bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathology of deaths associated with "ecstasy" and "eve" misuse.
Authors: Milroy C M , Clark J C , Forrest A R
Published: June 2007

AIMS: To study the postmortem pathology associated with ring substituted amphetamine (amphetamine derivatives) misuse. METHODS: The postmortem findings in deaths associated with the ring substituted amphetamines 3,4-methylenedioxymethyl-amphetamine (MDMA, ecstasy) and 3,4-methylenedioxyethylamphetamine (MDEA, eve) were studied in seven young white men aged between 20 and 25 years. RESULTS: Striking changes were identified in the liver, which varied from foci of individual cell necrosis to centrilobular necrosis. In one case there was massive hepatic necrosis. Changes consistent with catecholamine induced myocardial damage were seen in five cases. In the brain perivascular haemorrhagic and hypoxic changes were identified in four cases. Overall, the changes in four cases were the same as those reported in heart stroke, although only two cases had a documented history of hyperthermia. Of these four cases, all had changes in their liver, three had changes in their brains, and three in their heart. Of the other three cases, one man died of fulminant liver failure, one of water intoxication and one probably from a cardiac arrhythmia associated with myocardial fibrosis. CONCLUSIONS: These data suggest that there is more than one mechanism of damage in ring substituted amphetamine misuse, injury being caused by hyperthermia in some cases, but with ring substituted amphetamines also possibly having a toxic effect on the liver and other organs in the absence of hyperthermia.
Comparison of histological and biochemical hepatic iron indexes in the diagnosis of genetic haemochromatosis.
Authors: George P M , Conaghan C , Angus H B , Walmsley T A , Chapman B A
Published: June 2007

AIMS: To compare a histological hepatic iron index with a biochemical hepatic iron index, derived from atomic absorption spectroscopy measurements of hepatic iron content, for the diagnosis of genetic haemochromatosis (GH). METHODS: Histological sections of liver biopsy specimens from 70 subjects, who had previously had their biochemical hepatic iron index measured, were examined. The iron stores were scored to derive a histological hepatic iron index and were also graded from 0 to 4 by a standard grading system. The case history of each patient was then reviewed to establish a definitive clinical diagnosis and patients were classified as GH, non-GH or indeterminate. RESULTS: There were 26 cases of GH, 40 cases of non-GH and four indeterminate cases in whom a definite clinical diagnosis was not established. Using a biochemical hepatic iron index cut off level of 2.0, two cases were misclassified, with one case of GH having a biochemical hepatic iron index of 1.8 and one non-GH case having a biochemical hepatic iron index of 3.1. This could not have been improved by altering the cut off level. Using the recommended cut off level of 0.15, the histological hepatic iron index was raised in all cases of GH, but was also increased in 11 of the 40 non-GH patients. The specificity of this histological index can be improved by increasing the cut off level to 0.30. A histological iron grade of > or = 3 is more specific than the histological index but has a lower sensitivity, which particularly affects the diagnosis of younger patients with GH. CONCLUSIONS: The biochemical hepatic iron index is a reliable method for establishing a diagnosis of homozygous GH. In contrast, the histological hepatic iron index as originally described is non-specific and does not reliably distinguish patients with GH from others with a raised hepatic iron index due to other causes. The specificity of this index can be improved by increasing the cut off level used, but the discrimination provided by the histological index is still inferior to that provided by the biochemical hepatic iron index.
Helicobacter pylori infection in patients with Barrett's oesophagus: a prospective immunohistochemical study.
Authors: Ricaurte O , Fléjou J F , Vissuzaine C , Goldfain D , Rotenberg A , Cadiot G , Potet F
Published: June 2007

The prevalence of Helicobacter pylori infection in patients with Barrett's oesophagus was studied prospectively. A sensitive immunohistochemical staining of H pylori was performed in oesophageal and gastric biopsies of 73 patients from a surveillance group with this condition. H pylori was detected in 11 cases of Barrett's mucosa (15%) and in 26 gastric mucosa specimens (35.6%). All cases positive in Barrett's mucosa were also positive in the stomach. In Barrett's oesophagus, H pylori was never found on specialised epithelium. The percentage of Barrett's mucosa showing inflammatory changes was similar in specimens with and without H pylori, both for chronic (81% v 79%) and acute (9% v 10%) infiltrates. These results indicate that H pylori infection does not play an aetiological role in Barrett's oesophagus and that colonisation of the metaplastic mucosa by this bacteria is related with the presence of gastric type mucosa in the oesophagus and of H pylori infection in the stomach.
Thymidine phosphorylase expression in Kaposi sarcoma.
Authors: Dada M A , Boshoff C H , Comley M A , Turley H , Schneider J W , Chetty R , Gatter K C
Published: June 2007

