Differentiation of resistance phenotypes among erythromycin-resistant streptococci

Although macrolide antibiotics have proved to be a valuable alternative to beta-lactam antibiotics in the treatment of respiratory tract infections, resistance to these agents is now becoming established in streptococci, especially among Streptococcus pneumoniae isolates. Of particular concern is the emergence of cross-resistance to 14-, 15- and 16-membered macrolides, licosamides and group B streptogramins (MLSb phenotype). MLS resistance can be expressed either constitutively (cMLS phenotype) or inducibly (iMLS phenotype). MLS resistance is mediated by two classes of methylase genes--the conventional erm(B) and recently described erm(A) determinants. A new macrolide efflux mechanism has been described for streptococci, in which it is associated with a new resistance pattern (M phenotype) characterized by resistance to 14- and 15-membered macrolides, and susceptibility to 16-membered macrolides, lincosamides and streptogramin B. The recognition of the prevalence of M phenotype in streptococci has implications for sensitivity testing and may have an impact on the choice of antibiotic therapy in clinical practice. While M resistance is similar in S. pyogenes and S. pneumoniae being mediated by mef(A) and mef(E), respectively, MLS resistance in both species appears to be genotypically and phenotypically more varied. Differentiation of M and MLS phenotypes of erythromycin-resistant strains can be performed using the erythromycin-clindamycin double-disc method (ECDD). Distinguishing not only M resistance but also constitutively or inducibly MLS phenotype by ECDD in S. pyogenes is easily and reliably achieved. Inducible MLS phenotype S. pyogenes strain is genotypically and phenotypically heterogeneous and is further subdivided into three recently described subtypes, iMLS-A, iMLS-B and iMLS-C, by a triple-disk test with erythromycin plus clindamycin and josamycin. While distinguishing M from MLS resistance in S. pneumoniae by ECDD test is easily and reliably achieved, the differentiation between constitutive and inducible MLS resistance is by far more uncertain. The meaning of inducible MLS resistance appears to be different in S. pneumoniae from that in S. pyogenes. In order to easily differentiate, within erythromycin-resistant pneumococci, not only the strains of the M phenotype from those with MLS resistance but also among the latter, cMLS from iMcLS strains, a triple-disk test has been set up by adding a rokitamycin disk to the conventional     

Removal of immunoglobulins by a protein A versus an antihuman immunoglobulin G-based system: evaluation of 602 sessions of extracorporeal immunoadsorption

Elimination of IgG can be achieved by extracorporeal immunoadsorption (IA) based on specific binding to either staphylococcal protein A (Excorim) or sheep polyclonal antibodies directed against human IgG (Therasorb). In 602 analyzed sessions of IA, elimination of IgG was 60% through 80% depending on the treated plasma volume, with no significant difference between the mentioned systems. However, the decrease of IgM and IgA was approximately 50% in the anti-IgG compared to 20-40% in the protein A system. Plasma albumin concentration decreased by 20% in the anti-IgG system compared to 15% in the protein A system, and hemoglobin values increased by 2% in the anti-IgG system and decreased by 6% in the protein A system. In conclusion, a clinical relevance for these findings cannot be ruled out, and the individual choice might depend on the clinical situation and laboratory findings.     

Particle release in extracorporeal low-density lipoprotein lowering therapies

Release of microparticles into the blood during extracorporeal circulation must be kept low because of possibly serious acute and chronic adverse effects. Concentration and size distribution of microparticles were measured during simulated treatments (n = 7) on original equipment for 2 standard low-density lipoprotein (LDL) elimination procedures (DALI 750, Fresenius AG, St. Wendel, Germany and Liposorber, Kaneka Corporation, Osaka, Japan) and compared to hemofiltration solutions. For both systems as well as in hemofiltration solutions, the mean particle concentrations in 500 ml portions gathered from the efferent blood line stayed below 10% of pharmacopoeia standards for infusion solutions (United States Pharmacopoeia, European Pharmacopoeia) in all measured size classes. Although particle concentrations were comparable in all systems, the mean total number of particles > or =2 microm released per session was lowest in the DALI (167,000) compared to the Liposorber (465,000) and hemofiltration solutions (2,240,000). This was mainly due to different total processed blood volumes necessary to achieve the required LDL reduction.     

