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Introduction: Since the beginning of the current century, the Galilee Medical Center (formerly Nahariya Hospital) has held "Nahariya conferences on medicine and the Holocaust". It is a unique and ongoing enterprise that tells the wonderful story of Holocaust medicine on the one hand, and the terrible consequences of survivors' health and their offspring on the other. Discussions were held that contributed to intensive research and publications on these issues, as well as to the authorities' recognition of the later stages of Holocaust survivors' illnesses and injuries.

Background: Findings of studies addressing outcomes of war-related famine in non-Jewish populations in Europe during the Second World War (WWII) confirmed an association between prenatal/early life exposure to hunger and adult obesity, diabetes, hypertension, cardiovascular disease and the metabolic syndrome. Fetal programming was suggested as the explanatory mechanism., Objectives: To study the association between being born during WWII in Europe and physical long-term outcomes in child Holocaust survivors., Methods: We conducted a cross-sectional study on all Jewish Clalit Health Services (CHS) North District members born in 1940-1945 in Europe ('exposed', n = 653) or in Israel to Europe-born parents ('non-exposed', n = 433). Data on sociodemographic variables, medical diagnoses, medication procurement, laboratory tests and health services utilization were derived from the CHS computerized database and compared between the groups., Results: The exposed were significantly more likely than the non-exposed to present with dyslipidemia (81% vs. 72%, respectively), hypertension (67% vs. 53%), diabetes mellitus (41% vs. 28%), vascular disease (18% vs. 9%) and the metabolic syndrome (17% vs. 9%). The exposed also made lower use of health services but used anti-depressive agents more often compared to the non-exposed. In multivariate analyses, being born during WWII remained an independent risk marker for hypertension (OR = 1.52), diabetes mellitus (OR = 1.60), vascular disease (OR = 1.99) and the metabolic syndrome (OR = 2.14)., Conclusions: The results of this cross-sectional study based on highly validated data identify a high risk group for chronic morbidity. A question regarding potential trans-generational effects that may impact the 'second generation' is also raised.

Background: Previous studies suggest that exposure to starvation and stress between conception and early infancy may have deleterious effects on health later in life; this phenomenon is termed fetal origin of adult disease., Objectives: To determine whether exposure to the Holocaust from preconception to early infancy is a cause of chronic morbidity in adulthood., Methods: This pilot study involved 70 European Jews born in countries under Nazi rule (exposed group) during the period 1940-1945 who were interviewed to determine the presence of chronic diseases. A control group of 230 Israeli-born individuals of the same descent, age, and gender distribution were extracted from the Israel National Health Interview Survey-2 (unexposed group). The prevalence of selected risk factors and chronic diseases was compared between the groups., Results: The prevalence of cardiovascular risk factors and morbidity was significantly higher in the exposed group: body mass index (BMI) (29.06 +/- 3.2 vs. 26.97 +/- 4.42, P = 0.015), hypertension (62.9% vs. 43%, P = 0.003), dyslipidemia (72.9% vs. 46.1%, P < 0.001), diabetes (32.9% vs. 17.4%, P = 0.006), angina pectoris (18.6% vs. 4.8%, P = 0.001) and congestive heart failure (8.6% vs. 1.7%, P = 0.013). The prevalence of cancer (30.0% vs. 8.7% P < 0.001), peptic ulcer disease (21.4% vs. 7%, P = 0.001), headaches/migraines (24.3% vs. 12.6%, P < 0.001) and anxiety/depression (50.0% vs. 8.3%, P < 0.001) was also higher in the exposed group., Conclusions: These results suggest that exposure to Holocaust conditions in early life may be associated with a higher prevalence of obesity, dyslipidemia, diabetes, hypertension, cardiovascular morbidity, malignancy and peptic diseases in adulthood. These findings set the stage for further research, which might define those exposed as a high risk group for chronic morbidity.

On the morning of November 7, 1938 vom Rath, a diplomat at the German embassy in Paris, was shot by Herschel Grynzspan, a Jewish teenager. Of the 5 shots fired, 2 hit vom Rath, one in the right shoulder and one in the abdomen. He was rushed to Alma Women's Hospital near the embassy, where emergency surgery was undertaken. Two days later his condition deteriorated rapidly and succumbed 55 hours after the shooting. It is believed that the assassination triggered the "Kristallnacht"--the organized Nazi pogrom against Jews across Germany. Based on the Alma hospital registry, autopsy findings and articles from recent years, the course of his condition and possible cause of his death are discussed. The possibility of malpractice, and even medical fraud, which led to his death are also mentioned.

The term "eugenics" was coined by Francis Galton in 1883 and was defined as the science of the improvement of the human race by better breeding. "Positive eugenics" referred to methods of encouraging the "most fit" to reproduce more often, while "negative eugenics" was related to ways of discouraging or preventing the "less fit" from reproducing by birth control and sterilization. Many western countries adopted eugenics programs including Britain, Canada, Norway, Australia, Switzerland and others. In Sweden more then 62,000 "unfits" were forcibly sterilized. Many states in the U.S.A. had adopted marriage laws with eugenics criteria including forced sterilization. Approximately 64,000 individuals were sterilized. Eugenics considerations also lay behind the adoption of the Immigration Restriction Act of 1924. The Largest plan on eugenics was adopted by the Nazi regime in Germany. Hundreds of thousands of people, who were viewed as being "unfit", were forcibly sterilized by different methods: Surgical sterilization or castration with severe complications and high mortality rates. X-ray irradiation. The method was suggested by Brack, and tested by Schuman using prisoners in Block No. 10 in Auschwitz and Birkenau. Experiments were also performed by Brack on prisoners using the "window method". "Klauberg method"--injection of irritating materials into the uterus. Experiments were conducted using the plant Caladium Seguinum which was believed to have sterilization and castration properties.

