Impact of hospital environmental cleaning with a potassium peroxymonosulphate-based environmental disinfectant and antimicrobial stewardship on the reduction of hospital-onset Clostridioides difficile infections.

BACKGROUND: A 1% potassium peroxymonosulphate-based environmental disinfectant (PPED) produces sodium hypochlorite when combined with sodium chloride, which functions as a disinfectant. However, little is known about the impact of hospital cleaning with PPED on hospital-onset Clostridioides difficile infection (HO-CDI). AIM: To reduce HO-CDI, we promoted antimicrobial stewardship and hospital ward cleaning with PPED: this study was conducted to evaluate their impact. METHODS: We began a promotion of post-prescription review with feedback for broad-spectrum antimicrobials and hospital ward cleaning with PPED. We reviewed the ratio of HO-CDI, PPED consumption, and days of therapy (DOT) of broad-spectrum antimicrobials between July 2014 and March 2018, dividing this time into the pre-promotion (July 2014 to June 2015) and post-promotion periods (July 2015 to March 2018). FINDINGS: Using interrupted time series analysis, an immediate significant change in HO-CDI was observed after intervention (P=0.03), although a downward trend was not observed over this period (P=0.19). Trends in PPED consumption significantly changed over this period (P=0.02). DOT of carbapenems decreased immediately after the intervention began (P<0.01). A Poisson regression analysis showed that PPED consumption and DOT of carbapenems were independent factors affecting HO-CDI (P=0.039 and 0.016, respectively). CONCLUSION: We revealed that DOT of carbapenems and use of PPED were associated with the HO-CDI ratio and that both interventions reduced the rate of HO-CDI. This is the first report on the impact of hospital ward cleaning with PPED on the reduction of HO-CDI.

[Evaluation of thoracography for secondary pneumothorax in elderly people].

The thoracoscopic surgery for patient with pneumothorax has been considered to be safe and easy. In recent years, there is a growing number of secondary pneumothorax due to advanced pulmonary emphysema in elderly patients. To confirm the existence of adhesion and the site of air leakage are important prior to surgery. In our institution, thoracography was performed before surgery in 9 cases of emphysema and secondary pneumothorax over 60 years old patients. The mean age was 72.2 years old and all patients were male. Air leakage and its site could be identified in 6 cases by thoracography. In the remaining 3 cases, adhesion sites were identified. There were no complications in all cases. The operation time was 117 minutes, and blood loss was 9.9 ml in average. The mean postoperative drainage period was 1.6 days and total hospital stay was 5.9 days. We conclude that the thoracoscopic surgery can be performed more safely by obtaining information of thoracic cavity using thoracography before surgery.

[Early and late sugical results of emergency operation for acute type A aortic dissection].

We evaluated the results of 213 emergency operations of acute type A aortic dissection in our center from January 2003 to December 2006. They were 101 male and 112 female, and the mean age was 64.6 years. The hospital mortality rate of all cases was 13.6% (29/213). And that of cases with malperfusion was 31.9% (15/47). They consisted of stroke 8/17 (47.1%), myocardial ischemia 5/27 (18.5%) [right coronary artery: 2/22 (9.1%), left main trunk: 3/5 (60.0%)], and intestinal ischemia 2/3 (66.7%). The hospital mortality rate of pulseless electrical activity (PEA) cases was 57.1% (4/7), and that of aortic rupture cases was 33.3% (3/9). On the other hand, the mortality rate of cases with cardiac tamponade alone was 4/45 (8.9%). That of cases without cardiac tamponade and malperfusion was 3/105 (2.9%), and was significantly (p < 0.05) lower than that with malperfusion.

A ninety-day oral toxicity study of a new type of processed gum arabic, from Acacia tree (Acacia senegal) exudates, in F344 rats.

