Reduced disease severity following therapeutic treatment with angiotensin 1-7 in a mouse model of multiple sclerosis.

Multiple Sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by autoimmune and neurodegenerative pathologies for which there is no cure and no defined etiology. Although several, modestly effective, disease modifying drugs are available to treat MS, there are presently no treatments that offer neuroprotection and prevent clinical progression. Therapies are needed that control immune homeostasis, prevent disease progression, and stimulate regeneration in the CNS. Components of the renin-angiotensin-system (RAS) have recently been identified as chemical mediators in the CNS and in neurological disease. Here we show the beneficial effect of therapeutic treatment with the Mas receptor agonist and metabolite of the protective arm of RAS, angiotensin 1-7 (A(1-7)), in the experimental autoimmune encephalomyelitis (EAE) animal model of MS. Therapeutic treatment with A(1-7) caused a dose-dependent reduction both in clinical disease severity and progression, and was dependent on Mas receptor activation. Further analysis of the most optimal dose of A(1-7) treatment revealed that the reductions in clinical disease course were associated with decreased immune infiltration and demyelination, axonal loss and oxidative stress in the spinal cord. In addition A(1-7) treatment was also associated with increases in circulating alternatively activated monocytes/macrophages.

Haematological and histopathological findings after ovariectomy in Trypanosoma cruzi infected mice.

The aim of this study was to investigate the influences of ovariectomy on histopathological and hematological parameters during the course of Trypanosoma cruzi infection. Hematological and immunological homeostasis is influenced by gonadal steroid hormones. Ovariectomy exerts profound influences on parasitic diseases including T. cruzi infection through modulation of the host's immune response. Three groups of female Mus musculus were infected with 4000 blood trypomastigotes of the Y strain of T. cruzi. One group was subjected to ovariectomy, another to simulated surgery before the infection, and a third group of unoperated animals were used as controls. Marked differences were detected in the responses of blood and tissue parasites. On day 9, post-infection parasitism was significantly higher in ovariectomized animals (P<0.05). These results were confirmed by histopathological studies, in which ovariectomized animals displayed hearts with higher number of amastigote burdens, increased inflammatory infiltrate, enhanced tissue fibers disorganization and decreased lytic antibody percentage, when compared to their counterparts. On day 9 the hematological changes were more apparent, with a decrease in erythrocytes, platelets and leucocytes for ovariectomized infected animals. Simulated surgery, as a stressful agent, did not cause any imbalance in parasitism or in the hemogram profile. The results confirm the importance of the female steroids in resistance against T. cruzi infection.

Hyperthyroidism and familial hypertrophic cardiomyopathy.

A kindred with a high incidence of hypertrophic cardiomyopathy (HC) was studied to identify the presence of clinical hyperthyroidism. Two and possibly three members with HC had associated hyperthyroidism. In the propositus, clinical, ECG, and vectorcardiographic evidence for HC resolved after treatment of the hyperthyroidism. We hypothesize that the disproportionately high correlation of hyperthyroidism and HC and the resolution found in the propositus after treatment may indicate that antithyroid therapy should be considered in this form of cardiomyopathy.

Increased eosinophil granule proteins in gut lavage fluid from patients with inflammatory bowel disease.

OBJECTIVE: To explore the potential role of eosinophils in the pathogenesis of inflammatory bowel disease (IBD). DESIGN: We measured the concentrations of eosinophil granule proteins-namely, major basic protein, eosinophil peroxidase, eosinophil cationic protein, and eosinophil-derived neurotoxin-in gut lavage fluid. MATERIAL AND METHODS: Ten healthy persons and 17 patients with IBD (9 with Crohn's disease and 8 with ulcerative colitis) underwent gut lavage. Each study subject submitted an early specimen when lavage effluent became liquid and a late specimen when the output became clear. The concentrations of the granule proteins were measured by immunoassay. RESULTS: The median concentrations of eosinophil-derived neurotoxin and eosinophil cationic protein were significantly higher in patients with IBD than in control subjects for both early and late lavage specimens. Excretion of eosinophil peroxidase was also significantly higher in patients with IBD than in the healthy control subjects, but only in the early specimens. No differences were noted in the concentrations of any of the proteins between patients with ulcerative colitis and those with Crohn's disease. CONCLUSION: Concentrations of eosinophil granule proteins were increased in whole gut lavage fluid from patients with IBD in comparison with healthy control subjects. These results encourage further studies of the role of eosinophils in the pathogenesis of IBD.

Objective autorefraction in posterior chamber pseudophakia.

