Analysis of 10 urinary BTEX metabolites using LC-MS/MS.

Benzene, toluene, ethylbenzene, and xylene (BTEX) are a group of volatile organic compounds that are ubiquitous in the environment due to numerous anthropogenic sources. Exposure to BTEX poses a health hazard by increasing the risk for damage to multiple organs, neurocognitive impairment and birth defects. Urinary BTEX metabolites are useful biomarkers for the evaluation of BTEX exposure, because of the ease of sampling and their longer physiological half-lives compared with parent compounds. A method that utilizes LC-MS/MS was developed and validated for simultaneously monitoring of 10 urinary BTEX metabolites. During the sample preparation an aliquot of urine was diluted with an equal volume of 1% formic acid; internal standard solution was added, and then the sample was centrifuged and analyzed. The analytes were separated on the Kinetex-F5 column by applying a linear gradient, consisting of 0.1% formic acid and methanol. The method was validated according to the FDA Bioanalytical Method Validation Guidance for Industry. The mean method's accuracies of the spiked matrix were 81-122%; the inter-day precision ranged from 4 to 20%; the limits of quantitation were 0.5-2 µg/L. The method was used for the evaluation of baseline levels of urinary BTEX metabolites in 87 firefighters.

The Prevalence of Hypomagnesemia in Hospitalized Type 2 Diabetic Patients Treated with Diuretics and/or Proton Pump Inhibitors.

BACKGROUND: Hypomagnesemia (serum magnesium level < 1.7 mg/dl) occurs more frequently in patients with type 2 diabetes mellitus (T2DM).Serum magnesium levels are not routinely tested in hospitalized patients, including in hospitalized patients with T2DM. OBJECTIVES: To evaluate the prevalence of hypomagnesemia among hospitalized T2DM patients treated with proton pump inhibitors (PPIs) and/or diuretics. METHODS: A total of 263 T2DM patients hospitalized in general departments were included in the study and were further divided into four groups: group 1 (patients not treated with PPIs or diuretics), group 2 (patients treated with PPIs), group 3 (patients treated with diuretics), and group 4 (patients treated with both PPIs and diuretics).  Blood and urine samples were taken during the first 24 hours of admission. Electrocardiogram was performed on admission. RESULTS: Of the 263 T2DM patients, 58 (22.1%) had hypomagnesemia (serum magnesium level < 1.7 mg/dl). Patients in group 2 had the lowest mean serum magnesium level (1.79 mg/dl ± 0.27). Relatively more patients with hypomagnesemia were found in group 2 compared to the other groups, although a statistically significant difference was not observed. Significantly more patients in group 3 and 4 had chronic renal failure. Patients with hypomagnesemia had significantly lower serum calcium levels. CONCLUSIONS: Hospitalized T2DM patients under PPI therapy are at risk for hypomagnesemia and hypocalcemia.

[HOW DOES A NEW MEDICAL PROFESSION COME TO LIFE?]

AIMS: In our article we seek to describe the initiation of new medical specialty fields in Israel, including the different considerations in the decision-making process and recent trends. BACKGROUND: Physicians' specialization by postgraduate training and specialty certification satisfies the publics' need for high quality medical treatment, supports medical institutions confidence in their medical staff qualifications, guarantees physicians' social accountability and is also linked with positive medical results. Nevertheless, fragmentation of medicine enfolds a hazard to continuity of medical care and loss of holistic perspectives, as well as hazards of systematic malfunction such as brain drain in vital basic specialties and high costs. METHODS: Information was gathered from the protocols of relevant deliberations conducted at the Scientific Council of the Israeli Medical Association, dealing with the initiation of new medical specialty fields and from relevant regulations. Numerical data was extracted from the IMA database. The information gathered was qualitatively analyzed by Template Analysis. RESULTS: Over two decades ranging between 1999 and 2019, three new medical specialties were initiated, including Emergency Medicine (1999), Pain Relief Medicine (2008) and Palliative Medicine (2012). The initiation of two other specialties, Invasive Neuro-Radiology and Metabolic Diseases, is still under process. The field of Child Development has joined an existing specialty in Pediatric Neurology, becoming a new specialty in Pediatric Neurology and Child Development in 2008, a new route for Pediatric Emergency Medicine branched out of Emergency Medicine (2008) and a new route for Pediatric Rheumatology branched out of Rheumatology (2013). We describe the different considerations taken into account, the prerequisites to initiation and milestones of the process, including grandfathering and accreditation. CONCLUSIONS: The trend of specialization in more medical fields will probably continue in the foreseen future. It will therefore continue to challenge the Scientific Council of the Israeli Medical Association with complex decision-making regarding the initiation of new medical professions or new routes within exciting professions.