This study was designed to evaluate and characterize any subchronic toxicity of a new type of gum arabic (SUPER GUM [Acacia(sen)SUPER GUM]), a naturally processed polysaccharide exudate from gum acacia trees (Acacia senegal), when administered to both sexes of F344 rats at dietary levels of 0 (control), 1.25%, 2.5%, and 5.0% (10 rats/sex/group). During the study, the treatment had no effects on clinical signs, survival, body weights, and food and water consumption, or on findings of urinalysis, ophthalmology, hematology, or blood biochemistry. Gross pathology and histopathology exhibited no differences of toxicological significance between control and treated rats. Increased relative cecum (filled) weights, evident in both sexes of 5.0% group and females of 1.25% and 2.5% groups, were considered to be a physiological adaptation. Thus, the results indicated the toxic level of SUPER GUM to be more than 5.0%, and the no observed adverse effect level (NOAEL) was concluded to be 5.0% (3,117 mg/kg body weights/day for males, and 3,296 mg/kg body weights/day for males) from the present study.

Transcatheter arterial chemoembolization therapy for hepatocellular carcinoma using polylactic acid microspheres containing aclarubicin hydrochloride.

Transcatheter arterial chemoembolization therapy using polylactic acid microspheres containing aclarubicin hydrochloride (ACR) was performed in 62 patients with primary hepatocellular carcinoma. These microspheres were about 200 microns in diameter and contained 10% (w/w) aclarubicin. A single dose of polylactic acid microspheres containing ACR (50-100 mg of ACR) was administered 1 to 8 times with a mean of 2.2 doses (a total of 160 treatments) in 62 patients. Antitumor effects were observed from the decrease in serum alpha-fetoprotein levels (82.1% of the patients) and in two dimensional size of tumor on computed tomography (93.6%). The cumulative survival rate was 54.3% at 1 year, 24.6% at 2 years, and 19.2% at 3 years, respectively, among 59 patients with unresectable tumors. In 3 resected liver specimens, there was a significant accumulation of ACR in the tumor, and severe necroses of the tumors were observed histologically. Systemic toxicity was mild and all patients tolerated this treatment. These results suggest that transcatheter arterial chemoembolization with the use of polylactic acid microspheres containing ACR is a useful tumor-targeting chemotherapy and is effective in the treatment of hepatocellular carcinoma.

Characterization of a new fetal hemoglobin variant, Hb F Izumi A gamma 6Glu replaced by Gly, by molecular secondary ion mass spectrometry.

Molecular secondary ion mass spectrometry has characterized the structure of a new fetal hemoglobin variant, Hb F Izumi, without separation of peptides or amino acid analysis. First, the mass spectrum of a tryptic digest of the abnormal gamma globin revealed a decreased by 72 mass units in the molecular mass of peptide T-1,2, indicating the presence of a Glu leads to Gly substitution. Next, the analysis of the digest produced by the addition of staphylococcal protease, which specifically cleaves glutamyl peptide bonds, determined the site of substitution at 6th glutamic acid residue in peptide T-1,2 which contains two glutamic acid residues. Since this mass spectrometric approach provides digitalized data on peptide analysis, we call it 'digit printing'. The high sensitivity of this technique is especially promising for the analysis of molecular abnormality in various genetic disorders.

Comparative study of electrothermal bipolar vessel sealer and ultrasonic coagulating shears in laparoscopic colectomy.

BACKGROUND: As an alternative to suture ligatures of the vessels, an electrothermal bipolar vessel sealer (EBVS) was recently developed. Meanwhile, ultrasonic coagulating shears (UCS) have been widely used clinically to provide hemostatic cutting in laparoscopic procedures. We conducted a comparative study to investigate the relative advantages of these two instruments. METHODS: The study included 30 patients with colon cancer who underwent laparoscopic colectomy using either the EBVS or the UCS. We performed a comparative analysis of the instruments by viewing videotapes showing their application in laparoscopic transverse colectomy and sigmoidectomy. RESULTS: Average patient age was 71.6 +/- 1.4 years. Average hospital stay was 14.2 +/- 1.0 days. There were no statistical differences between the groups in age and hospital stay. The incidence of rebleeding was significantly lower in the EBVS group than in the UCS group for both surgical procedures (0.3 vs 1.2 in transverse colectomy, 0.3 vs 2.0 in sigmoidectomy, respectively). In addition, the required time for mesocolon dissection was also significantly shorter when the EBVS was used in both laparoscopic transverse colectomy and sigmoidectomy (7.9 vs 18.4, 15.0 vs 27.6, respectively). CONCLUSION: The use of the EBVS will enable surgeons to reduce the total operating time for laparoscopic colectomy.

