bluuebunny/crossref_metadata_2025 huggingface dataset:
CD44 expression in normal adrenal tissue and adrenal tumours.
Authors: Barshack I , Goldberg I , Nass D , Olchovsky D , Kopolovic J
Published: January 2009

BACKGROUND: CD44 is a cell surface glycoprotein found on many normal cells, mainly lymphoid and epithelial. Normal cells usually express standard CD44 (CD44-S), whereas malignant tumours may express CD44 variant isoforms (CD44-V). CD44 expression has been described for neural crest derivatives. Characterisation of differences in CD44 expression may help in the diagnosis and differentiation of distinct adrenal tumours. AIMS: To examine CD44 expression in different layers of cortical cortex, in adrenal medulla, and in adrenal tumours. METHODS: CD44-S and CD44-V6 expression were studied in 12 cases of adrenal cortical adenoma, 3 of adrenal cortical carcinoma, 10 of pheochromocytoma, and 4 normal adrenal glands. RESULTS: CD44-V6 staining showed cytoplasmic expression in normal adrenal cortex and in cortical adenomas and carcinomas. Pheochromocytomas also showed CD44-V6 expression but in 5 of the 10 cases it was sparse, focal, and sometimes perinuclear. Strong membranous staining for CD44-S was observed in normal adrenal medulla. Analysis of CD44-S expression revealed differences between cortical adrenal tumours and pheochromocytomas. Ten of 12 cortical adenomas and 2 of 3 cortical carcinoma cells showed weak to moderate cytoplasmic staining, but all cases of pheochromocytoma had strong membranous staining. CONCLUSIONS: Membranous CD44-S staining may help to distinguish pheochromocytoma from adrenal cortical adenoma.
Identification of multiresistant Staphylococcus epidermidis in neonates of a secondary care hospital using pulsed field gel electrophoresis and quantitative antibiogram typing.
Authors: Sloos J H , Horrevorts A M , Van Boven C P , Dijkshoorn L
Published: January 2009

AIMS: To determine the diversity of types of Staphylococcus epidermidis in a neonatal care unit of a secondary care hospital in the Netherlands. METHODS: In a prospective study, specimens from nose, ear, axilla, umbilicus, and groin were taken from patients twice a week during a period of up to two weeks. All isolates were typed by both pulsed field gel electrophoresis (PFGE) and antibiogram analysis. RESULTS: Fifty three S epidermidis isolates from 15 of 24 patients were obtained in one to four surveys. Fourteen isolates from six patients had a common PFGE pattern and were of one multiresistant antibiogram type. The remaining 39 isolates were allocated to 24 sporadic PFGE types and were more susceptible to antibiotics. Colonisation with the multiresistant strain correlated with a long period of stay and with the use of specific antibiotics. The multiresistant isolates were related closely to isolates of S epidermidis found in a recent study in a teaching hospital in the vicinity of the secondary care hospital. CONCLUSION: Repeated sampling and the use of two typing methods allowed the identification of two closely related multiresistant S epidermidis strains in two hospitals in the same area.
Accuracy and precision of the TAS analyser for near-patient INR testing by non-pathology staff in the community.
Authors: Cachia P G , McGregor E , Adlakha S , Davey P , Goudie B M
Published: January 2009

AIMS: To assess the accuracy and precision of INR measurement by trained practice and district nursing staff using the Thrombolytic Assessment System (TAS) analyser. METHODS: Seventeen nurses from four practices were trained to measure INR using the TAS analyser on citrated capillary blood samples. Quality control (QC) consisted of: daily internal QC using normal and abnormal commercial plasmas; monthly local external QC scheme using fresh citrated venous blood; and registration of all analysers in the NEQAS (national external quality assessment scheme) main users scheme. RESULTS: Analysis of internal QC results demonstrated satisfactory interanalyser and intra-analyser precision with no evidence of analytical drift in any of the four practice analysers over an eight month period. Local and national external QC results confirmed the interanalyser precision but INR was underestimated by the TAS analysers compared with the CA 1000 using either Diagen rabbit brain thromboplastin or Innovin, and with other NEQAS users. CONCLUSIONS: The TAS analyser has many features to commend it for use by nonpathology staff to determine INR. Local internal and external QC and entry into the NEQAS main users group are possible because the TAS analyses citrated plasma or blood. The TAS analyser underestimates INR when the geometric mean normal prothrombin time (GMNPT) is determined by conventional methods. A local correction factor can be introduced by adjusting the normal PT to give INR results comparable with the local laboratory. This is particularly desirable when INRs are measured using both near-patient and laboratory analytical systems on different occasions.
Familial pancreatic lymphoma.
Authors: James J A , Milligan D W , Morgan G J , Crocker J
Published: January 2009

Non-Hodgkin's lymphoma is not commonly a familial condition. This is believed to be the first two cases of primary pancreatic lymphoma within a single family. The two cases, a brother and sister, both presented in their 60s and were diagnosed histologically as having high grade B cell lymphoma affecting the pancreas, an uncommon primary site. Both responded well to treatment with chemotherapy and were in remission at the time of writing. On further investigation it was found that their mother also presented with a malignant lymphoma of cervical nodes 30 years earlier and subsequently died of the disease.
Persistent damage to Enterocytozoon bieneusi, with persistent symptomatic relief, after combined furazolidone and albendazole in AIDS patients.
Authors: Dionisio D , Manneschi L I , Di Lollo S , Orsi A , Sterrantino G , Leoncini F , Pozzi M , Vinattieri M A , Tani A , Papucci A
Published: January 2009

