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עמוד בית Thu, 14.11.19

March 2007


preface
Original Articles
R. Farah, A. Samokhvalov, F. Zviebel and N. Makhou

Background: Hyperglycemia is common among patients admitted to intensive care units, and carries the risk for complications and prolonged ICU[1] stay. With intensive insulin control of blood glucose, morbidity and mortality can be reduced.

Objectives: To determine whether intensive or conventional insulin control of blood glucose in hyperglycemic ICU patients correlated with the prognosis.

Methods: Following admission to the ICU, hyperglycemic patients were randomly assigned to a group treated intensively with insulin targeting glucose at 110–140 mg/dl, or to a conventional insulin therapy group, where glucose, upon exceeding 200 mg/dl, was controlled at 140–200 mg/dl. Rates of morbidity and mortality, hypoglycemic episodes, and insulin dosage were compared.

Results: In the 41 patients treated intensively with insulin the glucose level was 142 ± 14 mg/dl, as compared to 174 ± 20 mg/dl in the 48 patients on conventional insulin treatment. Both groups were similar in age, acute physiology and chronic health evaluation score. Morbidity was also similar, except for increased vascular damage in the conventional treatment group and slightly shorter ICU stay in the intensive therapy group. Both groups had similar in-ICU, in-hospital, and 28 day mortalities, and similar rates of hypoglycemic episodes. The daily dosage of insulin was significantly higher with the conventional treatment (P = 0.004).

Conclusions: Intensive insulin treatment did not affect the mortality or morbidity rates in ICU patients. The increased insulin dosage of conventional insulin treatment was attributable to the group's higher prevalence of diabetes. Future studies should address this bias and determine the optimal glucose target.  

 






[1] ICU = intensive care unit


A. Melman, N. Bar-Chama, A. McCullough, K. Davis and G. Christ

Background: Ion Channel Innovations has developed a gene transfer product, ftMaxi-K, and has begun clinical trials to investigate the effect of increased expression of Maxi-K channels in the smooth muscle of the penis or bladder in patients with erectile dysfunction and those with overactive bladder. The primary function of K channels is to modulate Ca++ influx through Ca-channels (i.e., L-type, voltage-dependent). The amount of Ca++ that enters the cell through these channels is a major determinant of the free intracellular calcium levels inside the smooth muscle cell, which in turn determines the degree of smooth muscle cell contraction. Increased Maxi-K channel activity is associated with smooth muscle cell relaxation, resulting in, for example, penile erection and detrussor muscle relaxation. A phase I clinical trial that used dMaxi-K has been completed and a similar trial to assess safety of the transfer for overactive bladder is about to begin.

Objectives: To assess the safety and tolerability of escalating dMaxi-K doses by clinical evaluations and laboratory tests, and to measure efficacy objectives by means of the International Index of Erectile Function scale.

Methods: In the erectile dysfunction trial 11 patients with moderate to severe erectile dysfunction were given a single-dose corpus cavernosum injection of dMaxi-K, a "naked" DMA plasmid carrying the human cDNA encoding for the gene for the a, or pore-forming, subunit of the human smooth muscle Maxi-K channel, hSIo. Three patients each were given 500,1000, and 5000 pg and two patients were given 7500 pg doses of ftMaxi-K and followed for 24 weeks. Patient responses were validated by partner responses.

Results: There were no serious adverse events and no dose-related adverse events attributed to gene transfer for any patient at any dose or study visit. No clinically significant changes from baseline were seen in physical evaluations (general and genitourinary), hematology, chemistry and hormone analyses, or in cardiac events evaluated by repeated electrocardiograms. Importantly, no plasmid was detected in the semen of patients at any time after the injections. Patients given the two highest doses of dMaxi-K had apparent sustained improvements in erectile function as indicated by improved IIEF-EF domain scores over the length of the study. One patient given 5000 (jg and one given 7500 [jg reported EF category improvements that were highly clinically significant and were also maintained through the 24 weeks of study.
Conclusions: Efficacy conclusions cannot be drawn from results of a phase 1 trial with no control group. However, the promising primary safety outcomes of the study and preliminary indications of effectiveness provide evidence that ftMaxi-K gene transfer is a viable approach to the treatment of erectile dysfunction and other smooth muscle diseases with targeted access

J. Harju, M. Pääkkönen and M. Eskelinen

Background: Earlier studies comparing minilaparotomy cholecystectomy with laparoscopic cholecystectomy did not find significant differences between the MC[1] and the LC[2] groups in operating times and patients' recovery.

Objectives: To compare the postoperative quality of life between the MC and LC groups.

