Mogens Rørbæk Madsen

Drug Therapy for Improving Walking Distance in Intermittent Claudication: A Systematic Review and Meta-analysis of Robust Randomised Controlled Studies

OBJECTIVES To evaluate the efficacy of pharmacological interventions in improving walking capacity and health-related quality of life for people with intermittent claudication. DATASOURCES: We searched Medline, EMBASE, Cochrane library and relevant websites for studies published from the start of the databases to February 2009. In addition, reference lists were manually searched. REVIEW METHODS Based upon a power calculation, only robust (n>56), peer-reviewed, double-blinded, randomised and placebo-controlled trials were included. The main outcomes evaluated were maximal walking distance (MWD) and pain-free walking distance on a treadmill. Random models were used in the statistical analysis, and chi-square test were used to test for heterogeneity. RESULTS Among 220 trials, only 43 trials fulfilled the quality criteria. Treatment periods, follow-up and treadmill protocols varied substantially. Vasodilator agents and phosphodiesterase inhibitors show robust significant results compared to placebo, but the improvements in MWD are modest. The highest benefit was caused by lipid-lowering agents, which in mean gained above 160 m in MWD, while the other agents only improved MWD about 50 m. CONCLUSION Several drugs have shown to improve MWD, but with limited benefits. Statins seem to be the most efficient drug at the moment.

Direct detection of early-stage cancers using circulating tumor DNA

Noninvasive liquid biopsy analysis of circulating tumor DNA permits direct detection of early-stage cancers. Finding smaller needles in haystacks The detection and analysis of cell-free DNA in patients’ blood are becoming increasingly accepted in oncology. However, this approach has generally been applied for the monitoring of patients with existing tumors. It has not been useful for early diagnosis of cancer because of insufficient sensitivity to detect really small tumors that only shed minute quantities of DNA into the blood, as well as difficulties with identifying cancer-associated genetic changes without knowing what mutations are present in the primary tumor. A method developed by Phallen et al., called targeted error correction sequencing, addresses both of these limitations and demonstrates the feasibility of detecting circulating cell-free DNA from many early tumors, suggesting its potential use for cancer screening. Early detection and intervention are likely to be the most effective means for reducing morbidity and mortality of human cancer. However, development of methods for noninvasive detection of early-stage tumors has remained a challenge. We have developed an approach called targeted error correction sequencing (TEC-Seq) that allows ultrasensitive direct evaluation of sequence changes in circulating cell-free DNA using massively parallel sequencing. We have used this approach to examine 58 cancer-related genes encompassing 81 kb. Analysis of plasma from 44 healthy individuals identified genomic changes related to clonal hematopoiesis in 16% of asymptomatic individuals but no alterations in driver genes related to solid cancers. Evaluation of 200 patients with colorectal, breast, lung, or ovarian cancer detected somatic mutations in the plasma of 71, 59, 59, and 68%, respectively, of patients with stage I or II disease. Analyses of mutations in the circulation revealed high concordance with alterations in the tumors of these patients. In patients with resectable colorectal cancers, higher amounts of preoperative circulating tumor DNA were associated with disease recurrence and decreased overall survival. These analyses provide a broadly applicable approach for noninvasive detection of early-stage tumors that may be useful for screening and management of patients with cancer.

Metabolic effects of caffeine ingestion and physical work in 75-year old citizens. A randomized, double-blind, placebo-controlled, cross-over study

Objective  Whereas caffeine has been demonstrated to impact substantially on the metabolic response to exercise in healthy young subjects, this issue remains to be addressed in healthy elderly subjects.

Summer mastitis in heifers: a bacteriological examination of secretions from clinical cases of summer mastitis in Denmark.

A total of 166 samples of secretions collected from Danish heifers suffering from clinically diagnosed summer mastitis were examined bacteriologically. One hundred and sixty three samples yielded positive findings whereas no growth was obtained from 3 specimens. The majority of samples revealed a mixed flora in which the predominant components were Actinomyces pyogenes, Peptostreptococcus indolicus, a microaerophilic coccus (Stuart-Schwan coccus), Fusobacterium necrophorum, Bacteriodes melaninogenicus and Streptococcus dysgalactiae. Pure cultures were recovered in only 7% of cases. P. indolicus was isolated from 875 of the cases, a microaerophilic coccus from 84%, A. pyogenes from 72%, Fusobacterium necrophorum from 52%, Str. dysgalactiae from 37%, B. melaninogenicus from 33% and various unidentified obligate anaerobic Gram-negative rods from 31%. The results confirm the complex bacterial aetiology of summer mastitis.

Randomized double-blind placebo-controlled crossover study of caffeine in patients with intermittent claudication.

Intermittent claudication is a disabling symptom of peripheral arterial disease for which few medical treatments are available. This study investigated the effect of caffeine on physical capacity in patients with intermittent claudication.

Summer mastitis in heifers : studies on the seasonal occurrence of Actinomyces pyogenes, Peptostreptococcus indolicus and bacteroidaceae in clinically healthy cattle in Denmark

With the aim of investigating the seasonal occurrence of Actinomyces pyogenes, Peptostreptococcus indolicus, Bacteroides melaninogenicus ss. levii and Fusobacterium necrophorum, and thus the potential for development of summer mastitis, clinically healthy Danish Holstein-Friesian heifers due to calve in the autumn were sampled from the teat tip, the conjunctiva and the oral cavity at 2-6 week intervals from 1979 to 1981. The overall isolation rates of F. necrophorum, P. indolicus and B. melaninogenicus ss. levii, in order of significance, were significantly higher during the pasture period whereas no differences in isolation rates of A. pyogenes between housed and pastured animals were detected. F. necrophorum was recovered almost exclusively from the oral cavity, P. indolicus and A. pyogenes occurred most frequently in samples from the teat skin, whereas isolates of B. melaninogenicus ss. levii were evenly distributed between conjunctiva and teat tip samples. A distinct seasonal pattern of the isolation rates of summer mastitis pathogens was recorded, which corresponded closely to the seasonal activity of symbovine insects, in particular the headfly Hydrotaea irritans (Fallén). However, the high proportion of clinically healthy bacterial carriers as compared with the incidence of clinical disease strongly suggests that as yet unknown contributing or triggering factors, apart from the mere presence of the relevant bacterial species, are required for the establishment and development of clinical summer mastitis.

