Optic neuritis: A mechanistic view

Acute demyelinating optic neuritis is a condition of the optic nerves characterized by inflammation, demyelination, and neurodegeneration. Optic neuritis is a relatively common demyelinating event, strongly associated with multiple sclerosis. A number of clinical, radiographic, retinal imaging, and electrophysiologic techniques have provided significant insight into the pathologic and pathophysiologic mechanisms of optic neuritis and its related disorder multiple sclerosis. The development of validated biomarkers within the anterior visual system has paved the way for novel investigations aimed at characterizing the processes of axonal loss and neurodegeneration, neuroprotection, and perhaps even neurorestoration strategies.     

Functional abnormalities of heparan sulfate in mucopolysaccharidosis-I are associated with defective biologic activity of FGF-2 on human multipotent progenitor cells

In mucopolysaccharidosis-I (MPS-I), alpha-L-iduronidase deficiency leads to progressive heparan sulfate (HS) and dermatan sulfate (DS) glycosaminoglycan (GAG) accumulation. The functional consequences of these accumulated molecules are unknown. HS critically influences tissue morphogenesis by binding to and modulating the activity of several cytokines (eg, fibroblast growth factors [FGFs]) involved in developmental patterning. We recently isolated a multipotent progenitor cell from postnatal human bone marrow, which differentiates into cells of all 3 embryonic lineages. The availability of multipotent progenitor cells from healthy volunteers and patients with MPS-I (Hurler syndrome) provides a unique opportunity to directly examine the functional effects of abnormal HS on cytokine-mediated stem-cell proliferation and survival. We demonstrate here that abnormally sulfated HS in Hurler multipotent progenitor cells perturb critical FGF-2-FGFR1-HS interactions, resulting in defective FGF-2-induced proliferation and survival of Hurler multipotent progenitor cells. Both the mitogenic and survival-promoting activities of FGF-2 were restored by substitution of Hurler HS by normal HS. This perturbation of critical HS-cytokine receptor interactions may represent a mechanism by which accumulated HS contributes to the developmental pathophysiology of Hurler syndrome. Similar mechanisms may operate in the pathogenesis of other diseases where structurally abnormal GAGs accumulate.     

Health behaviors and their determinants in multiethnic, active Israeli seniors

To assess factors that affect the adoption of healthy lifestyles among a variety of active Israeli seniors, a survey was conducted in 2002 at the Peiluyada, a physical activity-oriented health fair for seniors held annually in Israel from 1995 to 2002. A multi-language, self-administered questionnaire, assessing predisposing factors, barriers and health-protective behaviors, was fielded to potential participants. Response rate at the event was 51%. Hebrew and Arabic speakers generally characterized their health as good to very good, while Russian speakers' health was rated only poor to fair. Over 80% engaged in regular physical activity, were satisfied with their diet, and conformed to international nutritional recommendations. Vaccination coverage against influenza (81%) and pneumocccocus (58%) was highest among Arabic speakers, and lowest among Russian speakers (33.5% and 12%, respectively). Higher age (> or =75 years) was significantly associated with receiving a vaccination against influenza. Major barriers to exercise included low motivation and poor physical health or disability. Health-related dietary restrictions were the leading nutritional barrier. Prominent barriers to vaccination included concerns about vaccine effectiveness (39%) and side effects (29%). Leading cues to action were a recommendation from one's doctor (67%) and from a healthcare worker (51%).     

Vaginal Delivery After Ileal Pouch-Anal Anastomosis: A Word of Caution

PURPOSE This study was designed to evaluate the impact of childbirth on anal sphincter integrity and function, functional outcome, and quality of life in females with restorative proctocolectomy and ileal pouch-anal anastomosis.METHODS The patients who had at least one live birth after ileal pouch-anal anastomosis were asked to return for a comprehensive assessment. They were asked to complete the following questionnaires: the Short Form-36, Cleveland Global Quality of Life scale, American Society of Colorectal Surgeons fecal incontinence severity index, and time trade-off method. Additionally, anal sphincter integrity (endosonography) and manometric pressures were measured by a medical physician blinded to the delivery technique. Anal sphincter physiology also was evaluated with electromyography and pudendal nerve function by nerve terminal motor latency technique.RESULTS Of 110 eligible females who had at least one live birth after ileal pouch-anal anastomosis, 57 participated in the study by returning for clinical evaluation to the clinic and 25 others by returning the quality of life and functional outcome questionnaires. Patients were classified into two groups: patients who had only cesarean section delivery after ileal pouch-anal anastomosis (n = 62) and patients who had at least one vaginal delivery after ileal pouch-anal anastomosis (n = 20). The mean follow-up from the date of the most recent delivery was 4.9 years. The vaginal delivery group had significantly higher incidence of an anterior sphincter defect by anal endosonography (50 percent) vs. cesarean section delivery group (13 percent; P = 0.012). The mean squeeze anal pressure was significantly higher in the patients who had only cesarean section delivery (150 mmHg) after restorative proctocolectomy than patients who had at least one vaginal delivery (120 mmHg) after restorative proctocolectomy (P = 0.049). Quality of life evaluated by time trade-off method also was significantly better in the cesarean section delivery group (1) vs. vaginal delivery group (0.9; P < 0.001).CONCLUSIONS The risk of the sphincter injury and quality of life measured by time trade-off method are significantly worse after vaginal delivery compared with cesarean section in patients with ileal pouch-anal anastomosis. In the short-term, this does not seem to substantially influence pouch function or quality of life; however, the long-term effects remain unknown, thus obstetric concern may not be the only factor dictating the type of delivery in this group of patients. A planned cesarean section may eliminate these potential and factual concerns in ileal pouch-anal anastomosis patients.Podium presentation at the meeting of The American Society of Colon and Rectal Surgeons, Dallas, Texas, May 8 to 13, 2004.     

