bluuebunny/crossref_metadata_2025 huggingface dataset:
A human skin explant model for predicting graft-versus-host disease following bone marrow transplantation.
Authors: Sviland L , Dickinson A M
Published: January 2009

Graft-versus-host disease (GVHD) is the most serious complication following bone marrow transplantation, with an incidence of 40-60%. The disease can be fatal in 50% of cases, even in patients receiving marrow from an HLA identical sibling. Several assays have been developed to try to predict the development of GVHD, including mixed lymphocyte culture reaction, cytotoxic T lymphocyte precursor, and helper T lymphocyte precursor frequency assays. This review describes an in vitro skin explant model which has been used since 1988 for both predicting acute GVHD in HLA identical sibling bone marrow transplantation and studying the pathophysiology of the disease. The model involves sensitising donor lymphocytes in vitro in a primary mixed lymphocyte reaction and then evaluating the secondary response on patient skin biopsies by grading the graft-versus-host reactivity (grades I-IV) histopathologically. From analysis of collective data the model is a clear predictor of GVHD and superior to the other assays widely used, with a correlation of 82% with clinical outcome. The skin explant model allows the investigator to study the pathogenesis of GVHD. The cytokines TNF alpha and IFN gamma are shown to be important mediators of cellular damage in graft-versus-host reactions. Recent work has also involved using the model to study the alloreactivity of cord blood. The model is currently being assessed in several bone marrow transplantation centres in Europe on different patient groups including those who receive marrow from haploidentical and matched unrelated donors.
A reliable method for the simultaneous identification of H pylori and gastric metaplasia in the duodenum.
Authors: el-Zimaity H M , Wu J , Akamatsu T , Graham D Y
Published: January 2009

While an association of Helicobacter pylori infection with duodenal mucosa gastric metaplasia has been described, the details and extent of the interaction are lacking. One of the limiting factors has been the lack of a staining technique that allows simultaneous visualisation of the bacteria and gastric metaplasia in the duodenum. This report describes a new stain that allows the simultaneous visualisation of duodenal gastric metaplasia and H pylori and compares the new stain with the component stains.
Immunohistochemical identification of erythroid precursors in paraffin embedded bone marrow sections: spectrin is a superior marker to glycophorin.
Authors: Sadahira Y , Kanzaki A , Wada H , Yawata Y
Published: January 2009

AIM: To investigate whether spectrin can be used as an immunohistochemical marker for erythroid precursors in routinely processed paraffin embedded bone marrow sections. METHODS: Bone marrow biopsies and clot sections were stained with rabbit antihuman erythrocyte spectrin antibodies, specific for erythroid cells as shown by western blotting and bone marrow smears, and compared to sections stained with antiglycophorin monoclonal antibodies (JC159 and Ret49f). RESULTS: Antispectrin antibodies resulted in diffuse cytoplasmic staining of early erythroblasts and membranous staining of late erythroblasts as well as erythrocytes. In haematopathological samples, immature erythroid cell clusters were clearly identified. In contrast, antiglycophorin monoclonal antibodies resulted in only membranous staining of late erythroblasts, and faint staining of early erythroblasts. CONCLUSIONS: Spectrin may be a superior marker to glycophorin for the identification of erythroid precursors in paraffin embedded sections.
Accuracy and cost of intraoperative lymph node frozen sections at radical prostatectomy.
Authors: Young M P , Kirby R S , O'Donoghue E P , Parkinson M C
Published: January 2009

AIM: To assess the value of intraoperative diagnostic examination of frozen sections of lymph nodes removed during radical prostatectomy. METHODS: Pelvic lymph nodes from patients with prostatic carcinoma were obtained (1) as frozen sections during radical prostatectomy, to exclude patients from non-curative surgery, and (2) as paraffin sections postoperatively from lymphadenectomy performed at radical prostatectomy, to stage the tumour and assess need for adjuvant treatment. Findings from the two approaches were used to assess the accuracy and cost of frozen section diagnosis, and to judge the results of omitting intraoperative diagnosis. RESULTS: In 82 patients frozen section revealed metastasis in six (7.3%), and metastases were found in a further four (4.9%) on paraffin sections (false negatives). Of the 195 patients undergoing staging lymphadenectomy (without frozen section), metastatic cancer was seen in nine cases (4.6%). The frozen section cost of metastatic cancer detection per patient was calculated as 7516 Pounds (550 Pounds x 82/6), with an associated false negative rate of 33%. CONCLUSIONS: Frozen section diagnosis of metastatic carcinoma in pelvic lymph nodes before radical prostatectomy has a high false negative rate and is costly. It may not be justified with the observed low incidence of lymph node metastasis.
Cryptococcal meningitis in an HIV negative patient with systemic sarcoidosis.
Authors: Botha R J , Wessels E
Published: January 2009

A case of Cryptococcus neoformans meningitis is described in an HIV negative patient with undiagnosed systemic sarcoidosis. The patient presented with signs of meningitis together with generalised lymphadenopathy and hepatosplenomegaly. Cryptococcal meningitis was diagnosed on lumbar puncture. She was treated with intravenous amphotericin B but died within two weeks of admission. Necropsy revealed lesions in the lungs, liver, spleen, lymph nodes, small intestine, and bone marrow consistent with sarcoidosis. Microscopically the lesions contained non-caseating epithelioid cell granulomas typical of sarcoidosis. No Schaumann or Hamazaki-Wesenberg bodies were identified. Cryptococcus neoformans meningitis is generally associated with immunosuppressive disorders. As T cell abnormalities have been described in sarcoidosis, this could have been a case of opportunistic infection. Although rare, sarcoidosis merits consideration in patients with cryptococcal disease in the absence of HIV infection.
Detection of human papillomavirus DNA in urinary bladder carcinoma by in situ hybridisation.
Authors: De Gaetani C , Ferrari G , Righi E , Bettelli S , Migaldi M , Ferrari P , Trentini G P
Published: January 2009

