Screening for colorectal cancer: possible improvements by risk assessment evaluation?

Emerging results indicate that screening improves survival of patients with colorectal cancer. Therefore, screening programs are already implemented or are being considered for implementation in Asia, Europe and North America. At present, a great variety of screening methods are available including colono- and sigmoidoscopy, CT- and MR-colonography, capsule endoscopy, DNA and occult blood in feces, and so on. The pros and cons of the various tests, including economic issues, are debated. Although a plethora of evaluated and validated tests even with high specificities and reasonable sensitivities are available, an international consensus on screening procedures is still not established. The rather limited compliance in present screening procedures is a significant drawback. Furthermore, some of the procedures are costly and, therefore, selection methods for these procedures are needed. Current research into improvements of screening for colorectal cancer includes blood-based biological markers, such as proteins, DNA and RNA in combination with various demographically and clinically parameters into a “risk assessment evaluation” (RAE) test. It is assumed that such a test may lead to higher acceptance among the screening populations, and thereby improve the compliances. Furthermore, the involvement of the media, including social media, may add even more individuals to the screening programs. Implementation of validated RAE and progressively improved screening methods may reform the cost/benefit of screening procedures for colorectal cancer. Therefore, results of present research, validating RAE tests, are awaited with interest

Nosocomial outbreak of cryptosporidiosis in AIDS patients.

OBJECTIVE--To describe a nosocomial outbreak of cryptosporidiosis during four months after June 1989. SETTING--A department of infectious diseases in Copenhagen, seeing about half the patients with AIDS in Denmark. SUBJECTS--73 HIV antibody negative subjects and 60 antibody positive subjects admitted as inpatients during the transmission period of the outbreak (20 June-14 August), of whom 18 (17 with AIDS, one with AIDS related complex), developed cryptosporidiosis. Two further HIV negative subjects (one departmental secretary, one visiting relative) developed cryptosporidiosis. MAIN OUTCOME MEASURES--Cryptosporidia in stool samples, clinical symptoms, CD4 cell count, HIV antigen concentration, chemotherapeutic treatment. RESULTS--The source of the outbreak was identified as ice from an ice machine in the ward, contaminated by an incontinent, psychotic patient with cryptosporidiosis picking out ice for cold drinks. The mean incubation time was at least 13 days-that is, twice that in HIV-negative patients. Of the 18 patients with AIDS who developed cryptosporidiosis, five recovered, two were symptomless carriers, three died of unrelated causes, and eight died after prolonged diarrhoea. Among the 57 exposed HIV antibody positive inpatients (excluding two patients and the index case with cryptosporidiosis diagnosed elsewhere), significantly more of those who developed symptomatic cryptosporidiosis received oral sulphonamides than those who did not (91%, 10/11 v 48%, 21/44, p less than 0.05). CONCLUSIONS--The clinical and epidemiological findings indicate that infection was the consequence of very small inocula. Increased sensitivity to cryptosporidiosis may be an unrecognised side effect of oral sulphonamide treatment in patients with AIDS

High-level endothelial E-selectin (CD62E) cell adhesion molecule expression by a lipopolysaccharide-deficient strain of Neisseria meningitidis despite poor activation of NF-κB transcription factor

Binding of host inflammatory cells to the endothelium is a critical contributor to the vascular damage characteristic of severe meningococcal disease and is regulated by endothelial cell adhesion molecules such as ICAM-1, VCAM-1 and CD62E. Intact meningococci induce far higher levels of CD62E than lipopolysaccharide (LPS) alone, whereas LPS is at least as potent as meningococci at inducing both VCAM-1 and ICAM-1 expression. This suggests that meningococci possess additional factors other than LPS present in whole bacteria that result in differential adhesion molecule expression. To investigate this possibility, we studied the capacity of an LPS-deficient isogenic strain of serogroup B Neisseria meningitidis H44/76 (lpxA-) to induce endothelial cell adhesion molecule expression and translocation of the transcription factor NF-κB, and compared it to both parent and unencapsulated strains of both B1940 and H44/76 and purified LPS. Although the LPS-deficient isogenic mutant of strain H44/76 was found to be a poor inducer of NF-κB, it induced higher levels of CD62E expression than LPS alone. These data provide evidence that intact meningococci induce a range of signals in the endothelium that are distinct from those seen with purified LPS alone and that they occur in a LPS-dependent and LPS-independent manner. These signals may explain the potent effects of N. meningitidis on CD62E expression on vascular endothelium and provide a basis for the complex endothelial dysregulation seen in meningococcal sepsis

Serum angiogenic profile of patients with glioblastoma identifies distinct tumor subtypes and shows that TIMP-1 is a prognostic factor

Angiogenesis plays a key role in glioblastoma biology and antiangiogenic agents are under clinical investigation with promising results. However, the angiogenic profiles of patients with glioblastoma and their clinical significance are not well understood. Here we characterize the serum angiogenic profile of patients with glioblastoma, and examine the prognostic significance of individual angiogenic factors. Serum samples from 36 patients with glioblastoma were collected on admission and simultaneously assayed for 48 angiogenic factors using protein microarrays. The data were analyzed using hierarchical cluster analysis. Vessel morphology was assessed histologically after immunostaining for the pan-endothelial marker CD31. Tumor samples were also immunostained for tissue inhibitor of metalloproteinase-1 (TIMP-1). Cluster analysis of the serum angiogenic profiles revealed 2 distinct subtypes of glioblastoma. The 2 subtypes had markedly different tumor microvessel densities. A low serum level of TIMP-1 was associated with significantly longer survival independent of patient age, performance status, or treatment. The serum angiogenic profile in patients with glioblastoma mirrors tumor biology and has prognostic value. Our data suggest the serum TIMP-1 level as an independent predictor of survival