Cytokine concentrations during the first days of life

OBJECTIVE: To evaluate the cytokine concentration patterns during the first 5 days of life by measuring serum concentrations of type-1 cytokines, like interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) and type-2 cytokines, like IL-4, as well as the receptors of IL-2 (sIL-2R) and IL-4 (sIL-4R) during the early neonatal period. SUBJECTS AND METHODS: Forty-two healthy term neonates were included in the study. Cytokine concentrations were measured in umbilical cord, in the 1st and 5th day after birth and compared with those in serum of 30 healthy adults. RESULTS: IL-2 concentrations presented a decrease trend from umbilical cord to 5th day, while sIL-2R showed a significant elevation from umbilical cord to 5th day after birth. IL-4 concentrations did not differ significantly among umbilical cord, the 1st and the 5th day, while the sIL-4R showed the highest values in the 1st day after birth. Both IL-4 and sIL-4R concentrations in neonatal samples were elevated compared to adults. IFN-gamma concentrations increased significantly from umbilical cord to 5th day of life. CONCLUSION: Our findings indicate a dysregulation among IL-2, IL-4 and IFN-gamma concentrations during the 1st day after birth, favoring a more precocious expression of IL-2 and IL-4 against IFN-gamma that seems to be ameliorated in the end of the 1st week of life.     

Too far away to work with each other: Does location impact on pharmacists’ perceptions of interprofessional interactions?

In recent years, the delivery of health services has seen a shift towards interprofessional teamwork in order to effectively utilise the skills of each member of the healthcare team to deliver optimal patient care. Nevertheless, a variety of barriers, including lack of communication between healthcare professionals (HCPs), have been identified. The expanding clinical services provided by community pharmacies have increased the potential for pharmacist-HCP interaction; however, primary care pharmacy environments vary from individual distinct premises to part of interprofessional ‘health centres’. As such, one potential factor affecting interprofessional communication could be the geographical location (‘space’) of HCPs. This study sought to determine whether these different primary healthcare ‘spaces’ impact on the frequency of interprofessional interactions. An anonymous, self-complete questionnaire was sent to all community pharmacies in Wales (n = 716) to quantify the frequency of interprofessional interactions between community pharmacists and other HCPs. A response rate of 62% was achieved. Results showed that pharmacists working in pharmacies physically linked to general practitioner (GP) surgeries had significantly more frequent interaction with HCPs based within the surgeries. This suggests that housing HCPs in the same physical space will enable more interprofessional interaction, supporting the drive to improve the quality of patient care.     

Generation of a selectively cytotoxic fusion protein against p53 mutated cancers

ABSTRACT: BACKGROUND: A significant number of cancers are caused by defects in p21 causing functional defects in p21 or p53 tumour-suppressor proteins. This has led to many therapeutic approaches including restoration by gene therapy with wild-type p53 or p21 using viral or liposomal vectors, which have toxicity or side-effect limitations. We set out to develop a safer, novel fusion protein which has the ability to reconstitute cancer cell lines with active p21 by protein transduction. METHODS: The fusion protein was produced from the cell-translocating peptide Antennapedia (Antp) and wild-type, full-length p21 (Antp-p21). This was expressed and refolded from E. coli and tested on a variety of cell lines and tumours with differing p21 or p53 status. RESULTS: Antp-p21 penetrated and killed cancer cells that do not express wild type p53 or p21. This included cells that were matched to cogenic parental cell lines. Antp-p21 killed cancer cells selectively that were malignant as a result of mutations or nuclear exclusion of the p53 and p21 genes and over-expression of MDM2. Non-specific toxicity was excluded by showing that Antp-p21 penetrated but did not kill p53- or p21- wild-type cells. Antp-p21 was not immunogenic in rabbits. Recombinant Antp peptide alone was not cytotoxic, showing that killing was due to the transduction of the p21 component of Antp-p21. Antp-p21 was shown to penetrate cancer cells engrafted in vivo and resulted in tumour eradication when administered with conventionally-used chemotherapeutic agents, which alone were unable to produce such an effect. CONCLUSIONS: Antp-p21 may represent a new and promising targeted therapy for patients with p53-associated cancers supporting the concept that rational design of therapies directed against specific cancer mutations will play a part in the future of medical oncology.     