AIM: To investigate morphological changes in Enterocytozoon bieneusi and the duration of symptomatic relief after combination treatment with furazolidone and albendazole in AIDS patients. METHODS: Four severely immunocompromised AIDS patients with symptomatic E bieneusi infection of the gut received an 18 day course of combined furazolidone and albendazole (500 + 800 mg daily). All patients were monitored for parasite shedding in stool by light microscopy at the end of treatment and monthly during follow up. At the end of treatment, duodenal biopsy specimens obtained from three patients were studied by transmission electron microscopy by two pathologists blind to the patients' treatment or clinical outcome. Duodenal biopsy specimens obtained from one of the patients two months after completion of treatment were also studied electronmicroscopically. RESULTS: All patients had long lasting symptomatic relief, with a major decrease--or transient absence--of spore shedding in stools from completion of treatment. After treatment, changes in faecal spores were persistently found by light microscopy in all cases, and there was evidence of both a substantial decrease in the parasite load and ultrastructural damage in the parasite in all biopsy specimens. The treatment was well tolerated, and no patient had clinical or parasitological relapse during follow up (up to 15 months). CONCLUSIONS: The long lasting symptomatic relief observed in all four treated patients correlated with the persistent decrease in parasite load both in tissue and in stool, and with the morphological changes observed in the life cycle of the protozoan. These data suggest that combined treatment with furazolidone and albendazole is active against E bieneusi and may result in lasting remission even in severely immunocompromised patients.
Hybrid capture II, a new sensitive test for human papillomavirus detection. Comparison with hybrid capture I and PCR results in cervical lesions.
Authors: Clavel C , Masure M , Putaud I , Thomas K , Bory J P , Gabriel R , Quereux C , Birembaut P
Published: January 2009

AIM: To test a new assay for the detection of human papillomavirus (HPV) DNA, hybrid capture II (HC II), compared with the previous commercialized hybrid capture I (HC I) and polymerase chain reaction (PCR) results on cervical scrapes from fresh cone excision biopsy samples. METHODS: The three methods were used on cervical scrapes from 42 fresh cone excision biopsy samples. There were nine metaplastic and inflammatory lesions, five low grade lesions, and 28 high grade lesions. PCR was performed using the general primers GP5+/GP6+. The viral load of high risk HPV DNA was estimated by the ratio of relative light units to positive control values in the samples. RESULTS: The sensitivity of HC I for the detection of high grade lesions was 71.4%, while it was 92.8% for HC II and 96.4% for the PCR. Considering only the absence of detectable cervical in situ neoplasia, the specificity was 88.9% for HC I, 66.7% for HC II, and 66.7% for PCR. With HC II, for a ratio of cervical sample to normal control of > 200, the sensitivity for the detection of high grade lesion was only 34.6% with a specificity of 66.7%. CONCLUSIONS: HPV detection with the HC II assay is more sensitive than the previous HC I and represents a more convenient and easier test than PCR for routine use. Nevertheless the viral load estimated with this test cannot be a reliable predictive indicator of high grade lesions.
Expression of nitric oxide synthase in inflammatory bowel disease is not affected by corticosteroid treatment.
Authors: Leonard N , Bishop A E , Polak J M , Talbot I C
Published: January 2009

AIM: To examine the effect of corticosteroid treatment on the expression of inducible nitric oxide synthase (iNOS) in the colon of patients with inflammatory bowel disease. METHODS: Four groups of patients were studied: (1) ulcerative colitis treated with high dose corticosteroids (six patients, 10 blocks); (2) ulcerative colitis patients who had never received corticosteroids (10 patients, 16 blocks); (3) Crohn's disease treated with high dose corticosteroids (12 patients, 24 blocks); (4) Non-inflammatory, non-neoplastic controls (four patients, six blocks). Full thickness paraffin sections of colons removed at surgery were immunostained with an antibody raised against the C terminal end of iNOS. Sections were assessed semiquantitatively for the presence and degree of inflammation and immunoreactivity for nitric oxide synthase. RESULTS: Cases of ulcerative colitis and Crohn's disease with active inflammation showed strong staining for nitric oxide synthase. The staining was diffuse in ulcerative colitis and patchy in Crohn's disease, in accordance with the distribution of active inflammation. Staining was seen in epithelial cells and was most intense near areas of inflammation such as crypt abscesses. Non-inflamed epithelium showed no immunoreactivity. Treatment with corticosteroids made no difference to the amount of nitric oxide synthase. CONCLUSIONS: Expression of nitric oxide synthase is increased in both ulcerative colitis and Crohn's disease and appears to be unaffected by treatment with corticosteroids. Disease severity necessitated surgery in all the cases included in this study, regardless of whether or not the patients had received long term corticosteroid treatment. It seems therefore that a high level of iNOS expression and, presumably, production of nitric oxide characterise cases which are refractory to clinical treatment; this suggests that specific inhibition of the enzyme may be a useful therapeutic adjunct.
Immunohistochemical expression of mdm2 and p21WAF1 in invasive cervical cancer: correlation with p53 protein and high risk HPV infection.
Authors: Troncone G , Martinez J C , Palombini L , De Rosa G , Mugica C , Rodriguez J A , Zeppa P , Di Vizio D , Lucariello A , Piris M A
Published: January 2009

