Israel Medical Association Journal

Background: Adjuvant/neoadjuvant chemotherapy in breast cancer patients may be associated with amenorrhea and a marked reduction in ovarian reserve.

Objectives: To assess the use of letrozole with follicle-stimulating hormone (FSH) in gonadotropin-releasing hormone (GnRH) analogue protocols, based on reported attempts to avoid the estradiol (E2) increase during controlled ovarian hyperstimulation for embryo cryopreservation in breast cancer patients using a combination of low dose FSH and aromatase inhibitor (letrozole) in a GnRH-antagonist protocol.

Methods: Twenty-four breast cancer patients were treated with recombinant FSH (150–450 U/day) and letrozole (5 mg/day) in a long GnRH-agonist (n=7) or GnRH-antagonist (n=17) protocol. After oocyte retrieval, insemination and/or intracytoplasmic sperm injection was performed. The embryos were frozen.

Results: The average interval from surgery to oocyte retrieval was 40 days. Average duration of treatment was 9.6 days and mean peak E2 level 1342 ± 1091 pmol/L, yielding 16.0 ± 16.3 oocytes (range 0–82). Mean fertilization rate was 69.5 ± 20.4% and mean number of embryos cryopreserved 10.3 ± 9.3. More oocytes were retrieved with the long GnRH protocol, but the difference was not statistically significant (24.8 ± 24.6 vs. 12.0 ± 8.8 pmol/L, P = 0.07).

Conclusions: As previously reported, ovarian stimulation with letrozole and FSH, in both the long GnRH-agonist and GnRH-antagonist protocols, is apparently effective in breast cancer patients and spares them exposure to high E2 levels.
 

Suicide is universal within the range of human behaviors and is not necessarily related to psychiatric morbidity, though it is considerably more prevalent among psychiatric patients. Considering the limitations of medical knowledge, psychiatrists cope with an unfounded and almost mythical perception of their ability to predict and prevent suicide. We set out to compose a position paper for the Israel Psychiatric Association (IPA) that clarifies expectations from psychiatrists when treating suicidal patients, focusing on risk assessment and boundaries of responsibility, in the era of defensive medicine. The final draft of the position paper was by consensus. The IPA Position Paper established the first standard of care concerning expectations from psychiatrists in Israel with regard to knowledge-based assessment of suicide risk, elucidation of the therapist's responsibility to the suicidal psychotic patient (defined by law) compared to patients with preserved reality testing, capacity for choice, and responsibility for their actions. Therapists will be judged for professional performance rather than outcomes and wisdom of hindsight. This paper may provide support for psychiatrists who, with clinical professionalism rather than extenuating considerations of defensive medicine, strive to save the lives of suicidal patients.
 

Background: In the past, carotid endarterectomy (CEA) was the only modality for invasive intervention in cases of carotid stenosis. Due to improvements in endovascular techniques (stenting), there is a growing debate regarding the preferred procedure for carotid intervention.

Objectives: To compare the 30 day complication rate after CEA and carotid angioplasty and stenting (CAS) in a tertiary medical center in Israel between the years 2008 and 2010.

Methods: We reviewed the medical charts of all the patients who underwent either CEA or CAS of the internal carotid artery due to symptomatic and asymptomatic stenosis during the period 2008–2010 (total of 128 patients).

Results: There was no difference between the groups in the rate of severe complications in the peri-procedural period. Mild complications were non-significantly more common in the CEA group (17%) compared to the CAS group (7.1%).

Conclusions: There was no significant difference in the mild and severe complications rate between CEA and CAS in the peri-procedural period.

Background: The rate of infection with Clostridium difficile colitis and its associated mortality have been increasing in the last decade. The molecular epidemiology of C. difficile in Israel has as yet not been studied.

Objectives: To screen for the existence of the 027 and 078 ribotypes and determine the longitudinal molecular epidemiology of the circulating clinical C. difficile isolates in a large hospital in central Israel.

Methods: Polymerase chain reaction (PCR) ribotyping was performed on C. difficile isolates obtained from hospitalized patients from November 2003 to May 2004 (first study period) and September 2009 (second study period). Isolates with PCR[1] ribotype patterns, unlike those of the available reference strains (078 and 027), were labeled with letters. Forty-six isolates from the first study period and 20 from the second were analyzed.