Future conflicts in our region will no longer be limited to clashes between opposing armies. Unlike past wars, which by and large did not target places of worship and hospitals, such structures will not be immune from attack in the "total wars" of the future, nor will the civilian population be spared. Hospitals may be hit by enemy fire and must, therefore, be ready to work under adverse conditions and emergency situations. This article describes the accumulated experience of our hospital as a confrontation Line medical facility for over 30 years, sustaining direct hits with injuries to people and damage to buildings. Lessons from those confrontations, particularly the second Lebanon war, are discussed and recommendations to other hospitals formulated, essentially highlighting the following: The need to protect the hospital's physical structures in order to guarantee the safety of patients, staff and visitors in the event of conventionaL or non-conventional war. The provision of protected transportation for the staff and in-hospitaL day-camps and dormitories for their children in order to bolster the presence of the staff on board and enable them to work unperturbed. Preparation of the hospital for work under fire, drafting emergency procedures that are custom-tailored to the needs of the hospital, particularly the evacuation of patients from vulnerable wards to protected areas, and drilling the entire staff regularly and methodically.

The mental and physical health of the HoLocaust survivors has interested many researchers around the world. In spite of the assumption that the survivors are prone to develop premature morbidities (based on paralLeL findings among disabled people or people who survived severe trauma), apparently, excessive morbidity was significantly found only in two areas: malignancy and skeLetaL disorders. Survivors should ultimately benefit from broad and sincere assistance in sociaL, economic, mental and medical issues.

Background and Aim: Testicular damage due to ischemia during torsion is aggravated after reduction and reperfusion. The severity of the damage depends on the degree and duration of the torsion. Hypothermia has been successfully used in preserving the viability of ischemic organs for a prolonged period. Our aim is to evaluate the effect of external scrotal cooling in preserving testicular viability after spermatic cord torsion in rats., Methods: 100 adult male Sprague-Dawley rats were equally divided into ten groups. Exposure of the right testicle for either 4 or 8 h in groups 1 and 2 were the control groups. The rats in eight groups (3-10) underwent clockwise torsion of 1,080 degrees of the right testis around its longitudinal axis, for either 4 or 8 h. External scrotal cooling was applied during the torsion period in four groups. Half of the rats were sacrificed at the end of the torsion period, while the other rats underwent detorsion and were sacrificed 2 weeks later. All testicles were excised for histology., Results: The histological results showed that external scrotal cooling decreased both immediate and late damage to the testis, caused by torsion. A moderate degree of injury was found in the contralateral testicle in rats after torsion of the right testicle for 8 h with application of external cooling and detorsion., Conclusion: External scrotal cooling is effective in preserving the viability of the torsed testis in rats. The injury of ischemia-reperfusion, although reduced by external cooling, may endanger the contralateral testis as well, if the duration of torsion is longer than 4 h. With increased duration of torsion, orchiectomy should be considered. Application of this treatment may reduce the injury in humans awaiting surgery.

The harsh life in the ghettos and concentration/extermination camps during the Holocaust was characterized by hunger, exposure to extreme cold temperatures, continuous threats, infectious diseases and injuries with acute or permanent disabilities and extreme psychological stress. There is no definite scientific evidence that the Holocaust survivors are exposed to premature aging or premature appearance of various physical diseases. These aspects were thoroughly investigated in other populations: ex-prisoners of war, ex-displaced persons, prisoners and survivors of torture. Famine, disabilities, diseases and stress, particularly at the beginning of or during puberty, were found to increase vulnerability to later morbidity, especially hypertensive and cardiovascular disease and to increased mortality. This article discusses the possibility of premature aging among Holocaust survivors as a late effect of their life conditions during the Holocaust.

Between 1942 and 1944 millions of prisoners were subjected to forced labor in concentration camps throughout the Third Reich, all the while being the victims of a systematic and "scientific" extermination policy. Though the policy was directed mainly against Jews, it was implemented against other "inferior races" as well. The prisoners, stripped of all rights, experienced constant humiliation, uncertain survival and terror. The harsh living condition, characterized by crowding, absent sanitation and poor personal hygiene led to considerable morbidity, mainly due to injuries, infectious diseases and famine, and to high mortality rates. Medical care in the camps was the responsibility of the S.S. Each camp had a chief S.S. physician accompanied by a number of assistants and orderlies. There was also a parallel system of "prisoner-physicians." There was a chief prisoner-physician in every camp, and each block was assigned a "block doctor" who was responsible for sanitation, the removal of corpses, setting up the sick- call and authorizing sick leave. Work teams were accompanied by "mobile doctors" (Streckenpfleger), who dispensed first aid for work injuries. Prisoner-physicians were also charged with disinfecting the blocks and maintaining hygienic conditions in the camp. Every camp had one or more blocks, called "Reviers", that were used for treatment and hospitalization. In the larger camps a number of blocks were designated to function as a sort of hospital (Krankenbau). At times one camp out of a group of camps would be set aside as quarantine, primarily for patients with infectious diseases. Officially, the "Revier" was the responsibility of an S.S. physicians', assisted by a chief prisoner-physician, his assistants and, at times, nurses. But in actuality the Reviers were managed by prisoners (Capos) who did not have medical training but were authorized to make decisions in medical matters such as operations and, on occasion, even performed them. The Reviers suffered from shortage of everything: beds, manpower, diagnostic and therapeutic means, sterile supplies and drugs for anaesthesia. Crowding was the rule, and each cot was occupied simultaneously by several patients regardless of their condition or the nature of their disease. Life-saving procedures could not be performed and surgery, if done, was usually without anaesthesia. Mortality was high, and the Revier was commonly perceived by the prisoners as a place of death, not of healing. Occasionally there were visits, or inspections, by the S.S. physicians. The main purpose of those visits was "selection". Patients with no chance of recovery were sent to their death and the others were returned to work in spite of their condition. The prisoner-physicians made every effort to prevent this "selection" in various ways. They were often punished or even executed for their efforts.

