Differential chemokine expression patterns in tonsillar disease.

Expression profiles of CXC- and CC-chemokines in various forms of tonsillar disease were studied to evaluate whether certain chemokines play a predominant role in a specific subset of tonsillar disease. Total RNA was isolated from 89 biopsies (21 hyperplastic palatine tonsils, 25 adenoids, 16 chronic inflammatory palatine tonsils and 27 chronic inflammatory palatine tonsils with histological prove of acute inflammation), reverse transcribed and subjected to PCR amplifying IL-8, Gro-alpha, eotaxin-1, eotaxin-2, MCP-3, MCP-4 and RANTES. 2% agarose gel electrophoresis revealed a predominance of IL-8 in the chronic inflammatory palatine tonsil group compared to tonsillar hyperplasia. Furthermore, eotaxin-2 was strongly overexpressed in adenoid samples compared to chronic inflammatory specimens. Our data suggest that the majority of diseases related to adenoid formation are mediated via an eotaxin-2 expression, whereas chronic inflammatory tonsillitis is associated with IL-8 upregulation. These data imply that adenoids are related to a Th-2, and chronic inflammatory tonsillitis to a Th-1 based immune response.

Activation of the cell membrane angiotensin AT2 receptors in human leiomyosarcoma cells induces differentiation and apoptosis by a PPARγ - dependent mechanism.

Angiotensin II (Ang II), the main effector peptide of the renin-angiotensin system (RAS), acting on AT1 and AT2 receptors participates in the regulation of proliferation, differentiation and apoptosis in tumour cells. The peroxisome-proliferator activated receptor γ (PPARγ) and its ligands exert anti-tumour effects in various human cancer cell lines. The present study investigates the effects initiated by AT1- and AT2 receptor stimulation in SK-UT-1 cells, a human leiomyosarcoma cell line, and clarifies the role of the PPARγ in the AT2 receptor-induced differentiation and apoptosis.Selective stimulation of AT1- and AT2 receptors was achieved by incubation of the cells with Ang II (10-6 M) in the presence of the selective AT2 receptor antagonist, PD 123177 (10-6 M) and the AT1 receptor antagonist, losartan (10-5 M), respectively, the selective PPARγ antagonist, GW 9662, was used at concentration 10-6 M. The expression of smooth muscle cell differentiation markers, SM22α and calponin, was analysed at RNA- and protein levels using RT PCR and Western blot, which was also used to quantify Bcl-2-, Bax- and cleaved caspase-3 proteins. The translocation of the AT2-receptor interacting protein 1 (ATIP1) to the nuclei was studied by Western blot and immunofluorescence staining. The mitochondrial status and the metabolic activity in response to AT1- and AT2 receptor activation were assessed by the quantification of 99mTc - sestamibi and 2´-deoxy-2´-[18F]fluoro-D-glucose uptake.AT1 receptor stimulation did not exert any profound effects in quiescent SK-UT-1 cells. The effects induced by Ang II acting on AT2 receptors were time-dependent. A short, 3 - 6 h lasting stimulation promotes differentiation, i.e increases in the mRNA- and protein levels of SM22α and calponin, whereas a sustained stimulation for 48 h activates the intrinsic apoptotic pathway, as evidenced by reduced cell numbers, down-regulation of the anti-apoptotic Bcl-2 protein and increased levels of the Bax protein and cleaved caspase-3. The effects were reversed by the PPARγ antagonist, GW 9662, clearly implying a PPARγ-dependent mechanism. Our results also demonstrate a co-localisation of the AT2-receptor interacting protein, ATIP1, and the PPARγ in nuclei of SK-UT-1 cells and an accumulation of ATIP1 in the nuclear fraction in response to AT2 receptor stimulation. The regulation of the differentiation and apoptosis via the AT2 receptor favours an important functional role of this receptor in quiescent, slow-cycling SK-UT-1 cells and provides the rationale for the use of AT1 receptor antagonists for the treatment of human leiomyosarcomas.

