Imaging-based characterization of convective tissue properties.

Convective transport is an important phenomenon for nanomedicine delivery. We present an imaging-based approach to recover tissue properties that are significant in the accumulation of nanoparticles delivered via systemic methods. The classical pharmacokinetic analysis develops governing equations for the particle transport from a first principle mass balance. Fundamentally, the governing equations for compartmental mass balance represent a spatially invariant mass transport between compartments and do not capture spatially variant convection phenomena. Further, the parameters recovered from this approach do not necessarily have direct meaning with respect to the governing equations for convective transport. In our approach, a framework is presented for directly measuring permeability in the sense of Darcy flow through porous tissue. Measurements from our approach are compared to an extended Tofts model as a control. We demonstrate that a pixel-wise iterative clustering algorithm may be applied to reduce the parameter space of the measurements. We show that measurements obtained from our approach are correlated with measurements obtained from the extended Tofts model control. These correlations demonstrate that the proposed approach contains similar information to an established compartmental model and may be useful in providing an alternative theoretical framework for parameterizing mathematical models for treatment planning and diagnostic studies involving nanomedicine where convection dominated effects are important.

Multiple cytokines for the detection of Mycobacterium tuberculosis infection in children with tuberculosis.

SETTING: Interferon-gamma (IFN-γ) release assays (IGRAs) play an important role in the diagnosis of Mycobacterium tuberculosis infection. However, in children with tuberculosis (TB), some studies have shown increased frequencies of false-negative or indeterminate IGRA results. OBJECTIVE: To analyse the spectrum of different cytokines to improve the diagnostic accuracy of IGRAs in latent tuberculous infection (LTBI) and active TB. DESIGN: We performed multiplex cytokine expression analysis of QuantiFERON® Gold In-Tube supernatants in children with active TB (n = 21) and disease-free contacts with (n = 15) and without LTBI (n = 12), to determine the sensitivity and specificity of the modified tests. RESULTS: Of 21 initial cytokines analysed, IFN-γ and six other candidates (interleukin [IL] 2, inducible protein 10 [IP-10], IL-13, IL-1α, tumour necrosis factor alpha [TNF-α] and granulocyte-macrophage colony-stimulating factor [GM-CSF]) were significantly more elevated in children with TB and those with LTBI than in the non-infected controls. Sensitivity and specificity were similar for IFN-γ and IL-2, but lower for the remaining candidates. Notably, a subset of candidates, including IP-10, showed M. tuberculosis antigen-induced specific expression in non-infected children. None of the candidates showed differences in expression between children with TB and those with LTBI. CONCLUSIONS: Our results did not suggest that alternative IGRA cytokines can distinguish between children with active TB and those with LTBI. IFN-γ and IL-2 showed comparable capacity in diagnosing M. tuberculosis infection in our study groups.

Assessing pre- and post-zygotic barriers between North Atlantic eels (Anguilla anguilla and A. rostrata).

Elucidating barriers to gene flow is important for understanding the dynamics of speciation. Here we investigate pre- and post-zygotic mechanisms acting between the two hybridizing species of Atlantic eels: Anguilla anguilla and A. rostrata. Temporally varying hybridization was examined by analyzing 85 species-diagnostic single-nucleotide polymorphisms (SNPs; FST ⩾0.95) in eel larvae sampled in the spawning region in the Sargasso Sea in 2007 (N=92) and 2014 (N=460). We further investigated whether genotypes at these SNPs were nonrandomly distributed in post-F1 hybrids, indicating selection. Finally, we sequenced the mitochondrial ATP6 and nuclear ATP5c1 genes in 19 hybrids, identified using SNP and restriction site associated DNA (RAD) sequencing data, to test a previously proposed hypothesis of cytonuclear incompatibility leading to adenosine triphosphate (ATP) synthase dysfunction and selection against hybrids. No F1 hybrids but only later backcrosses were observed in the Sargasso Sea in 2007 and 2014. This suggests that interbreeding between the two species only occurs in some years, possibly controlled by environmental conditions at the spawning grounds, or that interbreeding has diminished through time as a result of a declining number of spawners. Moreover, potential selection was found at the nuclear and the cytonuclear levels. Nonetheless, one glass eel individual showed a mismatch, involving an American ATP6 haplotype and European ATP5c1 alleles. This contradicted the presence of cytonuclear incompatibility but may be explained by that (1) cytonuclear incompatibility is incomplete, (2) selection acts at a later life stage or (3) other genes are important for protein function. In total, the study demonstrates the utility of genomic data when examining pre- and post-zyotic barriers in natural hybrids.

