Microbiologic contamination of peripheral blood progenitor cells collected for hematopoietic cell transplantation

BACKGROUND: Peripheral blood progenitor cells (PBPCs) rather than bone marrow are used increasingly to provide hematologic reconstitution when transfused after marrow-ablative chemotherapy. PBPCs often are collected via central venous catheters that have remained in place for long periods of time and that may become infected. STUDY DESIGN AND METHODS: The investigators reviewed their 5-year experience in collecting PBPCs for the prevalence of bacterial contamination. Except for cotrimoxazole therapy given to prevent Pneumocystis cariini pneumonia, patients were not given antibiotic prophylaxis. RESULTS: Each patient underwent a median of 7 (range, 2–21) PBPC collections; 0.2 percent (3/1040 collections) were culture positive for bacteria (two collections contained coagulase-negative staphylococci and one contained Serratia marcescens). All culture-positive collections were discarded; no PBPCs were culture positive at the time of thawing and transfusion. CONCLUSION: This contamination rate is below that previously reported for bone marrow harvests and platelet concentrate collections. Obtaining PBPCs through large-bore central venous catheters has not added to the risk of infection in transplant patients. A program of screening in vitro cultures and strict adherence to sterility techniques can result in very low microbiologic contamination and thus obviates the need for prophylactic antimicrobials in the PBPCs and in the patient.     

CLIMACTERIC SYMPTOMS IN HEALTHY MIDDLE-AGED WOMEN

SUMMARY The incidence of climacteric symptoms was determined in 247 healthy premenopausal women in a community setting. These volunteers had been recruited to a longitudinal study of bone density. Of these subjects, 46 ceased to menstruate during the study, and in this subgroup symptoms were compared before and after cessation of menstruation. Only hot flushes increased after cessation of menstruation in the longitudinal study and showed age correlation in the cross-sectional study. Hot flushes thus emerged as a true menopausal symptom. Although evidence for this is weaker, cold sweats and suffocation seem likely to be genuinely menopausal. Breast discomfort and the four mood symptoms of irritability, excitability, depression and poor concentration improved after cessation of menstruation, and this study gives no support for their being part of the menopausal syndrome; it suggests that these symptoms are more likely to be related to menstruation than to the menopause.     

Nonrandom chromosome abnormalities in acute leukemia and dysmyelopoietic syndromes in patients with previously treated malignant disease

Cytogenetic studies were performed on 26 patients who developed acute nonlymphocytic leukemia (ANLL) or a dysmyelopoietic syndrome after treatment of a primary malignancy. Fifteen patients had radiotherapy and chemotherapy, seven had only chemotherapy, and four had only radiotherapy. The median times from diagnosis of the initial disease to the development of bone marrow dysfunction for these treatment groups were 50, 46, and 49 mo, respectively. Twenty-five patients had an abnormal karyotype in myeloid cells. Loss of part or all of no. 5 and/or no. 7 was noted in 23 of 25 patients with aneuploidy. Loss of no. 5 was noted only in patients who previously had malignant lymphoma, whereas loss of no. 7 was seen in these patients as well as in those who had other malignancies. Abnormalities of both nos. 5 and 7 occurred in 53% of the patients treated with combined therapy and in only 27% of patients treated with either modality alone. Although these changes are distinctly different from those noted in lymphomas, they are similar to those seen in 25% of aneuploid patients with ANLL de novo.     

Hypoxic hepatitis in children after cardiac surgery

<正>To the Editor: Hypoxic hepatitis(HH), also known as ischemic hepatitis or shock liver, is a liver injury characterized by necrosis of centrilobular hepatocytes with a rapid increase in serum aminotransferase levels. The incidence rate of HH among patients in the intensive care unit(ICU) was found to be 0.9%-11.9% [1]. Occurrence of HH appears to have a significant impact on the clinical outcome.     

Impact of laparoscopic right hemicolectomy for colon cancer

INTRODUCTION

This study specifically examined right colonic cancer resection, a common operation for colorectal surgeons starting laparoscopic resection, to assess the impact of commencing laparoscopy.

