The Dropsy of Popes (1555-1978): A Bad Prognostic Sign Foreboding of Death.

The purpose of this study is to explore the historical background of edema as a prognostic sign in popes, a special category of medical subjects whose health status was closely monitored and chronicled because of their unique important status in the events of their times. Nine out of 51 popes, who reigned in the years 1555-1978, died edematous at a mean age of 75.5 years of age. The cause of edema was: heart failure for John Paul I, liver disease, obstructive nephropathy associated with anemia for Paul IV, who also suffered from deep vein thrombosis, and malnutrition for Innocent XIII. Chronic kidney disease due to renal stones of gouty origin caused edema in Clement VIII, Clement X, Clement XI, and Benedict XIV. Obstructive nephropathy due to renal stones of non-gouty origin caused edema in Clement XIII, whereas toxic nephropathy due to the use of mercurials caused edema in Clement XIV. Innocent XI, Benedict XIV, and Clement XIV were bled before death because of impending pulmonary edema. It is not surprising that chronic kidney disease was a significant cause of edema in popes with chronic kidney disease which is associated with impaired sodium excretion. The edema was likely aggravated by the excessive dietary salt intake of the period when the importance of sodium chloride restriction was still not discovered and effective diuretic agents were not available.

Comparison between men and women of volume regulating hormones and aquaporin-2 excretion following graded central hypovolemia.

Central hypovolemia induced by orthostatic loading causes reno-vascular changes that can lead to orthostatic intolerance. In this study, we investigated volume regulating hormonal responses and reno-vascular changes in male and female subjects as they underwent central hypovolemia, induced by graded lower body negative pressure (LBNP). Aquaporin-2 (AQP2) excretion was measured as a biomarker for the renal system response to vasopressin. 37 young healthy subjects (n = 19 males; n = 18 females) were subjected to graded LBNP until - 40 mmHg LBNP. Under resting conditions, males had significantly higher copeptin (a stable peptide derived from vasopressin) levels compared with females. Adrenocorticotropin (ACTH), adrenomedullin (ADM), vasopressin (AVP) and brain natriuretic peptide (BNP) were not affected by our experimental protocol. Nevertheless, an analysis of ADM and BNP with the data normalized as percentages of the baseline value data showed an increase from baseline to 10 min after recovery in the males in ADM and in the females in BNP. Analysis of BNP and ADM raises the possibility of a preferential adaptive vascular response to central hypovolemia in males as shown by the normalized increase in ADM, whereas females showed a preferential renal response as shown by the normalized increase in BNP. Furthermore, our results suggest that there might be a difference between men and women in the copeptin response to alterations in orthostatic loading, simulated either using LBNP or during posture changes.

Malaria as a Papal Disease.

OBJECTIVES: In this study, we aimed to investigate the effects of malaria on the lives of Roman pontiffs. MATERIALS AND METHODS: The histories of all 264 popes from Saint Peter to John Paul II were extensively studied. RESULTS: Malaria affected the lives of Roman pontiffs. Between 999 AD and 1644 AD, 21 of 99 popes were affected by malaria (21.4%). The first affected was Gregory V and the last was Urban VII, the 138th and the 235th pope, respectively. There were 15 deaths (15.2%). Six pontiffs (6.1%) were infected but survived. Many cardinals and their assistants, especially those coming from northern countries, contracted malaria during conclaves, and many died. CONCLUSIONS: By about 450 BC, malaria had arrived in Rome. By the second century BC, malaria was endemic. It affected the lives of Roman people. To prevent infection, the popes adopted the custom of ancient affluent Romans who used to spend summer months in high plains far from Rome. The first to adopt the custom was Paul I in 767, who just moved his residence to Saint Paul, out of the walls. Sixtus V started the Congregation of Waters and Streets, which was routinely reinforced by his successors until 1860, when the Kingdom of Italy was born.

Acute Kidney Injury as a Leading Cause of Papal Deaths in the Years 1277 to 2005: A Review of 21 Cases.

OBJECTIVES: This study was devised to investigate papal deaths due to acute kidney injury, a topic for which scarce data exist. MATERIALS AND METHODS: We studied all popes between John XXI, who died in 1277 of crush syndrome, and John Paul II, who died of anuria and urinary sepsis in 2005. RESULTS: Between pontification years from 1277 to 2005, 21 of 78 popes (26.9%) died of acute kidney injury. Sepsis was identified as the leading cause of acute kidney injury and death in 20 of 21 popes (95.2%). Mean ± SE age at death of the 21 popes was 69.4 ± 2.26 years. Six popes (28.6%) died of stroke. CONCLUSIONS: Sepsis-associated acute kidney injury, a syndrome with a complex pathogenesis and poor prognosis, which is far from being fully understood, contributed to a high number of papal deaths.

