Effective treatment of liver metastases with photodynamic therapy, using the second-generation photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC), in a rat model

The only curative treatment for patients with liver metastases to date is surgery, but few patients are suitable candidates for hepatic resection. The majority of patients will have to rely on other treatment modalities for palliation. Photodynamic therapy (PDT) could be a selective, minimally invasive treatment for patients with liver metastases. We studied PDT in an implanted colon carcinoma in the liver of Wag/Rij rats, using the photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC). mTHPC tissue kinetics were studied using ex vivo extractions and in vivo fluorescence measurements. Both methods showed that mTHPC kinetics were different for liver and tumour tissue. After initial high levels at 4 h after administration (0.1 and 0.3 mg kg−1) mTHPC in liver tissue decreased rapidly in time. In tumour tissue no decrease in photosensitizer levels occurred, with mTHPC remaining high up to 48 h after administration. Both concentration data and fluorescence data showed an increase in tumour to liver ratios of up to 6.3 and 5.0 respectively. Illumination with 652 nm (15 J) resulted in extensive damage to tumour tissue, with necrosis of up to 13 mm in diameter. Damage to normal liver tissue was mild and transient as serum aspartate aminotransferase and alanine aminotransferase levels normalized within a week after PDT treatment. Long-term effects of mTHPC-PDT were studied on day 28 after treatment. Regardless of drug dose and drug–light interval, PDT with mTHPC resulted in complete tumour remission in 27 out of 31 treated animals (87%), with only four animals in which tumour regrowth was observed. Non-responding tumours proved to be significantly larger (P < 0.001) in size before PDT treatment. This study demonstrates that mTHPC is retained in an intrahepatic tumour and that mTHPC-PDT is capable of inducing complete tumour remission of liver tumours. © 1999 Cancer Research Campaig

Predictors of Hospitals with Endemic Community-Associated Methicillin-Resistant Staphylococcus aureus

OBJECTIVE: We sought to identify hospital characteristics associated with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) carriage among inpatients. DESIGN: Prospective cohort study. SETTING: Orange County, California. PARTICIPANTS: Thirty hospitals in a single county. METHODS: We collected clinical MRSA isolates from inpatients in 30 of 31 hospitals in Orange County, California, from October 2008 through April 2010. We characterized isolates by spa typing to identify CA-MRSA strains. Using California’s mandatory hospitalization data set, we identified hospital-level predictors of CA-MRSA isolation. RESULTS: CA-MRSA strains represented 1,033 (46%) of 2,246 of MRSA isolates. By hospital, the median percentage of CA-MRSA isolates was 46% (range, 14%–81%). In multivariate models, CA-MRSA isolation was associated with smaller hospitals (odds ratio [OR], 0.97, or 3% decreased odds of CA-MRSA isolation per 1,000 annual admissions; P < .001), hospitals with more Medicaid-insured patients (OR, 1.2; P = .002), and hospitals with more patients with low comorbidity scores (OR, 1.3; P < .001). Results were similar when restricted to isolates from patients with hospital-onset infection. CONCLUSIONS: Among 30 hospitals, CA-MRSA comprised nearly half of MRSA isolates. There was substantial variability in CA-MRSA penetration across hospitals, with more CA-MRSA in smaller hospitals with healthier but socially disadvantaged patient populations. Additional research is needed to determine whether infection control strategies can be successful in targeting CA-MRSA influx

Elastic and vibrational properties of alpha and beta-PbO

The structure, electronic and dynamic properties of the two layered alpha (litharge) and beta (massicot) phases of PbO have been studied by density functional methods. The role of London dispersion interactions as leading component of the total interaction energy between layers has been addressed by using the Grimme's approach, in which new parameters for Pb and O atoms have been developed. Both gradient corrected and hybrid functionals have been adopted using Gaussian-type basis sets of polarized triple zeta quality for O atoms and small core pseudo-potential for the Pb atoms. Basis set superposition error (BSSE) has been accounted for by the Boys-Bernardi correction to compute the interlayer separation. Cross check with calculations adopting plane waves that are BSSE free have also been performed for both structures and vibrational frequencies. With the new set of proposed Grimme's type parameters structures and dynamical parameters for both PbO phases are in good agreement with experimental data.Comment: 8 pages, 5 figure

Differential miRNA expression profiles in cumulus and mural granulosa cells from human pre-ovulatory follicles