A 90-day oral toxicity study of beta-carotene derived from Blakeslea trispora, a natural food colorant, in F344 rats.

A subchronic oral toxicity study of beta-carotene derived from Blakeslea trispora, a natural food colorant, was performed with groups of 10 male and 10 female F344 rats fed the agent at dietary levels of 0%, 0.2%, 1.0% and 5.0% for 90 days. There were no treatment-related adverse effects with regard to body weight, food and water consumption, urinalysis, ophthalmology, hematology, serum biochemistry, and organ weight data. On clinical observation, red coloring of fur was noted in both sexes of the 1.0% and 5.0% group rats, with red feces observed in all treated group animals, and necropsy revealed all rats of the treated groups to have reddish coloration of the contents of the gastro-intestinal tract, due to the pigmentation and thus lacking toxicological significance. On histopathological examination, sporadic spontaneous lesions known to occur in this strain of rats were the only findings, with no specific relation to the test substance. Thus, the no-observed-adverse-effect-level (NOAEL) was judged to be a dietary level of at least 5.0% (3127 mg/kg body weight/day for males, 3362 mg/kg body weight/day for females) for beta-carotene derived from B. trispora under the present experimental conditions.

Selectively induced high MRP gene expression in multidrug-resistant human HL60 leukemia cells.

A subclone HL60/DOX was selected from a human leukemic HL60 cell line for resistance to doxorubicin (DOX) by exposure to stepwise increasing concentrations of the drug and coexposure to a potential P-glycoprotein (P-gp) inhibitor, cepharanthine (a biscoclaurine alkaloid). Compared with the parent HL60 cells, the HL60/DOX cells were 13.0-fold more resistant to DOX and showed multidrug-resistant (MDR) phenotype characterized by 4.6-fold, 2.3-fold, and 5.7-fold cross-resistance to vincristine, pirarubicin, and etoposide, respectively, but no cross-resistance to alkylating agent, cisplatin. Immunocytochemical analyses using the specific monoclonal antibody, MRPr1, and quantitative analyses using a competitive reverse transcription-polymerase chain reaction (CRT-PCR) confirmed overexpression of MRP gene products (about 8-fold determined by CRT-PCR) in this resistant clone. The P-gp expression was not detectable by the monoclonal antibody, C219, in the HL60/DOX cells, and that was consistent with extremely low levels of mdr1 mRNA expression determined by CRT-PCR in this clone. Drug accumulation and efflux studies demonstrated the significantly increased efflux rate of DOX compared to the parent HL60 cells. This enhancement of DOX efflux was reversed by the addition of 10 microM verapamil. To investigate the additional underlying mechanisms contributing to MDR phenotype in the HL60/DOX cells, the levels of DNA topoisomerases (Topo) including Topo I, Topo IIalpha, and Topo IIbeta, and gamma-glutamylcystein synthetase (y-GCS) expression were determined using CRT-PCR techniques. Normal expression of each enzyme at the transcriptional level was demonstrated in this resistant clone. Southern blot analysis of the gene organization in the HL60/DOX cells revealed the amplification of MRP gene. These results indicate that alteration of the drug accumulation from enhanced efflux appears to be a major mechanism(s) of MDR phenotype and attributable to high levels of MRP expression in the HL60/DOX cells. Overexpression of MRP in this clone is regulated by the genomic amplification of DNA and increased levels of the MRP mRNA, independently with the normal expression of Topo I, Topo IIalpha, Topo IIbeta, or gamma-GCS.