Results: PCR strain typing of C. difficile isolates yielded approximately 26 unique ribotypes. During the first study period, ribotype A and B accounted for 30% and 28%, respectively, whereas ribotype E and K accounted for 6.5% for each. During the second study period, ribotypes A, E and K disappeared, and the incidence of ribotype B decreased from 28% to 15%. One isolate (1/20, 5%) emerged during the second period and was identified as ribotype 027. Moxifloxacin resistance was found in 93% of ribotype A isolates, 81% of the ribotype B group, and in 44% of other ribotypes.

Conclusions: The predominant ribotypes circulating in our institution were diverse and changing. This is the first report on the emergence of the 027 ribotype in Israel.

Background: Familial Mediterranean fever (FMF) is a recessively inherited disease with a variety of clinical presentations. The disease is associated with mutations in the FMF gene (MEFV), which encodes for the pyrin protein. The role of the E148Q pyrin mutation in the FMF phenotype remains inconclusive, and some authors even view it as a disease-insignificant polymorphism. The calculated change, imposed by this mutation on pyrin structure, may help to understand the role of this mutation

Objectives: To calculate the relative electrochemical effect of the E148Q mutation on the structure of pyrin protein.

Methods: The electronic properties of the wild-type pyrin molecule and its common mutated forms were computed for the full-length molecule and its segments, encoded by exons 2 and 10, using the HyperChem 7.5 program with one of the molecular mechanical methods (MM+). The change in the structure of the molecule, expressed as a change in energy gain, conferred by the mutations was determined.

Results: The E148Q mutation caused deviation from the wild-type pyrin segment encoded by exon 2 by 1.15% and from the whole pyrin molecule by 0.75%, comparable to the R202Q mutation and less than the M694V mutation which caused a deviation from the wild-type structure of the whole pyrin molecule by 1.5%.

Conclusions: A quantum-chemistry based model suggests that the structural effect of the E148Q mutation is indeed low, but not zero. 
 

Background: Multiple sclerosis (MS) is a common demyelinating disorder of the central nervous system (CNS) and although it is a well-established autoimmune disease its ethiopathogenesis has yet to be fully elucidated. The disease may present in several clinical forms that are closely associated with disease morbidity. In recent years various environmental and hormonal factors have been implicated in the pathogenesis of autoimmunity.

Objectives: To evaluate ferritin and prolactin levels in MS patients and their correlation with clinical manifestations of the disease.

Methods: Serum samples from 150 multiple sclerosis patients were evaluated for demographic characteristics, clinical parameters as well as prolactin and ferritin levels utilizing the Liaison chemiluminescent immunoassays (DiaSorin, Italy). Sera from 100 matched healthy donors were used as controls.

Results: Hyperprolactinemia was documented in 10 of 150 MS patients (6.7%) and hyperferritinemia in 12 (8%), both of which were significantly more common in this group compared with healthy controls (P ≤ 0.01 and P = 0.02 respectively). Among female MS patients, elevated prolactin levels were related to the secondary progressive type of disease (P = 0.05), whereas hyperferritinemia was associated with male gender (P = 0.03) and with the relapsing progressive type of the disease (P = 0.02). An inverse association was found between hyperferritinemia and the relapsing-remitting type of MS in male patients (P = 0.05)

Conclusions: Our results suggest a plausible association between these biomarkers and certain clinical types and gender among MS patients. Further studies combining clinical data, CNS imaging and these markers are warranted.
 

Background: The incidence of cutaneous leishmaniasis in northern Israel began to rise in 2000, peaking at 41.0 per 100,000 in the Kinneret subdistrict during the first half of 2003.

Objectives: To examine the morbidity rates of CL[1] in northern Israel during the period 1999–2003, which would indicate whether new endemic areas were emerging in this district, and to identify suspicious hosts.

Methods: The demographic and epidemiologic data for the reported cases (n=93) were analyzed using the GIS and SPSS software, including mapping habitats of suspicious hosts and localizing sites of infected sand flies.