Automated refraction with the Canon RK-1 Autoref keratometer was evaluated in 110 eyes (110 patients) six to eight weeks after they had undergone extracapsular cataract extraction with posterior chamber intraocular lens implantation and achieved a best corrected visual acuity of at least 6/12. Autorefraction readings were obtained in 100 (91%) of these eyes. The agreement between autorefraction and clinical refraction data was 98% for spherical equivalence less than 0.51 dioptres (D), 95% for sphere power less than 0.51D, 94% for cylinder power less than 0.51D, and 85% for cylinder axis less than 11 degrees. Autorefraction can provide acceptably accurate postoperative refraction values in pseudophakic eyes.

Blindness in schoolchildren: importance of heredity, congenital cataract, and prematurity.

Of 99 children in the Royal Blind School, Edinburgh (which serves Scotland and part of N E England), 15 had optic atrophy (hydrocephalus 4, intracranial haemorrhage 2, prematurity 2, fetal distress 2, birth asphyxia 2, cerebral atrophy 1, cardiac arrest during hernia operation 1, and leukaemia 1). Fourteen had congenital cataract, 12 congenital retinal aplasia (Leber's congenital amaurosis) and 11 retinopathy of prematurity. There were small numbers in many other diagnostic categories, including three with non-accidental head injury. Mental retardation, spasticity, and nystagmus were frequent other correlates in all diagnostic categories. 'Very probably hereditary' was a conservative attribution in 36, while 'probable' seemed appropriate for 12-that is, almost 48% were hereditary. Only about 11 cases might have been prevented through genetic counselling, which testifies to the frequency of autosomal recessive hereditary disease, although no parents were consanguineous.

Posterior synechiae after glaucoma operations: aggravation by shallow anterior chamber and pilocarpine.

Posterior pupillary synechiae affect a proportion of eyes subjected to iridectomy with or without drainage operation because (1) aqueous humour bypasses the pupil; (2) traumatic iridocyclitis occurs; (3) there is immobility of the iris in the iridectomy sector; (4) in eyes with angle closure glaucoma closer apposition of the iris to the anterior lens capsule increases the tendency; (5) pilocarpine aggravates (4) both in angle closure glaucoma and open angle glaucoma and produces a small immobile pupil facilitating pupillary membrane formation (occlusio pupillae). Pilocarpine should be avoided if possible as medical treatment at any time after a drainage operation. A beta blocker is the drug of choice. To eliminate posterior synechiae over a fair number of degrees of pupil (say 30 degrees) sector iridectomy can be done.

Penetration of timolol eye drops into human aqueous humour: the first hour.

Samples of aqueous humour were removed from 26 eyes at the start of cataract extraction. Two drops of timolol 0.5% had been instilled into the conjunctival sac 12-71 minutes before operation. Analysis by gas chromatography showed a mean timolol concentration of 55.46 ng/mg, with a range of 8 to 100 ng/mg.

Probably Norrie's disease due to mutation. Two sporadic sibships of two males each, a necropsy of one case, and, given Norrie's disease, a calculation of the gene mutation frequency.

Two sibships, each with two affected males but no other affected family members, are described. All four patients at birth had small eyes with white masses visible behind clear lenses. Support for a diagnosis of Norrie's disease lies in the probable mental retardation and sudden death of one child and mental retardation in the other in one of the families, and strong support in the sensorineural deafness in one child in the other family. A necropsy was performed on the dead child. Both eyes showed the retinae to be totally non-attached. The optic nerves were thin. If the diagnosis is Norrie's disease (highly probable), the birth of the second affected child in each family supports the postulate of a mutation in the X chromosome of a germ cell of a maternal grandparent or an earlier maternal ancestor, no previous member of the family having been affected. That implies a 50% risk of the disease in future male siblings and a 50% risk of the carrier state in female sibs. When only one child is affected, the explanation could also be a mutation in that individual. Given Norrie's disease, we have calculated a mutation rate of 3.9 per million chromosomes in the Scottish population--remarkably similar to the mutation rates calculated for many dominant diseases. A diagnosis of autosomal recessive non-attachment of retina implies a 25% risk to later siblings.

Chicken-embryo fibroblasts produce two types of interferon upon stimulation with Newcastle disease virus.

Controversy has long surrounded the question of whether chickens, like mammals, can produce two types of interferon (IFN). Recently, type-I and type-II chicken IFNs have been cloned. Our study focuses on the further characterization of native fibroblast and spleen IFNs and shows that chicken embryo fibroblasts (CEFs) produce a mixture of type-I and type-II IFNs. IFN was purified by three different methods, controlled pore-glass chromatography, ion-exchange chromatography and preparative SDS-PAGE. Three protein bands showing IFN-like anti-viral activity, from CEFs which had been virus-stimulated for IFN production, were detected at 25, 27 and 29 kDa. Polyclonal antibodies produced against these bands showed partial cross-reaction with purified media from mitogen-stimulated spleen cells in ELISA, western blot analysis and anti-viral activity neutralization assay. Differences between purified conditioned media from CEF and spleen were found with respect to the stimulation of macrophages for nitric oxide production, pH stability and signal transduction pathways; only CEF IFN activated the IFN-stimulated gene factor-3 complex, whereas both CEF and spleen IFNs activated the IFN regulatory factor-1 gene. These findings concur with the differences that are known to exist between mammalian type-I and type-II IFNs. Attempts at sequencing the 25 and 27 kDa proteins by Edman degradation yielded evidence of N-terminal blockage.