Antagonistic effects of interleukin 6 and G-CSF in the later stage of human granulopoiesis in vitro.

The effect of recombinant human interleukin 6 (rhIL-6) on the in vitro growth of human bone marrow myeloid progenitors (granulocyte-macrophage colony-forming units, CFU-GM) was investigated. Recombinant human IL-6 by itself did not induce colony formation. When rhIL-6 at various concentrations was added to the CFU-GM colony cultures containing recombinant human granulocyte colony-stimulating factor (rhG-CSF) or recombinant human granulocyte-monocyte/macrophage colony-stimulating factor (rhGM-CSF), rhIL-6 significantly suppressed the colony formation induced by rhG-CSF, but not by rhGM-CSF. This suppressive effect of rhIL-6 on rhG-CSF-induced, but not rhGM-CSF-induced colony formation was confirmed by using an MY10(+)-cell-enriched population. Neither interleukin 3 nor interleukin 1 alpha suppressed the growth of myeloid progenitors. The preincubation of bone marrow cells with rhIL-6 for a short time (30 min) resulted in a reduction of colonies induced by rhG-CSF, but not by rhGM-CSF. The suppressive effect of rhIL-6 on rhG-CSF-induced colony formation was not observed when the cells were preincubated together with rhG-CSF at a high ratio of rhG-CSF to rhIL-6. The rhIL-6-mediated suppressive effect was further confirmed by blocking the effect by the anti-IL-6 antibody. These results suggest antagonistic interaction between IL-6 and G-CSF in the later differentiation of myeloid progenitors.

Flow cytometric functional analysis of multidrug resistance by Fluo-3: a comparison with rhodamine-123.

Using four cell lines including drug-sensitive K562/Parent cells, P-glycoprotein (Pgp)-mediated multidrug resistant (MDR) K562/VCR, K562/ADR and revertant K562/ADR-R cells, two fluorescent agents, Fluo-3 and rhodamine-123 (Rh-123), were compared as indicators in a functional assay of MDR. Cells were incubated with 4 microM Fluo-3 or 1 microM Rh-123 for 45 min and then the intracellular accumulation of the agent was measured using a flow cytometer. Verapamil (20 microM) or cepharanthine (biscoclaurine alkaloid, 10 microM) was added just before the fluorescent agents. Efflux patterns were also studied 60 min after incubation with or without verapamil and cepharanthine. Increased intracellular accumulation and a delayed efflux pattern of Fluo-3 by verapamil and cepharanthine were demonstrated in multidrug resistant K562/VCR and K562/ADR cells, indicating that Fluo-3 is another good indicator of MDR. However, a similar, but lower, increase in uptake and a delayed efflux pattern of Fluo-3 by verapamil and cepharanthine were also demonstrated even in Pgp-non-overexpressed K562/Parent cells. In contrast, accumulation of Rh-123 was not affected by verapamil and cepharanthine. To further study the Pgp dependency of Fluo-3, another cell line, K562/NC16 expressing minimum MDR1 mRNA, was cloned. Increased uptake and a delayed efflux pattern of Fluo-3, but not Rh-123, with verapamil or cepharanthine were again demonstrated in K562/NC16 cells, indicating that intracellular accumulation of Fluo-3 may be non-specifically influenced by verapamil and cepharanthine at very low levels of Pgp-related MDR, while the influx and efflux patterns of Rh-123 may be specifically affected by Pgp overexpression.

Glut1 expression in T1 and T2 stage colorectal carcinomas: its relationship to clinicopathological features.