Results: The maximal incidence rate in the district was found in the city Tiberias in 2003: 62.5/100,000 compared to 0–1.5/100,000 in other towns. The cases in Tiberias were centered on the peripheral line of two neighborhoods, close to the habitats of the rock hyraxes. Sand flies infected with Leishmania tropica were captured around the residence of those affected. Results of polymerase chain reaction were positive for Leishmania tropica in 14 of 15 tested patients.

Conclusions: A new endemic CL area has emerged in Tiberias. The most suspicious reservoir of the disease is the rock hyrax.

Background: Optimil® is an infant formula, manufactured in Israel and introduced to the market in May 2008.

Objectives: To assess, for the first time, the effect of this formula on infant growth.

Method: The study group comprised 52 infants who for the first 6 months of life consumed Optimil, which constituted at least 25% of their total daily intake. Anthropometric data were collected from the records of the well-baby clinics. Weight, length and head circumference at baseline and 3 months thereafter were converted to gender and age-matched standard deviation Z-scores. As an exploratory uncontrolled analysis, questionnaires were sent to the caregivers to assess satisfaction with the formula and to note the rate of constipation, irritability and vomiting as well as apparent palatability.

Results: The baseline Z-scores of all three parameters were below zero but increased significantly after 3 months (-0.2 ± 0.88 to 0.12 ± 0.88, P = 0.013 for weight; -0.44 ± 0.87 to 0.10 ± 0.72, P < 0.001 for length; and -0.58 ± 0.78 to -0.1 ± 0.76, P < 0.001 for head circumference). There was a significant dose-response effect of the formula with weight gain. The formula was generally well accepted, with 8% constipation, 8% vomiting and 6% significant irritability.

Conclusions: This study provides the first evidence that infants consuming Optimil under age 6 months have adequate growth. Nonetheless, breastfeeding during this period should be preferred in almost all cases.

Background: Kikuchi-Fujimoto disease is a benign and self-limited disease, first reported in Japan in 1972. The characteristic features of this disorder include lymphadenopathy and fever.

Objectives: To summarize our experience with Kikuchi disease with regard to clinical manifestations and outcome.

Methods: The patients included in the study were those diagnosed with Kikuchi disease during the years 2005–2008 in two departments of internal medicine at Sheba Medical Center.

Results: We identified five patients with Kikuchi disease; four of them were women and the mean age was 22.6 years. All the patients had cervical lymphadenopathy; three had other sites of lymphadenopathy. Four of the patients had fever higher than 39ºC. Two of them had splenomegaly and three reported weight loss. Three of the five patients experienced a relapse of the disease and were treated with steroids or non-steroidal anti-inflammatory agents. The diagnosis was confirmed in all the patients by an excisional biopsy of lymph node.

Conclusions: Kikuchi disease must be considered in every young patient with fever and lymphadenopathy. The disease usually has a benign course.

Background: Many patients present to the emergency department with chest pain. While in most of them chest pain represents a benign complaint, in some patients it underlies a life-threatening illness.

Objectives: To assess the routine evaluation of patients presenting to the ED[1] with acute chest pain via the utilization of a cardiologist-based chest pain unit using different non-invasive imaging modalities.

Methods: We evaluated the records of 1055 consecutive patients who presented to the ED with complaints of chest pain and were admitted to the CPU[2]. After an observation period and according to the decision of the attending cardiologist, patients underwent myocardial perfusion scintigraphy, multidetector computed tomography, or stress echocardiography.

Results: The CPU attending cardiologist did not prescribe non-invasive evaluation for 108 of the 1055 patients, who were either admitted (58 patients) or discharged (50 patients) after an observation period. Of those remaining, 445 patients underwent MDCT[3], 444 MPS[4], and 58 stress echocardiography. Altogether, 907 patients (86%) were discharged from the CPU. During an average period of 236 ± 223 days, 25 patients (3.1%) were readmitted due to chest pain of suspected cardiac origin, and only 8 patients (0.9%) suffered a major adverse cardiovascular event.

Conclusions: Utilization of the CPU enabled a rapid and thorough evaluation of the patients’ primary complaint, thereby reducing hospitalization costs and occupancy on the one hand and avoiding misdiagnosis in discharged patients on the other.
 

[1] ED = emergency department

[2] CPU = chest pain unit

[3] MDCT = multidetector computed tomography

[4] MPS = myocardial perfusion scintigraphy