Israel Medical Association Journal

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 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.

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

Background: Drug-induced thyrotoxicosis is not uncommon. It may worsen life-threatening arrhythmias and may be refractory to medical treatment. Near-total thyroidectomy presents a valid alternative to medical therapy and should be considered early in the management of the disease.

Objectives: To assess whether near-total thyroidectomy was a viable approach for our patients.

Methods: Twelve patients – 7 men and 5 women, aged 63 to 82 years – presented with drug-induced fulminant thyrotoxicosis following 1 to 12 months of amiodarone treatment (11 patients, mean 7 months) and after a 6 months course of interferon-alpha treatment (one patient). Medical therapy included propylthiouracil in doses up to 1200 mg/day in all patients and a beta-receptor antagonist in seven. Five patients had to stop amiodarone treatment and start high doses of steroids. A thyroid scan was performed in all patients using 5 mCi of Tc-99m pertechnetate. The thyroid scan showed absent uptake of the tracer in the thyroid bed in all patients, precluding the use of radioablation.

Results: Four patients (three with AIT[1] and one with interferon therapy) who did not respond to 3 months of medical therapy required surgical thyroidectomy due to severe unremitting thyrotoxicosis. A near-total thyroidectomy resulted in rapid correction of thyrotoxicosis, enabling continuation of the anti-arrhythmic drug. There were no intraoperative or postoperative arrhythmias. Subsequently, all patients recovered rapidly and remained well and euthyroid on thyroxine replacement therapy.

Conclusions: Since surgery results in rapid control of thyrotoxicosis and permits continued therapy with amiodarone, we suggest that near-total thyroidectomy warrants consideration as a definitive treatment for resistant amiodarone or interferon-induced thyrotoxicosis.

Background: Testicular torsion associated with undescended testis is uncommon but requires immediate treatment. Ultrasound Doppler is recognized as the preferred imaging modality for testicular torsion due to its high specificity, sensitivity and availability.

Objectives: To determine the accuracy of ultrasound Doppler in diagnosis of torsion of undescended testis.

Methods: We describe three patients with known undescended testis who were admitted with groin pain and had preoperative ultrasound Doppler. The discrepancy between these and the intraoperative findings is discussed.

Results: In two patients incarcerated inguinal hernia was diagnosed with ultrasound Doppler; however, surgery revealed torsion of an undescended testis. In the third patient ultrasound Doppler diagnosed torsion of undescended testis, but at surgery incarcerated inguinal hernia was found, without evidence of testicular torsion.

Conclusions: Torsion of undescended testis should be a clinical rather than radiologic diagnosis.
 

Background: Measurement of function is an essential component of routine rehabilitation work (mainly for quantifying function at different phases in the rehabilitation process), rehabilitation policy (admission and discharge criteria, length of stay in rehabilitation), goal setting, and outcome measurement.

Objective: To explore the scope of the scales used for function assessment by the various disciplines of rehabilitation medicine in rehabilitation facilities.

Method: A structured questionnaire was sent to 36 rehabilitation facilities. Respondents were asked to specify the scales they use for functional assessment for each of 15 selected pathologies. Also examined were satisfaction with the scales, as well as the existence of a computerized database of routine function assessment in the facility and the willingness to create a national agreed “common data set” of the assessments.

Results: The general response rate was 86.1% (31 of 36 questionnaires were returned). For the sake of data presentation, rehabilitation facilities were classified into four categories: general, geriatric, pediatric, and community. Most facilities performed function assessment using a total of 125 scales. Heterogeneity was found between facilities and between pathologies. The highest number of scales was found in the area of neurologic pathologies. For most pathologies, assessment of impairment was used more than assessment of disability. Most facilities in the survey did not have a computerized database of function assessments.

Conclusions: A “common data set” of function assessments in everyday clinical work would ensure standardization without necessarily limiting the use of additional scales and at the same time significantly minimize the current heterogeneity.
 

Background: Syndromic surveillance systems have been developed for early detection of bioterrorist attacks, but few validation studies exist for these systems and their efficacy has been questioned.

Objectives: To assess the capabilities of a syndromic surveillance system based on community clinics in conjunction with the WSARE[1] algorithm in identifying early signals of a localized unusual influenza outbreak.

Methods: This retrospective study used data on a documented influenza B outbreak in an elementary school in central Israel. The WSARE algorithm for anomalous pattern detection was applied to individual records of daily patient visits to clinics of one of the four health management organizations in the country.