AIMS: To investigate the sensitivity of an in situ hybridisation system to detect human papillomavirus (HPV) infection in transitional cell bladder cancer and to evaluate the advantages of analysing multiple biopsies; to examine the correlation between HPV tumour infection detected by in situ hybridisation and the presence of serum anti-HPV antibodies detected by enzyme linked immunosorbent assay (ELISA); and to relate the presence of viral infection to grade, stage, and follow up in cases of bladder cancer. METHODS: The in situ hybridisation technique was used with broad spectrum and type specific (6/11, 16/18, 31/33/35) probes against HPV DNA in formalin fixed, paraffin embedded tissues from 43 cases of bladder cancer. The results were analysed for the presence and type of papillomavirus and correlated with clinicopathological variables. RESULTS: The presence of HPV DNA was identified by the in situ hybridisation technique in 17 of 43 cases of bladder cancer; 12 of these were serum antibody positive and 10 had had multiple biopsies. Fifteen of the cases that were negative for HPV DNA by in situ hybridisation had positive serum serology when tested by ELISA. In 14 cases, the HPV was either types 16/18 or types 31/33/35, both of which carry high oncogenic risk. The stage (p < 0.05) and grade (NS) of the tumour and the outcome on follow up (p < 0.05) were correlated with the presence of HPV infection. CONCLUSIONS: ELISA is not useful in identifying patients with HPV positive bladder cancer, but the use of several probes and multiple biopsies increases the detection rate of HPV in neoplastic tissues. The association between tumour virus infection and high grade/high stage tumours and worse outcome suggests that HPV infection of neoplastic tissue has a negative effect on the behaviour and evolution of transitional cell bladder carcinoma.
Ki-67 labelling index and invasiveness among anterior pituitary adenomas: analysis of 103 cases using the MIB-1 monoclonal antibody.
Authors: Mastronardi L , Guiducci A , Spera C , Puzzilli F , Liberati F , Maira G
Published: January 2009

AIMS: To investigate the relation between proliferative activity of anterior pituitary adenomas, quantified by the Ki-67 labelling index, and their invasive behaviour. METHODS: Expression of Ki-67 was evaluated in 103 anterior pituitary adenomas consecutively operated on in a 36 month period and correlated with surgical evidence of invasiveness. RESULTS: Non-invasive (n = 65) and invasive (n = 38) adenomas were identified from surgically verified infiltration of sellar floor dura and bone. The wall of the cavernous sinus was infiltrated in 16 cases. Forty one adenomas were non-functioning and 62 functioning (24 prolactin, 21 growth hormone, 10 ACTH, seven mixed). The overall mean (SD) Ki-67 labelling index was 2.64 (3.69) per cent (median 1.5). The mean index was 3.08 (4.59) per cent in functioning and 1.97 (1.78) per cent in non-functioning tumours; 5.47 (9.52) per cent in ACTH adenomas and 2.33 (2.42) per cent in others (p = 0.01); 3.71 (5.17) per cent in invasive and 2.01 (2.45) per cent in non-invasive adenomas (p = 0.027); and 5.58 (7.24) per cent in cavernous sinus infiltrating v 2.10 (2.39) per cent in cavernous sinus non-infiltrating adenomas (p = 0.0005). To identify a value of labelling index beyond which adenomas should be considered invasive and another beyond which cavernous sinus infiltration should be suspected, normality Q-Q plots were obtained: a threshold labelling index of 3.5% for invasive adenomas and of 5% for cavernous sinus infiltrating adenomas was defined, with statistically significant differences (p = 0.02 and p = 0.004, respectively). CONCLUSIONS: The Ki-67 labelling index can be considered a useful marker in determining the invasive behaviour of anterior pituitary adenomas.
Relation of cervical glandular intraepithelial neoplasia to microinvasive and invasive adenocarcinoma of the uterine cervix: a study of 121 cases.
Authors: Kurian K , al-Nafussi A
Published: January 2009

AIMS: To examine the relation between invasive adenocarcinoma and its alleged precursor, cervical glandular intraepithelial neoplasia (CGIN), and to assess the management and outcome of CGIN and the validity of using the term "microinvasive adenocarcinoma." METHODS: The clinical and pathological features of 121 cases of glandular neoplasia of the cervix diagnosed between the years 1990 to 1995 were examined for the following: histological diagnosis, smear records, type of treatment, the association between the precursor lesions and invasive disease, and follow up. RESULTS: 27 cases were identified as low grade CGIN (L-CGIN) and 38 as high grade CGIN (H-CGIN), 10 as microinvasive adenocarcinoma (less than 5 mm in depth), and 46 as invasive adenocarcinoma. The ratio of non-invasive to invasive disease was 1.12:1. The mean age of women was 39, 43, 43, and 48 years for L-CGIN, H-CGIN, microinvasive, and invasive adenocarcinoma, respectively. L-CGIN was seen in 13% and 18% of H-CGIN and microinvasive disease, respectively. H-CGIN was seen in 100% of microinvasive and 26% of invasive adenocarcinomas. The available smears before diagnosis predicted 59% of L-CGIN, 70% of H-CIGN, 100% of microinvasive adenocarcinoma, and 32% of invasive adenocarcinomas. Treatment of 74% of L-CGIN, 52% of H-CIGN, and 10% of microinvasive adenocarcinoma was by diathermy loop excision only. The remaining cases had hysterectomy. Residual disease was found in 43%, 50%, and 33% of hysterectomies for L-CGIN, H-CGIN, and microinvasive adenocarcinoma, respectively. This is correlated with positive margins, or disease within 3 mm of margins on loop specimens. Cervical smear follow up for two to seven years revealed no recurrence of glandular lesions in any of the cases of CGIN or microinvasive adenocarcinoma. CONCLUSIONS: Precursor glandular lesions tend to progress to invasive carcinoma. There is a progressive increase in age of patients from L-CGIN to invasive disease, a span of approximately 10 years. There is a high association between H-CGIN and invasive disease. In the management of such alleged precursors, it is important to ensure adequate free margins of at least 3 mm. Microinvasive adenocarcinoma appears to have an excellent prognosis if treated by hysterectomy.
An assessment of the histological criteria used to diagnose infection in hip revision arthroplasty tissues.
Authors: Pandey R , Drakoulakis E , Athanasou N A
Published: January 2009