AIMS: To examine the immunohistochemical distribution of thymidine phosphorylase (TP) in all clinicopathological subtypes of Kaposi sarcoma. METHODS: Thirty two biopsy specimens of Kaposi sarcoma (29 patients) were studied. Six of these patients represented classic, six endemic, eight HIV associated, seven post-immunosuppression/transplant related, and two unclassified variants of Kaposi sarcoma. The average age was 49 years (range 22-83 years) and the male: female ratio 24:5. Four samples of angiosarcoma and one of spindle cell haemangio-endothelioma were stained in parallel. All specimens were fixed in formalin, embedded in paraffin wax and processed routinely. Immunohistochemistry was carried out using an antibody directed against CD31 (JC70) and the monoclonal antibody P-GF.44C against TP. RESULTS: All biopsy specimens showed immunoexpression for TP. The spindle cell component stained more strongly than newly formed endothelium lined vessels and normal, resident vessels at a distance from the lesions. CONCLUSIONS: The strong immunoexpression of TP suggests up-regulation of TP and a role for TP in angiogensis in Kaposi sarcoma. The mechanism for the up-regulation of TP remains unknown, but viral infections may trigger it. The differential staining of the various cell components of Kaposi sarcoma also suggest that TP either plays a role in the differentiation and maturation of Kaposi sarcoma or is a reflection of such changes.
The pathology of cornea in Tangier disease (familial high density lipoprotein deficiency).
Authors: Winder A F , Alexander R , Garner A , Johnston D , Vallance D , McCreanor G , Frohlich J
Published: June 2007

AIMS: To clarify the underlying causes of corneal opacification in Tangier disease. METHODS: Both corneas were removed at death from a 62 year old man with Tangier disease, and were examined by direct and transmission electron microscopy, histochemistry, biochemical analysis by thin-layer and gas-liquid chromatography after extraction, and by differential scanning calorimetry. RESULTS: Membranous inclusions in the stroma were seen on transmission electron microscopy. Direct analysis confirmed enrichment with phospholipids and cholesterol, with acyl patterns and proportions as ester broadly similar to those of normal cornea. Tangier cornea showed major thermotropic phase transitions in the range 28-37 degrees C, peak 30-33 degrees C, extending above profiles of normal clear cornea and without the complexity of those seen with cornea with heavy arcus involvement. CONCLUSIONS: Lipid accumulation underlies corneal opacification in Tangier disease. The excess material is mainly phospholipid and cholesterol esters. As at other sites which are below body core temperature, notably tonsil, accumulation may be enhanced by local impaired mobilisation of material as the phase transitions of the excess lipid present extend above ambient corneal temperatures.
Cellular distribution of androgen receptors in the liver.
Authors: Hinchliffe S A , Woods S , Gray S , Burt A D
Published: June 2007

In order to determine the cellular distribution of androgen receptors (AR) in normal liver and to examine whether phenotypic changes occur in a variety of non-neoplastic liver diseases, cryostat sections of explanted livers removed from 52 consecutive patients undergoing orthotopic transplantation were immunostained using an anti-androgen receptor monoclonal antibody. In histologically normal liver, AR was immunolocalised to the nuclei of hepatocytes. The proportion of positive hepatocytes varied from about 50% to greater than 90%. Staining, of variable intensity, was restricted to parenchymal cells with no evidence of zonal heterogeneity with respect to labelling intensity. In tissue from patients with biliary cirrhoses and in some cases of alcoholic cirrhosis, labelling for AR was observed in areas of ductular metaplasia but not in areas of "typical" ductular reaction (ductular proliferation). Otherwise, no consistent abnormalities in immunolabelling were seen in any of the diseased livers.
Anti-GM1 antibodies in polyneuropathies of unknown origin.
Authors: Finsterer J , Muellbacher W , Halbmayer W M , Fischer M , Mamoli B
Published: June 2007

