Israel Medical Association Journal

Primary biliary cirrhosis is an autoimmune cholestatic liver disease characterized by humoral and cellular response directed at mitochondrial autoantigens, mainly the E2 component of the pyruvate dehydrogenase complex. The etiology of PBC[1], like most polygenic autoimmune diseases, belongs to the "complex" category, including genetic elements and environmental factors. Many environmental factors, such as xenobiotics, smoking, hormonal therapy, toxins, oxidative stress and recurrent urinary tract infections, are associated with PBC. Infectious agents can trigger autoimmunity via several mechanisms and are associated with various autoimmune diseases. A relationship between PBC and several infectious agents, and a possible role for Escherichia coli in the pathogenesis of PBC has been suggested. The identification of a culprit agent that induces or exacerbates PBC might have diagnostic and therapeutic implications. This review evaluates the evidence for an infectious agent role in the pathogenesis of PBC.

Background: Studies from many countries have reported an increasing prevalence of autistic spectrum disorder in childhood. No comprehensive epidemiological studies of ASD[1] have been performed in Israel.

Objectives: To describe time trends in the reported number of patients with ASD in Israel and to characterize the demographic features of the reported patients.

Methods: We reviewed the charts of the National Insurance Institute of Israel from 1972 to 2004 for all children with a diagnosis of ASD receiving disability benefits.

Results: A total of 3509 children met the study criteria. Eighty percent were boys and 98% were Jewish. The incidence data showed an increase in the number of cases from zero in 1982–84 and 2 (1.2 per million capita under 18 years) in 1985 to a high of 428 cases in 2004 (190 per million).

Conclusions: This is the first comprehensive study of the incidence of ASD in Israel. According to data derived from official health records, the rate of occurrence of ASD has substantially increased in the last 20 years. Further studies are needed to determine if this is a true increase or if the findings were confounded by external factors, such as recent improvements in diagnostic measures and social stigmas.

Synovial plicae are membranous inward folds of the synovial lining of the knee joint capsula. Such folds are regularly found in the human knee, but most are asymptomatic and of little clinical consequence. However, they can become symptomatic and cause knee pain. In this review, we will discuss medial plica syndrome. Medial plica irritation of the knee is a common source of anterior knee pain. The main complaint is an intermittent, dull, aching pain in the area medial to the patella above the joint line and in the supramedial patellar area. Pain increases with activity, especially when knee flexion and extension are required. Treatment includes physiotherapy, reducing activity and rest. In cases that do not respond initially to an exercise program, corticosteroid injections and non-steroidal anti-inflammatory medication are given. Results of conservative treatment seem to be more appropriate in young patients with a short duration of symptoms. If conservative treatment fails, surgical treatment using arthroscopy is appropriate. During arthroscopy, excision of the whole plica should be achieved.

Asthma is an airway disease, yet that airway extends all the way to the alveolar tissue area. Pathohistiological as well as physiological and clinical studies have recently documented this aspect of asthma. The implications of this are important for all asthmatic patients, but particularly for those whose asthma is more difficult to control. Many of the inhaled preparations used as therapy for asthma are of relatively large particle size. 

Thus, the deposition of these medications is mainly in the central and medium sized airways and very little of a given actuation gets to the distal airways. Ultrafine inhaled steroid particles have been shown to reach the more peripheral portions of the airway, and improvement in outcome variables such as air trapping as well as symptomatic outcomes have been demonstrated. This review focuses on anatomic airway changes, physiological changes of the distal airways, clinical outcome data, and particle size of inhaled preparations.

Background: Over the last two decades, the epidemiology, treatment strategy and mortality rate for congenital diaphragmatic hernia have changed.

Objectives: To retrospectively analyze our experience with CDH[1] of the last 22 years.

Methods: We reviewed the charts of all infants suffering from CDH between 1985 and 2007. Prenatal and maternal as well as perinatal and neonatal data were collected, including outcome parameters. The 71 infants that we identified were divided them into two historical groups: from 1985 to 1995 (group 1, 123 patients) and from 1996 to 2007 (group 2, 45 patients).