AIM: To characterise the number and nature of the inflammatory cells seen in cases of septic or aseptic loosening of hip arthroplasty, and to establish reliable histological criteria to distinguish between these two conditions. METHODS: Histological examination of paraffin sections of periprosthetic tissues (pseudocapsule, femoral and acetabular pseudomembranes) of 523 cases of aseptic loosening and 79 cases of microbiology culture proven septic loosening. The cellular composition of the inflammatory cell infiltrate was determined semiquantitatively. RESULTS: The finding of a 2+ or greater neutrophil polymorph infiltrate (one or more cells per high power field (x400) on average after examination of 10 fields) in arthroplasty tissues correlated strongly with the microbiological diagnosis of septic loosening: diagnostic sensitivity 100%, specificity 97%, accuracy 99%, positive predictive value 92%, negative predictive value 100%. The finding of a 3+ neutrophil polymorph infiltrate (five or more cells on average per high power field) had a diagnostic sensitivity of 72%, specificity 100%, accuracy 98%, positive predictive value 100%, and negative predictive value 97%. In some cases of septic loosening the finding of a heavy lymphocytic and plasma cell infiltrate was of low diagnostic sensitivity. A neutrophil polymorph infiltrate (generally less than one cell per 10 high power fields) was also seen in cases of aseptic loosening. CONCLUSIONS: The presence of 2+ or more (more than one neutrophil polymorph per high power field (x400) on average after examination of at least 10 high power fields) in periprosthetic tissues provides the most sensitive and accurate histopathological criterion for distinguishing between septic and aseptic loosening of hip arthroplasty.
A cytotoxic phenotype does not predict clinical outcome in anaplastic large cell lymphomas.
Authors: Dukers D F , ten Berge R L , Oudejans J J , Pulford K , Hayes D , Miseré J F , Ossenkoppele G J , Jaspars L H , Willemze R , Meijer C J
Published: January 2009

AIM: To investigate whether anaplastic large cell lymphomas (ALCL) expressing cytotoxic proteins have a relatively worse clinical outcome compared with ALCL lacking a cytotoxic phenotype. METHODS: 59 primary cases of ALCL originating from different sites were investigated by immunohistochemistry for the presence of the cytotoxic proteins T cell intracytoplasmic antigen (TIA-1) and granzyme B in the neoplastic cells. Since site of origin and expression of anaplastic lymphoma kinase (ALK) strongly influence prognosis, the presence of a cytotoxic phenotype was also investigated in relation to the primary site of origin (lymph node, gut, or skin) and ALK expression. The prognostic value was investigated by analysis of overall and relapse-free survival time, including Cox regression analysis. RESULTS: 39 of 59 ALCL (66%) appeared to have a cytotoxic phenotype as shown by expression of TIA-1 or granzyme B or both in the neoplastic cells. The presence of a cytotoxic phenotype did not have any influence on prognosis. Even when the survival data were corrected for site of origin and stage at presentation or were analysed separately for ALK positive and negative cases, no prognostic influence of a cytotoxic phenotype was observed. CONCLUSIONS: In primary biopsies of patients with ALCL, the presence of a cytotoxic phenotype is not related to clinical outcome of the disease.
Use of alcohol fixed cytospins protected by 10% polyethylene glycol in immunocytology external quality assurance.
Authors: Maxwell P , Patterson A H , Jamison J , Miller K , Anderson N
Published: January 2009

AIMS: To provide cytospins as a means of external quality assurance (EQA), while maintaining antigen expression integrity and achieving uniformity of material for all participating laboratories. METHODS: Cells were collected from two adenocarcinoma and one reactive pleural effusion specimens. Lymphoid cells were also collected through aspiration of a resected tonsil specimen. All cells were collected in Hanks balanced salt solution (HBSS); cytospins were made and fixed in methanol or acetone alone or protected using a layer of 10% polyethylene glycol (PEG) in 50% methanol. Two laboratories participated (RGHT and UCL). RESULTS: Cytokeratin expression detected using either CAM5.2 or AE1/AE3 antibodies was sensitive to temperature. Without PEG, unacceptable or negative staining was seen within six weeks of preparation. LCA was not sensitive to temperature, with good staining scores being achieved after eight weeks following preparation. CONCLUSIONS: It is possible to send alcohol fixed, air dried cytospins to laboratories participating as part of an EQA scheme for immunocytology. Some antigens will require protection from temperature variations during transit. A layer of 10% PEG in 50% methanol, allowed to air dry, is suitable for this purpose. Participating laboratories will only have to remove this layer using methanol before their localisation technique for assessment.
Calcium oxalate crystals (Weddellite) within the secretions of ductal carcinoma in situ--a rare phenomenon.
Authors: Singh N , Theaker J M
Published: January 2009

