Israel Medical Association Journal

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: Many patients in the internal medicine ward have anemia. The etiology for the anemia may be multifactorial and, in the setting of inflammatory process when the ferritin is increased, it is difficult to diagnose iron deficiency anemia. Soluble transferrin receptor (sTfR) had been suggested as an indicator for iron deficiency. No study has investigated the meaning of high sTfR as the only positive marker of iron deficiency anemia (IDA) caused by gastrointestinal tract (GIT) bleeding in hospitalized patients.

Objectives: To demonstrate the importance of high levels of sTfR as a marker for further GIT investigation in cases of anemia where the level of ferritin was normal or increased

Methods: We retrospectively assessed all patients in an internal medicine ward in our facility with anemia, high sTfR[1] levels (> 5.0 mg/L) and normal or high ferritin levels who underwent esophagogastroduodenoscopy and colonoscopy.

Results: Of 32 patients with anemia and normal or high ferritin levels and high sTfR, 22 patients (68%) had findings that explained IDA[2] (in some patients more than one finding). Those findings were colonic polyps (n=9), carcinoma of colon (n=4), duodenal ulcer (n=4), carcinoma of stomach (n=3), colitis (n=3), atrophic gastritis (n=1), erosive gastritis (n=1) and angiodysplasia (n=1).

Conclusions: High sTfR may be a good indicator of IDA caused by GIT[3] bleeding when the ferritin level is normal or high. GIT investigation is warranted in such cases.

Background: Hypovitaminosis D has been shown to be extremely common in various regions around the world, mostly at high latitudes. Israel is characterized by certain features – cultural (e.g., ethnic isolates) and geographic (e.g., sunny climate) – that have been identified for their possible association with vitamin D status.

Objectives: To conduct an ecological study on a representative sample of the population of Israel, testing vitamin D status across age groups, genders, ethnic groups, and seasons.

Methods: We obtained serum samples from 195 healthy Israeli volunteers representing a broad demographic spectrum. Serum concentrations of 25(OH)D were measured with the commercial kit Liaison 25(OH)D Assay (DiaSorin, Italy).

Results: The mean vitamin D level for the entire cohort was surprisingly low (22.9 ± 10.1 ng/ml), with 149 subjects (78%) suffering from vitamin D insufficiency (< 30 ng/ml). Vitamin D status was better in infants than in older age groups. Differences by gender were significant only in the infant age group (i.e., vitamin D status was worse among females) and were not prominent across older ages. Israelis of Ashkenazi origin had higher vitamin D mean levels than those of Sephardic origin, who, in turn, had higher vitamin D levels than Arab subjects (31.4 ± 12, 24.1 ± 10, and 17.6 ± 9 ng/ml respectively). With regard to season, there were no differences between the samples collected in winter and the samples collected in summer.

Conclusions: The results suggest that hypovitaminosis D is common across all ages, genders and seasons in Israel, a country characterized by a sunny Mediterranean climate. Specific ethnic groups may be at especially high risk.

Background: Human parvovirus B19 is a global and common infectious pathogen in humans, primarily in children.

Objectives: To assess the immunoglobulin G seroprevalence of B19 in children in Israel.

Methods: Overall, 128 previously healthy children (1.5–17 years old) hospitalized for various diseases other than acute human parvovirus B19 infection were assessed for IgG[1] to the virus by enzyme-linked immunosorbent assay. 

Results: The IgG seroprevalence increased from 22% in children aged 1.5–9 years to 52% in older children (P = 0.001).

Conclusions: Our data suggest that most acute parvovirus B19 infections in Israel occur in the early school years, and that by 18 years of age 50% of Israeli children have been infected by the virus.

[1] IgG = immunoglobulin G

Background: Although the comprehensive evaluation of the fetal heart includes echocardiography by an experienced pediatric cardiologist, economic constraints sometimes dictate the need to select patients.

Objectives: To analyze the usefulness of fetal echocardiography in the detection of congenital heart disease according to the referral indication.

Methods: This retrospective survey relates to all 3965 FE studies performed in our center from January 2000 to December 2004. The diagnosed cardiac anomalies were classified as significant and non-significant malformations. All FE[1] studies were done by a single operator (A.L.) at Meir Medical Center, a referral center for a population of about 400,000. The 3965 FE studies were performed for the following indications: abnormal obstetric ultrasound scans, maternal and family history of cardiac malformations, medication use during the pregnancy, and maternal request. The relative risk of detecting CHD[2] was calculated according to the various referral indications.

Results: Overall, 228 (5.8%) cases of CHD were found. The most common indication for referral was suspicion of CHD during a four-chamber view scan in a basic system survey or during a level II ultrasound survey. No correlation was found between maternal age and gestational age at the time of scanning and the likelihood of finding CHD.

Conclusions: Our data suggest that a suspicious level-II ultrasound or the presence of polyhydramnios is an important indication for FE in the detection of significant CHD.

Background: Chronic heart failure is associated with excessive hospitalizations and poor prognosis.

Objectives: To summarize the 5 year experience of a single-center CHF[1] day care service, detect the cardiovascular and non-cardiovascular events, and evaluate the safety of the treatments provided.

Methods: We retrospectively studied all patients admitted to the CHF day care service of the Sheba Medical Center between September 2000 and September 2005.

