Tumoral calcinosis simulating osteomyelitis

A case of tumoral calcinosis simulating osteomyelitis and associated with bunion formation in a 20-year-old female is presented. The most striking findings in this patient were the soft tissue calcifications. There was no evidence of any of the known causes of heterotopic calcifications. This kind of simulation between tumoral calcinosis bunion formation and osteomyelitis has not been previously described.     

Sham in CAM

Several unique methodological challenges exist concerning the choice of the most appropriate comparator or control group for clinical research in complementary and alternative medicine (CAM). This article reviews the four major types of control groups (active control, placebo or sham, no intervention control, and different protocols of the experimental intervention), noting the different questions they answer and the different contexts in which they may be used, and discusses how this framework may be applied to CAM research in an effort to avoid methodologically flawed study designs. The choice of comparator depends on complex factors such as the research question being asked, the most plausible competing rival hypotheses, and logistical considerations related to ethics, methodology and feasibility. For example, for sham to be an effective comparator it must capture the ‘nonspecific’ elements of the treatment without containing those that are ‘specific’ to the research question at hand. However, as demonstrated by the examples of acupuncture and energy medicine, designing such sham intervention is not always easy. Controlling for social interaction between practitioners and subjects, addressing issues around ethics, having good-quality measurement of treatment integrity and intensity, and selecting practitioners of sufficient competence when doing a sham process are other important parts of correct design choices. In the light of these complexities, clinicians and researchers alike need a better match between the research questions and the design employed in order for their research to be both scientifically valid and clinically meaningful.     

Interleukin-2 treatment potentiates induction of oral tolerance in a murine model of autoimmunity.

The present study addresses the feasibility of potentiating oral tolerance by immunomanipulation, using the murine model of experimental autoimmune uveoretinitis (EAU) induced by immunization with the retinal antigen interphotoreceptor retinoid binding protein (IRBP). Three feedings of 0.2 mg IRBP every other day before immunization did not protect against EAU, whereas a similar regimen of five doses was protective. However, supplementing the nonprotective 3x regimen with as little as one injection of 1,000 U of human recombinant interleukin-2 (IL-2) resulted in disease suppression that was equal to that of the protective 5x regimen. The protective effect was maintained across a range of IL-2 doses and times of administration; none of the IL-2 regimens tested resulted in disease enhancement. Peyer's Patch cells of 3x-fed and IL-2-treated mice showed greatly increased production of TGF-beta, IL-4, and IL-10 compared with animals given the nonprotective 3x regimen and to animals given the protective 5x regimen. We propose that IL-2 treatment enhances protection from EAU at least in part by stimulating production of antiinflammatory cytokines by regulatory cells in Payer's Patches. Moreover, the observed lymphokine production patterns suggest that whereas protection induced by the 3x + IL-2 regimen is likely to involve antiinflammatory cytokines, protection induced by the 5x regimen might involve anergy or deletion of the uveitogenic T cells. These results could have practical implications for use of IL-2 as a safe and effective way of potentiating oral tolerance.     

Delayed muscular rigidity and respiratory depression following fentanyl anesthesia

A delayed effect of fentanyl used for anesthesia may be respiratory distress several hours after surgery. The findings are muscular rigidity, fall in chest wall compliance, hypoventilation, respiratory acidosis, and hypotension. In the past, to our knowledge, this complication was exclusively reported in patients undergoing cardiac surgery, when large fentanyl dosages are employed. This article describes three general surgical patients in whom respiratory distress developed three to five hours following colon surgery when a moderate dose of fentanyl citrate, 55 to 75 micrograms/kg, was used. Initially, all patients had a normal recovery from anesthesia. Later, respiratory distress was successfully treated with a fentanyl antagonist and ventilatory assistance. This delayed toxic phenomenon is thought to be due to the reentry of fentanyl into plasma from deposits in adipose tissue, muscle, and the gastrointestinal tract, leading to a secondary rise in the plasma concentration. It is more likely to be encountered when hypothermia, rewarming, and acidosis are present in the postoperative period. This life-threatening complication is treacherous, since it may occur when the patient has been transferred to the surgical ward and is less closely monitored.     

Computed tomographic (CT) demonstration of calcification of the ligamenta flava of the lumbosacral spine associated with protrusion of the intervertebral disc

Axial computed tomographic (CT) scan of the lumbosacral region was performed in 220 patients. The patient population was divided into three groups. The control group included 40 elderly patients without calcification of the ligamenta flava. The second group included 150 patients with posterior protrusion of the intervertebral discs. The third group included 30 patients with spinal stenosis. More than 80% of the patients of the second and the third group had calcification of the ligamenta flava. The diagnostic and practical importance of these findings is discussed.     

