Solitary splenic metastases from lung cancer--one-time surgical procedure

Splenic metastasis from lung cancer is a rare clinical event, most often diagnosed at the time of an autopsy. We report a case of a 68 year old man with splenic metastasis from the primary lung cancer. Staging procedures before the resection of the primary lung tumor detected the splenic lesion. Upper left lobectomy and splenectomy were done by the left postero-lateral thoracotomy with phrenotomy. The rarity of solitary spleen metastasis from lung cancer and the treatment are discussed.     

The schilling test cannot be replaced by an absorption test with unlabeled vitamin B12

Summary It was the purpose of this study to evaluate the diagnostic usefulness of an oral absorption test using nonlabeled Vit B12 suggested by a commercial distributor as an alternative for the more expensive Schilling test (ST). Plasma levels of Vit B12 were measured with a commercial kit before and 4 h after oral administration of 1 mg Vit B12 in 32 normals, in 16 patients with normal ST, and in 14 patients with abnormal ST for determination of sensitivity and specificity with the ST as golden standard. In normals, a mean of 767±404 pg/ml before and 1096±776 pg/ml after oral Vit B12 with a mean increase of 331±453 pg/ml was measured. Because of the obvious large variation, no meaningful range for normal absorption could be established. In the two patient subsets, there was no Gaussian distribution of the results, with a meridian of Vit B12 increase after absorption of 142 pg/ml, range 27–2668 pg/ml, in the group with normal ST and a meridian of 244 pg/ml ranging from 40 to 2453 pg/ml in the group with abnormal ST. Statistical nonparametric analysis did not reveal any difference between the two groups. Assuming a minimum required increase of 100 pg/ml, as suggested by the kit distributor, a sensitivity of only 27% and a specificity of 75% was obtained. The lack of any diagnostic value of this approach might be caused by the known nonintrinsic-factor mediated absorption of approximately 1% of any B12 given orally even in complete intrinsic factor deficiency and by the relatively large amount of oral Vit B12 needed for a cold absorption test. The latter can, thus, not replace the Schilling test.Abbreviations Vit B12 Vitamin B12     

Correlation of penicillin Binding protein 2a detection with oxacillin resistance in Staphylococcus aureus and discovery of a novel penicillin binding protein 2a mutation

We compared a rapid slide latex agglutination test (LAT; Oxoid, Basingstoke, United Kingdom) that detects penicillin binding protein 2a (PBP2a) with MicroScan conventional panels (Dade Behring, West Sacramento, CA) for detection of oxacillin resistance in Staphylococcus aureus. The PBP2a LAT demonstrated 99% agreement with MicroScan oxacillin MIC results for 388 isolates of S. aureus. All 249 oxacillin-resistant isolates gave strong positive reactions in the LAT (100% sensitivity). Three of the 139 oxacillin-susceptible isolates were also strongly positive and one was weakly positive in the LAT (97.1% specificity). The three oxacillin-susceptible isolates with strongly positive reactions were further characterized. The mecA gene was detected in all three by PCR; one isolate was determined to be resistant to oxacillin by reference broth microdilution testing (MIC, 8 microg/ml), one isolate was inducibly resistant to oxacillin (MIC of 16 microg/ml after overnight induction), and one isolate remained susceptible regardless of the method used for testing. Sequence analysis of a 2.1-kb gene fragment of the mecA gene from the susceptible isolate revealed a one-base substitution at nucleotide position 1449 which results in a Met-to-Ile change for amino acid residue 483. This amino acid substitution has not been previously reported and may be associated with a change in the function of PBP2a resulting in oxacillin susceptibility. An additional 487 isolates were tested in parallel with the both the LAT and MicroScan panels using criteria in which only strong (3 to 4+) or repeatedly weak (1 to 2+) LAT reactions were considered positive, and the results showed 99.4% agreement. The PBP2a LAT provided rapid and reliable detection of oxacillin resistance and proved a useful adjunct to the phenotypic method. Both methods provided reliable detection of oxacillin-resistant S. aureus and facilitated the discovery of a novel, functionally impaired form of PBP2a.     

