Cisplatin and vinorelbine first-line chemotherapy in non-resectable malignant pleural mesothelioma

The aim was to evaluate the activity of cisplatin and vinorelbine in previously untreated, inoperable patients having histologically verified malignant pleural mesothelioma (MPM), normal organ function, and performance status 0–2. Treatment was vinorelbine 25 mg m−2 i.v. weekly and cisplatin 100 mg m−2 i.v. every 4 weeks with hydration and standard prophylactic antiemetic treatment. Patients gave written informed consent. Characteristics of 54 consecutive patients were: males 85%, epithelial subtype 74%, IMIG stages III and IV 35 and 46%, performance status 0, 1, and 2, 26, 69, and 6%, and median age 63 years (31–78 years). CTC grade 3 or 4 toxicity occurred with respect to leukocytopenia (48% of patients, grade 4 in 13%), nausea (13%), neurotoxicity (11%), nephrotoxicity (4%), and other toxicities (9%). There were no toxic deaths. The median number of cycles was four. The fraction of patients alive at 1-, 2-, and 3-years were 61, 31, and 4%, respectively, and median survival and median time to progression were 16.8 months (0.5 to 46.4 +months) and 7.2 months (1.6 to 40.6 + months). There were two CRs and 14 PRs (response rate 29.6%). Cisplatin and intravenous vinorelbine is a highly active regimen in MPM with a response rate and survival comparable to the most active regimens so far reported

Differential cell reaction upon Toll-like receptor 4 and 9 activation in human alveolar and lung interstitial macrophages

BACKGROUND: Investigations on pulmonary macrophages (MΦ) mostly focus on alveolar MΦ (AM) as a well-defined cell population. Characteristics of MΦ in the interstitium, referred to as lung interstitial MΦ (IM), are rather ill-defined. In this study we therefore aimed to elucidate differences between AM and IM obtained from human lung tissue. METHODS: Human AM and IM were isolated from human non-tumor lung tissue from patients undergoing lung resection. Cell morphology was visualized using either light, electron or confocal microscopy. Phagocytic activity was analyzed by flow cytometry as well as confocal microscopy. Surface marker expression was measured by flow cytometry. Toll-like receptor (TLR) expression patterns as well as cytokine expression upon TLR4 or TLR9 stimulation were assessed by real time RT-PCR and cytokine protein production was measured using a fluorescent bead-based immunoassay. RESULTS: IM were found to be smaller and morphologically more heterogeneous than AM, whereas phagocytic activity was similar in both cell types. HLA-DR expression was markedly higher in IM compared to AM. Although analysis of TLR expression profiles revealed no differences between the two cell populations, AM and IM clearly varied in cell reaction upon activation. Both MΦ populations were markedly activated by LPS as well as DNA isolated from attenuated mycobacterial strains (M. bovis H37Ra and BCG). Whereas AM expressed higher amounts of inflammatory cytokines upon activation, IM were more efficient in producing immunoregulatory cytokines, such as IL10, IL1ra, and IL6.CONCLUSION: AM appear to be more effective as a non-specific first line of defence against inhaled pathogens, whereas IM show a more pronounced regulatory function. These dissimilarities should be taken into consideration in future studies on the role of human lung MΦ in the inflammatory response

The efficacy of serial physical examination in penetrating abdominal trauma

Over a 10-year period we reviewed the records of 370 consecutive patients with potentially penetrating abdominal wounds (48 gunshot and 322 stab wounds). Selective non-operative management for abdominal stab wounds was introduced, guided by serial physical examination. In our study the terms therapeutic and non-therapeutic laparotomies were used, the latter comprising negative as well as insignificant findings. Initially diagnostic peritoneal lavage and local wound exploration were used, but these methods were later abandoned. Mortality was 10.2% and morbidity 25% in the group of gunshot wounds and 1.2% and 8.6% in the group of stab wounds. During this period the rate of laparotomies for stab wounds decreased from 55% to 30%, while the rate of non-therapeutic laparotomies decreased from 24% to 0% in the last year. Delayed laparotomy did not cause death or increase morbidity. Our results support the concept of selective non-operative management of abdominal stab wounds using repeated physical examination. Peritoneal perforation and haemoperitoneum should not be an indication for routine laparotomy. (C) 1999 Elsevier Science Ltd. All rights reserve

Neurotrophic factors in prostate and prostatic cancer

Recent progress in growth factor research has led to a reexamination of the involvement of neurotrophic factors outside their classical domain of the nervous system. These last few years have seen a substantial accumulation of data concerning Nerve Growth Factor (NGF)'s prevalence within the prostate. NGF and its receptors were reported from the normal prostatic tissue, benign hyperplasia and prostatic cancer. Divergent ideas about the biological role of this factor, its specific distribution pattern within the tissue and its implication in the progression of carcinogenesis have been proposed. Especially the role of NGF in the metastatic process bears direct clinical relevance for research in this area. Many questions remain to be solved like the one on the prevalence of other neurotrophic factors. It is now increasingly becoming clear that neurotrophic factors do play a role in normal physiology and pathology of prostatic cells, opening up new prospects for diagnosis and treatment

Nonantibiotic prophylaxis for recurrent urinary tract infections: a systematic review and meta-analysis of randomized controlled trials

