Left main coronary artery stenosis no longer a risk factor for early and late death after coronary artery bypass surgery--an experience covering three decades.

OBJECTIVE: To analyse early and late mortality after coronary artery bypass grafting (CABG) in patients with and without left main coronary artery (LMCA) stenosis during the 30-year period 1970-1999. METHODS: A total of 1888 of 10,647 patients (18%) who underwent a first isolated CABG at the Karolinska Hospital in Stockholm, Sweden, during 1970-1999 had significant left main coronary artery stenosis. The Swedish National Cause of Death Register was used to determine mortality up to five years after the operation. RESULTS: The proportion of patients with LMCA stenosis of all CABG patients increased from 7% during the 1970s to 26% in 1999. During 1970-1984 early mortality was 5.8% in patients with LMCA stenosis compared with 1.5% in patients without LMCA stenosis (odds ratio (OR) 3.7 (95% confidence interval (CI) 1.8-7.6)). The corresponding rates during 1995-1999 were 2.0% versus 2.2% (OR 0.8 (95% CI 0.5-1.5)), respectively. The increased risk of early death in patients with LMCA stenosis was neutralised in males during 1985-1994 and in females during 1995-1999. Five-year survival in males was 88% after operations performed during 1994-1999 compared with 82% after CABG performed during 1970-1984. Five-year mortality, exclusive of early deaths, during 1970-1984 was higher in patients with LMCA stenosis (12.8%) than in those without (8.4%) (relative risk 1.7 (95% CI 1.1-2.5)). An increased risk of late mortality in patients with LMCA stenosis was neutralised in males during 1985-1994 and in females during 1995-1999. CONCLUSIONS: During 1970-1999 there was a decrease of early and five-year mortality in patients with LMCA stenosis after CABG despite increase of patient age and risk factors. There were gender differences so that the risk of death in patients with compared with in those without LMCA stenosis was neutralised in males during 1985-1994 and in females during 1994-1999. The continuous decline of mortality during three decades most likely reflects improvement of the peri- and postoperative management of patients undergoing CABG during this period.     

Australian-German collaborative studies on the immunology of Sarcocystis infections.

This paper reviews a decade of collaborative studies performed between two laboratories in Germany and Australia on the life cycle, pathogenicity and immunology of infections by the cyst-forming sporozoan parasites Sarcocystis spp. in domestic animals. Experimental transmission studies demonstrated that certain parasite species could cause an acute clinical disease in sheep and pigs severely affecting their health, productivity and reproductivity. Despite the high prevalence of infections found in farm animals, few outbreaks of naturally-occurring clinical disease have ever been recorded. Host animals exposed to low levels of infection were found to develop a strong protective immunity against subsequent lethal challenge and clinical disease even though parasites were not completely eliminated nor prevented from further establishment (premunitive immunity rather than sterile immunity). Modern molecular biological techniques are currently being used to examine the parasite antigens and host immune responses involved in the acquisition of the protective immunity.     

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.     

Primary Burkitt Lymphoma of the Chest Wall

IntroductionBurkitt lymphoma (BL) originating in the skin and soft tissue is very rare. To our knowledge, this case of primary sporadic BL presenting as an isolated chest wall mass arising from the soft tissue in an adult may be the first report.Case ReportA previously healthy 33-year-old Caucasian man presented with a 1-month history of a painful lump over the left breast that he initially noticed as a small “pimple-like” lesion in the area. After a week, the skin lesion became larger, erythematous, and painful. At a local hospital, he underwent an incision and drainage procedure for a presumed chest wall abscess. Several days after debridement, a similar lump recurred around the incised area, which rapidly grew in size. He also started experiencing fever and chills for which he was readmitted with a diagnosis of necrotizing chest wall infection. A second debridement with excisional biopsy of the chest wall revealed atypical lymphoid cells, prompting transfer to our institution. Upon transfer, a large, gaping, erythematous and indurated wound with indistinct, thickened borders and extensive edema and necrosis of subcutaneous tissue and musculature of almost the entire left chest wall was noted. No palpable peripheral lymphadenopathy or organomegaly were observed. He underwent minimal debridement and partial excision. The histopathology revealed atypical lymphocytes with prominent nucleoli, deeply basophilic cytoplasm, and abundant lipid vacuoles in a “starry-sky” pattern. The lymphoid population was CD-20 and CD-10 positive, negative for CD-5 and BCL-2, nearly 100% Ki-67 positive, and indeterminate for light chain restriction. Molecular cytogenetic analysis revealed fusion signals with IgH/Myc t(8;14) dual fusion probe, supporting the diagnosis of BL. Staging positron emission tomography (PET)/computed tomography (CT) scan showed a large subcutaneous defect of the left hemithorax involving the dermis, subcutaneous tissue, and musculature, measuring 19.3 × 13.9 × 31.0 cm, with maximal SUV of 9.8 and an average of 6.2. No additional involved sites were seen. The bone marrow biopsy showed minimal involvement by BL and abnormal hybridization pattern for IgH/Myc t(8;14) and Epstein-Barr virus, while the peripheral blood and cerebrospinal fluid showed no involvement. HIV and hepatitis serologies were negative. Three days after surgery, chemotherapy with granulocyte colony-stimulating factor (G-CSF) support was initiated for high-risk disease. He received CODOX-M (intravenous cyclophosphamide, doxorubicin, vincristine, methotrexate; intrathecal cytarabine, methotrexate) as cycle 1 followed by IVAC (intravenous ifosfamide, etoposide, cytarabine; intrathecal methotrexate) with rituximab as cycle 2. He developed tumor lysis without end-organ damage. However, a few days after completion of cycle 2, he developed neutropenic fever and pneumonia, and died in septic shock.DiscussionPrimary chest wall tumors are uncommon. Approximately 50% are malignant, and chest wall lymphoma accounts for < 2%, with extranodal diffuse large B-cell lymphoma being the most common. Primary skin and soft tissue involvement of the chest wall in the absence of detectable lymphadenopathy and visceral disease in an adult by BL has not yet been reported. While there are isolated reports of skin and soft tissue involvement, they were in the setting of immunodeficiency state and were felt to be the result of either iatrogenic tumor seeding after nodal biopsies or local tumor invasion as a manifestation of recurrent disease. This patient's clinical presentation began with the development of an isolated rapidly enlarging chest wall mass that progressed despite surgical debridements.ConclusionThis case illustrates a primary sporadic BL originating in skin and soft tissue in an adult. Whether this case represents a BL that began in the skin and soft tissue and spread to the bone marrow, or began in the bone marrow and spread to the chest wall cannot be determined. The role of tumor debulking procedure is uncertain, although aggressive chemoimmunotherapy with central nervous system (CNS) prophylaxis is warranted as with other BL presentations.     

