Israel Medical Association Journal

The antiphospholipid syndrome is characterized by recurrent fetal loss, venous and/or arterial thrombosis, and thrombocytopenia associated with elevated titers of lupus anticoagulant and anticardiolipin antibodies. Although thrombosis is the characteristic vascular involvement in APS[1], the development of vascular aneurysms in patients with APS has been reported. We describe four patients with established APS, who developed abdominal aortic aneurysm, and review the literature on previous published cases of arterial aneurysms developing in patients with APS. In addition, we discuss the possible pathophysiological association between APS and the development of this vascular abnormality.

Background: Germline mutations in BRCA1 and BRCA2 genes account for only 20–40% of familial breast cancer cases. The CHEK2 gene encodes a checkpoint kinase, involved in response to DNA damage, and hence is a candidate gene for breast cancer susceptibility. Indeed, the CHEK2*1100delC truncating mutation was reported in a subset of mostly North European breast cancer families. The rate of the CHEK2*1100delC variant in the Ashkenazi* Jewish population was reported to be 0.3%.

Objectives: To evaluate whether CHEK2 germline mutations contribute to a breast cancer predisposition in Ashkenazi-Jewish high risk families.

Methods: High risk Ashkenazi Jewish women, none of whom was a carrier of the predominant Jewish mutations in BRCA1/BRCA2, were genotyped for germline mutations in the CHEK2 gene by exon-specific polymerase chain reaction followed by denaturing gradient gel electrophoresis and sequencing of abnormally migrating fragments.

Results: Overall, 172 high risk women were genotyped: 75 (43.6%) with breast cancer (average age at diagnosis 49.6 ± 9.6 years, mean ± SD) and 97 asymptomatic individuals (age at counseling 48.3 ± 8.2 years). No truncating mutations were noted and four previously described missense mutations were detected (R3W 1.2%, I157T 1.2%, R180C 0.6% and S428F 5%), one silent polymorphism (E84E 20.5%) and one novel missense mutation (Y424H 1.2%). Segregation analysis of the I157T and S428F mutations (shown to affect protein function) with the cancer phenotype showed concordance for the CHK2*I157T mutation, as did two of three families with the CHK2*S428F mutation.

Conclusions: CHEK2 missense mutations may contribute to breast cancer susceptibility in Ashkenazi Jews.

Background: Diabetes mellitus is associated with microvascular and macrovascular diseases, potentially manifested as endothelial dysfunction. In adults with type 2 diabetes the haptoglobin genotype 1-1 has been shown to have a protective role in inhibiting the development of complications. Although complications from type 1 diabetes are infrequent during childhood, endothelial dysfunction, which is an early marker of vascular complications, may occur.

Objectives: To evaluate endothelial function in adolescents with type 1 diabetes before the development of complications and to test for potential relationships between endothelial dysfunction and haptoglobin genotype.

Methods: The study group comprised 15 adolescents with type 1 diabetes. All underwent a general physical examination, diabetes control evaluation (including HbA1c levels), endothelial function assessment and haptoglobin genotype determination.

Results: There was a significant negative correlation between HbA1c levels and endothelial function (r = -0.48, P < 0.05), and HbA1c was significantly higher in patients with endothelial dysfunction than in those with normal endothelial function (9.9 ± 2.2 vs. 7.7 ± 1.0 mg/dl, P < 0.05). In addition, there was a tendency toward a positive correlation between high density lipoprotein and endothelial function (r = 0.4, P < 0.1). There was no correlation between the haptoglobin genotype and endothelial function.

Conclusions: These results show that even in patients without complications, uncontrolled type 1 diabetes is associated with endothelial dysfunction, which may lead to microvascular complications in the future.
 

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.
 

Objectives: To evaluate the national Israeli experience with lung transplantation in patients with CF[1].

Methods: We reviewed the medical charts of all CF patients who underwent lung transplantation between January 1996 and June 2005 at the two Israeli centers that performed this procedure.

Results: Eighteen transplantations were performed in 17 patients. Mean patient age at transplantation was 25.3 ± 9.1 years, and mean duration of follow-up in survivors (n=14) was 37.2 months (range 1–113 months). The actuarial survival rate was 88% at 1 year and 74% at 5 years. Pulmonary function, expressed as percent of predicted normal forced expiratory volume in 1 sec, improved from 22.4 ± 8.1% to 76 ± 16.8% at one year after transplantation. Bronchiolitis obliterans syndrome was diagnosed in 5 patients (29%), of whom 2 died and 2 are currently candidates for retransplantation. Median time to onset of BOS[2] was 34.2 months (range 17–64 months).

Conclusion: In Israel, the early and intermediate-term results of lung transplantation for cystic fibrosis are encouraging. BOS remains a major complication that threatens long-term outcome.

Background: Men and postmenopausal women with iron deficiency anemia are routinely evaluated to exclude a gastrointestinal source of suspected internal bleeding. Iron deficiency anemia in premenopausal women is often treated with simple iron replacement, under the assumption that the condition is due to excessive menstrual blood loss.