Glucose uptake is mediated by glucose transporter (Glut) proteins, which exhibit altered expression in a variety of malignant neoplasms. Glut1 expression is thought to be a potential marker for malignant transformation. The aim of the present study was to investigate the expression of Glut1 protein in colorectal adenomas, T1 and T2 stage carcinomas. Immunohistochemical detection of Glut1 protein was examined in 141 formalin-fixed and paraffin-embedded colorectal tumour specimens (57 adenomas, 84 carcinomas). The degree of Glut1 immunostaining of a specimen was graded according to the proportion of Glut1-positive cells in it; absent (positive cells are 0%), weakly positive (less than 10%), moderately positive (10-50%), and strongly positive (more than 50%). Glut1 expression was present in 18% of the adenomas with low-grade dysplasia, and in 63% of the adenomas with high-grade dysplasia. The positivity in such lesions was usually weak, but was moderate in 8% of the adenomas with high grade dysplasia. For the carcinomas, there were significant correlations between Glut1-positivity and depth of invasion (T1 45% versus T2 74%, P<0.01), histological differentiation (well 49% versus moderately to poorly 74%, P< 0.05) and morphological type (polypoid 42% versus depressed 73%, P< 0.05), if the cut-off value was set at 10% of cells. In conclusion, we clarified the relationship between Glut1 expression and clinicopathological features in T1 and T2 stage colorectal carcinomas, and our results suggested a high malignant potential of the depressed-type carcinoma.

Compton scatter compensation using the triple-energy window method for single- and dual-isotope SPECT.

The spatial distribution of scattered photons varies depending on many factors such as object size and source distribution. We propose a triple-energy window (TEW) scatter compensation method for determining position-dependent Compton scatter. We estimated the count of primary photons at each pixel in the acquired image using the 24% main window centered at the photo peak energy and 3 keV scatter rejection windows on both sides of the main window. We conducted a physical evaluation of this method using phantoms and also applied this method to patients in a clinical trial. The TEW method performed Compton scatter compensation with good accuracy.

Dynamic acquisition with a three-headed SPECT system: application to technetium 99m-SQ30217 myocardial imaging.

A method for SPECT data acquisition, "continuous repetitive rotation acquisition," was developed with a high-sensitivity three-headed SPECT system. The method was applied to the dynamic imaging of 99mTc-SQ30217, a new myocardial imaging agent. After acquisition and reconstruction of SPECT data every minute, projection images at arbitrary intervals were used for tomographic reconstruction to determine the best timing of SPECT imaging in 99mTc-SQ30217. Based on a comparison of several possible acquisition intervals, SPECT data acquisition within 9 min after injection is recommended because of high myocardial uptake (myocardium-to-lung ratio, 2.83 +/- 0.42 (mean +/- s.e.m.) at 3-6 min) and relatively low hepatic uptake (myocardium-to-liver ratio, 0.85 +/- 0.13 at 3-6 min). The rate constant of the clearance of 99mTc-SQ30217 from the myocardium obtained by SPECT was: k1 = 0.249 +/- 0.050 per min (average half-life = 2.8 min) and k2 = 0.012 +/- 0.004/min (average half-life = 58 min). The continuous repetitive rotation acquisition SPECT study appears useful for imaging SQ30217 with its rapidly changing myocardial distribution.

A simulation of dynamic SPECT using radiopharmaceuticals with rapid clearance.

Data acquisition in SPECT assumes that there is no change in radionuclide distribution during data collection. However, this assumption is not valid in radiopharmaceuticals with rapid temporal changes in radioactivity. Artifacts and quantitative errors are studied using phantom studies, mathematical models, and clinical myocardial data. Projection data of each model were sequentially multiplied by weighting coefficients that varied mono-exponentially with time, and the SPECT images were reconstructed. A long data acquisition time in comparison to the clearance of the tracer can be a significant cause of artifact. When the myocardial septum-to-lateral count ratio is used as an index of distortion, a shorter acquisition time than the effective half-life of the tracer is required to reduce the error of the septum-to-lateral count ratio to within 10%. Since 180 degrees rotation acquisition causes artifacts depending on the direction of rotation, 360 degrees acquisition is preferable. Continuous repetitive rotation acquisition is a suitable method for dynamic SPECT to reduce quantitative errors and artifacts.