2. Survival Impact of HER-2/Neu, Cox-2, Urokinase Plasminogen Activator (upa), Cytokeratin 17/5,6 and other Markers with Long-Term Outcome of Early Breast Cancer. Report from the British Columbia Tissue Micro-Array Project (BCTMAP)

Tumor samples are available from over 19,600 Stage I-III breast cancer patients treated according to evolving British Columbia guidelines from 1978 to 1990. A tissue mico-array (TMA) was constructed from 930 of these patients, all of whom participated in randomized or phase II studies. Outcome was defined as 20-year Breast Cancer specific Survival (BrCaSS), with events defined as Breast Ca death. Follow up was median 17.8 years (ranges 11–28). Multiple tumor markers were tested, and results correlated with 20-year BrCaSS for markers expressed versus non-expressed. No difference in BrCaSS was found for aromatase, integrin-linked kinase (ILK), IGF-1 and Topo-isomerase-2. The negative predictive value of IHC versus FISH and ACIS-IHC versus FISH was 96 and 97%, respectively. The positive predictive value of IHC versus FISH and ACIS-IHC versus FISH was 84 and 84%, respectively. All tests, with the exception of HER-2 FISH were done by IHC. Results of other markers (VEGF, ER/PgR, hypoxia markers, etc.), and an interactive multivariate analysis adjusting for conventional prognostic factors and for all above markers, are in progress. Conclusions 1. The TMA is a technique which provides opportunity for rapid screening of multiple genetic markers.2. Expression of Her-2/Neu, uPA, Cox-2 and Cytokeratin 17/5,6 (but not of Aromatase, ILK, TOPO-II and IGF-1) is associated with inferior BrCaSS.3. HER-2 determination by ACIS-IHC provides comparable results to IHC done manually (with a potential for more uniform reporting), and both provide comparable results to Her-2 assessment by FISH. ^** ACIS-IHC:IHC red by Automated Cell Image System (M.L.)     

Hemangiomas of the external auditory canal:a literature review and two new case reports

Aim  

The aim of this paper is to present two case reports of patients with hemangiomas of the external auditory canal, and to overview all cases published in English language literature so far.     

Diagnostic uncertainty and recall bias in chronic low back pain

Patients’ beliefs about the origin of their pain and their cognitive processing of pain-related information have both been shown to be associated with poorer prognosis in low back pain (LBP), but the relationship between specific beliefs and specific cognitive processes is not known. The aim of this study was to examine the relationship between diagnostic uncertainty and recall bias in 2 groups of chronic LBP patients, those who were certain about their diagnosis and those who believed that their pain was due to an undiagnosed problem. Patients (N = 68) endorsed and subsequently recalled pain, illness, depression, and neutral stimuli. They also provided measures of pain, diagnostic status, mood, and disability. Both groups exhibited a recall bias for pain stimuli, but only the group with diagnostic uncertainty also displayed a recall bias for illness-related stimuli. This bias remained after controlling for depression and disability. Sensitivity analyses using grouping by diagnosis/explanation received supported these findings. Higher levels of depression and disability were found in the group with diagnostic uncertainty, but levels of pain intensity did not differ between the groups. Although the methodology does not provide information on causality, the results provide evidence for a relationship between diagnostic uncertainty and recall bias for negative health-related stimuli in chronic LBP patients.     

Intraperitoneal Sodium Thiosulfate for the Treatment of Calciphylaxis

Calcific uremic arteriolopathy (or calciphylaxis) is a severe complication of renal failure characterized by subcutaneous calcification of the small arteries and tissue necrosis. We describe the case of a woman receiving continuous cycling peritoneal dialysis with calciphylaxis involving upper and lower extremities. After intolerance of intravenous sodium thiosulfate and limited intravenous access options, we administered sodium thiosulfate intraperitoneally and quantitated the amount of extra calcium removed. Intraperitoneal administration of sodium thiosulfate was well tolerated and led to removal of extra calcium with peritoneal dialysis.