AIM: To investigate the immunocytochemical staining pattern of mdm2 and p21WAF1 proteins in invasive cervical cancer and to determine its relation with the expression of p53 and with the high risk HPV infection. METHODS: Immunocytochemistry for p53, mdm2, and p21WAF1 was performed in 31 paraffin embedded sections of invasive cervical cancer. The results were assessed by image analysis, evaluating for each protein the optical density of the immunostained area, scored as percentage of the total nuclear area. The presence of high risk human papillomavirus (HPV) infection was detected by using the polymerase chain reaction. RESULTS: Immunostaining for both mdm2 and p21WAF1 was correlated with p53 expression; however, the correlation between p53 and mdm2 (R = 0.49; p < 0.01) was more significant than between p53 and p21WAF1 (R = 0.31; p < 0.05); the less stringent correlation between p53 and p21WAF1 might reflect the p53 independent mechanisms of p21WAF1 induction. Similar average levels of p53, mdm2, and p21WAF1 immunostaining were found in the presence or absence of high risk HPV-DNA, without significant differences between the two groups. CONCLUSIONS: These data suggest that mdm2 and p21WAF1 proteins are expressed in invasive cervical cancer and that their immunocytochemical staining pattern is not abrogated by the presence of high risk HPV genomic sequences.
Chemokine mRNA expression in gastric mucosa is associated with Helicobacter pylori cagA positivity and severity of gastritis.
Authors: Shimoyama T , Everett S M , Dixon M F , Axon A T , Crabtree J E
Published: January 2009

AIM: To investigate the association between the quantity of gastric chemokine mRNA expression, severity of gastritis, and cagA positivity in Helicobacter pylori associated gastritis. METHODS: In 83 dyspeptic patients, antral and corpus biopsies were taken for semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and histological grading of gastritis. Gastritis was evaluated by visual analogue scales. Quantities of chemokine (IL-8, GRO alpha, ENA-78, RANTES, MCP-1) RT-PCR products were compared with G3PDH products. Each sample was also evaluated for the presence of cagA and ureA mRNA by RT-PCR. RESULTS: mRNA expression of all five chemokines was significantly greater in H pylori positive than in H pylori negative mucosa. In H pylori positive patients, in the antrum C-X-C chemokine mRNA expression was significantly greater in cagA positive patients than in cagA negative patients, but there were no significant differences in C-C chemokine mRNA expression. In H pylori positive patients, chemokine mRNA expression in the corpus was less than in the antrum. In contrast to the antrum, only GRO alpha mRNA expression was significantly greater in cagA positive infection. Polymorphonuclear cell infiltration was correlated with C-X-C chemokine mRNA expression. Significant correlations were also found between bacterial density and C-X-C chemokine mRNA expression. CONCLUSIONS: In H pylori infection, C-X-C chemokines may play a primary role in active gastritis. Infection with cagA positive H pylori induces greater gastric chemokine mRNA expression in the antral mucosa, which may be relevant to the increased mucosal damage associated with cagA positive H pylori infection.
Effect of desiccation on the ultrastructural appearances of Acinetobacter baumannii and Acinetobacter lwoffii.
Authors: Houang E T , Sormunen R T , Lai L , Chan C Y , Leong A S
Published: January 2009

An Acinetobacter baumannii isolate survived desiccation beyond 30 days and an Acinetobacter lwoffii isolate up to 21 days. For both species, desiccation resulted in a significant increase in the proportion of round cells (A baumannii, 40% to 80%; A lwoffii, 51% to 63%) and a significant decrease in rod shaped cells (A baumannii, 58% to 13%; A lwoffii, 46% to 34%). Electronmicroscopic examination showed that there was also a corresponding significant increase in the cell wall thickness (A baumannii, up to 53%; A lwoffii, up to 26%). Desiccated A baumannii cells became more electron-dense and had significantly thicker cell walls (x1.3) than those of A lwoffii. Cell wall structures of A baumannii strains with different abilities to resist desiccation deserve further study.
De novo expression of CD44 in prostate carcinoma is correlated with systemic dissemination of prostate cancer.
Authors: Paradis V , Eschwège P , Loric S , Dumas F , Ba N , Benoît G , Jardin A , Bedossa P
Published: January 2009

AIMS: To evaluate the role of CD44 in early steps in the development of prostate cancer, and to assess the biological significance of preneoplastic lesions in prostate cancer. METHODS: 38 patients with clinically localised prostate cancer were studied. The standard form of CD44 (CD44H) and v6 isoform expressions were semiquantitatively evaluated on paraffin embedded tumour tissue by immunohistochemistry. Disseminated prostatic cells were detected by prostate specific membrane antigen reverse transcriptase polymerase chain reaction in the blood of each patient before radical prostatectomy. RESULTS: In normal or benign prostate glands, only basal cells showed CD44H and v6 labelling. Fourteen of the 38 prostate cancers (37%) had CD44H membranous staining of prostatic tumour cells. In 18 patients (47%), circulating prostatic cells were detected in blood before surgery. Although no correlation between the expression of CD44 and the Gleason score or staging was observed, a significant correlation was found between the expression of CD44H by tumour cells and prostatic cell blood dissemination (p = 0.04). In 28 cases, foci of prostatic intraepithelial neoplasia were observed, and nine had CD44H immunostaining. CONCLUSIONS: De novo expression of CD44 by prostatic tumour cells is associated with systemic dissemination of prostate cells independently of pathological criteria.
Increased sialylation of oligosaccharides on IgG paraproteins--a potential new tumour marker in multiple myeloma.
Authors: Fleming S C , Smith S , Knowles D , Skillen A , Self C H
Published: January 2009

