Israel Medical Association Journal

Background: In the last decade the diagnosis of celiac disease has increasingly been made in adults.

Objectives: To determine disease prevalence (including silent and potential disease) in this population group.

Methods: We performed serologic screening of celiac disease in a representative and homogenous sample of a young adult general population in Israel, namely, 18 year old military conscripts, in 2003. Serologic screening was performed on serum samples randomly obtained from 850 healthy recruits (male/female = 1.1). Immunoglobulin A anti-tissue transglutaminase was determined by enzyme-linked immunosorbent assay. In cases of IgA[1] deficiency, IgG anti-endomysial antibodies were determined. A small intestinal biopsy was offered to all patients with positive serology.

Results: The prevalence of overt CD[2] diagnosed prior to recruitment was 0.12% (0.1% in men and 0.14% in women). The overall prevalence based on positive serology was 1.1%. Six of nine subjects with positive serology agreed to undergo endoscopy and intestinal biopsies. In all cases, biopsies were compatible with celiac disease (five biopsies were graded as Marsh 3a and one as Marsh 3b). One subject previously reporting irritable bowel-like symptoms was diagnosed with overt atypical CD. The prevalence of overt CD diagnosed by screening was 0.12%. The ratio of overt to silent CD was 1:8. No cases of potential disease were encountered.

Conclusions: Our findings suggest that CD is highly prevalent in the young adult population in Israel. Serologic screening for CD is a reliable and simple method for diagnosing this disease before symptoms or complications develop. 

[1] Ig = immunoglobulin

[2] CD = celiac disease

Background: An accurate preoperative definition of tumor and lymph node status is needed for reaching the correct decision regarding rectal cancer treatment. Transrectal ultrasonography is the most commonly used diagnostic modality for the local staging of rectal cancer.

Objectives: To determine the accuracy of TRUS[1] in the staging of rectal cancer.

Methods: We conducted a retrospective study on 95 patients evaluated by TRUS. The rectum was subdivided into two parts (lower and upper).

Results: Sixty patients underwent radical surgery. Of these, 34 received no preoperative chemo-irradiation owing to µT1, µT2 tumor or the patient’s choice (neo-adjuvant treatment was suggested to patients with adenocarcinoma that proved to be µT3). The overall accuracy rate was 80% for T stage. Overstaging was found in 13.3% and understaging in 6.7%.The N-stage was correctly assessed in 70%. The overall accuracy rate for tumors was 73.9% in the lower part and 90.9% in the upper. A trend towards a lower accuracy rate for low-lying tumors compared to high-located rectal tumors was found (P = 0.532), which did not reach statistical significance.

Conclusions: TRUS gave better results for T1 and T3 stage rectal tumors but was inaccurate for stage T2, indicating the possible need for local excision in order to base the final treatment for T2 tumors on pathologic staging.
[1] TRUS = transrectal ultrasonography
 

Background: The best therapeutic alternative for patients suffering from in-stent restenosis after drug-eluting stent implantation remains to be elucidated.

Objective: To characterize the pattern, treatment and outcomes of DES[1]-related in-stent restenosis in patients treated at our institution.

Methods: We determined the incidence and major adverse clinical events in 71 consecutive patients with DES failure among 2473 patients who were treated with 2548 drug-eluting stents between 2004 and 2007. We analyzed the clinical data, procedural parameters and clinical outcomes.

Results: The type and number of stents implanted were as follows: Cypher (n=1808), Endeavor (421) and Taxus (319) of these, 53 (2.9%), 10 (2.4%), and 8 (2.5%) patients respectively presented with restenosis. The mean time to restenosis was 11.3 ± 9.9 months. Patients’ mean age was 65 ± 11 years 75% were male, and 68% had diabetes mellitus. Unstable angina was the clinical presentation in 52 (73%). At 6 months, 3 patients had developed myocardial infarction (4.2%), repeat restenosis at follow-up was diagnosed in 8 patients (11.3%), the overall major adverse clinical events rate was 18.3% (13 patients), and 2 patients died (2.8%).