Results: Advanced (New York Heart Association class III-IV) CHF patients (n=190), mean age 65 ± 12 years and left ventricular ejection fraction 25 ± 11%, were treated for 6 hourly biweekly visits; 77% had ischemic and 23% had non-ischemic cardiomyopathy. Treatment included: intravenous diuretic combinations (91%), intermittent low dose (≤ 5 mg/kg/min) dobutamine (87%), low dose (≤ 3 mg/kg/min) dopamine (38%), intravenous iron preparation and/or blood (47%), and intravenous nitropruside (36%). Follow-up of at least 1 year from initiation of therapy was completed in 158 of 190 patients (83%). Forty-six (29.3%) died: 23% due to CHF exacerbation, 5.7% from infection, 4.4% from sudden cardiac death, 3.8% from malignancy, 2.5% from malignant arrhythmias, 1.9% from renal failure, 1.3% from stroke, and 0.6% from myocardial infarction. There were only 0.68 rehospitalizations/patient/year; the most frequent cause being CHF exacerbation (16.5%).

Conclusions: Our study demonstrates the safety and potential benefits of a supportive day care service for advanced CHF patients. Multidrug intravenous treatment, accompanied by monitoring of electrolytes, hemoglobin and cardiac rhythm, along with education and psychological support, appear to reduce morbidity in advanced CHF patients and may have contributed to the lower than expected mortality/hospitalization rate.

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: Iron deficiency is the most common single cause of anemia worldwide. Treatment consists of improved nutrition along with oral, intramuscular or intravenous iron administration.

Objectives: To describe the efficacy and adverse effects of intravenous iron sucrose therapy in a group of children with iron deficiency anemia who did not respond to oral iron therapy.

Methods: We conducted a prospective investigation of 45 children, aged 11 months to 16 years, whose oral iron therapy had failed. The children attended the Pediatric Ambulatory Care Unit where they received intravenous iron sucrose infusion.

Results: Forty-four of the 45 patients were non-compliant. Nine had Helicobacter pylori gastritis and 16 patients suffered from intestinal malabsorption from different causes. Before treatment, the blood mean hemoglobin concentration was 7.43 g/dl (range 5–10.1 g/dl). Fourteen days after treatment the mean hemoglobin concentration increased to 9.27 g/dl (SD 1.23) and 6 months later to 12.40 g/dl (SD 1.28). One patient demonstrated a severe side effect with temporary and reversible reduced blood pressure during treatment.

Conclusions: These preliminary data suggest that administration of intravenous iron in pediatric patients is well tolerated and has a good clinical result, with minimal adverse reactions.

Background: Iron deficiency and lead poisoning are common and are often associated. This association has been suggested previously, mainly by retrospective cross-sectional studies.

Objective: To assess the impact of short-term lead exposure at indoor firing ranges, and its relationship to iron, ferritin, lead, zinc protoporphyrin, and hemoglobin concentrations in young adults.

Methods: We conducted a clinical study in 30 young healthy soldiers serving in the Israel Defense Forces. Blood samples were drawn for lead, zinc protoporphyrin, iron, hemoglobin and ferritin prior to and after a 6 week period of intensive target practice in indoor firing ranges.

Results: After a 6 week period of exposure to lead dust, a mean blood lead level increase (P < 0.0001) and a mean iron (P < 0.0005) and mean ferritin (P < 0.0625) decrease occurred simultaneously. We found a trend for inverse correlation between pre-exposure low ferritin levels and post-exposure high blood lead levels.

Conclusions: The decrease in iron and ferritin levels after short-term lead exposure can be attributed to competition between iron and lead absorption via divalent metal transport 1, suggesting that lead poisoning can cause iron depletion and that iron depletion can aggravate lead poisoning. This synergistic effect should come readily to every physician's mind when treating patients with a potential risk for each problem separately.
 

Background: Iron deficiency is the most prevalent anemia in infants and is known to be a major public health problem.

Objective: To examine mothers’ knowledge and adherence with recommendations regarding iron supplementation and assess their association with the prevalence of anemia in infants.

Methods: Data on 101 infants and mothers of infants born between November 2000 and February 2001, living in a small Jewish town in southern Israel, were collected using a structured questionnaire and the infants’ medical charts. Anemia was defined as serum hemoglobin less than 11 g/dl. Independent variables include socioeconomic data, mothers' knowledge, and adherence to treatment as reported by them. Chi-square test was used to analyze categorical variables, t-test was used for continuous variables, and hemoglobin was tested at 9–12 months of age.

Results: Of the 101 infants in the study, 47% had serum hemoglobin under 11 g/dl. Of the mothers, 62 (62%) were partially or completely non-compliant with iron supplementation; 34 (34%) had low level of knowledge regarding anemia. Multivariate logistic regression analysis revealed a significant and inverse relationship between the presence of anemia and the level of maternal knowledge (odds ratio = 5.6, 95% confidence interval 1.6–9.7; P = 0.006) and reported adherence with iron supplementation (3.2, 1.1–9.7; P = 0.04) after controlling for confounding factors: maternal education, socioeconomic status, breastfeeding, and meat consumption.

Conclusions: The presence of iron deficiency anemia in infants in southern Israel is inversely affected by the level of maternal knowledge of anemia and adherence to iron supplementation. Low level of knowledge is also directly related to low adherence.