AIMS: To investigate whether changes in carbohydrate structure of IgG are related to malignancy and stage of disease in myeloma and monoclonal gammopathy of uncertain significance (MGUS). METHODS: 61 patients were studied at diagnosis: 14 with MGUS, nine with stage I multiple myeloma, 11 with stage II, 21 with stage III, and five with solitary plasmacytoma. IgG was extracted from serum by protein G affinity chromatography. Oligosaccharides were cleaved from the protein backbone enzymatically by N-glycosidase F. Oligosaccharide analysis was performed by high pressure anion exchange chromatography with pulsed electrochemical detection (HPAE-PED). RESULTS: Up to 15 oligosaccharide peaks were identified in three major fractions: neutral, monosialylated, and disialylated. Patients with myeloma showed an increase in the proportion of sialylated oligosaccharides in comparison with patients with MGUS. The ratio of neutral to sialylated oligosaccharides (N:S) was reduced at all stages of myeloma compared with MGUS: MGUS, 11.35; myeloma stage I, 7.6 (p = 0.047); stage II, 5.20 (p = 0.035); stage III, 3.60 (p = 0.0002); plasmacytoma, 7.5 (p = 0.046). The N:S ratio was independent of paraprotein concentration (r = 0.05). CONCLUSIONS: The ratio of neutral to sialylated oligosaccharides may act as a new marker of malignancy in IgG paraproteinaemia and warrants further investigation.
Intraepithelial haemorrhage of the oesophagus: a terminal event in haematological disorders.
Authors: Shimizu M , Matsumoto T , Hirokawa M , Monobe Y , Iida M , Manabe T
Published: January 2009

AIMS: To investigate the clinicopathological findings in cases with intraepithelial haemorrhage of the oesophagus (IHO). METHODS: Necropsy records and the histopathology findings in the oesophagus were reviewed for the period 1990 to 1995. Six cases (0.7%) of IHO were found among 919 necropsy cases. Clinical records of these patients and gross and microscopic slides were reviewed in detail. RESULTS: The ages of the IHO cases ranged from 42 to 82 years (average 68 years), with a male to female ratio of 1:2. All cases had underlying haematological disorders with thrombocytopenia, but disseminated intravascular coagulation was not evident in any case. Macroscopically, solitary (two cases) or multiple (four cases) haemorrhagic lesions ranging from 6 to 79 mm in size were identified within the distal oesophagus. Microscopically, there was no inflammatory infiltration, destruction of red blood cells, or submucosal scar formation. CONCLUSIONS: IHO seems to occur shortly before death as a terminal event in haematological disorders. Based on these observations, the term "terminal IHO" can be suggested for this type of oesophageal lesion.
Improving the quality of perinatal and infant necropsy examinations: a follow up study.
Authors: Vujanić G M , Cartlidge P H , Stewart J H
Published: January 2009

AIM: To compare the quality of perinatal and infant necropsy examinations in 1996 with those performed in 1993. METHODS: Cohort analysis, with data from the All Wales Perinatal Survey, of 1027 deaths (540 in 1993; 487 in 1996) of babies between 20 weeks' gestation and one year of age. The quality of the necropsy was assessed by scoring aspects identified as being part of the investigation. RESULTS: Necropsy was performed in 335 cases (62%) in 1993 and in 320 cases (66%) in 1996. The proportion done in a regional centre increased significantly from 39% (131/335) in 1993 to 76% (243/320) in 1996 (p < 0.0001). The quality of necropsy was above the minimum standard in 54% of cases in 1993 (171/314) compared with 93% in 1996 (289/312) (p < 0.0001). Improvement occurred in all categories. For stillbirths, 35% (46/133) were above the minimum standard in 1993 compared with 90% (104/116) in 1996 (p < 0.0001); for cases not classified as sudden unexpected death in infancy (SUDI), the improvement was from 62% in 1993 (40/65) to 97% in 1996 (73/75) (p < 0.0001); and for SUDI cases, the improvement was from 32% in 1993 (10/31) to 91% in 1996 (21/23) (p < 0.0001). The quality of both non-regional and regional necropsies improved. For non-regional cases, the score was above the minimum standard in 28% (51/183) in 1993 compared with 69% (52/75) in 1996 (p < 0.0001); for regional cases it improved from 92% (120/131) in 1993 to 100% (237/237) in 1996 (p < 0.0001). CONCLUSIONS: The quality of perinatal and infant necropsies improved considerably between 1993 and 1996, reflecting better awareness of the importance of good quality examination and an increase in referrals to paediatric centres.
An immunoblotting procedure comprising O = 9,12 and H = d antigens as an alternative to the Widal agglutination assay.
Authors: Chart H , Ward L R , Rowe B
Published: January 2009

AIMS: To compare the established Widal agglutination assay with an immunoblotting procedure. METHODS: 110 sera were used to compare the established Widal agglutination assay with an immunoblotting procedure incorporating lipopolysaccharide (LPS) (O = 9,12) and flagellar (H = d) antigens. RESULTS: Antibodies to the LPS antigens were detected in 18 sera by the Widal assay and in 37 by immunoblotting. Antibodies to the flagellar antigens were detected in 27 sera by Widal assay and in 25 by immunoblotting. CONCLUSIONS: An immunoblotting procedure incorporating O = 9,12 LPS and H = d flagellar antigens was rapid and more sensitive than the established Widal agglutination assay for providing evidence of infection with S typhi.
Immunocytochemical detection of Candida albicans in formalin fixed, paraffin embedded material.
Authors: Williams D W , Jones H S , Allison R T , Potts A J , Lewis M A
Published: January 2009