Scatter and attenuation correction in technetium-99m brain SPECT.

UNLABELLED: We propose a practical method for scatter and attenuation compensation in 99mTc-ECD brain SPECT using a simultaneous emission CT (ECT) and transmission CT (TCT) acquisition system that includes the following major components: (a) triple-headed SPECT gamma camera equipped with fanbeam collimators; (b) external line sources containing 99mTc placed at the focal lines of the collimators; and (c) scatter correction by the triple-energy-window (TEW) method. METHODS: Projection images were obtained over a 360 degrees rotation scan. After acquisition, scatter correction was performed using the TEW method, which corrected scattered photons pixel by pixel in the projection data. Scatter-corrected ECT images were compensated for attenuation using the TCT images with Chang's iterative method, and were converted to activity concentration (kBq/ml) images by obtaining a cross-calibration scan. After validating this method with phantom studies, it was applied to clinical brain imaging using a combination of 925 MBq 99mTc-ECD as a radiopharmaceutical and 222 MBq 99mTc as an external source. ECT and TCT data were acquired separately or simultaneously. RESULTS: SPECT quantification and image quality were improved by performing this correction. The activity concentration images obtained with the simultaneous acquisition were almost identical to those obtained with the separate acquisition. CONCLUSION: This method was clinically practical and cost-effective for reconstructing quantitative 99mTc brain SPECT images.

Increased lung uptake of iodine-123-MIBG in diabetics with sympathetic nervous dysfunction.

UNLABELLED: Scintigraphy with 123I-MIBG and 201TI was compared in patients with various diseases including diabetes mellitus, with and without sympathetic nervous dysfunction. This study was done to assess lung uptake of these tracers semiquantitatively. METHODS: Thirty-eight patients with diabetes mellitus, seven patients with dilated cardiomyopathy (DCM), 12 patients with hypertrophic cardiomyopathy (HCM) and eight healthy subjects were studied. Sympathetic nervous dysfunction was observed in 13 of the 38 diabetic patients. Simultaneous imaging with 123I-MIBG and 201TI was performed. The ratio of lung to total injected dose count and washout rate in the lung were calculated from dynamic images acquired in the initial 2 min and static images acquired at 15 min and at 4 hr after injection of the tracers. RESULTS: Lung uptake of 123I-MIBG at 4 hr was significantly increased in the diabetic group as compared with those in the other groups. In diabetic patients with sympathetic nervous dysfunction, the lung uptake ratio of 123I-MIBG at 4 hr was significantly higher than that in the diabetic patients without sympathetic nervous dysfunction, due to decreased clearance of 123I-MIBG from the lung. On the other hand, increased lung uptake of 201TI was observed in DCM patients at both 15 min and 4 hr. There was no significant difference between lung uptake of 201TI in diabetic patients and that in healthy subjects. CONCLUSION: Lung uptake of 123I-MIBG was increased and lung washout of 123I-MIBG was decreased in diabetic patients with sympathetic nervous dysfunction, while lung uptake of 201TI was not altered. lodine-123-MIBG scintigraphy of the lung may provide information on sympathetic nervous activity in diabetic patients. It is a promising method for studying the kinetics of norepinephrine in the lung because MIBG is taken up in the lung by the same mechanism as norepinephrine.

Feasibility of simultaneous stress 99mTc-sestamibi/rest 201Tl dual-isotope myocardial perfusion SPECT in the detection of coronary artery disease.