Comparative Analysis of Apoptosis and Inflammation Genes of Mice and Humans

Apoptosis (programmed cell death) plays important roles in many facets of normal mammalian physiology. Host-pathogen interactions have provided evolutionary pressure for apoptosis as a defense mechanism against viruses and microbes, sometimes linking apoptosis mechanisms with inflammatory responses through NFκB induction. Proteins involved in apoptosis and NFκB induction commonly contain evolutionarily conserved domains that can serve as signatures for identification by bioinformatics methods. Using a combination of public (NCBI) and private (RIKEN) databases, we compared the repertoire of apoptosis and NFκB-inducing genes in humans and mice from cDNA/EST/genomic data, focusing on the following domain families: (1) Caspase proteases; (2) Caspase recruitment domains (CARD); (3) Death Domains (DD); (4) Death Effector Domains (DED); (5) BIR domains of Inhibitor of Apoptosis Proteins (IAPs); (6) Bcl-2 homology (BH) domains of Bcl-2 family proteins; (7) Tumor Necrosis Factor (TNF)-family ligands; (8) TNF receptors (TNFR); (9) TIR domains; (10) PAAD (PYRIN; PYD, DAPIN); (11) nucleotide-binding NACHT domains; (12) TRAFs; (13) Hsp70-binding BAG domains; (14) endonuclease-associated CIDE domains; and (15) miscellaneous additional proteins. After excluding redundancy due to alternative splice forms, sequencing errors, and other considerations, we identified cDNAs derived from a total of 227 human genes among these domain families. Orthologous murine genes were found for 219 (96%); in addition, several unique murine genes were found, which appear not to have human orthologs. This mismatch may be due to the still fragmentary information about the mouse genome or genuine differences between mouse and human repertoires of apoptotic genes. With this caveat, we discuss similarities and differences in human and murine genes from these domain families.     

Behavioural and ERP indices of response inhibition during a Stop-signal task in children with two subtypes of Attention-Deficit Hyperactivity Disorder.

Previous research has shown that children with Attention-Deficit Hyperactivity Disorder of the Combined Type (AD/HDcom) have problems with response inhibition, with poorer task performance and atypical inhibition-related ERPs relative to control subjects, while little is known about response inhibition in children with Attention-deficit Hyperactivity Disorder of the Predominantly Inattentive Type (AD/HDin). In this study children with AD/HDin (N=12), AD/HDcom (N=13) and age-matched controls (N=13) aged between 8 and 14 years completed a Stop-signal task, with visual Go and auditory Stop-signal stimuli, while EEG was recorded. The results indicated that the groups did not differ on any inhibitory task performance measure, but the AD/HD groups showed more errors of omission to Go stimuli than controls. ERPs to the visual Go stimuli differed between children with AD/HDin and controls (increased central N1 and N2, decreased central P2 and increased parietal P3), while the AD/HDcom group showed only minor scalp distribution differences for N2 and P3. The AD/HDin group showed amplitude differences from controls to Stop signals (larger central N1 and parietal P3; reduced midline N2) and did not show a Successful vs. Failed inhibition effect for P3. The AD/HDcom group showed reduced parietal P3 to Stop signals, with the Trial Type effect present for N2 but not P3. These data suggest that the apparent atypical inhibitory processing at N2 and P3 may stem, at least in part, from atypical early sensory/alerting processing of all stimuli in children with AD/HDin.     

Germinal center formation in mice lacking αβ T cells

T cells are essential for inducing clonal B cell expansion in germinal centers during T cell-dependent antibody responses. However, class-switched antibodies are readily detectable in TCRα-deficient mice that congenitally lack αβ T cells, including those such as IgG1 that are considered to be dependent on collaboration between B cells and αβ T cells. This observation suggests that a novel form of B:T collaboration may be evident in TCRα^?/? mice. We report that germinal centers develop spontaneously in mice lacking T cell receptor α genes (TCRα^?/?), despite the absence of αβ T cells. They are not seen in TCRβ^?/? mice kept in similar conditions. Both strains of mice have γδ T cells, but it is a subset of T cells expressing TCRβ and CD4 that is dominant in the germinal centers of TCRα^?/? mice. Exceptionally, germinal centers were associated with CD4⁺ γδ T cells. The expression of CD4 seems to be important, for few extrafollicular T cells have CD4 and CD4 is largely absent from TCRβ^?/? T cells. The CD4⁺ TCRβ cells may help B cells produce autoantibodies that have been identified in TCRα^?/? mice.     

Ca2+–calmodulin-dependent protein kinase expression and signalling in skeletal muscle during exercise