Release of EPA and DHA from salmon oil - a comparison of in vitro digestion with human and porcine gastrointestinal enzymes.

In the present study, we hypothesised whether in vitro digestion of salmon oil would release different amounts of PUFA depending on the origin of the lipolytic enzymes used. For this purpose, in vitro digestion of salmon oil (SO) was performed using human duodenal juice (HDJ) or a commercial enzyme preparation consisting of porcine pancreatin and bile (PB). The lipolytic effect was determined by measuring the release of fatty acids (FA) using solid-phase extraction and GC-flame ionisation detection, withdrawing samples every 20 min during digestion. The amount of FA released indicated that a plateau was reached after 80 min with approximately similar amounts of FA detected using both HDJ and PB (379 (sd 18) and 352 (sd 23) mg/g SO, respectively). However, the release of 18 : 2, EPA (20 : 5) and DHA (22 : 6) was significantly different during in vitro digestion. At 80 min, HDJ and PB released 43 and 33% of 18 : 2, 14 and 9% of EPA and 11 and 9% of DHA, respectively. Both enzyme preparations released approximately the same amounts of the other FA analysed. The effect of the addition of bile salts (BS) was significantly different in the two enzyme systems, where porcine pancreatin highly responded to the increase in BS concentration, in contrast to HDJ.

AAV serotype 2/1-mediated gene delivery of anti-inflammatory interleukin-10 enhances neurogenesis and cognitive function in APP+PS1 mice.

Brain inflammation is a double-edged sword. It is required for brain repair in acute damage, whereas chronic inflammation and autoimmune disorders are neuropathogenic. Certain proinflammatory cytokines and chemokines are closely related to cognitive dysfunction and neurodegeneration. Representative anti-inflammatory cytokines, such as interleukin (IL)-10, can suppress neuroinflammation and have significant therapeutic potentials in ameliorating neurodegenerative disorders such as Alzheimer's disease (AD). Here, we show that adeno-associated virus (AAV) serotype 2/1 hybrid-mediated neuronal expression of the mouse IL-10 gene ameliorates cognitive dysfunction in amyloid precursor protein+ presenilin-1 bigenic mice. AAV2/1 infection of hippocampal neurons resulted in sustained expression of IL-10 without its leakage into the blood, reduced astro/microgliosis, enhanced plasma amyloid-ß peptide (Aß) levels and enhanced neurogenesis. Moreover, increased levels of IL-10 improved spatial learning, as determined by the radial arm water maze. Finally, IL-10-stimulated microglia enhanced proliferation but not differentiation of primary neural stem cells in the co-culture system, whereas IL-10 itself had no effect. Our data suggest that IL-10 gene delivery has a therapeutic potential for a non-Aß-targeted treatment of AD.

Histopathologic features, immunophenotyping, clonality, and eubacterial fluorescence in situ hybridization in cats with lymphocytic cholangitis/cholangiohepatitis.

Feline lymphocytic cholangitis is a poorly characterized disease complex with respect to histologic lesions, immunophenotype, and etiopathogenesis. Seventy-eight cases of feline lymphocytic cholangitis (n = 51) and feline hepatic lymphoma (n = 27) were reviewed using standardized histopathology, immunophenotyping (B cell and T cell), polymerase chain reaction for T-cell receptor (TCR) gene rearrangement, and fluorescence in situ hybridization (FISH) for eubacteria. Five histopathologic features in cases of lymphocytic cholangitis assisted in its differentiation from hepatic lymphoma: bile duct targeting (n = 32, 62.7%), ductopenia (n = 9, 17.6%), peribiliary fibrosis (n = 37, 72.5%), portal B-cell aggregates (n = 36, 70.6%), and portal lipogranulomas (n = 38, 74.5%). The majority of lymphocytic cholangitis cases (n = 35, 68.6%) were T cell predominant; 15 (29.4%) had an equal mix of B cells and T cells, and 1 (1.9%) had a B cell-predominant infiltrate; 66.6% of hepatic lymphoma cases were T-cell lymphomas. TCR clonality results were unexpected, with 17.1% of cases of lymphocytic cholangitis having clonal or oligoclonal populations and with T-cell lymphomas having variable TCR clonality (63.6% clonal or oligoclonal, 36.3% polyclonal). The majority of lymphocytic cholangitis (n = 32 of 36, 88.8%) and all hepatic lymphoma cases had no detectable eubacteria using FISH. As demonstrated here, bile duct targeting, ductopenia, peribiliary fibrosis, portal B-cell aggregates, and portal lipogranulomas are lymphocytic cholangitis features that, along with polyclonal TCR (83%), help differentiate it from hepatic lymphoma. No strong evidence was found implicating in situ bacterial colonization as an etiopathogenesis of lymphocytic cholangitis.