Methods: The 157 patients with uncomplicated symptomatic gallstones, confirmed by ultrasound, were randomized to two groups: 85 for MC and 72 for LC. The study was prospective and randomized but not blinded or consecutive. The study groups were similar in patients' age, gender, body mass index, American Association of Anesthesiology physical fitness classification, and the operating surgeon. Patients were reevaluated 4 weeks after operation using the RAND-36 quality of life questionnaire.

Results: The RAND-36 questionnaire did not identify statistically significant differences between the study groups in general health perceptions, physical functioning, emotional well-being, social functioning, energy, bodily pain, and role functioning/emotional. Only the role functioning/physical score was slightly higher in the LC group (P = 0.038).
Conclusions: The results of this study showed that the MC procedure is a good alternative to the LC procedure, when postoperative quality of life ia measured







[1] MC = minilaparotomy cholecystectomy

[2] LC = laparoscopic cholecystectomy


A. Farfel, M.S. Green, T. Shochat, I. Noyman, Y. Levy and A. Afek

Background: Most Israeli males aged 16–17 undergo a thorough medical examination prior to recruitment into the army. During the last 50 years, extensive data have been gathered enabling a study of time trends in the prevalence of common diseases in this age group.

Objectives: To examine the current prevalence of common diseases, compare the results with those of previous cohorts, and assess the influence of the massive immigration during the 1990s.         

Methods: The health examination at the recruitment centers includes a medical history, complete physical examination, and review of medical documentation provided by the family physician. If needed, additional tests and referral to specialists are ordered. The prevalence of selected diseases and severity was drawn from the computerized database of the classification board. Two cohorts, 1992–94 and 2003–04, were examined and compared with three previous cohort studies in 1957–61, 1977–78 and 1982–84. Data were stratified according to origin and country of birth.

Results: The prevalence of asthma increased dramatically during the years from 10.2 per 1000 examinees in 1957–61 to 111.6 per 1000 examinees in 2003–04. The prevalence of tuberculosis declined and then increased from 0.6 per 1000 adolescents in 1982–84 to 2.4 per 1000 adolescents in 2003–04. The prevalence of type 1 diabetes mellitus increased from 0.2 cases per 1000 examinees in 1957–61 to 0.8 cases in 1977–78 and 1982–84 and 0.9 cases per 1000 examinees in 2003–04. The prevalence of severe heart defects and severe epilepsy declined in the last 20 years (1.4 and 1.7 cases per 1000 examinees in the 1982–84 cohort to 0.4 and 0.3 cases per 1000 examinees in the 2003–4 cohort respectively). The patterns of disease prevalence were different for immigrants: tuberculosis was more common while asthma and allergic rhinitis were less prevalent.

Conclusions: The prevalence of common diseases among adolescents in Israel has changed over the last 50 years. There is a different pattern for immigrants and for those born in Israel.

 
 

Reviews
J. Bornstein

The human papillomavirus family of viruses causes a variety of benign, premalignant and malignant lesions in men and women. All cervical cancers are caused by HPV[1]. It is the leading cause of death from cancer in women in developing countries; every year some 493,000 women develop cervical cancer and 230,000 women die every year of this disease. The vaccine against HPV includes virus-like particles, composed of the major viral capsid protein of HPV without the carcinogenic genetic core. Large-scale studies have shown that the vaccine is tolerated well, leads to high antibody levels in both men and women, and prevents chronic HPV infection and its associated diseases. To achieve effective coverage the vaccine should be given prior to sexual debut. Introduction of the vaccine into specific countries, particularly Israel, should take into account the local incidence of cervical cancer as well as the increasing incidence of precancerous cervical lesions and genital warts, which reduce quality of life and are associated with considerable costs.

 






[1] HPV = human papillomavirus


D. Kristt, J. Stein and T. Klein

Quantitative chimerism testing has become an indispensable tool for following the course and success of allogeneic hematopoietic stem cell transplants. In this paper, we describe the current laboratory approach to quantitative chimerism testing based on an analysis of short tandem repeats, and explain why performing this analysis longitudinally is important and feasible. Longitudinal analysis focuses on relative changes appearing in the course of sequential samples, and as such exploits the ultimate potential of this intrinsically semi-quantitative platform. Such an analysis is more informative than single static values, less likely to be confused with platform artifacts, and is individualized to the particular patient. It is particularly useful with non-myeloablative conditioning, where mixed chimerism is common. When longitudinal chimerism analysis is performed on lineage-specific subpopulations, the sensitivity, specificity and mechanistic implications of the data are augmented. Importantly, longitudinal monitoring is a routinely feasible laboratory option because multiplex STR-PCR[1] kits are available commercially, and modern software can be used to perform computation, reliability testing, and longitudinal tracking in a rapid, easy to use format. The ChimerTrack© application, a shareware program developed in our laboratory for this purpose, produces a report that automatically summarizes and illustrates the quantitative temporal course of the patient’s chimeric status. Such a longitudinal perspective enhances the value of quantitative chimerism monitoring for decisions regarding immunomodulatory post-transplant therapy. This information also provides unique insights into the biological dynamics of engraftment underlying the fluctuations in the temporal course of a patient’s chimeric status.

