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SM047 is a recently developed monoclonal antibody generated against an ovarian adenocarcinoma cell line. A recent immunohistochemical study has shown that SM047 is strongly expressed in tissue sections of most ovarian serous adenocarcinomas. This study aimed to ascertain whether SM047 staining is of value in cytological preparations of peritoneal fluid. A total of 206 consecutive peritoneal fluids were stained immunocytochemically with SM047, CA125, monoclonal carcinoembryonic antigen (mCEA), Ber-EP4 and cytokeratins (CK7 and 20). SM047 positivity was present in reactive mesothelial cells in 117 of 141 (83%) benign cases in which these were present. SM047 positive tumour cells were present in 22 of 23 (96%) ovarian serous adenocarcinomas and in small numbers of gastric adenocarcinomas (two of three), mesotheliomas (one of two) and pancreatic adenocarcinomas (one of one). All six colorectal and two breast adenocarcinomas were negative with SM047. Reactive mesothelial cells in all cases were positive with CK7 and in most cases with CA125. They were negative with CEA, Ber-EP4 and CK20. All adenocarcinomas were positive with Ber-EP4 and mesothelial cells were always negative. All colorectal adenocarcinomas were positive with CK20. This study shows that SM047 staining may be of value in the diagnosis of an ovarian serous adenocarcinoma in peritoneal fluids. Negative staining helps to exclude a primary ovarian serous adenocarcinoma and is characteristic of colorectal adenocarcinoma. The small numbers of other malignancies in the study precludes a judgement of the value of SM047 staining in these neoplasms. SM047 staining may be useful, as part of a larger panel, in the work up of patients with peritoneal effusions.

In this paper we report on invertebrate communities and habitat associations of species in summer-dry streams of western Oregon. Overall, we recorded 202 aquatic and semi-aquatic species, including at least 13 previously undescribed taxa. Species richness in temporary forest streams (≥125 species) exceeded that in a permanent headwater (100 species). Richness in ephemeral streams was 35 species or less. Duration of flow, exposure (shaded or open), riffle-pool structure and summerdrought conditions were key factors shaping community composition between and within stream types. We conclude that the potential of summer-dry streams with respect to habitat function is still widely underestimated. Such systems need more attention both from limnologists and landscape ecologists.

Fine needle aspiration cytology (FNAC) of mammary granular cell tumour: a report of three cases This report describes the FNAC findings in three cases of granular cell tumour of the breast. The patients comprised two females aged 59 and 62 years and one male aged 28 years. All patients presented with a breast lump which was clinically and radiologically suspicious of malignancy. FNAs yielded moderately cellular specimens which on cytologic examination consisted of groups of cells and single cells with small regular nuclei and abundant granular cytoplasm. Bare nuclei were also present but these did not have the characteristic bipolar appearance of myoepithelial cells. In two cases there was a granularity to the background. The aspirates were reported as equivocal or atypical, probably benign, and surgical biopsy was performed. Histological examination showed typical benign granular cell tumours with strong positive staining for S-100 protein. Pathologists should be aware that granular cell tumour may occur in or around the breast and should consider this diagnosis in aspirates containing a population of cells with regular nuclei and abundant granular cytoplasm. The main cytologic differential diagnoses are likely to be apocrine cells and histiocytes. The suspicion of a granular cell tumour should be heightened when these features are present in an aspirate from a clinically and radiologically suspicious mass. These cases highlight the role of the triple approach encompassing clinical, radiological and cytological features in the assessment of a breast lesion.

mccluggage w. g., patterson a., white j. and anderson n. h. (1998) Cytopathology9, 336–342 Immunocytochemical staining of ovarian cyst aspirates with monoclonal antibody against inhibin Inhibin is a peptide hormone which is produced by ovarian granulosa cells during normal follicular development. It is important that granulosa cells are recognized in fine needle aspirates (FNAs) of ovarian cystic lesions, as this allows definite recognition of a functional cyst and exclusion of a potentially neoplastic epithelial lined cyst. Occasionally the distinction between granulosa and epithelial cells may be difficult, especially when aspirates from functional cysts are unusually cellular. In the present study, FNAs from 33 ovarian cystic lesions were immunostained with a monoclonal antibody against inhibin. Nine cases of peritoneal fluid containing malignant cells in patients subsequently confirmed to have ovarian adenocarcinoma were also stained. Where possible the cytological and immunocytochemical findings were correlated with subsequent biopsy. In most cases in which cytology suggested a functional cyst there was a strong positive staining with anti-inhibin, although occasional cases were negative. One case originally thought to contain epithelial cells stained strongly positive with anti-inhibin and on review was felt to represent a cellular functional cyst. In all other cases where cells were considered to be epithelial there was no staining with anti-inhibin. The study shows that immunocytochemical staining with anti-inhibin may be of value in confirming the presence of granulosa cells, thus establishing a diagnosis of functional cyst. Although negative staining does not exclude a functional cyst, positive staining with anti-inhibin allows exclusion of an epithelial lined cyst and may avoid unnecessary surgical intervention. Immunocytochimie des liquides de kyste de l'ovaire avec un anticorps anti-inhibine L'inhibine est une hormone peptidique produite par les cellules de la granulosa de l'ovaire au cours du developpement normal du follicule. Il est important de bien reconnaitre les cellules de la granulosa dans les ponctions a l'aiguille fine des kystes de l'ovaire afin d'identifier les kystes fonctionnels et d'exclure une lesion kystique epitheliale potentiellement tumorale. Parfois, la distinction entre cellules de la granulosa et cellules epitheliales est difficile, particulierement lorsque les liquides de kystes fonctionnels sont tres cellulaires. Dans cette etude, la ponction a l'aiguille fine de 33 lesions kystiques de l'ovaire a fait l'objet d'une etude immunocytochimique avec un anticorps monoclonal dirige contre l'inhibine. Neuf cas de liquide peritoneal contenant des cellules malignes ont egalement eteetudies, chez des patientes dont le diagnostic d'adenocarcinome ovarien a ete confirme. La correlation des donnees cytologiques et immunocytochimiques avec les biopsies ulterieures a ete realisee chaque fois que possible. Dans la plupart des cas ou la cytologie suggerait un kyste fonctionnel, le marquage avec l'anticorps anti-inhibine etait tres positif, bien que de rares cas soient negatifs. Un cas classe en type epithelial dans un premier temps, fortement positif avec l'anti-inhibine, a ete reclasse en kyste fonctionnel. Dans tous les autres cas, ou les cellules avaient ete considerees comme etant epitheliales, le marquage anti-inhibine etait negatif. Cette etude montre que le marquage immunocytochimique avec l'anti-inhibine peut etre interessant pour confirmer la presence de cellules de la granulosa, etablissant ainsi le diagnostic de kyste fonctionnel. Bien qu'un marquage negatif ne permette pas d'exclure un kyste fonctionnel, un marquage positif avec l'anti-inhibine permet d'eliminer le kyste epithelial et ainsi d'eviter une intervention chirurgicale inutile. Die immunzytochemische Darstellung von Ovarialzystenpunktaten mit dem monoklonalen Antikorper gegen Inhibin Inhibin ist ein Hormoneiweiss, das von den Granulosazellen wahrend der normalen Follikelentwicklung produziert wird. Die Identifizierung der Granulosazellen erlaubt die Abgrenzung funktionaler Zysten von moglicherweise neoplastischen, epithelialen Zysten des Ovars. In zellreichen Praparaten kann diese Identifikation Schwierigkeiten bereiten. Es Wurden deshalb 33 FNP mit dem monoklonalen Antikorper gegen Inhibin gefarbt. Als Kontrolle dienten Aszitespraparate von 9 gesicherten Fallen von ovariellem Adenokarzinom. Wenn moglich wurden die Befunde mit Biopsiepraparaten korreliert. In dem miesten Fallen mit dem zytologischen Bild einer funktionellen Zyste war die Reaktion stark positiv, allerdings blieben einige Falle negativ. Ein erst als epithelial eingestufter Fall war ebenfalls stark positiv, erwies sich abver bei der Uberprufung als funktional. Alle anderen als epithelial beurteilten Falle blieben negativ. Die Studie belegt den Nutzen einer Identifizierung der Granulosazellen, auch wenn einzelne Falle mit Anti-Inhibin nicht darstellbar sind. Epitheliale Zysten konnen ausgeschlossen und somit chirurgische Eingriffe vermieden werden.

