Israel Medical Association Journal

Background: Ultrasound is useful in detecting acromioclavicular pathologies in cases of trauma, inflammations and degenerative changes.

Objectives: To describe the sonographic findings of the acromioclavicular joint pathology in patients with anterior shoulder pain.

Methods: Sonographic examination of the ACJ[1] was used to examine 30 adults with anterior shoulder pain. As a control group we studied 30 asymptomatic patients and compared the findings to plain radiographs of the symptomatic group.

Results: The pathologic findings consisted of swelling of the joints, bone irregularities, widening and/or narrowing of the ACJ, soft tissue cyst formation, excessive fluid collection, and calcification. All these signs represent degenerative changes compatible with early osteoarthritis. We encountered one case of septic arthritis that required joint aspiration and antibiotic treatment.

Conclusions: It is our belief that ultrasonography should be used routinely in cases of anterior shoulder pain since it demonstrates various pathologies undetected by plain radiographs.

Melanoma is the leading cause of death from skin tumors worldwide, with an annual increase in incidence over the past decade. The molecular mechanisms involved in melanoma pathogenesis are beginning to be unraveled. While a family history of melanoma and exposure to ultraviolet irradiation have been known for years as risk factors in melanoma development, the precise genes involved in inherited predisposition were defined only in the past decade. Germline mutations in two genes that play a pivotal role in controlling cell cycle and division – CDKN2A and cyclin-dependent kinase 4 (CDK4) – have been detected in autosomal, dominant, high penetrance familial melanoma cases. In addition to these two highly penetrant genes, germline mutations and polymorphisms in a few low penetrance genes have been reported in familial melanoma cases: melanocortin-1 receptor, epidermal growth factor, glutathione s-transferase M1, cytochrome p450 debrisoquine hydroxylase locus (CYP2D6) and vitamin D receptor.

While some claim that germ-line engineering is a definite possibility, the law in Israel and in most countries states that it should be avoided. This paper suggests that using GLE[1] in order to ‘self-evolve’ (when it becomes safe) is not only inevitable but also morally justified. This paper argues that,  

• The great achievements of healthcare during the last century, enabling longer life, have made almost everyone prey to late-onset diseases.


• The conundrum of healthcare allocation is worsening, partly due to late-onset dysfunctional genes that have escaped the barriers of natural selection.


• Trying to free future generations from late-onset diseases (such as Alzheimer’s for instance) may be considered as ‘eugenics’ but, if pursued freely and justly, is a noble goal.


• We will be affecting future generations whether or not we use GLE.


• By definition, GLE might be reversible; it follows therefore that GLE may not necessarily represent the dramatic change inserted in the germ line forever – as is usually suggested.


• Reproductive freedom and justice are paramount in this scenario. These values are not necessarily incompatible if the right policies are in place.

Background: Laron Syndrome, first described in Israel, is a form of dwarfism similar to isolated growth hormone deficiency caused by molecular defects in the GH[1] receptor gene.

Objective: To characterize the molecular defects of the GH-R[2] in Laron syndrome patients followed in our clinic.

Methods: Of the 63 patients in the cohort, we investigated 31 patients and 32 relatives belonging to several ethnic origins. Molecular analysis of the GH-R gene was performed using the single strand conformation polymorphism and DNA sequencing techniques.

Results: Eleven molecular defects including a novel mutation were found. Twenty-two patients carried mutations in the extracellular domain, one in the transmembrane domain, and 3 siblings with typical Laron syndrome presented a normal GH-R. Of interest are, on one hand, different mutations within the same ethnic groups: W-15X and 5, 6 exon deletion in Jewish-Iraqis, and E180 splice and 5, 6 exon deletion in Jewish-Moroccans; and on the other hand, identical findings in patients from distinct regions: the 785-1 G to T mutation in an Israeli-Druze and a Peruvian patient. A polymorphism in exon 6, Gly168Gly, was found in 15 probands. One typical Laron patient from Greece was heterozygous for R43X in exon 4 and heterozygous for Gly168Gly. In addition, a novel mutation in exon 5: substitution of T to G replacing tyrosine 86 for aspartic acid (Y86D) is described.

Conclusions: This study demonstrates: a) an increased focal incidence of Laron syndrome in different ethnic groups from our area with a high incidence of consanguinity; and b) a relationship between molecular defects of the GH-R, ethnic group and geographic area.

The management of uncontrolled bleeding in trauma patients is difficult in the prehospital setting, especially when transfer time to a care facility is prolonged. The goal of treatment is to stabilize the patient until surgery can be performed. In modern practice, the major aspects of optimal patient stabilization are the timing and volume of resuscitation and the use of blood products. The main problems are the logistics of handling the blood products as well as achieving the appropriate endpoint or resuscitation, while balancing the need to maintain blood pressure with the need to avoid deleterious coagulopathy. This work reviews current therapeutic modalities for prehospital management of uncontrolled bleeding trauma patients, namely low volume resuscitation, packed red blood cells, hemoglobin solutions, perfluorocarbons, hypertonic saline solutions, and recombinant activated factor VII.

