Israel Medical Association Journal

Background: The practice of administering intravenous contrast to children varies by institution depending on their routine. 

Objectives: To assess the necessity of routine contrast administration in brain magnetic resonance imaging (MRI) of pediatric outpatients referred for chronic headache workups. 

Methods: We conducted a retrospective review of consecutive pediatric brain MRI examinations performed during January and February 2014 in 30 pediatric outpatients referred for evaluation of chronic headache. Independent review was performed by two board-certified neuroradiologists. The raters reviewed each MRI first as a non-contrast examination (without seeing the post-contrast images) and then with post-contrast images. 

Results: No abnormalities were found in six patients. One patient had an indeterminate finding of a tubular cerebellar lesion requiring follow-up. In the remaining patients (n=23), the findings were subclinical and included: mucosal thickening in the paranasal sinuses in 9 patients, cystic changes of the pineal gland in 8 (size 2–9 mm), small developmental venous anomalies in 6, non-specific FLAIR hyperintensities in 4, opacification of the mastoids in 2, and telangiectasia in 1 patient. The subclinical cases that were missed on pre-contrast images were: one small developmental venous anomaly, one telangiectasia and one small pineal cyst, none of which hold clinical significance. All kappa inter-rater and intra-rater agreement scores resulted in values above 0.75, excellent agreement according to Fleiss guidelines.

Conclusions: There seems to be little reason to medically justify large-scale use of routine IV contrast administration to evaluate a brain MRI of pediatric patients referred for chronic headache. 

 

Background: Systemic sclerosis (SSc) is a chronic disease with prominent vasculopathy, inflammation, production of autoantibodies, and tissue fibrosis. Periodontitis is a chronic inflammatory oral condition manifesting as microbial infection, inflammation and destruction of the alveolar bone. In both conditions tumor necrosis factor-alpha (TNFα) and other pro-inflammatory cytokines play an important role in pathogenesis. 

Objectives: To assess the periodontal status in SSc patients and compare these parameters to TNFα level in gingival crevicular fluid (GCF) of SSc patients and healthy controls.

Methods: Twenty SSc patients and 20 controls underwent periodontal examination, including probing depth (PD), plaque index (PI), gingival index (GI), bleeding on probing (BOP), and measurement of TNFα levels in collected GCF. 

Results: SSc patients had a greater PD (3.74 ± 0.32 mm vs. 3.35 ± 0.31 mm, P > 0.003), GI (1.53 ± 0.34 vs. 1.12 ± 0.54, P > 0.049), and non-significantly higher BOP than controls. TNFα levels in GCF were higher in SSc patients (1.63 ± 0.36 vs. 1.15 ± 0.34 pg/ml, P = 0.001). Periodontitis parameters correlated with several SSc variables; PI in particular was higher in patients with longer disease duration, sclerodactyly, more severe skin involvement, and SSc activity score.

Conclusions: Patients with SSc have higher indices of periodontal inflammation and higher TNFα level in GCF than did healthy individuals. These changes probably reflect the complexity of factors that influence oral health in SSc. Common pathologic pathways may be responsible for the association between SSc and periodontitis, which requires further study.

 

Background: Admission glucose levels correlate with clinical outcome in patients with type 2 diabetes mellitus (T2DM) hospitalized in general medicine wards. 

Objective: To investigate whether in-hospital hyperglycemia alone and after adjustment for age, gender and lipidemia correlates with in- and out-of-hospital mortality.

Methods: Capillary glucose, serum lipids and diagnoses at discharge among patients with T2DM hospitalized in the general medical wards of our hospital were documented. Correlation with in- and out-of-hospital mortality was determined through uni- and multivariate analyses. 

Results: Of the 4607 patients included in the study 22% died while hospitalized. From a median of five capillary glucose tests obtained per patient, average capillary glucose level was significantly lower in those who survived than in those who died (174 ± 64 vs. 180 ± 65 mg/dl, P = 0.005). Overall, blood cholesterol was higher in those who survived than in those who died (P < 0.001). Multivariate analysis, however, including age, gender, lipidemia and glycemia, showed that only age and male gender correlated with mortality.