Results: We found an increase in the incidence of prenatal diagnosis and a subsequent significant decrease in gestational age at diagnosis in group 2 (25 weeks gestation, compared with 30 weeks gestation in group 1, P = 0.018). In addition, we noted a trend toward a reduced number of infants with right-sided hernia and associated cardiac anomalies. The timing to post-delivery surgery was significantly longer in group 2 (20 hours in group 1 vs. 53 hours in group 2, P < 0.001). A significant reduction in postoperative mortality was demonstrated in group 2 compared with group 1 (13.5% vs. 38.7% respectively, P = 0.04),

Conclusion: Our data suggest a higher survival rate for operated infants in group 1 during the last decade, probably due to changes in preoperative methods of treatment as well as later surgery timing compared to group 1. We speculate that today’s cases of congenital diaphragmatic hernia are probably milder than in the past due to earlier and more detailed prenatal diagnosis and subsequent termination of pregnancies for the more severe forms of the disorder. 

Background: Myeloperoxidase levels were shown to reflect endothelial dysfunction, inflammation, atherosclerosis and oxidative stress.

Objectives: To examine the role of circulating myeloperoxidase, a leukocyte-derived enzyme, as a predictor of mortality in patients with congestive heart failure.

Methods: Baseline serum MPO[1] levels were measured in 285 consecutive CHF[2] patients and 35 healthy volunteers. N-terminal pro-brain natriuretic peptide and high sensitivity C-reactive protein concentrations were also measured. The primary outcome endpoint was overall mortality.

Results: MPO levels were significantly elevated in patients with CHF compared to healthy volunteers (P = 0.01). During a mean follow-up of 40.9 ± 11.3 months there were 106 deaths. On a univariate Cox regression analysis MPO levels were of marginal value (P = 0.07) whereas NT-proBNP[3] was of considerable value (P < 0.0001) in predicting all-cause mortality. By dividing our cohort according to NT-proBNP levels into high, intermediate and low risk groups a clear difference in mortality was shown. By further dividing the patient cohort according to MPO levels above or below the median (122.5 ng/ml), mortality prediction improved in the patients with intermediate NT-proBNP values.

[1] MPO = myeloperoxidase

[2] CHF = congestive heart failure

[3] NT-proBNP = N-terminal pro-brain natriuretic peptide

Background: Medication errors are a common cause of morbidity and mortality.

Objectives: To evaluate the rate of acknowledgment of medication errors as reported by physicians working in the community and in hospitals.

Methods: An anonymous questionnaire was sent to 9320 active physicians (about 48% community physicians, 17% hospital physicians and 35% working in both places), with questions on the rate and type of medication errors that they had encountered during their professional career. The questions specified errors in dosage, type of medicine (wrong indication), route of administration and drug interactions.

Results: Only 627 physicians (6.7%) responded. Of these, nearly 79% admitted having made an error in prescribing medication; the majority admitted to more than one error. Physicians with fewer years of experience admitted having made a mistake more than did physicians with more experience (P = 0.019). Pediatricians and geriatricians made more dosage mistakes (P = 0.02), while family physicians and psychiatrists made more mistakes in drug interactions (P = 0.001).

Conclusions: It is possible that indifference, fear of identification, or lack of awareness may have contributed to the low response rate despite the fact that the questionnaire was anonymous. Educational programs should be implemented in medical schools to encourage physicians to report errors before the onset of adverse reactions.
 

Background: In recent years, mother to child transmission of human immunodeficiency virus in the west has decreased markedly due to the advent of antiretroviral drugs given during pregnancy, cessation of lactation and careful monitoring of viral load in the perinatal period.

Objective: To assess mother to child transmission of HIV[1] among Ethiopian immigrants and non-Ethiopians in the Jerusalem area.

Methods: We conducted a prospective analysis of all deliveries of HIV-positive women in the Jerusalem district over a 10 year period.