Life in the concentration camps of the Third Reich was like living on another planet. The prisoners, stripped of all rights, experienced constant humiliation, uncertain survival and endless terror. Living conditions were harsh, characterized by crowding, poor sanitation and personal hygiene, lack of proper clothing and heating. The days began early with long marches and slave labor. Sleep was short and interrupted, and fatigue was constant and severe. Above all hoovered the dark cloud of ever-present famine. The prisoners were given about a fourth of the daily calorie requirements, and the food lacked vital components such as vitamins and other essential ingredients. The psychological stress was extreme, yet morbidity and mortality were mainly due to infections, injuries and hunger. Lice, scabies and other skin diseases were common. Typhus fever was ever-present, both endemic and epidemic, with a fatal outcome. Many suffered from tuberculosis, typhoid, dysentery, pneumonia and other infections diseases. Injuries were common, caused by beating, punitive whiplashing and other forms of physical abuse, gunshot wounds and dog-bites. Skull injuries with brain contusions and hemorrhages were prevalent, as well as fractured limbs, ribs and pelvic bones. Blunt injuries to chest and abdomen often had fatal outcomes due to the perforation of viscera and peritonitis or as a result of massive hemorrhage from ruptured blood vessels. The harsh winters were marked by frozen gangrenous limbs and hypothermia. Yet, the most ominous condition was the "hunger disease" with its multiple clinical expressions which, in their extreme form, led to the emaciated "musleman" and eventual death.

Background: Peripheral neuropathy is considered a common complication in patients suffering from advanced chronic kidney disease (CKD). Superimposed peripheral multiple neuropathies may complicate arteriovenous (A-V) fistulas construction., Aim: To evaluate, prospectively, the influence of brachiocephalic A-V fistulas construction on the peripheral nerves of the same extremity and to characterize the patients at risk for developing ischemic and neurological complications., Patients and Methods: Twenty patients suffering from advanced CKD were enrolled in the study: 10 diabetic and 10 non-diabetic patients. All patients underwent electrophysiological evaluation one week before, 3 weeks and 3 months after surgery. Median, ulnar and radial nerves were studied., Results: In non-diabetic patients MNCV was normal before and after surgery, but were significantly lower and reduced progressively and significantly after surgery in diabetic patients (p< or =0.02). In both non-diabetic and diabetic patients SNCV was reduced, but were significantly lower in diabetic patients before and after surgery (p< or =0.03). In diabetic patients it reduced progressively and significantly after surgery (p<0.01). Thirty percent of patients developed local edema and significant decrease of CMAP of median nerve three weeks after surgery (p=0.02) with complete resolution at three months., Conclusion: Diabetic uremic patients are at increased risk to develop disabling neurological complications after the construction of A-V fistulas. Diabetes was the only predictive risk factor for developing these complications. Prevention requires careful preoperative electrophysiological evaluation and postoperative follow-up.

Erythropoietin (EPO) is a well-known hematopoietic factor and a major determinant of tissue oxygenation. EPO receptors have been identified on a wide variety of non-erythroid cell types including human central nervous system and peripheral nervous system of animal models. The presence or function of EPO receptors in human peripheral nervous system is unknown. By examining nerve segments from radicular and autonomic nerves using immunohistochemical methods, we demonstrated the presence of EPO receptors on myelin sheath of radicular nerves in the human peripheral nervous system.

Bacteriophages are viruses that only infect bacteria. They have played an important role in the development of molecular biology and have been used as anti-bacterial agents. Since their independent discovery by Twort and d'Herelle, they have been extensively used to prevent and treat bacterial infections, mainly in Eastern Europe and the former Soviet Union. In western countries this method has been sporadically employed on humans and domesticated animals. However, the discovery and widespread use of antibiotics, coupled with doubts about the efficacy of phage therapy, led to an eclipse in the use of phage in medicine. The emergence of antibiotic resistant bacteria, especially strains that are multiply resistant, has resulted in a renewed interest in alternatives to conventional drugs. One of the possible replacements for antibiotics is the use of bacteriophages as antimicrobial agents. This brief review aims to describe the history of bacteriophage and early clinical studies on their use in bacterial disease prophylaxis and therapy, and discuss the advantages and disadvantages of bacteriophage in this regard.

Background: Anaemic haemodialysis (HD) patients are treated with erythropoietin and intravenous iron for effective erythropoiesis. Since iron is a potent inducer and aggravator of pre-existing oxidative processes in HD patients, this study was aimed to evaluate the acute in vivo effect of two recommended iron doses on protein oxidation during the HD session., Methods: Iron gluconate was intravenously administered to HD patients in doses of 62.5 or 125 mg per session. A dialysis session without iron administration served as a control for each patient. Carbonylated fibrinogen and iron profile parameters were monitored before and after each session. Plasma carbonylated fibrinogen levels from healthy subjects and HD patients before dialysis were compared. Protein associated carbonyls were identified in plasma by derivatization with 2,4-dinitrophenylhydrazine followed by western analysis and were quantified by densitometry., Results: HD patients on maintenance iron showed elevated carbonylated fibrinogen compared with healthy subjects. During a HD session, carbonyls on fibrinogen further increased when 125 mg iron gluconate was administered, but no changes were detected with 62.5 mg iron gluconate or in the absence of iron. The changes in carbonylated fibrinogen during dialysis showed a significant linear correlation with the calculated values of transferrin saturation and free transferrin., Conclusions: The significant acute increase in carbonylated fibrinogen with 125 mg iron gluconate suggests that this iron dose should be used with caution. As fibrinogen is highly susceptible to iron-induced oxidation in vivo, it may serve as a marker reflecting acute iron oxidative damage and as a tool in refinement of the existing clinical dose guidelines for intravenous iron therapy.

