Israel Medical Association Journal

Background: Transthyretin (TTR)-associated familial amyloid polyneuropathy (FAP) is an autosomal dominant multisystem disease with neurological and extra-neurological manifestations. It is caused by various mutations in the TTR gene leading to the formation of insoluble amyloid.

Objectives: To describe the clinical and genetic findings in patients with TTR-associated FAP in Israel.

Methods: We evaluated eight patients clinically and genetically during the years 2006 to 2011.

Results: At onset, all the patients exhibited sensory loss of the lower and upper limbs, five patients experienced muscle pain, and one patient had lower limb weakness. Five patients had autonomic nervous system manifestations, and four demonstrated evidence of amyloid cardiomyopathy. Nerve conduction studies showed sensorimotor axonal neuropathy in all patients. Sural nerve biopsies were obtained in five patients; only three biopsies revealed amyloid deposit. In four patients of Yemenite descent, genetic analysis of the TTR gene demonstrated ser77tyr mutation. One patient of Tunisian descent and one Ashkenazi patient harbored the val30met mutation. One patient of Iranian descent showed val32ala mutation, and another Ashkenazi patient showed phe33leu mutation.

Conclusions: TTR-associated FAP is a progressive and fatal disease that exists in the Israeli population and is unproportionally common among Yemenite Jews. This disease may be under-diagnosed and should be considered in the differential diagnosis of any patient with rapidly progressive neuropathy, especially with autonomic involvement or extra-neural features. The absence of amyloid in nerve biopsy should not rule out the diagnosis.  
 

Background: Atherosclerosis is a well-established inflammatory disease in which T helper 1 (Th1) cells play a key role. Regulatory T (Treg) cells drive a shift from Th1 to Th2 response and were shown to be reduced in atherosclerosis. ST2/interleukin (IL)-33 signal was found to promote Th2 response, attenuating atherosclerotic plaque progression.

Objectives: To evaluated the effect of IL-33 on Treg cell number.

Methods: We employed flow cytometry to determine Treg cell number, as well as ST2 levels, among splenocytes of C57BL/6J vs ApoE-/- mice. Soluble ST2 (sST2) levels were detected by enzyme-linked immunosorbent assay. 

Results: IL-33 contributed to an increase in Treg cells, but this association was attenuated in ApoE knockout (ApoE-/-) atherosclerotic mice. As a possible mechanism we demonstrated a reduction in the levels of CD4+ST2+ cells by flow cytometry, which is cotemporary to the previously described decrease in Treg cells in ApoE-/- mice. Additionally, the serum level of the soluble ST2 (sST2) decoy receptor was higher in ApoE-/- mice than in control animals.

Conclusions: Our results suggest that a repressed ST2/IL-33 signaling may contribute to the decrease in Treg cells observed in atherosclerosis.
 

Background: Myotonic dystrophy type 2 (DM2) is an autosomal dominant, multisystem disorder caused by a CCTG tetranucleotide repeat expansion located in intron 1 of the zinc finger protein 9 gene (ZNF9 gene) on chromosome 3q 21.3.

Objectives: To describe the clinical, electrophysiologic and pathologic findings in patients with myotonic dystrophy 2.

Methods: We evaluated 10 patients genetically, clinically and electrophysiologically during the years 2007 to 2008.

Results: All patients were of Jewish European ancestry. Among affected individuals, eight patients had symptoms of proximal muscle weakness, two had muscle pain, and two exhibited myotonia. On physical examination six patients had severe weakness of hip flexor muscles. Seven individuals underwent cataract surgery, and cardiac involvement was seen in one case. On the initial electromyographic (EMG) examination five patients demonstrated myotonic discharges; repeated studies showed these discharges in nine cases. Six muscle biopsies showed non-specific pathological changes. Seven patients had an affected first-degree relative with either a diagnosed or an undiagnosed muscular disorder, consistent with an autosomal dominant trait.

Conclusions: DM2 may often present with proximal muscle weakness without myotonia. EMG may initially fail to show myotonic discharges, but these discharges may eventually show in most cases on repeated EMG. Thus, DM2 may be underdiagnosed and should be included in the differential diagnosis of adult patients of Jewish European ancestry presenting with proximal lower limb weakness.
 