This study was undertaken to determine whether anti-GM1 titres are raised in polyneuropathies of unknown origin and whether determination of these titres is useful for diagnosing these conditions. The study population comprised 20 controls (aged 36-88 years), 12 patients with polyneuropathies of known origin (aged 31-81 years) and 15 patients with polyneuropathies of unknown origin (aged 40-77 years). Antibody levels were measured using a commercial GM1 enzyme linked immunosorbent assay kit (Buehlmann Laboratories). Mean anti-GM1 IgG and IgM antibody titres were not raised in patients with polyneuropathies of unknown origin. Anti-GM1 IgG antibody titres were raised in one and GM1 IgM antibody titres in none of the patients with polyneuropathies of unknown origin. In conclusion, GM1 antibody levels are rarely raised in polyneuropathies of unknown origin and probably play a minor role in the pathogenesis of these conditions.
Immunocytochemistry of mucosal changes in patients infected with the intestinal nematode Strongyloides stercoralis.
Authors: Coutinho H B , Robalinho T I , Coutinho V B , Almeida J R , Filho J T , King G , Jenkins D , Mahida Y , Sewell H F , Wakelin D
Published: June 2007

AIM: To investigate the immunopathological changes in duodenal tissues induced by strongyloidiasis and to relate these to degrees of clinical severity. METHODS: Tissues taken from 21 patients showing mild, moderate or severe symptoms of strongyloidiasis, and from non-infected controls, were sectioned and stained immunocytochemically for IgA, secretory component (SC) and HLA-DR. Immunopathology was assessed by changes in numbers, intensity and distribution of stained cells. RESULTS: Parasitised individuals showed villous atrophy and crypt hyperplasia. There was notable infiltration of the lamina propria by IgA positive plasma cells and of the epithelium by intraepithelial lymphocytes. Infection was also associated with increased expression of SC and decreased expression of HLA-DR in epithelial cells. Changes in all parameters correlated with degree of clinical severity. CONCLUSIONS: Profound mucosal changes are induced by strongyloidiasis. Some are analogous to those seen in coeliac disease, but others seem quite unusual. It is likely that these changes are functionally related to the immunopathophysiological consequences of infection seen in patients with severe disease.
Ki-67 expression in early prostate cancer and associated pathological lesions.
Authors: Feneley M R , Young M P , Chinyama C , Kirby R S , Parkinson M C
Published: June 2007

AIM: To assess cell proliferation in early prostate cancer and associated pathological lesions. METHODS: Using the Ki-67 antibody, the cell proliferation index was measured in early stage prostatic carcinoma in 37 incidental tumours diagnosed at transurethral prostatectomy (TURP) and in 20 low volume cancers treated by radical prostatectomy. Proliferation indexes have also been measured in areas of normal peripheral zone, transition zone hyperplasia, atrophic appearing lobules, and high grade prostatic intraepithelial neoplasia in the radical prostatectomy cases. RESULTS: In the TURP series the proliferation index correlated with grade and stage. Logistic regression analysis, however, showed that Gleason grade was the most reliable predictor of biopsy proven residual disease and clinical progression. In the radical series transition zone carcinoma the proliferation index was half that of peripheral zone carcinoma. The atrophic lobules also showed a high proliferation index of the same order as seen in the peripheral zone carcinoma. Normal peripheral zone showed the lowest proliferation index and in hyperplastic transition zone it was also less than the other areas. CONCLUSIONS: There is only limited support for the correlation of proliferation index with grade in early stage prostatic carcinoma. The findings do not suggest that proliferation index adds to the prognostic information given by grade and stage in pT1 disease. The significant difference in proliferation index in transition zone and peripheral zone carcinomas supports the morphological distinction of these tumour types and is consistent with differences in biological behaviour. The high proliferation index in lobules considered morphologically atrophic is reminiscent of previous observations in which carcinoma was spatially associated with atrophy.
Immunoglobulin light chain mRNA detected by in situ hybridisation in diagnostic fine needle aspiration cytology specimens.
Authors: Stewart C J , Farquharson M A , Kerr T , McCorriston J
Published: June 2007

AIMS: To demonstrate expression of immunoglobulin light chain mRNA in diagnostic fine needle aspiration (FNA) cytology specimens using an in situ hybridisation (ISH) technique; and to evaluate ISH in a series of reactive lymphoid proliferations and malignant lymphomas. METHODS: Forty diagnostic FNA specimens showing a lymphoid cell population were examined for immunoglobulin light chain mRNA expression using ISH. Aspirates were obtained from lymph node (n = 34), salivary gland (n = 3), subcutaneous tissue, thyroid and breast (n = 1 each). The cases included 20 B cell lymphomas, five cases of Hodgkin's disease and 15 reactive lymphoid proliferations. Comparison with light chain immunoreactivity was made in 36 cases and histological correlation from biopsy material was available in 24. RESULTS: Immunoglobulin light chain restriction was demonstrated in 14 of 20 B cell lymphomas using ISH and in six of 17 B cell lymphomas using immunocytochemistry. A polytypic pattern of light chain expression was observed in four of five cases of Hodgkin's disease with both techniques, and in 12 of 15 and 11 of 14 reactive lymphoid proliferations using ISH and immunocytochemistry, respectively. CONCLUSIONS: The assessment of immunoglobulin light chain expression is a useful adjunct to morphology in the diagnosis of reactive and malignant lymphoid proliferations in FNA specimens. Light chain restriction can be shown using either immunocytochemistry or ISH, but the latter is more sensitive in the diagnosis of B cell lymphoma.
The value of immunohistochemistry on paraffin wax embedded tissue sections in the differentiation of small lymphocytic and mantle cell lymphomas.
Authors: Singh N , Wright D H
Published: June 2007