[A PUBLIC HOSPITAL IN THE ERA OF 'INNOVATION-DRIVEN MEDICINE' - HUMAN EXCELLENCE AND EVOLVING TECHNOLOGY].

INTRODUCTION: Assaf Harofeh Medical Center is the fourth largest governmental hospital in Israel, with 900 beds, approximately 165,000 annual ER visits, and 23,000 operations. The Medical Center encourages human excellence and medical innovation, together with "patient centered" perspectives, providing optimal holistic service, alongside caring for the staff. The management concept of "participatory leadership" leads to multi-sectorial integration, conducting combined physician-nurse quality projects in all departments. As part of leading the field of quality and accreditation and the desire to share knowledge and experience, the School for Quality and Accreditation was established to train medical teams from the hospital and other medical centers. This issue presents articles that illuminate some of the work on our flourishing campus. The hospital serves a diverse population both demographically, and socio-economically. We feel responsibility for this population beyond the provision of medical care. The many centers of excellence in prominent clinical fields and the platform for providing continuous education for the medical staff to carry out basic and clinical research, are at the forefront for the future. Following demographic expansion of the population around the hospital, the task of providing optimal and equitable medical services is challenging. Over the next decade, the hospital is expected to be united with psychiatric and geriatric hospitals to create an integrated medical center.

The Use of Complementary and Alternative Medicine Among Dialysis Patients.

Context • The use of complementary and alternative medicine (CAM) has been on the rise in the last decade. Subpopulations of patients with chronic diseases are at risk for adverse events and potential drug-herb interactions, among them dialysis patients. Objective • The study aimed to evaluate the prevalence of CAM consumption among dialysis patients and to search for potential interactions. Design • The study was cross-sectional, based on questionnaires. Setting • The study occurred in the hemodialysis unit at Assaf Harofeh Medical Center (Zeriffin, Israel). Participants • Participants were patients of the hemodialysis unit. Outcome Measures • The questionnaires obtained demographic data, information about a patient's medical history and use of prescription medication, and all relevant history of CAM use, including the interest of the medical team in the patient's use of supplements. Results • Eighty-four patients participated in the study. Eight patients (9.5%) had used CAM, 5 of whom were women (62.5%). Of the CAM consumers, 4 (50%) had more than 12 y of education vs 14 (8.4%) in the nonconsumer group (P = .061). Six of the consumers were professionals (75%) in comparison with 30 (39.5%) of the nonconsumers, although that difference was not statistically significant (P = .22). The CAM users' monthly incomes were significantly better than that of the nonconsumers (P = .01). No differences were found regarding smoking, alcohol consumption, or physical activity. The study found potential drug-herb interactions in 4 (50%) of the CAM consumers. Moderate potential interactions were found between Aloe vera and diuretics; Aloe vera and insulin; pyridoxine and calcium-channel blockers and diuretics; and niacin and statins. Those interactions had the potential to result in hypoglycemia, hyperglycemia, hypokalemia, and lower blood pressure. Conclusions • The study found a lower prevalence of CAM consumption in dialysis patients than had been found in other studies of the general population. Still, the unawareness of the harm and potential interactions and the lack of data sharing between the patients and caregivers might have had disastrous consequences. Therefore, caregivers need to inquire of their patients specifically about their use of CAM, especially for populations with chronic diseases, let alone patients undergoing dialysis.