 







[1] STR-PCR = short tandem repeats-polymerase chain reaction


M. Khaikin, Y. Chowers and O. Zmora
Perianal Crohn's disease refers to the involvement of the anal region in this chronic inflammatory bowel disease. It most commonly presents with the formation of perianal abscesses and fistulas, although other forms of presentations such as fissures and skin tags may also be present. Perianal activity often parallels abdominal disease activity, but may occasionally be the primary site of active disease, and significantly compromises the quality of life in affected patients. The primary treatment of patients with perianal Crohn's disease combines medical and surgical management with the aim of improving quality of life and alleviating suffering. A multidisciplinary approach involving the patient, surgeon, gastroenterologist, radiologist, pathologist, nutritionist, and other specialists makes the successful treatment of PCD[1] possible. This paper reviews the management of patients with perianal Crohn's disease, focusing on contemporary medical and surgical treatments such as infliximab, endorectal advancement flap, instillation of fibrin glue, and the potential use of extracellular matrix plugs






[1] PCD = perianal Crohn's disease


Case Communications
R. AL-Mahfoudh, D.A O'Reilly and M.G.T. Raraty
A. Brautbar, Y. Esyag, G.S Breuer, Y. Wiener-Well and G. Nesher

The human papillomavirus family of viruses causes a variety of benign, premalignant and malignant lesions in men and women. All cervical cancers are caused by HPV[1]. It is the leading cause of death from cancer in women in developing countries; every year some 493,000 women develop cervical cancer and 230,000 women die every year of this disease. The vaccine against HPV includes virus-like particles, composed of the major viral capsid protein of HPV without the carcinogenic genetic core. Large-scale studies have shown that the vaccine is tolerated well, leads to high antibody levels in both men and women, and prevents chronic HPV infection and its associated diseases. To achieve effective coverage the vaccine should be given prior to sexual debut. Introduction of the vaccine into specific countries, particularly Israel, should take into account the local incidence of cervical cancer as well as the increasing incidence of precancerous cervical lesions and genital warts, which reduce quality of life and are associated with considerable costs.

 

 







[1] HPV = human papillomavirus


Medical Ethics
M. Gordon
Cardiopulmonary resuscitation is an emotion-ridden issue that often leads to conflicts when crucial decisions have to be made. The purported benefits of this 40 year old procedure in the frail elderly have been scrutinized, establishing its lack of efficacy. A review of the medical, ethics and halakhic* literature on the potential merits of CPR[1] in the frail elderly revealed that in secular medical practice, CPR is often routinely provided to elderly frail individuals for whom its clinical benefit is questionable. For patients suffering from dementia, surrogates are usually responsible for decision making, which complicates the process. With such poor clinical outcomes, the halakhic interpretation of what steps should be taken, and currently are, may not be valid and CPR may be applied too frequently. When clinical ambiguity is combined with strong cultural and religious influences, an acceptable CPR/DNR (Do Not Resuscitate) approach to cardiac arrest can be daunting. A clinically responsible, ethically sound and religiously sensitive approach to CPR requires a deep understanding of the factors involved in decision making. It seems timely for the halakhic interpretation of the duty to provide CPR in the frail elderly to be reevaluated. Perhaps a more humane and halakhically sound approach might be reached by stringently limiting CPR to clinically unusual circumstances rather than the common practice of providing frail Jewish elders with CPR in the absence of a DNR order.