A case is described in which calcium oxalate (Weddellite) crystals were identified in an area of ductal carcinoma in situ of the breast. Seventy other cases were examined but no evidence of Weddellite was detected. This is evidently a rare phenomenon in carcinoma in situ.
Metastatic endometrial stromal sarcoma masquerading as pulmonary lymphangioleiomyomatosis.
Authors: Mahadeva R , Stewart S , Wallwork J
Published: January 2009

A 39 year old female presented with bilateral pneumothoraces and interstitial shadowing on chest x ray. A diagnosis of lymphangioleiomyomatosis was made following an open lung biopsy. Over the next eight years she developed respiratory failure leading to single lung transplantation but she died in the immediate postoperative period. Necropsy examination and review of the previous open lung biopsy revealed multiple pulmonary metastases from a low grade endometrial stromal sarcoma of the uterus. This case high-lights the importance of an accurate diagnosis before transplantation.
A comparison of three methods of orienting cervical punch biopsies.
Authors: Heatley M K
Published: January 2009

AIMS: To compare methods of orienting cervical punch biopsies, since well oriented biopsies are needed to optimise the diagnosis and grading of cervical intraepithelial neoplasia. METHODS: The orientation, the presence and preservation of the squamocolumnar junction, and the presence or absence of the surface layers of the squamous epithelium were compared in 345 cervical biopsies that had either been attached to paper (n = 112), floated directly into 10% formalin (n = 107), or floated into a solution of 10% formalin including 0.05% eosin (n = 126) in the colposcopy clinic. RESULTS: When the specimens were mounted on filter paper before fixation, they were more likely to be optimally oriented, to have a preserved squamocolumnar junction, and to have intact surface epithelium than specimens that were handled using the other methods, even when the specimens floated off the paper in transit. CONCLUSIONS: Cervical biopsy specimens should be mounted on paper before fixation and submission to the laboratory.
Hypokalaemic paralysis revealing Sjögren syndrome in an elderly man.
Authors: al-Jubouri M A , Jones S , Macmillan R , Harris C , Griffiths R D
Published: January 2009

A 73 year old white man presented with life threatening hypokalaemic paralysis requiring admission to an intensive care unit. Biochemical investigations showed severe hypokalaemia with hyperchloraemic metabolic acidosis, a spot urine pH of 6.5, and a positive urinary anion gap, establishing the diagnosis of distal renal tubular acidosis. Autoimmune tests revealed Sjögren syndrome as the underlying cause of the distal renal tubular acidosis. Full recovery followed potassium and alkali replacement. This dramatic presentation of Sjögren syndrome has not previously been reported in an elderly man.
The effect of specimen processing delay on borate urine preservation.
Authors: Gillespie T , Fewster J , Masterton R G
Published: January 2009

AIM: To investigate the effect on urine culture results and their clinical interpretation of delaying the processing of urine samples in which boric acid had been used as a preservative. METHODS: 792 mid-stream specimens of urine from patients attending their general practitioner were received in borate containing plastic jars. The specimens were cultured upon receipt, stored at room temperature, and then recultured the following morning. RESULTS: After overnight delayed culture, the results were altered in 16% of samples and the clinical interpretation of these findings differed in 8% of specimens. In 28 samples (3.5%) the bacterium isolated on initial culture was not the same as that obtained by culture after overnight storage. CONCLUSIONS: Boric acid urine preservation used for overnight delayed processing of samples is associated with a significant alteration in culture results and the attendant clinical interpretation of such specimens. Rapid transportation/processing of urine specimens must remain the optimum procedure.
Atypical C-ANCA following high dose intravenous immunoglobulin.
Authors: Jolles S , Deacock S , Turnbull W , Silvestrini R , Bunn C , White P , Ward M
Published: January 2009

AIMS: (1) To assess a range of intravenous immunoglobulin products for atypical classical antineutrophil cytoplasmic antibody (C-ANCA) staining and to determine if this is present in patients treated with high dose intravenous immunoglobulin (2 g/kg/month) and replacement doses (200 mg/kg fortnightly); (2) using the United Kingdom national external quality assessment scheme (NEQAS), to determine if laboratories could differentiate this pattern from classical ANCA. METHODS: ANCA testing was performed on 30 batches of intravenous immunoglobulin from several manufacturers. Six patients treated with high dose intravenous immunoglobulin and 11 receiving replacement doses of immunoglobulin for hypogammaglobulinaemia were tested for ANCA by indirect immunofluorescence on cytospin preparations of ethanol fixed neutrophils and by enzyme linked immunosorbent assay (ELISA). One of the positive immunoglobulin batches was tested blindly by 125 laboratories involved in NEQAS by indirect immunofluorescence and by ELISA in some laboratories. RESULTS: 16 of 31 batches of intravenous immunoglobulin from six different manufacturers were atypical C-ANCA positive. Three of six patients receiving high dose intravenous immunoglobulin and none of 11 patients on replacement doses were atypical C-ANCA positive. The results of the NEQAS assessment by indirect immunofluorescence were 68% C-ANCA positive, 17% negative, 9% atypical C-ANCA, and 6% P-ANCA. CONCLUSIONS: Some but not all intravenous immunoglobulin products yield a positive atypical cANCA by indirect immunofluorescence. An identical pattern may be observed in patients receiving high dose intravenous immunoglobulin but not in those on replacement doses. Of laboratories participating in NEQAS, 68% reported this pattern as cANCA. This reinforces the importance of reporting only "classical ANCA," defined by international ANCA workshops, to maintain the specificity of ANCA immunofluorescence and its close disease associations.
Fully automated microvessel counting and hot spot selection by image processing of whole tumour sections in invasive breast cancer.
Authors: Beliën J A , Somi S , de Jong J S , van Diest P J , Baak J P
Published: January 2009