Differential expression of antimicrobial peptides in psoriasis and psoriatic arthritis as a novel contributory mechanism for skin and joint disease heterogeneity.

OBJECTIVES: This study tested the hypothesis that a differential innate immune antimicrobial peptide (AMP) profile was evident between the skin and joints in psoriasis and psoriatic arthritis (PsA) and that PsA synovitis may have a distinct AMP pattern compared to other arthropathies. METHOD: Twenty-two cases had knee biopsies [10 PsA, eight rheumatoid arthritis (RA), and four osteoarthritis (OA)]. Lesional and non-lesional skin biopsies in psoriasis and control tissue were also obtained (n = 4 each). Immunohistochemistry with semi-quantitative scoring of both synovium and skin was performed using the following panel of AMPs: S100 A8, S100 A9, human neutrophil peptides 1-3 (HNP1-3), human ß-defensins 2 and 3 (hBD-2 and hBD-3), cathelicidin LL-37, psoriasin (S100 A7), and ribonuclease 7 (RNase 7). RESULTS: Similar expression of S100 A8, S100 A9, and HNP1-3 was detectable in PsA and RA synovium but only in the synovium sublining layer (SSL). No expression of psoriasin, RNase 7, hBD-2, and hBD-3 could be detected in the synovial tissue of PsA, RA, or OA. All psoriasis skin samples exhibited broad expression of all investigated AMPs, with strong keratinocyte expression. CONCLUSIONS: Given that some AMPs, especially hBD-2, are genetically linked to psoriasis and are only expressed in the skin, these findings show how differential AMP expression in innate immune responses may contribute to disease heterogeneity between PsA and psoriasis and provides a genetic basis for the non-progression of psoriasis subgroups to PsA.

Changes of salivary estrogen levels for detecting the fertile period.

OBJECTIVES: Is the saliva test, Geratherm ovu control, as accurate as the established urinary luteinizing hormone (LH) test for detecting ovulation and the following the fertile period? STUDY DESIGN: The voluntary participants were 74 healthy women with regular menstrual cycles and not using any hormonal contraceptives. The women used Geratherm ovu control, a small plastic hand-held microscope, for detecting the fertile period. A drop of saliva from sublingual was put onto the lens of the microscope. Three results were possible: non-fertile (dot pattern), transitional and fertile (ferning pattern). The participants performed the saliva test from the 5th till the 22nd day of the menstrual cycle and noted the respective result in a table. In addition to Geratherm ovu control, the EXACTO test for determining urinary LH concentration and the time of peak fertility was also performed. RESULTS: Positive LH shows a sharp increase beginning on the 10th cycle day with a maximum on the 17th cycle day. The curve for positive saliva and questionable positive saliva (one curve) is almost parallel with the curve for positive LH, reaching a maximum on the 16th cycle day. There is a high level of conformity for the same test results from the 5th (100%) till the 14th (84%) cycle day and from the 18th (80%) till the 22nd (96%) cycle day which corresponds to the pre- and post-ovulatory period. CONCLUSION: The saliva and the LH test both detect the fertile window of a menstrual cycle. Caused by the different hormones (estrogen for the saliva and LH for the LH test) leading to the respective positive test results, saliva turns positive 24h before LH. Consequently, the saliva test can be used as an ovulation test and help women maximize their chances of conceiving. There is also a high congruence between LH and saliva in the pre- and post-ovulatory period, indicating that the saliva test can also be used for contraception purposes.

LC-MS/MS based determination of basal- and ACTH-stimulated plasma concentrations of 11 steroid hormones: implications for detecting heterozygote CYP21A2 mutation carriers.

