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Biomedical subjects

Yaniv Sherer

Publications and source records attributed to Yaniv Sherer.

35 records · Page 2Linked to original sources

The maintenance of wakefulness test as a predictor of alertness in aircrew members with idiopathic hypersomnia.

Aviators are required to maintain a high level of alertness during their missions. Two conditions that may disrupt this alertness are fatigue and hypersomnia. Fatigue is a physiological state, while hypersomnia is a pathologic state, also termed excessive daytime sleepiness (EDS), which is manifested by the tendency to fall asleep in inappropriate places or situations, such as during flight or driving. Hypersomnolence may be diagnosed by subjective measurements, such as the Epworth sleepiness scale, but the diagnosis is established by two objective tests: the Multiple Sleep Latency Test (MSLT) and the Maintenance of Wakefulness Test (MWT). The first consists of four 20-min sessions used to determine the time it takes the patient to fall asleep when given the opportunity and is considered positive when the sleep latency time is shorter than 5 min, although some authors use 8 min as the cut-off for the diagnosis. The Maintenance of Wakefulness Test (MWT) consists of four 40-min sessions during which the patient attempts to maintain wakefulness while seated in a dark, quiet room during the day. Herein we report 2 cases of aviators who were returned to flying duty despite a pathologic MSLT. These aviators were waivered based on a normal MWT and safety history obtained from their commanders.

Adult↗

Arrhythmogenic right ventricular dysplasia: a possible cause of sudden incapacitation.

Arrhythmogenic right ventricular dysplasia (ARVD) is an important cause of sudden death in the young. The classic presentation is with sustained ventricular tachycardia, with an electrocardiographic pattern of a left bundle branch block, but a proportion of the patients may present as sudden cardiac death. Establishing the diagnosis in aviators may be particularly important since it may prevent sudden incapacitation. We present a case of an aviator with ARVD, in whom the diagnosis was delayed despite an abnormal ECG pattern witnessed over 20 yr. The aviator presented with symptomatic sustained ventricular tachycardia at the age of 46 after nearly 3 decades of active flight duty as a rotary wing pilot in the Israeli air force. This case illustrates the potential of ARVD to result in in-flight incapacitation and emphasizes the need to establish the diagnosis early, particularly in aviators.

Arrhythmogenic Right Ventricular Dysplasia↗

Acute cerebellar vertigo in a fighter pilot.

Vertigo is a frequently encountered complaint among aviators. This complaint is usually labyrinthine in origin. We present a case of a combat jet fighter pilot who experienced a vertiginous episode during flight that nearly resulted in a mishap. Work-up revealed a dissecting aneurysm of the posterior inferior cerebellar artery. Coiling of the aneurysm was performed. This case emphasizes the importance of performing a complete vestibular evaluation in aviators with acute vertigo. Since central nervous system causes may be responsible for vertiginous events, and when undiagnosed may result in a recurrence during flight, magnetic resonance scanning should be considered in those with no obvious peripheral cause for their vertigo.

Acute Disease↗

Oral drug therapy for erectile dysfunction: overview and aeromedical implications.

Approximately 150 million men worldwide experience erectile dysfunction, whereby they are unable to maintain an erection adequate for satisfactory sexual performance. This population is projected to more than double in the next 25 yr. Introduction of the phosphodiesterase inhibitors has revolutionized the management of this common problem, encouraging many more men to seek treatment. The issue of erectile dysfunction treatment is a growing concern in the aviation community as well. This is particularly relevant in civil aviation, as this population is older and has co-morbidities that may contribute to the development of erectile dysfunction. In this article we will review the available options for oral treatment of erectile dysfunction and discuss implications regarding their use in aviators based on the information available in the literature.

Administration, Oral↗

Functional class in patients with heart failure is associated with the development of diabetes.