* Pertaining to Halakha, the corpus of Jewish law


[1] CPR = cardiopulmonary resuscitation


M.A. Weingarten

Preventive medicine is taking an increasingly central place in modern clinical practice, at least in primary care. What, if anything, does the Jewish rabbinic tradition have to say about keeping healthy? The delayed response of contemporary rabbis to the dangers of smoking, in particular, raises questions about the underlying principles that Halakhah* employs to approach health promotion. As is often the case in Halakhah, we may detect different streams of thought in the classical sources, which may be felt in the way contemporary issues are handled. Three approaches will be discussed. First, Maimonides, famous for the practical preventive approach in his medical writings, makes his philosophy clear both in his halakhic works and in his Guide for the Perplexed. For him, a healthy body is a prerequisite for a healthy soul. We must be free of physical suffering in order to be able to do the work of perfecting our souls. Second, the view that health is the reward for goodness and illness a punishment for sin as expounded or implied in the writings of Nahmanides, and of Ibn Ezra that the way to good health is to lead a good life. Third, an early midrashic** source picked up again much later by Rabbi Israel Meir Kagan (the Hafetz Hayim) gives the argument from custodianship – since the body is divine property we have a duty to look after it well. So for Maimonides there is a prior duty to keep healthy, while for Nahmanides the prior requirement is to repent of sin. For the Hafetz Hayim, keeping the body healthy is an independent duty in its own right. These then are the differences in basic approach that may affect the emphases that different rabbis today place on health maintenance and promotion.






* The corpus of Jewish Law

** Biblical commentary forming part of the Talmudic literature


Medical and the Holocaust
Y. Barak

The association between the Holocaust experience and suicide has rarely been studied systematically. The dearth of data in this area of old-age psychiatry does not necessarily imply that Holocaust survivors are immune from suicide. Recent work on the aging of survivors seems to suggest that as a group they are at high risk for self-harm. Published reports on suicide and the Holocaust identified by means of a MEDLINE literature search were reviewed. A similar search was performed on the Internet using the Google search engine. Thirteen studies were uncovered, 9 of which addressed the association of suicide and the Holocaust experience and 4 focused on the suicide within the concentration camps during the genocide. Eleven of the 15 studies explicitly reported on the association of suicide, suicidal ideation or death by suicide with the Holocaust experience, or reported findings suggesting such an association. The Internet search yielded three sites clearly describing increased suicide rates in the concentration camps. An increased rate of suicidal ideation and suicide attempts among the elderly who were exposed to the Holocaust experience is confirmed. There is a need for further study, intervention and resource allocation among the growing numbers of elderly persons who suffered traumatic events in earlier phases of their lives. This is especially critical for Holocaust survivors.

  
 

T. Chelouche

This paper does not attempt to deal with the legitimate ethical or moral debate on abortion. Utilizing abortion as a subject I will show how science and medicine in general, and abortion in particular, were used as weapons of mass destruction by Nazi physicians in their zeal to comply with the political climate of the time. Nazi policy on abortion and childbirth was just one of the methods devised and designed to ensure the extermination of those whom the Nazis deemed had "lives not worth living." Physicians implemented these policies, not with the fate of their patients in mind, but rather in the name of the "state." When discussing pregnancy, abortion and childbirth during the Holocaust it is imperative to include an essay of how these issues affected the Jewish prisoner doctors in the ghettos and camps. Nazi policy dictated their actions too. From an extensive search of their testimonies, I conclude that for these doctors ethical discourse comprised a fundamental component of their functioning. I do not propose to judge them in any way and one should not, in my opinion, argue whether their behavior was or was not morally acceptable under such duress; nevertheless, unlike their Nazi counterparts, a key theme in their testimonies was to "keep their medical values."

  
 

R.D. Strous and M.C. Edelman

Eponyms are titles of medical disorders named for individuals who originally described the condition. They also help us remember and identify the disorder. Medicine is replete with them, and changing them or eradicating them, for whatever reason, is not simple. But when there is a moral issue involved – for example, the research conducted under overwhelming unethical conditions – we believe it wrong to perpetuate and thus “reward” the memory of the individual for whom the disorder is named. The name of a syndrome should thus be discontinued if described by an individual whose research used extreme or who was involved in atrocities against humanity. Ethical considerations should be introduced into medical nosology just as they exist in patient care and research. This article details a group of notable eponyms, the names of which are associated with overt crimes of the medical community during the Nazi era, and provides alternative medical nomenclature. In addition, examples are provided of eponyms named after Nazi era victims, eponyms of those who protested such injustices, and eponyms of those who had to flee discrimination and death. These should be remembered and even strengthened, as opposed to those of the perpetrators, which should be obliterated. Since the greatest accolade a physician can earn is praise from his colleagues as expressed in an eponym entrenched in one's name, the medical profession should remove any honor given to physicians involved in crimes to humanity.

 
 

הבהרה משפטית: כל נושא המופיע באתר זה נועד להשכלה בלבד ואין לראות בו ייעוץ רפואי או משפטי. אין הר"י אחראית לתוכן המתפרסם באתר זה ולכל נזק שעלול להיגרם. כל הזכויות על המידע באתר שייכות להסתדרות הרפואית בישראל. מדיניות פרטיות
ז'בוטינסקי 35 רמת גן, בניין התאומים 2 קומות 10-11, ת.ד. 3566, מיקוד 5213604. טלפון: 03-6100444, פקס: 03-5753303