SNHG16 is regulated by the Wnt pathway in colorectal cancer and affects genes involved in lipid metabolism

It is well established that lncRNAs are aberrantly expressed in cancer where they have been shown to act as oncogenes or tumor suppressors. RNA profiling of 314 colorectal adenomas/adenocarcinomas and 292 adjacent normal colon mucosa samples using RNA‐sequencing demonstrated that the snoRNA host gene 16 (SNHG16) is significantly up‐regulated in adenomas and all stages of CRC. SNHG16 expression was positively correlated to the expression of Wnt‐regulated transcription factors, including ASCL2, ETS2, and c‐Myc. In vitro abrogation of Wnt signaling in CRC cells reduced the expression of SNHG16 indicating that SNHG16 is regulated by the Wnt pathway. Silencing of SNHG16 resulted in reduced viability, increased apoptotic cell death and impaired cell migration. The SNHG16 silencing particularly affected expression of genes involved in lipid metabolism. A connection between SNHG16 and genes involved in lipid metabolism was also observed in clinical tumors. Argonaute CrossLinking and ImmunoPrecipitation (AGO‐CLIP) demonstrated that SNHG16 heavily binds AGO and has 27 AGO/miRNA target sites along its length, indicating that SNHG16 may act as a competing endogenous RNA (ceRNA) “sponging” miRNAs off their cognate targets. Most interestingly, half of the miRNA families with high confidence targets on SNHG16 also target the 3′UTR of Stearoyl‐CoA Desaturase (SCD). SCD is involved in lipid metabolism and is down‐regulated upon SNHG16 silencing. In conclusion, up‐regulation of SNHG16 is a frequent event in CRC, likely caused by deregulated Wnt signaling. In vitro analyses demonstrate that SNHG16 may play an oncogenic role in CRC and that it affects genes involved in lipid metabolism, possible through ceRNA related mechanisms.

Effect of darbepoetin alfa on physical function in patients undergoing surgery for colorectal cancer. A randomized, double-blind, placebo-controlled study

Objective: To study whether perioperative treatment with darbepoetin alfa (DA) improves physical performance following colorectal cancer surgery. Methods: Patients admitted for planned colorectal cancer surgery were randomized to receive either weekly placebo or DA 300 or 150 µg depending on the hemoglobin (Hb) concentration. Patients were assessed 10 days before, as well as 7 and 30 days after surgery for work capacity, postural sway, muscle strength, fatigue and quality of life (QoL). The primary outcome measure were the changes in patients’ physical performance from preoperative to postoperative day 7. Results: Of 221 included patients, 151 were evaluable. Baseline characteristics were similar in the 2 groups. Patients receiving DA had a significantly better working capacity on day 7 (p = 0.03) and day 30 (p = 0.03) compared with the placebo group. There were no statistically significant differences between the 2 groups on days 7 or 30 for fatigue, postural sway and QoL. DA treatment significantly (p < 0.01) reduced the decrease in Hb concentrations on day 7 and resulted in an earlier return (p < 0.01) to the preoperative Hb concentration compared to placebo treatment. Conclusion: Perioperative DA treatment improved postoperative work capacity and Hb concentrations, but had no effect on postoperative fatigue, postural sway, QoL and muscle strength.

Low technology water purification by bentonite clay flocculation as performed in sudanese villages: bacteriological examinations☆

Abstract The effects of a water purification method traditionally used in Sudan to treat turbid waters were studied with respect to removal of faecal indicator bacteria as well as selected enteric bacterial pathogens. Water treatment was performed with natural bentonite clays (rauwaq) from the banks of the Nile, and the technique employed corresponded closely to that used to clarify Nile water in Sudanese villages. Employing various types of waters a primary bacterial reduction of 1–3 log units (90–99.9%) was obtained within the first 1–2 h of flocculation. During the 24 h observation period bacterial multiplication in the water phase occurred consistently for Vibrio cholerae and test organisms belonging to the Enterobacteriaceae group, but not for Streptococcus faecalis and Clostridium perfringens. Some of the conditions influencing the hygienic effects obtained were examined. The potential and limitations of the method as a local alternative in water improvement are discussed.

Studies on the possible role of cattle nuisance flies, especially Hydrotaea irritans, in the transmission of summer mastitis in Denmark.

Abstract. The summer mastitis pathogens Actinomyces pyogenes, Peptococcus indolicus, Bacteroides melaninogenicus ss. levii, Fuso‐bacterium necrophorum and Streptococcus dysgalactiae were isolated from the polyphagous symbovine dipterans Hydrotaea irritans (Fallen) and Morellia sp. caught around dairy heifers on pasture, but not from the haematophagous species Haematobia irritans (L.), Haematobosca stimulans (Meigen), Culicoides sp. and Simulium sp. Secretions from clinical cases of summer mastitis proved to be sources of summer mastitis bacteria for more than 3 weeks despite antibiotic treatment and teat amputation.