1. Field data and results from laboratory rearing are combined to describe shredder–collector interactions in western Oregon temporary streams. 2. The composition of functional feeding groups in the temporary streams conforms to that predicted for permanent headwaters by the River Continuum Concept (RCC). 3. A distinct functional feeding group phenology was found, with shredders emerging first and collectors emerging last in the season. Scrapers were intermediate. 4. Presence of shredders enhanced collector growth in laboratory experiments (P < 0.01;n = 12). The species reared in the study trials accounted for 67% of the shredder biomass and 76% of the collector biomass in the natural systems. 5. Field data and laboratory rearing trials both support the hypothesis of a close shredder–collector interaction in the processing of allochthonous material in the summer-dry headwaters studied.

1. We measured sodium-lithium countertransport, sodium-hydrogen exchange and membrane microviscosity in 48 individuals with familial hypercholesterolaemia, 33 subjects with hypertriglyceridaemia and 54 normolipaemic controls. Full lipid profile, blood pressure, body mass index, fasting glucose and insulin levels were also measured. 2. Subjects with hypertriglyceridaemia had higher blood pressure, body mass index, fasting glucose and insulin levels than normal controls. 3. Vmax of the sodium-lithium countertransport was elevated in the hypertriglyceridaemic group compared with controls. Across the whole group loge triacylglycerols correlated with Vmax of the sodium-lithium countertransport. There was no difference in sodium-lithium countertransport Km between the groups. 4. Sodium-hydrogen maximal proton efflux rate (Vmax) and Km were not different between the three groups. There were no correlations between sodium—hydrogen exchange and sodium—lithium countertransport parameters. 5. Microviscosity as measured by diphenylhexatriene was reduced at the core of the membrane in subjects with hypertriglyceridaemia compared with those with familial hypercholesterolaemia or normolipaemic controls, suggesting an alteration in membrane structure. 6. Changes in sodium transport in hyperlipidaemia may be mediated by changes in membrane structure resulting in altered protein conformation or turnover.

Summary The paper considers the problem of identifying spatial clustering, for instance of one group of individuals in relation to the spatial distribution of another. First, some of the literature is reviewed, some operational problems of practical investigations are discussed and a data set is introduced that involves a group of laryngeal cancer patients and a group of lung cancer patients in south Lancashire. Two techniques, an integrated squared difference statistic and a two-dimensional version of the scan statistic, are then outlined, some of their properties are discussed and they are applied to the data set. The final section takes stock of the data analysis and the characteristics of the techniques.

Trauma, infection, neoplasia, and inflammation can all disrupt the intact intestinal mucosal barrier to intraluminal bacteria and bacterial antigens. This study investigated the relation between colonic inflammation and colonic mucosal barrier function in three experimental models of colitis. There were significantly increased systemic endotoxin concentrations in rats with acetic acid (7.5 (1.7-119.5) pg/ml), ethanol (13.7 (0-111.2) pg/ml), and hapten induced (14.4 (5-31.1) pg/ml) colitis compared with saline controls (3.3 (0-13.7) pg/ml). Data expressed as median (range). There were significant correlations between the systemic endotoxin concentration and both the severity of colitis and of illness in acetic acid induced colitis. A significant increase in colonic permeability to 14C-polyethylene glycol was shown in rats with acetic acid (3.42 (1.36-5.63)%) and hapten induced colitis (2.86 (1.03-8.10)%) compared with saline controls (1.20 (0.67-1.36)%). Data expressed as median (range) of percentage of the intracolonic bolus excreted in urine. There was a significant positive correlation between the severity of colitis and % colonic permeability to 14C-polyethylene glycol. This and other studies provide evidence that mucosal barrier dysfunction is a feature of colitis irrespective of aetiology or species. Such barrier dysfunction may be responsible for the systemic inflammatory response and complications seen in patients with inflammatory bowel disease.