The harsh life in the ghettos were characterized by overcrowding, shortage of supplies (e.g. money, sanitation, medications), poor personal hygiene, inclement weather and exhaustion. Under these conditions, morbidity was mainly due to infectious diseases, both endemic and epidemic outbreaks with a high mortality rate. The dominant feature was hunger. Daily caloric allowance was 300-800, and in extreme cases (i.e. Warsaw ghetto) it was only 200 calories. The food was lacking important nutrients (e.g. vitamins, trace elements) leading to protean clinical expression, starvation and death. The clinical manifestations of starvation were referred to as "the Hunger Disease", which became the subject of research by the medical doctors in the ghettos, mainly in the Warsaw ghetto in which a thorough documentation and research were performed. The first victims of hunger were children. First they failed to thrive physically and later mentally. Like their elders, they lost weight, but later growth stopped and their developmental milestones were lost with the loss of curiosity and motivation to play. The mortality rate among babies and infants was 100%, as was described by the ghetto doctors: "when the elder children got sick, the small ones were already dead...". In the last weeks of the ghettos there were no children seen in the streets. In this article the environmental conditions and daily life of children in the ghettos are reviewed, and the manifestations of "Hunger Disease" among them is scrutinized.

Background: Peripheral neuropathy commonly develops in patients with advanced chronic renal failure. The uremic neuropathy is often subclinical and detectable only by electrophysiological studies. Receptors to erythropoietin (EPO) have been described on non-hematopoietic cells including neuronal cells., Methods: In order to evaluate the effect of five months' EPO therapy on polyneuropathy in predialytic patients, nerve conduction studies (NCS) were done in 46 anemic predialytic patients without neurological complaints. In 22 (twelve non-diabetic and ten diabetic) neuropathy was detected and these patients were included in the study. After five months of subcutaneous EPO therapy NCSs were repeated., Results: Hemoglobin increased significantly (p=0.0001) with no significant increase in plasma creatinine. Motor nerve conduction velocity (MNCV) and compound muscle action potentials (CMAP) of the ulnar nerve were normal before EPO therapy and at the end of the study. MNCV of the median, peroneal and tibial nerves improved significantly (p<0.05). CMAP of the median nerve rose significantly, to the normal range (p=0.01). Sensory nerve conduction velocity (SNCV ) and sensory nerve action potentials (SNAP) were reduced in all sensory nerves and did not improve. The improvement in non-diabetic patients was better than in diabetic patients. No significant correlation was found between the increase in hemoglobin and the improvement in MNCV., Conclusions: Subcutaneous EPO therapy improved motor polyneuropathy in uremic patients, especially non-diabetic individuals. The improvement in MNCV may reflect remyelination. This non-hematopoietic effect may be related to some direct action through EPO receptors on peripheral neuronal cells.

Background: Cigarette smoking is a well-known risk factor for the development of endothelial dysfunction and the progression of atherosclerosis. Oxidative stress and inflammation have recently been implicated in endothelial dysfunction., Objectives: To assess the concomitant contribution of polymorphonuclear leukocytes to systemic oxidative stress and inflammation in cigarette smokers., Methods: The study group comprised 41 chronic cigarette-smoking, otherwise healthy males aged 45.0 +/- 11.5 (range 31-67 years) and 41 male non-smokers aged 42.6 +/- 11.3 (range 31-65) who served as the control group. The potential generation of oxidative stress was assessed by measuring the rate of superoxide release from separated, phorbol 12-myristate 13-acetate-stimulated PMNL and by plasma levels of reduced (GSH) and oxidized (GSSG) glutathione. Inflammation was estimated indirectly by: a) determining the in vitro survival of PMNL, reflecting cell necrosis; b) in vivo peripheral PMNL counts, reflecting cell recruitment; and c) plasma alkaline phosphatase levels, indicating PMNL activation and degranulation., Results: PMA-stimulated PMNL from cigarette smokers released superoxide at a faster rate than PMNL from the controls. Smokers had decreased plasma GSH and elevated GSSG levels. In vitro incubation of control and smokers' PMNL in sera of smokers caused necrosis, while control sera improved smoker PMNL survival. Smokers' PMNL counts, although in the normal range, were significantly higher than those of controls. Plasma ALP levels in smokers were significantly higher than in controls and correlated positively with superoxide release and PMNL counts., Conclusions: Our study shows that PMNL in smokers are primed in vivo, contribution concomitantly to systemic oxidative stress and inflammation that predispose smokers to endothelial dysfunction, and explains in part the accelerated atherosclerosis found in smokers.

The effect of erythropoietin (EPO) on the oxidative stress (OS) and inflammation caused by polymorphonuclear leukocytes (PMNLs) in end-stage renal failure patients undergoing continuous ambulatory peritoneal dialysis (CAPD) was investigated in vivo and in vitro. The studies were performed on isolated PMNLs from peripheral blood of CAPD patients before and following 6 weeks of EPO treatment and from healthy controls. OS was expressed by the rate of superoxide release from phorbol 12-myristate 13-acetate (PMA) stimulated isolated PMNLs and the inflammatory state was evaluated by PMNL counts of the enrolled subjects. Following 6 weeks of EPO treatment in CAPD patients, both the rate of superoxide release from PMNLs and PMNL counts fell significantly when compared with the pretreatment values. In vitro incubation of PMNLs from CAPD patients with increasing amounts of EPO displayed a significant reduction in their rates of superoxide release. EPO, by direct interaction with PMNLs, attenuated their primed state, causing reduction in oxidative stress and inflammation., (Copyright 2002 S. Karger AG, Basel)

The environmental conditions and daily life in the ghettos of Europe during the holocaust are reviewed, and their effect on morbidity in different ghettos is scrutinized in an attempt to construct a typical morbidity profile. The outstanding characteristics were: crowding, shortage of basic necessities (such as food, clothing and medications), harsh environmental and sanitary conditions, inclement weather, poor personal hygiene, chronic undernutrition and malnutrition, physical and mental exhaustion. Morbidity was mainly due to infectious diseases, both endemic and epidemic outbreaks with high mortality, and high infestation rates of lice and other parasites. The dominant feature was "hunger disease" with its protean clinical expressions, endocine pathology, growth and development retardation in children, and amenorrhea and infertility among women of child-bearing age. Polyuria, nocturia and increased frequency of bowel movement were common. The typical presentation of a ghetto dweller was of extreme emaciation (a loss of up to 50% body weight); muscle weakness and skeletal abnormalities; pale, dry skin with excoriations; pedal edema; anxiety and nervousness; often goiter in children. Most of the inhabitants had some, or all, of those signs and symptoms (there were times when more than half the population was sick). This syndrome complex was termed "Ghetto Sickness" or "Ghetto Fatigue" (ghetto schwachkeit).