High Prevalence of Kidney Stone Disease of Gouty Origin in Roman Pontiffs Reigning in the Years 537-2005.

OBJECTIVES: Many Roman pontiffs are known to have had kidney stone disease. However, no specific report has explored the prevalence of the various stones in popes, which is the purpose of this study. MATERIALS AND METHODS: We extensively studied the histories of all popes (n = 264) from Saint Peter to John Paul II (34-2005). RESULTS: Among 206 popes reigning from 537 to 2005, 26 popes (12.6%) had uric acid stones. In the same period, 11 of 206 popes (5.3%) had nongouty stones (mainly calcium stones). In total, 37 of 208 (17.8%) popes complained of kidney stone disease. The ratio of calcium stone formers to other stone formers (including uric acid) was 0.42. CONCLUSIONS: The data suggest a higher prevalence of uric acid stones, which is linked to higher consumption of meat and sodium chloride. However, the last pope with kidney stone disease died in 1914. Although renal stone disease disappeared from papal palaces, population studies now indicate an increase in uric acid levels in the general population. The data can be explained based on the "Theory of Epidemiological Transition," pointing to the importance of education in eradicating poor lifestyles.

Survival is not enough.

Survival is not enough is a yearly international event started in 2007 in Naples, Italy, in the week of the World Kidney Day to discuss the needs of renal patients and the quality of life of a category of patients living a machine-dependent life. Renal patients and their associations, philosophers, economists, nephrologists, and health care managers are enrolled to discuss about the possibility to grant the best cures and care without reducing the quality and the quantity of the services the patients need. Various quests have arisen for (1) a new cadre of managers capable of keeping health accounts in balance without cutting expenditure but by reducing waste of resources, (2) the promotion of prevention as the only measure capable of reducing costs in the long run, and (3) the promotion of clinical and translational research. The changes occurring in the health system should be viewed as a window of opportunity, including the advent of the medical-industrial complex firstly described in 1980, an event originating in the United States of America and now spreading worldwide.

[Health Technology Assessment to evaluate the economic advantage of offering of low-protein diet to pre-dialysis patients in Campania (Italy)]. / Un modello HTA a sostegno dell'offerta della dieta ipoproteica ai nefropatici della Campania.

A low-protein diet is well known to slow the progression of chronic renal failure, delay initiation of dialysis, while achieving significant economic benefits. In the context of a Health Technology Assessment (HTA), a budget impact analysis model was implemented to evaluate the economic advantage of offering of low-protein diet to nephropathic patients in Campania (Italy). The implemented model takes into account only the direct costs to the national healthcare system. In particular, costs related to supplying low-protein foods are compared to dialysis costs avoided, in a scenario that evaluates different indices of Numbers Needed to Treat and compliance to treatment. Results indicate that when compliance to treatment is at least 50% and NNT is £ 50, supplying a low-protein diet to all kidney disease patients in the pre-dialysis phase, namely with an estimated Glomerular filtration rate > 45, in Campania (which in the year 2009 were equal to 25,000 subjects), is economically advantageous. In this perspective, the authors argue that distribution of low-protein foods by local pharmacies could be an appropriate choice as it would allow the products to be offered at a discounted price and create a favorable setting for increasing adherence to treatment.

Pius X (1835-1914): the last gouty pope.

Gout is a common, complex, systemic and well-studied form of chronic inflammatory arthritis in adults. It is due to the deposition of sodium monourate crystals in peripheral joints and periarticular tissues driven by hyperuricemia. Gout is the oldest recorded inflammatory arthritis to affect humankind, with roots stretching back to 2460 BC. It is known as "the rich man's disease", "the patrician malady", "a disease of plenty", "disease of kings", "disease of Western Society", and also "a life-style disease". Few studies have addressed the problem of gout among popes, affluent people who usually live longer than their contemporaries and are among the most scrutinized persons. Pius X (1835-1914) was the last pope with gout. Gout seems to have affected 26 out of 265 popes (9.81%) from Saint Peter to Benedict XVI (34-2013 AD). The first was Gregory I Magnus, who was pope in the years 590-604, the last was Pius X, who reigned from 1903 to 1914 at age 79. Their age at death was 71.7 ±9.2 years (Mean ± SD). All popes were elderly men, some had voracious appetites and/or were wine drinkers. Several were sedentary and obese, while others were sober eaters, who took long walks or went riding. Chiragra (arthritic pain in the hands), podagra (arthritic pain in the big toe) and renal stone disease were among the most frequent disturbances. The causes of death, due to CKD, strokes and infections are discussed along with the fact that gout disappeared from the Vatican Palace on August 22, 1914. However, in accordance with the Theory of Epidemiological Transition, gout seems likely to become a problem for the general population, increasingly adopting unhealthy lifestyle choices, in the absence of a correct education.