BACKGROUND: mural granulosa cells (MGCs) and cumulus cells (CCs) are two specialized cell types that differentiate from a common progenitor during folliculogenesis. Although these two cell types have specialized functions and gene expression profiles, little is known about their microRNA (miRNA) expression patterns.OBJECTIVE: to describe the miRNA profile of mural and cumulus granulosa cells from human pre-ovulatory follicles Methods: using small RNA sequencing, we definedinvestigated the miRNA expression profiles of human primary MGCs and CCs, isolated from healthy women undergoing ovum pick-up for in vitro fertilization (IVF).RESULTS: small RNA sequencing revealed expression of several hundreds of miRNAs in MGCsMGC and CCsCC with 53 miRNAs being significantly differentially expressed between MGCs and CCs. We validated differential expression for miR-146a-5p, miR-149-5p, miR-509-3p and miR-182-5p by RT-qPCR. Analysis of proven targets revealed 37 targets for miR-146a-5p, 43 for miR-182-5p, 2 for miR-509-3p and 9 for miR-149-5p. Gene ontology (GO) analysis for these 4 target gene sets revealed enrichment of 12 GO terms for miR-146a-5p and 10 for miR-182-5p. The GO term ubiquitin-like protein conjugation was enriched within both miRNA target gene sets.CONCLUSION: we generated miRNA expression profiles for MGCs and CCs and identified several differentially expressed miRNAs.</p

Infections after auxiliary partial liver transplantation. Experiences in the first ten patients

Summary In ten auxiliary partial liver transplant recipients selective bowel decontamination (SBD) was used to reduce infections due to gram-negative microorganisms and fungi. During SBD no gram-negative infections occurred. Candida peritonitis was observed in one patient. After discontinuation of SBD serious infections of gram-negative origin did occur and three fungal infections were seen. SBD seems to have a favourable effect in reducing infections by gram-negative microorganisms and fungi. Most striking was the number of enterococcal infections that occurred. Five out of ten patients developed enterococcal infections which in two cases contributed to a fatal outcome. These infections occurred after increase of the number of enterococci in faeces and concomitant positive cultures of bile, ascites or wound drains. This increase could be due to the use of SBD. Also, the kind of biliary anastomosis may play an important role in the relatively high incidence of enterococcal infections. In the postoperative period, recurrence of hepatitis B infection in the liver graft was observed in all patients with cirrhosis due to this virus. Problems caused by other viral infections or protozoal infections remained limited in these ten patients. Zusammenfassung Bei Patienten, bei denen eine auxiliäre, partielle Lebertransplantation durchgeführt wurde, wurde die selektive Darmdekontamination (SBD) eingesetzt, um Infektionen durch gramnegative Mikroorganismen und Pilze zu vermindern. Während SBD traten keine Infektionen durch gramnegative Bakterien auf. Bei einem Patienten wurde eine Candida-Peritonitis beobachtet. Nach Beendigung der SBD kam es zu schweren Infektionen durch gramnegative Bakterien, außerdem zu drei Pilzinfektionen. SBD hat offensichtlich einen günstigen Einfluß im Hinblick auf eine Verminderung von Infektionen durch gramnegative Erreger und Pilze. Bemerkenswert hoch war die Zahl der aufgetretenen Enterokokkeninfektionen. Bei fünf der zehn Patienten traten Enterokokkeninfektionen auf, die in zwei Fällen den letalen Ausgang mitbestimmten. Diesen Infektionen gingen ein Anstieg der Enterokokkenzahlen im Stuhl und zugleich positive Kulturen in Galle, Aszites und Wunddrainagen voraus. Es ist möglich, daß die SBD die Zunahme von Enterokokkeninfektionen begünstigte. Auch die Art der Gallengangsanastomose kann hierzu wesentlich beigetragen haben. Bei allen Patienten, bei denen die Zirrhose durch Hepatitis B Virus verursacht war, kam es postoperativ zu einem Rezidiv durch dieses Virus im Lebertransplantat. Probleme durch andere virale oder Protozoeninfektionen hielten sich bei diesen zehn Patienten in Grenzen

Sequence analysis and molecular characterization of the temperate lactococcal bacteriophage r1t

The temperate lactococcal bacteriophage r1t was isolated from its lysogenic host and its genome was subjected to nucleotide sequence analysis. The linear r1t genome is composed of 33 350 bp and was shown to possess 3' staggered cohesive ends. Fifty open reading frames (ORFs) were identified which are, probably, organized in a life-cycle-specific manner, Nucleotide sequence comparisons, N-terminal amino acid sequencing and functional analyses enabled the assignment of possible functions to a number of DNA sequences and ORFs. In this way, ORFs specifying regulatory proteins, proteins involved in DNA replication, structural proteins, a holin, a lysin, an integrase, and a dUTPase were putatively identified. One ORF seems to be contained within a self-splicing group I intron. In addition, the bacteriophage att site required for site-specific integration into the host chromosome was determined