Metformin Does Not Induce Hyperlactatemia in Patients Admitted to Internal Medicine Ward.

BACKGROUND: Concerns about metformin-associated lactic acidosis (MALA) prohibit the use of metformin in a large subset of diabetic patients, mostly in patients with chronic kidney disease. Increasing evidence suggests that the current safety regulations may be overly restrictive. OBJECTIVES: To examine the association between chronic metformin treatment and lactate level in acute illness on the first day of admission to an internal medicine ward. METHODS: We compared diabetic and non-diabetic hospitalized patients treated or not treated with metformin in different sets of kidney function. RESULTS: A total of 140 patients participated in the study, 54 diabetic patients on chronic metformin treatment, 33 diabetic patients without metformin and 53 patients with no diabetes. Most participants were admitted for conditions that prohibit metformin use, such as heart failure, hypoxia and sepsis. Average lactate level was significantly higher in the diabetes + metformin group compared to the diabetes non-metformin group. Metformin treatment was not associated with higher than normal lactate level (hyperlactatemia) or low pH. No patient was hospitalized for lactic acidosis as the main diagnosis. CONCLUSIONS: Chronic metformin treatment mildly increases lactate level, but does not induce hyperlactatemia or lactic acidosis in acute illness on the first day of admission to an internal medicine ward. These data support the expansion of metformin use.

[Mentoring newly appointed department heads--a new project review and initial findings].

BACKGROUND: In Israel, the training of a department head is based mostly on clinical and professional aspects and often does not include any training in other facets of management he or she will encounter. The newly appointed department head is expected from the start to deal with many diverse tasks, and is exposed to great physical and emotional stress. The Israeli Medical Association, taking note of this situation, initiated a mentoring program for newly appointed heads of medical departments, clinics and units. This article seeks to present a preliminary description of our experience with this mentoring project, in which senior managers mentor novices in the position. METHOD: An announcement of the new project was sent to both senior and beginning managers, detailing the project's goal. The project's content and structure were determined together with the participants, mentors and mentees. The values attending the project were delineated as full and genuine partnership, attention to needs, and personal choice of the mentee. Basic guidelines, adaptive to modification according to personal preferences, were developed based on these values. Though not readily assumed, our decision to allow mentees to choose their mentors was found to be suitable for this project. All participants, mentors and mentees, were asked to complete feedback forms in preparation for the final gathering of the group. RESULTS: The first session of the project included 8 mentor and mentee couples. Feedback indicated a high suitability rate between mentor and mentee, which resulted in high levels of satisfaction among the mentees. Responses to feedback questionnaires depicted that the relationships between the mentors and mentees included trust, openness and a non-judgmental approach, which allowed mentees to share personal difficulties and develop plans to overcome them. Most mentees described the mentorship as providing leverage to personal growth. Mentors expressed satisfaction for the opportunity to contribute of their experience. CONCLUSIONS: The success of the first session and the satisfaction expressed by its participants serve as an indication that the project met an existing need of beginning managers. The successful cooperation between mentors and mentees, closely accompanied by the professional staff, proved that beginning managers are more than willing to work alongside senior managers and learn from their vast experience. The writers believe there is a true need for mentorship for managers in our health system. The method depicted in this project was found to be efficient at this point. The next sessions of the project will allow us to identify more ways to match and oversee the mentor-mentee couples.

Physician-Patient Communication Course: When the Inauguration of a New Israeli Medical School Coincided with COVID-19 Pandemic.

