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עמוד בית
Sat, 28.11.20

February 2012

Original Articles
L.V. Lage, J.F. de Carvalho, M.T.C. Caleiro, N.H. Yoshinari, L.M.H. da Mota, M.A Khamashta and W. Cossermelli

Background: Antibodies directed against endothelial cell surface antigens have been described in many disorders and have been associated with disease activity. Since the most prominent histopathologic feature in mixed connective tissue disease (MCTD) is the widespread and unique proliferative vascular lesion, our aim was to evaluate the frequency of anti-endothelial cell antibodies (AECA) in this condition.

Objectives: To evaluate the frequency of AECA in this disease and assess its clinical and laboratory associations.

Methods: Seventy-three sera from 35 patients with MCTD (Kasukawa’s criteria), collected during a 7 year period, were tested for immunoglobulins G and M (IgG and IgM) AECA by cellular ELISA, using HUVEC (human umbilical vein endothelial cells). Sera from 37 patients with systemic lupus erythematosus (SLE), 22 with systemic sclerosis (SSc) and 36 sera from normal healthy individuals were used as controls. A cellular ELISA using HeLa cells was also performed as a laboratory control method.

Results: IgG-AECA was detected in 77% of MCTD patients, 54% of SLE patients, 36% of SSc patients and 6% of normal controls. In MCTD, IgG-AECA was associated with vasculitic manifestations, disease activity and lymphopenia, and was also a predictor of constant disease activity. Immunosuppressive drugs were shown to reduce IgG-AECA titers. Since antibodies directed to HeLa cell surface were negative, AECA was apparently unrelated to common epitopes present on epithelial cell lines.

Conclusions: AECA are present in a large proportion of patients with MCTD and these antibodies decrease after immunosuppressive treatment.

D. Itzhaky, D. Amital, K. Gorden, A. Bogomolni, Y. Arnson and H. Amital

Background: Vitamin D is increasingly associated with the pathology of cognition and mental illness. Vitamin D receptors have been detected on neurons that regulate behavior.

Objective: To assess vitamin D serum concentrations in patients with major depression and schizophrenia as compared to healthy controls and to determine if a correlation exists between serum levels of vitamin D and disease activity.  

Methods: We recruited 50 patients with schizophrenia and compared them to 33 patients with major depression and 50 controls with no major psychopathology. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia and the Hamilton Depression scale for depression were administered on the same day the blood samples were drawn. We used LIAISON® 25-OH vitamin D (DiaSorin) immunoassay to measure serum concentrations of 25-OH vitamin D.

Results: Lower serum vitamin D concentrations were detected among patients with schizophrenia (15.0 ± 7.3 ng/ml) compared to patients with depression (19.6 ± 8.3 ng/ml) and to controls (20.2 ± 7.8 ng/ml, P < 0.05). We found no correlation between disease activity, measured by the PANSS score, and vitamin D levels.   

Conclusions: Serum vitamin D levels were lower in patients with schizophrenia as compared to patients with depression and to healthy controls. No correlation was found between serum concentration and disease activity. Additional studies are needed to elucidate the role of vitamin D in the autoimmune mechanism and in the pathogenesis of schizophrenia.

A. Farfel, E. Derazne, D. Tzur, N. Linder and Z. Laron

Background: Measurements of adolescents who at birth were large (long and/or heavy) for gestational age are scant.

Objectives: To determine the correlation between birth length and weight in female and male neonates born long and/or overweight for gestational age, with their height and weight at age 17.

Methods: We reviewed the records of the Rabin Medical Center for birth data of 96 full-term neonates born long and overweight for gestational age (FT-lo,ow), 33 full-term neonates born long but with normal weight for gestational age (FT-lo,nw), 148 full-term neonates born overweight but with normal length for gestational age (FT-nl,ow), and 401 full-term neonates born with normal birth length and weight (FT- nl,nw).

Results: Neonates of both genders born long and overweight at birth (FT-lo,ow) were taller and heavier at age 17 years than those born FT-nl,nw: females: 167.8 ± 5.1 cm and 64.6 ± 10.3 kg vs. 162.6 ± 5.5 cm and 59.3 ± 11.1 kg (P < 0.001 for height and P = 0.026 for weight) and males: 182.4 ± 8.1 cm and 80.6 ± 20.4 kg vs. 174.5 ± 6.2 cm and 67.4 ± 12.3 kg (P < 0.001). The correlations between birth length and height at age 17 for both genders were statistically significant (P < 0.001), as were those between birth weight and the weight and body mass index (BMI) at age 17 for both genders (P < 0.001). There was no correlation between birth length and weight or BMI at age 17.

Conclusions: Full-term neonates of both genders born large for gestational age become tall adolescents and weigh more at age 17 than children with a normal birth length and weight.

V. Semionov, Y. Singer and P. Shvartzman

Background: The prevalence and severity of the most troublesome symptoms in terminally ill patients are well known and have been studied in many settings. However, these symptoms change during the course of advanced disease.