PURPOSE: Recent reports suggest that decreased functional capacity in patients with heart failure may be associated with abnormalities in glucose metabolism. We followed patients with coronary artery disease who participated in the Bezafibrate Infarction Prevention study to determine the incidence of diabetes by baseline functional status during a 7.7-year follow-up. METHODS: The sample comprised 2616 nondiabetic patients aged 45 to 74 years with a fasting blood glucose level <7 mmol/L (126 mg/dL). They were divided into three groups by New York Heart Association (NYHA) criteria: class I (n = 1986 patients), class II (n = 518), and class III (n = 112). The detection of a fasting blood glucose level > or =7 mmol/L during follow-up was defined as the criterion for the development of diabetes. RESULTS: The study groups had similar demographic and clinical characteristics, except that patients with symptomatic heart failure (NYHA class II or III) were more likely to have angina. During follow-up, diabetes developed in 259 patients (13%) in NYHA class I, 76 (15%) in class II, and 22 (20%) in class III (P for trend = 0.05). At the last visit, patients in NYHA class III were twice as likely (17% [n = 19]) to have fasting blood glucose levels > or =7 mmol/L as those in NYHA class I (7.8% [n = 154]) or class II (8.7% [n = 45]) (P = 0.005). In a multivariate analysis, NYHA class III was associated with a 1.7-fold (95% confidence interval [CI]: 1.1 to 2.6) increase in the rate of development of diabetes, but NYHA class II was not (hazard ratio = 1.0; 95% CI: 0.8 to 1.3). CONCLUSION: Among patients with coronary artery disease, advanced heart failure (NYHA class III) is associated with a significantly increased risk of developing diabetes during a 6- to 9-year follow-up.

Age Distribution↗

Multiple autoantibodies associated with autoimmune reproductive failure.

PURPOSE: Autoimmune factors are involved in some of the cases of reproductive failure. The aim of this paper is to discuss the association between autoantibodies and reproductive failure. METHODS: Literature review of autoantibodies associated with reproductive failure. RESULTS: Several autoantibodies were found in association with such clinical manifestations, mainly in patients having systemic lupus erythematosus or the antiphospholipid syndrome. These autoantibodies include "classical" antiphospholipid antibodies such as anticardiolipin, anti-beta2-glycoprotein-I, antiphosphatidylserine, and antiphosphatidylethanolamine. There are also some "nonclassical" antiphospholipid antibodies directed to prothrombin, thromboplastin, or mitochondrial antibodies of M5 type, which were also found in patients with reproductive failure. Moreover, animal models as well as some human studies support a role for other autoantibodies in these clinical manifestations including antihyroglobulin, antilaminin-1, anti-corpus luteum, antiprolactin, anti-poly(ADP-ribose), and lymphocytotoxic antibodies. CONCLUSIONS: Even though there is not enough data currently to support a firm association between some of these autoantibodies and reproductive failure, future studies are likely to help us determine and expand the number of autoantibodies screened in these patients.

Abortion, Habitual↗

Antiphospholipid antibodies: are they pro-atherogenic or an epiphenomenon of atherosclerosis?

Antiphospholipid antibodies are the hallmark of the antiphospholipid syndrome which is characterized by thrombosis. There are currently data supporting an association between these autoantibodies and atherosclerosis as well. Human studies suggest that anti-cardiolipin and anti-beta2-glycoprotein-I antibodies are elevated in patients having coronary artery disease compared with controls. Anti-cardiolipin antibodies are also associated with typical chest pain, significant coronary artery stenosis on angiography and prediction of myocardial infarction. Laboratory studies and murine models support the pro-atherogenic role of these autoantibodies, as they are involved in uptake of oxidized LDL into macrophages, and immunization of mice with them results in enhanced atherosclerosis. There is some evidence that high anti-beta2-glycoprotein-I antibodies can present a risk factor for atherosclerosis, but more epidemiological data are required in order to confirm whether the pro-atherogenic properties of anti-phospholipid antibodies signifies an independent risk factor for atherosclerosis and its complications.

Animals↗

Anti-idiotypes to oxidized LDL antibodies in intravenous immunoglobulin preparations--possible immunomodulation of atherosclerosis.

OBJECTIVE: The aim of this study was to examine whether intravenous immunoglobulin (IVIg) preparations contain anti-oxLDL and anti-anti-oxLDL antibodies. BACKGROUND: Oxidized low-density lipoprotein (oxLDL) is one of the major players in atherogenesis. IVIg can reduce atherosclerosis in experimental animal models. METHODS: Six commercial IVIg preparations were tested for the presence of anti-oxLDL antibodies by EIA. Inhibition studies were performed with the different IVIg preparations and IgGs purified from a pool of sera from patients with high anti-oxLDL antibody levels. Absorption assays were carried out to evaluate the presence of anti-idiotypes against anti-oxLDL antibodies in IVIg preparations. RESULTS: IVIg preparations tested had various degrees of reactivity towards oxLDL. Absorption experiments suggested that the reactivity was specific because it could be effectively absorbed by oxLDL and not by an irrelevant antigen PPD. The reactivity was smaller than that observed with the IgG from the pool with high anti-oxLDL antibody levels. Inhibition studies with IVIg demonstrated 20-45% inhibition of anti-oxLDL binding to oxLDL, compared to 76% inhibition by the pool with high anti-oxLDL levels. To investigate the presence of anti-idiotypes against anti-oxLDL antibodies within IVIg, F(ab')2 fragments of IVIg IgG were used to absorb IgG F(ab')2 fragments from the pool of sera with high anti-oxLDL levels. The decreased binding to oxLDL of the absorbed supernatants shows that IgG F(ab')2 fragments of the IVIg preparations had high inhibitory capacities ranging from 65 to 90%. CONCLUSIONS: IVIg preparations contain both anti-oxLDL and anti-anti-oxLDL activity. This finding may explain the immunomodulating effect of IVIg in atherosclerosis.