OBJECTIVE: Heterozygosity in 21-hydroxylase deficiency (21OHD) has been associated with hyperandrogenemic symptoms in children and adults. Moreover, the carrier status is mandatory for genetic counseling. We aimed at defining a hormonal parameter for carrier detection by mass spectrometry. DESIGN: Eleven basal and ACTH-stimulated steroid hormones of heterozygous carriers of CYP21A2 mutations and control individuals were compared. METHOD: Hormones were determined in plasma samples by liquid chromatography tandem mass spectrometry (LC-MS/MS) in 58 carriers (35 males, 23 females, age range 6-78 years) and 44 random controls (25 males, 19 females, age range 8-58 years). RESULTS: Heterozygotes could be identified best applying the 17-hydroxyprogesterone+21-deoxycortisol/cortisol×1000 ((17OHP+21S)/F×1000) equation 30  min after ACTH injection. An optimal cut-off value of 8.4 provided 89% sensitivity and specificity. Considering this data and a published frequency of heterozygotes of 1/50 to 1/61, the positive predictive value (PPV) of this cut-off is 12%. Of note, the negative predictive value (NPV) excluding heterozygosity in a given patient is 99.8%. CONCLUSION: Considering only marginal biochemical effects anticipated from heterozygosity, the stimulated ((17OHP+21S)/F×1000) identifies and excludes heterozygotes remarkably well. Nevertheless, LC-MS/MS cannot replace genetic testing, since sensitivity and specificity did not reach 100%. However, due to the considerably high NPV of the optimal cut-off and to a specificity of even 100% applying a cut-off higher than 14.7, hormonal assessment of heterozygosity can be of significant aid in conditions with limited access to genetic testing, as in some health care systems. The ((17OHP+21S)/F×1000) equation can guide diagnostic considerations in the differential diagnosis of hyperandrogenism.

In vitro comparison of different carrier materials with rat bone marrow MSCs.

OBJECTIVES: Injectable or implantable scaffolds seeded with autologous chondrogenic cells may represent a promising option for treatment of cartilage defects in the future. Current problems with the autologous chondrocyte implantation including dedifferentiation and the development of fibrocartilage suggest the use of alternative chondrogenic cell sources such as mesenchymal stromal cells (MSCs). The aim of this study was to compare the early effects of different scaffolds on the proliferation and metabolic activity of chondrogenic MSCs in vitro. MATERIALS AND METHODS: Multipotent stromal cells were isolated from rat bone marrow, phenotyped by flow cytometry, and differentiated into distinct lineages proved by lineage-specific staining and gene expression (RT-PCR) pattern. Cell proliferation on Tutodent® Membrane, Bio-Gide®, TissuFleece E, and Belotero® Soft was quantified by the MTT and WST-1 assay and direct determination of total cell numbers. Potential cytotoxic effects of eluates obtained from the materials were quantified by lactate dehydrogenase (LDH) and 5-bromo-2-deoxyuridine (BrdU) assay. RESULTS: TissuFleece E displayed the best results regarding cell proliferation on the biomaterials and metabolic activity (MTT, WST-1) (p < 0.001). Yet, the eluates of TissuFleece E caused an increased LDH release and lower values in the BrdU test. Cell proliferations on Bio-Gide®, Tutodent® Membrane, and Belotero® Soft were similar to the control. The eluates of Belotero® Soft exhibited the highest LDH release and lowest values in the BrdU assay (p < 0.05). CONCLUSIONS: Our results support the use of Tissufleece E as scaffold for chondrogenic rat MSCs. However, it should be prewashed with culture medium before seeding of the cells. CLINICAL RELEVANCE: Tissufleece E may serve as a promising carrier material for chondrogenic MSCs for cartilage tissue engineering attempts.

Investigation of the agreement of a continuous non-invasive arterial pressure device in comparison with invasive radial artery measurement.

