Toxic oil syndrome: a current clinical and epidemiologic summary, including comparisons with the eosinophilia-myalgia syndrome

In the spring and summer of 1981, an epidemic of a new illness now referred to as the toxic oil syndrome occurred in central and northwestern Spain, resulting in some 20,000 cases, 12,000 hospital admissions and greater than 300 deaths in the 1st year of the epidemic. The initial onset of illness was usually acute, and patients presented primarily with a respiratory syndrome involving cough, fever, dyspnea, hypoxemia, pulmonary infiltrates and pleural effusions. While approximately 50% of patients recovered from this acute phase of the illness without apparent sequelae, the remaining patients developed an intermediate or chronic phase, or both, of illness involving severe myalgia, eosinophilia, peripheral nerve damage, sclerodermiform skin lesions, sicca syndrome, alopecia and joint contractures, among other findings. Epidemiologic and analytic chemical studies have clearly linked the toxic oil syndrome to the ingestion of oil mixtures containing rapeseed oil denatured with aniline. However, the precise identity of the etiologic agent within this oil has never been determined. Aniline itself did not cause the illness, but the causal agent may be a reaction product of aniline with some oil component. Although many aspects of disease activity in the involved patients have lessened with time, the ultimate consequences of their disease are not clear and are the subject of ongoing study. The recently described eosinophilia-myalgia syndrome in the United States clinically resembles the toxic oil syndrome.     

Cholinergic response of isolated rat atria to recombinant rat interferon-gamma

Addition of recombinant rat interferon-gamma (IFN-gamma) to beating rat atria decreased the contractile strength in a dose-dependent manner. The effect was specific of IFN-gamma since it was abrogated by monoclonal anti-rat IFN-gamma. It required the activation of the cholinergic system of the heart as inhibition of both nicotinic (10(-7) M hexametonium) and muscarinic cholinoceptors (10(-7) M atropine) prevented the reaction. Hemicholinium (2 x 10(-5) M) and tetrodotoxin (5 x 10(-7) M) also reduced the response. Likewise, IFN-gamma potentiated the action of the muscarinic agonist carbachol. IFN-gamma simulated the biological effect of cholinergic agonists because: (a) it increased cGMP formation; (b) it decreased cAMP formation; and (c) it reduced heart contractility at doses that can be considered physiologic. IFN-gamma also modified the muscarinic receptor by interfering with the binding of the radiolabelled antagonist quinuclidinyl benzilate [( 3H]QNB). It is suggested that IFN-gamma binding to IFN-gamma receptors in the heart may lead to a cholinergic response by interaction of both receptor systems on the surface of atrial cells.     

Prognostic factors of spontaneous expulsion in ureteral lithiasis

Medical treatment, extracorporeal shock wave lithotripsy (ESWL) and ureteroscopy are therapeutic options for ureteral stones. EWSL and endoscopic treatment of ureteral stones have a high success rate. However it has surgical as well as anaesthetic risks. For many patients, a medicinal treatment without invasive procedures is an option. Watchful waiting does not always result in stone clearance and may be associated with recurrent renal colic. The study of the prognostic factors for expulsion and the medical therapy will help us to select candidates for medical expulsive treatment.ObjectivesTo evaluate the characteristics of the stones and the medication administered (alpha blockers, NSAIDs or a combination of both) as predictors of spontaneous passage of the stone.Material and methodsA retrospective observational study of 260 patients with 278 ureteral stones was conducted. Primary endpoint was stone expulsion. Univariate and multivariate analysis were conducted testing the effect of stone location, size and composition, and medication (alpha-blockers, NSAIDs, or combination) on stone clearance.Results34,2% of the stones studied were spontaneously eliminated. Stone location (pelvic ureter, OR= 1,823, p=0,013), size (<5 mm, OR=3,37, p<0,02), and medication (combination of alpha blockers and NSAIDs, OR= 8,70, p<0.001) were predictors of spontaneous clearance. Multivariate analysis confirmed size (p=0,006) and medication (p<0,001) as independent predictive factors. The use of the combination of NSAIDs and alpha-blockers versus observation multiplied times 8,21 (95% CI 3.37–20,01) the possibilities of spontaneous expulsion.ConclusionsSize of stone and medication were confirmed as independent factors for spontaneous expulsion of ureteral stones.     

Increase nitric oxide synthase activity in parotid glands from rats with experimental periodontitis

Oral Diseases (2010) 16 , 801–806 Objective: In this study we investigated the activity of the nitric oxide synthase (NOS) in parotid glands from rats with experimental periodontitis and controls. Methods: Periodontitis was produced by a ligature placed around the cervix of the two lower first molar. Experiments were carried out 22 days after the ligature. Results: Ligation caused an increase in parotid NOS activity. The selective blocker of the inducible isoform of the enzyme partially inhibited its activity in parotid glands from rat with ligature. In controls, the activity was partially inhibited by the antagonists of the selective neural and endothelial isoforms. NOS activity in rats with ligature was cyclic adenosine monophosphate (cAMP)‐dependent while in controls it was calcium‐dependent. Prostaglandin E₂ concentration was increased in parotid gland from rats with ligature. The inhibitor of prostaglandin production, FR 122047, diminished both, prostaglandin production and NOS activity. In rats with ligature unstimulated amylase released is increased. Both, prostaglandin and NOS were involved in the increment of amylase release. Conclusion: It can be concluded that in parotid glands from ligated rats, prostaglandin E₂ production is increased and, through cAMP accumulation, activates the inducible NOS isoform. The increment of nitric oxide production participates in the increase in basal amylase release.     

Experimental models for research and training in renal transplant

An update on aspects and use of different experimental models applied in kidney transplant research is presented . This paper includes qualities, as long as similarities between most frequently used animal models and human clinical standards. Contributions of those models based on microsurgical or laparoscopic techniques are revised. The physiological consequences (hemodynamic, immunologic) of surgical technique (laparoscopy), applied in experimental models as long as non-heart beating organ donor models and organ preservation methods are also reviewed. Finally, an update of those models applied in research in prothocols of either immunosupression or xenotransplant is done.     

Sj?gren autoantibodies modify neonatal cardiac function via M1 muscarinic acetylcholine receptor activation.

Isolated congenital heart block may be associated with primary Sj?gren syndrome. In this work we describe circulating antibodies in the sera of primary Sj?gren syndrome patients that are able to interact with neonatal myocardium by activating muscarinic acetylcholine receptors of M1 subtype. We report on the presence of autoantibodies against the second extracellular loop of human M1 muscarinic acetylcholine receptors in primary Sj?gren syndrome mothers whose children have congenital heart block using a synthetic peptide in indirect immunofluorescence technique. Autoantibodies from primary Sj?gren syndrome patients gave positive image on neonatal atria but not on adult atria slices. The synthetic M1 peptide selectively abrogated indirect immunofluorescence recognition. The primary Sj?gren syndrome-immunoglobulin G also displayed an 'agonist like' activity modifying the intracellular events associated with muscarinic acetylcholine receptor activation. The mechanism appears to occur secondarily to stimulation of phosphoinositides turnover via phospholipase C activation. This, in turn, triggers cascade reactions involving calcium/calmodulin and leads to activation of nitric oxide synthase and soluble guanylate cyclase. All of these effects were selectively blunted by pirenzepine and neutralized by M1 synthetic peptide. These biological effects were not obtained using adult instead of neonatal rat atria and neither occurred with the sera of normal healthy women of childbearing age. It could be concluded that antibodies against neonatal M1 muscarinic acetylcholine receptor may be another serum factor to be considered in the pathophysiology of the development of congenital heart block associated with primary Sj?gren syndrome mothers.