Impact of prompt intervention in response to positive blood culture results during weekends by collaboration between infectious disease specialists and microbiology laboratory staff.

The purpose of this investigation was to elucidate the impact of prompt intervention for patients whose blood culture results became positive during weekends, as this is not standard care in some countries. A retrospective cohort study was conducted in a tertiary referral hospital. From June 2015, results of positive blood cultures became available during weekends. If infectious disease specialists identified cases of bacteremia on suboptimal antimicrobial coverage, they contacted the primary team for modification of antibiotic treatment. We reviewed patients whose blood culture results became positive during weekends, comparing the pre-intervention (September 2014 to May 2015) and post-intervention (June 2015 to February 2016) periods. In total, 1081 (post-intervention 568 [52.5%]) bacteremia episodes were included (median patient age [interquartile range, IQR]: 72 [60-82] years; men: 625 [57.8%]). During the post-intervention period, 187 (32.9%) bacteremia episodes were detected during weekends. Infectious disease specialists evaluated the positive blood culture results 1, 2, and ≥3 days prior in 77 (13.6%), 88 (15.5%), and 22 (3.9%) cases, respectively. Although the 7- and 30-day mortality did not significantly improve after the intervention, the length of hospital stay (LOS) in the hospital-acquired bacteremia group was significantly reduced during the post-intervention period after controlling for confounders (post- vs. pre-intervention: median days [IQR]: 37 [19-63] vs. 46.5 [24.8-86.3], p = 0.030). Blood culture results became positive during weekends in one-third of bacteremia cases. The LOS was shortened after the intervention in the hospital-acquired bacteremia group. This could be an important antimicrobial stewardship target.

Dietary intake estimations of polybrominated diphenyl ethers (PBDEs) based on a total diet study in Osaka, Japan.

This study presents the results of a total diet study performed for estimating the dietary intake of polybrominated diphenyl ethers (PBDEs) in Osaka, Japan. The concentrations of 36 PBDEs were measured in samples from 14 food groups (Groups I-XIV). PBDEs were detected only in Groups IV (oils and fats), V (legumes and their products), X (fish, shellfish, and their products), and XI (meat and eggs) at concentrations of 1.8, 0.03, 0.48, and 0.01 ng g⁻¹, respectively. For an average person, the lower bound dietary intakes of penta- and deca-formulations were estimated to be 46 and 21 ng day⁻¹, respectively. A high proportion of the decabrominated congener (DeBDE-209) was observed in Group IV. To confirm the presence of DeBDE-209 in vegetable oils, an additional analysis was performed using 18 vegetable oil samples. Of these, seven contained ng g⁻¹ levels of DeBDE-209.

Effect of hyperthermia combined with external radiation therapy in primary non-small cell lung cancer with direct bony invasion.

PURPOSE: Local control in lung cancer directly invading the bone is extremely poor. Effects of regional hyperthermia combined with conventional external beam radiation therapy were evaluated. MATERIALS AND METHODS: Thirteen patients with non-small lung cancer (NSCLC) with direct bony invasion were treated with hyperthermia plus irradiation (hyperthermia group). The treatment outcome was compared with the historical treatment results in 13 patients treated with external radiation therapy alone (radiation alone group). In patients with no distant metastasis, radiation therapy at a total dose of 60-70 Gy was administered to both groups. Hyperthermia was performed for 45-60 min immediately after irradiation for two-four sessions with radiofrequency capacitive heating devices. RESULTS: For primary response, 10 of the 13 tumours responded to the treatment (3 CR, 7 PR) in the hyperthermia group, whereas seven tumours responded (1 CR, 6 PR) in the radiation alone group. The 2-year local recurrence-free survival rate for clinical M(0) patients in the hyperthermia group and that in the radiation alone group were 76.1 and 16.9%, respectively. Three patients died of distant metastases within 2 years in the hyperthermia group, but two out of three tumours histologically disappeared, even in the autopsy examination. The 2-year overall survival rate for clinical M(0) patients in the hyperthermia group and that in the radiation alone group were 44.4 and 15.4%, respectively. No severe pulmonary complication was observed in either group. CONCLUSIONS: Regional hyperthermia combined with conventional irradiation could be a tool to improve local control in patients with NSCLC deeply invading the chest wall.

Bilateral crossed cerebello-cerebral diaschisis and mutism after surgery for cerebellar medulloblastoma.