Purpose: The curriculum of the Adelson School of Medicine at Ariel University, the newly established sixth medical school in Israel, includes a simulation center-based extended course on physician-patient communication, aiming to help students master the core competency of interpersonal and communication skills. For more than a year following the emergence of the COVID-19 pandemic, the school suspended most face-to-face (F2F) encounters, transforming most teaching activities to remote platforms. The paper outlines the ways we adapted teaching of this course to these circumstances, the reactions of students and mentors to the changes and results of 1st year students' survey. Methods: During the lockdown in the first year 48 of 70 first-year students participated in a voluntary anonymous online evaluation of the course assessing motivation to become a physician; perceptions, feelings and attitudes towards the communication course, and advantages and disadvantages of online and F2F medical interviews. Results: 46.1% of the responding students reported that the pandemic strengthened their desire to become physicians. 56.3% claimed that they were able to a relatively large extent to empathize with COVID-19 patients who were exposed to the virus; 79.1% viewed their mentors as positive role models of communication skills. The students were able to receive and offer social support to their peers. They evaluated very highly the short instructional videos produced by the faculty. Conclusion: During the lockdown, the respondents generally indicated positive attitudes towards the communication course, the mentors and the inclusion of physician-patient communication as a topic in medical education. The students and mentors reported many disadvantages and few advantages of remote learning. Yet inevitably remote learning including online-based simulations is a step towards preparations for future practice within virtual medical care and telemedicine. The limitations of this study include the cross-sectional design, small sample size and self-reporting.

N-3 fatty acid supplementation to routine statin treatment inhibits platelet function, decreases patients' daytime blood pressure, and improves inflammatory status.

OBJECTIVES: N-3 fatty acids reduce the risks of cardiovascular morbidity and mortality. Administration of N-3 fatty acids to patients treated with statins may potentiate the treatment effects. We examined the operating mechanisms underlying such a combination. METHODS: Thirty-two hypercholesterolemic patients aged 30-70 years with hypercholesterolemia controlled by statins, received sequential treatments with placebo followed by 1.9 g/day of N-3 fatty acids for 23 weeks. Scheduled clinical visits included physical examination, 24-h blood pressure measurement, endothelial function evaluated by pulse wave analysis, analyses for platelet function, inflammation markers [interleukin (IL)-6, plasminogen activator inhibitor-1 (PAI-1)] and oxidative stress parameters (STAT-8-Isoprostane) were undertaken at baseline, after placebo treatment, and after 6 and 20 weeks of N-3 fatty acid intake. RESULTS: Platelets functions were significantly inhibited, whereas endothelial function parameters were unaltered. IL-6 significantly decreased whereas PAI-1and STAT-8-Isoprostane levels remained unaffected. Daytime blood pressure significantly decreased; however, nighttime pressure and heart rate remained unchanged. No evidence of lipid-profile improvement was observed following combined treatment with statins and N-3 fatty acids. CONCLUSIONS: In hypercholesterolemic patients, combination of statins and N-3 fatty acid inhibits platelet aggregation, alters inflammatory status, and positively affects daytime blood pressure. Close long-term follow-up might reveal additional beneficial effects of N-3 fatty acids in this patient population.

Hematological Biomarkers, Mortality, Transfusion and Acute Heart Disease.

BACKGROUND: Patients hospitalized with acute heart disease [acute myocardial infarction (MI); heart disease exacerbation] may require red blood cell (RBC) transfusion. These patients are at increased risk for morbidity and mortality. Hematological biomarkers may help to identify increased mortality risk. The aim of the study was to evaluate the association between hematological biomarkers and survival in these patients. METHODS: A historical cohort study of all patients admitted to an internal medicine department, who were diagnosed with acute heart disease and requiring RBC transfusion, was carried out in a tertiary medical center between 2009-2014. The association between hematological biomarkers and 30-, 90-day and 5-year mortality was studied. RESULTS: A total of 254 patients (median age 80 years, IQR 74-86.25; 40.9% females; acute MI 24.8%), were included. During the 5-year follow-up 212(83.5%) patients died. In a multivariate analysis the lower platelet to neutrophil ratio (PNR) was significantly associated with increased 30-, 90-day and 5-year mortality (p<0.001, 0.041, 0.003 respectively). A higher red cell distribution width (RDW) was significantly associated with 30- and 90-day mortality (p=0.003, 0.023 respectively), while higher neutrophil to lymphocyte ratio (NLR) was associated with increased 30-day and 5-year mortality (p= 0.036, 0.033 respectively). CONCLUSIONS: Hematological biomarkers may help to identify increased mortality risk of acute heart disease patients, receiving RBC transfusions in an internal medicine department.