AIM: To assess the ability of the commercially available monoclonal antibody 1B12 (BioGenex, San Ramon, USA) to identify C albicans in formalin fixed, paraffin wax embedded material (FFPE). METHODS: Broth cultures of 20 strains of seven Candida species were resuspended in 4% agarose blocks, fixed in formalin for 24 hours, and embedded in paraffin wax. In addition, 16 blocks of FFPE tissue known to contain periodic acid-Schiff positive fungal hyphae were examined. Antigen retrieval involved microwave treatment of specimens in citrate buffer (0.01 M; pH 6.5) before addition of 1B12 antibody for 24 hours. Bound antibody was subsequently detected using a biotinylated link antibody and a peroxidase conjugated streptavidin. RESULTS: Only C albicans strains were 1B12 positive in the agarose blocks. All FFPE tissue blocks were found to contain 1B12 positive hyphal structures, indicating the presence of C albicans. CONCLUSIONS: The ability to identify candida organisms penetrating the lesional tissue in cases of chronic hyperplastic candidosis will help to clarify the role of individual Candida spp in this important form of oral candidosis.
An unusual cutaneous manifestation of myelodysplastic syndrome: "pseudo-Koebner phenomenon".
Authors: DasGupta R , Fairham S A , Womack C , Burton C , Sivakumaran M
Published: January 2009

An unusual and hitherto unreported complication of myelodysplastic syndrome is reported: the "pseudo-Koebner phenomenon." The skin lesions were characterised by exuberant "fleshy" masses at the sites of intravenous cannulation and skin trauma, and by histological evidence of chronic inflammation with focal necrosis and abscess formation. No evidence of dermal infiltration by malignant haemopoietic cells was seen. The exact aetiopathology of the phenomenon is unclear but an inappropriate and exaggerated inflammatory response owing to aberrant mediator mechanisms that are known to occur in some cases of myelodysplastic syndrome may be implicated.
CD5 positive breast carcinoma in a patient with untreated chronic lymphocytic leukaemia: molecular studies of chromosome 13q.
Authors: Shousha S , Costello C , Luqmani Y A , Sinnett H D
Published: January 2009

A 67 year old woman presented with a right breast lump which proved to be a grade 2 invasive ductal carcinoma with axillary lymph node metastasis. She had a five year history of CD5 positive chronic lymphocytic leukaemia, which never required treatment. Immunoperoxidase stains for CD5, using the monoclonal antibody NCL-CD-54C7, showed that there was extensive infiltration of axillary lymph nodes with CD5 positive B lymphocytes. Strong staining for CD5 was also seen in the carcinoma cells within the breast and lymph node metastases. It has recently been suggested that there is a tumour suppresser locus in chronic lymphocytic leukaemia at 13q12.3 near or at the BRCA2 locus. Deletion of regions on chromosome 13q containing the BRCA2 and RB1 genes has also been reported in sporadic breast cancers. These observations suggest that there may be a link between these two diseases acting through chromosome 13, but amplification of several microsatellite repeat markers failed to show any loss of heterozygosity or repeat instability at either these or several other loci on chromosome 13. Examination of additional such cases is needed to perform a more comprehensive study of the significance of positive CD5 staining of breast carcinoma.
Pancreatic cancer and fibrinogen storage disease.
Authors: Radhi J M , Lukie B E
Published: January 2009

BACKGROUND: Ductal adenocarcinoma is the most common type of pancreatic carcinoma while squamous, carcinosarcoma, sarcoma, giant cell carcinoma, and clear cell types are all rare. Hepatocellular fibrinogen storage disease is also an uncommon disorder which may be associated with hepatocellular carcinoma. Two cases of pancreatic carcinoma were encountered in a family with fibrinogen storage disease, further raising the possibility of a predilection to malignancy in this unusual disorder. The tumour in one case was of the rare clear cell type. These two cases are the basis for this report. METHODS: Sections were cut from retrieved paraffin embedded tissue and stained for routine histology. Immunohistochemistry using the avidin-biotin technique was applied for the expression of the markers p53 (D07), carcinoembryonic antigen (CEA), c-erbB-2, epithelial membrane antigen (EMA), and alpha-fetoprotein (AFP). RESULTS: Both cases were adenocarcinoma of pancreatic ductal origin. The tumour in one case showed features of a clear cell carcinoma. The tumour cells expressed p53, CEA, and EMA immunoreactivity and were negative for c-erbB-2 and AFP. CONCLUSIONS: Hepatocellular fibrinogen storage disease is rare and has been described in association with chronic hepatitis, cirrhosis, and rarely with hepatocellular carcinoma. This represents the first report of its association with carcinoma outside of the liver.
Malignant fibrothecomatous tumour of the ovary: diagnostic value of anti-inhibin immunostaining.
Authors: McCluggage W G , Sloan J M , Boyle D D , Toner P G
Published: January 2009

Malignant ovarian tumours of the fibrothecoma group are rare. The clinicopathological features of a case of ovarian malignant fibrothecoma in which there was metastatic disease in the small intestine and peritoneum at presentation are described. A number of differential diagnoses were considered but positive immunohistochemical staining of the resected ovarian and small intestinal neoplasms with anti-inhibin was of value in confirming a sex cord-stromal tumour and in excluding other lesions. The two tumours were also ultrastructurally identical. Classical malignant fibrothecomas are said to show four or more mitotic figures per 10 high power fields (HPF). Although the intestinal secondary was mitotically active, the primary ovarian tumour contained only one to two mitoses per 10 HPF, showing that formal mitotic counts are not an absolute indicator of malignant behaviour in this group of tumours.
Histochemical investigation into the molecular mechanisms of malignant transformation in a benign glomus tumour.
Authors: Hegyi L , Cormack G C , Grant J W
Published: January 2009

