Israel Medical Association Journal

Objectives: To retrospectively determine the clinical response to ¹³¹I-MIBG therapy at low doses in patients with refractory neuroblastoma.

Methods: We performed a retrospective chart review of 10 patients with neuroblastoma treated with ¹³¹I-MIBG at Rambam Health Care Campus from 1994 to 2012. Clinical data, number of ¹³¹I-MIBG courses delivered, toxicities, and clinical responses were reviewed. MIBG scan was performed after each course.

Results: Twenty-one courses of ¹³¹I-MIBG were delivered to 10 patients (3 girls, 7 boys). Their mean age was 3.8 years (range 1.5–6 years). All patients received several protocols of chemotherapy including the high dose form. Three patients received three courses of ¹³¹I-MIBG with a minimum of 6 weeks between each course, five patients received two courses, and two patients received only one course. An objective response to the first course was obtained in nine patients and to the second course in six of eight, and in three children who underwent the third course the pain decreased. One patient has no evidence of disease, four are alive with disease, and five died of the disease. No unanticipated toxicities were observed.

Conclusions: Low dose ¹³¹I-MIBG is an effective and relatively non-toxic treatment in neuroblastoma disease palliation. Rapid and reproducible pain relief with ¹³¹I-MIBG was obtained in most of the children. Treatment with systemic radiotherapy in the form of low dose ¹³¹I-MIBG was easy to perform and effective in cases of disseminated neuroblastoma, demonstrating that this primary therapy can be used for palliative purposes.

Background: The effectiveness of intensive versus standard physical therapy for motor progress in children with cerebral palsy is controversial. Sitting acquisition is considered an important developmental milestone.  

Objectives: To assess the acquisition of sitting and gross motor progress in infants with cerebral palsy treated with intermittent intensive physical therapy as compared to a matched group treated with a standard physical therapy regimen.

Methods: We conducted a randomized controlled crossover study in 10 infants aged 12–22 months with cerebral palsy; 5 were assigned to the intensive intermittent therapy group and 5 to the control group. After 4 weeks of baseline intervention, the intervention program was administered to the experimental group for 8 weeks and the regularly scheduled weekly program to the comparison group, targeting sitting as the treatment goal. Thereafter the comparison group crossed over. The Gross Motor Function Measure 66 and 88 (GMFM 66 and 88) were used at 4 week intervals.

Results: The intermittent intensive regimen yielded a mean improvement of 7.8% and 1.2% in the two groups respectively. However, these results were attributed to infants with a low functional level only (P < 0.01).

Conclusions: Goal-directed intensive intermittent regimen could possibly be beneficial in infants with a low functional level.
 

Background: Determining the prognosis of patients with heart failure is essential for patient management and clinical trial conduct. The relative value of traditional prognostic criteria remains unclear and the assessment of long-term prognosis for individual patients is problematic.

Objectives: To determine the ability of clinical, hemodynamic and echocardiographic parameters to predict the long-term prognosis of patients with idiopathic dilated cardiomyopathy.

Methods: We investigated the ability of clinical, hemodynamic and echocardiographic parameters to predict the long-term prognosis of individual patients in a large, representative, contemporary cohort of idiopathic dilated cardiomyopathy (IDCM) patients referred to Johns Hopkins from 1997 to 2004 for evaluation of cardiomyopathy. In all patients a baseline history was taken, and physical examination, laboratory studies, echocardiogram, right heart catheterization and endomyocardial biopsy were performed.

Results: In 171 IDCM patients followed for a median 3.5 years, there were 50 long-term event-free survivors (LTS) (median survival 6.4 years) and 34 patients died or underwent ventricular assist device placement or transplantation within 5 years (NLTS; non-long-term survivors) (median time to event 1.83 years. Established risk factors (gender, race, presence of diabetes, serum creatinine, sodium) and the use of accepted heart failure medications (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers) were similar between the two groups. Although LTS had younger age, higher ejection fraction (EF) and lower New York Heart Association (NYHA) class at presentation, the positive predictive value of an EF< 25% was 64% (95% CI 41%–79%) and of NYHA class > 2 was 53% (95% CI 36–69%). A logistic model incorporating these three variables incorrectly classified 29% of patients.

Conclusions: IDCM exhibits a highly variable natural history and standard clinical predictors have limited ability to classify IDCM patients into broad prognostic categories. These findings suggest that there are important host-environmental factors still unappreciated in the biology of IDCM.
 