Adjuvants, Immunologic↗

The pathogenic role of anti-thyroglobulin antibody on pregnancy: evidence from an active immunization model in mice.

BACKGROUND: The presence of antibodies to thyroglobulin (Tg) is associated with fetal loss even in the absence of thyroid dysfunction. The aim of this study was to examine whether active immunization with Tg could elicit anti-Tg autoantibodies and reproductive failure without interfering with thyroid function. METHODS: BALB/c mice that were immunized with human Tg in complete Freund's adjuvant (CFA) or injected with only CFA were studied for the development of antibodies to Tg, T4, dsDNA, ssDNA and cardiolipin. Total T4, free T4 and thyroid-stimulating hormone (TSH) levels were also assessed before and during pregnancy. Percentages of resorbed fetuses (the equivalent to human missed abortion) were compared and autoantibody presence on the placentae and fetuses was examined. RESULTS: Following immunization, high levels of anti-Tg were observed in mice immunized with Tg, compared with mice injected with CFA [0.83 +/- 0.23 versus 0.012 +/- 0.016 respectively; mean +/- SD optical density (OD) at 405 nm; P < 0.001]. The specificity of binding to Tg was confirmed by competition assay. Although total T4 levels were increased in comparison with control mice, this was associated with the presence of antibodies to T4. Indeed, free T4 levels and TSH were similar to control mice. Mice were killed after 14 days of pregnancy. The thyroid function and the histology of the thyroid glands were normal. Increased fetal wastage was found among the Tg-immunized mice compared with the CFA-injected mice (P = 0.04), with lower fetal and placental weights (fetal weights: 194 +/- 4 mg versus 240 +/- 6 mg; placental weights: 105 +/- 2 mg versus 130 +/- 3; P < 0.001 for both). Antibodies to Tg were demonstrated only on the placentae of Tg-immunized mice. CONCLUSION: Immunization with Tg results in the production of Tg antibodies and fetal resorption. These effects occur in the absence of thyroid dysfunction.

Animals↗

Induction of oral tolerance in experimental antiphospholipid syndrome by feeding with polyclonal immunoglobulins.

Intravenous immunoglobulins (IVIG) contain a wide spectrum of anti-idiotypes associated with autoimmune diseases. Since part of these anti-idiotypes may bear an internal image of the eliciting antigen, IVIG might be suitable for induction of oral tolerance. In the current study we attempted to induce tolerance in an experimental model of anti-phospholipid syndrome (APS) by oral administration of IVIG. Naive mice were fed with IVIG, or anti-beta 2GPI-specific anti-idiotypic IVIG(alpha Id). Significantly diminished humoral response was noted in mice IVIG/ IVIG-F(ab')(2)or IVIG(alpha Id)-tolerized mice, accompanied by a significant attenuation of clinical manifestations. The maximal effect was achieved in the mice tolerized before disease induction. Abrogation of T lymphocyte proliferation to beta 2GPI was detected in the mice fed with IVIG prior to beta 2GPI immunization, mediated by TGFbeta and IL-10 secretion. The tolerance induced by IVIG-feeding was nonspecific and could be adoptively transferred to syngeneic mice by CD8alpha (+) cells. These CD8alpha (+) T cells, were found to secrete high levels of TGFbeta and IL-10. In summary, IVIG-induced oral tolerance has a nonspecific immunomodulatory effect in experimental APS, mediated by TGFbeta and IL-10-secreting CD8alpha (+) cells. Our results point to a possible application of IVIG in the induction of oral tolerance against various autoimmune diseases.

Administration, Oral↗

Immunomodulation for treatment and prevention of atherosclerosis.

In recent years, it has become clear that the immune system has a major role in atherosclerosis development and progression. More specifically, atherosclerosis fulfills all four criteria to define a condition as being an autoimmune in nature. This association also suggests that modification of the immune response in atherosclerosis could affect this process. In this review, we summarize different aspects of immunomodulation in atherosclerosis. These include immunosuppression, active immunization, induction of tolerance, administration of intravenous immunoglobulin, gene therapy, cytokine network manipulation and statins.