A glomangiosarcoma arose in a benign glomus tumour. The histological and immunohistochemical characteristics of the tumour were investigated. Apoptotic cells were identified by terminal deoxynucleotidyl transferase (TdT) mediated dUTP-biotin nick end labelling (TUNEL). The proportion of apoptotic cells was found to be low and TUNEL positive nuclei were present in the benign part of the tumour. Bcl-2 protein, an inhibitor of apoptosis, was strongly expressed in the glomangiosarcoma with only weak staining in the benign area. The proliferation index of the glomangiosarcoma was almost 10-fold higher than that of the benign glomus tumour. Numerous nuclei in the glomangiosarcoma were intensely stained for the tumour suppressor protein p53. The results of the this study may contribute to an understanding of the molecular basis of malignant transformation in benign glomus tumours.
Borderline malignant change in recurrent müllerian papilloma of the vagina.
Authors: Dobbs S P , Shaw P A , Brown L J , Ireland D
Published: January 2009

Malignant change occurred in a benign, recurrent vaginal müllerian polyp. The patient, a 49 year old woman with cerebral palsy, presented with a polypoid mass in the vagina. At four years of age she had presented with a haemorrhagic polyp, and over the following years she had recurrent irregular bleeding and regrowth of the polypoidal mass, requiring a total of 10 operations to excise the polyp. Histological examination of the specimen showed typical müllerian features with tubal, endometrioid, and endocervical cell types. There were significantly abnormal nuclei, indicating low grade or borderline malignancy. Review of previous biopsies showed similar müllerian features but no atypia. This is the first reported case of borderline malignant change in a previously benign recurrent müllerian papilloma of the vagina. Definitive radical surgery or radiotherapy is contraindicated in this patient and she remains under follow up.
Detection of small numbers of immature cells in the blood of healthy subjects.
Authors: Oertel J , Oertel B , Schleicher J , Huhn D
Published: January 2009

AIMS: To determine the frequency of immature haemopoietic cells in the peripheral blood of healthy persons. METHODS: Cytocentrifuge preparations were made using mononuclear leucocytes separated by a Ficoll-Hypaque density gradient. The slides were stained by May-Grünwald-Giemsa. The combination with immunoperoxidase technique allowed immunotyping of uncommon blood cells. RESULTS: Blast cells expressing the progenitor cell marker CD34 represented 0.11 (0.06) per cent (mean (SD)) of the total mononuclear leucocyte count; these were the haemopoietic progenitor cells in the peripheral blood. Dark blue cells expressing CD38, CD45, HLA-DR, CD4, CD11a, CD29, CD49d, CD50, and CD54 represented 0.30 (0.21) per cent of the mononuclear leucocytes; most of these cells did not express T, B, NK, myelomonocytic, progenitor cell, proliferation, activation, blood dendritic cell, or follicular dendritic cell markers. These were dendritic cell precursors in the peripheral blood. Very small numbers of cells expressing CD83 were found. Blast-like cells expressing CD45, HLA-DR, CD11a, and CD50 represented 0.15 (0.10) per cent of the mononuclear leucocytes; morphology and immunotyping supported the conclusion that these cells were poorly differentiated monocytes. CONCLUSIONS: Morphological investigation of mononuclear leucocytes in peripheral blood of healthy persons can be used to detect small numbers of blasts, dark blue cells, and blast-like cells. The immunoperoxidase technique can then be used for immunotyping of these cells. This simple method may be helpful in diagnosing haematological disorders.
An assessment of the operation of an external quality assessment (EQA) scheme in histopathology in the South Thames (West) region: 1995-1998.
Authors: Carter R L , Cook M G
Published: January 2009

AIMS: To describe the design and organisation of a voluntary regional external quality assessment (EQA) scheme in histopathology, and to record the results obtained over a three year period. METHODS: A protocol is presented in which circulation of EQA slides alternated with teaching sessions. Procedures for the choice of suitable cases, evaluation of submitted diagnoses, and feedback of results to participants are described. The use of teaching sessions, complementary to the slide circulations, and dealing with current diagnostic problems is also outlined. RESULTS: Participation rates in the nine slide circulations varied between 66% and 89%, mean 85%. Overall scores were predictably high but 4% of returns, from 10 pathologists, were unsatisfactory. These low scores were typically isolated or intermittent and none of the participants fulfilled agreed criteria for chronic poor performers. CONCLUSIONS: This scheme has been well supported and overall performances have been satisfactory. The design was sufficiently discriminatory to reveal a few low scores which are analysed in detail. Prompt feedback of results to participants with identification of all "incomplete" and "wrong" diagnoses is essential. Involvement of local histopathologists in designing, running, and monitoring such schemes is important.
Qualitative and semiquantitative polymerase chain reaction testing for cytomegalovirus DNA in serum allows prediction of CMV related disease in liver transplant recipients.
Authors: Evans P C , Soin A , Wreghitt T G , Alexander G J
Published: January 2009