The role of the l-arginine-nitric oxide pathway in the pathogenesis of colonic inflammation was assessed using l-arginine and its competitive analogue Nω-nitro-l-arginine methyl ester (l-NAME) in a rat model of colitis. In the first study oral l-arginine 2 per cent (control: 3.4 per cent l-glycine) was administered with and without l-NAME 100 mg/l. Orally administered l-arginine increased colonic inflammation (P = 0.004) and decreased thymic weight (P = 0.0007). Addition of l-NAME reduced the colonic inflammation and prevented loss of body-weight (P < 0.04). In the second study l-NAME was administered orally in concentrations of 100, 200 and 500 mg/l (control: no l-NAME). l-NAME 500 mg/l reduced colonic inflammation and increased thymic weight and body-weight (P < 0.01). Thymic weight and body-weight correlated positively with the concentration of l-NAME administered orally (rs≥0.3, P = 0.04). l-NAME l g/l was administered topically as an enema (control: suspension agent). Topical l-NAME reduced colonic inflammation and increased thymic weight (P < 0.05). These results suggest that the l-arginine-nitric oxide pathway mediates colonic inflammation in this model.

SUMMARY 1. Field data and results from laboratory rearing are combined to describe life cycles and food habits of the mayflies Paraleptophlebia gregalis and Ameletus n. sp., and the stoneflies Soyedina interrupts, Ostrocerca foersteri, Sweltsa fidelis and Calliperla luctuosa. 2. P. gregalis, A. n. sp., S. interrupts and O. foersteri have univoltine life cycles which are characterized by a high degree of plasticity. S. fidelis and C. luctuosa have semivoltine life cycles which are more tightly synchronized. 3. Laboratory feeding trials and field observations characterize P. gregalis as a collector, A. n. sp. as a scraper, O. foersteri and S. interrupta as shredders and C. luctuosa as a predator mainly of midge larvae. Late-instar larvae of S. fidelis are believed to be scavengers. 4. Laboratory rearing yielded a negative correlation between growth rates (Y) and larval size in autumn (X) for S. interrupta. This indicates compensatory growth by small larvae in order to achieve synchronized emergence. The correlation can be described by the equation: Y = 0.0053–0.0036X (R2= 0.82; P < 0.01; n = 22) 5. The field and laboratory data indicate that photoperiod mainly determines the rate of development and size of emerging subimagos in P. gregalis.

To regenerate coefficients for the New Zealand customised birthweight centile calculator using an updated birth cohort, and compare the identification of at-risk small-for-gestational-age (SGA) infants between full customisation (including maternal characteristics) and an ultrasound-based fetal weight and infant gender partial customisation.Retrospective cohort study of prospectively collected maternity data.National Women's Health Auckland, New Zealand.Singleton pregnancies in the period 2006-2009; n = 24,176.Multiple linear regression analysis was performed for full customisation (adjusted for gestation, infant gender, maternal characteristics and pathological variables) and ultrasound-and-gender customisation (adjusted for gestation and infant gender).Risks of SGA-related perinatal death were compared between models.Changes occurred in some ethnicity coefficients, including Chinese (-135 g), Tongan (-101 g) and Samoan (-89 g), and ten ethnicities were added. Overall, full customisation identified SGA infants with higher odds of perinatal death (OR 5.6, 95% CI 3.6-8.7) than infants classed as SGA by ultrasound-and-gender customisation (OR 2.1, 95% CI 1.4-3.3) (P = 0.02). In subgroup analyses, infants classed as SGA by full but not ultrasound-and-gender customisation (n = 888, 3.4%) had an increased risk of perinatal death (RR 4.7, 95% CI 2.7-7.9); however, those identified as SGA by ultrasound-and-gender customisation alone were not at an increased risk (n = 676, 2.6%, RR 1.1, 95% CI 0.4-3.6). The population attributable risk (PAR) of SGA-related perinatal death was higher for full (49.8%) than for ultrasound-and-gender (43.0%) customisation.Updating the New Zealand customised birthweight centile calculator resulted in revised coefficients that better reflect a contemporary birth cohort. Inclusion of maternal characteristics in a birthweight customisation model increases the detection of SGA infants at risk of perinatal death.

We hypothesised that among nulliparous women with pre-eclampsia, overweight or obese women would have a different phenotype of pre-eclampsia compared with normal weight women with pre-eclampsia. Specifically, they are more likely to develop term pre-eclampsia and less likely to have indicators of impaired placental perfusion, e.g. abnormal uterine artery Doppler or a small-for-gestational-age (SGA) infant.Prospective, multicentre, cohort SCOPE study (n = 3170).New Zealand and Australia.Nulliparous women who developed pre-eclampsia.Participants were interviewed at 14-16 weeks of gestation, uterine artery Doppler studies were performed at 19-21 weeks and pregnancy outcome was tracked prospectively.Rates of abnormal uterine artery Doppler indices, term/preterm birth and SGA infants were compared between normal, overweight and obese women with pre-eclampsia. Multivariable analysis was performed to examine the association between body mass index (BMI) and term pre-eclampsia.Of 178 women with pre-eclampsia, one underweight woman was excluded and 66 (37%) were normal weight, 52 (29%) were overweight and 59 (34%) were obese. Pre-eclampsia developed preterm in 26% of women and at term in 74% of women. There were no differences in the rates of term/preterm pre-eclampsia, abnormal uterine artery Doppler indices or SGA infants between BMI groups (P0.10). No independent association between BMI and term pre-eclampsia was found (P = 0.56).Among women with pre-eclampsia, those who are overweight or obese in early pregnancy are not more likely to have term pre-eclampsia compared with women with a normal BMI. Overweight and obese women require vigilant surveillance for the development of preterm as well as term pre-eclampsia.

Systematic patterns are revealed when sequences of pseudo-random uniform deviates are generated from multiplicative congruential generators. If the initial seeds, x 0 and y 0, for two such sequences are related by y 0 = (n 1/n 2)x 0, where n 1 and n 2 are relatively prime, positive integers, then an approximate argument suggests that the asymptotic correlation coefficient between corresponding members of the two sequences is (n 1 n 2)−1. This unsettling phenomenon is discussed in the context of related, existing literature.

