Israel Medical Association Journal

Background: Systemic lupus erythematosus is an autoimmune disease with diverse clinical manifestations that cannot always be regulated by steroids and immunosuppressive therapy. Intravenous immunoglobulin is an optional immunomodulatory agent for the treatment of SLE[1], but the appropriate indications for its use, duration of therapy and recommended dosage are yet to be established. In SLE patients, most publications report the utilization of a high dose (2 g/kg body weight) protocol.

Objectives: To investigate whether lower doses of IVIg are beneficial for SLE patients.

Methods: We retrospectively analyzed the medical records of 62 patients who received low dose IVIg[2] (approximately 0.5 g/kg body weight).

Results: The treatment was associated with clinical improvement in many specific disease manifestations, along with a continuous decrease in SLEDAI scores (SLE Disease Activity Index). However, thrombocytopenia, alopecia and vasculitis did not improve following IVIg therapy.

Conclusions: Low dose IVIg is a possible therapeutic option in SLE and is associated with lower cost than the high dose regimen and possibly fewer adverse effects.

Background: Infectious agents are important in the pathogenesis of autoimmune disease since they are a major part of the environmental trigger of autoimmunity. A negative relationship between latitude and infectious disease species richness has been suggested.

Objectives: To examine whether their prevalence differs in two latitudinally different populations.

Methods: The prevalence of infections with Toxoplasma gondii, rubella virus, cytomegalovirus, Epstein-Barr virus and Treponema pallidum was compared between subjects from Italy and Colombia.

Results: We found high titers of antibodies against four of five microorganisms tested, Toxoplasma gondii (50.8%), rubella virus (German measles) (75%), cytomegalovirus (86.3%), Epstein-Barr virus (83.3%) and Treponema pallidum (6.3%) in completely healthy individuals from a tropical country (Colombia) and a European country (Italy). Differences between two groups of volunteers were noted regarding two infectious agents. The prevalence of immunoglobulin G anti-rubella antibodies was significantly higher among Italian subjects (85% vs. 67.9%, P = 0.002), whereas antibodies against CMV[1] were less prevalent among Italian as compared to Colombian subjects (77% vs. 92.9%, P < 0.001).

Conclusions: These differences might also result in a different tendency towards development of autoimmune diseases associated with these infectious agents in different populations.

The most troublesome complication of acute pericarditis is recurrent episodes of pericardial inflammation, which occur in 15–32% of cases. It was recently found that viral infection has a major role, but in many cases the cause is unknown. The optimal method for prevention has not been fully established; accepted modalities include non-steroidal anti-inflammatory drugs, corticosteroids, immunosuppressive agents, and pericardiectomy. Based on the proven efficacy of colchicine in familial Mediterranean fever, several small and large-scale international clinical trials have shown the beneficial effect of colchicine therapy in preventing recurrent pericarditis. Indeed, colchicines-treated patients consistently display significantly fewer recurrences, longer symptom-free periods, and even when attacks occur they are weaker and shorter in nature. It was also found that pretreatment with corticosteroids substantially attenuates the efficacy of colchicine, as evidenced by significantly more recurrences and longer therapy periods. Colchicine is a safe and effective modality for the treatment and prevention of recurrent pericarditis, especially as an adjunct to other modalities, since it provides a sustained benefit superior to all current modalities. The safety profile seems superior to other drugs such as corticosteroids and immunosuppressive drugs.

Among the several mechanisms that play a role in maintaining peripheral self-tolerance is the existence of a unique CD4+CD25+ population of naturally occurring regulatory T cells, which actively prevent both the activation and the effector function of autoreactive T cells that have escaped different mechanisms of tolerance. Many studies have shown the benefit of targeting this cell population by restoring self-tolerance. Therapies that could possibly increase the suppressive ability of T regulatory cells were proven to improve the course of autoimmune diseases.

Treatment of vasculitides has progressed markedly over the past few decades. Recent therapeutic strategies in severe and refractory anti-neutrophil cytoplasmic antibodies-associated vasculitides include immunomodulating methods (e.g., plasma exchanges), products (such as intravenous immunoglobulins) and, more recently, new agents called biotherapies. Some of them (e.g., anti-tumor necrosis factor-alpha and anti-CD20 monoclonal antibodies) have achieved promising results and are now often used to treat severe cases.

