Israel Medical Association Journal

Background: During the horrific war in the Democratic Republic of Congo during the years 1996–2007 the number of casualties is estimated to be 5.4 million. In addition, 1.8 million women, children and men were raped, many as a social weapon of war. Many of these women still suffer from post-traumatic stress disorder (PTSD) and mutilated genitals.

Objectives: To assess a short-term interventional team for the evaluation and treatment of sexual trauma victims.

Methods: The intervention program comprised four components: training the local staff, medical evaluation and treatment of patients, psychological evaluation and treatment of trauma victims, and evacuation and transport of patients with mutilated genitals. A diagnostic tool for post-traumatic stress disorder (PTSD) – the Impact Event Scale (IES) – was used. The psychological treatment was based on EMDR (eye movement desensitization and reprocessing) principles. Using questionnaires, the information was obtained from patients, medical staff and medical records.

Results: Three primary care clinics were chosen for intervention. Of the 441 women who attended the clinics over a period of 20 days, 52 women were diagnosed with severe PTSD. Psychological intervention was offered to only 23 women because of transport limitations.  The most common medical problems were pelvic inflammatory disease and secondary infertility. Nine patients had their genitals mutilated and were transferred for surgical correction. The 32 local nurses and 2 physicians who participated in the theoretical and practical training course showed improved knowledge as evaluated by a written test.

Conclusions: With the short-term interventional team model for sexual assault victims the combined cost of medical and psychological services is low. The emphasis is on training local staff to enhance awareness and providing them with tools to diagnose and treat sexual assault and mutilation.
 

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: 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.
 

The Dutch painter Rembrandt van Rijn (1606–1669) left behind the largest collection of self-portraits in the history of art. Although about 40 of his oil paintings could be considered “self-portraits,” controversy still exists regarding 14 of them. We undertook to determine the identity of the painter or the subject. Our work was based on the generally accepted premise that these portraits represent a “realistic” rendering of the subject. Self-portraits on which there is consensus regarding the authenticity were chosen as the basis for our measurements. Using a computerized technique we measured the brow ptosis. We also subjectively analyzed Rembrandt's facial aging and the unique asymmetrical elements in his face. We could not add any useful information on 6 of the 14 portraits and suggest that 8 should be considered authentic. Facial aging analysis and the unique surface anatomy allowed us to confirm Rembrandt as the painter in four of six self-portraits. We confirmed Rembrandt as the subject and painter in three more paintings. Of the two paintings in which the subject’s identity was controversial, we determined Rembrandt as the subject in one. We were able to date Rembrandt’s age in two other works and considered another portrait to be a copy. Our methodology may serve as an additional tool for the authentication of self-portraits.
 

The role of carbon in the development of life and as the structural backbone of all organisms is universally accepted and an essential part of evolution. However, the molecular basis is largely unknown and the interactions of carbon with nitrogen and oxygen in space are enigmatic. In 1985, the previously unknown form of carbon, coined fullerene, was discovered. We hypothesize that by virtue of the unique properties of fullerene, this hollow, ultra-robust, large, purely carbon molecule was the earliest progenitor of life. It acted as a stable universal biologic template on which small molecules spontaneously assembled and then formed, by further assembly, a surface mantle (here termed rosasome) of larger molecules. We submit that this process, by its inherent flexibility, initiated evolution, allowing the emergence of parallel diverse rosasome lines responding selectively to varying spatial environments. For example, rosasomal lines mantled with nucleotide and peptide layers are conceived as primordial forerunners of the ubiquitous ribosome. Moreover, the parallel independent and interdependent evolution of rosasome lines would be more rapid than sequential development, refute precedence of either DNA or RNA, and explain the evolution of integration of two subunits with different structures and functions in ribosomes and of the triplet nature of the codon. Based on recent astronomical data, this hypothesis supports the concept that life is not a singularity. This concept also suggests a potential vehicle for therapeutics, biotechnology and genetic engineering.

 Background: Vitamin D status is not evaluated routinely in cancer patients with bone metastasis who are treated with bisphosphonates.

Objectives: To assess the effect of vitamin D status on risk of hypocalcemia and quality of life in these patients.

Methods: We performed laboratory tests for routine serum biochemistry, 25(OH)D, plasma parathyroid hormone (PTH) and bone turnover markers (CTX, P1NP) in 54 patients aged 57.5 ± 13 years treated with intravenous bisphosphonates.

Results: Most of the patients (n=44, 77.8%) did not receive calcium and vitamin D supplementation. Their mean serum 25(OH)D levels (12.83 ± 6.86 ng/ml) correlated with vitamin D daily intake (P = 0.002). In 53 patients (98.1%) 25(OH)D levels were suboptimal (< 30 ng/ml). Albumin-corrected calcium levels correlated with plasma PTH (P = 0.001). No correlation was observed between daily calcium intake and serum calcium (P = 0.45). Hypocalcemia was observed in one patient. Mean plasma PTH was 88.5 ± 65 ng/L. Plasma PTH correlated negatively with 25(OH)D serum levels (P = 0.003) and positively with P1NP (P = 0.004). Albumin-corrected calcium correlated negatively with P1NP (mean 126.9 ± 191 ng/ml) but not with CTX levels (mean 0.265 ± 0.1 ng/ml) (P < 0.001). There was no correlation among quality of life parameters, yearly sun exposure and 25(OH)D levels (P = 0.99).

Conclusions: Vitamin D deficiency is frequent in oncology patients with bone metastasis treated with bisphosphonates and might increase bone damage. Our results indicate a minor risk for the development of severe hypocalcemia in vitamin D-deficient patients receiving bisphosphonate therapy. Although vitamin D deficiency might have some effect on the quality of life in these patients, it was not proven significant.
 

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: Understanding the mechanism and the main components involved in rheumatic mitral regurgitation (MR) associated with dominant pliable mitral stenosis (MS) may improve our ability to repair some mixed rheumatic mitral valve pathologies.

Objectives: To assess mitral valve structural components in pure mitral stenosis versus mitral stenosis associated with mild regurgitation

Methods: Using two-dimensional echocardiography, we performed mitral valve structural analysis in two groups of patients prior to balloon mitral valvuloplasty (BMV). The first group, consisting of 13 females and 2 males (mean age 39 ± 5 years), suffered from pure pliable mitral stenosis (PPMS), while the second group, with 22 females and 2 males (mean age 44 ± 5 years), had mixed mitral valve disease (MMVD) characterized by mild MR in the presence of dominant pliable MS. All echocardiographic measurements relating to the mechanism of MR were undertaken during the systolic phase.

Results: The mean Wilkins scores of the PPMS and MMVD groups were 7 ± 1 and 8 ± 1 respectively (P = 0.004). No significant differences were found between the MMVD group and the PPMS group regarding annular circumference (15.5 ± 1.4 cm vs. 15.4 ± 1.6 cm, P = 0.84), annular diameter (36 ± 4 mm vs. 38 ± 5 mm, P = 0.18), and chordae tendinae length directed to the anterior mitral leaflet (AML) (10 ± 2 mm vs. 11 ± 2 mm, P = 0.137). However, anterior vs. posterior mitral leaflet length during systole was significantly lower in the MMVD than in the PPMS group (2.2 ± 0.5 vs. 2.8 ± 0.4, P = 0.02), whereas the AML thickness at the co-aptation point was greater in the MMVD than in the PPMS group (7 ± 1 vs. 5 ± 1 mm, P = 0.0004).

Conclusions: In rheumatic valves, thickening and shortening of the AML are the main factors determining the appearance of mild MR in the presence of dominant pliable MS.