Background: Intracellular ionized calcium ([Ca2+]i) is a key mediator in the activation and oxidant production by peripheral polymorphonuclear leukocytes (PMN). Primed PMN contribute to oxidative stress (OS) and inflammation in essential hypertension (EH). Elevated [Ca2+]i has been described in insulin-resistant states and in various cell types in EH but not in EH PMN. The aim of this study was to evaluate the levels of [Ca2+]i in peripheral EH PMN in relation to plasma insulin levels and blood pressure (BP)., Methods: The PMN were separated from blood of 20 nonsmoking, nonobese untreated EH patients, age range 20 to 60 years and from 20 age- and gender-matched healthy individuals (NC). Plasma glucose and insulin levels 2 h after a 75-g oral glucose load, reflected insulin resistance. PMN [Ca2+]i was measured by flow cytometry in isolated cells stained with Fluo-3., Results: The EH PMNs showed significantly increased [Ca2+]i compared to NC PMN. Eighty percent of EH patients showed significantly higher plasma insulin levels after glucose load. Linear regression analysis showed significant correlation between 1) PMN [Ca2+]i and mean arterial pressure (MAP) (r = 0.5, P < .006); 2) PMN [Ca2+]i and fasting plasma insulin (r = 0.7, P < .005); and 3) fasting plasma insulin and MAP (r = 0.4, P < .04)., Conclusions: This study adds PMN to previously described cells exhibiting elevated [Ca2+]i, contributing to OS and inflammation. The correlation of individual BP with both PMN [Ca2+]i and plasma insulin levels, together with the fact that elevated [Ca2+]i mediates PMN priming, suggest that elevated [Ca2+]i and insulin are involved in the pathogenesis of hypertension-induced vascular injury in EH.

During the period between the 12th and 16th century, most European universities were under Papal control and Jews were restricted. An exception to this was the University of Padua, established in 1222. As "Universa Universis Patavina Liberta", outside of papal control, Jewish students were permitted to study and qualify for academic degrees. The Medical School, opened in 1250, was generally regarded as the best medical school in Europe. The universities tolerant and liberal approach attracted students the world-over, particularly drawing European Jews to Padua to study medicine. However, these young Jews lacked the necessary prerequisites, including a basic knowledge of Latin, the official university language. They benefited from the generous support of the Jewish community of Padua and, in particular, that of the Paduan medical alumni, the best known of whom was Dr. Salomo Conigliano. Between the years 1409 and 1816, 325 Jewish physicians graduated from the University of Padua. Among them were many distinguished scholars including Joseph Del Medigo, Joseph Hamiz, Benjamin Mussafia and Tovia Cohen, and many families of physicians who returned to their home countries to practice medicine. In addition to their medical contribution, Jewish graduates served their communities as religious and social leaders. They shared a common university background and cultural heritage, common interests and values. They also maintained close contact among themselves and among non-Jewish colleagues and hence were influenced by new social and cultural movements in Europe. These Jewish graduates of Padua played a crucial role in the developments of the Jewish culture and society, including the "Haskala" movement.

A previous study from our laboratory has shown that erythropoietin (EPO), beside its traditional role in erythropoiesis, acts as an alleviator of oxidative stress and inflammation in chronic hemodialysis (HD) patients, conferred in part by activated polymorphonuclear leukocytes (PMNLs). To substantiate this phenomenon, the existence of EPO receptors (EPO-Rs) on PMNL membrane was examined at the transcriptional and translational levels. mRNA for EPO-R was detected in PMNLs using specific primers directed towards the extracellular region of human EPO-R cDNA. The predicted 300-bp fragment was amplified by reverse transcriptase-polymerase chain reaction. Subcloning and sequence analysis revealed 100% homology of this fragment with human EPO-R. The receptor protein was detected on the surface of intact PMNLs using (125)I-EPO. The protein was further demonstrated by flow cytometric analysis using a fluorescent monoclonal anti-EPO-R. The percentage of PMNLs expressing EPO-R showed a strong correlation with the level of EPO in the serum, suggesting an upregulation of the receptor by the hormone. Taken together with our recent findings that EPO attenuates the oxidative stress and inflammation contributed by PMNLs in HD patients, the detection of functional EPO-R expression in PMNLs places these cells among the nonerythroid, EPO-responsive target populations., (Copyright 2001 S. Karger AG, Basel)

Background: Reactive oxygen species (ROS) play a key role in renal ischaemia-reperfusion injury. After establishing the in vitro anti-oxidative potential of mesna, a sulfhydryl-containing compound, its effect on kidney function and morphology in a rat model of ischaemic acute renal failure (ARF) was examined., Methods: Mesna (180 mg/kg) was administered at different time points relative to ischaemia and/or reperfusion onset. Kidney function was assessed by glomerular filtration rate (GFR) and fractional sodium excretion (FE(Na)) before a 45-min period of unilateral renal artery clamping and following 90 min of reperfusion. Mesna was administered by bolus, 30 min before the induction of ischaemia, 5 min before ischaemia, 5 min before reperfusion, and 5 min after the onset of reperfusion., Results: Mesna improved function of the ischaemic kidney at each administration. When mesna was administered 5 min before the onset of reperfusion, GFR reached 90-100% of its pre ischaemic value and FE(Na) was improved by 75%. The beneficial effect of mesna was also demonstrated by light and electron microscopy. Kidneys treated with mesna 5 min before reperfusion resembled ischaemic non-reperfused kidneys and showed subtle morphological and ultrastructural changes compared with ischaemic-reperfused kidneys. Mesna had no haemodynamic effect on renal blood flow and did not induce any osmotic diuresis., Conclusions: We suggest that mesna acts as an antioxidant. Its antioxidant potential together with optimal protection achieved when administered 5 min before reperfusion, supports the conclusion that mesna scavenges ROS generated at the onset of reperfusion, thus diminishing reperfusion injury and organ damage.