Long QT and death in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease is not related to electrolyte disorders.

Objectives: COPD is the fourth-leading cause of mortality worldwide. Prolonged QTc has been found to be a long-term negative prognostic factor in ambulatory COPD patients. The aim of this study was to evaluate the extent of prolonged-QTc syndrome in COPD patients upon admission to an internal medicine department, its relationship to hypomagnesemia, hypokalemia, and hypocalcemia, and the effect of COPD treatment on mortality during hospital stay. Methods: This prospective cohort study evaluated COPD patients hospitalized in an internal medicine department. The study evaluated QTc, electrolyte levels, and known risk factors during hospitalization of COPD patients. Results: A total of 67 patients were recruited. The median QTc interval was 0.441 seconds and 0.434 seconds on days 0 and 3, respectively. Prolonged QTc was noted in 35.8% of patients on admission and 37.3% on day 3 of hospitalization. The median QTc in the prolonged-QTc group on admission was 0.471 seconds and in the normal-QTc group 0.430 seconds. There was no significant difference in age, sex, electrolyte levels, renal function tests, or blood gases on admission between the two groups. Mortality during the hospital stay was significantly higher in the prolonged-QTc group (3 deaths, 12%) than in the normal QTc group (no deaths) (P=0.04). A subanalysis was performed, removing known causes for prolonged QTc. We found no differences in age, electrolytes, or renal functions. There was a small but significant difference in bicarbonate levels. Conclusion: Our findings demonstrated that there was no correlation between QTc prolongation in hospitalized COPD patients and electrolyte levels, comorbidities, or relevant medications. A higher rate of mortality was noted in patients with prolonged QTc in comparison to normal QTc. As such, it is suggested that prolonged QTc could serve as a negative prognostic factor for mortality during hospitalization in COPD patients.

The effect of levothyroxine on arterial stiffness and lipid profile in patients with subclinical hypothyroidism.

BACKGROUND: The influence of treatment for subclinical hypothyroidism (SCH) on cardiovascular morbidity and mortality, arterial stiffness, and lipid profile has not been elucidated yet. The aim of this study was to evaluate the effect of levothyroxine on arterial stiffness, lipid profile, and inflammation. METHODS: The study included 30 patients with SCH. Patients were treated with levothyroxine and were assessed at baseline and at 1, 4, and 7 months. Blood samples were taken for lipid profile and highly sensitive C-reactive protein (hs-CRP). Arterial stiffness was evaluated by augmentation index (AIx). In conditions that cause arterial stiffness, the pulse wave traveling from the periphery to the heart reaches the heart during systole, resulting in augmentation of the central pressure. This increase, calculated as the AIx, is a good expression of central aortic pressure. RESULTS: After accomplishing euthyroidism, the AIx decreased from 17.2 +/- 8.3 to 14.3 +/- 6.5 (p < 0.01) and AIx percentage decreased from 36.2 +/- 11.5 to 33.2 +/- 9.1 (p = 0.03). Systolic blood pressure (SBP) decreased from 134.7 +/- 20 to 127.6 +/- 13.7 mmHg (p < 0.01). In those patients whose AIx decreased, low-density lipoprotein (LDL) levels decreased by 0.4 +/- 0.96 mmol/L compared to the patients whose AIx did not decrease and LDL increased by 0.62 +/- 1.48 mmol/L (p = 0.057). Total cholesterol decreased by 0.72 +/- 1.64 mmol/L in the patients whose AIx decreased and increased by 1 +/- 2.53 mg/dL in the patients whose AIx did not improve (p = 0.06). CONCLUSIONS: In patients with SCH, treatment with levothyroxine had a significant beneficial effect on arterial stiffness and SBP, and no effect on lipid profile or hs-CRP.