Suppressor of cytokine signaling-3 is affected in T-cells from tuberculosisTB patients.

T-cells and T-cell-derived cytokines are crucial mediators of protection against Mycobacterium tuberculosis infection, but these factors are insufficient as biomarkers for disease susceptibility. In order to define T-cell molecules involved in tuberculosis (TB), we compared gene expression profiles of T-cells from patients with active TB, healthy donors with latent M. tuberculosis infection (LTBIs) and non-infected healthy donors (NIDs) by microarray analysis. Pathway-focused analyses identified a prevalent subset of candidate genes involved in the Janus kinase (JAK)-signal transducer and activator of transcription signalling pathway, including those encoding suppressor of cytokine signalling (SOCS) molecules, in the subset of protection-associated genes. Differential expression was verified by quantitative PCR analysis for the cytokine-inducible SH2-containing protein (CISH), SOCS3, JAK3, interleukin-2 receptor α-chain (IL2RA), and the proto-oncogene serine/threonine protein kinase (PIM1). Classification analyses revealed that this set of molecules was able to discriminate efficiently between T-cells from TB patients and those from LTBIs, and, notably, to achieve optimal discrimination between LTBIs and NIDs. Further characterization by quantitative PCR revealed highly variable candidate gene expression in CD4(+) and CD8(+) T-cells from TB patients and only minor differences between CD4(+) and CD8(+) T-cell subpopulations. These results point to a role of cytokine receptor signalling regulation in T-cells in susceptibility to TB.

IL-1beta-induced chemokine and Fas expression are inhibited by suppressor of cytokine signalling-3 in insulin-producing cells.

AIMS/HYPOTHESIS: Chemokines recruit activated immune cells to sites of inflammation and are important mediators of insulitis. Activation of the pro-apoptotic receptor Fas leads to apoptosis-mediated death of the Fas-expressing cell. The pro-inflammatory cytokines IL-1beta and IFN-gamma regulate the transcription of genes encoding the Fas receptor and several chemokines. We have previously shown that suppressor of cytokine signalling (SOCS)-3 inhibits IL-1beta- and IFN-gamma-induced nitric oxide production in a beta cell line. The aim of this study was to investigate whether SOCS-3 can influence cytokine-induced Fas and chemokine expression in beta cells. METHODS: Using a beta cell line with inducible Socs3 expression or primary neonatal rat islet cells transduced with a Socs3-encoding adenovirus, we employed real-time RT-PCR analysis to investigate whether SOCS-3 affects cytokine-induced chemokine and Fas mRNA expression. The ability of SOCS-3 to influence the activity of cytokine-responsive Fas and Mcp-1 (also known as Ccl2) promoters was measured by reporter analysis. RESULTS: IL-1beta induced a time-dependent increase in Mcp-1 and Mip-2 (also known as Cxcl2) mRNA expression after 6 h of stimulation in insulinoma (INS)-1 and neonatal rat islet cells. This induction was inhibited when Socs3 was expressed in the cells. In INS-1 cells, IL-1beta + IFN-gamma induced a tenfold and eightfold increase of Fas mRNA expression after 6 and 24 h, respectively. This induction was inhibited at both time-points when expression of Socs3 was induced. In promoter studies SOCS-3 significantly inhibited the cytokine-induced activity of Mcp-1 and Fas promoter constructs. CONCLUSIONS/INTERPRETATION: SOCS-3 inhibits the expression of cytokine-induced chemokine and death-receptor Fas mRNA.