Results: Between 1996 and 2006, 35 HIV⁺ women gave birth to 45 infants. Thirty-one (88%) of these women were of Ethiopian origin and gave birth to 39 infants. Of the 35 HIV⁺ women, 30 were aware of being HIV positive. They gave birth to 40 infants. Another 5 women (14%) were not aware of being HIV⁺ during delivery. They gave birth to five infants. Of the group of known HIV⁺ women, 26 (87%) were Ethiopian immigrants who delivered 34 infants and 4 were non-Ethiopians who delivered 6 infants. In the group of five women not aware of being HIV⁺, all were Ethiopians. Breast-feeding data were available for 32 of the 35 women. Only 2 women (6.2%) breast-fed their babies. Neither was aware of being HIV⁺. In the Ethiopian immigrant group (both known and unknown HIV status), 11 deliveries (28%) were vaginal, 18 (46%) were elective cesarean section and 10 (26%) were delivered by emergency cesarean section. Of the 26 known HIV⁺ Ethiopian women, 3 (12%) refused to take antiretroviral treatment despite repeated counseling. In the non-Ethiopian group, all deliveries were elective cesarean sections. Mother to child transmission of HIV occurred in 4 of the total 45 deliveries (8.8%). Of the 4 transmission cases, 2 occurred among 40 deliveries of known HIV⁺ women (5%), and 2 occurred among the 5 deliveries of women not aware of being HIV⁺ (40%, P = 0.05). In the group of Ethiopian women only, HIV transmission occurred in 4 of 39 deliveries (10%), of which 2 occurred among 34 deliveries (5.8%) of women know to be HIV⁺ and 2 among 5 deliveries (40%) of women not aware of being HIV⁺ (P = 0.08).

Conclusions: Pregnant Ethiopian immigrants whose HIV status was known during pregnancy were at relatively high risk of HIV transmission despite the availability of antiretroviral drugs and counseling. This is likely due to inadequate adherence to ART[2] preventive regimens and is not dissimilar to the poor adherence observed among other immigrant groups in western countries. The substantial proportion of women, all Ethiopians, unaware of being HIV⁺ at delivery, together with the significantly higher HIV transmission in that group compared to women who knew their HIV status, call for a revision of the current Ministry of Health opt-in policy for prenatal HIV screening.

Background: The co-morbidity rate of illicit substance abuse and major mental problems in Israel is far from clear.

Objectives: To investigate the extent of drug abuse in a sample of psychiatric patients hospitalized in a psychiatric hospital and in the psychiatric department of a general hospital in Israel, to compare demographic and other background factors in dual-diagnosis patients with those of abuse-free mental inpatients, and to examine the time correlation between drug abuse and the appearance of major mental problems.

Methods: Our data were derived from self-report and urine tests. The study population comprised 470 consecutively admitted patients – 250 patients in the mental health center and 220 patients in the psychiatric department of the general hospital.

Results: The lifetime prevalence of drug abuse was 24%; cannabis abuse was found in 19.7%, opiates in 5.7%, cocaine in 2.7%, amphetamines in 3.4% and methamphetamine in 1.1%. Active abuse of drugs (during the last month) was registered in 17.3%, cannabis in 11.5%, opiates in 4.9%, amphetamine in 3.8%, cocaine in 1.3% and methamphetamine in 1.1%. We also found that 28.2% of active abusers used two or more substances. In 41.6% the drug abuse appeared prior to symptoms of the mental disorder; in 37.1% the duration of the mental disorders and the drug abuse was relatively similar, and in 21.3% of cases the duration of mental problems was longer than the duration of drug abuse. Dual-diagnosis patients were younger than non-abusers, more often male, unmarried, and of western origin.

Conclusions: Substance abuse (especially cannabis) among hospitalized psychiatric patients in Israel is a growing problem.

Background: General hospital staff are often required to care for physically ill patients who arouse concern regarding risk of harm to themselves or others. Some of these patients will receive one-to-one "constant observation." This is the first Israeli study of general hospital patients with high risk behavior.

Objectives: To examine a population of general hospital patients whose behavioral management required the use of constant observation. Demographic and clinical parameters including physical diagnoses were examined, and risk factors for constant observation were identified. The findings of this study were compared to findings in previous studies.

Methods: This prospective observational study examined 714 inpatients referred for psychiatric consultation; 150 were found to require constant observation, and 156 who did not served as a control group.

Results: In this study younger age, suicidal concerns and alcohol/substance abuse were identified as risk factors for ordering constant observation. Ischemic heart disease and chronic obstructive pulmonary disease were the only physical diagnoses found to be significantly correlated with a longer duration of observation, regardless of admission duration. Constant observation was less frequently used in the management of organic brain syndrome patients in this study compared to other studies.  

Conclusions: Some of our results (predictive factors for constant observation) confirmed the findings of overseas studies. Our finding that a diagnosis of organic brain syndrome was not a predictive factor for constant observation was unexpected and requires further investigation. The correlation between a diagnosis of ischemic heart disease or COPD[1] and duration of observation has not been reported previously and warrants further studies.