A 7-year-old boy developed mutism after surgery for cerebellar medulloblastoma. Postoperative magnetic resonance imaging (MRI) showed atrophy of the cerebellar vermis and both cerebellar hemispheres, predominantly on the right side. Single photon emission computed tomography (SPECT) with technetium-99m-ethyl cysteinate dimer (Tc-99m ECD) revealed decreased cerebral blood flow (CBF) in the bilateral thalami, bilateral medial frontal lobes, and left temporal lobe in addition to the cerebellar vermis and both cerebellar hemispheres when mutism was manifest, indicating the existence of bilateral crossed cerebello-cerebral diaschisis (BCCCD). Circulatory disturbance in both cerebellar hemispheres secondary to tumor resection probably caused BCCCD in both cerebral hemispheres, predominantly in the left, via the dentatothalamocortical pathway (DTCP). With recovery of his mutism, CBF increased in the right thalamus, bilateral medial frontal lobes and left temporal lobe. Thus BCCCD was improved, with only a slight decrease in CBF still persisting in the left thalamus. The mechanism of mutism may have involved damage to the cerebellar vermis (the site of incision at operation), the left dentate nucleus (heavily infiltrated by the tumor) and the right dentate nucleus of the cerebellum (affected by circulatory disturbance secondary to acute postoperative edema). The SPECT findings suggested that mutism was associated with BCCCD-induced cerebral circulatory and metabolic hypofunction in the supplementary motor area mediated via the DTCP.

Clinical application of low dose-rate brachytherapy combined with simultaneous mild temperature hyperthermia.

BACKGROUND: Recent biological research has shown that mild temperature hyperthermia (MTH) around 41 degrees C simultaneously combined with low dose-rate irradiation (LDRI) is an effective treatment modality for cancer. The aim of the study was to assess the clinical usefulness of a combination of MTH and simultaneous low dose-rate brachytherapy. MATERIALS AND METHODS: Seven superficial and 8 deep-seated tumors were included in this protocol. Two tumors had no previous treatment and the remainder were recurrent tumors which had arisen from previously treated sites. The average major diameters of superficial and deep tumors were 8.6 and 7.0 cm, respectively. The average values for Tmin in superficial and deep tumors were 41.5 and 40.7 degrees C, respectively. Brachytherapy was delivered by 137Cs and/or 192Ir LDRI sources. RESULTS: For superficial tumors, six of the seven tumors responded to the treatment (4 achieved CR, 2 PR, 1 NC) and four tumors did not recur within the follow-up period of 5-15 months. All of the deep tumors responded and 5 achieved CR, 3 PR. Four tumors recurred 4-17 months after the treatment and the remainder showed no local recurrence within the follow-up period of 4-31 months. CONCLUSION: MTH simultaneously combined with LDRI was an effective method for treating progressive and bulky tumors with a previous treatment history.

Biological cell survival mapping for radiofrequency intracavitary hyperthermia combined with simultaneous high dose-rate intracavitary irradiation.

We examined the best way to combine recently developed radiofrequency intracavitary hyperthermia with simultaneous high dose-rate intracavitary brachytherapy in an original experimental model. Temperature distribution was measured with an experimental phantom which was immersed in a water bath with the temperature controlled at 37 degrees C. Radiation dose distribution was calculated with a treatment-planning computer. Cell survival was measured by colony assay with HeLa-TG cells in vitro. Radiation dose response at 1 - 7 Gy and time response with hyperthermia in the range of 40 - 46 degrees C were estimated. Radiation dose-response curves in simultaneous treatment with hyperthermia for 30 min at 37 to 46 degrees C were estimated and the surviving fractions in combined treatment were plotted against temperature. For intracavitary radiation alone, cell survival rates increased with increasing distance from the source. For intracavitary hyperthermia alone, the maximum temperature was observed at a depth of 13 mm from the surface of the applicator under suitable treatment conditions. Homogeneous cell killing from the surface of the applicator to a tumor depth of 13 mm was observed under a specific treatment condition. Our experimental model is useful for evaluating the best simultaneous combined treatment.

Radiologic spectrum of rectal stenosis.

Rectal stenosis is a common condition caused by a wide variety of diseases, including both intrinsic and extrinsic disorders, as well as both malignant and benign pathologies. Barium enema, CT, and MRI are the primary modalities for the evaluation of the disease, and careful observation of the characteristic radiologic features usually leads to correct diagnosis. However, some of the lesions looks very similar and are difficult to differentiate from each other. The purpose of this study is to review the literature on diseases that cause rectal stenosis, to clarify the characteristics of radiologic features, and to suggest the limitations in differential diagnosis. Deliberate analysis of these imaging features and correlation with clinical manifestations can facilitate a more specific diagnosis.

Intussusception: the role of general anesthesia during hydrostatic barium reduction.