Conclusions: Drug-eluting stent-related restenosis is relatively infrequent but remains a clinical challenge. It occurs more frequently in complex lesion subsets, but the overall intermediate-term prognosis is tolerable.  

[1] DES = drug-eluting stent

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: An outbreak of pertussis occurred in a daycare center with 87.5% vaccination coverage.

Objectives: To assess the effectiveness of the acellular pertussis vaccine and prevention of pertussis after chemoprophylaxis with azithromycin.

Methods: We studied 31 daycare children aged 3–5.5 years exposed to a child with pertussis. Nasopharyngeal swabs were obtained for Bordetella pertussis culture and polymerase chain reaction initially, and at days 21 and 60 of follow-up, in cases exhibiting symptoms.

Results: Of the 31 daycare children 6 (19%) tested positive for B. pertussis by PCR[1], 4 of whom had not been vaccinated against the disease. Of the two vaccinated children who contracted pertussis, one had milder symptoms and the other was asymptomatic. The incidence of pertussis was significantly lower in the vaccinated group (2/27) than in the unvaccinated group (4/4) (P = 0.000), with efficacy of the vaccine calculated to be 92.5%. Azithromycin chemoprophylaxis was taken only by 14 of the 25 exposed children (56%). On day 21 follow-up, there was no further laboratory-diagnosed B. pertussis cases in any of the exposed children, regardless of whether or not chemoprophylaxis was taken.

Conclusions: Based on the children’s clinical manifestations and PCR findings a pertussis outbreak had occurred in the daycare center studied. Our findings support the importance of pertussis vaccination since all the unvaccinated children in the daycare center contracted the infection.

Background: Normal-tension glaucoma is a chronic progressive optic neuropathy of unknown etiology. Neuroimaging workup in these patients is controversial.

Objectives: To determine the value of routine neurologic and neuro-ophthalmologic evaluations in patients with NTG[1].

Methods: We conducted a retrospective review of all patients diagnosed with NTG in our institution between 2001 and 2006. Neurologic and neuro-ophthalmologic data were evaluated.

Results: Sixty-eight patients were considered suitable for the study (35 males, 33 females age range 43–90 years). Neurologic and neuro-ophthalmologic findings were normal in all of them. The computed tomography brain scan was normal in 88% and duplex carotid Doppler scan was normal in 92%.

Conclusions: Pathologic findings in neurologic and neuro-ophthalmologic assessments were uncommon in NTG. Therefore, contrary to earlier suggestions, neurologic and neuro-ophthalmologic evaluations in typical normal-tension glaucoma patients appear to have no added value.

Background: The prognostic significance of biologic markers in women with ductal carcinoma in situ is not fully understood. HER2/neu is a marker of prognostic significance that is routinely assessed in invasive cancer but its correlation with clinical outcome in DCIS[1] is still obscure.

Objectives: To evaluate the significance of HER-2/neu expression as a prognostic marker in DCIS.

Methods: Clinical and pathologic data from 84 patients treated for DCIS were analyzed. HER-2/neu expression was determined by immunohistochemical staining. Histopathologic parameters (nuclear grade, histologic subtype, necrosis, calcifications, margins) were reviewed by an experienced pathologist. Local recurrence and/or metastatic spread were used as endpoints to determine the prognostic significance of HER-2/neu expression.

Results: With a median follow-up of 94.8 months, nine recurrences were reported. Neither univariate nor multivariate analysis showed a significant correlation between HER-2/neu expression and disease recurrence or the time to disease recurrence. Although HER-2/neu expression demonstrated a significant association with high nuclear grade (P < 0.0001) and comedo subtype (P < 0.0001), there was no correlation between these histologic features and recurrence rate. The correlation between high nuclear grade and disease recurrence approached statistical significance (P = 0.07).