Background: Splanchnic nerve stimulation evokes adrenomedullary catecholamine secretion via acetylcholine release and occupation of nicotinic cholinergic receptors on chromaffin cells.

Objectives: To assess whether among cultured adrenomedullary cells there exists a population that tonically secretes acetylcholine. If so, then blockade of enzymatic breakdown of acetylcholine by addition of a cholinesterase inhibitor to the medium would increase occupation of nicotinic receptors by endogenous acetylcholine and thereby induce catecholamine release.

Methods: Primary cultures of bovine adrenomedullary cells in 24-well plates (1 million cells per well) were incubated after 48–72 hours with fresh incubation medium (control), medium with added secretagogues (nicotine, angiotensin II, or K+) or the acetylcholinesterase inhibitor, edrophonium (10-7 to 10-³ M), for 1–20 minutes. Fractional release rates of epinephrine, norepinephrine and dopamine were compared to a control. We also examined whether co-incubation with edrophonium enhanced the effects of the secretagogues. All experiments were performed in quadruplicate and repeated three times.

Results: Nicotine, angiotensin II, and K+ each elicited time-related release of epinephrine, norepinephrine and dopamine by up to fourfold compared to the control. At all tested concentrations, edrophonium had no such effect. Co-incubation with edrophonium also failed to augment the secretory responses to nicotine, angiotensin II, or K+.

Conclusion: Bovine adrenomedullary cells in primary culture do not include a population of tonically active cholinergic cells.

The ubiquitin-proteasome pathway has a central role in selective degradation of intracellular proteins. Among the key proteins degraded by the system are those involved in the control of inflammation, cell cycle regulation and gene expression. With numerous important cellular pathways affected, derangements in the ubiquitin system were shown to result in a variety of human diseases including malignancies, neurodegenerative diseases and hereditary syndromes, and proteasome inhibition was implicated as a potential treatment for cancer and inflammatory conditions. Two proteasome inhibitors are currently under clinical evaluation for multiple myeloma and acute ischemic stroke. The ubiquitin system also has an important function in the immune and inflammatory response. It is involved in antigen processing and presentation to cytotoxic T cells, and the activation of nuclear factor-kappa B – the central transcription factor of the immune system. Since the proteasome is the central source of antigenic peptides that are presented to the immune system, some viruses, such as the Epstein-Barr virus, developed escape mechanisms that manipulate the ubiquitin-proteasome system in order to persist in the infected host. Understanding the mechanisms underlying the production of viral antigens by the ubiquitin-proteasome system may have therapeutic applications such as future development of vaccines.

Background: Dysphagia is a common disorder among the elderly population. As many as 50% of nursing home residents suffer from dysphagia. It is important to identify patients at increased risk for colonization of dental and denture plaque by pathogenic organisms for prevention of associated disease.

Objectives: To quantify the prevalence and evaluate the effect of dental and denture plaque colonization by Candida albicans in hospitalized elderly dysphagic patients as a complication of stroke, as well as the effect of systemic antimicrobial therapy on C. albicans colonization in these patients.

Methods: We evaluated dysphagia and antibiotic therapy as risk factors for dental and denture plaque colonization by C. albicans in elderly stroke rehabilitating patients with dysphagia, as compared to elderly non-dysphagic stroke and non-stroke rehabilitating patients on days 0, 7 and 14 following admission to the Fliman Geriatric Rehabilitation Hospital.

Results: The risk of C. albicans colonization of dental plaque was greater in dysphagic patients than in those without dysphagia on day 0 (50% vs. 21%, P = 0.076), day 7 (58 vs. 15.2%, P = 0.008) and day 14 (58 vs. 15.2%, P = 0.08). Similarly, patients on antibiotic therapy were at greater risk for C. albicans colonization of dental plaque on day 0 (56 vs. 11%, P = 0.002), day 7 (44 vs. 14.8%, P = 0.04) and day 14 (39 vs. 19%, P = 0.18). The risk of C. albicans colonization of denture plaque as opposed to dental plaques in non-dysphagic patients was significantly greater on day 0 (45.7 vs. 21.2%, P = 0.03), day 7 (51.4 vs. 15.1%, P = 0.0016) and day 14 (54.3 vs. 15.1%, P = 0.0007). Dysphagia did not increase the risk of denture plaque colonization by C. albicans.

Conclusiona: Both dysphagia and antibiotic therapy are risk factors for C. albicans colonization of dental plaque, and although dysphagia does not significantly increase colonization of denture plaque, denture wearers are at greater risk of such colonization.