AIM: To identify cytomegalovirus (CMV) infection in liver transplant recipients by polymerase chain reaction (PCR) techniques and to separate the cases in which CMV related disease will occur, for whom treatment is indicated, from those in whom infection will remain innocuous. METHODS: The combination of qualitative and semiquantitative PCR of serum and urine was assessed to determine whether these assays can identify those at risk of CMV related disease and compared their performance with conventional approaches to diagnosis. RESULTS: Qualitative PCR of serum had superior specificity, sensitivity, and positive and negative predictive values compared with urine DEAFF (detection of early antigen fluorescent foci) and PCR of urine. All episodes of CMV related disease were associated with the presence of CMV DNA by PCR in serum or urine; CMV was detected before clinical onset in 70% and 60% of cases, respectively. The period over which CMV DNA could be detected was not correlated with CMV related disease. Both peak viral load and cumulative viral load estimated using a semiquantitative PCR method on serum samples positive by the qualitative method could be used to distinguish asymptomatic infection from CMV related disease with 100% specificity and sensitivity. In contrast semiquantitative PCR of urine was of little value. CONCLUSIONS: An approach based on PCR testing with a combination of qualitative and subsequently semiquantitative serum samples would improve the diagnosis of CMV infection and aid identification of those patients at risk of CMV related disease, allowing treatment to be targeted specifically.
A rapid polymerase chain reaction technique for detecting M tuberculosis in a variety of clinical specimens.
Authors: Kearns A M , Freeman R , Steward M , Magee J G
Published: January 2009

A rapid in-house polymerase chain reaction (PCR) assay is described for the direct detection of Mycobacterium tuberculosis complex in clinical material. Its performance is compared with two kit based systems. The results of the in-house assay were comparable with the commercial assays, detecting M tuberculosis in 100% of smear positive, culture positive samples. The in-house assay proved to be rapid, easy, and inexpensive to perform, and the inclusion of an internal inhibitor control permitted validation of the PCR results.
Vaginal epithelioid angiosarcoma.
Authors: McAdam J A , Stewart F , Reid R
Published: January 2009

A case of epithelioid angiosarcoma of the vagina is described. Only five cases of angiosarcoma at this site have been reported, three of which followed radiotherapy for other gynaecological malignancies. None is described as an epithelioid angiosarcoma, an unusual and recently described variant which is readily confused with carcinoma. This is thought to be the first reported epithelioid angiosarcoma at this site and highlights the difficulties in diagnosis.
Primary yolk sac tumour of the liver in adulthood.
Authors: Wong N A , D'Costa H , Barry R E , Alderson D , Moorghen M
Published: January 2009

Primary yolk sac tumour of the liver is exceedingly rare. A 28 year old woman presented with a cystic liver mass and a markedly raised serum alpha-fetoprotein concentration. She underwent a partial hepatectomy for a suspected hepatocellular carcinoma but histological examination of the tumour revealed the classical morphological and immunohistochemical features of a yolk sac tumour. There was no evidence of an extrahepatic primary source. Review of this case, together with the six previously reported adult cases of primary yolk sac tumours of the liver, revealed several features of the tumour that may aid differentiation from hepatocellular carcinoma, with potential therapeutic implications.
Thorotrast associated nodular regenerative hyperplasia of the liver.
Authors: Beer T W , Carr N J , Buxton P J
Published: January 2009

A case of nodular regenerative hyperplasia (NRH) of the liver is described in association with exposure to the radiographic contrast medium Thorotrast. This is the first case in which the pathological findings have been fully documented. It is suggested that NRH may have developed through Thorotrast induced damage to portal vein radicles.
Immunohistochemical staining of normal, hyperplastic, and neoplastic adrenal cortex with a monoclonal antibody against alpha inhibin.
Authors: McCluggage W G , Burton J , Maxwell P , Sloan J M
Published: January 2009

AIMS: To investigate the immunohisto-chemical staining of normal, hyperplastic, and neoplastic adrenal cortex with a monoclonal antibody against alpha inhibin. Also, to determine whether immunostaining with this antibody is useful in differentiating between adrenal cortical neoplasms and other tumours involving the adrenal gland that might mimic them. METHODS: Normal adrenal tissue (n = 20) and specimens from cases of adrenal hyperplasia (n = 13), adrenal cortical adenoma (n = 15), adrenal cortical carcinoma (n = 4), phaeochromocytoma (n = 8), and adrenal metastatic tumour (n = 7) were stained with a monoclonal antibody against the alpha subunit of human inhibin. RESULTS: Positive staining with the anti-alpha inhibin monoclonal antibody was seen in all normal adrenal glands. Immunoreactivity was largely confined to the inner cell layers of the adrenal cortex, with no staining of the adrenal medulla. All hyperplastic adrenal glands and adrenal cortical adenomas and carcinomas were also immunoreactive. The other tumours studied were negative. CONCLUSIONS: There is consistent immunoreactivity with the anti-alpha inhibin monoclonal antibody in normal adrenal cortex and in hyperplastic and neoplastic adrenal cortical lesions. In the normal adrenal cortex, positive staining is mainly confined to the zona reticularis. Other neoplasms involving the adrenal gland are negative. Immunohistochemical staining with anti-alpha inhibin monoclonal antibody, performed as part of a panel, may prove to be of value in the distinction between adrenal cortical carcinoma and phaeochromocytoma or metastatic tumour.
Age related somatic mitochondrial DNA deletions in bone.
Authors: Papiha S S , Rathod H , Briceno I , Pooley J , Datta H K
Published: January 2009