Coniferous forests of the Pacific Northwest provide a unique setting for stream ecology research because of the great age of the forests and the important role of wood debris in structuring aquatic systems. The composition and diversity of the insect community in Mack Creek, a stream in a 450 yr conifer forest, was compared with that in Grasshopper Creek where it flowed through a recent clearcut, and at Quartz Creek, which had a 40 yr deciduous canopy. Of the 256 taxa identified, Mack Creek had the highest species richness (196) and evenness. The open site had 191 taxa but high dominance of a few grazer taxa. The deciduous-canopy site had 165 taxa with abundant detritivores. Despite differences in density, the biomass of emergence was similar at the three sites, ranging from 1.53 to 1.65 g m−2 yr−1. The importance of disturbance in structuring stream communities was demonstrated in phenomenological studies after a debris torrent at Quartz Creek, and by monitoring stream recovery following the eruption of Mt. St. Helens in 1980. At Quartz Creek, the debris torrent eliminated the fauna from a 300 m reach, but there was rapid recovery. Emergence density in the same year was similar to that of the control site. The major shift in populations was a decrease in detritivores and moss associates and an increase in grazers, especially Baetis mayflies. At Ape Creek on Mt. St. Helens, over 200 taxa were recorded by 1987 but most occurred in very low densities. This site is reset by winter freshets and by infilling with glacial fines in the summer so the fauna continues to be dominated by weedy, or early successional species. At Clearwater Creek, the presence of wood debris as a stable substrate and limited inputs of fine sediment after 1980 have hastened population recovery. A decade after the eruption this site can be characterized as being in the mid-stages of succession with high insect productivity from an algal-based food web. With further growth of the riparian vegetation I predict a shift towards a detritus-based food web and fauna more similar to Mack Creek than it is at present.

Background: Fine-needle aspiration cytology (FNAC) is used as a screening test to evaluate lymphadenopathy. The combined use of genetic analysis and flow cytometry for immunophenotyping has increased the accuracy of diagnosis and correct categorisation of lymphomas on cytological preparations. Aim: To show the utility of immunocytochemistry and polymerase chain reaction (PCR) in the evaluation of cytological preparations of lymph nodes. Methods: Fine needle aspirates were obtained from 33 patients (initial presentation, n = 27; recurrence, n = 6). Routine examination was undertaken using immunocytochemistry and DNA PCR to detect clonality and specific translocations. The cytodiagnosis and subclassification of lymphoma was correlated with histological diagnosis in the available follow-up biopsies. Results: 14 patients had a cytological diagnosis of non-Hodgkin’s lymphoma (NHL), 4 had suspected NHL, 2 had atypical lymphoid proliferation and 13 had reactive hyperplasia. A World Health Organization (WHO) subtype was suggested in 8 patients. Incorporating the results of immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements enabled diagnosis of lymphoma in 17 patients, including 5 of the 6 patients suspected to have NHL or an atypical lymphoid proliferation. Identification of the translocations t (14;18) and t (2;5) helped WHO categorisation in 3 of the patients. The cytological findings were confirmed in 12 out of the 13 patients for whom histological follow-up was available. Seven of the 18 lymphoma patients were managed without a subsequent biopsy. We made one false–positive diagnosis of B-cell NHL on cytology. Conclusion: The use of immunocytochemistry and PCR is valuable in the definitive diagnosis and subtyping of malignant lymphomas on cytological preparations. The use of these techniques may avoid lymph node biopsies in some cases and allow definitive treatment based on aspirate findings alone.

SM047 is a recently developed monoclonal antibody generated against an ovarian adenocarcinoma cell line. A recent immunohistochemical study has shown that SM047 is strongly expressed in tissue sections of most ovarian serous adenocarcinomas. This study aimed to ascertain whether SM047 staining is of value in cytological preparations of peritoneal fluid. A total of 206 consecutive peritoneal fluids were stained immunocytochemically with SM047, CA125, monoclonal carcinoembryonic antigen (mCEA), Ber-EP4 and cytokeratins (CK7 and 20). SM047 positivity was present in reactive mesothelial cells in 117 of 141 (83%) benign cases in which these were present. SM047 positive tumour cells were present in 22 of 23 (96%) ovarian serous adenocarcinomas and in small numbers of gastric adenocarcinomas (two of three), mesotheliomas (one of two) and pancreatic adenocarcinomas (one of one). All six colorectal and two breast adenocarcinomas were negative with SM047. Reactive mesothelial cells in all cases were positive with CK7 and in most cases with CA125. They were negative with CEA, Ber-EP4 and CK20. All adenocarcinomas were positive with Ber-EP4 and mesothelial cells were always negative. All colorectal adenocarcinomas were positive with CK20. This study shows that SM047 staining may be of value in the diagnosis of an ovarian serous adenocarcinoma in peritoneal fluids. Negative staining helps to exclude a primary ovarian serous adenocarcinoma and is characteristic of colorectal adenocarcinoma. The small numbers of other malignancies in the study precludes a judgement of the value of SM047 staining in these neoplasms. SM047 staining may be useful, as part of a larger panel, in the work up of patients with peritoneal effusions.

Bcl-2 is an important determinant of transitional cell carcinoma of the bladder recurrence and progression as well as a factor in patient response to chemotherapy or radiotherapy. We determined Bcl-2 down-regulation after antisense oligonucleotide therapy and synergism with mitomycin C in transitional cell carcinoma of the bladder.Bcl-2 protein was quantified using flow cytometry and immunohistochemistry in 4 bladder cancer cell lines, in bladder washings from 6 patients with carcinoma in situ and in 16 patient tumor samples. The synergistic effects of antisense oligonucleotides G3139 and 2009, and mitomycin C were investigated in 4 cell lines, while 2009 down-regulation was examined in 20 tumor explants in an ex vivo model.Bcl-2 protein expression was found in all 4 cell lines and in 5 of the 6 cell populations derived from patients with carcinoma in situ. Of the 16 tumors 7 were classified positive by frozen section immunohistochemistry and quantitative flow cytometry. G3139 and 2009 down-regulated Bcl-2 protein expression in all 4 cell lines and 2009 down-regulated Bcl-2 protein expression in half of the Bcl-2 positive tumor specimens. There was only evidence in 1 cell line, T24/83, that Bcl-2 protein expression down-regulation enhanced mitomycin C induced apoptotic cell death.Bcl-2 was expressed in a significant proportion of bladder tumors and in carcinoma in situ. Therefore, antisense oligonucleotides represent a viable strategy for Bcl-2 protein down-regulation. However, it may not always translate into an increased level of mitomycin C induced apoptosis in transitional cell carcinoma of the bladder.