BACKGROUND: Arterial pressure (AP) monitoring should be accurate, easy to use, free of risks, and ideally continuous. The continuous non-invasive arterial pressure (CNAP) device is non-invasive and provides continuous pressure readings. This study was performed to compare the agreement of CNAP and invasive AP monitoring. METHODS: Ninety patients undergoing surgery under general anaesthesia were enrolled. Invasive pressure monitoring was established at the radial artery. CNAP monitoring using a finger sensor recording was begun before induction of anaesthesia. Statistical analysis was conducted with the Bland-Altman method for comparisons of repeated measures. RESULTS: We obtained 16 843 valid pressure readings from 85 patients. Mean (sd) bias during maintenance of anaesthesia was: systolic AP: 4.2 (16.5) mm Hg; mean AP (MAP): -4.3 (10.4) mm Hg; and diastolic AP: -5.8 (6) mm Hg. The results of a subgroup analysis of patients who had a mean intra-arterial pressure of <70 mm Hg were as follows: systolic pressure: -0.3 (9.7) mm Hg; mean pressure: -6.8 (7.6) mm Hg; and diastolic pressure: -7.9 (7.2) mm Hg. Bias and percentage error during the induction period were greater in both the main and subgroup analyses, probably due to recalibration being omitted after induction. CONCLUSIONS: The CNAP monitor showed an acceptable agreement and was interchangeable with invasive pressure monitoring for MAP during normotensive conditions. During induction of anaesthesia and when the AP was low, the agreement was less good and interchangeability was not achieved. These results suggest that CNAP is not statistically equivalent to invasive monitoring during all periods of anaesthesia but may be a useful additional AP monitor.

Biocompatibility of bone graft substitutes: effects on survival and proliferation of porcine multilineage stem cells in vitro.

Bone graft substitutes (BGS) are widely used in clinical practice. For stem cellbased approaches to bone tissue engineering BGS need to show sufficient biocompatibility in the in vitro setting. This study was designed to demonstrate the influence of six different BGS on the proliferation and metabolic activity of porcine mesenchymal multilineage stem cells (pMSC) in vitro. Bone-marrow derived pMSC were cultivated for 24 hours with the eluates of six different BGS. The eluates were generated by incubating the BGS three times in succession for 24 hours with a culture medium and collecting the supernatants. pMSC vitality and proliferation in the presence of eluates from the first, second, and third incubation were assessed by WST-test quantification of metabolically active cells. Culture of pMSC with eluates in all cases resulted in decreased cell numbers in an eluate concentration-dependent manner. At least a 65% loss of cells compared to controls (culture medium without eluates) could be observed in the presence of undiluted eluates. The negative influence of eluates varied significantly among BGS. In all cases, second and third eluates were less potent in their negative effects on cellular vitality/proliferation. In conclusion, the BGS examined here should be submitted to thorough preincubation before in vitro use for cell-based constructs to maximize cell viability for the tissue engineering of bone.

Surgical treatment for brain metastases: Prognostic factors and survival in 309 patients with regard to patient age.

Brain metastases are the most common intracranial tumors. Overall, the only accepted prognostic factors are patient age and performance status. However, several other factors are considered before surgery. We performed a retrospective analysis of 309 patients who underwent surgical resection of newly diagnosed brain metastases between 1994 and 2004. Univariate survival analysis revealed age, performance status, extracranial metastases, complete resection, radiotherapy and re-craniotomy as prognostic indicators. Multivariate analysis determined that patient age, performance status, extracranial metastases, radiotherapy and re-craniotomy are independent factors of prolonged survival. We statistically estimated the age threshold separating patients with favorable outcomes from those with unfavorable prognoses. Using the Kaplan-Meier analysis this threshold can be set at 65 years. Multivariate analysis of patients >65 years revealed the presence of co-morbidities, the number of brain metastases, post-operative performance status and radiotherapy as independent prognostic factors.

Breast ultrasound elastography--results of 193 breast lesions in a prospective study with histopathologic correlation.