AIMS: To determine whether immunohistochemistry applied to paraffin wax embedded biopsy tissue can be used to distinguish between B-small lymphocytic lymphoma (B-SLL) and mantle cell lymphoma (MCL). METHODS: Formalin fixed, paraffin wax embedded tissue blocks of 12 cases of B-SLL and 12 cases of MCL were retrieved from the files of the Department of Pathology, Southampton University Hospitals Trust. Following antigen retrieval, where appropriate, sections were stained for CD3, CD5, CD20, CD23, CD43, Cyclin D, PGP9.5, and MIB1 using a streptavidin-biotin complex technique. RESULTS: CD20 stained the neoplastic cells of B-SLL and MCL, and CD3 labelled the reactive T cells in these tumours. In B-SLL, the T cells were generally dispersed among the tumour cells, whereas in MCL they often formed bands around tumour cell nodules. CD5 could be detected on T cells, following antigen retrieval. The level of expression on B cells of B-SLL and MCL was generally too low to allow detection in paraffin wax embedded tissues. CD23 stained B-SLL but not MCL. However, it could be detected in only five of the 12 cases of B-SLL. CD43 could be detected in most cases of B-SLL and MCL. It is not, therefore, of value in distinguishing between these tumours. It will, however, help in the differentiation of B-SLL and MCL from other low grade B cell lymphomas, such as follicle centre cell and marginal zone lymphomas. Cyclin D was expressed in all of the MCL but in none of the B-SLL. PGP9.5 showed reactivity in most cases of MCL and much weaker reactivity in B-SLL. The proliferation indexes of MCL were generally higher than those of B-SLL, as measured by MIB1 labelling. Both tumours, however, showed a wide range of values and considerable overlap. CONCLUSION: Staining for Cyclin D is the most reliable immunohistochemical mean of differentiating between B-SLL an MCL. High levels of PGP9.5, expressed in MCL, may be related to the degradation of Cyclin D by the ubiquitin pathway.
Primary extramedullary plasmacytoma of the liver.
Authors: Demirhan B , Sökmensüer C , Karakayali H , Güngen Y , Doğan A , Haberal M
Published: June 2007

Extramedullary plasmacytoma of the liver is a rare tumour, only two cases of which have been reported so far. A third case arising in a 22 year old woman, who presented with abdominal pain and enlargement of the liver, is described. Ultrasound and a computed tomography scan showed a solitary hepatic mass, 12 cm diameter, involving both lobes of the liver. Serum immunoelectrophoresis revealed an IgG kappa monoclonal gammopathy. Histologically, the tumour was composed of mature plasma cells with mild atypia. The plasma cells infiltrated the liver parenchyma and showed kappa light chain restriction. The monoclonal nature of the tumour was also demonstrated by PCR amplification of the immunoglobulin heavy chain genes. There was no evidence of bone involvement and repeated bone marrow aspirates and biopsy specimens were normal. The patient was treated with eight courses of chemotherapy. One year after diagnosis, the patient is well, the size of the tumour has decreased and the paraproteinaemia has disappeared.
Re-engineering pathology: an IT solution to the data conundrum.
Authors: Simmons M D , Nadin J , Isaac M
Published: June 2007

AIMS: To develop a simple process for data transfer between disparate laboratory computer systems, and to assist in the rationalisation of services while maintaining or improving clinical care. METHODS: Using existing hardware and software in the laboratories, data manipulation was reduced in the sending and receiving laboratories by using scripting languages to perform the import and export routines from disparate laboratory systems. RESULTS: Data exchange between Carmarthen and Swansea laboratories (12,000 specimens per year) was achieved in a semiautomatic manner for most specimens. Turnaround times were equalled or improved with the new arrangements, and significant reductions were obtained in staff costs. CONCLUSIONS: Data exchange between disparate laboratory computer systems can be achieved inhouse using simple systems. The process offers a route to assist in the management of reducing resources. The process could be readily utilised in other pathology disciplines or with any data integration exercise. There is scope for further enhancement that is currently being investigated.
Completeness of reporting on prognostic factors for breast cancer: a regional survey.
Authors: Dey P , Woodman C B , Gibbs A , Coyne J
Published: June 2007