Conclusions: Hyperglycemia was associated with increased in- and out-of-hospital mortality on univariate analysis. However, it was not an independent risk factor when corrected for age, gender and hyperlipidemia. 

 

Background: Benign prostate hyperplasia (BPH) is a common age-dependent urological condition that can disrupt quality of life if the patient's treatment choice is inappropriate. 

Objectives: To examine whether patients’ demography and personality affect their decision regarding the type of treatment: namely, conservative or surgical. 

Methods: A total of 105 BPH patients treated during the period 2005–2008 were retrospectively categorized into three groups according to treatment received: (i) medication only (n=056), (ii) combined treatment (the initial medication treatment was switched to surgical treatment) (n=32), and (iii) surgery only (n=17). A prerequisite for inclusion in the study was use of BPH medication for at least half a year before the study (groups 1 and 2). These groups completed the International Prostate Symptom Score (IPSS) questionnaire at the start of BPH medical treatment (IPSS 1) and at the start of the trial (IPSS 2), and the staff calculated the difference (IPSS 1-IPSS 2 = Delta IPSS = DIPSS).  All three groups provided demographic data (age, country of origin, education) and completed tri-dimensional personality questionnaires (TPQ) to measure three independent "temperament" personality dimensions to evaluate how different individuals feel or behave: novel seeking (NS), harm avoidance (HA), and reward dependence (RD). Data were analyzed using chi-square, t-test, one-way ANOVA and logistic regression.

Results: Demographic variables and the RD dimension differed according to choice of BPH treatment. 

Conclusions: Our study suggests that symptomatic BPH treatment is influenced less by the patient's personality and more by his life circumstances. Israeli-born patients were more conservative, Russian-born patients were ambivalent, and other foreign-born patients predominantly preferred surgical treatment. We assume that personality has a more decisive effect on patients with malignant disease and they accept the medical advice more easily. 

 

Abstract

Background: Human herpes virus-6 (HHV-6) reactivation after hematopoietic stem cell transplantation (HSCT) is well known and has been linked with several clinical manifestations. The significance of HHV-6 viremia and related complications in this setting is still unclear.

Objective: To estimate the incidence of HHV-6 reactivation and associated morbidity in children undergoing allogeneic HSCT.

Methods: Blood samples obtained weekly (for cytomegalovirus surveillance) from children who underwent allogeneic HCST during the period January 2006–June 2010 were retrospectively tested for the presence of HHV-6 DNA using standard real-time polymerase chain reaction (PCR) assay. Clinical records were reviewed for correlation between viremia and clinical manifestations.

Results: Samples from 39 children were tested. Twenty patients had viral loads above 1000 copies/ml (51%) in at least one sample. Higher viral loads were seen in patients with primary immunodeficiency and in those with cord blood transplant. Attributable symptoms were present in 12 patients (60%) concurrently with positive PCR. Clinical manifestations spontaneously resolved without treatment in most cases, concomitantly with a decrease in viral load.

Conclusions: HHV6 reactivation during allogeneic HSCT is common. HHV-6 reactivation should be considered in patients with graft-vs-host disease-like rash, onset of CNS symptoms, delay in engraftment, and in patients after cord blood transplantation.

Abstract

Background: Scleroderma lung disease (ILD-SSc) is treated mainly with cyclophosphamide (CYC). The effectiveness of CYC was judged after 12–24 months in most reports.

Objectives: To analyze the effect of monthly intravenous CYC on pulmonary function tests including forced vital capacity (FVC) and diffusing lung capacity (DLCO), as well as Rodnan skin score (mRSS), during long-term follow-up.

