of urinary elements, to the history of diet in chronic kidney diseases. He was accustomed to working with limited funds, and developed his theories with relatively simple means, combined with the careful, long-term observation of single cases. His political ideas were progressive; his outlook on life was optimistic. This is deeply reflected in his Glomerular Nephritis: Diagnosis and Treatment, a book worth reading in the era of chronic kidney disease (CKD), as it contains sharp analyses of the organizational aspects, and accurate comments on the role of the physician - all subjects of interest for the present times and challenges. One of Addis' ingenious ideas was to follow his patients throughout their lifelong disease, thus anticipating the theories of continuum of care and of therapeutic alliance between patients and physicians. He used to tailor his prescriptions and frequency of controls to each patient and phase of the disease, thus anticipating the tailored therapies and the patient empowerment presently considered as fundamental in chronic diseases. Furthermore, he suggested that physicians should work outside the hospital in small coordinated teams, in which volunteers, dietitians and laboratory technicians would play a crucial role. Patient-centered care and the importance of nonmedical team members are clear from the first lines of his book. As far as we know, he was the first physician to stress the role of volunteers in CKD, anticipating by decades nonprofit organizations such as the National Kidney Foundation.

Thomas Addis, 1881-1949, clinical scientist, hematologist and pioneering nephrologist: a brief biography.

Thomas Addis is an important figure in the history of nephrology. Born in Scotland and trained in Edinburgh, he came to San Francisco in 1911 to the new Stanford School of Medicine to run the clinical laboratory. Over the next 38 years, he made many contributions to renal physiology, the investigation of the structure and function of the kidneys in Bright's disease, and studies of kidney growth, hypertrophy and protein metabolism. Largely forgotten today, he was one of the first to use urea clearance as a measure of kidney function and was the first to systematize examination of the urinary sediment - the Addis count. He was also a leader in the use of diet and rest in the treatment of Bright's disease. Unknown to most nephrologists, before he came to the United States during the first 6 years following his graduation, he became one of the leading clinical investigators in hematology. His special interests were the mechanism of blood clotting and hemophilia. He was the first to transfuse fresh blood into a hemophiliac patient and show that this shortened the patient's clotting time. Addis was a great, if eccentric, personality as well as a great scientist. He was beloved by his many colleagues and students and was honored in his lifetime both in the United States and Great Britain.

The death of Wolfgang Amadeus Mozart: an epidemiologic perspective.

The early death of the composer Wolfgang Amadeus Mozart on 5 December 1791 has fascinated the world for more than 2 centuries. It has been suggested that his final illness was caused by poisoning, renal failure, Henoch-Schönlein purpura, trichinosis, and many other conditions. The official daily register of deaths in Mozart's Vienna was evaluated to provide an epidemiologic framework into which the observations of contemporary witnesses of his death can be integrated. All recorded deaths in Vienna during November and December 1791 and January 1792 were analyzed, together with the corresponding periods in 1790 to 1791 and 1792 to 1793. The deaths of 5011 adults (3442 men, 1569 women) were recorded over these periods. The mean ages of death were 45.5 years (SD, 18.5) for men and 54.5 years (SD, 19.9) for women. Tuberculosis and related conditions accounted for the highest number of deaths; cachexia and malnutrition ranked second, and edema was the third most common cause. According to eyewitness accounts, the hallmark of Mozart's final disease was severe edema. Deaths from edema were markedly increased among younger men in the weeks surrounding Mozart's death compared with the previous and following years. This minor epidemic may have originated in the military hospital. Our analysis is consistent with Mozart's last illness and death being due to a streptococcal infection leading to an acute nephritic syndrome caused by poststreptococcal glomerulonephritis. Scarlet fever, which represents the same underlying disease from an etiologic perspective, is a less likely possibility.

Immunosuppressive therapy in glomerular diseases: major accomplishment of Tadeusz Orlowski and his school.

Glomerulopathies are the third most common cause of end-stage renal failure. Immunosuppressive treatment of glomerulonephritis in a systematic way was introduced in Poland by Professor Tadeusz Orlowski in the early 1960s. The studies were conducted at the First Department of Medicine and at the Transplantation Institute of the Medical Academy in Warsaw in the years 1962-1988. This paper critically reviews the results of studies on the use of combined, triple-drug (prednisone/chlorambucil/azathioprine), immunosuppressive protocol in various pathological forms of glomerulopathies. We conclude that immunosuppressive protocols pioneered by Tadeusz Orlowski continue to be the backbone of the treatment of glomerulonephritis, especially the one with nephrotic syndrome, progressive impairment of kidney function and poor prognosis.