Background: During an influenza pandemic, clinicians need easily available clinical and laboratory criteria to distinguish influenza from similar respiratory illnesses. We compared A/H1N1/2009-polymerase chain reaction (PCR)-positive and matched PCR-negative hospitalized patients with suspected H1N1 influenza to identify factors that could assist physicians at patient admission.

Objectives: To identify factors significantly associated with A/H1N1/2009 infection.

Methods: A group of 145 patients with PCR-confirmed A/H1N1 2009 influenza admitted between 27 May 2009 and 3 December 2009 was matched with 145 PCR-negative patients by age, epidemiological week and pregnancy status. Epidemiological and clinical parameters and radiological findings on initial chest X-ray were compared between the two groups.

Results: Asthma (PCR+ 26%, PCR- 12%, P = 0.006) and military service (PCR+ 13%, PCR- 4%, P = 0.15) were associated with PCR-positive status in non-pregnant patients. At presentation, fever, cough, myalgia and fulfilling the pandemic influenza case definition were significantly more frequent in non-pregnant PCR+ patients (62/90/43/59% in PCR+ versus 38/69/30/35% in PCR-). In pregnant patients, fever and fulfilling the case definition were significantly associated with PCR-positive status. Mean leukocyte and absolute lymphocyte counts were significantly lower in both pregnant and non-pregnant PCR-positive patients. Significantly more PCR-negative non-pregnant patients (43% vs. 22% PCR+, P = 0.004) had abnormal chest X-ray (CXR) findings on presentation. In PCR-positive patients, patchy consolidation and interstitial infiltrates were the most common abnormalities.

Conclusions: Under the conditions generated by the A/H1N1/2009 pandemic, radiological findings did not distinguish reliably between influenza and other febrile respiratory illnesses. Asthma, military service, the pandemic case definition (particularly fever, cough and myalgia) and lymphopenia were associated with confirmed H1N1 infection.
 

Background: Recently, cognitive assessments of patients with Fabry disease highlighted neurocognitive impairment using test batteries that are time and labor intensive.

Objectives: To introduce a user-friendly self-administered tool for cognitive testing in patients with Fabry disease.

Methods: We used a computerized system requiring about 1 hour for patient follow-up. All patients with enzymatic and/or molecular diagnosis of Fabry disease seen in our clinic underwent assessment with the Fabry-specific Mainz Severity Score Index (MSSI) with subscores (neurological, renal, cardiac, and general) and a Mindstreams neurocognitive battery for mild impairment, evaluating memory, executive function, attention, information processing, visual spatial processing, verbal function, and motor skills. A Global Cognitive Score (GCS) was also computed.

Results: Ten patients (3 males, 7 females) were tested (mean age 41.5, range 25–56 years). Males were younger, had moderate nephropathy and no cerebrovascular accident (CVA); their Mindstreams GCS was 85.6–107 points. Three females had mild-moderate (8,10,15 points) neurological MSSI subscores (two CVA); all females had Mindstreams GCS of 59–107.7 points. Below-average performance was prevalent, particularly in information processing and motor skills consistent with mild impairment. Average GCS in females (90.3 points) was lower than in males (98.2 points). For individual patients, performance was poorest in information processing (n=4), attention (n=2), motor skills (n=2), verbal function (n=1), and visual spatial processing (n=1).

Conclusions: MindStreams may simplify cognitive assessment monitoring in Fabry disease.
 

Background: Acute, as opposed to chronic, anterior uveitis is rarely associated with macular or optic nerve  edema. Nevertheless, mild changes may not be visible on examination.

Objectives: To implement non-invasive ocular coherence tomography (OCT) for obtaining quantitative and qualitative data in the assessment of changes in macular morphology and peripapillary retinal nerve fiber layers in eyes with acute anterior uveitis.

Methods: This retrospective case-control study was conducted in patients with unilateral acute anterior uveitis lasting for up to one month. Patients with evidence of other ocular disease or who had undergone intraocular surgery were excluded. We reviewed the charts of 14 consecutive patients who were diagnosed with acute unilateral anterior uveitis between 2007 and 2008 at the Tel Aviv Medical Center. Data on demographic details, ophthalmic examination, macular thickness and peripapillary retinal nerve fiber layer (RNFL) thickness (as demonstrated by OCT) were retrieved. Retinal and RNFL thickness was compared between the healthy fellow eye (control) and the uveitic eye in the central and four perifoveal quadrant regions, and RNFL thickness was compared in the mean and four quadrant values by Student’s t-test.