MATERIALS AND METHODS: A total of 74 patients with intussusception were divided into two groups: 43 cases in 39 patients between April 1974 and June 1988 were treated under general anesthesia, and 39 cases in 35 patients between July 1988 and January 1994 were treated without it. We compared the success rates of barium reduction of intussusception in the two groups and used Fisher's exact probability test to assess whether they differed significantly. RESULTS: The overall success rates with general anesthesia and without general anesthesia were 91% (39/43) and 95% (37/39), respectively. The use of general anesthesia did not significantly affect the success rate of barium reduction (p > 0.3). CONCLUSION: The use of general anesthesia for hydrostatic barium reduction of intussusception did not improve the success rate of this procedure. Therefore we recommend that, in view of its associated disadvantages, general anesthesia should not be used during this procedure.

[The use of predeposited autologous blood transfusion for radical prostatectomy and total cystectomy].

BACKGROUND: To avoid homologus blood transfusion, we performed the operation for intra-pelvic malignancy with predeposited autologus blood using recombinant human erythropoietin (rH-EPO). MATERIALS AND METHODS: The seven cases of radical prostatectomy and the 15 cases of total cystectomy were analyzed retrospectively. All cases were given ferrons sulfate/200 mg of iron orally every day to the day before the operation and treated with 24,000 unit of rH-EPO subcutaneously every week. The target volumes of preoperative autologus blood collection were 800 to 1,000 ml and 800 to 1,200 ml for radical prostatectomy and total cystectomy, respectively. For each case, 400 ml blood was collected once a week. RESULTS: In cases of radical prostatectomy, the preserved blood volume was 885.7 +/- 157.4 ml and 6 out of 7 operations were successfully performed without additional homologus blood transfusion (85.7%). In total cystectomy, the preserved blood volume was 1,033.3 +/- 167.6 ml and 14 out of 15 operations were successfully performed without additional homologus blood transfusion (93.3%). The bleeding volume during operation showed no significant difference compared to control group where used homologus blood transfusion. Postoperative courses were uneventful and there encountered no severe side effects and complications in all our procedures. CONCLUSIONS: Our study indicates that in cases of radical prostatectomy and total cystectomy, the operation with predeposited autologus blood using rH-EPO is possible to be performed in safe. The effect on long term prognosis of malignancy is not clear, however, this technique is helpful able to avoid hazardous issues related to homologus blood transfusion during the operation.

Interaction between low dose-rate irradiation, mild hyperthermia and low-dose caffeine in a human lung cancer cell line.

PURPOSE: To investigate cell killing by means of low dose-rate irradiation (LDRI) combined with concurrent mild hyperthermia and to determine the effect of low-dose caffeine on this combination treatment. MATERIALS AND METHODS: Human lung adenocarcinoma cells, LK87, were treated with LDRI (50 cGy/h) in combination with mild hyperthermia at 41 degrees C and low-dose caffeine (1 mM). Cell survival was estimated by clonogenic assay. Flow-cytometry was performed with PI staining using FACScan. Heat-shock protein (HSP72/73) was measured by the Western blotting method. All treatments were simultaneously performed for up to 48 h (24 Gy). RESULTS: LDRI cytotoxicities were enhanced by hyperthermia at 41 degrees C. D0 calculated from the dose-response curve for LDRI combined with 41 degrees C was 3.46 Gy whereas it was 6.55 Gy for LDRI alone. The survival curve for LDRI +41 degrees C demonstrated no chronic thermotolerance up to 48 h. For LDRI + simultaneous low-dose caffeine, cell killing was also enhanced, where D0 was 3.38 Gy at 37 degrees C. Radiosensitization caused by caffeine was enhanced by combination with simultaneous mild hyperthermia at 41 degrees C, where D0=1.78 Gy. Cell cycle analysis demonstrated remarkable G2 and mild G1 arrest for LDRI alone, but only G1 arrest was observed for LDRI combined with 41 degrees C and for LDRI combined with caffeine. Strong and early G1 arrest was observed in the treatment with LDRI + caffeine at 41 degrees C. The amount of HSP72/73 in the combination of LDRI with caffeine at 41 degrees C was less than that at 41 degrees C alone. CONCLUSION: LDRI cytotoxicity was enhanced by non-lethal hyperthermia. Low dose caffeine produced further cell killing in the combination of LDRI with mild hyperthermia.

31P NMR spectroscopy can predict the optimum interval between fractionated irradiation doses.