Characterization of in vitro metabolites of the aryl hydrocarbon receptor ligand 6-formylindolo[3,2-b]carbazole by liquid chromatography-mass spectrometry and NMR.

The tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) exhibits the highest aryl hydrocarbon receptor (AhR) binding affinity reported so far. In different cells, in vitro, both extracts of UV-irradiated tryptophan and the synthesized pure compound FICZ induce a rapid and transient expression of AhR-regulated genes. The transient induction suggests that the biotransformation gene battery induced by AhR activation takes part in a metabolic degradation of the ligand, whereby a low steady-state level is regained. The down-regulation of AhR-regulated gene expression was previously shown to be dependent on cytochrome P450 1A1 (CYP1A1). Metabolism of FICZ generates five major metabolites, which appeared as three peaks (M1-M3) in the high performance liquid chromatography. The aim of the present study was to use rat liver S9 from Aroclor-pretreated rats to produce large enough quantities of FICZ metabolites for structure characterization and to determine their product precursor relationship. NMR analysis of large combined fractions of the metabolites indicated that M3 and M2 contained 2 isomers, respectively. By means of liquid chromatography-mass spectrometry (negative ion electrospray mode) and NMR spectroscopy (by (1)H-NMR, correlation spectroscopy, and nuclear Overhauser effect spectroscopy techniques) five metabolites of FICZ were identified, and their structures were elucidated. The molecular weights of the two M3 isomers were 300 and both M2 and M1 compounds demonstrated molecular weights of 316, corresponding to addition of one (M3) and of two oxygen (M2 and M1), respectively. The structures were assigned as 2- and 8-hydroxy (M3), 2,10- and 4,8-dihydroxy (M2) and 2,8-dihydroxy derivatives of indolo[3,2-b]carbazole-6-carboxaldehyde (6-formylindolo[3,2-b]carbazole).     

Inclusion of a non-immunoglobulin binding protein in two-site ELISA for quantification of human serum proteins without interference by heterophilic serum antibodies

Measurement of human serum molecules with two-site ELISA can be biased by the presence of human heterophilic anti-animal immunoglobulin antibodies (HAIA) that cause false-positive signals by cross-linking the monoclonal (mAb) and/or polyclonal antibodies (pAb) used for the pre- (capture) and post-analyte steps (detection). To evaluate a novel ELISA format designed to avoid interference by HAIA, a target-specific non-immunoglobulin (Ig) affinity protein (affibody) was used to replace one of the antibodies. First, a human IgA-binding affibody (Z(IgA)) selected by phage display technology from a combinatorial library of a single Staphylococcus aureus protein A domain was used. The detection range of IgA standard using an ELISA based on Z(IgA) for capture and goat pAb against IgA (pAb(IgA)) for detection was comparable with that of using pAb(IgA) for both capture and detection. Secondly, another affibody (Z(Apo)) was combined with mAb and used to detect recombinant human apolipoprotein A-1. The affibody/antibody ELISAs were also used to quantify human serum levels of IgA and apolipoprotein A1. To verify that human serum did not cause false-positive signals in the affibody/antibody ELISA format, the ability of human serum to cross-link affibodies, mAb (mouse or rat) and/or pAb (goat) displaying non-matched specificities was assessed; affibodies and antibodies were not cross-linked whereas all combinations of mAb and/or pAb were cross-linked. The combination of affibodies and antibodies for analysis of human serum molecules represents a novel two-site ELISA format which precludes false-positive signals caused by HAIA.     

Salience of Guilty Knowledge Test items affects accuracy in realistic mock crimes.

Guilty Knowledge Test measuring electrodermal reactions was carried out in order to investigate the quality of different questions and the validity of the test in a situation that resembled a true crime. Fifty participants were randomly assigned to commit one of two realistic mock crimes, and were later tested with GKTs concerning both the crime they had enacted and the one they had no knowledge of. Different scoring systems (SCRs and peak amplitudes as well as raw and standardised scores) were employed and compared when analyzing the results. Although there were some false positives, the test was able to differentiate between the groups of guilty and innocent participants. With the best scoring systems, the test was able to classify up to 84% of the innocent and up to 76% of the guilty correctly according to a logistic regression analysis. ROC areas reflecting these same results reached values above .80. Questions on matters that demanded the participants' attention and were easier to remember had better discriminative power. With nearly all scoring methods, there was a significant interaction between the salience of the relevant items and the guilt of the participants. Participants reacted more strongly to salient relevant items when they were guilty, while no different reactions were observed for the non-salient items between guilty and innocent participants. It is suggested that, although the Guilty Knowledge Test appears to be a valid measure of guilty knowledge even in crimes that are close to real crimes, the principles on which guilty knowledge test questions are constructed should be more clearly specified.