Objectives: To evaluate the range and trajectory of symptoms in the final stage of life as measured a month prior to death.

Methods: Patients with an expected prognosis of less than 6 months were recruited for the study. Excluded were non-Hebrew or Russian speakers, and patients with a diagnosis of brain tumor or with cognitive impairment. A structured questionnaire was used to interview patients and their caregivers at home every 2 weeks until death. We present a comparison analysis of 45 patients who completed both interviews 2 and 4 weeks before death.

Results: There were five symptoms (fatigue, pain, reduced well-being, lack of appetite, somnolence) that were reported most frequently, occurring in more than 70% of the patients. Most of the symptoms showed a worsening trend towards death.

Conclusions: Assessing the presence and severity of symptoms as a guide to start or modify treatment is recommended. Knowledge of how symptoms change in the final stage of life could better assist in the management of resources and could help patients and their families in their final preparations.

R. Haimov-Kochman, C. Adler, E. Ein-Mor, D. Rosenak and A. Hurwitz

Background: ‘Religious (halachic[1]) infertility’ results from precoital ovulation prior to immersion in a ritual bath (mikveh) 7 days after menstruation, as mandated by Jewish religious law. Previous authors recommended treatment with estradiol to postpone ovulation and enhance pregnancy rates.

Objectives: To evaluate the prevalence of halachic infertility in an ultra-Orthodox Jewish community, and assess the efficacy of estradiol treatment in postponing ovulation and increasing pregnancy rates.

Methods: We reviewed 88 cycles, of which 23 were control cycles and 65 estradiol-treated cycles, and analyzed the files of 23 women who were treated with 6 mg estradiol/day from day 1 for 5 days of the cycle.

Results: The prevalence of precoital ovulation in the infertile population was 21%. Most of the patients (94%) ovulated before day 13 of the cycle. A short follicular phase due to low ovarian reserve or thyroid endocrinopathy was noted in 12% of the patients. While 64% of the women reported consultation with a Rabbinate authority, 68% of the patients sought medical therapy. Estradiol postponed ovulation for at least one day in 89% of the treatment cycles. Ovulation post-mikveh occurred in 73% of estradiol-treated cycles. The pregnancy rate was 12.5% per cycle and the cumulative pregnancy rate 35% per woman. Half the patients reported spotting during estradiol-treated cycles, and this postponed coitus.

Conclusions: Precoital ovulation is a major reason for infertility among observant couples attending fertility clinics. Estradiol treatment is effective in delaying ovulation and restoring fecundity however, it causes some adverse effects that may decrease its effectiveness.



[1] Referring to Halacha, the body of Jewish Law

A. Zabari, E. Lubart, F. DeKeyser Ganz and A. Leibovitz

Background: Pain following hip fracture and internal fixation is a major factor during the treatment of elderly patients on rehabilitation programs. A proactive pain management program was instituted in our geriatric rehabilitation ward in 2005.

Objectives: To compare retrospectively two groups of patients, one before and one after implementation of the proactive pain management program.

Methods: The study group comprised 67 patients and the control group 77 patients. Pain in the study group was evaluated daily by the visual analogue scale (VAS) and the outcome of the rehabilitation process by the Functional Independence Measure (FIM). During the study period (2003–2006) no changes were made in the rehabilitation team, methods or facilities other than introduction of the pain control program. We compared the FIM scores between admission and discharge in both groups.

Results: Improvement in FIM scores between admission and discharge was significantly higher in the study group than in the control group (11.07 ± 7.9 vs. 8.4 ± 7.3, P < 0.03). There was no significant difference between the average lengths of stay.

Conclusions: These data support the view that the proactive monitoring of pain in surgical hip fracture patients is associated with a better outcome of the rehabilitation process.

D. Bendayan, A. Hendler, K. Litman and V. Polansky
Background: Interferon-gamma release tests are appealing alternatives to the tuberculin skin test (TST) for latent tuberculosis infection.

Objectives: To determine the yield of the Quantiferon TB Gold test (QFT-G) in the diagnosis of active tuberculosis disease, with a focus on elderly patients, human immunodeficiency virus (HIV) co-infection, and extra-pulmonary tuberculosis (EPTB).

Methods: The QFT-G test was performed in 98 patients suspected of having active tuberculosis. The results were evaluated for each subgroup of patients and compared to the results of the TST.

Results: Active tuberculosis was diagnosed in 92 of the 98 patients. Sixteen (17.3%) were elderly patients (over age 70), 15 (16%) were co-infected with HIV, and 14 (15%) had EPTB. QFT-G was positive in 49 patients (53%) and indeterminate in 4. The results were not significantly affected by HIV co-infection (P = 0.17), old age (P = 0.4), or the presence of EPTB (P = 0.4). There was a good correlation between the TST and the QFT-G test (P < 0.001). In EPTB and in the elderly, the QFT-G test appears to be better than the TST.

