Historical perspectives in clinical pathology: Bence Jones protein-early urine chemistry and the impact on modern day diagnostics.

This is the third in the series of historical articles dealing with developments in clinical pathology. Bence Jones proteins are immunoglobulin light chains found in excessive quantities in urine in multiple myeloma and are believed to be one of the first tumour markers ever discovered . Dr Henry Bence Jones is credited with the discovery of this protein in 1847 that bears his name and he can also be regarded as the first chemical pathologist/clinical chemist. Since then, numerous advances and refinements have been made in the measurement and detection of urine light chain proteins which have resulted in the current sensitive serum free light chain assays used today.

Biometrics and citizenship: Measuring diabetes in the United States in the interwar years.

In 1936, the journalist Hannah Lees published "Two Million Tightrope Walkers," drawing attention to the significant number of people in the United States estimated to have diabetes. Focusing on how people with diabetes should live, she emphasized the importance of recording the exact values of everything they ate and avoiding all "riotous living" lest they be unable to keep careful measurements of calories, insulin, and sleep. Employing two meanings of measured - as counted and as moderate - Lees was doing more than communicating how someone might control their disease; she was also calling for a "controlled and self-reliant citizenry." Indeed, Lees insisted that diabetics who followed a regime of measurement "make a good deal better citizens than the average." Drawing on the writings of Lees and other social commentators, I explore the link between biometrics, citizenship, and diabetes in the United States in the interwar years. In particular, I look at how this disease came to symbolize both the regimes of discipline thought to be necessary in a society moving to consumption as its economic motor, and the fears of what could happen if consumption ran amok. Biometrics, I argue, offered clinicians and patients a potent tool for measuring deviance and, potentially, for restoring a person to the "norm."

[The history of urine analysis].

The history of urine analysis spreads over 6,000 years. This review highlights the most important people and events during that period.

The concept of the urine test and specific reaction of the urine in various diseases according to Enrico Cauchi - member of the medical council of Malta (1933).

The Study of urine from the outset has always aroused the interest of scientists and physicians all over the world, from ancient Greeks and Romans to Hindus , Hulcos in Mexico, Australian native etc. The urine in such case was considered not only as a waste product but also as a therapeutic product. In the late XIX century scientific knowledge had already identified the function of substances that favor the increase of urinary output, and physicians over the centuries have always tried to analyze urine in various ways. In Cauchis work in 1933 all chemistry and pathophysiological knowledge of the time was condensed. Cauchi signed the preface as Member of the medical council of Malta. He was a medical doctor of the early20thcentury, He wrote about the physiopathology of urine ranging from chemical and physical behavior, to the analysis of sediments and the special reactions of the urine in various pathologies. In particular Cauchi emphasizes the main diseases of the time combines the behavior of the reaction of urine as a diagnostic and prognostic instrument, stressing the importance of the urine test and describing the method used for analysis at the time. The analyses of the text in the issue seems to belong to archaic medicine, and it is difficult to think today, that what was presented as very up-to-date- science at that time, took place only 80 years ago. Reading the full original text with today experience we are led to consider the increasing importance that scientific community gave in the past, and still gives to urine test.

A history of urine microscopy.

The naked-eye appearance of the urine must have been studied by shamans and healers since the Stone Age, and an elaborate interpretation of so-called Uroscopy began around 600 AD as a form of divination. A 1000 years later, the first primitive monocular and compound microscopes appeared in the Netherlands, and along with many other objects and liquids, urine was studied from around 1680 onwards as the enlightenment evolved. However, the crude early instruments did not permit fine study because of chromatic and linear/spherical blurring. Only after complex multi-glass lenses which avoided these problems had been made and used in the 1820s in London by Lister, and in Paris by Chevalier and Amici, could urinary microscopy become a practical, clinically useful tool in the 1830s. Clinical urinary microscopy was pioneered by Rayer and his pupils in Paris (especially Vigla), in the late 1830s, and spread to UK and Germany in the 1840s, with detailed descriptions and interpretations of cells and formed elements of the urinary sediment by Nasse, Henle, Robinson and Golding Bird. Classes were held, most notably by Donné in Paris. After another 50 years, optical microscopy had reached its apogee, with magnifications of over 1000 times obtainable free of aberration, using immersion techniques. Atlases of the urinary sediment were published in all major European countries and in the US. Polarised light and phase contrast was used also after 1900 to study urine, and by the early 20th century, photomicroscopy (pioneered by Donné and Daguerre 50 years previously, but then ignored) became usual for teaching and recording. In the 1940s electron microscopy began, followed by detection of specific proteins and cells using immunofluorescent antibodies. All this had been using handheld methodology. Around 1980, machine-assisted observations began, and have dominated progress since.

″I will not cut, even for the stone″: origins of urology in the Hippocratic Collection.