Animals↗

Autoantibodies to cardiolipin and beta-2-glycoprotein-I in coronary artery disease patients with and without hypertension.

BACKGROUND: Autoantibodies to cardiolipin (aCL) and beta2-glycoprotein-I (beta2GPI) are considered proatherogenic. Elevated levels of both antibodies have been reported in hypertension. Nonetheless, there are no data regarding an association between these autoantibodies and hypertension in coronary artery disease. METHODS: The levels of aCL and anti-beta2GPI antibodies were measured in patients having coronary artery disease with (n = 82) or without (n = 36) hypertension, in association with other major risk factors for coronary artery disease. RESULTS: The levels of aCL and anti-beta2GPI antibodies were (OD at 405 nm) 0.23 +/- 0.14 and 0.22 +/- 0.12 in the normal blood pressure group, as opposed to 0.24 +/- 0.12 and 0.20 +/- 0.12 in the hypertensive group, respectively (p = 0.67; 0.42). No significant difference in either antibody levels was found between hypertensive patients with normal and abnormal blood pressure measurements. The presence of additional risk factors did not affect antibody levels in normotensive patients. However, in the hypertensive group, the presence of smoking was associated with significantly decreased anti-beta2GPI antibody levels, whereas no change was found in aCL. Further, patients who had hypertension, smoking and hypercholesterolemia, had significantly decreased anti-beta2GPI antibody levels compared with patients without any of these risk factors (0.13 +/- 0.04 versus 0.23 +/- 0.13, respectively; p = 0.02). CONCLUSION: Hypertension is not associated with modification of aCL and anti-beta2GPI antibody levels in coronary artery disease patients. However, there are elevated anti-beta2GPI antibody levels in patients without conventional risk factors compared with patients with these risk factors.

Anticoagulants↗

Atherogenesis inhibition induced by magnesium-chloride fortification of drinking water.

Magnesium (Mg) modulates blood lipid levels, atherogenesis, and atherosclerosis in rabbits, when supplemented to diet. We have recently reported that a high concentration (50 g/L) of Mg sulfate fortification of drinking water attenuates atherogenesis in male and female LDL-receptor-deficient mice fed a high-cholesterol diet. The aims of the current study were to examine whether lower concentrations and another Mg salt could also have such an antiatherogenic effect. Thirty male LDL-receptor-deficient mice were divided into three groups (n=10 in each group). The mice received either distilled water or water fortified with 0.83 g or with 8.3 g Mg-chloride per liter. In the first (27 wk) and second (5 wk) stages of the experiment, the mice received normal chow and Western-type diet, respectively. Blood was drawn for determination of plasma Mg, calcium, and lipid levels. The extent of atherosclerotic lesions was determined at the aortic sinus. Magnesium-chloride fortification of drinking water did not result in higher plasma Mg concentrations, whereas a trend toward lower plasma calcium concentrations did not reach statistical significance. Even though plasma lipid levels were similar at the beginning and the end of the study, there were decreased plasma cholesterol and triglyceride levels in the Mg groups after stage I. The atherosclerosis extent at the aortic sinus was significantly decreased in the 8.3-g Mg-chloride/L group (23,437 +/- 10,083 micron2) compared with the control group (65,937 +/- 31,761 microm2). There was also a trend toward lower atherosclerosis extent at the aortic sinus in the 0.83-g Mg-chloride/L group. An additional Mg salt (Mg-chloride) fortification of drinking water is capable of inhibiting atherogenesis in male LDL-receptor-deficient mice. That is done in a lower concentration of Mg than previously reported.

Animals↗

IVIG in autoimmunity and cancer--efficacy versus safety.

Intravenous immunoglobulin (IVIG) is an accepted treatment for certain immunodeficiency states, but also for some autoimmune diseases. In other autoimmune conditions (i.e., systemic lupus erythematosus), it is still empirical although very efficacious. Based mainly on animal studies, IVIG has been shown to exert different antitumour mechanisms that result in metastases suppression. This effective therapy is associated with frequent occurrence of either immediate, delayed or late adverse effects, most of which are mild and transient. Efforts are taken in order to minimise these adverse effects both by pharmaceutical companies that attempt to decrease the risk of infectious agents transmission, and by physicians who monitor closely patients and choose the appropriate mode of administration of IVIG with respect to dose, duration of treatment and preparations used. Overall, IVIG is used in severe medical conditions and it is quite safe. Future research would help to further minimise its associated risks.

Autoimmune Diseases↗