Background: Patients on chronic hemodialysis (HD) are exposed to oxidative stress. An HD session is used in this study as an in vivo model for studying the influence of heparin on oxidative stress caused partially by activated peripheral blood polymorphonuclear leukocytes (PMNLs) during a HD session., Methods: Each patient underwent HD once with and once without heparin. Oxidative stress was determined by evaluating both the rate of superoxide release from phorbol 12-myristate 13-acetate (PMA)-stimulated PMNLs and plasma levels of oxidized glutathione (GSSG), both measured before and after the dialysis session., Results: In vitro, heparin reduced the rate of superoxide release from separated PMA-stimulated PMNLs. In vivo, the rate of superoxide release from PMNLs was always increased after the dialysis session, regardless of the presence of heparin. However, in the presence of heparin, this increase was significantly smaller. The augmentation in the rate of superoxide release after the dialysis session without heparin was accompanied by a significant elevation of GSSG, reflecting a preceding oxidation of plasma glutathione., Conclusions: The increase in both parameters, the rate of superoxide release, and the plasma GSSG concentration after HD treatment suggest that heparin in vivo alleviates the oxidative stress induced by the dialysis process. Based on our results, heparin should be the anticoagulant of choice because of its suppressant action on HD-induced oxidative stress.

Pregnancies in women suffering from advanced chronic renal failure are frequently associated with deterioration of maternal renal function, premature births and low birth weights. Prophylactic dialysis is sometimes instituted since this intervention ameliorates the uremic milieu and improves maternal status and fetal uterine environment. This report describes a successful pregnancy and delivery in a hypertensive woman with advanced chronic renal failure due to polycystic kidney disease without accelerating the natural deterioration of renal function and without instituting prophylactic dialysis. The infant was delivered at full term with a normal birth weight. Thirty months after delivery, growth and development of the child were normal and the rate of deterioration of maternal renal function, assessed by 1/creatinine, was unaffected by pregnancy. Conservative management and effective control of blood pressure may be sufficient to achieve successful pregnancy outcome when women with advanced chronic renal failure become pregnant., (Copyright 2001 S. Karger AG, Basel)

Objective: To determine the extent to which peripheral polymorphonuclear leukocytes (PMNs) contributed to oxidative stress (OS) and inflammation in type 2 diabetic patients., Research Design and Methods: PMNs and plasma were separated from blood withdrawn from 18 type 2 diabetic patients and 16 age- and sex-matched normal control subjects. The rate of superoxide release from phorbol 12-myristate 13-acetate (PMA)-stimulated PMNs and the plasma glutathione (GSH) levels served as measures of OS. Inflammation was assessed by PMN recruitment, expressed by peripheral blood PMN counts, and the in vitro survival of PMNs, which reflects cell necrosis., Results: PMA-stimulated PMNs from diabetes released superoxide significantly faster, and plasma-reduced GSH was lower in diabetic patients than in normal control subjects. The rate of superoxide release from diabetic PMNs showed no correlation with the plasma glucose concentrations, whereas a positive linear correlation with HbA1c was found. The in vitro survival of diabetic PMNs was lower than normal control PMNs when each was incubated in its own serum. The in vitro survival of normal control PMNs was reduced when incubated with diabetic serum, whereas normal control sera promoted the survival of diabetic PMNs. Peripheral PMN counts were higher in diabetic patients than in normal control patients., Conclusions: Type 2 diabetes is accompanied by a priming of PMNs, resulting in OS and increased self-necrosis. Necrosis starts a chain of inflammatory reactions that result in cell recruitment and in the long run, with OS, may result in endothelial dysfunction. Understanding the contribution of PMNs to OS and inflammation in diabetes may illuminate new mechanisms through which endothelial dysfunction evolves and causes angiopathy and atherosclerosis.

The effect of erythropoietin (EPO) on the oxidative stress and inflammation caused by polymorphonuclear leukocytes (PMNLs) in chronic hemodialysis (HD) patients was investigated in vivo and in vitro. The studies were performed on isolated PMNLs from peripheral blood of healthy controls and HD patients before and following 6 weeks of EPO treatment. The oxidative stress was expressed by the rate of superoxide release from phorbol 12-myristate 13-acetate stimulated PMNLs, and the inflammatory state was evaluated by in vitro PMNL survival, in addition to white blood cell and PMNL counts of the enrolled subjects. Following 6 weeks of EPO treatment, in HD patients, the rate of superoxide release from PMNLs as well as WBC and PMNL counts fell significantly when compared with the pretreatment values. PMNLs from HD patients and healthy controls incubated in vitro with increasing amounts of EPO displayed a significant reduction in their rates of superoxide release and a significant improvement in survival. We have concluded that EPO interacts with PMNLs, attenuating their primed state in HD patients, thus reducing oxidative stress and the extent of inflammation. To the best of our knowledge, this attenuation of the primed state of PMNLs by EPO is a new finding.

During the period of the 11th to 17th century, the access of Jews to European universities was restricted and even those who were fortunate enough to be admitted to a university were not awarded a degree at the end of their studies. An exception to this situation was the University of Padua that allowed Jewish students to study and awarded them degrees; indeed 229 physicians graduated from this university between 1409 and 1721. Among these physicians there were many luminaries such as Joseph Del Medigo, Salmon Congeliano and Toviah Cohen. The latter made many contributions to the field of nephrology. In this treatise Maaseh Toviah he discussed uroscopy, kidney function, body fluid homeostasis and obstructive uropathy.

