Clinical and genetic findings in eight Israeli patients with transthyretin-associated familial amyloid polyneuropathy.

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 sensorimotoraxonal 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.

Clinical, electrophysiologic and pathologic findings in 10 patients with myotonic dystrophy 2.

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.

Effect of hyaluronic acid on random-pattern flaps in rats.

BACKGROUND: Hyaluronic acid is a common component of the extracellular matrix, has many medical applications, and is widely used as a soft tissue filler in patients who simultaneously or eventually undergo cosmetic procedures to the areas treated. OBJECTIVE: The objective was to study the effect of hyaluronic acid on wound healing and viability of random-pattern flaps in rats. METHODS AND MATERIALS: Twenty-six male rats were randomly divided into two groups. A cephalically based random dorsal flap was used-14 rats received hyaluronic acid to the bed of the flap immediately after surgery; 12 served as controls. After 1 week, flap survival was evaluated by fluorescein fluorescence. A t-test statistical analysis of survival relationships was performed. RESULTS: Flap viability in hyaluronic acid-treated rats was slightly better than in controls (average flap length survival 46.7 and 40.6 mm, respectively; p<.2). CONCLUSIONS: Although hyaluronic acid had a slight beneficial effect on flap viability, no significant improvement in flap survival was shown. The lack of any deleterious effect of hyaluronic acid on relatively ischemic tissues is further evidence of its harmless effect during surgical intervention. Further studies should be performed to clarify the potential benefit of hyaluronic acid on random flaps. The authors have indicated no significant interest with commercial supporters.

The association between psoriasis, diabetes mellitus, and atherosclerosis in Israel: a case-control study.

BACKGROUND: Previous reports demonstrated an association between psoriasis and other diseases including heart failure and diabetes mellitus. OBJECTIVES: Our aim was to describe the association between psoriasis, diabetes mellitus, and atherosclerosis in Israel. METHODS: A cross-sectional study was performed utilizing the database of Maccabi Healthcare Services (MHS), a large health provider organization in Israel. Case patients were defined as subjects who were diagnosed with psoriasis. Patients with diabetes and atherosclerosis were identified by using the MHS diabetes and cardiovascular registries, respectively. The control group included MHS enrollees without psoriasis. The proportion of diabetes and atherosclerosis among case and control groups was compared. Chi-square tests were used to compare categorical parameters. Logistic regression models were used for multivariate analyses. RESULTS: The study included 46,095 patients with psoriasis (case patients) and 1,579,037 subjects without psoriasis (control patients). The age-adjusted proportion of diabetes was significantly higher in psoriasis patients as compared with the control group (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.1-1.48). The age-adjusted proportion of atherosclerosis was significantly higher in psoriasis patients as compared with the control group (OR 1.28, 95% CI 1.04-1.59). In patients with psoriasis, a multivariate logistic regression model demonstrated an association between diabetes and the multiple use of very potent topical steroids (P < .05) or use of systemic medication for psoriasis (methotrexate, cyclosporine or acitretin) (P < .001). A similar model demonstrated an association between atherosclerosis and the use of phototherapy (P < .001). LIMITATIONS: Our study was based on a computerized database. The diagnosis of psoriasis was based on digitally transmitted data. Therefore overestimation (false-positive cases) and underestimation (false-negative cases) of psoriasis patients may exist, thereby being a source for information bias. A second limitation is selection bias that may occur due to the possibility that reporting of both psoriasis and associated illnesses is higher in individuals who are seeking medical care. A third limitation concerns the causal effect between occurrence of psoriasis and atherosclerosis or diabetes. The dataset of MHS records diagnoses only from 1997 and does not record the date of disease onset. CONCLUSIONS: Our study supports previous reports for an association between psoriasis and atherosclerosis and psoriasis and diabetes. Further study is needed to support this observation.