HIRA-TAN detects pathogens of pneumonia with a progressive course despite antibiotic treatment

BackgroundEmpiric antibiotics are administered for pneumonia when the causative pathogens are unidentified. Pathogen-directed therapy is impeded by negative culture results and/or culture time lag. This circumstance necessitates a salvage method for pathogen identification, especially when antibiotic therapy has failed. Here, we aimed to preliminarily investigate the HIRA-TAN method in pneumonia with a progressive course despite prior empiric antibiotic therapy.MethodsThis prospective study was conducted for patients who were referred to Dr. Zainoel Abidin Hospital, Aceh, Indonesia, from December 2016 to January 2017, owing to pneumonia with a progressive course. Sputum or pleural effusion was subjected to culture and the HIRA-TAN assay. The HIRA-TAN identified the candidate causative pathogens based on the difference in the cycle threshold (Ct) between the targeted pathogen and the single-copy human gene.ResultsPatients (n=27) were predominantly males (22 patients, 81.5%), with a median age of 62 years. All patients had comorbid disease and were classified as hospital-acquired pneumonia (25 patients, 92.6%) with multilobar infiltrates (22 patients, 81.5%). Bacterial culture identified causative pathogen(s) in some (14 patients, 51.8%), whereas the HIRA-TAN identified pathogen(s) in most (23 patients, 85.2%). The rapid pathogen identification by the HIRA-TAN will provide valuable information in guiding pathogen-directed therapy.ConclusionsThe result warrants a larger clinical trial to confirm the clinical efficacy of the HIRA-TAN in patients with progressive pneumonia despite previous antibiotic treatment.     

Del(5q) and MLL amplification in homogeneously staining region in acute myeloblastic leukemia: a recurrent cytogenetic association

We report here a 71 year-old female presenting with acute myeloblastic leukemia (FAB-M1) after treatment of essential thrombocythemia with Vercyte. Conventional cytogenetic techniques showed a complex karyotype, 44,XX,−5,−7,−11,add(11)(q23),−14,+mar,+r. The use of several fluorescent in situ hybridizations (FISH) lead to the identification of these complex rearrangements. The marker was found to be tricentric, with pericentromeric material of chromosome 7 inserted in the short arm of chromosome 5, resulting in monosomy 5q and 7q. The derivative chromosome 11 was dicentric and had subtelomeric sequences of 11p on both ends; several copies of the MLL gene were located in two different regions separated by a centromere of chromosome 11. Twenty-one cases, including ours, of myelodysplastic syndromes and acute myelogenous leukemia with MLL amplification present in hsr or dmin were found in the literature. Most of these patients shared some characteristics: they were old, they had de novo acute myeloid leukemia (AML) with a complex karyotype and a short survival, 90% of them having also a del(5q). Therefore, the simultaneous presence of MLL amplification and del(5q) appears to be a nonrandom association that could be the signature of AML in elderly patients with a poor prognosis.     

Double minutes containing amplified bcr-abl fusion gene in a case of chronic myeloid leukemia treated by imatinib

Amplification of the bcr-abl fusion gene has recently been associated with resistance to imatinib therapy in chronic myeloid leukemia (CML). A 55-yr-old man was diagnosed with Philadelphia (Ph) chromosome-positive CML. Resistance to interferon treatment and occurrence of blastic phase lead to the decision of imatinib therapy. After two autologous stem cell transplantation, the patient reverted to chronic phase with a decrease in the proportion of Ph chromosome-positive cells under imatinib. A second blastic phase occurred 4 months after transplantation, of which the patient died. Cytogenetic studies, including fluorescent in situ hybridization, showed a (9;22)(q34;q11) translocation and one bcr-abl fusion gene during the whole evolution, but for the last 2 months. Bcr-abl gene amplification (over 25 copies) was noted while banding cytogenetics showed a karyotype of 55-62 chromosomes with multiple double minutes (dmin). To the best of our knowledge, dmin containing amplified bcr-abl gene has never been reported in patients with CML. Therefore, although we cannot exclude that the gene amplification was strictly associated with disease progression, our data may suggest that the amplification resulted in resistance to imatinib.     