T-cell responses against tuberculin and sensitin in children with tuberculosis and non-tuberculosis mycobacterial lymphadenopathy.

Multi-colour flow cytometry was applied to determine T-cell-specific interferon-gamma, interleukin-2 and tumour necrosis factor-alpha expression in children with tuberculosis and non-tuberculosis mycobacterial lymphadenopathy (NTM-L). In vitro stimulation of peripheral blood mononuclear cells with purified protein derivative from Mycobacterium tuberculosis (tuberculin) and M. avium (sensitin) revealed differential recognition of tuberculin and sensitin in both study groups. Ratios of tuberculin-specific and sensitin-specific T-cell proportions in individual patients discriminated between children with tuberculosis or NTM-L. These findings have the potential to improve the differential diagnosis of mycobacterial infections.

Curative rectal cancer surgery in a low-volume hospital: a quality assessment.

AIMS: Hospital volume or caseload is often used as a surrogate measure for quality of care in rectal cancer treatment. The aim of this study was to assess outcome in a low-volume hospital and secondly to examine the impact of surgeon volume on the results. METHODS: A retrospective review of 131 patients' charts identified 102 patients receiving apparently curative resections for rectal cancer in the period 1993-2002. Our study population did not differ significantly from the national average except for shift towards more advanced Dukes stage (p=0.00) and a higher rate of node positive patients at time of diagnosis (p=0.00). RESULTS: There were no significant differences from the national outcome results, neither in perioperative mortality or complications, nor 5-year survival or local recurrences. Thirteen different on-staff surgeons performed rectal cancer surgery in our hospital in the decade, and median annual caseload was four. We detect a difference in 5-year survival when grouping the surgeons by annual caseload, but the significance is inconclusive. It is, however, interesting that in 85% of the resections, two or more certified gastrointestinal surgeons with specific training were involved. A relatively high number (9%) of discrepancies between the Norwegian Rectal Cancer Registry (NRCR) database and the local hospital database were identified. CONCLUSION: Adequate results for surgical outcome can be achieved in a low-volume hospital. Surgeon volume showed inconclusive impact for our results of outcome. A local quality initiative is justified in addition to national registries.

Synthesis of C8-modified 2''-deoxyadenosine with carcinogenic arylamines.

The synthesis of phosphoramidites of C8-modified 2'-deoxyadenosine with carcinogenic arylamines p-anisidine and 4-aminobiphenyl is described. Two different methods were studied related to the glycon and base protection groups.

Assessment of the decision support needs of women from HIV endemic countries regarding voluntary HIV testing in Canada.

OBJECTIVE: To describe the decision support needs of immigrant and refugee women from HIV endemic countries regarding decision-making about voluntary counseling and testing for HIV (VCT) in Canada; and the needs of practitioners who support these women in making this decision, in a culturally appropriate manner. METHODS: Adapted, semi-structured questionnaires, based on the Ottawa Decision Support Framework (ODSF), were used to interview practitioners and patients. Practitioners from diverse backgrounds were purposefully selected from centers providing VCT in Ottawa. Adult, English-speaking immigrant and refugee women from HIV endemic countries were recruited from a clinic specializing in immigrant health services. Responses were tabulated using descriptive statistics, and emerging themes coded to identify unique factors affecting decision-making. RESULTS: Analysis revealed differences between practitioner and patient perceptions of the decision-making needs of women from HIV endemic countries regarding VCT. Practitioners identified women's lack of knowledge about HIV transmission and prevention as a primary need, while patients identified inadequate awareness of HIV screening and treatment services, and their benefits and harms. Patients also perceived that women would not be aware of the various VCT options, while few practitioners highlighted this concern. Both groups held similar viewpoints about counseling strategies that could improve decision-making. CONCLUSION: Women were unaware of the options available to them for VCT. Both practitioners and patients highlighted the issue of stigma and negative outcomes associated with testing that created barriers or contributed to delays in women receiving testing. Women preferred anonymous testing, and recommended that information and decision support regarding HIV testing be provided via non-targeted strategies, and integrated within general health services or public education. PRACTICE IMPLICATIONS: Decision support in the context of VCT can improve decision quality, empowering patients to make informed decisions based on personal values. Study findings can inform the development of clinical guidelines for the routine offering of VCT.