This report describes the FNAC findings in three cases of granular cell tumour of the breast. The patients comprised two females aged 59 and 62 years and one male aged 28 years. All patients presented with a breast lump which was clinically and radiologically suspicious of malignancy. FNAs yielded moderately cellular specimens which on cytologic examipation consisted of groups of cells and single cells with small regular nuclei and abundant granular cytoplasm. Bare nuclei were also present but these did not have the characteristic bipolar appearance of myoepithelial cells. In two cases there was a granularity to the background. The aspirates were reported as equivocal or atypical, probably benign, and surgical biopsy was performed. Histological examination showed typical benign granular cell tumours with strong positive staining for S-100 protein. Pathologists should be aware that granular cell tumour may occur in or around the breast and should consider this diagnosis in aspirates containing a population of cells with regular nuclei and abundant granular cytoplasm. The main cytologic differential diagnoses are likely to be apocrine cells and histiocytes. The suspicion of a granular cell tumour should be heightened when these features are present in an aspirate from a clinically and radiologically suspicious mass. These cases highlight the role of the triple approach encompassing clinical, radiological and cytological features in the assessment of a breast lesion.

Pseudoangiomatous stromal hyperplasia (PASH) is an unusual benign breast lesion that may occasionally present as a palpable mass.This report describes the fine needle aspiration cytology (FNAC) features of a case of mammary PASH that presented as a palpable mass. This is the second description of the FNAC features of this lesion and the first reported case in which a diagnosis of phyllodes tumor was considered. The aspirate was cellular and contained cohesive groups of cells in which there was a dual population of epithelial and myoepithelial cells. Occasional cellular stromal fragments were present, as were typical, bipolar, bare nuclei. Admixed with the bare nuclei were large numbers of plump, spindle-shaped cells, some with intact cytoplasm. Histologic examination of the excised mass showed features typical of PASH.Mammary PASH may present as a palpable mass and is likely to be encountered in FNAC specimens. This diagnosis should be considered when one is confronted with an aspirate containing cohesive epithelial groups, cellular stromal fragments and large numbers of single, spindle-shaped cells. These features on FNAC may result in consideration of a phyllodes tumor. The single, spindle-shaped cells may be a characteristic cytologic feature of PASH.

AIM: To develop a method for the detection of amplification of the erbB2 oncogene in breast cancer fine needle aspirates using fluorescence in situ hybridisation (FISH) and to compare amplification with immunohistochemical detection of the erbB2 protein. METHODS: A digoxigenin labelled probe to the erbB2 gene was hybridised to 15 aspirates prepared from operative breast cancer specimens. A chromosome 17 centromere probe was also hybridised to the aspirates either separately or in combination with the erbB2 probe. The aspirates were scored for erbB2 amplification and chromosome 17 centromere number. Subsequently, paraffin wax embedded sections of the tumours were stained with the antibody CB11 and scored for the presence of membrane staining. RESULTS: Three of the 15 tumour aspirates showed high level amplification of erbB2 detected by FISH. These three tumours also showed chromosome 17 polysomy and diffuse membrane staining by immunohistochemistry. CONCLUSIONS: FISH can be used to detect erbB2 amplification in fine needle aspirates and results correlate with conventional immunohistochemical staining. Difficulties were encountered in the visualisation of the signals in non-amplified cases without the use of specialised digital imaging.

To review progress on the development of machine vision and image understanding in prostate tissue histology and to discuss the problems and opportunities afforded to pathology through the use of these techniques.A variety of concepts in machine vision are explored, and methodologies are described that have been developed to deal with the complexities of histologic imagery. The theory of human vision and its impact on machine vision are discussed. Software has been specifically developed for the analysis of prostate histology, allowing accurate gland segmentation, basal cell identification and measurement of vascularization within lesions.Image interpretation can be achieved using knowledge-based image analysis and the application of local object-oriented processing. This successfully allows an automated quantitative analysis of histologic morphology in the diagnosis of prostate intraepithelial neoplasia and invasive prostatic cancer. The use of low-power image scanning, based on textural or n-gram mapping, permits the development of fully automated devices for the rapid detection of tissue abnormalities. High-power, knowledge-guided scene segmentation can be carried out for the quantitative analysis of cellular features and the objective grading of the lesion.Automated tissue section scanning and image interpretation is now possible and holds much promise in prostate pathology and other diagnostically demanding areas. Issues of standardization still need to be addressed, but the development of such systems will undoubtedly enhance our diagnostic capabilities through the automation of time-consuming procedures and the quantitative evaluation of disease processes.

Inhibin is a peptide hormone which is produced by ovarian granulosa cells during normal follicular development. It is important that granulosa cells are recognized in fine needle aspirates (FNAs) of ovarian cystic lesions, as this allows definite recognition of a functional cyst and exclusion of a potentially neoplastic epithelial lined cyst. Occasionally the distinction between granulosa and epithelial cells may be difficult, especially when aspirates from functional cysts are unusually cellular. In the present study, FNAs from 33 ovarian cystic lesions were immunostained with a monoclonal antibody against inhibin. Nine cases of peritoneal fluid containing malignant cells in patients subsequently confirmed to have ovarian adenocarcinoma were also stained. Where possible the cytological and immunocytochemical findings were correlated with subsequent biopsy. In most cases in which cytology suggested a functional cyst there was a strong positive staining with anti-inhibin, although occasional cases were negative. One case originally thought to contain epithelial cells stained strongly positive with anti-inhibin and on review was felt to represent a cellular functional cyst. In all other cases where cells were considered to be epithelial there was no staining with anti-inhibin. The study shows that immunocytochemical staining with anti-inhibin may be of value in confirming the presence of granulosa cells, thus establishing a diagnosis of functional cyst. Although negative staining does not exclude a functional cyst, positive staining with anti-inhibin allows exclusion of an epithelial lined cyst and may avoid unnecessary surgical intervention.