BACKGROUND: Effective management of breast cancer is dependent on adequate pathological reporting of the surgical specimen. OBJECTIVE: To describe the frequency with which histopathological features of known prognostic importance are routinely recorded. STUDY POPULATION: 885 cases of invasive breast cancer diagnosed in NHS laboratories in Lancashire and Greater Manchester. METHODS: Pathology reports were reviewed for details for tumour histological type, size, and grade, the presence or absence of tumour in blood or lymphatic vascular channels, and a comment on the proximity of tumour to the lines of surgical excision. Laboratories were categorised according to their throughput of cases of breast cancer, involvement in the breast screening programme, and whether they were attached to a teaching hospital. RESULTS: Histological type, tumour size, presence or absence of tumour in vascular channels, and adequacy of excision were recorded for 843 (95%), 803 (91%), 436 (49%), and 761 (86%) cases, respectively. Non-screening and low throughput laboratories were significantly less likely to record certain histopathological features. No significant differences were observed between teaching and non-teaching hospitals. CONCLUSIONS: The substantial interlaboratory variation in the histopathological reporting of breast cancers can, in part, be related to throughput of cases and involvement in the breast screening programme.
Value of routine, non-targeted biopsies in the diagnosis of gastric neoplasia.
Authors: Cadman B , Dixon M F , Wyatt J I
Published: June 2007

AIM: To explore how often a diagnosis of gastric neoplasia is made on routine, non-targeted biopsies taken for determination of Helicobacter pylori status, compared with directed biopsies from endoscopically abnormal mucosa. METHODS: Records of all patients with a biopsy diagnosis of gastric cancer or dysplasia during a two year period were reviewed to determine whether the biopsy had been targeted at an area of mucosal abnormality, and whether there was any evidence of dysplasia or malignancy before endoscopy. RESULTS: Of the 8907 endoscopic examinations that included biopsy, histology showed malignancy in 115 cases and dysplasia in 20. Of these, in 128 cases the biopsies were targeted from focal abnormal areas of mucosa, and six were from areas of diffuse mucosal thickening. In one case, adenocarcinoma was diagnosed in a patient with a "normal" endoscopic appearance; this patient was undergoing repeat endoscopy for previous dysplasia. CONCLUSIONS: Gastric malignancy or dysplasia was detected histologically in 1.5% of endoscopies that included biopsy. The performance of routine biopsies not targeted at a visible lesion from patients without previous diagnosis of neoplasia did not increase the detection of gastric malignancy. Such biopsies are indicated, however, if histological aspects of a patient's gastritis (such as atrophy or intestinal metaplasia) influence the clinical management, as in the treatment of helicobacter gastritis.
Beta 2 microglobulin haemodialysis related amyloidosis: distinctive gross features of gastrointestinal involvement.
Authors: Shimizu M , Manabe T , Matsumoto T , Monobe Y , Hirokawa M , Moriya T , Iida M
Published: June 2007

Two cases of beta 2 microglobulin amyloidosis following long term haemodialysis found during necropsy are reported. The patients were 59 and 65 year old Japanese men, respectively. In both cases, systemic distribution of beta 2 microglobulin amyloid deposits was observed. The gastrointestinal tract including the stomach, small intestine, and colon showed the distinctive gross feature of rippled appearance, which was characterised by serosal wrinkles along the muscle layer arrangement. These areas were confirmed to contain deposits of beta 2 microglobulin in the muscularis propria. Although the outline of the muscle layers was preserved, most muscle fibres, encircled by the amyloid deposits, were atrophic or had disappeared microscopically. In neither case could a definite diagnosis of amyloidosis be made while the patient was alive. Interestingly, the oesophagus presented less involvement compared to the remainder of the gastrointestinal tract. In comparison with the AA or AL type of amyloidosis, beta 2 microglobulin haemodialysis related amyloidosis showed a rippled appearance of the serosal rather than mucosal changes, which may explain the difficulty in diagnosing amyloid deposits using biopsies of the gastrointestinal tract.
To operate or not to operate? The value of fine needle aspiration cytology in the assessment of thyroid swellings.
Authors: Leonard N , Melcher D H
Published: June 2007

