Individualized significance of the -251 A/T single nucleotide polymorphism of interleukin-8 in severe infections.

Based on the concept of the individualized nature of sepsis, we investigated the significance of the -251 A/T (rs4073) single nucleotide polymorphism (SNP) of interleukin (IL)-8 in relation to the underlying infection. Genotyping was performed in 479 patients with severe acute pyelonephritis (UTI, n = 146), community-acquired pneumonia (CAP, n = 109), intra-abdominal infections (IAI, n = 119), and primary bacteremia (BSI, n = 105) by restriction fragment length polymorphism of the polymerase chain reaction (PCR) product and compared with 104 healthy volunteers. Circulating IL-8 was measured within the first 24 h of diagnosis by an immunosorbent assay. Carriage of the AA genotype was protective from the development of UTI (odds ratio 0.38, p: 0.007) and CAP (odds ratio 0.30, p: 0.004), but not from IAI and BSI. Protection from the development of severe sepsis/septic shock was provided for carriers of the AA genotype among patients with UTI (odds ratio 0.15, p: 0.015). This was accompanied by greater concentrations of circulating IL-8 among patients with the AA genotype. It is concluded that carriage of rs4073 modifies susceptibility for severe infection in an individualized way. This is associated with a modulation of circulating IL-8.

Evaluating the strength of potential misplaced priorities in opportunistic cancer screening practice in Greece.

PURPOSE: Screening is a significant method for cancer control, nevertheless the implementation of non cost-effective screening tests at national level may constitute a major burden to health economics. The purpose of this study was to determine the cancer screening activities of a large sample of the Hellenic population, in a country with opportunistic screening practice. METHODS: A large survey on cancer screening in Greece was organized and conducted by the Panhellenic Association for Continual Medical Research (PACMeR). Screening performance of evidence-based (EB), non-evidence-based (non EB) and of undefined benefit tests was analysed. RESULTS: 7001 individuals were analysed. Eighty-eight percent of males and 93% of females stated that they were interested in cancer screening practices. Gynecological cancer screening was performed in the range of 23-38%. Colorectal cancer screening was rarely performed in both genders (1- 2%), while non-evidence-based tests were regularly performed (urinalysis 50% and chest radiography 15-18%). Full blood count and PSA measurement were widely accepted (over 45% in both genders and 19.5% in males, respectively). Sociodemographic characteristics did not influence the performance of EB tests in males while females' activities were highly influenced by such parameters. CONCLUSION: Opportunistic cancer screening in a primary health care system where national guidelines are missing may cause ambiguous results. Reconsideration of health policy in such cases is mandatory.

Screening practice and misplaced priorities

PURPOSE: To estimate cancer screening coverage among a large sample of Greek individuals. METHODS: 7012 adults from 30 Hellenic areas were surveyed. Tests included: faecal occult blood test, sigmoidoscopy,chest X-ray, urine test, testicular examination,trans-rectal ultrasound, full blood count, skin examination,digital rectal examination, PSA, Pap test, mammography,clinical breast examination (CBE), self breast examination and breast ultrasound. RESULTS: Eighty-eight percent of males and 93% of females declared being interested in cancer screening; 37.8% of men and 37.9% of women had had a medical consultation for screening purpose in the previous 2 years. Less than 2%reported having received screening for colorectal cancer or skin malignancies. Screening for cervical cancer, mammography and CBE was reported by 39.6%, 22.8% and 27.9% of females respectively. Twenty percent of males reported screening for prostate cancer. CONCLUSION: The actual opportunistic screening approach presents important deficiencies with displaced priorities in test performance and a low proportion of individuals undergoing recommended tests (AU)

Tyrosine kinase inhibitors in treatment of fibrous histiocytoma.

AIM: To describe potential beneficial effects of tyrosine kinase inhibitor in the treatment of unresectable/metastatic fibrous histiocytoma. METHODS: We report a case of advanced stage fibrous histiocytoma with locally recurrent disease plus lung and bone metastatic deposits. Patient was treated with the tyrosine kinase inhibitor sunitinib. RESULTS: Treatment with Sunitinib resulted in disease stabilization in the regional lesion and in good partial response for metastatic foci (reduction in number and size). After 13 months of treatment the patient is doing well with no tumor progression. CONCLUSIONS: This case appears to be one of the first documentations of beneficial effect and potential long-term benefit of TKIs in the treatment of fibrous histiocytoma.

Moving ahead in diabetics' cancer screening; food for thought from the Hellenic experience.