Conclusions: No significant association was found between HER-2/neu expression in DCIS and disease recurrence. However, HER-2/neu correlated with negative markers such as nuclear grading and comedo necrosis, and its role should therefore be investigated in larger studies.
 

[1] DCIS = ductal carcinoma in situ

Immunization coverage is a major health indicator. In Israel, routine childhood immunizations are provided at community public well-baby clinics. Immunization monitoring is an important cornerstone of a national health policy however, data obtained through sampling carries the risk of under-representation of certain population strata, particularly high risk groups. Despite high national average immunization coverage, specific sub-populations are under-immunized, as highlighted by outbreaks of vaccine-preventable diseases. The mean national immunization coverage at age 2 years (2006 data) was: DTaP[1]-IPV[2]-Hib4[3] (all 93%), HBV[4]3 (96%), MMR1[5] (94%), HAV1[6] (90%). These reports are based on a 17% population-based sample in some districts and on cumulative reports in others. A national immunization registry requires data completeness, protection of confidentiality, compulsory reporting by providers, and links to other computerized health records. It should provide individual immunization data from infancy to adulthood and be accessible to both providers and consumers. In 2008 the Israel Ministry of Health launched a national immunization registry based on immunization reporting from well-baby clinics using a web-based computerized system. As of January 2010, 120 well-baby clinics are connected to the nascent registry, which includes the records of some 50,000 children. The implementation of a comprehensive national immunization registry augurs well for the prospect of evidence-based assessment of the health status of children in Israel. 

 
[1] DTaP = diphtheria-tetanus-acellular pertussis

[2] IPV = inactivated polio vaccine

[3] Hib = Haemophilus influenzae b

[4] HBV = hepatitis B virus

[5] MMR = measles-mymps-rubella

[6] HAV = hepatitis B virus

Background: Obesity has become a major public health problem worldwide.

Objectives: To examine the effect of orlistat in promoting weight loss and its specific effect on the visceral adipose tissue and subcutaneous adipose tissue as evaluated by computed tomography.

Methods: A prospective case series study of 10 obese subjects was conducted. The 6 women and 4 men, age 50–67 years (mean 59 ± 8 years), had a mean body mass index of 34.1 ± 3.2 kg/m². All subjects were prescribed a mildly hypocaloric diet (600 kcal/day deficit). In addition, all subjects were treated with orlistat 120 mg 3 times a day for 20.1 ± 7 weeks.

Results: The subjects had lost approximately 8.2 kg each, or 8.4% of their initial body weight. Mean body weight decreased from 98 ± 13 to 89.8 ± 13.6 kg at the last follow-up visit (P = 0.0001) mean BMI[1] decreased from 34.1 ± 3.2 to 30.3 ± 3.9 kg/m² (P = 0.0001), and mean waist circumference from 113.8 ± 11.4 to 107.6 ± 10 cm (P = 0.0006). Mean total abdominal adipose tissue volume, evaluated by computed tomography, decreased from 426 ± 104.3 to 369.8 ± 99.6 mm³ (P = 0.0001). Mean abdominal SAT[2] volume decreased from 251.1 ± 78.8 to 224 ± 81.1 mm³ (P = 0.006), and mean abdominal VAT[3] volume decreased from 176 ± 76.7 to 141.6 ± 67 mm³ (P = 0.0001). Thus, the total abdominal adipose tissue volume for the whole group decreased by 15.4%, and most of this decrease was attributable to the reduction in VAT (24.8%) as opposed to SAT (only 12% reduction) (P = 0.03). The weight reduction that occurred during the study was accompanied by a statistically significant reduction in levels of total cholesterol, low density lipoprotein-cholesterol, triglycerides, and fasting blood glucose.

Conclusions: Our results demonstrate the effect of orlistat in reducing human visceral adipose tissue as evaluated by CT. The benefit of the treatment is further supported by the statistically significant reduction in cardiovascular risk factors.