AIMS: To evaluate all thyroid fine needle aspirations (FNA) done over a six year period to assess the accuracy and value of the technique. METHODS: There were 335 FNAs of which 184 had subsequent histology and 49 others had clinical follow up, providing 233 patients for analysis. All cytology and histology was reviewed with no significant alterations in diagnosis. The FNAs were classified into three groups: benign, suspicious (recommend excision), and malignant. The histology and medical records were reviewed to determine whether the cytology was accurate. RESULTS: There were 130 benign FNAs, 126 had non-malignant histology or normal clinical follow up, and four had malignancies on histology (two lymphomas, one follicular carcinoma, and one carcinoma not otherwise specified). There were 45 suspicious FNAs. Of these five had either follicular or papillary carcinoma, 14 had follicular adenomas, and 26 had colloid nodular goitres or normal clinical follow up. Of the 21 malignant FNAs, 11 had carcinoma and 10 had either a non-malignant histology or normal follow up. There were 126 true negatives, 30 true positives, 4 false negatives, and 36 false positives. This gives a sensitivity of 88%, a specificity of 78%, a positive predictive value of 46%, a negative predictive value of 97%, and an accuracy of 80%. CONCLUSIONS: FNA cytology of the thyroid has a high negative predictive value, which is useful to reassure the majority of patients presenting with thyroid enlargement. However, a negative FNA should never exclude malignancy if there is a strong clinical suspicion. If this rule is adhered to a large number of patients will be spared unnecessary surgery and no malignant nodule will go untreated.
Gastric outflow obstruction caused by gall stones and leading to death by complex metabolic derangement.
Authors: Wight C O , Seed M , Yeo W W , McCulloch T A
Published: June 2007

A 67 year old woman was admitted with a three week history of vomiting, having become increasingly confused for three days. Investigations revealed deranged serum biochemistry consistent with a combination of a diabetic non-ketotic hyperosmolar state and a metabolic alkalosis consistent with gastric outflow obstruction. She was treated with intravenous saline, intravenous insulin, and subcutaneous heparin, but did not improve clinically and had an asystolic cardiac arrest the following day; she was transferred to the intensive care unit and despite treatment with inotropes she died 40 hours after admission. Necropsy revealed that the stomach was massively dilated with gas and stomach contents, and contained many small black faceted gall stones. In addition a large nonfaceted brown-yellow gall stone was wedged in the pyloric antrum causing total obstruction. The patient had died from a complex metabolic derangement including non-ketotic hyperosmotic diabetic coma and metabolic alkalosis precipitated by the acute gastric outflow obstruction complicated by previously undiagnosed type II diabetes mellitus.
Primary epithelioid haemangioendothelioma of the liver: case report and review of the literature.
Authors: Pokharna R K , Garg P K , Gupta S D , Dutta U , Tandon R K
Published: June 2007

A 31 year old female patient presented with a one and a half year history of pain in the upper abdomen. The pain was mild, constant, dull aching, and increased with change in posture or sudden movements. There was no definite relation to meals. She also had a lump in the right upper quadrant, which had been gradually increasing in size over three months. She had mild anorexia and reported a 5 kg weight loss over one year. She had no history of intake of oral contraceptive drugs, exposure to vinyl chloride, thorotrast or any other industrial toxin. Ultrasonography of the abdomen revealed multiple space occupying lesions of altered echotexture in both lobes of the liver. The portal venous system and hepatic vascular system were normal. Computed tomography of the abdomen confirmed the ultrasound findings. Histopathology was diagnostic for primary epithelioid haemangioendothelioma; the first such case reported from India. The patient has been put on a waiting list for a liver transplant.
A solitary benign lymphoid polyp of the rectum in a 51 year old woman.
Authors: Lloyd J , Darzi A , Teare J , Goldin R D
Published: June 2007

A 51 year old woman presented with rectal bleeding from a mass lying just above the dentate line. Multiple biopsies were taken before the diagnosis of a benign lymphoid polyp was made. This is a rare condition that more commonly presents in children and poses a diagnostic challenge.
A review of 50 consecutive cytology cell block preparations in a large general hospital.
Authors: Mayall F , Chang B , Darlington A
Published: June 2007