Conclusions: The QFT-G test is suboptimal in its ability to detect active tuberculosis and should not be used to exclude it.
L. Nesher, K. Riesenberg, L. Saidel-Odes, F. Schlaeffer and R. Smolyakov
Background: The southern region of Israel has recently experienced an influx of African refugees from the Eastern Sub-Sahara desert area. These influxes led to a significant increase in incidence of tuberculosis (TB) in that region.

Objectives: To review the data of African refugees diagnosed with TB between January 2008 and August 2010 at a tertiary care regional hospital.

Results: Twenty-five TB cases were diagnosed, 22 of which presented with pulmonary TB, 3 with  extra-pulmonary TB (EPTB), and 7 with combined pulmonary and EPTB. Only one case had concomitant human immunodeficiency virus (HIV) infection and multidrug-resistant TB. Fifteen patients underwent extensive radiological investigations including chest, abdominal and spine computed tomography, 1 was reviewed by magnetic resonance imaging, and 9 underwent tissue biopsy. Eighteen patients were admitted as suspected TB and 4 as suspected pneumonia or pulmonary infiltrates that could have been defined as suspected TB. All 24 HIV-negative cases were sensitive to first-line drugs for TB except one case that was resistant to streptomycin and one to rifampicin. All patients responded well to first-line therapy. The average duration of hospitalization was 8.7 days (range 1–36). Following diagnosis 23 patients were transferred to a quarantine facility.

Conclusions: We identified overutilization of medical resources and invasive procedures. For African refugees from the eastern Sub-Sahara who were HIV-negative and suspected of having TB, a sputum acid-fast smear and culture should have been the primary investigative tools before initiating treatment with four drugs (first-line), and further investigations should have been postponed and reserved for non-responders or for patients for whom the culture was negative. Physicians should maintain a high index of suspicion for EPTB in this population.
M. Vardi, T. Kochavi, Y. Denekamp and H. Bitterman

Background: Extended-spectrum beta-lactamase (ESBL) resistance is a growing concern in and outside hospitals. Physicians often face a true clinical dilemma when initiating empirical antibiotic treatment in patients admitted to internal medicine departments.

Objectives: To determine the prevalence of risk factors for ESBL resistance in patients with urinary tract infection (UTI) admitted to internal medicine departments.

Methods: We conducted a retrospective analysis of the medical records of patients with UTI admitted to an internal medicine division in a community-based academic hospital over a 1 year period. We collected clinical, laboratory and imaging data that were available to the treating physician at admission. Outcome measures included ESBL resistance and death.

Results: Of the 6754 admissions 366 patients were included in the study. Hospitalization during the previous 3 months (odds ratio 3.4, P < 0.0001), residency in a long-term-care facility (OR[1] 2.4, P = 0.004), and the presence of a permanent urinary catheter (OR 2.2, P = 0.015) were correlated to ESBL resistance with statistical significance. These risk factors were extremely prevalent in our patient cohort.

Conclusions: ESBL resistance is becoming prevalent outside hospital settings, and patients admitted to an internal medicine department with UTI frequently carry risk factors for harboring resistant bacteria. In such patients a high index of suspicion and early targeted antibiotic treatment for ESBL-producing Enterobacteriaceae may be justified.



[1] OR = odds ratio

N. Shoenfeld, O. Rosenberg, M. Kotler and P.N. Dannon

The phenomenon of hair pulling has been recognized for centuries, yet the true prevalence of trichotillomania (TTM) is largely unknown and the topic has been sparsely studied. TTM is classified as an impulse-control disorder despite much debate about its etiology. In this review we summarize the different hypotheses, including impulse-control disorders, obsessive-compulsive disorders, behavioral problems and addiction, and the appropriate treatment methods. The combination of selective serotonin reuptake inhibitors and antipsychotic medications are shown to be most effective. Treatment with anti-addiction drugs seems relevant. Further research is needed to increase our knowledge regarding the etiology of TTM.

D. Boltin and Y. Niv
Eradication of Helicobacter pylori is accompanied by an array of metabolic and hormonal changes in the host. Weight gain following H. pylori eradication is a poorly understood phenomenon and probably results from an interaction between multiple factors. Ghrelin, a peptide hormone secreted by the stomach, is involved in the regulation of food intake and appetite and may account for some of these changes. Although several observational studies have demonstrated that H. pylori infection suppresses circulating ghrelin levels, it has yet to be proven that ghrelin levels increase following eradication. On the other hand, gastric expression of ghrelin, also suppressed by H. pylori, clearly increases following eradication. The determinants of plasma ghrelin levels remain elusive, as do the effects of eradication on these levels. Weight gain following H. pylori eradication may be attributable to changes in plasma and gastric ghrelin however, this hypothesis needs to be further investigated.
Case Communications
N. Moustafa-Hawash, T. Smolkin, A. Ilivitzki, A. Zimberg-Bossira, A. Gildish, R. Gershoni-Baruch and I.R. Makhoul
U. Netz, Z. Perry, S. Libson and M. Bayme
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