Background: There is a wide treatment gap between evidence-based guidelines and their implementation in primary care.

Objective: To evaluate the extent to which physicians "literally" follow guidelines for secondary prevention of dyslipidemia and the extent to which they practice "substitute" therapeutic measures.

Methods: We performed a post hoc analysis of data collected in a prospective cluster randomized trial. The participants were 130 primary care physicians treating 7745 patients requiring secondary prevention of dyslipidemia. The outcome measure was physician "literal" adherence or "substitute" adherence. We used logistic regressions to evaluate the effect of various clinical situations on “literal” and “substitute” adherence.

Results: "Literal" adherence was modest for ordering a lipoprotein profile (35.1%) and for pharmacotherapy initiations (26.0%), but rather poor for drug up-titrations (16.1%) and for referrals for specialist consultation (3.8%). In contrast, many physicians opted for "substitute" adherence for up-titrations (75.9%) and referrals for consultation (78.7%). Physicians tended to follow the guidelines “literally” in simple clinical situations (such as the need for lipid screening) but to use "substitute" measures in more complex cases (when dose up-titration or metabolic consultation was required). Most substitute actions were less intense than the actions recommended by the guidelines.

Conclusions: Physicians often do not blindly follow guidelines, but rather evaluate their adequacy for a particular patient and adjust the treatment according to their assessment. We suggest that clinical management be evaluated in a broader sense than strict guideline adherence, which may underestimate physicians' efforts.
 

Background: An outbreak of respiratory illness caused by a novel swine-origin influenza virus (influenza A/H1N1 2009) that began in Mexico was declared a global pandemic by the World Health Organization in June 2009. The pandemic affected many countries, including Israel.

Objectives: To compare the course of chest radiographic and computed tomography findings in patients who survived and those who died following admission to the intensive care unit (ICU) or intubation due to severe laboratory-confirmed swine-origin influenza A/H1N1 2009.

Methods: We retrospectively reviewed the patient records (267 radiographs, 8 CTs) of 22 patients (10 males, 12 females) aged 3.5–66 years (median 34) with confirmed influenza A/H1N1 2009, admitted to the ICU and/or intubated in five major Israeli medical centers during the period July–November 2009. We recorded demographic, clinical, and imaging findings –including pattern of opacification, extent, laterality, distribution, zone of findings, and presence/absence of nodular opacities– at initial radiography and during the course of disease, and compared the findings of survivors and non-survivors. Statistical significance was calculated using the Wilcoxon (continuous variables) and Fisher's exact tests (categorical variables).

Results: The most common findings on the initial chest radiography were airspace opacities, which were multifocal in 17patients (77%) and bilateral in 16 (73%), in the lower or lower and middle lung zones in 19 patients (86%). Large airspace nodules with indistinct margins were seen in 8 patients (36%). Twelve patients survived, 10 died. Patients who died had multiple background illnesses and were significantly older than survivors (P = 0.006). Radiologic findings for the two groups were not significantly different.

Conclusion: Airspace opacities, often with nodular appearance, were the most common findings among patients with severeinfluenza A/H1N1 2009. The course of radiologic findings was similar in patients with severe influenza A/H1N1 2009 whosurvived and those who died.

Background: Gastric stump cancer is often described as a tumor with a poor prognosis and low resectability rates.

Objectives: To compare the pathological characteristics of gastric stump cancer patients with those of patients with proximal gastric cancer.

Methods: This retrospective study was based on the demographic and pathological data of patients diagnosed with gastric cancer and treated at Assaf Harofeh Medical Center during an 11 year period. The patients were divided into two groups: those undergoing proximal gastrectomy for proximal gastric cancer and those undergoing total gastrectomy for gastric stump cancer.

Results: Patients with gastric stump cancer were predominantly male, older (P = 0.202, not significant), and had a lower T stage with less signet-ring type histology, fewer harvested and fewer involved lymph nodes (P = 0.03, statistically significant) and less vascular/lymphatic involvement than patients with proximal gastric cancer.

Conclusions: The lower incidence of involved lymph nodes and lymphovascular invasion in gastric stump cancer as compared to proximal gastric cancer in this study may imply that the prognosis of gastric stump cancer may be better than that of proximal gastric cancer. However, to verify this assumption a study comparing patient survival is required.