Results: We evaluated 28 eyes of 7 males and 7 females (mean age 37.7 years, range 20–65). The diagnoses were: idiopathic in five patients, ankylosing spondylitis in five, Crohn’s disease in one patient and reactive arthritis in one. Nine patients were HLA-B27 positive. The retina and the peripapillary NFL in each area were thicker in the uveitic eyes compared to the controls. The difference was statistically significant. There was no correlation between the differences in OCT values and patients’ demographic characteristics.

Conclusions: OCT demonstrated that eyes with acute anterior uveitis had thicker maculae and thicker peripapillary RNFL than controls. This finding suggests that even milder anterior uveitis may be associated with some degree of posterior segment manifestations.

Background: Human brucellosis is common in southern Israel among the semi-nomadic Bedouin, a population that consumes unpasteurized dairy products. Though camel milk ingestion is a known mechanism for brucellosis acquisition, only a few reports of sporadic cases have been published in the medical literature.

Objectives: To describe a local brucellosis outbreak in 15 extended Bedouin family members, following ingestion of infected camel milk.

Methods: Data regarding patient’s clinical manifestations, laboratory findings, treatment and outcome were collected from the hospital and the health fund clinics’ computerized database. Camel’s blood and milk were tested for Brucella serology and culture. Cases were defined by positive Rose Bengal test, symptoms correlating with brucellosis, and consumption of infected camel milk.

Results: Fifteen patients were diagnosed with acute brucellosis from March to June 2011. Sixty percent of cases had serum agglutination test titers of 1:160 or higher and 4/8 (50%) had positive blood culture for Brucella melitensis. Arthralgia and fever were the most consistent clinical manifestations. Blood and milk serology and milk culture taken from the female camel were positive for Brucella melitensis.

Conclusions: The treating physicians must consider the possibility of infected camel milk ingestion as the mode of infection, both in sporadic cases and in outbreaks of brucellosis.

Background: The pathogenesis of anemia associated with acute infection in children has not been well delineated.

Objectives: To characterize this type of anemia in children with acute infection, mainly in relation to iron status.

Methods: These two cross-sectional studies compared the prevalence and severity of anemia between outpatient febrile children and age-matched non-febrile controls.

Results: In part 1 of the study, children with acute infection (n=58) had a significant decrease in hemoglobin levels compared with 54 non-febrile controls. Mean corpuscular volume (MCV) did not change this association. Moreover, there was no significant difference in MCV, mean cell hemoglobin or red cell distribution width values between the two groups. Regarding part 2, of the 6534 blood counts obtained in community clinics, 229 were defined as “bacterial infection.” Chart survey confirmed this diagnosis. White blood cell level was significantly inversely associated with hemoglobin level (r = -0.36, P < 0.0001). Anemia was significantly more prevalent among children with bacterial infection compared to those without: 21.4% vs. 14.1% (P = 0.002). Mean values of iron status parameters were all within normal limits.

Conclusions: Acute illness is associated with anemia. The pathogenesis of this anemia does not appear to be associated with disruption of iron metabolism.

Background: Clefts of the lip and palate are the most common significant congenital birth anomaly of orofacial region. The condition may vary from a minor easily correctable cleft to a significant functional and cosmetic incapacitation. This is the first epidemiological study of orofacial clefts in the Negev region in Israel.

Objectives: To establish the frequency of cleft lip and palate in the population of the Negev, characterize the demographic features of affected individuals and find possible risk factors, compare the risk in two major population groups: Bedouin and Jewish in a well-defined geographic area, and determine whether there is a change over time in the birth of babies with facial clefts.

Methods: We conducted a retrospective survey of the Soroka Medical Center archives. The sample population comprised all 131,218 babies born at Soroka during the 11 year period 1 January 1996 to 31 December 2006. Statistical tests used Pearson's chi-square test, Student’s t-test and Spearman's correlation coefficient test according to the type of parameter tested.

Results: During the study period 140 babies were born with orofacial cleft. The overall incidence of cleft lip and palate was 1.067/1000. The incidence of facial clefts was 1.54/1000 among Bedouins and 0.48/1000 among Jews (P < 0.001). Cleft palate was significantly more frequent in female than male babies (P = 0.002). Over the study years we found a significant decrease in the incidence of facial clefts in the Bedouin population, with Spearman's correlation coefficient rank -0.9 (P < 0.01).

Conclusions: A significant decrease occurred in the incidence of facial clefts among Bedouin. This change may be attributed to prenatal care in the Bedouin Negev population as part of social and health-related behavior changes. The reduction in rates of congenital malformations, however, does not mean a reduction in the number of cases in a growing population. Also, with a modern western lifestyle, the expectancy and demand for reconstructive facial surgery and comprehensive care for these children are on the rise.