PURPOSE: To evaluate the diagnostic performance of ultrasound elastography in breast masses. MATERIAL AND METHODS: 193 lesions (129 benign, 64 malignant) were analyzed with the EUB 8500 Logos-ultrasonic-unit (Hitachi Medical, Japan) and a linear-array-transducer of 7.5-13-MHz. Standard of reference was cytology (FNAfine needle aspiration) or histology (core biopsy). The elastic-score was classified according to a 6-point colour-scale (Ueno classification; 1-3 = benign, 4-5 = malignant). Conventional B-mode ultrasound (US) findings were classified according to the BI-RADS classification. Statistical analysis included sensitivity, specificity, ROC-analysis and kappa-values for intra-/interobserver reliability. RESULTS: The mean score for elasticity was 4.1 ± 0.9 for malignant lesions, and 2.1 ± 1.0 for benign lesions (p < 0.001). With a best cut-off point between elasticity scores 3 and 4, sensitivity was 96.9%, and specificity 76%. Setting a best cut-off point for conventional US between BI-RADS 4 and 5, sensitivity was 57.8%, and specificity 96.1%. Elastography provided higher sensitivity and lower specificity than conventional US, but two lesions with elasticity score 1 were false negative, whereas no lesion scored BI-RADS 1-3 were false negative. ROC-curve was 0.884 for elastography, and 0.820 for conventional US (p < 0.001). Weighted kappa-values for intra-/interobserver reliability were 0.784/0.634 for BI-RADS classification, and 0.720/0.561 for elasticity scores. CONCLUSION: In our study setting, elastography does not have the potential to replace conventional B-mode US for the detection of breast cancer, but may complement conventional US to improve the diagnostic performance.

Development of a permanently controllable rotating biopsy device, part II: Competitive in-vitro testing of a cannula-like prototype compared to established end-cut and side-notch biopsy devices.

PURPOSE: To evaluate the quantitative and qualitative efficiency of a permanently controllable biopsy-cannula prototype with lancet-like helically bent cutting edge for safer biopsy compared to established end-cut and side-notch biopsy devices. MATERIALS AND METHODS: Each of the n = 100 specimens per organ and system were obtained by the prototype, an end-cut device and a side-notch device (18 gauge each) using a bovine liver, kidney and myocardium as the biopsy tissue. Quantitatively, the number of fragments, length in mm and weight in mg of the specimen were analyzed. Qualitatively, a histopathological analysis was performed with respect to tissue fragmentation, crush artifact and adequacy of tissue (score per category min. 1 and max 3). To identify significant differences (p < 0.025), chi-square and Kruskal-Wallis tests were calculated in the statistical analysis. RESULTS: For each of the n = 300 specimens, the one-piece fragment/mean length/mean weight were n = 232 / 10.34 mm/ 4.86 mg for the prototype, n = 210 / 12.16 mm/ 5.35 mg for the end-cut system and n = 248 / 11.63 mm/ 4.08 mg for the side-notch system. The differences reached a level of significance with p < 0.001. The mean histopathological score for the prototype/end-cut system/side-notch system was 5.60 / 5.60 / 5.25 for the liver, 5.65 / 4.65 / 4.60 for the kidney and 5.05 / 5.35 / 4.85 for the myocardium. The differences did not reach a level of significance for the liver/kidney/myocardium with p = 0.665 /p = 0.186 /p = 0.436. CONCLUSION: Compared to established core biopsy systems, the biopsy-cannula prototype offers diagnostically equivalent biopsy specimen quality in an in-vitro setting in bovine liver, kidney and myocardium.

Olfactory dysfunction in Wegener's granulomatosis.

Necrotizing granulomatous inflammation of the upper respiratory tract is one of the hallmarks of Wegener's granulomatosis (WG), which may explain the reason for olfactory dysfunction in WG. However, a systematic analysis using modem olfactory testing tools has not been performed and potential causes of dysfunction at different levels of olfactory information processing remain obscure so far. In this study a group of 76 WG-patients was examined with sniffin'sticks screening 12, odour threshold (T)/discrimination (D)/identification (I) TDI-score, active anterior rhinomanometry and a standardized questionnaire for olfactory function. WG-patients were aware of their olfactory dysfunction, as proven by psychophysiological test results. An altered olfactory function was significantly correlated to local administration of mupirocin and to the time interval between first diagnosis and study entry. None of the other variables had a statistical significant effect on the olfactory dysfunction.

Development of a permanently controllable rotating biopsy device, Part I: theoretical considerations and in-vitro results for five different prototypes.