Genetic variation of the glucocorticoid receptor (GR) locus is associated with differences in blood pressure. To define the intermediate phenotypes associated with this variation, we investigated the biochemical and clinical significance of a BclI restriction fragment length polymorphism of the GR locus in 64 normal male volunteers. Blood samples were genotyped as either AA (homozygous large allele; n = 6), Aa (heterozygous; n = 51), or aa (homozygous small allele, n = 7). Four primary glucocorticoid variables were measured including GR binding characteristics and glucocorticoid-sensitive lysozyme release of leukocytes in vitro and the blanching response of forearm skin to budesonide. A large number of secondary variables (urinary and plasma steroid measurements, blood pressure and indices of body fat metabolism, and routine biochemical and hematological measurements) were also considered. In vivo sensitivity to budesonide was greater in AA than aa individuals (mean +/- SE EC50 values: 13 +/- 5 and 42 +/- 10 ng; P0.01). In contrast, leukocytes of AA subjects tended to have lower affinity and reduced sensitivity for dexamethasone, although these effects were not statistically significant. Based on urinary steroid measurements, 11 beta-hydroxysteroid dehydrogenase activity [ratio of tetrahydrocortisol (THF) to tetrahydrocortisone (THE) metabolites] was not affected by genotype. The relative activities of 5 alpha- and 5 beta-reductase activity (allo-THF/THF + THE) appeared lower in AA than aa subjects (0.22 +/- 0.04 cf. 0.33 +/- 0.06; P0.005) but were not judged to be significantly different when corrected for multiple comparisons. Single and multivariate analyses were carried out to determine which variables influence GR binding characteristics and glucocorticoid responsiveness and to see whether cardiovascular risk factors (blood pressure and body fat) were influenced by glucocorticoid-dependent functions. Only 15-20% of the variations in the dissociation constant (Kd) and maximum binding capacity (Bmax) were influenced by other variables; plasma cholesterol was the most important for affinity and plasma sodium concentration for binding capacity. Multivariate analysis showed that several factors including GR genotype and urinary cortisol account for 10% of the variation of in vivo responses to glucocorticoid hormones; plasma calcium concentration was the only variable that contributed to in vitro sensitivity of leukocytes to dexamethasone. Glucocorticoid-dependent responses were of negligible importance in determining blood pressure or percentage body fat within the narrow physiological ranges of the present study. We conclude that GR genotype affects steroid sensitivity in a tissue-specific manner because of altered GR function or possibly because of linkage to a locus that controls hormone access to the receptor by influencing steroid metabolism.

Automation in histopathology is an attractive concept and recent advances in the application of computerized expert systems and machine vision have made automated image analysis of histological images possible. Systems capable of complete automation not only require the ability to segment tissue features and grade histological abnormalities, but, must also be capable of locating diagnostically useful areas from within complex histological scenes. This is the first stage of the diagnostic process. The object of this study was to develop criteria for the automatic identification of focal areas of colorectal dysplasia from a background of histologically normal tissue. Fields of view representing normal colorectal mucosa (n = 120) and dysplastic mucosa (n = 120) were digitally captured and subjected to image texture analysis. Two features were selected as being the most important in the discrimination of normal and adenomatous colorectal mucosa. The first was a feature of the co-occurrence matrix and the second was the number of low optical density pixels in the image. A linear classification rule defined using these two features was capable of correctly classifying 86 per cent of a series of training images into their correct groups. In addition, large histological scenes were digitally captured, split into their component images, analysed according to texture, and classified as normal or abnormal using the previously defined classification rule. Maps of the histological scenes were constructed and in most cases, dysplastic colorectal mucosa was correctly identified on the basis of image texture: 83 per cent of test images were correctly classified. This study demonstrates that abnormalities in low-power tissue morphology can be identified using quantitative image analysis. The identification of diagnostically useful fields advances the potential of automated systems in histopathology: these regions could than be scrutinized at high power using knowledge-guided image segmentation for disease grading. Systems of this kind have the potential to provide objectivity, unbiased sampling, and valuable diagnostic decision support.

The distinction between ductal hyperplasia (DH) and ductal carcinoma in situ (DCIS) still remains a problem in the histological diagnosis of non-invasive breast lesions. In this study, a method was developed for the automatic segmentation and quantitative analysis of breast ducts using knowledge-guided machine vision. This permitted duct profiles and intraduct lumina to be identified and their shape, size, and number computed. These were used to derive measures of duct cribriformity and architectural complexity which were examined as an objective tool in the characterization of duct pattern in proliferative lesions. A total of 215 images of ducts were digitally captured from 22 cases of DCIS and 21 cases of DH diagnosed independently by two pathologists. The cribriformity index proved to be a useful measure of duct architecture, showing a nosotonic increase with increasing duct complexity. The number of lumins also increased with increasing overgrowth of ductal epithelium until the duct was filled. Discriminant analysis of the duct characteristics for benign and malignant groups selected the lumen area/duct area ratio and the duct area as significant discriminatory variables and they were combined into a discriminant function. Of the lumens features, the mean area of the lumen and the polar average (mean of the distribution of the number of events with an increasing spiral from the centre of the duct) were combined into a second discriminant function. Plotting cases against these two functions provided good separation of DH and DCIS groups, with correct classification estimated on the training sample as being over 80 per cent. With an increasing incidence of complex proliferative lesions arising from mammography, the ability to diagnose these lesions correctly is more important than ever. The use of expert system-guided machine vision facilitates the quantitative evaluation of breast duct architecture; along with established histological and cytological criteria, it is hoped that this will lead to a more objective means of diagnosis and disease classification.