This study was performed to clarify whether changes in the metabolites observed by phosphorous-31 magnetic resonance spectroscopy (31P-MRS) could indicate an optimum interval between two doses of radiation in a murine tumor model. Murine mammary carcinoma cells, FM3A, were irradiated 7 days after transplantation with a single 5 Gy dose without anesthesia. 31P spectra were measured with a spectrometer up to 30 days. The beta-ATP/Pi and PCr/Pi values were calculated from the peak area of each spectrum. In a fractionation experiment, two fractions of irradiation at a 5 Gy per fraction were given at 0, 1, 2, 3 and 6 day intervals. Tumor growth delay was also scored to determine the fractionated radiation effect. In the control group, beta-ATP/Pi and PCr/Pi decreased with tumor growth. In the single irradiation group, the tumor did not grow up to day 6, and an initial rise and subsequent decrease in beta-ATP/Pi and PCr/Pi were observed. Maximum beta-ATP/Pi and PCr/Pi were observed on day 2 after irradiation. In a fractionation experiment, the greatest growth delay was observed in the two day interval group, in which maximum beta-ATP/Pi and PCr/Pi were demonstrated in 31P-MRS. Our results suggested that changes in the metabolites observed by 31P-MRS could be useful indicators for determining the fractionation schedule in radiation therapy.

Effects of guizhi-fuling-wan on male infertility with varicocele.

Thirty-seven infertile patients with varicocele were treated with Guizhi-Fuling-Wan (7.5 g/day) for at least 3 months. Before and after the administration, semen qualities such as sperm concentration and motility were examined, and the varicocele was graded. A varicocele disappearance rate of 80% was obtained with 40 out of 50 varicocele, and improvement of sperm concentration and motility were found in 71.4% and 62.1% of patients, respectively. From these results, Guizhi-Fuling-Wan is considered to be effective for circulation disorders in varicocele as well as semen quality.

Distinctive developmental origins and specificities of murine CD5+ B cells.

CD5+ B cells constitute a small fraction of cells in the spleen of adult mice that exhibit numerous features serving to distinguish them from the bulk of IgD++CD5- "conventional" B cells. In this review we focus on two major questions relating to this population: 1) the relationship of CD5+ B cells to other B cells; and 2) the distinctive enrichment of particular autoreactive specificities in this subset. The nature of their origins is clarified by a thorough analysis of intermediate stages of early B-cell development in both fetal and adult tissues. The reactivity to bromelain-treated mouse red blood cells serves as a prototype system for the investigation of biased specificities in CD5+ B cells. These lines of investigation lead us to propose that CD5+ B cells in the adult are the remnant of a distinct fetal B-cell differentiation pathway wherein selection of cells from this fetal/neonatal population into the adult long-lived pool results in the over-expression of certain germline-encoded autoreactivities.

Electrolyte disturbances caused by intravenous contrast media.

The changes in serum electrolytes (sodium, potassium, ionized calcium, and total calcium) produced by high-dose (3 ml/kg) intravenous contrast media were investigated in Japanese white rabbits. The test solutions included sodium/meglumine diatrizoate (370 mgI/ml), sodium/meglumine ioxaglate (320 mgI/ml), iohexol (350 mgI/ml), iopamidol (370 mgI/ml), 20% mannitol, and isotonic saline. The alterations in serum ionized calcium were relatively small and transient, and correlated with changes in the hematocrit. Diatrizoate caused a significant decrease in ionized calcium in comparison with other contrast media and mannitol. The ratio of ionized calcium to total calcium showed no significant decrease in any group. The changes in potassium did not correlate with those in hematocrit. Diatrizoate caused a smaller decrease in potassium than low-osmolality contrast media, which may suggest that diatrizoate caused a shift in potassium from extravascular space to intravascular space. In conclusion, intravenous infusion of high doses of low-osmolality contrast media did not cause clinically significant alterations in serum electrolytes.

Developmental origins, specificities and immunoglobulin gene biases of murine Ly-1 B cells.

Ly-1 B cells in mouse show numerous phenotypic and functional features that distinguish them from the bulk of IgDhigh/Ly-1- B cells. Their association with autoantibody production and the presence of Ly-1 on a group of murine B lymphomas that also exhibit certain specificities enriched in the normal population has stimulated continuing interest in this population. We have taken two approaches in our investigations of these cells: 1) defining the origins of Ly-1 B cells (the "lineage question"); and 2) studying the expression of particular specificities and associated immunoglobulin V genes enriched in this population. In this review we present the experimental background that supports our current understanding of Ly-1 B cells as the remnant of a fetal B cell differentiation pathway and suggest that the selection of cells from this fetal/neonatal population into the adult long-lived pool results in the over-expression of certain germline-encoded autoreactivities, such as antibody to bromelain-treated mouse red blood cells and intact thymocytes.

A single VH gene is utilized predominantly in anti-BrMRBC hybridomas derived from purified Ly-1 B cells. Definition of the VH11 family.