Increasing antimicrobial resistance has stimulated interest in nonantibiotic prophylaxis of recurrent urinary tract infections. We assessed the effectiveness, tolerability and safety of nonantibiotic prophylaxis in adults with recurrent urinary tract infections. MEDLINE®, EMBASE™, the Cochrane Library and reference lists of relevant reviews were searched to April 2013 for relevant English language citations. Two reviewers selected randomized controlled trials that met the predefined criteria for population, interventions and outcomes. The difference in the proportions of patients with at least 1 urinary tract infection was calculated for individual studies, and pooled risk ratios were calculated using random and fixed effects models. Adverse event rates were also extracted. The Jadad score was used to assess risk of bias (0 to 2-high risk and 3 to 5-low risk). We identified 5,413 records and included 17 studies with data for 2,165 patients. The oral immunostimulant OM-89 decreased the rate of urinary tract infection recurrence (4 trials, sample size 891, median Jadad score 3, RR 0.61, 95% CI 0.48-0.78) and had a good safety profile. The vaginal vaccine Urovac® slightly reduced urinary tract infection recurrence (3 trials, sample size 220, Jadad score 3, RR 0.81, 95% CI 0.68-0.96) and primary immunization followed by booster immunization increased the time to reinfection. Vaginal estrogens showed a trend toward preventing urinary tract infection recurrence (2 trials, sample size 201, Jadad score 2.5, RR 0.42, 95% CI 0.16-1.10) but vaginal irritation occurred in 6% to 20% of women. Cranberries decreased urinary tract infection recurrence (2 trials, sample size 250, Jadad score 4, RR 0.53, 95% CI 0.33-0.83) as did acupuncture (2 open label trials, sample size 165, Jadad score 2, RR 0.48, 95% CI 0.29-0.79). Oral estrogens and lactobacilli prophylaxis did not decrease the rate of urinary tract infection recurrence. The evidence of the effectiveness of the oral immunostimulant OM-89 is promising. Although sometimes statistically significant, pooled findings for the other interventions should be considered tentative until corroborated by more research. Large head-to-head trials should be performed to optimally inform clinical decision makin

The genome of Gynandropsis gynandra provides insights into whole-genome duplications and the evolution of C4 photosynthesis in Cleomaceae

Gynandropsis gynandra (Cleomaceae) is a cosmopolitan leafy vegetable and medicinal plant, which has also been used as a model to study C4 photosynthesis due to its evolutionary proximity to Arabidopsis. Here, we present a high-quality genome sequence of G. gynandra, anchored onto 17 main super- scaffolds with a total length of 740 Mb, an N50 of 42 Mb and 30,933 well-supported gene models. The G. gynandra genome and previously released genomes of C3 relatives in the Cleomaceae and Brassicaceae make an excellent model for studying the role of genome evolution in the transition from C3 to C4 photosynthesis. We revealed that G. gynandra and its C3 relative Tarenaya hassleriana shared a whole-genome duplication event (Gg-α), then an addition of a third genome (Th-α, +1x) took place in T. hassleriana but not in G. gynandra. Analysis of syntenic copy number of C4 photosynthesis-related gene families indicates that G. gynandra generally retained more duplicated copies of these genes than C3 T. hassleriana, and also that the G. gynandra C4 genes might have been under positive selection pressure. Both whole-genome and single-gene duplication were found to contribute to the expansion of the aforementioned gene families in G. gynandra. Collectively, this study enhances our understanding of the impact of gene duplication and gene retention on the evolution of C4 photosynthesis in Cleomaceae

Cancer detection and complications in transperineal prostate biopsy, with antibiotics only when indicated

Objectives: To describe the prostate cancer (PCa) detection rate, including clinically significant prostate cancer (csPCa), in a large cohort of patients who underwent transperineal ultrasonography-guided systematic prostate biopsy (TPB-US) using a probe-mounted transperineal access system, with magnetic resonance imaging (MRI) cognitive fusion in case of a Prostate Imaging–Reporting and Data System grade 3–5 lesion, under local anaesthesia in an outpatient setting. Additionally, to compare the incidence of procedure-related complications with a cohort of patients undergoing transrectal ultrasonography-guided (TRB-US) and transrectal MRI-guided biopsies (TRB-MRI). Patients and Methods: This was an observational cohort study in men who underwent TPB-US prostate biopsy in a large teaching hospital. For each participant, prostate-specific antigen level, clinical tumour stage, prostate volume, MRI parameters, number of (targeted) prostate biopsies, biopsy International Society of Uropathology (ISUP) grade and procedure-related complications were assessed. csPCa was defined as ISUP grade ≥2. Antibiotic prophylaxis was only given in those with an increased risk of urinary tract infection. Results: A total of 1288 TPB-US procedures were evaluated. The overall detection rate for PCa in biopsy-naive patients was 73%, and for csPCa it was 63%. The incidence of hospitalization was 1% in TPB-US (13/1288), compared to 4% in TRB-US (8/214) and 3% in TRB-MRI (7/219; P = 0.002). Conclusions: Contemporary combined systematic and target TPB-US with MRI cognitive fusion is easy to perform in an outpatient setting, with a high detection rate of csPCa and a low incidence of procedure-related complications