Diagnosis of coronary artery disease by thallium 201 myocardial scintigraphy during atrial pacing

Rapid atrial pacing may reveal myocardial ischemia but the sensitivity for the diagnosis of coronary artery disease is not high enough for routine use. Therefore, the value of atrial pacing coupled with Thallium 201 scintigraphy was evaluated. Sixty-two patients (53 men and 9 women) referred for investigation of angina or chest pain were divided into two groups: a control group of 13 patients (9 men and 4 women, average age: 57.1 years) with insignificant coronary lesions (less than 50%) (N = 5) or normal coronary angiography (N = 8), and a group of 49 patients (44 men and 5 women, average age: 55.5 years) 27 of whom had a history of myocardial infarction (17 posterior, 10 anterior). Coronary angiography showed single vessel disease in 44.9% of cases, double vessel disease in 34.7% and triple vessel disease in 18.4% of cases, and 1 patient with left main stem disease. All 62 patients underwent the same study protocol which comprised: incremental atrial pacing (to the calculated maximal heart rate), Thallium 201 myocardial scintigraphy immediately after pacing and during the redistribution phase, and coronary angiography. The sensitivities of anginal pain (36.7%) and ECG changes during atrial pacing (57.1%) were too low for the diagnosis of myocardial ischemia. On the other hand, Thallium 201 scintigraphy with atrial pacing was more sensitive (87.8%) and specific (84.6%) for coronary artery disease. Stenosis of the left anterior descending artery was diagnosed with a sensitivity of 96.4% and that of the right coronary artery with a sensitivity of 90.9%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Automatization of microscopic blood smear analyses and quality control using reference virtual slides

MEKOC microscopy complexes have a group of specialized automatic functions for medical analyses of biomaterials integrated with general virtual microscopy accessories. Such functions provide a way of making specialized reference virtual slides (RVS). The latter contain the results of virtual analysis or expert evidence of the automatic analysis results presented in the virtual slide. The use of RVS yields an open system with a step-by-step control of the quality of automatic operations. RVS as realistic preparation models are also used to train staff. The results of step-by-step trials of the MEKOC--2 are presented in the paper.     

Helpful Only When Elevated: Initial Serum Lactate in Stable Emergency Department Patients with Sepsis Is Specific,but Not Sensitive for Future Deterioration

Background

Early emergency department (ED) identification of septic patients at risk of deterioration is critical. Lactate is associated with 28-day mortality in admitted patients, but little evidence exists on its use in predicting short-term deterioration.

Neuronal circuits of fear extinction

Fear extinction is a form of inhibitory learning that allows for the adaptive control of conditioned fear responses. Although fear extinction is an active learning process that eventually leads to the formation of a consolidated extinction memory, it is a fragile behavioural state. Fear responses can recover spontaneously or subsequent to environmental influences, such as context changes or stress. Understanding the neuronal substrates of fear extinction is of tremendous clinical relevance, as extinction is the cornerstone of psychological therapy of several anxiety disorders and because the relapse of maladaptative fear and anxiety is a major clinical problem. Recent research has begun to shed light on the molecular and cellular processes underlying fear extinction. In particular, the acquisition, consolidation and expression of extinction memories are thought to be mediated by highly specific neuronal circuits embedded in a large‐scale brain network including the amygdala, prefrontal cortex, hippocampus and brain stem. Moreover, recent findings indicate that the neuronal circuitry of extinction is developmentally regulated. Here, we review emerging concepts of the neuronal circuitry of fear extinction, and highlight novel findings suggesting that the fragile phenomenon of extinction can be converted into a permanent erasure of fear memories. Finally, we discuss how research on genetic animal models of impaired extinction can further our understanding of the molecular and genetic bases of human anxiety disorders.