Hemoglobin transfusion trigger in an internal medicine department - A "real world" six year experience.

BACKGROUND: Transfusion guidelines advocate restrictive rather than liberal use of red blood cells (RBC) and are based mostly on randomized trials in intensive care and surgical departments. We aimed to study RBC transfusion practice in the medical patients' population. METHODS: The data in this study were collected from patients over the age of 18 years admitted to an Internal Medicine department between 2009 and 2014 who received at least one unit of packed red blood cells (RBC). In addition, data on demographics, patients' diagnoses, laboratory tests and number of transfused RBC units were extracted from the electronic health records. RESULTS: One thousand three hundred and twenty eight patients were included, having mean age of 75 ± 14 years. The median hemoglobin (Hb) trigger for RBC transfusion was 8.0 g/dl (IQR 7.3-8.7g/dl), and most patients received either one (43.4%) or two (33.4%) RBC units. There was no significant difference in Hb trigger between males and females (Hb 8.0 g/dl and 7.9 g/dl, respectively, p = 0.098), and a weak correlation with age (r = 0.108 p = 0.001). Patients with cardiovascular and lung diseases had a statistically significant higher Hb trigger compared to patients without those diagnoses, however the median difference between them was 0.5 g/dl or less. CONCLUSIONS: These "real world" data we collected show a Hb trigger compliant with the upper limit of published guidelines and influenced by medical patients' common diagnoses. Prospective trials addressing patients hospitalized in internal medicine departments could further contribute to transfusion decision algorithms.

Lower hemoglobin transfusion trigger is associated with higher mortality in patients hospitalized with pneumonia.

Patients hospitalized with pneumonia may require packed red blood cell (RBC) transfusion during their hospital stay. Patient survival may be associated with the transfusion trigger. These patients may need a higher hemoglobin (Hb) trigger than that suggested by the AABB guidelines (7 g/dL).The objective of this study was to evaluate the association between the initial transfusion Hb trigger and in-hospital mortality.A historical cohort study of all patients hospitalized in an internal medicine ward between 2009 and 2014 with pneumonia, who received at least 1 unit of RBC, was evaluated. The primary outcome was all-cause in-hospital mortality.One hundred males and 77 females with a median age of 80 (interquartile range 71-87) years were included. The median Hb trigger was 8.10 g/dL. Mortality rate was 56% in patients with Hb trigger ≤7 g/dL, 43.8% in Hb trigger 7 to 8 g/dL, and 29.5% in Hb trigger >8 g/dL (P = .045). Patients in the 3 Hb trigger categories did not differ in age, sex, comorbidities, albumin, creatinine, C-reactive protein, white blood cells, and platelet counts. The result of a multivariate analysis showed that only lower Hb trigger (odds ratio [OR]≤ 7vs.>8 = 5.24, OR7-8vs.>8 = 2.13, P = .035) and higher neutrophil count (P = .012) were associated with increased in-hospital mortality.In conclusion, a lower transfusion trigger is associated with increased risk for in-hospital mortality in patients hospitalized with pneumonia requiring RBC transfusion.

Enhanced angiotensin II production by renal mesangium is responsible for apoptosis/proliferation of endothelial and epithelial cells in a model of malignant hypertension.