PURPOSE: To develop different prototypes of permanently controllable rotating biopsy devices with determination of the most efficient prototype in biopsies in bovine myocardium. MATERIALS AND METHODS: Five different prototypes of 18-gauge rotating biopsy devices were designed and constructed, four (1 - 4) with various drill-like cutting edges and one (5) cannula type with a lancet-like helically bent cutting edge. Using bovine myocardium as the biopsy tissue, n = 100 specimens per prototype were obtained, and a quantitative analysis including tissue fragmentation, length in mm and weight in mg was carried out. For statistical analysis, the chi-square test for tissue fragmentation and Kruskal-Wallis test for the parameters length and weight were calculated. RESULTS: Prototype 5 showed the highest rate of extraction of one-fragment specimens in n = 66 cases and the lowest rate of failure to obtain tissue in n = 11 cases. The mean length/weight were 4.15 mm/ 3.91 mg for prototype 1, 1.80 mm/ 1.66 mg for prototype 2, 4.61 mm/ 3.28 mg for prototype 3, 5.20 mm/ 3.74 mg for prototype 4, and 9.57 mm/ 6.97 mg for prototype 5. In all three categories, prototype 5 was significantly superior to the prototypes 1 - 4 with p < 0.001. CONCLUSION: The cannula type with a lancet-like helically bent cutting edge proved to be the most efficient prototype and may now be tested competitively against established automated biopsy devices in vitro.

Influence of anaesthesia resident training on the duration of three common surgical operations.

We investigated the influence of resident training on anaesthesia workflow of three standard procedures--laparoscopic cholecystectomy, diagnostic gynaecological laparoscopy and transurethral prostate gland resection (TURP)--comparing 259 non-emergency resident vs 341 consultant cases from 20 German hospitals. Each hospital provided 10 random cases for each procedure, yielding 600 cases for analysis. Standard time intervals as documented in the hospital information system were: 'Case Time' (the time from the start of anaesthesia induction to discharge of the patient to the recovery area) and 'Anaesthesia Control Time' (which was the Case Time minus the time from the start of surgery to the end of surgical closure). Case Time was significantly shorter for consultants in all three procedures (p < 0.05, analysis of variance) and Anaesthesia Control Time shorter for consultants only in gynaecological laparoscopy and TURP. Patient comorbidity, patient age and geographical location of the hospital were not influential factors in the analysis of variance. We conclude that resident training significantly increases duration of elective operative times.

Should the aortic valve be replaced in patients with mild aortic stenosis admitted for coronary surgery?

BACKGROUND: The question whether the aortic valve in patients with mild aortic stenosis undergoing coronary artery bypass grafting (CABG) should be replaced or left alone is still controversial. METHODS: Between 01/1995 and 03/2004, 38 patients (30 male, 8 female, mean age 70.9 +/- 7.8 years) required redo AVR 7.1 +/- 4.8 years after primary CABG, while 202 patients (125 male, 77 female, mean age 72.7 +/- 7.8 years) underwent combined AVR and CABG (1.9 +/- 0.8 grafts/patient). To evaluate the different approaches, the data of the redo-AVR group were compared with the data of a propensity-score matched group of AVR + CABG patients. RESULTS: All patients survived the procedure; the 30-day survival was 94.7 % in both groups. The 1- and 5-year survival rates were 94.7 % and 83.8 % in the AVR after CABG group, and 94.7 % and 86.9 % in the AVR + CABG group, respectively. The late mortality was 28.9 % in the AVR after CABG and 25 % in the AVR + CABG group. Statistically, significant differences regarding perioperative mortality and morbidity could not be detected, neither with nor without propensity score analysis. CONCLUSION: Combined AVR and CABG in patients with coronary artery disease and mild to moderate aortic stenosis seems advisable in an institution with an equally low perioperative risk for both procedures, because the patient will need only one surgical procedure instead of undergoing surgery with all the associated risks twice.

[Pseudotumor cerebri: quantitative in-vivo measurements of markers of intracranial hypertension]. / Pseudotumor cerebri: Quantitative Normalwerte anatomischer Kennstrukturen im kraniellen MRT.

