Risk factors for hospital-acquired bacteremia

OBJECTIVE: Bacteremia is one of the most serious health problems associated with high morbidity and mortality. The aim of this study was to identify risk factors for bacteremia in daily medical care to facilitate rapid and accurate clinical decisions about treatment. PATIENTS AND METHODS: We studied 306 inpatients retrospectively. Age, peripheral neutrophil count, C-reactive protein (CRP), platelets, serum total cholesterol, total protein, albumin and cholinesterase were compared in patients with positive- and negative-blood cultures. The associations between blood culture positivity and glucose tolerance, bedridden state, presence of a central venous catheter (CVC) or urinary catheter were examined. On October 14, 2002, strategies for prevention of catheter-related infection were altered in our hospital. We studied the impact of these changes on the risk of bacteremia. RESULTS: Sixty-seven patients had positive and 239 had negative blood cultures. Age, neutrophil, platelets, total protein, albumin, and cholinesterase were significantly different between the culture-positive patients and the culture-negative patients. Multivariate analysis showed albumin and platelets as independent predictors. The bedridden state and catheter-inserted states (central venous or urinary) conferred significantly higher positive blood culture rates. Multivariate analysis showed using urinary catheters and indwelling femoral CVCs as independent risk factors. There was no significant difference in the blood culture-positive rate before and after the change in prevention strategies; before the change, 6 of 9 catheter-inserted blood culture-positive cases yielded MRSA, while 4 of 12 cultures yielded Staphylococcus epidermidis after the change. CONCLUSION: Our study highlights the risk factors of bacteremia in vulnerable patients.     

A multicenter study of a new Helicobacter pylori selective medium. Columbia horse blood agar HP

We conducted a study for the growth of and selectivity for the desired microorganisms using a newly developed selective culture medium for Helicobacter pylori, Columbia horse blood agar HP (CHBHP), at three different Japanese clinical laboratories, Hokkaido, Kanto and Kyusyu. When standard strains and clinical isolates of H. pylori were examined, the recovery of the organism on the CHBHP media was comparable to that of conventional selective and nonselective media. However, colonies were obviously larger on the CHBHP media. These media yielded the highest H. pylori positive rate for clinical specimens at all the three laboratories. The detection rate of the CHBHP media in H. pylori-positive specimens was higher than that of media commonly used at the three laboratories (98.1% to 100% vs. 88.0% to 96.2%). The CHBHP media also achieved a higher detection rate for specimens from H. pylori-infected animals. CHBHP media have an excellent growth supporting ability and selectivity originating from Columbia agar base and do not require the combined use of non-selective media for the growth and isolation of the organism, resulting in lower cost. Thus, they are useful media for the selective culture and isolation of H. pylori from clinical and animal specimens.     

Common cytological and cytogenetic features of Epstein-Barr virus (EBV)-positive natural killer (NK) cells and cell lines derived from patients with nasal T/NK-cell lymphomas,chronic active EBV infection and hydroa vacciniforme-like eruptions

In this study, we describe the cytological and cytogenetic features of six Epstein-Barr virus (EBV)-infected natural killer (NK) cell clones. Three cell clones, SNK-1, -3 and -6, were derived from patients with nasal T/NK-cell lymphomas; two cell clones, SNK-5 and -10, were isolated from patients with chronic active EBV infection (CAEBV); and the other cell clone, SNK-11, was from a patient with hydroa vacciniforme (HV)-like eruptions. An analysis of the number of EBV-terminal repeats showed that the SNK cell clones had monoclonal EBV genomes identical to the original EBV-infected cells of the respective patients, and SNK cells had the type II latency of EBV infection, suggesting that not only the cell clones isolated from nasal T/NK-cell lymphomas but also those isolated from CAEBV and HV-like eruptions had been transformed by EBV to a certain degree. Cytogenetic analysis detected deletions in chromosome 6q in five out of the six SNK cell clones, while 6q was not deleted in four control cell lines of T-cell lineage. This suggested that a 6q deletion is a characteristic feature of EBV-positive NK cells, which proliferated in the diseased individuals. The results showed that EBV-positive NK cells in malignant and non-malignant lymphoproliferative diseases shared common cytological and cytogenetic features.     

Lack of correlation between P pulmonale and right atrial overload in chronic obstructive airways disease.