The contributions of nitric oxide (NO) and renal blood flow (RBF) were examined in ischemia-reperfusion injury in the rat kidney. The function of both kidneys was assessed by glomerular filtration rate (GFR), and fractional excretion of sodium (FENa), calculated before, during unilateral renal artery clamping (45 min), and following reperfusion (90 min). RBF was measured in the same model by ultrasonic flowmetry. Intrarenal NO levels were modulated by administration of S-nitroso-N-acetylpenicillamine (SNAP), L-arginine, acetylcholine, and the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). SNAP increased GFR from 0.20 +/- 0.04 ml/min in control ischemic kidney to 0.38 +/- 0.06 ml/min and reduced FENa from 19.3 +/- 3.4 to 9.5 +/- 1.8%. Similar results were observed when L-arginine was administered. Acetylcholine had no effect on GFR or FENa. RBF was fully restored within 60 min following reperfusion, with no change in the rate of recovery by L-arginine. L-NAME aggravated the ischemia-reperfusion injury, preventing full restoration of RBF, further reducing GFR and worsening FENa. In conclusion, ischemia-reperfusion injury ends in low intrarenal levels of NO. We propose that this low NO level results from damage to the endothelial receptor signal transduction process and is not due to impaired NO synthase activity or to changes in RBF.

Oxidative stress and inflammation have recently been linked to endothelial damage in essential hypertension (EH). Activated peripheral polymorphonuclear leukocytes (PMN) damage surrounding tissue by releasing reactive oxygen species (ROS) and proteolytic enzymes before self-necrosis. PMN necrosis further exacerbates inflammation and promotes chemotaxis and PMN recruitment. The number and properties of PMN from untreated EH patients is the focus of the present study. Oxidative stress was assessed by measuring the rate of superoxide anion release from separated, phorbol ester-stimulated PMN and the redox state of plasma glutathione. Inflammation was estimated indirectly by determining PMN number and their in vitro survival. PMN from EH patients (n = 37) released superoxide anion faster (P < .0001) than those of normotensives (NC, n = 37), 17.7 +/- 1.14 v 9.54 +/- 0.51 nmol/10 min/10(6) cells. The redox state of glutathione was twofold higher in EH plasma (P < .02) indicating systemic oxidative stress. PMN survival in vitro correlates linearly with the rate of superoxide release (r2 = 0.60, P < .02) and PMN count of EH patients, although in the normal range, were significantly higher (P < .0001), indicating necrosis and recruitment. Hypertensive plasma significantly reduced NC PMN viability, whereas normal plasma significantly increased EH PMN viability. What our studies show is that EH is accompanied by a primed state PMN that does not correlate with the levels of blood pressure. PMN priming in EH patients reflects an in vivo exposure to a constant stimulus ending in oxidative stress, increased self-necrosis, and cell recruitment. Oxidative stress and inflammation will result in endothelial damage and atherosclerosis in the long run.

This hospital has been certified by the Israel Standards Institute as having a quality assurance system fulfilling the requirements of the international standard, ISO 9002. This is the first hospital in this part of the world to be certified as fulfilling this standard. Its adoption is one of several accepted approaches to quality assurance in medicine. World-wide, very few health organizations, including hospitals, have implemented this system successfully. Opinions regarding its importance are divided, mostly because of lack of experience in its application. We describe its features, goals and structure, and its implementation in various sectors, including health organizations. The process of its adoption, application and implementation is described, and the problems which arose are discussed.

Both the Old Testament and the Talmud contain a great deal of information on medicine, nephrology, health and disease. The basic premise of early Jewish medicine is based on the notion that disease is due to structural changes in internal organs. This is in contrast to the mythical dogma of humoralism as the basis of health and disease espoused by Hippocrates and Galen. The Old Testament and the Mosaic Codes provided the basis for modern public health and for the hygienic rules practised in our times. The Talmudists laid the foundations for the science of pathology as we know it today. These issues are discussed in detail and the contributions of three prominent medieval physicians (Asaph Judaeus, Isaac Judaeus and Maimonides) are presented.

Programmed cell death, by apoptosis, has been shown to play an important role in the regulation of haemopoiesis. Using trypan blue exclusion for distinguishing intact membranes, flow cytometry for detection of sub G1 peak and in situ terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL), this study shows that heparin induces apoptosis in vitro in human peripheral blood neutrophils. The known anti-proliferative effect of heparin in several in vitro cell systems has therefore to be interpreted in the light of apoptosis. In addition, apoptosis may help explain the anti-inflammatory effects resulting from the interaction between vessel wall heparan sulphate and chemoattracted peripheral blood neutrophils.

Uremic patients undergoing hemodialysis (HD) are known to be highly susceptible to infections. Recent data indicate that in addition to its well-known stimulating effects on red cell production, erythropoietin (EPO) may also have immunomodulating properties. The aim of this study was to examine the effect of EPO on lectin-induced T-lymphocyte transformation in uremic patients, as part of its effect on the immune response. Sixteen HD patients and 20 age- and sex-matched healthy controls were compared before and after 6 and 20 weeks of EPO treatment. T lymphocytes were analyzed for their mitogenic activity following treatment with phytohemagglutinin (PHA), concanavalin A (CON A) and anti-CD3 by measuring 3H-thymidine incorporation. HD patients showed reduced mitogenic responses to all mitogens tested, compared to healthy controls. During the 6 weeks of EPO administration, a significant increase in T-lymphocyte activity could be demonstrated following exposure to all three mitogens (PHA, from 32 +/- 2 to 45 +/- 8; CON A, from 11 +/- 3 to 25 +/- 9; anti-CD3, from 11 +/- 3 to 22 +/- 5, means +/- SD). This increase was augmented after 5 months of EPO treatment. We conclude therefore that EPO improves in vitro T-cell mitogenic proliferation, even after short periods of treatment.

