Deriving relative risks from aggregate data. 2. An application to the relationship between unemployment and suicide.

In Part 1 of this study, the mathematical relations between micro and macro measures of effect were derived. The formulas thus obtained can be used for cross level comparisons of findings concerning the effect of some specific risk factor on, eg, mortality. The approach is illustrated by means of an empirical example relating to the association between unemployment and suicide. This relationship is estimated on micro data as well as on aggregate time series data. The findings from the two levels are fairly consistent.     

Local status of the urinary stoma--the relation to peristomal skin complications

Sixty-six patients with uretero-ileostomy were investigated with special regards to local status of the urinary stoma, i.e. stomal site, length, size/shape, and peristomal skin. Each variable was defined. In reports from other centres there has been a lack of definitions making it difficult to compare results from different studies. One fifth of our patients had inadequately located stomas and 85% had stomas shorter than 1 cm. The peristomal skin status was assessed according to CPS, Classification of Peristomal Skin. Eight per cent of the patients exhibited severe erythematous/erosive lesions and one fifth pseudoverrucose lesions. The relation between skin lesions and local status of the urinary stoma was analyzed. Patients with inadequately located stomas were more likely to show severe erythematous/erosive lesions and there was a tendency towards patients with stomas shorter than 1 cm, more frequently exhibiting pseudoverrucose lesions.     

Eosinophil cationic protein is stored in, but not produced by, peripheral blood neutrophils

BACKGROUND: Eosinophil cationic protein (ECP) is an eosinophil-derived protein, which has been shown to be present in circulating neutrophils. OBJECTIVE: To establish whether ECP is produced or internalized by peripheral blood neutrophils. METHODS: This was done using microscopy, flow cytometry, fractionation of cells and RT-PCR techniques. RESULTS: No ECP mRNA was detected after extensive cell purification to eliminate all traces of contaminating eosinophils. Examination of immunostained neutrophils by light, confocal, electron microscopy together with cell fraction experiments, established that ECP is present intracellularly and is mostly associated to cell granules. Uptake studies by flow cytometry and by using both cold and radiolabelled ECP showed that it is internalized by neutrophils and stored in some proportion in their primary granules. Upon stimulation with serum-treated Sephadex particles, the internalized ECP was partially released from cells. CONCLUSION: ECP is not produced but can be internalized by circulating neutrophils, which take it from the environment and partially store it in their primary granules.     

Altered tachykinergic influence on gastric mechanical activity in mdx mice

This study investigated whether alterations in gastric activity in dystrophic mdx mouse can be attributed to dysfunctions of tachykinins. Endoluminal pressure was recorded and the expression of neuronal nitric oxide synthase (nNOS), NK1 and NK2 neurokinin receptors was investigated by immunohistochemistry. SR48968, NK2 receptor antagonist, but not SR140333, NK1 receptor antagonist, decreased the tone only in mdx gastric preparations. In the presence of N(omega)-nitro-l-arginine methyl ester (l-NAME), inhibitor of NOS, SR48968 reduced the tone also in normal stomach. [Sar(9), Met(O(2))(11)]-SP, agonist of NK1 receptors, caused tetrodotoxin-sensitive relaxations, antagonized by SR140333 or l-NAME, with no difference in the potency or efficacy between normal and mdx preparations. [beta-Ala(8)]-NKA(4-10), an NK2 receptor agonist, induced SR48968-sensitive contractions in both types of preparations, although the maximal response of mdx tissues was significantly lower than normal preparations. Immunohistochemistry demonstrated a consistent reduction of nNOS and NK2 receptor expression in mdx stomach smooth muscle cells and no change in nNOS and NK1 receptor expression in neurones. In conclusion, in mdx stomach the activation of NK2 receptors plays a role in the development of the tone, associated with a reduced NO production by muscular nNOS. The hypo-responsiveness to NK2 receptors could depend on the reduced expression of these receptors.     

Crosslinking of fibrinogen and fibronectin by free radicals: a possible initial step in adhesion formation in osteoarthritis of the temporomandibular joint.

PURPOSE: Adhesion formation in osteoarthritis (OA) of the temporomandibular joint (TMJ) typically results in a sustained limitation of joint movement. We propose the hypothesis that free-radical-mediated crosslinking of proteins underlies this adhesion formation in affected joints. Free radicals may cause oxidative modification of proteins, creating an opportunity for the formation of intramolecular and intermolecular crosslinks via covalent bonds. This may stabilize protein aggregates, rendering them more resistant to degradation. In this study, the free-radical-mediated crosslinking of model proteins (fibrinogen and fibronectin) was investigated to test our hypothesis that free radicals contribute to adhesion formation via this mechanism in OA of the TMJ. MATERIALS AND METHODS: Physiological clot formation of fibrinogen by thrombin and free-radical-induced crosslinking of fibrinogen and of fibronectin were analyzed using spectrophotometric turbidity measurements, light-scattering techniques, polyacrylamide gel electrophoresis (PAGE), and rotary shadowing. RESULTS: Fibrinogen was shown to aggregate after free radical treatment, as detected using turbidity measurements and light-scattering techniques. Using PAGE, fibrinogen as well as fibronectin was shown to degrade under low oxidative stress. Under high oxidative stress, however, fragments from both proteins were found to be covalently crosslinked, resulting in high-molecular-weight protein aggregates. The aggregation was shown to be at random with rotary shadowing. CONCLUSION: The study shows that high oxidative stress contributes to the formation of crosslinked proteins that may serve as an initial scaffolding for the development of adhesions frequently seen in OA of the TMJ.     