AIMS: To review consecutive cell block preparations of cytological specimens in a large general hospital. METHODS: 50 cell blocks were made over an 18 month period in which about 1900 fine needle aspirations (FNAs) were performed. The aspirator was a cytologist or, for image guided FNAs, a radiologist with a cytologist at hand to collect the specimen. Forty eight cell blocks were from FNAs and two were from serous fluids. RESULTS: The cellularity of the cell blocks was inadequate in only four preparations. The main motive for making cell blocks was to obtain tissue for immunohistochemistry. This was performed on 28 cases and a total of 107 immunostained sections were produced. The most common diagnostic dilemma was between carcinoma and melanoma, and the second most common between carcinoma and lymphoma. Consequently cytokeratin, S-100, and LCA were the most frequently used antibodies. At least one of these three antibodies was positive in 17 cases. Five cases were immunostained only for prognostic breast markers. CONCLUSIONS: The use of cell block immunohistochemistry is a reliable and technically unsophisticated aid in the cytological examination of tumours other than lymphomas. Success depends on having highly experienced aspirators that reliably obtain sufficiently cellular material.
Mutation analysis of the p53, APC, and p16 genes in the Barrett's oesophagus, dysplasia, and adenocarcinoma.
Authors: González M V , Artímez M L , Rodrigo L , López-Larrea C , Menéndez M J , Alvarez V , Pérez R , Fresno M F , Pérez M J , Sampedro A , Coto E
Published: June 2007

AIMS: To study the loss of heterozygosity and the presence of mutations at the p53, p16/CDKN2, and APC genes in Barrett's oesophagus, low grade dysplastic oesophageal epithelium, and adenocarcinoma of the oesophagus; to relate the presence of alterations at these genes with the progression from Barrett's oesophagus to adenocarcinoma. METHODS: DNA was extracted from paraffin blocks containing tissue from Barrett's oesophagus (12 samples), low grade dysplasia (15 cases), and adenocarcinoma (14 cases). Loss of heterozygosity (LOH) at the p53, p16, and APC genes was determined by comparing the autoradiographic patterns of several microsatellite markers between the normal tissue and the malignant tissue counterpart. SSCP was used to determine the presence of mutations at p53 (exons 5 to 8), p16 (exon 2), and APC. Homozygous deletion of the p16 gene was defined through polymerase chain reaction followed by Southern blot. RESULTS: LOH at the p53, p16, and APC genes was not observed in Barrett's oesophagus without dysplasia, and increased to 90% (p53), 89% (p16), and 60% (APC) in the adenocarcinomas. The p53 gene was mutated in only two adenocarcinomas (codons 175 and 245). In one case a mutation at the APC gene (codon 1297) was found. No patient had mutation at the second exon of p16. However, this gene was homozygously deleted in three of the 12 adenocarcinomas. CONCLUSIONS: The tumour suppressor genes p53, p16, and APC are often deleted in adenocarcinomas derived from Barrett's oesophagus. Mutations at these genes are also found in the adenocarcinomas, including the homozygous deletion of the p16 gene. However, the absence of genetic alterations in the Barrett's oesophagus and the low grade dysplastic epithelia suggest that mutations at these genes develop later in the progression from Barrett's oesophagus to adenocarcinoma.
Analysis of HPV16, 18, 31, and 35 DNA in pre-invasive and invasive lesions of the uterine cervix.
Authors: Pirami L , Giachè V , Becciolini A
Published: June 2007

AIMS: To analyse the physical state of different human papillomavirus (HPV) DNAs in 55 intraepithelial and invasive HPV associated cervical neoplasms. METHODS: Restriction analysis, using a panel of five HPV type specific enzymes, was carried out for each sample; this was followed by Southern blot analysis. RESULTS: Six (25%) of 24 cervical intraepithelial neoplasms had integrated DNA of different HPV types. In contrast, integration was detected in 25 (81%) of 31 cervical carcinomas. Tumour samples revealed differences in the integration profile of HPV16 and the other HPV types. Six (26%) of 23 HPV16 associated cancers contained only episomal DNA. In contrast, all eight tumours containing HPV18, 31, or 35 revealed integrated DNA exclusively. CONCLUSIONS: The results suggest that in advanced cervical intraepithelial neoplasia lesions, a subset of lesions can be identified in which the viral genome is integrated and there is a greater risk of malignant progression. In addition, HPV16 DNA was not present in the integrated form in 26% of tumours, suggesting that integration and subsequent inactivation of the transcriptional regulator, E2, are not essential steps for the development of HPV16 associated carcinoma. In this respect, the behaviour of HPV16 associated tumours is different from HPV18, 31, and 35 associated tumours, where the viral genome is always present in the integrated form.
Hemichannels in cardiomyocytes open transiently during ischemia and contribute to reperfusion injury following brief ischemia
Authors: Shintani-Ishida Kaori , Uemura Koichi , Yoshida Ken-ichi
Published: June 2007

