Israel Medical Association Journal

Background: Diabetes mellitus (DM) is a metabolic sequel in people infected with HIV, especially following the advent of HAART. This may be a particular concern in immigrants due to lifestyle changes. 

Objectives: To characterize the prevalence of DM in HIV-infected Ethiopians in Israel, and to define the risk factors.

Methods: We retrospectively screened the records of 173 HIV-infected Ethiopians and 69 HIV-infected non-Ethiopian HIV patients currently registered at the HIV Clinic of Meir Medical Center. Data were also retrieved from 1323 non-HIV Ethiopians treated in the hospital between 2007 and 2012. The presence of DM was determined by family physician diagnosis as recorded in the hospital database or by the presence of one or more of the following: fasting glucose > 127 mg/dl, hA1C > 6.5% (> 48 mmol/mol), or blood glucose > 200 mg/dl. Population data and risk factors for DM were analyzed by univariate and multivariate analyses. 

Results: Among HIV-infected Ethiopian subjects, the prevalence of DM was 31% (54/173) compared to 4% (3/69) in HIV-infected non-Ethiopians and 8% (102/1323) in non-HIV-infected Ethiopians (P < 0.0001). The relatively increased prevalence of DM was age independent, but most noticeable in those under the median age (< 42 years). Body mass index (BMI) was a predictor for DM (OR 1.263, CI 1.104–1.444, P = 0.001), although its values did not vary between the two ethnic groups. 

Conclusions: HIV-infected Ethiopians are more likely to develop DM at low BMI values compared to non-Ethiopians. This observation questions the relevance of accepted BMI values in this population and suggests that preventive measures against DM be routinely taken in these subjects. 

 

Background: Several studies have identified associations between low vitamin D concentrations and risk of upper respiratory infections (URI). T lymphocytes have a major anti-viral role, are affected by vitamin D metabolism, and may mediate the link between vitamin D and URIs. Competitive swimmers have a relatively high rate of URIs, alongside a high prevalence of low vitamin D concentration. 

Objectives: To examine the associations linking T cell receptor excision circles (TREC, markers of thymus activity), circulating 25(OH)D concentrations and the effect of vitamin D supplementation, and URI symptoms in young competitive swimmers.

Methods: We tested 82 adolescent swimmers for serum 25(OH)D and TREC concentrations and found that 55 had vitamin D insufficiency. Randomized supplementation of either vitamin D3 or placebo was given for 12 winter weeks. URI symptoms were recorded weekly. The associations between TREC copy numbers, vitamin D and URI burden were examined.

Results: TREC concentrations decreased with the participants’ age (r = -0.346, P = 0.003), with no significant between-gender difference. TREC concentrations did not materially differ among subjects with normal, insufficient or deficient vitamin D status, and were not affected by vitamin D supplementation. No significant correlations were found between TREC levels or their changes during the study period, and mean URI severity or duration. 

Conclusions: Thymus activity, represented by higher TREC levels, was not related to vitamin D concentrations or status, and was not affected by vitamin D supplementation in adolescent swimmers. TREC concentrations were not associated with URI severity or duration in this population.

 

Background: Mycetoma is a chronic and destructive infection caused by either fungus or bacteria. Mycetoma has a characteristic clinical presentation of a triad of tumor-like swelling, draining sinuses, and macroscopic grains. Mycetoma infection is extremely rare in Israel; however, in view of the recent immigration from mycetoma-hyperendemic regions of Africa to Israel, physicians in Israel may encounter this infection.

Objectives: To present two cases of mycetoma caused by Madurella mycatomatis in immigrants from endemic regions in Sudan treated at our hospital, and review the current literature. 

Conclusions: Health care professionals in Israel should suspect mycetoma in patients from endemic countries who present with tumor-like swelling especially in the lower extremity. Health care workers should be able to recognize mycetoma and provide the optimal treatment before the lesion progresses to an advanced and disabling disease. 