BACKGROUND: Manual counting of microvessels is subjective and may lead to unacceptable interobserver variability, which may explain conflicting results. AIMS: To develop and test an automated method for microvessel counting and objective selection of the hot spot, based on image processing of whole sections, and to compare this with manual selection of a hot spot and counting of microvessels. METHODS: Microvessels were stained by CD31 immunohistochemistry in 10 cases of invasive breast cancer. The number of microvessels was counted manually in a subjectively selected hot spot, and also in the same complete tumour sections by interactive and automated image processing methods. An algorithm identified the hot spots from microvessel maps of the whole tumour section. RESULTS: No significant difference in manual microvessel counts was found between two observers within the same hot spot, and counts were significantly correlated. However, when the hot spot was reselected, significantly different results were found between repeated counts by the same observer. Counting all microvessels manually within the entire tumour section resulted in significantly different hot spots than manual counts in selected hot spots by the same observer. Within the entire tumour section no significant differences were found between the hot spots of the manual and automated methods using an automated microscope. The hot spot was found using an eight connective path search algorithm, was located at or near the border of the tumour, and (depending on the size of the hot spot) did not always contain the field with the largest number of microvessels. CONCLUSIONS: The automated counting of microvessels is preferable to the manual method because of the reduction in measurement time when the complete tumour is scanned, the greater accuracy and objectivity of hot spot selection, and the possibility of visual inspection and relocation of each measurement field afterwards.
Evaluation of three commercial detection systems for Mycobacterium tuberculosis where clinical diagnosis is difficult.
Authors: Brown T J , Power E G , French G L
Published: January 2009

AIMS: To assess the performance of three commercially available Mycobacterium tuberculosis detection systems employing nucleic acid amplification, when applied directly to respiratory and non-respiratory specimens from patients where the diagnosis of tuberculosis is difficult using clinical and traditional bacteriological methods. METHODS: 42 respiratory and 21 non-respiratory specimens were concentrated, examined with auramine staining, and cultured on Lowenstein-Jensen slopes. These specimens were also assayed using the Amplicor Mycobacterium tuberculosis test (AM) (Roche Diagnostic Systems), the Amplified Mycobacterium tuberculosis direct test (AMD) (Gen-Probe), and the LCx Mycobacterium tuberculosis assay (LMA) (Abbott Laboratories). RESULTS: All three amplification systems used in this study gave specificities of 100% when used on respiratory specimens. When used on non-respiratory specimens, AM and LMA gave specificities of 100% and AMD 75%. With respiratory specimens the AM, AMD, and LMA systems gave sensitivities of 75%, 65.2%, and 79.2%, respectively. With non-respiratory specimens the sensitivities were 50%, 66.7%, and 60%, while with smear negative, culture positive specimens they were 33.3%, 66.7%, and 55.6%. Positive predictive values of 100% were seen with all specimens except non-respiratory specimens assayed using AMD where the value was 66.7%. CONCLUSIONS: The manufacturers of these systems recommend that they should only be used for the direct analysis of respiratory specimens, and the US Food and Drug Administration has approved them for use only with smear positive specimens. This study confirms that sensitivities are lower for non-respiratory and smear negative specimens, but positive predictive values are high. Provided they are interpreted with caution, positive results with these tests in respiratory and non-respiratory specimens are useful in tuberculous patients who are otherwise difficult to diagnose. Each amplification has advantages and disadvantages compared with the others.
The possible role of hypoxia in the formation of axonal bulbs.
Authors: Kaur B , Rutty G N , Timperley W R
Published: January 2009

AIMS: To assess the possible role of hypoxia in the formation of axonal bulbs. METHODS: Study material comprised sections from 28 brains showing evidence of cerebral hypoxia with no history of head injury, four with a history of head trauma but no evidence of hypoxic change, eight with a history of head trauma and hypoxic change, and four from control brains originally described as "diffuse axonal injury." These were subjected to microwave antigen retrieval and immunohistochemistry using monoclonal antibodies to beta amyloid precursor protein (beta APP), glial fibrillary acid protein (GFAP), and CD68-PGM1. RESULTS: Positive staining for beta APP was seen in all four controls, all four cases of head injury only, seven of eight cases of head injury and hypoxic changes, and 12 of 28 cases of hypoxia without history of head injury; 22 of 25 cases who had been ventilated showed positive staining. The majority of cases showed evidence of cerebral swelling. CONCLUSIONS: Axonal bulbs staining positively for beta APP may occur in the presence of hypoxia and in the absence of head injury. The role of hypoxia, raised intracranial pressure, oedema, shift effects, and ventilatory support in the formation of axonal bulbs is discussed. The presence of axonal bulbs cannot necessarily be attributed to shearing forces alone.
Helicobacter pylori non-cytotoxic genotype enhances mucosal gastrin and mast cell tryptase.
Authors: Basso D , Navaglia F , Brigato L , Di Mario F , Rugge M , Plebani M
Published: January 2009