Immunohistochemical peroxidase staining for p53 protein was performed on 22 condyloma acuminatum tissue samples from patients infected with human papillomavirus (HPV). The purpose of our study was to understand the benign character of this syndrome. The patients studied were infected by HPV type 6 and 11. Two monoclonal antibodies, PAbs DO-1 and 240, were used to detect the p53 protein. Overexpression of wild-type p53 was found in the nuclei of the basal cell layers. In healthy tissues and non-infected patients no p53 protein expression was detected. We would like to speculate that infection with HPVs and their viral protein E7, which is implicated in disruption of normal growth, may regulate the induction of wild-type p53 over-expression, as is known for DNA-damaging agents such as UV- or X-radiation.

Parathyroid hormone (PTH) is the main hormone controlling calcium concentration in the extracellular fluid (ECF) through its biological activity on bone, kidney and intestine. However, data published over the last two decades indicate that PTH may act as an immunomodulator. The purpose of the present review is to summarize the effects of PTH on various immune functions. Polymorphonuclear leukocytes of patients with chronic renal failure (CRF) and elevated blood levels of PTH showed impaired migration, reduced phagocytic and bactericidal activity, and inhibited granulocyte chemotaxis. Antibody production and T and B lymphocyte proliferation are affected by PTH, both in vivo and in vitro. Possible implications of the involvement of PTH and its fragments in CRF are discussed.

In the present study, activity of polymorphonuclear leukocyte (PMNL) intracellular antioxidant enzymes, i.e. catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPX), was assessed in CRF patients on hemodialysis (HD), or continuous ambulatory peritoneal dialysis (CAPD) and in healthy controls. The activity of SOD and GPX was reduced in HD and in CAPD (SOD: by 34.2 and 42%, respectively, and GPX 66 vs. 42%, respectively, taking the activity in normal controls as 100%). Catalase activity, on the other hand, was significantly augmented (298 and 175%, respectively) as compared to the healthy controls. This impairment in antioxidant enzymes activity, involved in the respiratory burst and phagocytosis, may contribute to the understanding of the reduced bactericidal ability of PMNL activity found in these patients.

We studied the increasing expression of the p53 tumor suppressor gene in Sprague-Dawley rats, chemically induced to develop colon cancer. p53 expression was evaluated histochemically at various stages of tumor progression (during a period of 40 weeks) that can be followed by colonic hyperproliferation labeled by 3H-thymidine incorporation. We found that high level nuclear expression of p53 protein correlates with progression of malignancy in carcinogen-induced animals, whereas cytoplasmic staining is related to the onset and early development of malignancy.

n-Butyl-2-cyanoacrylate (Histoacryl) is said to be as effective as microsurgery for tubal anastomosis. In a prospective controlled study at the regional teaching hospital research laboratories, 40 female laboratory rats underwent laparotomy, with ligation of the uterine horns, and reanastomosis by microsurgery or cyanoacrylate tissue adhesive. Main outcome measures were patency of uterine horns following anastomosis, histologic examination of anastomotic sites and pregnancy rate following anastomosis by each of the two methods. Patency rates were 100% with both methods of anastomosis, although foreign-body granulomas were more prominent in horns anastomosed by microsurgery. When cyanoacrylate was used on one horn and the contralateral horn ligated, a 90% pregnancy rate was achieved; when microsurgery was used, the pregnancy rate was 80%. In microsurgically anastomosed tubes there was a longer narrow segment, resulting in a lower number of embryos per rat. Cyanoacrylate tissue adhesive is successful in tubal reanastomosis and has certain advantages over classical microsurgical techniques: fewer foreign-body granulomas occur; there is less narrowing of the uterine horn; less skill is required in its use.

The relationship among daily cigarette consumption, washed and non-washed RBC filterability time (FT) as an indicator of erythrocyte deformability and echocardiographic left ventricular mass (LVM) were examined in 25 clinically healthy smokers and in 25 non-smoking controls matched for sex and age. FT of non-washed RBC was significantly higher in smokers than in non-smokers (25.2 +/- 3.6 vs. 16.8 +/- 2.2 min, P < 0.001). A highly significant linear correlation between number of cigarette consumption and FT was found. These differences were not observed when RBC were washed three times with isotonic saline. LVM was significantly greater in smokers (85.5 +/- 13.4 g/m2) than in controls (61.8 +/- 6.7 g/m2, P < 0.001). A linear correlation between daily cigarette consumption and LVM was observed. A positive relationship between LVM and FT of non-washed RBC was also found. These results demonstrated that LVM is significantly elevated in smokers and is linearly correlated with both cigarette consumption and RBC filtratibility. The increased deformability found in smokers may be a determinant to the cardiac hypertrophy. The association of both elevated LVM and rheological impairment may indicate unfavourable prognosis.

The aim of the present study was to examine the effect of exposing animals to 100% oxygen instead of room air on renal function and endogenous antioxidant enzymes of the postischemic reperfused rat kidney. Superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) were determined in the homogenate of the left kidney after 45 min of ischemia, caused by clamping the left renal artery, 10 and 90 min after reperfusion while the animals breathed room air or 100% O2. The right kidney served as a control. The possible influence of trapped blood in the clamped kidney was also investigated by the use of a correction factor based on the Hb concentration in the homogenate. The results indicate that such correction is necessary as the blood adds significant antioxidant activity. The activities of all 3 enzymes after 45 min of ischemia decreased significantly in the left (ischemic) compared to the right (control) kidney, to 64% of the control levels for catalase, 58% for SOD and 49% for GPX. After 10 min of reflow, a further decrease in the activities of catalase (to 49%) and of GPX (to 29%) was found. SOD activity, however, increased to 64%. After 90 min of reperfusion, restoration toward normal levels was noticed (SOD activity increased to 70%, catalase to 76% and GPX to 58%). Breathing 100% O2 resulted in a significant decrease in all enzyme activities (to 38.6% for catalase, 45% for SOD and to 27.4% for GPX). This inactivation can be explained by increased reactive oxygen species (ROS) activity during hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)