Methods: We retrospectively collected the data on 26 ILD-SSc patients who began CYC treatments before 2007. Changes in FVC, DLCO and mRSS before treatment, and at 1, 4 and 7 years after completion of at least six monthly intravenous CYC treatments for ILD-SSc were analyzed.

Results: Mean cumulative CYC dose was 8.91 ± 3.25 G. More than 30% reduction in FVC (0%, 8%, and 31% of patients), DLCO (15%, 23%, 31%), and mRSS (31%, 54%, 62%) at years 1, 4 and 7 was registered. During the years 0–4 and 4–7, annual changes in FVC, DLCO and mRSS were 3.2 vs. 0.42% (P < 0.040), 4.6 vs. 0.89% (P < 0.001), and 1.8 vs. 0.2 (P = 0.002). The greatest annual FVC and DLCO reduction over the first 4 years correlated with mortality (P = 0.022). There were no differences in the main variables regarding doses of CYC (< 6 G and > 6 G).

Conclusions: In patients with ILD-SSc, CYC stabilized the reduction of FVC during treatment, but this effect was not persistent. The vascular characteristic of ILD-SSc (DLCO) was not affected by CYC treatment. CYC rapidly improved the mRSS. This effect could be achieved with at least 6 G of CYC. Higher rates of annual reduction in FVC and DLCO in the first 4 years indicate the narrow window of opportunity and raise the question regarding ongoing immunosuppression following CYC infusions.

 

We are overwhelmed by warnings about inevitable geophysical and human problems. Earth is beset by escalating, man-made, environmental crises and our exploding population will eventually lack water, food and vital materials. This suggests, together with increasing poverty, deepening social unrest and advanced techniques for mass killing, that civilization will break down long before atmospheric CO₂ or resistant microbes become catastrophic. Despite intensive searching, life has not been found in space, even though thousands of planets have been found and life there may be as problematic and unpredictable as on Earth. The human brain is already a 'universe', with 85 billion neurons and a hundred trillion synapses, more than the stars in our galaxy. Understanding consciousness, the brain, its aging and pathologies, and eliminating the propensity for human aggression are urgent challenges. During 1958–2012, NASA spent $800 billion. In contrast, the annual cost of brain disease in the U.S. is $600 billion, more than cardiovascular disease and cancer combined. We suggest that a massive switching of financial and human resources is required to explore the full potential of the human brain. Visiting Mars can wait. We further propose a novel two-brain hypothesis: the animal 'brain' evolved as two fundamentally different though interdependent, complementary organs: one electroionic (tangible, known and accessible), and the other, electromagnetic (intangible and difficult to access) – a relatively independent, stable, structured and functional 3D compendium of variously induced interacting EM fields.

Background: Orofacial clefts are the most common craniofacial congenital malformations, with significant anatomic, ethnical, racial and gender differences.

Objectives: To investigate the prevalence, distribution and characteristic features of various types of non-syndromic clefts among Israeli Jews and Arabs.

Methods: We conducted a retrospective multi-center survey in 13 major hospitals in Israel for the period 1993–2005. To obtain the true prevalence and detailed clinical characteristics, data on liveborn infants with non-syndromic clefts were obtained from the Ministry of Health's National Birth Defect Registry and completed by chart reviews in the 13 surveyed hospitals.

Conclusions: The prevalence of non-syndromic clefts was 7.00/10,000 live births. The markedly higher rate in Arabs is related to the high rate of consanguinity. Both very young and old maternal age represents a higher risk of clefts in their offspring. 

Background: Hypertrophic cardiomyopathy (HCM) is a familial disease with autosomal dominant inheritance and age-dependent penetrance, caused primarily by mutations of sarcomere genes. Because the clinical variability of HCM is related to its genetic heterogeneity, genetic studies may improve the diagnosis and prognostic evaluation in HCM.

Objectives: To analyze the impact of genetic diagnosis on the clinical management of HCM.

Methods: Genetic studies were performed for either research or clinical reasons. Once the disease-causing mutation was identified, the management plan was reevaluated. Family members were invited to receive genetic counseling and encouraged to be tested for the mutation.