AIMS: To determine the association, if any, between H pylori genotype and the gastric mucosal variations in the levels of gastrin, somatostatin, tryptase, and histamine. METHODS: 49 patients affected by duodenal ulcer and 48 by non-ulcer dyspepsia were studied. To identify the H pylori genotype, the presence of the cagA gene and vacA alleles m1, m2, s1, and s2 were analysed by polymerase chain reaction. Gastrin, somatostatin, tryptase, and histamine were measured in antral mucosal biopsies. RESULTS: 57 patients were infected with H pylori (30 with duodenal ulcer and 27 with non-ulcer dyspepsia). Gastrin and tryptase were increased in patients with H pylori infection, although the variations were statistically significant only for gastrin; somatostatin and histamine were not influenced by H pylori infection. In patients with non-ulcer dyspepsia the absence of the cagA gene and the presence of vacA alleles s2 and m2 were associated with higher values of tryptase and to a lesser extent of gastrin. These associations were not found in patients with duodenal ulcer. CONCLUSIONS: The cagA negative s2m2 strain of H pylori may be less dangerous for the gastric mucosa than other H pylori strains since it enhances tryptase production by gastric mucosal mast cells; this enzyme is thought to stimulate tissue turnover and favour wound healing.
Antibody against Helicobacter pylori CagA and VacA and the risk for gastric cancer.
Authors: Yamaoka Y , Kodama T , Kashima K , Graham D Y
Published: January 2009

AIM: Helicobacter pylori is associated with gastric cancer. Our aim was to investigate whether CagA or VacA seropositivity provides additional risk for gastric cancer. METHODS: Sera from 110 gastric cancer patients were sex and aged matched with asymptomatic controls. H pylori status was determined by IgG enzyme immunoassay (HM-CAP EIA); CagA status was assessed by enzyme linked immunosorbent assay (ELISA) (OraVax) and immunoblotting (Chiron), and VacA status by immunoblotting using recombinant proteins as antigens. RESULTS: H pylori infection was associated with an increased risk of gastric cancer (odds ratio (OR) = 2.19, 95% confidence interval 1.17 to 4.1). Subgroup analysis showed a significant association with intestinal type (OR = 2.94, 1.35 to 6.41), distal type (OR = 2.97, 1.39 to 6.33), early gastric cancer (OR = 3.74, 1.54 to 9.06), and age < or = 55 years (OR = 8.33, 2.04 to 34.08), but not with diffuse type (OR = 0.83), proximal type (OR = 1.0), advanced gastric cancer (OR = 1.13), or age > 55 years (OR = 1.40). Serum CagA IgG and VacA antibody positivity was present in similar proportions in patients with and without cancer, with no significant differences in histological classification, clinical stage, or location (p > 0.3). CONCLUSIONS: H pylori infection causes chronic gastritis and is associated with the development of gastric cancer. Neither CagA nor VacA seropositivity added additional information or stratification.
Development and validation of an assay for urinary tissue factor activity.
Authors: Lwaleed B A , Chisholm M , Francis J L
Published: January 2009

BACKGROUND: Activation of blood coagulation is a common complication of cancer and inflammation in both humans and experimental animals. Increased production of tissue factor--the principal initiator of the coagulation process--by endothelial cells, monocytes, and macrophages has been implicated in these conditions. AIM: To investigate whether urinary tissue factor (uTF) might reflect the state of monocyte/macrophage activation and be a useful diagnostic test. METHODS: Urine was centrifuged at 51,000 g to sediment tissue factor containing membrane vesicles. The tissue factor was then solubilised in beta-octyl-glucopyranoside and assayed in a specific chromogenic assay adapted for use in microtitre plates. RESULTS: The assay proved to be sensitive, specific, and reproducible. The normal range of uTF was relatively narrow and unaffected by age, sex, or cigarette smoking. Levels were not significantly influenced by storage of urine samples before assay or by the presence of fresh blood in the urine sample. CONCLUSIONS: This method may have diagnostic application in the study of haemostatic activation in patients with cancer and other disease states.
Evaluation of the BBL Crystal MRSA ID System for detection of oxacillin resistance in Staphylococcus aureus.
Authors: Kampf G , Lecke C , Cimbal A K , Weist K , Rüden H
Published: January 2009

AIMS: To evaluate the BBL Crystal MRSA ID System for detection of oxacillin resistance in Staphylococcus aureus. METHODS: 52 methicillin resistant S aureus (MRSA) from five different countries and 85 methicillin susceptible S aureus (MSSA) were included. The species was confirmed by tube coagulation and detection of the clumping factor using the Staphaurex Plus. Clonal non-identity of the MRSA isolates was shown by pulsed field gel electrophoresis. MIC values (oxacillin) were determined using the Etest. Polymerase chain reaction was carried out to detect the mecA gene. The BBL Crystal MRSA ID System was carried out according to the manufacturer's instructions. RESULTS: The BBL Crystal MRSA ID System showed fluorescence in 45 of 52 MRSA (sensitivity 86.5%; negative predicitive value 92.2%), and the specificity was 97.6% (positive predicitive value 95.7%). Two of seven MRSA that failed to show fluorescence had MIC values (oxacillin) of 4 mg/litre. CONCLUSIONS: The BBL Crystal MRSA ID System is a valuable test for detecting oxacillin resistance in S aureus. Its major advantage is the short time (4-5 hours) required to perform the test when organisms are grown on tryptic soy agar or sheep blood agar. Difficulties may arise in borderline resistant isolates.
Telomerase expression in intracranial tumours: prognostic potential for malignant gliomas and meningiomas.
Authors: Falchetti M L , Pallini R , Larocca L M , Verna R , D'Ambrosio E
Published: January 2009