Pathological confirmation of cystic fibrosis in the fetus following prenatal diagnosis

Prenatal diagnosis of cystic fibrosis is presently based on the determination of microvillar enzyme activities in the amniotic fluid. However, there seems to be no accurate means for confirming the diagnosis of the aborted fetus. During the past year we performed pathological and histopathological examinations on 7 fetuses diagnosed in the second trimester of pregnancy to be affected by cystic fibrosis and compared them with 4 control age-matched fetuses. Glycol-methacrylate-embedded 2-3-mu thick sections of the pancreas, lungs, bronchial tree, and GI tract were stained with toluidine blue, H&E, PAS, and AB-PAS, and examined microscopically. In the controls, PAS-positive granules were dispersed throughout the cytoplasm of most pancreatic acinar and tracheal submucosal glandular cells. In the affected fetuses 2 distinct groups were identified. In one group of 4 fetuses, the pancreatic and tracheal submucosal glands were dilated and contained a weak PAS-positive material. The glandular epithelial cells had very little PAS-positive granules. In this group, the tracheal epithelium was either atrophic or metaplastic and devoid of microvilli. In the second group of 3 fetuses there was less dilation of the glands, and both pancreatic acinar cells and tracheal submucosal glandular epithelial cells contained few PAS-positive granules, which were confined mainly to a perinuclear location. The tracheal epithelial cells contained few microvilli which, when present, appeared thicker and shorter as compared to controls. We feel that histochemical evaluation of pancreatic and bronchial tissue may be of help in the pathological confirmation of cystic fibrosis in human fetuses where the results of the biochemical studies are suggestive of the disease.     

Males on the life-course-persistent and adolescence-limited antisocial pathways: follow-up at age 26 years

This article reports a comparison on outcomes of 26-year-old males who were defined several years ago in the Dunedin longitudinal study as exhibiting childhood-onset versus adolescent-onset antisocial behavior and who were indistinguishable on delinquent offending in adolescence. Previous studies of these groups in childhood and adolescence showed that childhood-onset delinquents had inadequate parenting, neurocognitive problems, undercontrolled temperament, severe hyperactivity, psychopathic personality traits, and violent behavior. Adolescent-onset delinquents were not distinguished by these features. Here followed to age 26 years, the childhood-onset delinquents were the most elevated on psychopathic personality traits, mental-health problems, substance dependence, numbers of children, financial problems, work problems, and drug-related and violent crime, including violence against women and children. The adolescent-onset delinquents at 26 years were less extreme but elevated on impulsive personality traits, mental-health problems, substance dependence, financial problems, and property offenses. A third group of men who had been aggressive as children but not very delinquent as adolescents emerged as low-level chronic offenders who were anxious, depressed, socially isolated, and had financial and work problems. These findings support the theory of life-course-persistent and adolescence-limited antisocial behavior but also extend it. Findings recommend intervention with all aggressive children and with all delinquent adolescents, to prevent a variety of maladjustments in adult life.     

IL-10 has a protective role in experimental autoimmune uveoretinitis

The role of IL-10 in the regulation of ocular autoimmune disease was studied in experimental autoimmune uveoretinitis (EAU) elicited in mice by immunization with the retinal antigen interphotoreceptor retinoid binding protein. IL-10-deficient mice were susceptible to EAU, indicating that pathogenesis can occur without presence of IL-10. Treatment of normal mice with IL-10 for 5 days after uveitogenic immunization ameliorated subsequent EAU scores, and down-regulated antigen-specific production of tumor necrosis factor-alpha and IFN- gamma. A concomitant treatment with IL-4 further reduced disease, and resulted in emergence of antigen-specific IL-4 and IL-10 production, as well as in enhancement of the IgG1 antibody isotype. IL-4 by itself was not protective. Only IL-10, but not IL-4, was able to inhibit the function of differentiated uveitogenic T cells in culture. Expression of mRNA for Th1 and Th2 cytokines in the eye during the course of EAU showed that while a Th1 pattern predominated early, IL-10 mRNA expression coincided with down-regulation of the Th1 response and resolution of EAU. Systemic neutralization of IL-10 during the expression phase of EAU resulted in elevated disease scores. Our results suggest that endogenous IL-10 limits expression of EAU and may play a role in the natural resolution of disease. The data further suggest that exogenous IL-10 may be useful in therapeutic control of autoimmune uveitis. While IL-10 by itself is sufficient to suppress Th1 effector development and function, a concomitant administration of IL-4 is required to shift the autoimmune response towards a non-pathogenic Th2 pathway.      

Ocular autoimmunity: the price of privilege?

Summary:  The eye is the prototypic immune-privileged organ. Its antigens were once believed to be expressed exclusively in the eye, which resides behind an efficient blood–organ barrier, and were believed to be unknown to the immune system. Self-tolerance to ocular components was therefore believed to be based not on immune tolerance but on immune ignorance. It is now known that the relationship between the immune system and the eye is much more complex. On the one hand, immune privilege is now known to involve not only sequestration but also active mechanisms that (i) inhibit innate and adaptive immune processes within the eye and (ii) shape the response that develops systemically to antigens released from the eye. On the other hand, retinal antigens are found in the thymus and have been shown to shape the eye-specific T-cell repertoire. However, thymic elimination of self-reactive T cells is incomplete, and such 'escapee' T cells are tolerized in the periphery as they recirculate through the body by encounter with self-antigen in healthy tissues. Due to the relative inaccessibility of the healthy eye to the immune system, peripheral tolerance mechanisms may not operate efficiently for ocular antigens, leaving a weak link in the homeostasis of tolerance. The case shall be made that although immune privilege protects vision by keeping the immune system at bay, a potential for developing destructive anti-retinal autoimmunity may be the price for the day-to-day protection afforded by immune privilege against inflammatory insults.