PATIENTS AND METHODS

A total of 56 patients undergoing open (n = 34) and attempted laparoscopic (n = 22) elective right hemicolectomy for colorectal cancer between November 2003 and March 2007 were compared. Postoperative stay was the primary outcome. Secondary outcomes included analgesic requirements, bowel recovery, morbidity and mortality. Frequency of laparoscopic versus open surgery over time was also examined.

RESULTS

Resections attempted laparoscopically increased from 9.1% to 75% in the first and last quarters of the study period, respectively (P = 0.0002). Uptake of ‘enhanced recovery’ was mainly in the laparoscopic group. Conversion was required in two of 22 patients. Attempted laparoscopic cases had a shorter median postoperative stay (6 vs 10 days; P < 0.0001), duration of parenteral or epidural analgesia (48 vs 72 h; P < 0.0001) and time to first bowel action (3 vs 4 days; P = 0.001) compared with open cases. Demography, tumour characteristics, morbidity and mortality were comparable between groups. Multivariate analysis identified decreased age, attempted laparoscopic surgery, use of enhanced recovery and absence of complications as independently shortening postoperative stay.

CONCLUSIONS

Advantages of laparoscopic surgery and enhanced recovery, even early in a surgeon''s experience, suggest this is the preferred mode for elective right colon cancer resection.     

High Imminent Vertebral Fracture Risk in Subjects With COPD With a Prevalent or Incident Vertebral Fracture

Subjects with chronic obstructive pulmonary disease (COPD) have an increased risk of vertebral fractures (VFs); however, VF incidence is largely unknown. Therefore, the aim of our study was to determine the incidence of new and/or worsening VF in subjects with COPD. Smokers and subjects with COPD (GOLD II–IV) from the ECLIPSE study with complete set of chest CT scans (baseline and 1‐ and 3‐year follow‐up) to evaluate vertebrae T₁ down to L₁ were included. If a VF was diagnosed on the last scan, detailed VF assessment of the previous scans was performed. VFs were scored according to the method of Genant as mild, moderate, or severe. Main outcome measure was the cumulative incidence of new and/or worsening VF at subject level, within 1 and 3 years. Of 1239 subjects (mean age 61 years, 757 males [61%], 999 subjects with COPD), 253 (20.5%) had ≥1 prevalent VF. The cumulative incidence of VFs was 10.1% within 1 year and 24.0% within 3 years. After adjustment for age, sex, body mass index (BMI), pack‐years, and smoking status, prevalence and incidence were similar between smokers and COPD GOLD stages. Within 1 year, 29.2% of the subjects with a prevalent VF had an incident VF, compared with 5.1% in absence of prevalent VF (hazard ratio [HR] = 5.1; 95% confidence interval [CI] 3.6–7.4) and 58.5% versus 15.0% within 3 years (HR = 3.6; 95% CI 2.9–4.6). The incidence of VF was higher with increasing number and severity of prevalent VFs. Among subjects having an incident VF within the first year, 57.3% had a subsequent VF within the next 2 years. In this study, more than half of the smokers and subjects with COPD with a prevalent VF or an incident VF within the first year sustained a subsequent VF within 3 years. The 3‐year risk was even higher in the presence of multiple or severe prevalent VFs. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.     

The cell and molecular basis of leukocyte common antigen (CD45)- triggered, lymphocyte function-associated antigen-1-/intercellular adhesion molecule-1-dependent, leukocyte adhesion