AIM: To evaluate the diagnostic value of telomerase expression in intracranial tumours. METHODS: 98 surgical specimens from different neoplasms were analysed by the telomeric repeat amplification protocol (TRAP) and the presence of telomerase compared with the histological diagnosis and the proliferation index. RESULTS: A high degree of positivity for telomerase activity was found in glioblastomas and atypical/anaplastic meningiomas. Telomerase activity was poorly detected in anaplastic astrocytomas. CONCLUSIONS: The TRAP assay seems to be a valuable index for identifying meningeal tumours with aggressive behaviour.
Human papillomavirus and the development of non-melanoma skin cancer.
Authors: Harwood C A , McGregor J M , Proby C M , Breuer J
Published: January 2009

Human papillomaviruses (HPV) are increasingly recognised as important human carcinogens. The best established association with human malignancy is that of high-risk mucosal HPV types and anogenital cancer. HPV-induced transformation of anogenital epithelia has been the subject of intense research which has identified the cellular tumour suppressor gene products, p53 and pRB, as important targets for the viral oncoproteins E6 and E7 respectively. Certain HPV types are also strongly associated with the development of non-melanoma skin cancer in the inherited disorder epidermodysplasia verruciformis (EV). However, in contrast with anogenital malignancy the oncogenic mechanisms of EV-HPV types remain uncertain, and there appears to be a crucial additional requirement for ultraviolet radiation. Cutaneous HPV types in the general population are predominantly associated with benign viral warts, but a role in non-melanoma skin cancer has recently been postulated. Polymerase chain reaction based HPV detection techniques have shown a high prevalence of HPV DNA, particularly in skin cancers from immunosuppressed patients and to a lesser extent in malignancies from otherwise immunocompetent individuals. No particular HPV type has yet emerged as predominant, and the role of HPV in cutaneous malignancy is unclear at present. It remains to be established whether HPV plays an active or purely a passenger role in the evolution of non-melanoma skin cancer.
Supplying commercial biomedical companies from a human tissue bank in an NHS hospital--a view from personal experience.
Authors: Gray N , Womack C , Jack S J
Published: January 2009

NHS histopathology laboratories are well placed to develop banks of surgically removed surplus human tissues to meet the increasing demands of commercial biomedical companies. The ultimate aim could be national network of non-profit making NHS tissue banks conforming to national minimum ethical, legal, and quality standards which could be monitored by local research ethics committees. The Nuffield report on bioethics provides ethical and legal guidance but we believe that the patient should be fully informed and the consent given explicit. Setting up a tissue bank requires enthusiasm, hard work, and determination as well as coordination between professionals in the NHS trust and in the commercial sector. The rewards are exiting new collaborations with commercial biomedical companies which could help secure our future.
Comparative study of seven commercial yeast identification systems.
Authors: Verweij P E , Breuker I M , Rijs A J , Meis J F
Published: January 2009

AIMS: To compare the performance of seven commercial yeast identification methods with that of a reference method, and to compare the costs of the commercial kits. METHODS: Clinical yeast isolates (n = 52), comprising 19 species, were identified using Vitek, Api ID 32C, Api 20C AUX, Yeast Star, Auxacolor, RapID Yeast Plus system, and Api Candida and compared with a reference method which employed conventional tests. RESULTS: The percentage of correctly identified isolates varied between 59.6% and 80.8%. Overall, the highest performance was obtained with Api Candida (78.8%) and Auxacolor (80.8%). Among germ tube negative yeast isolates, Auxacolor and Api Candida both identified 93.1% of isolates correctly. All systems failed to identify C norvegensis, C catenulata, C haemulonii, and C dubliniensis. In comparison with Auxacolor, the Api Candida is less expensive and requires less bench time. CONCLUSIONS: Auxacolor and Api Candida appeared to be the most useful systems for identification of germ tube negative yeast isolates in clinical microbiology laboratories, although one should be aware that several germ tube negative Candida species cannot be identified by these systems.
Endometrial pathology in postmenopausal tamoxifen treatment: comparison between gynaecologically symptomatic and asymptomatic breast cancer patients.
Authors: Cohen I , Perel E , Flex D , Tepper R , Altaras M M , Cordoba M , Beyth Y
Published: January 2009

AIMS: To evaluate whether endometrial pathology is more likely to be diagnosed in gynaecologically symptomatic rather than in gynaecologically asymptomatic postmenopausal breast cancer patients with tamoxifen treatment; and to evaluate the possible influence of various clinical factors on the incidence of endometrial pathology. METHODS: Endometrial histological findings, transvaginal ultrasonographic endometrial thickness, demographic characteristics, health habits, and risk factors for endometrial cancer were compared between 14 gynaecologically symptomatic (group I) and 224 gynaecologically asymptomatic (group II) postmenopausal breast cancer patients with tamoxifen treatment. RESULTS: Overall, 28.6% of the study population had endometrial pathology. The incidence of overall positive endometrial histological findings was significantly higher in group I than in group II (92.9% v 24.6%, p < 0.0001). Atrophic endometrium was more common in group II than in group I (75.3% v 7.1%, p < 0.0001). Most other endometrial pathology was significantly more common in group I than in group II (endometrial hyperplasia, 35.7% v 5.6%, p < 0.0001; endometrial polyps, 35.7% v 13.4%, p < 0.0111; endometrial carcinoma, 21.5% v 0.9%, p < 0.0001). Endometrial pathology appeared considerably later in the gynaecologically asymptomatic patients than in gynaecologically symptomatic patients (p = 0.0002). Vaginal bleeding or spotting occurred exclusively in group I. The incidence of endometrial pathology in the entire study population was consistent with that reported elsewhere, and higher than that reported for healthy postmenopausal women. CONCLUSIONS: Endometrial pathology is more likely to be diagnosed in gynaecologically symptomatic postmenopausal breast cancer patients with tamoxifen treatment, and after a shorter duration of time, than in gynaecologically asymptomatic patients.
Mutations of p53 gene and SV40 sequences in asbestos associated and non-asbestos-associated mesotheliomas.
Authors: Mayall F G , Jacobson G , Wilkins R
Published: January 2009