Ca²⁺ signalling is proposed to play an important role in skeletal muscle function during exercise. Here, we examined the expression of multifunctional Ca²⁺–calmodulin-dependent protein kinases (CaMK) in human skeletal muscle and show that CaMKII and CaMKK, but not CaMKI or CaMKIV, are expressed. Furthermore, the effect of exercise duration and intensity on skeletal muscle CaMKII activity and phosphorylation of downstream targets was examined. Eight healthy men exercised at ∼67% of peak pulmonary O₂ uptake     with muscle samples taken at rest and after 1, 10, 30, 60 and 90 min of exercise. Ten other men exercised for three consecutive 10 min bouts at 35%, 60% and 85%     with muscle samples taken at rest, at the end of each interval and 30 min post-exercise. There was a rapid and transient increase in autonomous CaMKII activity and CaMKII phosphorylation at Thr²⁸⁷ in skeletal muscle during exercise. Furthermore, the phosphorylation of phospholamban (PLN) at Thr¹⁷, which was identified as a CaMKII substrate in skeletal muscle, was rapidly (< 1 min) increased by exercise, and remained phosphorylated 5-fold above basal level during 90 min of exercise. The phosphorylation of serum response factor at Ser¹⁰³, a putative CaMKII substrate, was higher after 30 min of exercise. PLN phosphorylation at Thr¹⁷ was higher with increasing exercise intensities. These data indicate that CaMKII is the major multifunctional CaMK in skeletal muscle and its activation occurs rapidly and is sustained during continuous exercise, with the activation being greater during intense exercise.     

Phaeohyphomycosis caused by the fungal genera Bipolaris and Exserohilum. A report of 9 cases and review of the literature

We have reported 7 new cases of Bipolaris infection and 2 of Exserohilum infection, which demonstrate the capability of these 2 genera to cause invasive as well as "allergic" disease. As noted previously, it is likely that all of the cases of "Helminthosporium" and Drechslera infections reported in the literature were caused by Bipolaris or Exserohilum. Infections due to these 2 genera are probably more common than previously recognized. They should be included in the differential diagnosis of central nervous system and disseminated fungal disease, sinusitis, keratitis, peritonitis associated with continuous ambulatory peritoneal dialysis, and allergic bronchopulmonary disease. These various entities have distinct histopathologic characteristics. With disseminated disease in the immunocompromised patient, the most frequent findings are acute inflammation with prominent vascular invasion, thrombosis, and infarction. In contrast, granulomatous inflammation and leukocytoclastic vasculitis are seen in meningoencephalitis caused by these fungi. The histologic features of allergic bronchopulmonary disease and sinusitis are similar. A chronic inflammatory infiltrate of lymphocytes, plasma cells and eosinophils within edematous granulation tissue is found in addition to squamous metaplasia and thickening of the basement membrane. Infections caused by Bipolaris/Exserohilum and Aspergillus show many clinical and pathologic similarities despite the lack of taxonomic relationship between these fungi. Both cause disseminated disease in immunocompromised patients that is characterized by tissue necrosis and vascular invasion. Both cause central nervous system disease, osteomyelitis, and sinusitis and are associated with allergic bronchopulmonary disease. Sinusitis, the most common form of disease caused by Bipolaris and Exserohilum, occurs in otherwise healthy patients with nasal polyposis and allergic rhinitis. Although pathologic evidence of bone invasion may not be found, there frequently is radiographic evidence of invasive disease. Most patients who are treated initially with surgical debridement and amphotericin B have apparently been cured. However, longer follow-up will be necessary in these patients. Amphotericin B appears to be the treatment of choice for invasive infections caused by Bipolaris/Exserohilum species. Ketoconazole and other imidazole derivatives may also be effective in certain of the disease entities caused by these black moulds; however, their role has yet to be defined.(ABSTRACT TRUNCATED AT 400 WORDS)     

Autonomy and developing physicians: Reimagining supervision using self-determination theory

In this article, we address the question, ‘What is the role of autonomy in physician development?’ Medical education is a developmental process, and autonomy plays a motivational role in physician development. Calls for increased supervision of residents have raised concerns that the resulting decreased autonomy might interfere with resident development, leading the authors to explore the relationship between supervision and autonomy. The medical education literature posits a simple inverse relationship between supervision and autonomy. Within competency frameworks, autonomy is operationalised as independence and viewed as the end goal of training. Alternatively, there is emerging empirical literature describing autonomy and supervision as dynamic and developmental constructs and point towards more complex relationship between supervision and autonomy. Self-determination theory (SDT) presents a framework for understanding this dynamic relationship and the role of autonomy in physician development. Within SDT, autonomy is a fundamental psychological need, associated with motivation for learning, self-regulation and an internal locus of control. Supporting learner autonomy can afford learners the opportunity to internalise the values and norms of the profession, leading to an integrated regulation of their behaviours and actions. Conceptualising autonomy through the lens of SDT provides an avenue for education interventions and future research on supervision and autonomy. Educators can integrate supervision and autonomy support in the clinical setting, seeking to motivate learner development by balancing optimal challenge and support and integrating autonomy support with ‘hands-on’ approaches to supervision. SDT also provides a theoretical framework relevant to current discussions regarding feedback conversations and coaching in medical education. Lastly, conceptualising autonomy using SDT opens new avenues for investigation, exploring the complex relationship between supervision and autonomy and developing efforts to integrate autonomy support with clinical supervision.