The correlation between P pulmonale and right atrial overload in chronic lung disease was studied. Right atrial pressure, pulmonary artery pressure, and cardiac output were measured with a Swan-Ganz catheter in nine patients with chronic lung disease and P pulmonale on the electrocardiogram (P wave amplitude of greater than or equal to 2.5 mm (0.25 mV) in leads II, III, and a VF. The results were compared with those in six patients with an atrial septal defect (left to right shunt greater than or equal to 50%) and six patients with pulmonary hypertension (mean pressure greater than or equal to 30 mm Hg without left sided heart disease). Right atrial volume and wall thickness were measured in 10 cases of P pulmonale among 1000 necropsy cases and compared with 141 normal hearts from the same series. The patients with P pulmonale did not show a significant increase in right atrial or pulmonary artery pressures. None of the patients with an atrial septal defect or pulmonary hypertension had P pulmonale on the electrocardiogram. In the necropsy cases of P pulmonale mean (1 SD) in right atrial volume (32 (12) ml) and wall thickness (1.5 (0.7) mm) were not significantly increased (40 (14) ml and 1.4 (0.5) mm in the normal hearts). There was a significant inverse relation between the presence of P pulmonale and the cardiothoracic ratio. In all the patients with P pulmonale chest x ray showed a low cardiothoracic ratio, a considerably depressed diaphragm, and a pendulous heart. This study showed no correlation between P pulmonale and right atrial overload in chronic lung disease. A more vertical anatomical position of the heart, particularly of the right atrium, seems to be the major factor responsible for generation of P pulmonale in chronic airways disease.     

Strong CD8+ T-cell responses against tumor-associated antigens prolong the recurrence-free interval after tumor treatment in patients with hepatocellular carcinoma

Aim

We investigated whether tumor-specific CD8⁺ T-cell responses affect tumor-free survival as well as the relationship between CD8⁺ T-cell responses against tumor-associated antigens (TAAs) and the clinical course after tumor treatment in patients with hepatocellular carcinoma (HCC).

Methods

Twenty patients with HCC that were treated by radiofrequency ablation or trans-catheter chemo-embolization (TACE) and in whom HCC was undetectable by ultrasonography, CT, and/or MRI 1 month after treatment were enrolled in the study. Before and after treatment for HCC, analyses of TAA (glypican-3, NY-ESO-1, and MAGE-1)-specific CD8⁺ T-cell responses were evaluated with an interferon-γ enzyme-linked immunospot (ELISpot) assay using peripheral CD8⁺ T-cells, monocytes, and 104 types of 20-mer synthetic peptide overlapping by 10 residues and spanning the entirety of the 3 TAAs.

Results

Sixteen out of 20 patients (80%) showed a positive response (≥10 TAA-specific cells/10⁵ CD8⁺ T-cells) before or after treatment. When we performed univariate analysis of prognostic factors for the tumor-free period in the 20 patients, platelet count, prothrombin time, and the number of TAA-specific CD8⁺ T-cells after treatment were significant factors (P = 0.027, 0.030, and 0.004, respectively). In multivariate analysis, the magnitude of the TAA-specific CD8⁺ T-cell response (≥40 TAA-specific cells/10⁵ CD8⁺ T-cells) was the only significant prognostic factor for a prolonged tumor-free interval (hazard ratio 0.342, P = 0.022).

Conclusions

Our results suggest that strong TAA-specific CD8⁺ T-cell responses suppress the recurrence of HCC. Immunotherapy to induce TAA-specific cytotoxic T lymphocytes by means such as the use of peptide vaccines should be considered for clinical application in patients with HCC after local therapy.     

The multidrug-resistance protein 4 polymorphism is a new factor accounting for thiopurine sensitivity in Japanese patients with inflammatory bowel disease

Background  

Multidrug resistance protein 4 (MRP4) functions as an efflux pump of nucleoside monophosphate analogs, such as 6-mercaptopurine (6-MP) and 6-thioguanine nucleotide (6-TGN). A single-nucleotide polymorphism in human MRP4 (rs3765534) dramatically reduces MRP4 function and results in the intracellular accumulation of 6-TGN. In this study, we investigated the association between MRP4 G2269A polymorphism and thiopurine sensitivity in Japanese IBD patients.     

Phosphoenolpyruvate carboxylase intrinsically located in the chloroplast of rice plays a crucial role in ammonium assimilation

Phosphoenolpyruvate carboxylase (PEPC) is a key enzyme of primary metabolism in bacteria, algae, and vascular plants, and is believed to be cytosolic. Here we show that rice (Oryza sativa L.) has a plant-type PEPC, Osppc4, that is targeted to the chloroplast. Osppc4 was expressed in all organs tested and showed high expression in the leaves. Its expression in the leaves was confined to mesophyll cells, and Osppc4 accounted for approximately one-third of total PEPC protein in the leaf blade. Recombinant Osppc4 was active in the PEPC reaction, showing V_max comparable to cytosolic isozymes. Knockdown of Osppc4 expression by the RNAi technique resulted in stunting at the vegetative stage, which was much more marked when rice plants were grown with ammonium than with nitrate as the nitrogen source. Comparison of leaf metabolomes of ammonium-grown plants suggested that the knockdown suppressed ammonium assimilation and subsequent amino acid synthesis by reducing levels of organic acids, which are carbon skeleton donors for these processes. We also identified the chloroplastic PEPC gene in other Oryza species, all of which are adapted to waterlogged soil where the major nitrogen source is ammonium. This suggests that, in addition to glycolysis, the genus Oryza has a unique route to provide organic acids for ammonium assimilation that involves a chloroplastic PEPC, and that this route is crucial for growth with ammonium. This work provides evidence for diversity of primary ammonium assimilation in the leaves of vascular plants.