Inflammatory mediators are induced by dietary glycotoxins,a major risk factor for diabetic angiopathy

Diet is a major environmental source of proinflammatory AGEs (heat-generated advanced glycation end products); its impact in humans remains unclear. We explored the effects of two equivalent diets, one regular (high AGE, H-AGE) and the other with 5-fold lower AGE (L-AGE) content on inflammatory mediators of 24 diabetic subjects: 11 in a 2-week crossover and 13 in a 6-week study. After 2 weeks on H-AGE, serum AGEs increased by 64.5% (P = 0.02) and on L-AGE decreased by 30% (P = 0.02). The mononuclear cell tumor necrosis factor-alphabeta-actin mRNA ratio was 1.4 +/- 0.5 on H-AGE and 0.9 +/- 0.5 on L-AGE (P = 0.05), whereas serum vascular adhesion molecule-1 was 1,108 +/- 429 and 698 +/- 347 ngml (P = 0.01) on L- and H-AGE, respectively. After 6 weeks, peripheral blood mononuclear cell tumor necrosis factor-alpha rose by 86.3% (P = 0.006) and declined by 20% (P, not significant) on H- or L-AGE diet, respectively; C-reactive protein increased by 35% on H-AGE and decreased by 20% on L-AGE (P = 0.014), and vascular adhesion molecule-1 declined by 20% on L-AGE (P < 0.01) and increased by 4% on H-AGE. Serum AGEs were increased by 28.2% on H-AGE (P = 0.06) and reduced by 40% on L-AGE (P = 0.02), whereas AGE low density lipoprotein was increased by 32% on H-AGE and reduced by 33% on L-AGE diet (P < 0.05). Thus in diabetes, environmental (dietary) AGEs promote inflammatory mediators, leading to tissue injury. Restriction of dietary AGEs suppresses these effects.     

Diagnostic and prognostic significance of cardiovascular magnetic resonance native myocardial T1 mapping in patients with pulmonary hypertension

Background

Native T1 may be a sensitive, contrast-free, non-invasive cardiovascular magnetic resonance (CMR) marker of myocardial tissue changes in patients with pulmonary artery hypertension. However, the diagnostic and prognostic value of native T1 mapping in this patient group has not been fully explored. The aim of this work was to determine whether elevation of native T1 in myocardial tissue in pulmonary hypertension: (a) varies according to pulmonary hypertension subtype; (b) has prognostic value and (c) is associated with ventricular function and interaction.

Methods

Data were retrospectively collected from a total of 490 consecutive patients during their clinical 1.5 T CMR assessment at a pulmonary hypertension referral centre in 2015. Three hundred sixty-nine patients had pulmonary hypertension [58?±?15 years; 66% female], an additional 39 had pulmonary hypertension due to left heart disease [68?±?13 years; 60% female], 82 patients did not have pulmonary hypertension [55?±?18; 68% female]. Twenty five healthy subjects were also recruited [58 ±4 years); 51% female]. T1 mapping was performed with a MOdified Look-Locker Inversion Recovery (MOLLI) sequence. T1 prognostic value in patients with pulmonary arterial hypertension was assessed using multivariate Cox proportional hazards regression analysis.

Results

Patients with pulmonary artery hypertension had elevated T1 in the right ventricular (RV) insertion point (pulmonary hypertension patients: T1?=?1060?±?90 ms; No pulmonary hypertension patients: T1?=?1020?±?80 ms p <?0.001; healthy subjects T1?=?940?±?50 ms p <?0.001) with no significant difference between the major pulmonary hypertension subtypes. The RV insertion point was the most successful T1 region for discriminating patients with pulmonary hypertension from healthy subjects (area under the curve?=?0.863) however it could not accurately discriminate between patients with and without pulmonary hypertension (area under the curve?=?0.654). T1 metrics did not contribute to prediction of overall mortality (septal: p =?0.552; RV insertion point: p =?0.688; left ventricular free wall: p =?0.258). Systolic interventricular septal angle was a significant predictor of T1 in patients with pulmonary hypertension (p <?0.001).

Conclusions

Elevated myocardial native T1 was found to a similar extent in pulmonary hypertension patient subgroups and is independently associated with increased interventricular septal angle. Native T1 mapping may not be of additive value in the diagnostic or prognostic evaluation of patients with pulmonary artery hypertension.