Results: Two successive significant anomalies were detected in the HMO’s[2] data set that could signal the influenza outbreak. If data were available for analysis in real time, the first anomaly could be detected on day 3 of the outbreak, 1 day after the school principal reported the outbreak to the public health authorities.

Conclusions: Early detection is difficult in this type of fast-developing institutionalized outbreak. However, the information derived from WSARE could help define the outbreak in terms of time, place and the population at risk.

Background: Recently the Joint National Committee (7th report) introduced the term “pre-hypertension.” Little is known on its prevalence in the general population.

Objectives: To assess the prevalence of pre-hypertension in a large national cohort.

Methods: We analyzed the database of all ≥ 18 year old members of Leumit Health Services, one of the four health management organizations in Israel, from which we retrieved the recorded blood pressure levels. Pre-hypertension was defined according to the JNC-7[1] criteria.

Results: Of the 426,033 subjects 18.6% had a diagnosis of hypertension or used antihypertensive medications. Only 40.8% of the other 346,799 subjects had had their BP[2] measured in the preceding 2 years. BP recording rates were higher in females than in males (45.1% vs. 36.3%) and higher in elderly subjects than in young subjects (56% aged 66–75 years vs. 32% aged 18–25). Pre-hypertension was observed in 80,625 (23.2%) of the 346,799 while only 56,113 (16.2%) had normal BP records. The prevalence of pre-hypertension increased with age (13.3% aged 18–25 vs. 44.8% aged 66–75), and was more prevalent in men than in women (24.0% vs. 22.5%).

Conclusions: BP levels among young people are low, even though the prevalence of pre-hypertension in this population may be high. Thus, more emphasis should be given to routine BP measurements and confirmation of the findings in all age groups.

Background: The association between antibiotic use in the community and antimicrobial resistance is known. Attention has recently focused on the type of agents being prescribed.

Objectives: To implement, evaluate and compare the efficacy of two community interventions programs – continuous versus seasonal medical education – oriented to primary care physicians with emphasis on appropriate use of antimicrobial drugs.

Methods: From October 2000 to April 2003 we conducted two interventions: a) a monthly educational campaign in selected clinics promoting appropriate diagnosis of common infectious diseases and prudent antibiotic use (continuous intervention group); and b) a massive educational campaign, conducted before two consecutive winters, promoting the judicious use of antibiotics for treating respiratory infections (continuous intervention group and seasonal intervention group). Sixteen similar clinics were randomized (8 to each group). The total antibiotic use was measured as defined daily dose/1000 patients/day, and compared between the groups. 

Results: The total use of antibiotics decreased between 1999-2000 and 2002-2003 in both groups, but slightly more significantly in the continuous intervention group. The DDD/1000 patients/day for the seasonal group in 1999-2000 was 27.8 vs. 23.2 in 2002-2003; and for the continuous group 28.7 in 1999-2000 vs. 22.9 in 2002-2003, a reduction of 16.5% and 20.0% respectively (p<0.0001). The main change in antibiotic use was noted for broad-spectrum antibiotics.

Conclusions: We present a successful community intervention program aimed to reduce unnecessary antibiotic use. Amplification of this type of intervention is imperative to stop the increase in antimicrobial resistance.
 

Background: The significance of arrhythmia occurring after successful recanalization of an occluded artery during treatment following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction is controversial.

Objectives: To study the association of reperfusion arrhythmia with short and long-term survival.

Methods: We used a prospective registry of consecutive STEMI[1] patients undergoing PPCI[2]. Patients with an impaired epicardial flow (TIMI flow grade < 3) at the end of the procedure were excluded.

Results: Of the 688 patients in the study group, 22% were women. Mean (± SD) age of the cohort was 61 (± 14) years and frequent co-morbidities included diabetes mellitus (25%), dyslipidemia (55%), hypertension (43%) and smoking (41%). RA[3] was recorded in 200 patients (29%). Patients with RA had lower rates of diabetes (16% vs. 30%, P < 0.01) and hypertension (48% vs. 62%, P < 0.01), and a shorter median pain-to-balloon time (201 vs. 234 minutes, P < 0.01) than patients without RA. Thirty day mortality was 3.7% and 8.3% for patients with and without RA, respectively (P = 0.04). After controlling for age, gender and pain-to-balloon time the hazard ratio for mortality for patients with RA during a median follow-up period of 466 days was 0.46 (95% confidence interval 0.23–0.92).

Conclusions: The occurrence of RA immediately following PPCI for acute STEMI is associated with better clinical characteristics and identifies a subgroup with a particularly favorable prognosis.