Israel Medical Association Journal

Background: Infectious agents are important in the pathogenesis of autoimmune disease since they are a major part of the environmental trigger of autoimmunity. A negative relationship between latitude and infectious disease species richness has been suggested.

Objectives: To examine whether their prevalence differs in two latitudinally different populations.

Methods: The prevalence of infections with Toxoplasma gondii, rubella virus, cytomegalovirus, Epstein-Barr virus and Treponema pallidum was compared between subjects from Italy and Colombia.

Results: We found high titers of antibodies against four of five microorganisms tested, Toxoplasma gondii (50.8%), rubella virus (German measles) (75%), cytomegalovirus (86.3%), Epstein-Barr virus (83.3%) and Treponema pallidum (6.3%) in completely healthy individuals from a tropical country (Colombia) and a European country (Italy). Differences between two groups of volunteers were noted regarding two infectious agents. The prevalence of immunoglobulin G anti-rubella antibodies was significantly higher among Italian subjects (85% vs. 67.9%, P = 0.002), whereas antibodies against CMV[1] were less prevalent among Italian as compared to Colombian subjects (77% vs. 92.9%, P < 0.001).

Conclusions: These differences might also result in a different tendency towards development of autoimmune diseases associated with these infectious agents in different populations.

Background: The Muslim Circassians in Israel represent a unique ethnic community, distinct from Jews and Arabs. This endogamous group has a limited genetic variability that allows studying risk factors associated with type 2 diabetes.

Objectives: To estimate the prevalence of type 2 diabetes among Israeli Circassians and its correlation to obesity and genetic susceptibility.

Methods: Israeli Circassian women (n=450) and men (n=289) older than 35 were included in the study. They were classified as having or not having diabetes, and their risk factors, including hypertension, body mass index, family history of diabetes, and laboratory tests, were examined retrospectively.

Results: The age-adjusted prevalence of diabetes among the 739 participants was 12% (men 14.6%, women 10.7%). It was higher among those with BMI[1] > 30 than in those with lower BMI and a family history of diabetes without high BMI. But the risk of diabetes with BMI > 30 plus a family history was three times higher than when these factors were missing (odds ratio 2.96, 95% confidence interval 1.30–6.6). Multivariate analysis, however, found familial history of diabetes to be the strongest risk factor, independent of obesity (OR[2] 2.47, 95% CI[3] 1.45–4.20).

Conclusions: The results yielded by this homogeneous Circassian population, sharing the same environmental influences and having an endogamous pattern of marriage, suggest a role of genetic risk factors for diabetes. Israeli Circassians are suitable for additional genetic studies that may lead to the identification of susceptibility genes for type 2 diabetes.

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: Spinal dural arteriovenous fistulae comprise the majority of spinal vascular malformations. The most common clinical presentation is that of progressive myelor­adicuiopathy, probably related to venous hypertension, which may lead to permanent disability and even death.

Objective: To report our clinical experience with spinal dural arteriovenous fistulae.

Methods: Nine patients with spinal dural AVF were managed at our center during a one year period (1998-1999). The patients, eight men and one woman ranging in age from 46 to 75 years, presented with initially fluctuating and eventually permanent and progressive paraparesis, sensory disturbances and sphincter dysfunction. The neurological signs generally began symmetrically and progressed from the distal to proximal limb regions. The duration of symptoms before diagnosis ranged from 6 to 36 months during which the patients underwent an extensive but fruitless work-up and even unnecessary operations due to misdiagnosis. All patients finally underwent magnetic resonance imaging and spinal angiography, which demonstrated the pathological vascular fistula. Interruption of the AVF was achieved by embolization or by surgical resection.

Results: Following treatment, six patients experienced improvement of gait and sphincter control, and the severe neurological deficits stabilized in the other three patients with long duration of illness. There was no further deterioration in any of the treated patients.

Conclusions: The history, neurological findings and radiological changes on MRI scan should alert clinicians to the possibility of spinal dural AVF, leading to diagnostic spinal angiography. Early diagnosis and treatment may significantly improve outcome and prevent permanent disability and even mortality.