Nephrological excerpts from the Encyclopédie of Diderot and d'Alembert.

The Encyclopédie of Denis Diderot (1713-1784) and Jean-Baptiste le Rond d'Alembert (1717-1783), a 35-volume work published between 1751 and 1780, is the most representative work of the Enlightenment in France. Written to explain truths based on experiment, detected by the senses, and analyzed by reason, it was meant to be an inclusive systematic dictionary of the sciences, arts, and crafts. Medicine, considered an experimental but practical science based on measurement, is not mentioned in the frontispiece, but is covered in the text based on the work of several illustrious scientists and clinicians of the period. The renal entries describe kidney structure and function, normal and pathologic urine, diabetes, anuria, polyuria, dysuria, stranguria, incontinence, kidney stones, edema, diuretics, and nephritis. The contributions of Marcello Malpighi (1628-1698), Herman Boerhaave (1668-1738), and Guichard-Joseph Duverney (1648-1730) are highlighted. Accompanying illustrations of unique perfection show the position of the kidneys according to Albrecht Haller (1708-1777); their innervation according to Raymond Vieussens (1641-1715); their structure according to Anton Nuck (1650-1692), Exupère Joseph Bertin (1712-1781), and Frederick Ruysch (1638-1731); and the genitourinary tract according to Duverney. Overall, the Encyclopédie provides a unique summary of what was known about kidney structure, function, and disease in the 18th century.

[Voriconazole compromises renal function in an elderly CDK patient with Candida albicans infection]. / Aggravamento della funzione renale da Voriconazolo in paziente anziano con nefropatia cronica affetto da infezione da Candida albicans.

There has been a progressive increase in the number of intensive care patients being transferred to nephrology units because of improper dosage of drugs, especially patients with chronic kidney disease (CKD). Voriconazole is a new synthetic triazole derivative with stronger therapeutic activity against fungal infections than fluconazole or itraconazole. Its effectiveness is associated with high nephrotoxicity, affecting patients with CKD in particular. The adverse effects of voriconazole involve several segments of the nephron, particularly the proximal tubule, medullary thick ascending limb, and collecting duct, causing loss of potassium and magnesium and backdiffusion of hydrogen ions. We report the case of an 86-year-old man with moderate CKD who developed acute renal failure as a result of inadequate dosage of voriconazole. He developed oliguria, electrolyte imbalance and fluid overload requiring hemodialysis. Vericonazole withdrawal associated with short daily hemodialysis treatment led to the recovery of diuresis, kidney function, and electrolyte balance. In conclusion, in elderly patients with liver disease and moderate CKD, thorough evaluation is needed before the administration of voriconazole in order to establish the most appropriate dose.

Regulation of urinary calcium excretion by vasopressin.

BACKGROUND: The antidiuretic hormone (ADH) or arginine vasopressin (AVP) regulates the body's water balance. Recently, modifications in AVP levels have been related to osteoporosis during ageing and microgravity/bed rest. Therefore the present study was devised to assess whether the absence of AVP, as in patients with central diabetes insipidus (CDI), modulates renal calcium excretion. METHODS: We retrospectively analysed data from 12 patients with CDI with measured 24-h urinary excretion levels of calcium. Data were available at the moment of the diagnosis when patients were drug-free and after therapy with dDAVP, an analog of AVP. Hypercalciuria was defined as 24-h urinary Ca2+ >275 mg/day in males and >250 mg/day in females and a urinary calcium (Ca):creatinine (Cr) ratio >0.20 mg/mg. RESULTS: Untreated CDI patients had a daily urinary Ca2+ excretion of 383 ± 47 mg/day and a urinary Ca:Cr ratio of 0.26 ± 0.38 mg/mg. The urine osmolarity significantly increased after the administration of dDAVP by 210% and the urinary flow decreased by 72%. Furthermore, the estimated glomerular filtration rate (eGFR) increased by 7%, which did not reach statistical significance. dDAVP treatment did not significantly modify the urinary Ca2+ concentration; however, the daily calcium excretion and the urinary Ca:Cr ratio were significantly decreased (160 ± 27 mg/day and 0.11 ± 0.02 mg/mg, respectively). CONCLUSIONS: Patients with CDI show hypercalciuria even though urine is more diluted than normal controls, and dDAVP reverses this effect. These data support the intriguing relationship between AVP and osteoporosis in ageing and microgravity/bed rest.

Legislative proposal in Italy to facilitate contacts between deceased organ donor families and transplant recipients.