Sample selection for microarray gene expression studies.

OBJECTIVES: The choice of biomedical samples for microarray gene expression studies is decisive for both validity and interpretability of results. We present a consistent, comprehensive framework to deal with the typical selection problems in microarray studies. METHODS: Microarray studies are designed either as case-control studies or as comparisons of parallel groups from cohort studies, since high levels of random variation in the experimental approach thwart absolute measurements of gene expression levels. Validity and results of gene expression studies heavily rely on the appropriate choice of these study groups. Therefore, the so-called principles of comparability, which are well known from both clinical and epidemiological studies, need to be applied to microarray experiments. RESULTS: The principles of comparability are the study-base principle, the principle of deconfounding and the principle of comparable accuracy in measurements. We explain each of these principles, show how they apply to microarray experiments, and illustrate them with examples. The examples are chosen as to represent typical stumbling blocks of microarray experimental design, and to exemplify the benefits of implementing the principles of comparability in the setting of microarray experiments. CONCLUSIONS: Microarray studies are closely related to classical study designs and therefore have to obey the same principles of comparability as these. Their validity should not be compromised by selection, confounding or information bias. The so-called study-base principle, calling for comparability and thorough definition of the compared cell populations, is the key principle for the choice of biomedical samples and controls in microarray studies.

Outcome of four weeks' intervention with probiotics on symptoms and endoscopic appearance after surgical reconstruction with a J-configurated ileal-pouch-anal-anastomosis in ulcerative colitis.

OBJECTIVE: Pouchitis is a common and troublesome condition in patients operated on with ileal-pouch-anal-anastomosis (IPAA). A disturbed microecology in the pouch has been suggested as one possible explanation. In a previous double-blind, randomized, controlled study we demonstrated clinical improvement of symptoms in patients with ulcerative colitis (UC) operated on with IPAA, during intervention with live probiotic microbes Lactobacilli and Bifidobacteriae. The aim of the present study was to confirm our previous results in a much larger material, including clinical symptoms, faecal flora and endoscopic evaluation, and to compare the results in UC/IPAA patients with those of patients with familial adenomatous polyposis (FAP) with IPAA and UC patients with ileorectal anastomosis (IRA). MATERIAL AND METHODS: Five hundred millilitres of a fermented milk product (Cultura) containing live lactobacilli (La-5) and bifidobacteriae (Bb-12) was given daily for 4 weeks to 51 UC patients and 10 patients with FAP, operated on with IPAA, and six UC patients operated on for IRA. Stool samples were cultured for examination of lactobacilli, bifidobacteriae, fungi and pH before, during and after intervention. Before, during and after intervention, endoscopic evaluation was performed. Categorized symptomatology was examined prospectively using diary cards in addition to an interview, before and on the last day of intervention. RESULTS: The number of lactobacilli and bifidobacteriae increased significantly during intervention in the UC patients operated on with IPAA and remained significantly increased one week after intervention. Involuntary defecation, leakage, abdominal cramps and the need for napkins (category I), faecal number and consistency (category II) and mucus and urge to evacuate stools (category III) were significantly decreased during intervention in the UC/IPAA group. In the FAP group there was a significant decrease in faecal leakage, abdominal cramps and use of napkins (category I) during intervention. The median endoscopic score of inflammation was significantly decreased during intervention in the UC/IPAA patients. Blood tests, faecal fungi and faecal pH did not change significantly during intervention. CONCLUSIONS: Results of this extended study, showing an effect of probiotics on symptoms and endoscopic inflammation in UC patients operated on with IPAA confirm our previously reported effect of probiotics on clinical symptoms and endoscopic score in a smaller, double-blind, randomized, controlled study. The significantly higher response to probiotics in families with increased risk of IBD will have to be repeated in future studies.

Ultraviolet radiation and the risks of cutaneous malignant melanoma and non-melanoma skin cancer: perceptions and behaviours of Danish and American adolescents.