UNLABELLED: This study assesses feasibility and diagnostic accuracy of simultaneous stress 99mTc-sestamibi/rest 201 TI dual-isotope myocardial perfusion SPECT with Moore's correction method, in which contamination originating from lead x-rays produced in a collimator was subtracted in the 201TI windows. METHODS: Eighty-one patients with suspected coronary artery disease received exercise 99mTc-sestamibi injection, followed by rest 201TI injection 50 min later, and dual-isotope SPECT was performed (group 1). These results were compared with coronary angiographic findings. Furthermore, to estimate the accuracy of Moore's correction method, 201TI crosstalk into the 99mTc acquisition window (group 2A, n = 20) and 99mTc crosstalk into the 201TI acquisition windows (group 2B, n = 20) were studied. For group 2A, stress 99mTc-sestamibi SPECT (single 99mTc-sestamibi SPECT) was performed, followed by 201TI injection at rest and dual-isotope SPECT acquisition 50 min later. For group 2B, rest 201TI SPECT (single 201TI SPECT) was performed, followed by 99mTc-sestamibi injection at rest and dual-isotope SPECT acquisition 30 min later. RESULTS: Sensitivity and specificity in group 1 were 83% and 99%, respectively, when > or =75% coronary artery narrowing was considered significant. In groups 2A and 2B, SPECT images were divided into 24 segments, and relative regional uptake in each segment was obtained. In group 2A, relative regional uptake of single 99mTc-sestamibi SPECT correlated well with that of dual-isotope SPECT (r = 0.942). In group 2B, relative regional uptake of single 201TI SPECT correlated well with that of dual-isotope SPECT (r = 0.935). Furthermore, in low 201TI uptake segments with relative regional uptake in both single- and dual-isotope SPECT of < or =70%, the degree of concordance between single- and dual-rest 201TI was considered to be high with Bland-Altman analysis and the kappa statistic. Comparison of perfusion defect type demonstrated that, of 22 stress defects within infarct zones, 95% were irreversible and 5% were reversible. In contrast, of 28 stress defects within stenosed vessel zones in noninfarct zones, 89% were reversible and 11% were irreversible (P < 0.0001 versus infarct zones). CONCLUSION: Simultaneous dual-isotope imaging with Moore's correction method is feasible, with acceptable accuracy for detection of coronary artery disease and a small amount of crosstalk into each window.

Inhibition of liver glutathione S-transferase placental form-positive foci development in the rat hepatocarcinogenesis by Porphyra tenera (Asakusa-nori).

The effects of Asakusa-nori, Porphyra tenera (PT), a popular edible seaweed in Japan, on the development of putative preneoplastic lesions, glutathione S-transferase placental form (GST-P)-positive foci, in the male F344 rat liver were examined using a medium-term bioassay system. PT significantly decreased both the number and area of GST-P-positive foci in rat livers initiated with diethylnitrosamine (DEN). To investigate possible mechanisms of inhibition, effects of PT on 5-bromo-2'-deoxyuridine (BrdU) labeling in GST-P-positive foci and the surrounding area of hepatocytes were studied. The ratio of the GST-P-positive foci to surrounding tissue labeling indices was decreased in the PT-treated group as compared with the DEN alone group. Ornithine decarboxylase activity in the liver was slightly increased and spermidine/spermine N'-acetyltransferase activity was slightly decreased in the PT-treated animals. These results suggest that PT possesses chemopreventive effects against DEN-induced hepatocarcinogenesis.

Successful peritransplant therapy in children with active hepatosplenic candidiasis.

Two pediatric leukemic patients with hepatosplenic candidiasis during multidrug antileukemic chemotherapy successfully underwent bone marrow transplantation (BMT) after aggressive antifungal chemotherapy employing fluconazole and amphotericin B with or without splenectomy. One patient received allogeneic marrow graft and the other received an autologous graft. One patient has been disease-free for more than 21 months after BMT without any recurrence of Candida infection. The other patient showed tentative reactivation of hepatic lesions just after BMT by CT scanning, but these lesions disappeared again by continuous administration of the antifungal agents. The second patient died of leukemia relapse without recurrence of fungal infection. Our cases indicate the possibility of successful BMT once a fungal infection is well controlled by antifungal chemotherapy and surgical resection.