Israel Medical Association Journal

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.  

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

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

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.

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.

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.

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.