 
[1] BMI = body mass index

[2] SAT = subcutaneous adipose tissue

[3] VAT = visceral adipose tissue

 

Background: Pathologic breast conditions are rare in childhood and adolescence. The spectrum of breast disease in the pediatric age group is different from that in adults, and most lesions are benign

Objectives: To describe the causes and characteristics of breast asymmetry in adolescents with normal endocrine profiles and sexual development.

Methods: The files of patients with a diagnosis of breast asymmetry referred to a tertiary pediatric center from 1990 to 2007 were reviewed for history and findings on physical examination with or without imaging, treatment and outcome.

Results: Eleven patients aged 12.5 to 18 years were identified. The cause of the breast asymmetry was traced to unpreventable medical factors in eight patients (physiologic, Poland anomaly, scleroderma), preventable/iatrogenic factors in two patients (chest tissue biopsy, thoracic drain), and possible combined medical-iatrogenic factors in one patient (scoliosis treated by a body brace). All patients were referred for breast reconstruction after full breast development.

Conclusions: Severe breast asymmetry in adolescence may be due to congenital factors, diseases involving the breast tissue, or to the effects of medical treatment, and may have severe adverse psychological and social implications. To prevent iatrogenic breast asymmetry, physicians should be made aware of the sensitivity of the breast tissue and should avoid unnecessary tests/procedures that involve the chest wall. In most cases a precise medical history and physical examination can differentiate between physiologic and non-physiologic causes.

Background: Hypocalcaemia following thyroid and parathyroid surgery is a well-recognized potential complication.

Objectives: To determine the utility of intraoperative quick parathormone assay in predicting severe hypocalcemia development following parathyroidectomy for a single-gland adenoma causing primary hyperparathyroidism.

Methods: A retrospective cohort study was performed. IO-QPTH[1] values were measured at time 0 (T0) before incision, and 10 (T10) and 30 minutes (T30) following excision of the hyperfunctioning gland. Percent decrease in IO-QPTH at 10 minutes (T10), maximum percent decrease of IO-QPTH value, and lowest actual IO-QPTH value obtained at surgery were used to determine any correlation with the development of postoperative hypocalcemia requiring treatment.

Results: Percent decrease in IO-QPTH at 10 minutes, maximum percent decrease in IO-QPTH and lowest IO-QPTH value did not correlate with the lowest postoperative calcium levels measured 18 hours after surgery (r = 0.017, P = 0.860 r = 0.018, P = 0.850 and r = 0.002, P = 0.985 respectively). For the purposes of our analysis, patients were subdivided into three groups. Group 1 comprised 68 patients with normal calcium levels (serum Ca 8.6¨C10.3 mg/dl) Group 2 had 28 patients with hypocalcemia (8.1¨C8.6 mg/dl) Group 3 included 12 patients with severe hypocalcemia (calcium level ¡Ü 8.0 mg/dl) requiring calcium supplementation due to symptoms of hypocalcemia. There was no difference between the three groups in the lowest IO-QPTH value (P = 0.378), percent decrease in IO-QPTH (P = 0.305) and maximum percent decrease in IO-QPTH (P = 0.142).

Conclusions: IO-QPTH evaluation was not useful in predicting the group of patients susceptible to develop severe postoperative hypocalcemia.  

[1] IO-QPTH = intraoperative quick parathormone

Background: Myocardial blush grade is a useful marker of microvascular reperfusion that may influence left ventricular dilatation.

Objectives: To assess the impact of myocardial blush grade on LV[1] remodeling in patients undergoing successful primary  PCI³ for first anterior ST elevation myocardial infarction.

Methods: In 26 consecutive patients MB[2] grade was evaluated immediately after primary PCI[3]. Each patient underwent transthoracic echocardiography at 24 hours and 6 months after PCI for evaluation of LV volumes. LV remodeling was defined as an increase in end-diastolic volume by ≥ 20%.