Evaluation of a new dressing in the treatment of sports-related skin lesions.

Twenty-seven players with superficial wounds (abrasions, turf burns, and blisters) were treated with a new Hydroactive dressing. We conclude that this dressing provides an excellent alternative to other forms of treatment since it is easy to use, comfortable, hypoallergenic, and provides impressive healing results.

[Xenodiagnosis, hemoculture and the complement mediated lysis test, as criteria in selecting chronic chagasic patients for chemotherapy]. / Xenodiagnóstico, hemocultura e teste de lise mediada pelo complemento, como critérios de seleção de pacientes chagásicos crônicos para quimioterapia.

Normally specific treatment of chronic Chagas' disease begins only after a positive parasitological diagnosis has been established. Xenodiagnosis, hemoculture and complement mediated lysis were associated, and repeated, as an attempt to increase the number of selected candidates for specific treatment. Thirty six chronic chagasic patients were submitted to two series of the above tests, with a minimal interval of 60 days. In the first series of tests sensitivity of xenodiagnosis and hemoculture were 30.5% and 8.3% respectively. Processing of a second sample increased sensitivity to 36.1% (xenodiagnosis) and 19.4% (hemoculture); 47.2% were shown to be positive by at least one of these tests. From the positive cases, 29.4% were consistently negative in the complement mediated lysis test, and 17.6% exhibited discordant results, positive on one occasion and negative on the other. Among patients with negative parasitological tests, 47.4% had negative complement mediated lysis tests, 31.5% exhibited discordant results and 15.8% were positive. We conclude that complement mediated lysis test is not a method of choice in the selection of candidates for specific treatment of Chagas' disease in view of the observed variability of results. At this moment, parasitological test, in spite of a low sensitivity, are a safer tool for the clinician.

Effect of native chicken interferon on MDV replication.

Marek's disease virus (MDV) is an oncogenic alphaherpesvirus. Its specific phosphorylated protein, pp38 has been implicated in MDV oncogenesis. In order to check whether the known anti-viral or anti-proliferative actions of interferon (IFN) are of importance in Marek's disease (MD), chicken embryo fibroblasts (CEFs) were infected with attenuated serotype-1 MDV strain CVI988, or with herpesvirus of turkeys (HVT). Different concentrations of native chicken IFN were added to the cell cultures, prior to their infection. After incubation, MDV plaques were counted. Analysis by flow cytometry for pp38 expression was performed by using three monoclonal antibodies (MAbs) and for HVT by using an anti-glycoprotein B (gB) MAb. Increasing IFN quantities caused a reduction in a stepwise manner of plaque numbers as well as a suppression of pp38 and gB expression in the CVI988- and HVT-infected cells, respectively.

Sportsmedicine forum.

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The disabled athlete: an approach.

Treatment of the disabled athlete should allow the athlete to maximize his remaining abilities and perform at his highest level. The emotional and psychological benefits to the athlete are tremendous, as the athlete will have a greater feeling of self-esteem.

Sudden sinus slowing with junctional escape: a common mode of initiation of juvenile supraventricular tachycardia.

After noting bradycardia-induced supraventricular tachycardia (SVT) in two successive children with SVT, we analyzed Holter monitor recordings done on 66 children with suspected or proved SVT. Ten children had apparent reentry SVT. The most common mode of initiation (eight of 10 patients) was not premature atrial beats, but sudden sinus pause with a junctional escape beat (JEB), usually fused with the delayed sinus P wave, initiating the tachycardia. Electrophysiologic studies in five children who had this mode of initiation showed evidence of reentry in four, possibly by dual atrioventricular nodal (AVN) pathways. Since sudden sinus pause and JEB are relatively uncommon in adults, the disappearance of this phenomenon with age may be the most significant reason why children often have less tachyarrhythmia as they get older. Both propranolol and digoxin significantly increased the numbers of episodes of SVT in the three patients tested with serial Holter monitoring.

Sudden death in infants with chaotic atrial rhythm.

In four cases of chaotic atrial rhythm in infancy, three infants died, two unexpectedly. Chaotic atrial rhythm may be associated with a relatively high mortality in the first year of life.