[TWENTY YEARS OF NAHARIYA CONFERENCES ON MEDICINE AND THE HOLOCAUST].

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.

Chronic health conditions in Jewish Holocaust survivors born during World War II.

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.

Long-term health effects in adults born during the Holocaust.

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.

[Young man with gunshot wound (GSW)--what killed Ernst vom Rath?].

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.

[Sterilization and eugenics].

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.

[Hospital under fire--take home message from one war].

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.

[Late morbidity among Holocaust survivors].

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.

[Late morbidity among Holocaust survivors: myth or fact?].

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.

[Western Galilee Hospital in Nahariya--50+ years].

Initially beginning as a small birthing center, the Western Galilee Hospital (WGH) in Nahariya is now the largest hospital in Galilee. It serves a demographically mixed Israeli population of more then 400,000, the Galilee's mosaic of Jews, Moslems, Christians, Druze and large immigrant populations from the former Soviet Union and Ethiopia. The hospital is also a treatment center for IDF and UN soldiers. The staff, which reflects the ethnically mixed population of the region, is a long-standing model of cooperation and peaceful coexistence. Doctors and nurses of different faiths and cultural backgrounds work together in harmony and with respect to achieve a mutual goal: to provide the best and finest medical treatment to all in need. The hospital's proximity to the Lebanese border, together with its previous experience as the target of Katyusha rocket fire, has forced management to construct underground facilities for emergency situations. Five-hundred beds and eight modern operating rooms that are fully protected from conventional, biological and chemical warfare are an integral part of the preparedness program. The entire staff participates in preparatory drills for mass casualty events. WGH is a forerunner in quality of medical care. To date it is the only Israeli hospital to meet the demanding standards for ISO 9000 2000 certification for quality management, and has now adopted the standards of the European Federation of Quality Management (EFQM). The hospital won the Rabin National Award for Quality in 1995.

[Medicine in the concentration camps of the Third Reich].

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.

Electrophysiological abnormalities in upper extremities after brachiocephalic A-V fistulas construction in predialysis patients.

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.

[Bacteriophages as antibacterial agents].

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.

[Morbidity in the concentration camps of the Third Reich].

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.

[Clinical manifestations of "Hunger Disease" among children in the ghettos during the Holocaust].

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.

Carbonyl stress induced by intravenous iron during haemodialysis.

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.

Effect of erythropoietin therapy on polyneuropathy in predialytic patients.

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.

The involvement of peripheral polymorphonuclear leukocytes in the oxidative stress and inflammation among cigarette smokers.

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.

Interaction between erythropoietin and peripheral polymorphonuclear leukocytes in continuous ambulatory dialysis patients.

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.

[Medicine in the ghettos during the Holocaust].

The Health systems in several ghettos in Europe during the holocaust were studied in an attempt to construct a typical structural profile. The medical system in a typical ghetto consisted of a department of public health (sanitation) that belonged to the Yudenrat, several hospitals, outpatient clinics, first aid stations and physicians in the labor groups. The structure of the system in several ghettos is discussed and the functions of the various units in the prevention of epidemics, and health education are reviewed. Also described is the medical research that was carried out in the ghettos, emphasizing the work on "Hunger Disease" in the Warsaw ghetto, as well as the heroic endeavor to establish a clandestine medical school in the Warsaw ghetto during the holocaust.