Treatment of glomerulonephritis: will we ever have options other than steroids and cytotoxics?

Glomerulonephritis refers to a collection of primary renal disorders and those secondary to a systemic disease, all characterized by inflammation within the glomerulus. Given the underlying immunologic nature of these disorders, they are routinely treated with corticosteriods and various cytotoxic agents. Although in many instances such therapies are successful, they are associated with significant morbidity; as such, alternatives are clearly necessary. Our understanding of the pathogenesis of immunologic glomerular diseases has grown remarkably, in large part from the study of rodent disease models. Fundamental to each disorder is the development of an antigen-specific immune response followed by the effector stage of inflammation. To block the immune response, antigen-specific therapy can be used to induce tolerance, such as through the use of double-stranded DNA molecules in lupus nephritis. Since other antigen systems are less well characterized, inducing a more generalized impairment in the immune response by blocking costimulatory molecules CD40-CD154 and CD28-CD80/86 is a growing approach to treat various immunologic disorders and transplantation. To reduce glomerular inflammation, a variety of effector systems have been targeted, including complement, cytokines/chemokines, adhesion molecules, and mediators of cellular proliferation. Of these, antibodies targeting C5 in the complement system, and antibody and receptor antagonists of tumor necrosis factor-alpha (TNF-alpha) have already been used in glomerular disorders with some promise. Less specific blockade of receptor-mediated events stimulated by platelet-derived growth factors and cell cycle proteins may soon be applied to glomerulonephritis. Finally, interruption of fibrosing pathways, which lead to glomerulosclerosis and interstitial fibrosis common to the end-stage of all glomerulonephritis, is the subject of intense effort which may yield effective biologic therapies. In spite of all these advances, we still are dependent on steroids and cytotoxics to treat glomerulonephritis. To get past this, we must devote significant resources to take observations made in basic research laboratories to develop therapeutics and prove their utility in human disease.

On the central role of studies on the kidney in the recognition, conceptual evolution, and understanding of hypertension.

Elevated arterial pressure had long been surmised from the strength of the pulse. Its association with contracted kidneys and hypertrophied hearts was described by Richard Bright (1789-1858). Microscopic observations of the narrowed and obliterated vasculature initially observed in the kidneys of Bright's disease, and subsequently throughout the body, launched clinical research into hypertension. The description of these findings in the absence of symptoms of kidney disease led to the recognition of primary hypertension. Ultimately, the systematic recording of the blood pressure with a pneumatic cuff and mercury manometer established the significance of hypertension as a distinct disease entity. Subsequent experimental studies established the central role of the kidney in hypertension through the renin-angiotensin system and extracellular volume control. This finding provided the basis for the introduction of diuretics and angiotensin converting enzyme inhibitors, two of the most important and valuable antihypertertensive drugs now available. Thus, the study of kidney disease and function has played a pivotal role in the conceptual evolution of the understanding of hypertension as a disease, the identification of its mechanisms, and the development of clinically useful antihypertensive medications.

Friedrich Theodor von Frerichs (1819-1885) and Bright's disease.

BACKGROUND: Richard Bright (1789-1858) discovered that edema and proteinuria are linked with renal disease. Friedrich Theodor von Frerichs (1819-1885) performed microscopic studies on Bright's disease and wrote the first German textbook of nephrology. The present contribution analyzes Frerichs' work. METHODS: Frerichs' career and his book Die Bright'sche Nierenkrankheit und deren Behandlung are examined in terms of contemporary medical knowledge. RESULTS: Frerichs conducted clinical and microscopic studies that led him to conclude that Bright's disease is a single pathological entity with many possible causes. Frerichs identified three stages through which the condition progresses. Although an oversimplification, Frerichs' various stages are reflected in the current notion that chronic renal disease, irrespectively of its etiology, relentlessly progresses to end-stage renal failure with common features of tubulointerstitial fibrosis and tubular atrophy. After writing his monograph, Frerichs never touched on renal disease again and is actually better known for his contributions to hepatology. Frerichs was a volatile and difficult person who was not always fair to his students and colleagues. CONCLUSION: Frerichs put the study of renal diseases on the map in Germany and made the novel observation that chronic renal diseases follow similar morphological patterns despite multiple origins.