By establishing hybridomas from two distinct surface IgM+ splenic B cell populations, Ly-1 B cells and "conventional" (Ly-1-) B cells, we found that the Ly-1 B population includes a 30 to 70 times higher frequency (1 to 2%) of cells with specificity for bromelain treated autologous red blood cells (anti-BrMRBC) when compared with conventional B cells (0.03%). We cloned and sequenced the V genes encoding anti-BrMRBC antibody from two hybridomas made with Ly-1 B cells sorted from the spleen of SM/J mice. The VH sequence (for both) is identical with the previously reported sequence associated with this specificity and belongs to a new VH gene family. This gene family, defined here as VH11, has only two members and is the predominant VH rearranged in a collection of Ly-1 B derived anti-BrMRBC hybridomas, always in association with a single VL gene (a member of the V kappa 9 family). Furthermore, analysis of hybridomas made with Ly-1 B cells sorted from the peritoneum reveals a yet higher increased frequency of VH11-encoded anti-BrMRBC specificity (30%). This variation in frequency of anti-BrMRBC in the Ly-1 population depending on location, together with the repeated association of VH11 with a particular V kappa gene suggest that antigen driven selection is (at least in part) responsible for the biased V gene expression seen in this population. Furthermore, a mechanism that might contribute to biased expression, preferential rearrangement due to close proximity to J (as seen in pre-B lines), is excluded by localization of VH11 5' to several of the more J-proximal families (Q52, 7183).

Biotinidase in human breast milk.

Biotinidase activity in 19 samples of human breast milk was investigated with the sensitive high-performance liquid chromatography (HPLC)-fluorometric method that we developed. All samples exhibited biotinidase activity. For mature milk the mean activity of 17 samples was 0.208 nmol.min-1.mL-1 milk (range, 0.087-0.516 nmol.min-1.mL-1) and mean specific activity was 7.51 pmol.min-1.mg-1 protein (range, 2.17-17.2 pmol.min-1.mg-1). These values are relatively low compared with the activity in human serum (5.26 +/- 2.92 nmol.min-1.mL-1 serum and 95.6 +/- 53.1 pmol.min-1.mg-1 protein; n = 246). Biotinidase activities of milk obtained at various times after birth were not significantly different. However, biotinidase activity in colostrum was about five times higher than that of mature milk. The existence of biotinidase activity in all specimens suggests that this enzyme plays an important nutritional role during infancy.

Effects of PUVA therapy on skin surface lipids: skin surface lipid peroxidation in psoriasis vulgaris and its biological significance.

PUVA therapy (Psoralen + UVA irradiation) is an effective mode of photochemotherapy for psoriasis vulgaris. The biological significance of PUVA therapy for psoriasis vulgaris has mainly been considered to be based on DNA, especially the formation of DNA crosslinks between complementary DNA stands. On the other hand, we have already reported that skin surface lipids were oxidized by UVA irradiation in vitro and this reaction was enhanced in the presence of 8-methoxy-psoralen by a singlet oxygen mechanism. Keeping this in mind, we conducted an experiment to determine whether lipid peroxide can be formed in skin surface lipids following systemic PUVA therapy in psoriasis patients and the following results were obtained: 1) a marked increase of lipid peroxide values in skin surface lipids occurred following PUVA therapy; and 2) the amount of squalene in skin surface lipids was decreased by this treatment. These results indicate that skin surface lipids can be oxidized by PUVA therapy in vivo and this lipid peroxidation on the skin surface may be related to the effects of PUVA therapy on psoriasis vulgaris.

Ly-1 B cells: functionally distinct lymphocytes that secrete IgM autoantibodies.

Studies presented here introduce another perspective on the mechanisms responsible for IgM autoantibody production. A unique subpopulation of B lymphocytes (Ly-1 B) that concomitantly expresses IgM, IgD, Ia, and Ly-1 membrane glycoproteins is present at higher frequencies in NZB and NZB-related mice. The Ly-1 B subpopulation in these autoimmune animals is responsible for the "spontaneous" IgM secretion demonstrated with cultured NZB spleen cells and contains the cells that secrete typical NZB IgM autoantibodies to single-stranded DNA and to thymocytes. In addition, the Ly-1 B population in normal mouse strains (and in NZB) contains virtually all of the spleen cells that secrete IgM autoantibodies reactive with bromelain-treated mouse erythrocytes. Since a different B-cell subpopulation (IgM+, IgD-, Ly-1) secretes most of the IgM antibodies produced in responses to exogenous antigens, we conclude that Ly-1 B cells constitute a functionally distinct B-cell population important in certain kinds of autoimmunity.