To develop a computerized system to assist in the diagnosis of malignancy in breast fine needle aspiration cytology.A Bayesian belief network was designed to control uncertainty and allow a diagnostic decision to be reached based on the sequential collection of cytologic information. Ten cytologic features were defined as clues that contribute to the diagnostic discrimination of benign and malignant aspirates. The impact of each feature on the diagnostic decision was quantified by a conditional probability matrix.For the assessment of a new case, the computer guides the user through the diagnosis, prompting him or her for information on each of the diagnostic features in turn. For each feature, the user is presented with a series of digitally stored color microscopic images that have been selected to represent good examples of the different feature grades-e.g., pleomorphism: none, mild, moderate and severe. Each image is mapped to an overlapping curve, and by positioning a line on the spectrum where the user feels the case lies, a membership function vector is calculated and entered as evidence into the network. This results in an update in the belief in the diagnostic alternatives. After all the clues have been assessed, a final diagnostic probability is reported. In addition, a cumulative belief curve can be drawn that maps the change in the diagnostic probabilities after each piece of evidence has been submitted, providing unique insight into the diagnostic process.Systems like this represent an important step forward in the use of descriptive classifiers. They impose consistency in terminology, improve reproducibility in the grading of cellular abnormalities and remove subjectivity in interpreting the significance of pvisual clues to diagnosis. As such, they represent a necessary tool in pathologic decision making.

Systemic endotoxaemia is a well recognized feature of inflammatory bowel disease but its pathogenic role remains uncertain. This study examined plasma endotoxin and cytokine concentrations and the acute-phase protein response in a hapten-induced model of experimental colitis. On days 2, 8 and 14 after induction of colitis with trinitrobenzenesulphonic acid in ethanol (TNBS-E), plasma endotoxin, immunoglobulin (Ig) G and IgM endotoxin-core antibody (EndoCAb), tumour necrosis factor (TNF), interleukin (IL) 6 and α2-macroglobulin (α2M) concentrations and colon macroscopic inflammation score were determined. At all time points there was significant colonic inflammation when compared with control values (P

Belief revision in 5- to 9-year-olds was studied with an information integration approach. In the social task, children judged niceness of story children, having heard about their good and bad deeds. In the decision task, of parallel structure, they judged what proportion of a group of turtles' catch of starfish was red or gold. In both tasks, 4-5 samples were presented successively, with children adjusting their judgment after each. All ages took sample composition into account, and judgments could be described by a serial integration model previously supported for adults. Recency effects were found as well and were stronger for younger children and in the social task. Further model analysis showed, however, that much of this recency was short-lived and that a stable opinion, to which early and later informers contributed more evenly, developed underneath. Overall, similar processes may underlie serial belief formation across the age range and across domains.

The efficacy of lactulose as an antiendotoxin was studied and the effect of lactulose or colistin on faecal flora was investigated in a hapten-induced rat model of colitis. Enteral administration of lactulose to rats with colitis was associated with a significant reduction in the systemic concentration of endotoxin (median (range) 5.4 (0–19.9) versus 23.7 (0–145.0) pg/ml in colitic rats treated with water; 4.6 (0–10.8) pg/ml in healthy animals). Enteral administration of colistin significantly reduced the faecal count of aerobic Gram-negative bacilli (median (range) 2.84 (1.40–8.43) versus 8.26 (4.50–10.40) log10 colony-forming units per g faeces after treatment with water) but not the faecal load of endotoxin. Patients with inflammatory bowel disease may benefit from enteral treatment with lactulose to prevent systemic endotoxaemia and/or with colistin to modify enteric bacteria.

This study investigated the effects of glutamine and steroid enemas on disease activity in an animal model of colitis. Colitis was induced in male Wistar rats by intracolonic instillation of 30 mg trinitrobenzenesulphonic acid in 50% ethanol (TNBS/E). Controls were given an isovolumetric bolus of normal saline. After 24 h, animals were randomised to receive enemas (1 mL twice daily) of prednisolone (200 mg/L), or L-glutamine (500 g/L) or the suspending agent (placebo). On day 8, the colon was weighed and the degree of inflammation assessed using a colon macroscopic score (CMS). Thymic weight, splenic weight, percentage gain in body weight (%GBW), food intake, plasma interleukin-6 (IL6) and plasma alpha(2)-macroglobulin (alpha(2)M) were also determined. There was a significant increase in CMS, colon weight, splenic weight, IL6 and alpha(2)M in TNBS/E animals compared to controls (P0.01). There was also a significant decrease in %GBW, food intake and thymic weight in TNBS/E animals (P0.01). The therapeutic enema of prednisolone reduced colonic inflammation (CMS, colon weight), improved thymic weight, %GBW and food intake, and reduced plasma IL6 concentrations (P0.05). In contrast administration of glutamine enemas was associated with an exaggerated acute phase protein (alpha(2)M) response (P0.05) and failed to improve the colonic and systemic inflammatory response in this experimental model of colitis.

The indigenous intestinal flora and an intact mucosa are vital components of body defences against luminal pathogenic bacteria. Disruption of these defences in inflammatory bowel disease may permit bacterial translocation and contribute to disease severity. Support for this hypothesis comes from this study of a hapten-induced rat model of colitis. Induction of colitis was associated with a significantly increased colonic Gram-negative aerobic bacilli count. The results, expressed as log10 [colony-forming units per gram tissue] were: colitic 6.97–8.86 versus control 4.90–6.69 (P < 0.05). Colitis was also associated with a decreased Gram-positive cocci count at 4.00–8.04 versus control 6.45–8.30 (P < 0.05). Bacteria translocated to the mesenteric lymph nodes in five of eight colitic rats (P = 0.01), to the spleen in four (P = 0.04) and to the liver in five (P = 0.01) but to these organs in none of the eight control animals. There was a positive correlation between the severity of colonic inflammation and extent of bacterial translocation in colitic animals (rS = 0.86, P = 0.007).

The intestinal mucosa protects the body from a large reservoir of intraluminal pathogenic bacteria and endotoxins. This mucosal barrier is disrupted by the inflammation and ulceration of inflammatory bowel disease and may permit the absorption of toxic bacterial products. Systemic endotoxaemia has been demonstrated in ulcerative colitis and Crohn's disease and correlates with the extent and activity of disease. In this study the efficacy of absorbents as antiendotoxin agents in a hapten induced rat model of colitis is investigated. Induction of colitis was associated with systemic endotoxaemia. Enteral administration of terra fullonica and kaolin, but not of charcoal, significantly reduced systemic endotoxaemia (terra fullonica 4.2 (1.40) pg/ml; kaolin 5.29 (1.86) pg/ml; charcoal 32.7 (16.6) pg/ml; water 39.8 (12.6) pg/ml). Data expressed as mean (SE). With increasing severity of colitis, there was a decreasing ability of adsorbent therapy (terra fullonica) to control systemic endotoxaemia. Enteral administration of adsorbents controls gut derived systemic endotoxaemia in experimental colitis in animals and may be a useful antiendotoxin treatment in patients with inflammatory bowel disease.