BACKGROUND: It has been suggested that the accumulation of damage to mitochondrial DNA is a major cause of age related, degenerative disease. Aging is known to cause bone loss leading to a fall in bone mineral density and disruption of bone microarchitecture. However, despite the evidence of age related bone loss, no attempt has been made to detect specific deletions of mitochondrial DNA in the bone of aged individuals. AIMS: To detect bone specific, age related deletions in mitochondrial DNA. METHOD: Blood leucocytes and bone biopsies from patients who had undergone orthopaedic surgery were used as a source of mitochondrial DNA and screened for deletions using the polymerase chain reaction. RESULTS: Although no deletions were detected in the blood mitochondrial DNA, specific deletions in bone mitochondrial DNA were found in three of five elderly subjects. CONCLUSION: The findings of this study suggest that there could be a link between mitochondrial DNA deletions and free radical induced apoptosis of bone cells in the development of age related bone loss.
Assessment of invasion frequencies of cultured HEp-2 cells by clinical isolates of Helicobacter pylori using an acridine orange assay.
Authors: Wilkinson S M , Uhl J R , Kline B C , Cockerill F R
Published: January 2009

AIMS: Recent studies suggest that Helicobacter pylori is an invasive enteropathogen. However, the efficiency with which this pathogen invades mammalian cells remains unknown. Therefore, this study was designed to investigate the invasion frequencies of HEp-2 cells by clinical strains of H pylori. METHODS: An acridine orange assay and cultured HEp-2 cell monolayers were used to determine the HEp-2 cell penetration frequencies of 17 clinical isolates and one American Type Culture Collection (ATCC) strain of H pylori, and single clinical strains of Yersinia enterocolitica, Shigella flexneri, and a non-invasive ATCC Escherichia coli strain. RESULTS: The acridine orange assay demonstrated that invasion frequencies of HEp-2 cells by all H pylori isolates were significant and, in most instances, exceeded those for the S flexneri strain and equalled those for the Y enterocolitica strain. The assay also showed that internalised H pylori organisms remained viable for at least six hours, the maximum time that bacteria and HEp-2 cells were co-incubated. CONCLUSIONS: These results may have important implications for treatment and prevention strategies for this gastric pathogen. Furthermore, the acridine orange assay may be useful for assessing, in vitro, the ability of conventional and newer antibiotics, alone or in combination, to kill intracellular H pylori organisms.
Differential expression of CD44v6 in metastases of intestinal and diffuse types of gastric carcinoma.
Authors: Castellà E M , Ariza A , Pellicer I , Fernández-Vasalo A , Ojanguren I
Published: January 2009

AIMS: To assess whether standard and variant isoforms of CD44 (CD44s, CD44v5, and CD44v6) have a differential expression profile in early versus advanced gastric adenocarcinoma of the diffuse and intestinal types and their metastases. METHODS: Immunohistochemical expression of CD44s, CD44v5, and CD44v6 was evaluated in 14 early gastric cancers (nine intestinal and five diffuse) and 37 advanced adenocarcinomas (21 intestinal and 16 diffuse) as well as in 18 cases of perigastric lymph node metastasis. Ten normal and five metaplastic gastric mucosa samples were also included in the study. RESULTS: Although no significant association was found between the degree of invasion and the CD44 expression profile, CD44v6 positivity was detected more frequently in metastases of intestinal-type carcinomas (66%) than in metastases of diffuse-type neoplasms (11%) (p < 0.05). Weak CD44s, CD44v5, and CD44v6 expression was observed focally in both normal and metaplastic gastric mucosa samples. CONCLUSIONS: These data suggest that CD44v6 expression may be involved in the production of lymph node metastases in intestinal-type gastric carcinoma but not in the diffuse-type disease, the metastatic potential of which is most likely unrelated to the CD44 family of adhesion molecules.
Evaluation of immunoassays for the detection and typing of PCR amplified human papillomavirus DNA.
Authors: Venturoli S , Zerbini M , La Placa M , D'Antuono A , Negosanti M , Gentilomi G , Gallinella G , Manaresi E , Musiani M
Published: January 2009

AIMS: To evaluate different hybridisation techniques to detect and type human papillomavirus (HPV) DNAs amplified by consensus primer polymerase chain reaction (PCR) in biopsy and cytological specimens. METHODS: A hybrid capture-immunoassay in microtitre wells was performed to detect HPV sequences amplified by PCR and typed by specific oligoprobes. Consensus primers were used to amplify a sequence within the L1 open reading frame, and direct digoxigenin labelling of amplified products was performed during the amplification reaction. The amplified product was separately hybridised with six biotinylated type specific probes (HPV6, 11, 16, 18, 31, and 33); hybrids were then captured into streptavidin coated microtitre wells and detected by a spectrophotometer as an ELISA using antidigoxigenin Fab fragment labelled with peroxidase and a colorimetric substrate. The results were compared with the dot-blot immunoassay used to detect and type PCR amplified HPV DNA sequences. Consensus primers were used to generate the same unlabelled PCR product; digoxigenin labelled type specific probes for HPV6, 11, 16, 18, 31, and 33 were used and hybrids visualised by colorimetric immunoenzymatic reaction. Thirty nine biopsy specimens and 31 cytological samples were tested by the PCR-ELISA and by standard PCR followed by dot-blot hybridisation. RESULTS: The PCR-ELISA proved to be more sensitive than standard PCR with dot-blot hybridisation typing. All samples positive for HPV-DNA in standard PCR with dot-blot hybridisation method were confirmed positive by the PCR-ELISA assay; however, seven samples were positive only by PCR-ELISA. CONCLUSIONS: The PCR-ELISA assay, which can be performed in one day, is easily standardised and therefore seems to be a practical, sensitive, and reliable diagnostic tool for the detection and typing of HPV genomes in biopsy and in cytological specimens in the routine diagnostic laboratory.