 

Studies of the respiratory effects of air pollution in Israel published in peer-reviewed journals have been infrequent. Most empiric evidence relates to the association between air pollution and childhood asthma; other air pollution effects on other illnesses are less thoroughly studied. Our evaluation provides a possible explanation for the quite contradictory results demonstrated in the various studies. Actual effect estimates appear to differ considerably, ranging from no air pollution effect to a reasonably strong association detected between PM10 and asthma. We attribute these discrepancies to different research methodologies and different types of data used in various studies.

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: Findings of studies addressing outcomes of war-related famine in non-Jewish populations in Europe during the Second World War (WWII) confirmed an association between prenatal/early life exposure to hunger and adult obesity, diabetes, hypertension, cardiovascular heart disease and the metabolic syndrome. Fetal programming was suggested as the explanatory mechanism.

Objectives: To study the association between being born during WWII in Europe and physical long-term outcomes in child Holocaust survivors.   

Methods: We conducted a cross-sectional study on all Jewish Clalit Health Services (CHS) North District members born in 1940–1945 in Europe ('exposed', n=653) or in Israel to Europe-born parents ('non-exposed', n=433). Data on socio-demographic variables, medical diagnoses, medication procurement, laboratory tests and health services utilization were derived from the CHS computerized database and compared between the groups.

Results: The exposed were significantly more likely than the non-exposed to present with dyslipidemia (81% vs. 72%, respectively), hypertension (67% vs. 53%), diabetes mellitus (41% vs. 28%), vascular disease (18% vs. 9%) and the metabolic syndrome (17% vs. 9%). The exposed also made lower use of health services but used anti-depressive agents more often compared to the non-exposed. In multivariate analyses, being born during WWII remained an independent risk marker for hypertension (OR = 1.52), diabetes mellitus (OR = 1.60), vascular disease (OR = 1.99) and the metabolic syndrome (OR = 2.14).

Conclusions: The results of this cross-sectional study based on highly validated data identify a high risk group for chronic morbidity. A question regarding potential trans-generational effects that may impact the ‘second generation’ is also raised.

Abstract

Background: The familial Mediterranean fever 50 score (FMF50) score was recently devised to define response to treatment and as an outcome measure for clinical trials of FMF.

Objectives: To examine the performance of the FMF50 score in a previously published trial of rilonacept for patients whose FMF was resistant or intolerant to colchicine.

Methods: We reanalyzed the data from our controlled trial of rilonacept vs. placebo in 14 patients with colchicine-resistant or intolerant FMF using the FMF50 score as the primary outcome. The FMF50 score required improvement by ≥ 50 in five of six criteria (attack frequency, attack duration, global patient assessment, global physician assessment, frequency of attacks with arthritis, and levels of acute-phase reactants without worsening of the sixth criterion).

Results: In the original trial rilonacept was considered effective according to the primary outcome measure (differences in the attack frequency) with eight analyzable patients considered responders and four as non-responders. According to the FMF50 score, only two participants would have been considered responders to rilonacept, and one to placebo. Only two participants had ≥ 50% differences between rilonacept and placebo in five criteria. The major explanation for non-response to treatment was that with rilonacept the duration of attack decreased by ≥ 50% in only 2 participants and 5 participants had no attacks of arthritis either during screening (before randomization) or during treatment with rilonacept.

Conclusions: The proposed FMF50 score did not differentiate well between responders and non-responders compared to the a priori defined primary outcome measure in this successful controlled study. 

Abstract

Background: Gaucher disease is the most common lysosomal storage disorder and is caused by a deficiency of the enzyme glucocerebrosidase. Enzyme deficiency leads to the accumulation of undegraded substrates, mainly in cells of the monocyte/macrophage lineage, which is responsible for the clinical manifestations of the disease. To date, no study has attempted to identify the mutation spectrum of the glucocerebrosidase gene (GBA) in Slovak patients

Objectives: To identify mutations in 14 Slovak patients with confirmed glucocerebrosidase deficiency.