The highest prevalence rates of skin malignancy in the northern hemisphere occur in Scandinavia and the United States (USA). Most Danes and Americans receive 50% of their lifetime ultraviolet (UV) radiation before the age of 21, making it important to address sun exposure risks with adolescents. The project was undertaken to determine differences between Danish and American adolescents in knowledge of sun exposure and skin malignancy, activities accounting for sun exposure, and means used for sun protection. Questionnaires regarding skin cancer and sun exposure were distributed to 674 secondary school age students in Hilleroed, Denmark, and to 483 similarly aged students in Winston-Salem, North Carolina, USA. Differences in responses between and within groups were compared. American adolescents had more knowledge of the characteristics and malignant potential of melanoma than did Danish adolescents. Danish youth and females from both countries were significantly more likely to engage in sunbathing and tanning bed use. Black Danish students reported significantly more sunburn and were more likely to sunbathe or use a tanning bed than were black American students. Danish students were more likely than Americans to use sunscreen, however, Americans were more likely to apply sun protective factor (SPF) 15 or greater. In conclusion, given that sunbathing and tanning bed use are associated with the development of precancerous lesions and skin malignancy, Danish teens are at increased risk. The rates of skin malignancy are relatively high in Scandinavia and efforts to improve understanding of exposure and cancer risks should be undertaken in adolescents.

Testosterone modulates K(+)ATP channels in Sertoli cell membrane via the PLC-PIP2 pathway.

Testosterone at physiological intratesticular concentrations induces a dose-dependent depolarisation and an increase in input resistance together with an increment of 45Ca2+ uptake in the Sertoli cells from seminiferous tubules of immature rat. Previous studies have implicated K(+)ATP channels in these testosterone actions. This study demonstrates that testosterone and sulphonylureas (glibenclamide and tolbutamide) depolarise the membrane potential, augment resistance and 45Ca2+ uptake in the Sertoli cells of seminiferous tubules from 10-15 day-old rats. These actions were nullified by the presence of the K(+)ATP channel opener diazoxide. The depolarisation was also observed with the impermeant bovine serum albumin-bound testosterone. Testosterone actions were blocked by both pertussis toxin and the phospholipase C (PLC) inhibitor U73122 implying the involvement of PLC - phosphatidylinositol 4-5 bisphosphate (PIP2) hydrolysis via G protein in testosterone actions. Polycations, including spermine and LaCl3, depolarised the membrane potential and increased the resistance. Hyperpolarisation caused by EGTA was reversed by LaCl3 and by the presence of testosterone. This last effect was nullified by the presence of U73122. All of the above results indicate that the action of testosterone on the Sertoli cell membrane is exercised on the K(+)ATP channels through PLC-PIP2 hydrolysis that closes the channel, depolarises the membrane, and stimulates 45Ca2+ uptake.

[Further development of the International Pneumoconiosis Classification--from ILO 1980 to ILO 2000 and to ILO 2000/German Federal Republic version]. / Die Weiterentwicklung der Internationalen Staublungenklassifikation - von der ILO 1980 zur ILO 2000 und zur ILO 2000/Version Bundesrepublik Deutschland.

The ILO (1980) Classification has been revised during recent years. The new version is now available as the International Classification of Radiographs of Pneumoconioses (Revised edition 2000). The Guidelines booklet is currently available only in English. Those involved felt it was important to maintain continuity with the ILO (1980) edition, in particular to retain the standard radiographs, despite their restricted quality, so as to ensure comparability with earlier national and international data sets. The standard films illustrating pleural abnormalities, and 'u'-shadows, have been modified and reconstituted. The most important changes relate to assessment of film quality, pleural abnormalities, and additional symbols. In Germany, film quality is characterised as "+", "+-", "+--" and "u" according to whether the ability to assess pneumoconiosis is judged to be unimpeachable ("+") to unusable ("u"). If a film is not classified as "+", then written comments regarding defects are required. For "diffuse" pleural thickening, the ILO (2000) edition now requires the presence also of obliteration of the costophrenic angle. This was not required in the earlier (1980) edition and, as previously, is also not stipulated in the German version. A minimum width of 3 mm (previously 0-5 mm), coded "a", is required both for plaques as well as for the margin to the lateral chest wall. Congruence is thus achieved for criteria, which, in German practice, lead to an indication of suspect occupational disease. Plaques on the diaphragm are not considered for measurement of extent; they are only coded as present or absent. If calcification is identified, then this must also be classified and measured as a localised plaque. Extent of calcification on its own, previously coded "0" to "3", is no longer specified. The following new symbols, illustrated by new diagrams, have been introduced: aa = atherosclerotic aorta; at = apical thickening; cg = calcified granuloma (or other non-pneumocononiotic nodules); me = mesothelioma (already previously differentiated from "ca" on the German record sheet); pa = plate atelectasis; pb= parenchymal bands; ra = rounded atelectasis; od = other disease. (Examples of the latter are illustrated diagrammatically by lobar pneumonia, aspergilloma, goiter and hiatal hernia.) Earlier national differences (ILO 1980/German Federal Republic) on particular issues have also been agreed among German "double-readers" ["Zweitbeurteiler"]. However, conformity between the original (ILO 2000) text and the national (German) modified text has been retained in large measure. The detailed descriptions of the standard films differ in certain respects from the German (1980) definitions. Some revision of individual descriptions of the films are proposed. Except for a few differences, agreement was reached here too. The definitive date for the change in Germany is expected to be in early 2004. The standard films are already available now through ILO offices in Geneva or Bonn (addresses in appendix.)