Opioid peptides and receptors in joint tissues: study in the rat.

Using immunohistochemical and biochemical techniques, the occurrence of endogenous opioid peptides and their receptors in normal rat bone and joint tissues was investigated. Opioid receptors were detected, quantified, and characterized in homogenates from capsule/synovium and periosteum using radioligand binding assays. Receptor binding of the nonselective opioid [3H]naloxone to tissue homogenates was stereospecific and saturable, showing similar characteristics to that of brain tissue, although with lower binding capacities. By immunohistochemistry, the neuronal occurrence of four different enkephalins was demonstrated in synovium, bone marrow, periosteum, and juxta-articular bone, whereas no neuronal dynorphin immunoreactivity was detected. Double-staining studies disclosed that enkephalins coexisted with substance P in primary afferent fibers. The applied techniques can be used to assess changes in the distribution of endogenous opioids and their receptors in joint tissues in conditions associated with pain and inflammation. The endogenous opioid system now demonstrated might be targeted and exploited therapeutically to obtain peripheral control of symptoms in joint disorders.     

Pretransplant herpesvirus serology and acute graft-versus-host disease

Logistic regression was used to analyze the influence of pretransplant herpesvirus antibodies, in both patients and donors, on the development of acute graft-versus-host disease in 111 consecutive HLA-identical bone marrow recipients. In bivariate analysis, recipient seropositivity for cytomegalovirus (P = 0.01), donor seropositivity for herpes simplex virus (P = 0.02), and low bone marrow cell dosage (P less than 0.05) were associated with a high incidence of grade II-IV acute GVHD. In multivariate analysis the P values were P less than 0.05 for a positive recipient CMV serology and P = 0.07 for a positive donor HSV serology. Positive serology for 1-2 herpes-viruses among recipients or donors both resulted in a 12% incidence of grade II-IV acute GVHD. Positive serology for 3-4 herpesviruses among patients or donors resulted in an incidence of 32% and 38% of acute GVHD, respectively (P less than 0.05). It is concluded that recipient and donor pretransplant herpesvirus immunity can be used to calculate the risk of moderate-to-severe acute GVHD.     

Exfoliation syndrome and extracapsular cataract extraction with implantation of posterior chamber lens.

Extracapsular cataract extraction followed by implantation of a one-piece posterior chamber polymethylmethacrylate intraocular lens (IOL) into the capsular bag was performed in 25 eyes with exfoliation syndrome and 20 control eyes. The patients were investigated preoperatively and then 1 day, 1 week, 3, 6 and 12 months after surgery. Preoperatively, maximal pupil dilatation was significantly smaller in eyes with exfoliation syndrome compared to controls. During surgery the incidence of complications such as ruptures of the zonule or posterior lens capsule, were higher in eyes with exfoliation syndrome. Furthermore, postoperative complications, such as fibrinoid reaction anterior to the IOL followed by posterior synechias and cell deposits, were more common in eyes with exfoliation syndrome compared to control eyes. The results imply that compared to control eyes, eyes with exfoliation syndrome are likely to present more complications both during extracapsular cataract extraction with implantation of intraocular lenses and postoperatively.     

Infantile autism—fragile X: Molecular findings support genetic heterogeneity

Twenty-two members of 18 families with autism have been examined for the presence of mutations and abnormal methylation in the FMR-1 region at Xq27.3. All patients fulfilled diagnostic criteria of infantile autism. A characteristic pattern of insertion and methylation were detected after Southern blot analysis in 7 autistic individuals expressing the fragile site at Xq27.3. Normal DNA patterns were observed in 15 autistic boys cytogenetically negative for the fragile site. The results indicate a lack of involvement of the FMR-1 region in infantile autists negative for fragile X expression. © 1992 Wiley-Liss, Inc.     

High-risk AML evidenced by a monoclonal antibody

A monoclonal antibody has been raised against a surface membrane antigen present on leukemic myeloblasts. In 52 consecutive patients with acute myeloid leukemia treated in a standardized fashion with intensive chemotherapy the immunologic subclass with respect to this antigen was correlated to the clinical outcome. We found the expression of this antigen to predict a poor prognosis, when measured as survival of CR-patients and as survival after 1st relapse.