The Hippocratic Collection, including the most of ancient Greek medicine, remains still interesting, despite the recent advances that transformed definitely the urological healing methods. Considering the patient as a unique psycho-somatic entity and avoiding high risk surgical manipulations were the leading principles dictating the everyday practice. Contemporary physicians can still learn from the clinical observations in times of complete absence of laboratory or imaging aid, from the prognostic thoughts, the ethics, and the philosophical concepts, represented by the Hippocratic writings, tracing into them the roots of Rational Medicine in general and Urology in particular.

The rise and fall of uroscopy as a parable for the modern physician.

As the first documented laboratory test in history, urinalysis, (or 'uroscopy' as it was historically referred to), was revered as the ultimate skill for physicians. The matula, in which the physician would pensively inspect his urine, would become an emblem of physician status and omniscience, a glass bladder that held the power to foretell a patient's future. It would also reveal much about how early physicians refined the scientific method, evolving their practice from that of speculation and magic and adopting more rigour in their analysis. However, the practice of uroscopy fell from grace as rogue physicians and charlatans began exploiting its reputation for dishonest gain and deception of patients. For this reason, the practice of uroscopy is intriguing - its rise and fall reflect the haphazard chase for a 'silver bullet' diagnostic tool which we would do well to remember today.

Historical perspectives in clinical pathology: a history of glucose measurement.

This is the second in the series of historical articles dealing with developments in clinical pathology. As one of the most commonly measured analytes in pathology, the assessment of glucose dates back to the time of the ancient Egyptians. It was only in the 19th century that advances in chemistry led to the identification of the sugar in urine being glucose. The following century witnessed the development of more chemical and enzymatic methods which became incorporated into the modern analysers and point-of-care instruments which are as ubiquitous as the modern day cellphones. Tracking the milestones in these developments shows the striking paradigms and the many parallels in the development of other clinical chemistry methods.

A brief review of Rhazes, Avicenna, and Jorjani's views on diagnosis of diseases through urine examination.

The present survey aims at studying the opinions of three famous medical scholars in history (Rhazes, Avicinna, and Jorjani) on the diagnosis of diseases via urine examination and their compatiblity with modern science. Refering to original authentic sources in traditional medicine, including Al-Hawi (The Virtuous Life), Zakhireh-i Kharazmshahi (Thesaurus of the Shah of Khwarazm), and Al-Canon fi al Tibb (The Canon on Medicine), we compared the ideas of the authors with modern medicine. In traditional medicine, physicians would pay attention to the methods of urine collection and urinary features such as color, consistency, volume, frequency, odor, and foam as the means of diagnosis, all of which still serve as the bases for today's diagnostic approach. Moreover, symptoms of the diagnosis of the disease through urine are consistent in tradition and modern medicine; some examples are blood in the urine (hematuria), decreased urine output (oliguria), change in urine color together with headache (Alport syndrome), diluted urine (tubular dysfunction in reabsorption of water or initial polydipsy), and urinary floor with tiny bubbles (one of the main symptoms of proteinuria).

Ibn-Sina's life and contributions to medicinal therapies of kidney calculi.

Ibn-Sina (commonly known as Avicenna) is one of the most famous and influential scientists in the history of medicine. The Canon of Medicine, which is his most celebrated book in medicine, presents a summary of all the medical knowledge of his time. Ibn-Sina wrote a complete section about kidney calculi in his book. Totally, 65 herbal, 8 animal, and 4 mineral medicines are mentioned in the Canon of Medicine as beneficial drugs for dissolving, expelling, and preventing kidney calculi. Ibn-Sina introduced very advanced drug designing based on drug delivery, targeting the organ, deposition in the site of action, pain control, wound healing, clearance after action, and supporting the organ. Using Ibn-Sina's ideas help scientists to choose better drugs with a historical background to reduce the cost of therapies and research projects.

Rhazes, a genius physician in diagnosis and treatment of kidney calculi in medical history.

Abu Bakr Mohammad Ibn Zakariya Razi, known in the west as Rhazes (865 to 925 AD), was born in the ancient city of Rayy, near Tehran, Iran. He was a renowned physician in medical history and not only followed Hippocrates and Galen, but also greatly extended the analytical approach of his predecessors. Based on the existing documents, he was known as the most distinguished character in the world of medicine up to the 17th century. A great number of innovations and pioneering works in the medical science have been recorded in the name of Rhazes. His fundamental works in urology as part of his research in the realm of medicine have remained unknown. Pathophysiology of the urinary tract, venereal diseases, and kidney and bladder calculi are among his main interests in this field. He also purposed and developed methods for diagnosis and treatment of kidney calculi for the first time in medical history. He also presented a very exact and precise description of neuropathic bladder followed by vertebral fracture. He advanced urine analysis and studied function and diseases of the kidneys. Rhazes recommendations for the prevention of calculi are quite scientific and practical and in accordance with current recommendations to avoid hypercalciuria and increased saturation of urine. Rhazes was not only one of the most important Persian physician-philosophers of his era, but for centuries, his writings became fundamental teaching texts in European medical schools. Some important aspects of his contributions to medicine are reviewed.