We recently reported that cross-linking the leukocyte common antigen (CD45) can rapidly induce aggregation of human peripheral blood mononuclear cells via lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) interactions. Herein, we have examined both T-cell--monocyte cellular interactions and the molecular signaling that are involved in this phenomenon. Experiments using highly purified T lymphocytes showed that CD45-induced aggregation requires the presence of both T cells and monocytes. Cross- linking CD45 only on T lymphocytes, but not on monocytes, initiated cellular clustering after reconstituting to the respective untreated cell type. By several criteria, CD45-induced clustering of T cells to autologous monocytes was shown to be Fc-receptor--independent. When comparing intracellular signaling in leukocyte aggregation induced by CD45 cross-linking versus phorbol myristate-12-13-acetate (PMA) treatment, the former was found to be fivefold to 10-fold more sensitive to H-8, a reagent that effectively blocks cAMP- and cGMP- dependent protein kinases. On the other hand, reagents that increase intracellular cAMP levels (eg, dbcAMP, forskolin, and IBMX), protein kinase C (PKC) inhibitors (eg, staurosporine), and tyrosine kinase inhibitors (eg, herbimycin A and genistein) all readily inhibited PMA- induced, but not CD45 monoclonal antibody-induced, aggregation. We conclude that cross-linking the leukocyte common antigen on T cells induces LFA-1--/ICAM-1--dependent T-cell--monocyte aggregation through a unique signaling pathway independent of PKC, which involves instead cAMP-/cGMP-dependent protein kinases.     

Analysis of clonal expansions through the normal and premalignant human breast epithelium reveals the presence of luminal stem cells

It is widely accepted that the cell of origin of breast cancer is the adult mammary epithelial stem cell; however, demonstrating the presence and location of tissue stem cells in the human breast has proved difficult. Furthermore, we do not know the clonal architecture of the normal and premalignant mammary epithelium or its cellular hierarchy. Here, we use deficiency in the mitochondrial enzyme cytochrome c oxidase (CCO), typically caused by somatic mutations in the mitochondrial genome, as a means to perform lineage tracing in the human mammary epithelium. PCR sequencing of laser‐capture microdissected cells in combination with immunohistochemistry for markers of lineage differentiation was performed to determine the clonal nature of the mammary epithelium. We have shown that in the normal human breast, clonal expansions (defined here by areas of CCO deficiency) are typically uncommon and of limited size, but can occur at any site within the adult mammary epithelium. The presence of a stem cell population was shown by demonstrating multi‐lineage differentiation within CCO‐deficient areas. Interestingly, we observed infrequent CCO deficiency that was restricted to luminal cells, suggesting that niche succession, and by inference stem cell location, is located within the luminal layer. CCO‐deficient areas appeared large within areas of ductal carcinoma in situ, suggesting that the rate of clonal expansion was altered in the premalignant lesion. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

他汀类药物：增加糖尿病发生风险

他汀类药物是否会增加糖尿病发病风险,一直备受争论。本研究根据已发表和未发表的文献资料,用Meta方法分析该类药物使用与糖尿病发生的相关性。     

Vitamin D attenuates proteinuria by inhibition of heparanase expression in the podocyte

The glomerular filtration barrier consists of podocytes, the glomerular basement membrane, and endothelial cells covered with a glycocalyx. Heparan sulphate (HS) in the glomerular filtration barrier is reduced in patients with proteinuria, which is associated with increased expression of the HS‐degrading enzyme heparanase. Previously, we showed that heparanase is essential for the development of proteinuria in experimental diabetic nephropathy. Vitamin D supplementation reduces podocyte loss and proteinuria in vitro and in vivo. Therefore, we hypothesize that vitamin D reduces proteinuria by reducing glomerular heparanase. Adriamycin‐exposed rats developed proteinuria and showed increased heparanase expression, which was reduced by 1,25‐dihydroxyvitamin D₃ (1,25‐D₃) treatment. In vitro, adriamycin increased heparanase mRNA in the podocyte, which could be corrected by 1,25‐D₃ treatment. In addition, 1,25‐D₃ treatment reduced transendothelial albumin passage after adriamycin stimulation. In line with these results, we showed direct binding of the vitamin D receptor to the heparanase promoter, and 1,25‐D₃ dose‐dependently reduced heparanase promoter activity. Finally, 1,25‐D₃‐deficient 25‐hydroxy‐1α‐hydroxylase knockout mice developed proteinuria and showed increased heparanase, which was normalized by 1,25‐D₃ treatment. Our data suggest that the protective effect of vitamin D on the development of proteinuria is mediated by inhibiting heparanase expression in the podocyte. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.