Methods: Using molecular genetics methods PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) and direct sequencing of coding region GBA we identified the spectrum of mutations in our patients.

Results: Five mutations (N370S, L444P, G377S, D409H and RecNciI) accounted for 75% of the mutant alleles. The remaining 25% were rare and probably individual mutations.

Conclusions: The mutational spectrum in our patients is similar to that observed in other European countries and corresponds to a Caucasian population, with N370S, L444P, RecNciI being the most common mutation. Interestingly, mutation G377S was more frequent in our patients as compared to other published data. The C4W, L96P, H311N, 745delG and 1127_1128delTT mutations are described here for the first time in Gaucher disease, contributing to the panel of published GBA mutations.  

Background: The activated NLRP3 inflammasome is associated with the etiology of fibrotic diseases. The role of inflammasomes in SSc is still poorly understood.

Objectives: To determine the expression of NLRP3 (nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3) in the skin of patients with systemic sclerosis (SSc) and its relationship with pro-inflammatory cytokines and vascular mediators expression.

Methods: Skin biopsies were taken from 42 patients with either limited or diffuse SSc (21 lcSSc and 21 dcSSc), and from 13 healthy individuals. Using real-time polymerase chain reaction (PCR), the relative expression of caspase-1, IL-1β, IL-18, IL-33, TGF-β, ET-1, iNOS and eNOS genes, were measured. The location of NLRP3 and IL-1β were also determined by immunohistochemistry. Clinical characteristics were evaluated.

Results: The mean age of the patients was 49.3 ± 12.9 (lcSSc), 44.6 ±1 3.8 (dcSSc), and 45 ± 14.1 (healthy individuals). Compared to healthy individuals, the skin of both subtypes of SSc showed a significant increase (P < 0.05) in NLRP3, caspase-1, IL-1β, IL-18 and ET-1. Samples of lcSSc also showed a significant increase of eNOS (P < 0.029), iNOS (P < 0.04) and TGF-β (P < 0.05). Dermal fibrosis evaluated by modified Rodnan skin score (MRSS) had significant correlation with NLRP3, IL-1β, IL-18, and ET-1. Immunohistochemical analysis showed stronger staining of NLRP3 and IL-1β cytoplasmic expression in the keratinizing squamous epithelium of skin from SSc patients compared to controls.

Conclusions: This study identified NLRP3 over-expression in skin of patients with SSc. Skin thickness correlates positively with the NLRP3 inflammasome gene expression and with the vascular mediator and pro-fibrotic ET-1, suggesting that NLRP3 inflammasome plays a role in the pathophysiology of skin fibrosis in human SSc.

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: Trachea esophageal puncture (TEP) is performed following total laryngectomy to allow speech and communication. The most common reason for long-term speech failure in this population is hypertonicity of the constrictor muscle.

Objectives: To present our experience with the treatment of aphonic patients after total laryngectomy and TEP and suggest a protocol for treatment.

Methods: Of 50 patients who underwent total laryngectomy and TEP, 6 suffered from aphonia after surgery. All patients underwent radiotherapy with or without chemotherapy. Delay in speech continued for more than 6 months after surgery. The patients received percutaneous lidocaine injection to the neopharynx in different locations around the stoma in order to map the hypertonic segments in the neopharynx.

Results: Lidocaine injection immediately enabled free speech in five patients. One patient (patient 6) suffered from aphonia and from severe dysphagia and required a feeding tube. This patient succeeded to pronounce abbreviations after lidocaine injection. Another (patient 4) gained permanent ability to speak following a single lidocaine injection; this patient was not injected with botolinium toxin (BTX). For the other five, lidocaine had a transient effect on speech. These patients received BTX percutaneous injections. After BTX injections four regained free speech within 14 days. The fifth patient (patient 6) gained a conversational voice and experienced improvement in swallowing only after additional intensive speech therapy.

Conclusions: Percutaneous lidocaine and BTX injections represent first-line treatment in this population, with good success and minimal complications.