Background: In the course of occurrence of cerebral infarction, cerebral hemorrhage and subarachnoidal hemorrhage episodes, periodicities resembling those found in the solar and geomagnetic activity were found by Kováč and Mikulecký (2005).

Objectives: To investigate putative relationships between two indices of solar activity and one index of geomagnetic activity on one side and the occurrence of cerebral infarction on the other.

Methods: In addition to the 192 monthly cases out of 6100 new cases of cerebral infarction that occurred between January 1989 and December 2004, monthly averages for Wolf numbers, solar flares index and Ap index were included in the analysis. The cross-correlation between each cosmo-geophysical variable on the one hand and the number of new cases of the disease on the other was computed. The quadratic regression with the chosen time delay was also studied using, separately, the Wolf numbers, solar flares and Ap index as the explanatory variable and the number of cases of cerebral infarction as the responding variable.

Results: Significantly negative correlation coefficients between the monthly means of the Wolf numbers, of solar flares and of Ap index on the one hand and monthly numbers of new cases of the disease on the other were found for the delays between -6 and +17 months. The cross-regression results for the delay of +5 months (infarction delayed after each cosmo-geophysical variable by 5 months) displayed a linear decrease except for the Wolf numbers where the parabolic decrease of cases was significant.

Conclusions: An increased intensity of the studied cosmo-geophysical parameters appears to be significantly connected with decreased occurrence of cerebral infarctions, and vice versa. This effect seems to last up to 17 months. The results are supported by a few similar findings in the literature. Putative cosmo-biomedical connections warrant further study to verify them in larger samples and longer time scales. If confirmed, their mechanisms should be elucidated.
 

Background: The frequency of performing percutaneous endoscopic gastrostomy in demented older people has increased in recent years. Several reports indicate flaws in the criteria for performing PEG[1] and in the decision-making process, raising concerns about the adequacy of the consent.

Objectives: To examine knowledge and attitudes of referring doctors and gastroenterologists, and to evaluate attitudes and feelings of family members concerning PEG insertion.

Methods: We conducted a survey of 72 doctors who referred 126 demented patients for PEG, as well as 126 family members and 34 gastroenterologists. Closed-ended questionnaires were designed for each study group, completed by the participants, and computer analyzed.

Results: Approximately 50% of family members expressed dissatisfaction with the decision-making process. Referring physicians reported that PEG insertion was often dictated by the need to transfer patients to a nursing home, with 50% admitting institutional pressure. Most of the referring physicians believed that PEG improved quality of life and longevity, whereas gastroenterologists did not expect an improved quality of life and thought that administrative demands should not intervene in the decision to insert PEG.

Conclusions: The decision-making process in the patient's families regarding PEG insertion for their demented relative is unsatisfactory, often takes place under pressure, and does not provide sufficient information about the procedure or its complications. Interpersonal communication between the patient's family and the medical team need to be improved and institutional demands should not play a major role in the medical decision to insert PEG. Gastroenterologists should take a more active role in the deliberations regarding PEG.

Background: Surgical repair of tetralogy of Fallot may leave the patient with pulmonary regurgitation causing eventual right ventricle dilatation and dysfunction. Predicting clinical deterioration may help to determine the best timing for intervention.

Objectives: To assess whether the clinical and humoral status of patients in the second decade after repair of ToF[1] is worse than that of patients in the first decade after repair.

Methods: Twenty-one patients with repaired ToF underwent clinical assessment, electrocardiogram, echocardiogram and measurement of plasma B-type natriuretic peptide and N-terminal pro-BNP[2] as well as the 6 minute walk distance test. Patients were divided into two groups: group A – less than 10 years after repair (n=10, age < 12 years old), and group B – more than 10 years after repair (n=11, age > 12 years old). The age at repair was similar in both groups.

Results: In all but one patient the distance in the 6 min walk test was less than the minimum for age. RV[3] end-diastolic volume and the 6 min walk test correlated with age. NT-proBNP[4] levels were significantly higher in the ToF group compared to 26 healthy controls (P < 0.0001) and were inversely correlated with RV ejection fraction. Comparison of the two groups showed no difference in RV end-diastolic volume indexed for body surface area, pulmonary regurgitation severity, right or left ventricular myocardial performance index, RV ejection fraction, QRS duration, or 6 min walk indexed to minimum for age.