OBJECTIVE: The systemic renin-angiotensin system (RAS) plays a crucial role in the pathogenesis of malignant hypertension. However, the intrarenal RAS might be at least equally important. We investigated the relationship between intrarenal RAS and mesangial, epithelial and endothelial cell proliferation/apoptosis in a model of malignant hypertension. METHODS: Cultured murine mesangial cells were subjected to 160 mmHg hydrostatic pressure for 1 h. Angiotensin II was assessed by radio-immunoassay (RIA); pro-metalloproteinase-1 (pro-MMP-1) by enzyme-linked immunosorbent assay (ELISA); hydrogen peroxide (H2O2) by photocolorimetric assay, apoptosis by terminal dUTP (2-deoxyuridine 5'-triphosphate) nick-end labelling (TUNEL), p53 by western blot and proliferation by [H]thymidine incorporation, with or without angiotensin II and/or angiotensin II type 1/angiotensin II type 2 (AT-1/AT-2) receptor blockers. Endothelial and epithelial cells were similarly treated, and the same parameters evaluated. Further, untreated cells of both lines were cultured in conditioned medium of mesangial cells exposed to pressure. Their proliferation, apoptosis and angiotensin II production were also assessed. RESULTS: High hydrostatic pressure increased angiotensin II production by mesangial cells, coinciding with augmented apoptosis and proliferation. Co-stimulation with exogenous angiotensin II amplified both effects. Pressure per se evoked no response in endothelial/epithelial cells, while exogenous angiotensin II stimulated proliferation and apoptosis. No augmentation of p53 expression was evident. These effects were abolished by anti-angiotensin-II peptide, saralasine and losartan, but not by PD123319. Incubation of untreated cells in medium of mesangium subjected to pressure, augmented proliferation and apoptosis. No significant changes were noticed in pro-MMP or H2O2. CONCLUSIONS: Mesangium plays a deleterious role in the pathogenesis of malignant hypertension. High hydrostatic pressure stimulates angiotensin II synthesis by mesangial cells. The latter is responsible for hypercellularity and apoptotic death of mesangial, endothelial and epithelial cells. In this model, exaggerated apoptosis and proliferation are mediated via the angiotensin II pathway independently of p53 gene activation.

Rembrandt--aging and sickness: a combined look by plastic surgeons, an art researcher and an internal medicine specialist.

Rembrandt van Rijn (1606-1669) left behind the largest collection of self-portraits in the history of art. These portraits were painted over a period of 41 years, using a realistic technique. To evaluate Rembrandt's aging process we studied 25 uncontested Rembrandt oil self-portraits by means of objective and descriptive techniques. By measuring brow position changes through the years, we demonstrated that brow descent started in the second half of the third decade and began to level out in the fourth decade. Based on Rembrandts' aging physiognomy, from age 22 to 63, we believe that Rembrandt did not suffer from temporal arteritis, hypothyroidism, rosacea, or rhynophima and that no other facial signs of systemic diseases are evident, contrary to the opinions expressed by other medical professionals. We suggest that Rembrandt suffered from melancholia or mild depression, and propose the possibility of chronic lead poisoning as a theoretical illness that he might have had.

The daily incidence of acute heart failure is correlated with low minimal night temperature: cold immersion pulmonary edema revisited?

BACKGROUND: Previous studies suggested a higher incidence of acute heart failure (AHF) during cold months in regions with cold climate. We examined the daily incidence of AHF by same-day trough temperature and humidity in a warmer region. METHODS AND RESULTS: All admissions for AHF (340 patients) to a city hospital, providing the sole emergency medical care to a geographical region of approximately 500,000 people were recorded. Patients were followed through admission and for 6 months after discharge. Low minimal trough temperature was associated with an increase in the same-day AHF incidence. Lowest tercile trough night temperatures were associated with higher AHF incidence (3.5 +/- 2.1 versus 2.4 +/- 1.6, events/24 hours, P = .012). This association was mainly from increased AHF events in nights with the predetermined trough temperature of <7 degrees C (4 +/- 2.1 versus 2.5 +/- 1.7, events/24 hours, P = .0013). This association persisted even after excluding the coldest consecutive 30 days from the analysis. Humidity was not associated with increased AHF event rate. In a post-hoc analysis we have observed doubling of 6-month mortality in patients admitted with AHF during days with lower trough night temperature, despite no apparent worse baseline characteristics or disease severity at admission. CONCLUSIONS: AHF rate is increased during days with lower trough night temperature. If confirmed, these results may have implications on issues related to climate control in houses of the elderly or patients susceptible to heart failure.