AIM: To examine mesotheliomas for a possible relation between p53 immunostaining, p53 gene mutation, simian virus 40 (SV40), and asbestos exposure. METHODS: Paraffin sections from 11 mesotheliomas were used for p53 immunostaining and also to extract DNA. This was analysed for the presence of mutations in exons 5 to 8 of the p53 gene using a "cold" single strand conformational polymorphism method, together with sequencing. The DNA from the paraffin sections was also used to search for SV40 sequences. A 105 base pair segment at the 3' of the SV40 large T antigen (Tag) was targeted and any PCR amplification products were sequenced to confirm that they were of SV40 origin. EDAX electron microscopic differential mineral fibre counts were performed on dried lung tissue at a specialist referral centre. RESULTS: The fibre counts showed that seven of the mesotheliomas were associated with abnormally high asbestos exposure. Of these, two showed p53 immunostaining, none showed p53 gene mutation, and five showed SV40. Of the four other mesotheliomas, three showed p53 immunostaining, one showed a (silent) p53 mutation, and none showed SV40. The difference in frequency of SV40 detection was significant at the p < 0.05 level. CONCLUSIONS: Immunostaining for the p53 gene was relatively common but p53 mutations were rare in this series. SV40 virus sequence was detected in five of seven asbestos associated mesotheliomas but in none of the non-asbestos-associated mesotheliomas. This suggests there may be a synergistic interaction between asbestos and SV40 in human mesotheliomas. A study with a larger number of cases is needed to investigate these observations further.
An unusual presentation of systemic mastocytosis.
Authors: Kennedy R J , Scoffield J L , Garstin W I
Published: January 2009

A 47 year old man presented with mastocytosis, a disease process characterised by proliferation of mast cells. The clinical features and outcome are discussed.
Intraglomerular metastasis: a necropsy study.
Authors: Sridevi D , Jain D , Vasishta R K , Joshi K
Published: January 2009

Intraglomerular metastasis is a rare phenomenon. Four cases are reported here. The primary malignancies in these four cases were squamous cell carcinoma of the lung, adenocarcinoma of pancreas, haematological malignancy with a malignant intrapulmonary teratoma, and undifferentiated pleural mesothelioma. There was no significant renal functional impairment in any case except for mild proteinuria in one. Histopathology showed tumour cells in the mesangium, in the glomerular tufts replacing the endothelial cells, as well as in an extracapillary location replacing the parietal cells. In one case, tumour cells formed crescent-like structures. Such tumour deposits were better appreciated with special stains. The presence of intraglomerular metastasis indicates dissemination of the malignancy and hence a poor prognosis even though there is no significant impairment of renal function.
Adenocarcinoma arising within a tailgut cyst: clinicopathological description and follow up of an unusual case.
Authors: Graadt van Roggen J F , Welvaart K , de Roos A , Offerhaus G J , Hogendoorn P C
Published: January 2009

Full clinicopathological details and clinical follow up of a case of malignant transformation within a tailgut cyst are presented. A 43 year old woman presented with signs and symptoms of an imminent threatened abortion. Routine examination identified a coincidental, asymptomatic retrorectal/presacral mass. Following imaging studies, surgical resection was carried out and an adenocarcinoma arising within a pre-existent tailgut cyst was identified by microscopy. Four years later the patient presented with neurological symptoms consistent with local recurrence of the tumour. Surgical biopsies confirmed this diagnosis and she was subsequently started on chemotherapy. She died soon after from a cause unrelated to the disease, after declining further active intervention. Differential diagnosis of such cases includes (cystic) teratoma, epidermal cyst, rectal duplication cyst, anal gland cyst and carcinoma, extension of local carcinoma, and metastatic disease. It is recommended that these lesions be completely excised when detected incidentally.
Coexistent gastric MALT lymphoma and Kaposi sarcoma in an HIV positive patient.
Authors: Chetty R , Pillay S V
Published: January 2009

A 47 year old HIV positive male presented with haematemesis and epigastric pain. A gastrectomy was performed for intractable bleeding. The cause of the haematemesis proved to be a Kaposi sarcoma of the stomach which had resulted in mucosal ulceration. Several other smaller foci of Kaposi sarcoma were also present. Coexistent with the Kaposi sarcoma was a dense lymphoid infiltrate with lymphoid follicles and reactive germinal centres. Centrocyte-like cells caused marked effacement and destruction of gastric glands with the formation of lymphoepithelial lesions, typical of a MALT lymphoma. These cells were of B cell lineage and some expressed the HIV antigen, p24. Follicular dendritic cells and macrophages within germinal centres were also p24 positive. Immunohistochemistry and in situ hybridisation did not detect Epstein-Barr virus. Although Helicobacter pylori was not identified by light microscopy in the sections sampled, this does not preclude its possible role, with other cofactors such as HIV, in the causation of the MALT lymphoma.