A report on the pilot study of the Confidential Enquiry into Perioperative Deaths was published recently in the United Kingdom. The scheme was designed as a specialized form of clinical audit relating to perioperative patient care. Because the report placed little emphasis on autopsy, we have looked at all autopsied perioperative deaths, as defined by the enquiry, over a three-year period (1986-88) in a defined catchment area of Northern Ireland. Class I major discrepancies of diagnosis between clinical and postmortem records were found in 21% of 213 autopsied perioperative deaths. By definition, these represented instances in which an adverse impact on patient survival had resulted from the discrepancy. In an additional 29% of cases, there were Class II major discrepancies, which were discrepancies in the primary diagnosis not relevant to life-saving treatment. In 30% of cases there was a discrepancy in a secondary diagnosis, which might have affected the eventual prognosis, had the patient survived, but which was not related directly to the cause of death; these were termed Class III discrepancies. In 47% of cases, there were Class IV discrepant secondary diagnoses, which were 'incidental' findings and had no bearing on prognosis. To put these findings in context, the autopsy rate in Northern Ireland was 12% in 1987, with a higher rate (23%) in the two main teaching hospitals and a lower rate (8%) in all other hospitals. The rate of coroner's autopsies, 6%, is uniform throughout Northern Ireland. Coroner's autopsies are carried out mostly by the salaried staff of the State Pathologist's department. The observed differences in the rates of hospital autopsies reflect local deficiencies of pathologists in relation to the work load. In a series of consecutive autopsies carried out at one of the main teaching hospitals, the highest autopsy rate (68%) was found for paediatric patients, with rates of 29% for surgical and 23% for medical cases. The proportion of hospital autopsies carried out in perioperative surgical patients was the same as that for medical patients, reflecting the fact that no particular emphasis is placed on use of the autopsy as a form of clinical audit for the perioperative group.

A series of 213 perioperative deaths was studied out of a total of 1451 consecutive necropsies carried out over three years. Discrepancies between the clinical and the necropsy diagnosis were assessed under four classes of discrepant diagnosis: class I, patient survival affected, treatable; class II, patient survival affected but not treatable; class III, correlated to cause of death but treatable; and class IV, incidental diagnosis which could not have been made before death. Major discrepancies of classes I and II were found in 44 (21%) and 62 (29%) cases, respectively. Minor discrepancies of classes III and IV were found in 63 (30%) and 101 (47%) cases, respectively. No discrepancies were found in 50 (23.5%) cases. These results confirm the continuing value of the necropsy in the assessment of perioperative deaths.

Integrated agricultural and environmental policies in the EC integrated weed management landscape ecology of insect movement in arable ecosystems ecological aspects of integrated farming.

The aim of this study was to gather quantitative field and laboratory data on the utilization of deciduous leaves as food by Lepidostoma quercina Ross (Trichoptera: Lepidostoma- tidae) and estimate the effect of this food processing on the stream ecosystem. Samples were taken monthly in a riffle-pool section of Berry Creek, Benton County, Oregon. Maximum larval density was 382 per m2, instantaneous growth rate was 2.7% per day, instantaneous mortality rate was 1.4% per day, and production was 0.19 g m-2 yr-'. The life cycle of L. quercina and its period of maximum larval growth corresponded closely with the period of maximum availability of its preferred food (alder leaves) in the stream. Consumption and fecal production rates were measured gravimetrically. Rates (mg mg-1 day-') increased with temperature, food quantity, and conditioning time of the leaves, and decreased with increased size of the larvae. Mean respiration rates of larvae were higher at 10'C than at 5?, but there was no significant difference in mean rates at 10, 15, or 20'C. Respiration rate decreased with increased size of the larvae. Size-specific respiration rates showed regulation of respiration with respect to temperature for small individuals (present in the field in September and October when temperatures are variable) and little or no regulation by large individuals (present in December and January). Simulation modeling of larval growth based on laboratory data demonstrated that growth and production of L. quercina in the field may be limited by a lack of high-quality food (alder leaves) in late summer and early fall. Consumption of leaves by the simulated population was estimated as 3.1 -2 . -I g1m yr Lepidostoma quercina comprised only a small part of the secondary production in Berry Creek

The aim of this study was to gather quantitative field and laboratory data on the role of Lepidostoma cascadense (Milne) and Lepidostoma unicolor (Banks) in the processing of conifer needles in a stream ecosystem. Samples were collected monthly in a riffle-pool section of Mack Creek, Lane County, Oregon, USA. For L. cascadense, maximum larval density was 812/M2 and instantaneous growth rate was 1.5%/d. The larvae grew slowly throughout the winter and pupation occurred in May and June. In contrast, L. unicolor increased very little in size during the winter and grew very rapidly during June and early July, reaching a maximum larval density of 320/M2 and with an instantaneous growth rate (March through July) of 2.7%/d. Production of L. cascadense was estimated as 0.31 g.m-2 yr-I and that of L. unicolor was 0.23 g-m-2 yr-t. In addition to temporal separation in periods of maximum growth, the two species occurred in different microhabitats. L. cascadense larvae were found within the sediments and debris while L. unicolor occurred on the surface of the debris. Laboratory studies were conducted with L. unicolor larvae. Consumption and fecal production rates (measured gravimetrically) increased with higher temperature, greater food density, or longer conditioning time of the food, and decreased with increased size of the larvae. Production and biomass of L. cascadense and L. unicolor in Mack Creek are minor in relation to other insects in the system. However, because of high consumption rates and low assimilation efficiency, the processing of large particulate organic matter by these two species contributed signif- icantly to the food available to collectors in the study area.