Results: Ten mutations in sarcomere protein genes were identified in 9 probands: 2 novel and 8 previously described. Advanced heart failure or sudden death in a young person prompted the genetic study in 8 of the 9 families. Of 98 relatives available for genotyping, only 53 (54%) agreed to be tested. The compliance was higher in families with sudden death and lower in what appeared to be sporadic HCM or elderly-onset disease. Among the healthy we identified 9 carriers and 19 non-carriers. In 6 individuals the test result resolved an uncertainty about "possible HCM." In several cases the genetic result was also used for family planning and played a role in decisions on cardioverter-defibrillator implantation.

Conclusions: Recurrence of a same mutation in different families created an opportunity to apply the information from the literature for risk stratification of individual patients. We suggest that the clinical context determine the indication for genetic testing and interpretation of the results.

Background: Serum lactate dehydrogenase (LDH) is elevated in various diseases. 

Objectives: To analyze serum LDH as a distinguishing clinical biomarker and as a predictor of in-hospital outcome in admitted medical patients.

Methods: We analyzed a cohort of all 158 patients with very high isolated LDH (LDH ≥ 800 IU/ml – without concomitant elevations of alanine aminotransferase and aspartate aminotransferase) – admitted to our internal medicine department during a 3 year period. Epidemiologic and clinical data, as well as the final diagnosis and outcome were recorded and compared with those of a cohort of all 188 consecutive control patients.

Results: Very high isolated LDH was a distinguishing biomarker for the presence of cancer (27% vs. 4% in the LDH group and controls respectively, P < 0.0001), liver metastases (14% vs. 3%, P < 0.0001), hematologic malignancies (5% vs. 0%, P = 0.00019), and infection (57% vs. 28%, P < 0.0001). Very high isolated LDH was a marker for a severe prognosis, associated with more admission days (9.3 vs. 4.1, P < 0.0001), significantly more in-hospital major complications, and a high mortality rate (26.6% vs. 4.3%, P < 0.0001). Finally, very high isolated LDH was found in a multivariate regression analysis to be an independent predictor of mortality.

Conclusions: The presence of very high isolated LDH warrants thorough investigation for the presence of severe underlying disease, mostly metastatic cancer, hematologic malignancies and infection. Moreover, it is a marker for major in-hospital complications and is an independent predictor of mortality in admitted medical patients. 

Objectives: To determine the properties of HAM as an antigenic substrate for the detection of autoantibodies in pemphigus vulgaris and bullous pemphigoid.

Methods: Immunomapping and tandem liquid chromatography mass spectrometry were used to delineate the antigenic structure of HAM in 25 pemphigus patients, 41 pemphigoid patients, and 36 controls. Immunoblotting and indirect immunofluorescence were used to study the diagnostic utility of HAM, and the results were compared to those of indirect immunofluorescence on monkey esophagus, immunoblotting using normal human skin, and enzyme-linked immunosorbent assay (ELISA).

Results: Immunomapping demonstrated the presence of all the antigens known to be targeted in autoimmune bullous skin diseases, in both normal human skin and HAM, except for the absence of BP230, and low threshold levels of Dsg1, Dsg3 and Dsc3 in HAM. HAM indirect immunofluorescence demonstrated anti-basement membrane zone antibodies in 48.7% of the pemphigoid patients, and anti-intercellular space antibodies in 72.0% of the pemphigus patients. HAM immunoblotting did not demonstrate anti-BP230 antibodies, but detected anti-BP180 antibodies in 53.6% of the pemphigoid patients. It did not demonstrate anti-Dsg1 and/or anti-Dsg3 antibodies in any of the pemphigus patients. These results were inferior to those of ELISA and monkey esophagus indirect immunofluorescence.

Conclusions: Compared to other studied methods, HAM does not offer advantages in detecting autoantibodies in bullous pemphigoid and pemphigus vulgaris.