Objectives: To determine the yield of endoscopy evaluations in premenopausal women with iron deficiency anemia.

Methods: Upper and lower gastrointestinal endoscopic examinations were conducted in 45 premenopausal women with iron deficiency anemia not related to gynecologic or nutritional causes.

Results: Forty-three of the 45 women fulfilled the entry criteria and were enrolled. Their mean age was 35 ± 15 years and their mean hemoglobin level 9.3 ± 2.3 g/dl. Twenty‑eight upper gastrointestinal lesions were demonstrated in 24 of the 43 patients (55.8%): erosive gastritis in 12 (27.9%), erosive duodenitis in 4 (9.3%), erosive esophagitis in 3 (7.0%), hiatus hernia (with Cameron lesions) in 3 (7.0%), active duodenal ulcer in 1 (2.3%) and hyperplastic polyp (10 mm) in 1 (2.3%). Five lower gastrointestinal lesions were detected in 5 patients (16.3%): 2 (4.6%) had adenocarcinoma of the right colon, 2 (4.6%) had pedunculate adenomatous polyp > 10 mm, and 1 (2.3%) had segmental colitis (Crohn's disease). One patient (2.3%) had pathologic findings in both the upper and lower gastrointestinal tracts.

Conclusions: Our findings of a gastrointestinal source of chronic blood loss in 28 of 43 premenopausal women with iron deficiency anemia (65.1%) suggest that this population will benefit from bi‑directional endoscopic evaluations of the gastrointestinal tract.

Objective: To establish the frequency of A. haemolyticum in throat cultures in a northern Israeli population and to estimate the clinical significance of this pathogen in patients with sore throat.

Methods: We examined suspected colonies for A. haemolyticum by gram stain, catalase test and reverse CAMP test in 518 throat cultures sent to the microbiologic laboratory of HaEmek Medical Center.

Results: Of the throat cultures tested, A. haemolyticum was recovered from one patient (0.2%). In contrast, group A Streptococcus (Streptococcus pyogenes) was recovered from 135 patients (26%).

Conclusion: A. hemolyticum is an uncommon pathogen implicated in acute pharyngitis, therefore routine screening in throat swabs is not required.

Background: During ingestible capsule endoscopy, video images are recorded throughout the device's natural propulsion through the digestive system. Shortening the transit time of the wireless video capsule through the stomach and small bowel could reduce the time needed to read and analyze the resultant images, utilize more effectively the short life of the capsule battery (7 ± 1 hours) and make it possible to image the entire small bowel.

Objective: To measure gastric and small bowel transit times, with and without preparation, using capsule endoscopy.

Methods: Capsule transit times through the stomach, small bowel and colon were evaluated by analysis of the videos generated during the capsule's passage. The study group included 62 patients with small and large bowel pathologies (e.g., iron deficiency anemia, Crohn's disease). The patients were divided into three groups: prepared with polyethylene glycol (Group A, n = 9), prepared with sodium phosphate (Group B, n = 13), and with no preparation (Group C, n = 40).

Results: The gastric emptying times were 20.4 ± 15.2 minutes in group A, 55.7 ± 45.1 in group B, and 48.3 ± 28.7 in group C (P = 0.01). The capsule produced views of the cecum in only 49 of the 62 patients. The mean small bowel transit time for these 49 patients was 238.8 ± 82.1 minutes, making the mean times for the groups (A,B,C) 148.9 ± 32.6, 289.4 ± 77.2 and 249.3 ± 73.9 minutes respectively (P = 0.0001).

Conclusion: Compared to both SP[1] and no preparation, preparation of the colon with PEG[2] significantly shortened the transit time of the capsule through the stomach and small bowel.

Background: The highly tissue-specific trafficking of normal and malignant lymphocytes to particular organs is mediated by adhesion molecules, or “homing receptors.” Among our patients with B cell chronic lymphocytic leukemia 15% demonstrate predominantly splenic manifestations and are classified as stage II(S).

Objective: To investigate whether expression of cell surface adhesion molecules can distinguish stage II(S) patients from stage 0 or stage 0 and I CLL[1] patients.

Methods: Expression of adhesion molecules belonging to different families was studied in CD19-positive cells isolated from the blood of 42 patients by dual color flow cytometry. The families included: immunoglobulin superfamily (CD54, CD58), integrin family (β1, β2 and β3 chains, CD11a, CD11c CD49d), selectin family (L-selectin), and lymphocyte homing receptor family (CD44).

Results: The average percentage of leukemic cells expressing CD11c in the 23 patients with stage II(S) was 25.7 compared with 13.2% in the 14 patients with stage 0 disease (P = 0.047). The average percentage of leukemic cells expressing CD44 in patients with stage II(S) was 90.5 compared with 77.2% in patients with stage 0 (P = 0.007) and 80% in patients with stages 0 and I together (n=19, P = 0.008). Other adhesion molecules tested did not show a statistically significance difference in expression between the different disease stages.

Conclusions: The higher expression of CD44 and CD11c in cells of CLL patients with predominantly splenic manifestations may account for the tendency of their lymphocytes to home to the spleen.