Results: The presence of myocardial reperfusion (MB 2-3) after primary PCI was associated with a significantly lower rate of remodeling than the absence of myocardial reperfusion (MB 0-1) (17.6% vs. 66.6%, P = 0.012). Accordingly, at 6 months, patients with MB 2-3 had significantly smaller LV end-diastolic volume (94 ± 21.5 ml vs. 115.2 ± 26) compared with patients with MB 0-1. In univariate analysis, only MB (0-1 versus 2-3) was associated with increased risk of LV remodeling (odds ratio 9.3, 95% confidence interval 1.45–60.21, P = 0.019).

Conclusions: Impaired microvascular reperfusion, as assessed by MB 0-1, may be associated with LV remodeling in patients with STEMI[4] treated successfully with primary PCI.

Background: Hyperbilirubinemia of the newborn is common. Rarely is an underlying disease other than physiologic hyperbilirubinemia considered the cause of high bilirubin levels. Some of the laboratory tests recommended by the American Academy of Pediatrics are expensive and do not always lead to diagnosis.

Objective: To evaluate the efficacy of standard laboratory tests performed on newborn infants requiring phototherapy for hyperbilirubinaemia.

Methods: We conducted a retrospective chart review that included neonates born during a 6 month period with birth weight > 2500 g treated with phototherapy for hyperbilirubinemia (n=282) according to published guidelines. The main outcome measures were primary and maximal bilirubin values (mg/dl), time to jaundice (in days), the number of bilirubin tests undertaken and whether the patient showed abnormal functioning, and the number of days in follow-up.

Results: Thirty-three neonates (11.7%) were positive in at least one laboratory test (defined as "Abnormal" in our study), 45.5% of whom met the criteria for phototherapy during the first 48 hours of life. Among the newborns who were negative for all laboratory tests (defined as "Normal"), only 6.8% met phototherapy criteria within their first 48 hours of life (P < 0.001). In the Normal group there was a consistent decrease in total serum bilirubin values shortly after phototherapy was begun, while the Abnormal group presented an increase in serum bilirubin values during the first 12 hours of phototherapy. None of the infants had conjugated (direct) hyperbilirubinemia during the study period.

Conclusions: Most neonates presenting with a laboratory identifiable etiology for hyperbilirubinemia (i.e., hemolysis) can be distinguished from those who test negative, mainly based on the timing of presentation and response to phototherapy. A more meticulous selection of patients and reduction in the magnitude of routine laboratory testing can safely reduce discomfort to infants with hyperbilirubinemia as well as costs.

Background: Streptococcus pneumoniae is now the predominant pathogen causing meningitis. The resistance of S. pneumoniae to penicillin and third-generation cephalosporins has grown steadily.

Objectives: To assess the antibiotic susceptibility of S. pneumoniae isolated from the cerebrospinal fluid of children with meningitis, and determine the antibiotic regimen appropriate for suspected bacterial meningitis in Israel.

Methods:  The study group included 31 children with 35 episodes of meningitis hospitalized from 1998 to 2006. S. pneumoniae isolates from the cerebrospinal fluid were tested for susceptibility to penicillin and ceftriaxone.

Results: Of the 35 isolates, 17 (48.6%) showed resistance to penicillin (minimum inhibitory concentration ≥ 0.12 µg/ml). Only 3 isolates (8.6%) showed intermediate resistance to ceftriaxone (≥ 0.5 and < 2 μg/ml), and none showed complete resistance (MIC[1] ≥ 2 μg/ml). The rates of antibiotic resistance were higher in children who were treated with antibiotics prior to admission (penicillin 88.9% vs. 34.6%, P = 0.007; ceftriaxone 22.2% vs. 3.8%, P = 0.156).

Conclusions:  The rate of penicillin resistance is high in children with S. pneumoniae meningitis in Israel, especially in those treated with oral antibiotics prior to admission. Resistance to ceftriaxone is infrequent though not negligible. On the basis of these findings, current recommendations to empirically treat all children with suspected bacterial meningitis with ceftriaxone in addition to vancomycin until the bacterial susceptibility results become available are justified also in Israel.