Nasal and paranasal sinus carcinoma: are we making progress? A series of 220 patients and a systematic review.

BACKGROUND: The authors reviewed treatment results in patients with nasal and paranasal sinus carcinoma from a large retrospective cohort and conducted a systematic literature review. METHODS: Two hundred twenty patients who were treated between 1975 and 1994 with a minimum follow-up of 4 years were reviewed retrospectively. A systematic review of published articles on patients with malignancies of the nasal and paranasal sinuses during the preceding 40 years was performed. RESULTS: The 5-year survival rate was 40%, and the local control rate was 59%. The 5-year actuarial survival rate was 63%, and the local control rate was 57%. Factors that were associated statistically with a worse prognosis, with results expressed as 5-year actuarial specific survival rates, included the following: 1) histology, with rates of 79% for patients with glandular carcinoma, 78% for patients with adenocarcinoma, 60% for patients with squamous cell carcinoma, and 40% for patients with undifferentiated carcinoma; 2) T classification, with rates of 91%, 64%, 72%, and 49% for patients with T1, T2, T3, and T4 tumors, respectively; 3) localization, with rates of 77% for patients with tumors of the nasal cavity, 62% for patients with tumors of the maxillary sinus, and 48% for patients with tumors of the ethmoid sinus; 4) treatment, with rates of 79% for patients who underwent surgery alone, 66% for patients who were treated with a combination of surgery and radiation, and 57% for patients who were treated exclusively with radiotherapy. Local extension factors that were associated with a worse prognosis included extension to the pterygomaxillary fossa, extension to the frontal and sphenoid sinuses, the erosion of the cribriform plate, and invasion of the dura. In the presence of an intraorbital invasion, enucleation was associated with better survival. In multivariate analysis, tumor histology, extension to the pterygomaxillary fossa, and invasion of the dura remained significant. Systematic review data demonstrated a progressive improvement of results for patients with squamous cell and glandular carcinoma, maxillary and ethmoid sinus primary tumors, and most treatment modalities. CONCLUSIONS: Progress in outcome for patients with nasal and paranasal carcinoma has been made during the last 40 years. These data may be used to make baseline comparisons for evaluating newer treatment strategies.

Prevalence and risk factors of adenomyosis at hysterectomy.

BACKGROUND: The present study was performed to evaluate the prevalence and possible associated risk factors for adenomyosis. METHODS: Medical records were retrieved and histo-pathological material re-examined for 549 consecutive women undergoing hysterectomy in a two-year period from 1990-1991. RESULTS: The prevalence of adenomyosis in the study varied from 10.0-18.2%, depending on different diagnostic criteria. The presence of endometrial hyperplasia at the time of hysterectomy was the only variable significantly associated with adenomyosis (OR = 3.0; 95% CI: 1.2-8.3). No statistically significant association was found between adenomyosis and previous caesarean section, endometrial curettage or evacuation of the uterus. Furthermore, we did not see any significant association between adenomyosis and pain-related symptoms, indication for hysterectomy, age, parity or number of myometrial samples. CONCLUSIONS: Our study stresses the need for precise diagnostic criteria for adenomyosis, and furthermore indicates that endometrial hyperplasia and adenomyosis may have a common aetiology.