Contacts between organ donors and recipients might be possible in the near future in Italy. As suggested by The Italian Committee of Bioethics "anonymity is requested by the Italian National Transplant Centre" before transplantation anonymity shall be strict in order to grant privacy, gratuity, justice, solidarity and benefits and avoids organ trafficking. Following a period that is ethically correct and justifiable, organ donor families and recipients can meet after signing a valid declaration of consent, expressed on a template valid for the whole country. A third party within the body of the National Health Systems shall control the validity of the consent. The opinion stresses that contacts are not a right but a possibility justifiable on ethical grounds if the procedure is followed appropriately. A legislative proposal has been presented before the Chamber of deputies incorporating all suggestions made by the National Committee of Bioethics. The agreement between parties might be signed a year after transplantation. This is a long enough period of time for the recipients to fully appreciate the benefits of the procedure and for the donor families to see the effects of their decision (the opinion and the Law proposal hit the Zeitgeist, and keep Italy in the regulation of European Union).

Maximum Time-to-Rescue After the 1908 Messina-Reggio Calabria Earthquake was 20 Days: Hints for Disaster Planning?

Introduction Maximum time-to-rescue has been studied accurately for many earthquakes in the years 1985-2004. No study is available for historical quakes. Hypothesis/Problem This study aimed to evaluate long-term survivors (from the fifth day after the quake) of the Messina-Reggio Calabria earthquake (1908; Italy), which is considered, historically, to be the worst seismic event in Europe. METHODS: Accurate readings of 11 national newspapers from the fifth day after the quake looking for rescued persons and transferring, to an ad hoc form, all data relating to each rescued person. RESULTS: The maximum time-to rescue was 20 days. There were 225 survivors, among them 51 children (22.6 %). For 23 out 225 rescued persons, there was evidence of availability of foods and drinkable fluids while under the rubble. CONCLUSION: The maximum time-to-rescue under the debris following this historical earthquake far exceeds that of all other quakes that occurred in the years 1985-2004. The long survival under debris was probably due to the lack of an order to stop search and rescue. Recent strategies reducing the time for search and rescue carry the risk of missing survivors. De Santo NG , Bisaccia C , De Santo LS . Maximum time-to-rescue after the 1908 Messina-Reggio Calabria Earthquake was 20 days: hints for disaster planning? Prehosp Disaster Med. 2017;32(3):249-252.

Biotechnological traps for the reduction of inflammation due to cardiopulmonary bypass operations.

Cardiopulmonary bypass induces a systemic inflammatory response (SIR), characterized by the activation of cellular and humoral elements, with concomitant release of neutrophil elastase and matrix-metallo proteinases. In the present study, the protease release during extracorporeal circulation in 28 patients undergoing cardiac surgical operations was monitored using casein zymography. A peak in protease activity was found in all patients at the end of cardiopulmonary bypass. Plasma samples of patients were allowed to interact with different traps obtained by immobilizing different protease inhibitors on specific carriers. alpha1-Antitrypsin, Bovine Pancreatic Trypsin Inhibitor, Elastatinal or Leupeptin were used as inhibitors and were covalently immobilized by diazotization or by condensation. A reduction in the proteolytic activity of the plasma samples was observed after interaction with the different traps. The most efficient traps, i.e. the ones displaying greatest power to inhibit protease activity, were those obtained by immobilizing Bovine Pancreatic Trypsin Inhibitor and Leupeptin. The biocompatibility of traps was also tested. Results show that protease activity in blood can be decreased by our protease traps.

Diuretic plants in the Bible: ethnobotanical aspects.

Besides its religious importance, the Bible, because of its ancient origin represents a relevant witness of the way of life of the people mentioned in it. The Holy Scripture is also the first text revealing the utility of plants for man, as natural sources of food, wood, fibers, oils and medicinal herbs. In the last 60 years, several distinguished botanists have attempted to identify the scientific names of the plants cited in the Bible. Nonetheless, these scholars have provided different lists of plants appearing in the Bible, none of which could be accepted as indisputable. The authors have combined their expertise to focus on the identification of the diuretic plants, through an historical analysis of the literature on this issue.

Jacques Loeb (1859-1924) and His Forgotten Contributions to Electrolyte and Acid-Base Physiology in The Organism as a Whole.

Jacques Loeb (1859-1924) was the founder of the Journal of General Physiology which he co-directed in association with W.J.V. Osterhout in the years 1918-1924. Having worked (1889-1891)at the Marine Zoological Station of Naples, newly founded by Anton Dohrn, he was imprinted for life. A strong investigator used to perform the experiments personally. Loeb was engaged lifelong in the explanation of life on physico-chemical basis. He touched various fields (being a creative scientist full of ideas), and centered on the exchanges of electrolytes, acids and bases between the body and sea water in fish. He identified two equations: {[K+]+[Na+]}: {[Ca++]+[Mg++]} (Loebs 1st equation) {[K+]+[Na+]}: {[H+]+[Ca++]+[Mg++]} (Loebs final equation) Even nowadays these equations may have applications in a wide list of electrolyte and acid-base disturbances. Unfortunately his heredity has been dissipated.