PURPOSE: Intracranial hypertension can change the morphology of anatomical structures that are critical in the evaluation of pseudotumor syndromes. The purpose of our study was to establish the normal range of such markers of intracranial hypertension and to consider a dependency on sex, age and body-mass index (BMI). MATERIALS AND METHODS: 123 persons without signs or symptoms of intracranial hypertension (63 females, 60 males, 18- 86-years-old, mean 49.5 SD17.8 years, mean BMI 25.3 SD42) were prospectively enrolled and MRI was performed at 3T. A STIR sequence in the coronal plane was used to measure the width of the optic nerve, the perioptic fluid rim and the total optic nerve sheath diameter in 4 different locations behind the eyeball. The height and width of the pituitary and Meckel's cave were also measured and the area was calculated. RESULTS: The mean width of the optic nerve sheath narrows significantly from anterior (mean 5.3 SD 0.6 mm) to posterior (mean 4.1 SD 0.4 mm), as does the perioptic fluid rim (mean 1.4 SD 0.3 mm vs. mean 1.0 SD 0.2 mm) and--to a lesser extent--the optic nerve itself (mean 2.4 SD 0.4 mm vs. mean 2 SD 0.3 mm, p=0.000 for all). There was no statistically relevant correlation of the width of the optic nerve sheath with age. The coronal area of Meckel's cave was independent of sex, age or BMI (mean 39 SD 9.3 mm2). The height of the pituitary differed little in women (mean 4.4 SD 0.9 mm) and men (mean 4.2 SD 0.8 mm), but we found a significant negative correlation with age in women only (r = -0.38, p = 0.01). CONCLUSION: The presented typical values and their deviations serve as a basis for the evaluation of pathologies in patients suspected of having pseudotumor syndrome.

Selective upregulation and amplification of the lysyl oxidase like-4 (LOXL4) gene in head and neck squamous cell carcinoma.

Members of the lysyl oxidase family (LOX) are copper and lysyl-tyrosine quinone cofactor-containing amine oxidases that are important for the assembly and maintenance of components of the extracellular matrix. Our previous results demonstrated that a novel member, LOXL4, is overexpressed in head and neck squamous cell carcinoma (HNSCC) compared to normal squamous epithelium. Results of the current study showed overexpression of the LOXL4 transcript in 74% (46 of 62) of invasive HNSCC tumours and 90% of both primary and metastatic HNSCC cell lines. Significant correlation was found between LOXL4 expression and local lymph node metastases versus primary tumour types (p<0.01) and higher tumour stages (p<0.01). Immunocytochemistry demonstrated cellular overexpression of the LOXL4 protein that correlated with the increased mRNA transcription in HNSCC cells. HNSCC cell lines displayed in significant subset of nuclei increased copies of the LOX4 gene locus on chromosome 10q24, demonstrated by fluorescence in situ hybridization (FISH). Extensive metaphase cytogenetic analysis was performed on UTSCC19A cells, identifying an isochromosome i(10)(q10). Taken together, these results highlight LOXL4 expression as a distinctive trait and suggest a functional role for LOXL4 in the molecular pathogenesis of invasive head and neck carcinomas.

Feasibility, toxicity and quality of life of first-line chemotherapy with platinum/paclitaxel in elderly patients aged >or=70 years with advanced ovarian cancer--a study by the AGO OVAR Germany.