Although data from literature suggest that diabetic women are frequently under screened for gynaecological cancers little is known about screening implementation for other cancers for both genders. This study investigates comprehensive cancer screening practices of diabetics as compared with non-diabetics; analyses screening patterns both by gender and level of evidence and reveals target subgroups that should be paid more attention for screening implementation. 675 diabetics vs. 5772 non-diabetic Greek individuals entered the PACMeR 02 cancer screening study. Diabetic women reported significantly lower performance for the sex-specific evidence-based cancer screening tests and digital rectal examination (DRE) as compared with non-diabetics (P < 0.05). Diabetic women older than 60 years old, of elementary education, housewives and farmers showed the lowest performance rates (P < 0.01). Prostate cancer screening was higher among diabetic men with ultrasound and DRE reaching statistical significance (P < 0.05). Subgroups analysis did not reveal a hidden relationship. Both genders of diabetics reported never performing skin examination at higher rates (P < 0.001), although screening intent is extremely low in both diabetics and non-diabetics (<1%). Evidence-based screening coverage was inconsistent in both genders independently by the diabetic status. Primary care efforts should be provided to implement presymptomatic cancer control.

Pharmacokinetics of clarithromycin in the prostate: implications for the treatment of chronic abacterial prostatitis.

PURPOSE: We studied the pharmacokinetics of orally administered clarithromycin in prostatic tissue to define its role in the treatment of chronic abacterial prostatitis caused by intracellular pathogens. MATERIALS AND METHODS: A total of 45 men receiving 3 oral doses of 750 mg. clarithromycin at 12-hour intervals underwent suprapubic prostatectomy for benign prostate hyperplasia 4, 5, 6 and 7 hours after the last drug dose in 13, 12, 10 and 10 patients, respectively. Concentrations were determined in the prostate tissue and in plasma by an agar diffusion assay. RESULTS: A mean peak level of clarithromycin of 3.22 and 3.08 microg./gm. of tissue was achieved 4 hours after the third drug dose at the center and periphery of the adenoma, respectively. Tissue levels remained statistically superior to plasma levels at all intervals. CONCLUSIONS: The oral administration of clarithromycin achieved a prostate level much higher than the minimal inhibitory concentration of clarithromycin for the intracellular pathogens of chronic prostatitis. Thus, clarithromycin may be considered for treating chronic abacterial prostatitis.

The effects of exogenous growth factors on matrix metalloproteinase secretion by human brain tumour cells.

Matrix metalloproteinases (MMPs) are a growing family of zinc-dependent endopeptidases that are capable of degrading various components of the extracellular matrix. These enzymes have been implicated in a variety of physiological and pathological conditions including embryogenesis and tumour invasion. The synthesis of many MMPs is thought to be regulated by growth factors, cytokines and hormones. In this study, we investigated the effects of five exogenous growth factors known to be expressed by gliomas [epidermal growth factor (EGF), basic growth factor (bFGF), transforming growth factor beta (TGF-beta1,2) and vascular endothelial growth factor (VEGF)].on MMP-2 and MMP-9 expression in an ependymoma, two grade III astrocytomas, a grade III oligoastrocytoma and a benign meningioma. Zymogram analysis revealed that the effects of the growth factors depended upon the cell lines used in the study. Growth factors generally up-regulated MMP-2 and MMP-9 expression in the gliomas but were least effective in the meningioma; the effect being most prominent with TGF-beta1 and TGF-beta2 in all the cell lines. It is hypothesized that paracrine growth factor interplay may be crucial in the regulation of MMP expression by glioma invasion of the normal brain.

The role of integrin receptors in aspects of glioma invasion in vitro.

Integrins are heterodimers consisting of non-covalently associated alpha and beta subunits. They mediate adherence of normal and tumour cells to the extracellular matrix, a property which is essential for migration of neoplastic astrocytes as they invade into the normal brain parenchyma. Flow cytometry and immunocytochemical analysis of cultured cells derived from 10 gliomas (1 pilocytic astrocytoma, 1 astrocytoma, 1 oligoastrocytoma, 1 anaplastic oligoastrocytoma, 4 anaplastic astrocytomas and 2 glioblastoma multiforme) revealed that the beta1 integrin subunit was generally expressed more strongly than alpha4 or alpha(v) integrin subunits. Subsequent studies with function-blocking antibodies against the beta1 subunit inhibited adhesion, motility and invasion of the gliomas in vitro, to varying degrees, on all extracellular matrix substrates investigated (laminin, collagen type IV, fibronectin and vitronectin), the inhibition by beta1 subunit was greatest on collagen type IV. These studies therefore substantiate the case for a role of the beta1 integrin subunit in neoplastic glial cell invasion of the brain.