Conclusions: In this group of patients with similar age at operation and pulmonary regurgitation severity, most clinical, echocardiographic and humoral parameters were not worse in the second decade after repair of ToF. These data suggest that very early pulmonary valve replacement may not be of benefit.

Background: Fanconi anemia complementation group C and Bloom syndrome, rare autosomal recessive disorders marked by chromosome instability, are especially prevalent in the Ashkenazi* Jewish community. A single predominant mutation for each has been reported in Ashkenazi Jews: c.711+4A→T (IVS4 +4 A→T) in FACC[1] and BLM^Ash in Bloom syndrome. Individuals affected by both syndromes are characterized by susceptibility for developing malignancies, and we questioned whether heterozygote carriers have a similarly increased risk.

Objectives: To estimate the cancer rate among FACC and BLM^Ash carriers and their families over three previous generations in unselected Ashkenazi Jewish individuals.

Methods: We studied 42 FACC carriers, 28 BLM^Ash carriers and 43 controls. The control subjects were Ashkenazi Jews participating in our prenatal genetic screening program who tested negative for FACC and BLM^Ash. All subjects filled out a questionnaire regarding their own and a three-generation family history of cancer. The prevalence rates of cancer among relatives of FACC, BLM^Ash and controls were computed and compared using the chi-square test.

Results: In 463 relatives of FACC carriers, 45 malignancies were reported (9.7%) including 10 breast (2.2%) and 13 colon cancers (2.8%). Among 326 relatives of BLM^Ash carriers there were 30 malignancies (9.2%) including 7 breast (2.1%) and 4 colon cancers (1.2%). Controls consisted of 503 family members with 63 reported malignancies (12.5%) including 11 breast (2.2%) and 11 colon cancers (2.2%).

Conclusions: We found no significantly increased prevalence of malignancies among carriers in at least three generations compared to the controls.

Background: Babies born with extreme prematurity and low birth weight (< 1000 g) present a unique treatment challenge. In addition to the complexity of achieving survival, they may require surgical interventions for abdominal emergencies. Usually, these infants are transferred to a referral center for surgery treatment. Since 2000 our approach is bedside abdominal surgery at the referring center.

Objectives: To evaluate whether the approach of bedside abdominal surgery at the referring center is safe and perhaps even beneficial for the baby.

Methods: We retrospectively reviewed our data since 2000 and included only babies weighing < 1000 g who were ventilated, suffered from hemodynamic instability and underwent surgery for perforated bowel at the referring neonatal unit. Results were analyzed according to survival from the acute event (> 1 week), survival from the abdominal disease (> 30 days) and survival to discharge.

Results: Twelve babies met the inclusion criteria. Median weight at operation was 850 g (range 620–1000 g) and median age at birth was 25 weeks (range 23–27). Eleven infants survived the acute event (91.7%), 9 survived more than 30 days (81.8%), and 5 survived to discharge.

Conclusions: Our results show that bedside laparotomy at the referring hospital is safe and feasible. A larger randomized study is indicated to prove the validity of this approach.

Background: The Pittsburgh Sleep Quality Index is a standardized self-administered questionnaire for the assessment of subjective sleep quality. It has been translated into several languages and is widely used in clinical research studies.

Objectives: To assess the reliability and validity of the Pittsburgh Sleep Quality Index Hebrew translation in a sleep clinic sample and in comparison with the Technion Mini Sleep Questionnaire.

Methods: The PSQI[1] was translated into Hebrew based on standard guidelines. The final Hebrew version (PSQI-H) was administered to 450 patients from two sleep clinics and to 61 healthy adults from the community as a non-clinical control sample. The MSQ[2] was administered to 130 patients in one sleep clinic.

Results: For the PSQI-H[3], Cronbach's-alpha scores for sleep clinic and non-clinical samples were 0.70 and 0.52 respectively and 0.72 combined. Clinical sample scores were significantly higher than the non-clinical group, indicating lower sleep quality for the former. Significant correlations were found between the MSQ subscores and PSQI-H component scores for common underlying constructs.

Conclusions: The PSQI-H differentiated between clinical and non-clinical samples and showed adequate reliability and good validity. It may be used as a standardized tool for the assessment of subjective sleep quality in clinical research studies conducted in the Hebrew-speaking population.