Increased serum levels of YKL-40 in patients with inflammatory bowel disease

BACKGROUND AND AIMS: Initiation of a fibrotic process has been suggested as part of the intestinal response to chronic inflammation in inflammatory bowel disease. YKL-40 has been proposed as a new serum marker of fibrosis. We studied compared the serum levels of YKL-40 in patients with ulcerative colitis or Crohn's disease with inflammatory and healthy controls. PATIENTS AND METHODS: YKL-40 serum levels were measured in 179 patients with inflammatory bowel disease (94 ulcerative colitis, 85 Crohn's disease), in 23 with intestinal inflammation of other causes, and 70 matched healthy controls using a commercially available enzyme-linked immunosorbent assay. YKL-40 levels were assessed in terms of disease activity, type and localization. RESULTS: Mean serum YKL-40 levels were 102.6+/-82.7 ng/ml in ulcerative colitis patients and 112.2+/-83.7 ng/ml in Crohn's disease patients, significantly higher than in healthy controls (64.1+/-21.4 ng/ml) but not significantly different from inflammatory controls (77.8+/-23.1 ng/ml). Disease activity and C-reactive protein levels were significantly correlated with YKL-40 levels in both ulcerative colitis and Crohn's disease. Crohn's disease patients with ileum localization had significantly higher YKL-40 levels than those with ileocolonic or colonic disease. Patients with stenotic disease had mean YKL-40 levels not significantly different than those with nonstenotic disease. CONCLUSION: Serum levels of YKL-40 are increased in patients with inflammatory bowel disease, and this is associated with the inflammatory process rather than with the degree of fibrosis.     

Neuromuscular diseases and their cardiac manifestations under the spectrum of cardiovascular imaging

Heart Failure Reviews - Neuromuscular diseases (NMDs) include a broad spectrum of disorders that affect motor unit in every possible site, extending from the cell body of peripheral nerves to the...     

Accumulation of carbapenem resistance mechanisms in VIM-2-producing Pseudomonas aeruginosa under selective pressure

Pseudomonas aeruginosa has the potential to achieve resistance to carbapenems via the acquisition of carbapenemase-encoding genes, the downregulation of the OprD porin, the overexpression of efflux systems and the overproduction of cephalosporinases. One hundred and fifty carbapenem-non-susceptible isolates from 2008 to 2010 were screened for carbapenemase production, OprD porin loss, efflux pumps overexpression and inducible AmpC beta-lactamase production. For comparison reasons, the presence of the same mechanisms was also assessed in a previous collection of 30 carbapenem-non-susceptible P. aeruginosa isolated between 2003 and 2005. Results showed the accumulation of various resistance mechanisms among VIM-2 producers isolated between 2008 and 2010 with a parallel considerable increase in imipenem MIC₉₀ and the geometric mean of the MIC values of imipenem and meropenem between the two study groups. The accumulation of carbapenem resistance mechanisms highlights the potential of this formidable pathogen for evolutionary success under antibiotic selective pressure.     

Post‒cataract surgery endophthalmitis outbreak caused by multidrug-resistant Pseudomonas aeruginosa

In June 2010, a severe outbreak of 13 cases of post-cataract surgery endophthalmitis caused by multidrug-resistant Pseudomonas aeruginosa occurred. Pulse-field gel electrophoresis in eye isolates found 95% genetic similarity; however, extensive environmental and carriage investigation revealed no source of infection.     

Transjugular intrahepatic portosystemic shunt in cavernomatous portal vein occlusion

A 72-year-old patient with liver cirrhosis and cavernomatous portal vein occlusion presented with refractory ascites. We treated the patient with transjugular intrahepatic portosystemic shunt: transjugular transhepatic puncture of an intrahepatic hilar collateral vein was performed; transjugular intrahepatic portosystemic shunt was created between the right hepatic vein and the patent superior mesenteric vein using this hilar collateral vein as the connecting pathway. The ascites was resolved and the patient remains asymptomatic, while shunt patency is maintained 16 months after the intervention.