BACKGROUND: The purpose of the study was to evaluate first-line platinum/paclitaxel (Taxol) under phase III trial conditions in ovarian cancer (OC) patients aged >or=70 years. PATIENTS AND METHODS: Phase III results of 779 patients with OC International Federation of Gynecology and Obstetrics (FIGO) stage IIB/IV treated with cisplatin/paclitaxel versus carboplatin/paclitaxel were retrospectively analyzed according to feasibility, toxicity (National Cancer Institute Common Toxicity Criteria) and quality of life (QoL) [European Organization for Research and Treatment of Cancer QoL questionnaire (EORTC QLQ-C30)] in patients aged <70 or >or=70 years. RESULTS: One hundred and three (13%) patients were aged >or=70 years. Patient characteristics (<70 versus >or=70 years) showed significant differences with regard to Eastern Cooperative Oncology Group performance status, residual disease and constitutional factors but not to FIGO stage, histology or grading. Elderly patients received 98%, 100% and 96% of the recommended paclitaxel, carboplatin and cisplatin dose, respectively, per cycle. Early discontinuation was more frequent in elderly, although QoL, nonhematological and hematological toxicity were comparable between elderly and younger patients, except for febrile neutropenia (5% versus <1%, P = 0.005). There were no significant differences with regard to cycle delays, dose reductions or the use of granulocyte colony-stimulating factor and antibiotics. CONCLUSION: Platinum/paclitaxel appeared to be feasible and tolerable in elderly patients under clinical trial conditions, but there seems to be a different investigators' estimation of toxicity and less intention to maintain trial treatment in elderly.

Open versus laparoscopic appendicectomy: a critical review.

BACKGROUND: The benefit of laparoscopic appendicectomy remains unclear. We have analysed available randomised studies comparing laparoscopic and open appendicectomy regarding their clinical pitfalls and statistical relevance. METHODS: Thirty eight studies were analysed in terms of the following aspects: A. clinical problems (e.g., expertise of the surgeons, pre- and postoperative antibiotic treatment, definition of complications, blinding of outcomes) and B. statistical problems (e.g., definition of primary and secondary outcomes, power and sample size, statistical methods, confidence intervals, comparability of groups and studies). RESULTS: Most of the studies have clinical and statistical pitfalls. The most important pitfalls are the uncertain expertise of the operating surgeons, blinding, and the exploratory nature of the studies. Our analysis aims at giving useful information for the appraisal of existing studies and the conduct of further studies. It also gives some preliminary results. CONCLUSIONS: More than twenty years after Semm performed the first laparoscopic appendicectomy, it is necessary to clarify the superiority of laparoscopic or open appendectomy with well-defined, carefully designed randomised studies.

Endothelial and epithelial expression of eotaxin-2 (CCL24) in nasal polyps.

BACKGROUND: Nasal polyposis is mostly associated with eosinophilia of mucosal tissue. This points to the implication of CC chemokines in nasal eosinophilia. Recently the CC chemokine eotaxin-2 (CCL24) was identified. This study was initiated to localize the cellular source, analyze expression of mRNA, and quantify protein synthesis of CCL24. METHODS: Specimens of nasal inferior turbinates from controls and polypous tissue from patients suffering from chronic polypous sinusitis were collected. Furthermore, fibroblasts and epithelial cells were cultured. CCL24 protein was analyzed by immunohistochemistry and ELISA, expression of mRNA by SQ-RT-PCR. RESULTS: CCL24 was observed in endothelial and epithelial cells. Specimens from patients expressed significantly (>2fold) more CCL24 mRNA than controls. Fibroblasts and unstimulated cells did not express CCL24 mRNA. Upon stimulation with TNF-alpha, INF-gamma, IL-4, or costimulation with TNF-alpha and INF-gamma CCL24 mRNA was significantly enhanced (3.2-19.6%). In controls, fibroblast, and unstimulated cells CCL24 protein was below detection limit. Most polyps comprised significant amounts of CCL24 (mean 0.24 ng/mg). TNF-alpha, INF-gamma or IL-4 induced CCL24 protein (0.1-0.3 ng/ml) in epithelial cells. Costimulation with TNF-alpha and IL-4 (0.1-30 and 1-30 ng/ml, respectively) synergistically induced synthesis of CCL24 protein (0.18-0.31 ng/ml). CONCLUSION: In nasal polyps endothelial and epithelial cells are obviously the main source of CCL24, which was shown for transcription (mRNA) and production (protein) levels and was associated with diseases. Results gave evidence of CLL24- directed migration of cells from inside (the bloodstream) to the epithelial side (mucosa) in eosinophilic inflammatory diseases, e.g. nasal polyposis.