The aim of this study was to investigate changes in hemichannel activity during in vitro simulated ischemia [oxygen-glucose deprivation (OGD)] and the contribution of hemichannels to ischemia-reperfusion injury in rat neonatal cardiomyocytes. Dye uptake assays showed that hemichannels opened as OGD progressed, peaking after 1 h, and then closed, returning to the pre-OGD state after 2 h of OGD. The increase in dye uptake after 1 h of OGD was inhibited by hemichannel blockers (lanthanum chloride and a connexin 43 mimetic peptide, Gap26). During OGD, intracellular Ca2+concentration ([Ca2+]i) began to increase after 1 h and reached several micromolar after 2 h. After 1 h of OGD, Gap26 inhibited the increases in hemichannel activity and [Ca2+]i. In contrast, dantrolene [an endo(sarco)plasmic reticulum Ca2+release inhibitor] suppressed the increase in [Ca2+]i, but not in hemichannel activity. After 2 h of OGD, the combined administration of 2′,4′-dichlorobenzamil and dantrolene reduced [Ca2+]ito <1 μM and increased hemichannel activity to the level attained after 1 h of OGD. Simulated ischemia-reperfusion, induced by 1 h of OGD followed by 2 h of recovery, reduced cell viability to 54% of the control level. The addition of Gap26 to OGD medium improved viability to 80% of the control level. In conclusion, this study demonstrated that 1) hemichannels open transiently during OGD, 2) closure of hemichannels, but not their opening, is regulated by an increase in [Ca2+]iduring OGD, and 3) open hemichannels contribute to cell injury during recovery from OGD.
Elucidation of the temporal relationship between endothelial-derived NO and EDHF in mesenteric vessels
Authors: Harrington Louise S. , Carrier Martin J. , Gallagher Nicola , Gilroy Derek , Garland Chris J. , Mitchell Jane A.
Published: June 2007

Although the endothelium co-generates both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), the relative contribution from each vasodilator is not clear. In studies where the endothelium is stimulated acutely, EDHF responses predominate in small arteries. However, the temporal relationship between endothelial-derived NO and EDHF over more prolonged periods is unclear but of major physiological importance. Here we have used a classical pharmacological approach to show that EDHF is released transiently compared with NO. Acetylcholine (3 × 10−6mol/l) dilated second- and/or third-order mesenteric arteries for prolonged periods of up to 1 h, an effect that was reversed fully and immediately by the subsequent addition of l-NAME (10−3mol/l) but not TRAM-34 (10−6mol/l) plus apamin (5 × 10−7mol/l). When vessels were pretreated with l-NAME, acetylcholine induced relatively transient dilator responses (declining over ∼5 min), and vessels were sensitive to TRAM-34 plus apamin. When measured in parallel, the dilator effects of acetylcholine outlasted the smooth muscle hyperpolarization. However, in the presence of l-NAME, vasodilatation and hyperpolarization followed an identical time course. In vessels from NOSIII−/−mice, acetylcholine induced small but detectable dilator responses that were transient in duration and blocked by TRAM-34 plus apamin. EDHF responses in these mouse arteries were inhibited by an intracellular calcium blocker, TMB-8, and the phospholipase A2inhibitor AACOCF3, suggesting a role for lipid metabolites. These data show for the first time that EDHF is released transiently, whereas endothelial-derived NO is released in a sustained manner.
Heterogeneity of transcription factor expression and regulation in human airway epithelial and smooth muscle cells
Authors: Panebra Alfredo , Schwarb Mary Rose , Glinka Clare B. , Liggett Stephen B.
Published: June 2007

Transcription factors represent a major mechanism by which cells establish basal and conditional expression of proteins, the latter potentially being adaptive or maladaptive in disease. The complement of transcription factors in two major structural cells of the lung relevant to asthma, airway epithelial and smooth muscle cells, is not known. A plate-based platform using nuclear extracts from these cells was used to assess potential expression by binding to oligonucleotide consensus sequences representing >300 transcription factors. Four conditions were studied: basal, β-agonist exposure, culture under proasthmatic conditions (IL-13, IL-4, TGF-β, and leukotriene D4), and the dual setting of β-agonist with proasthmatic culture. Airway epithelial cells expressed 70 transcription factors, whereas airway smooth muscle expressed 110. High levels of multiple transcription factors not previously recognized as being expressed in these cells were identified. Moreover, expression/ binding patterns under these conditions revealed extreme discordance in the direction and magnitude of change between the cell types. Singular (one cell type displayed regulation) and antithetic (both cell types underwent expression changes but in opposite directions) regulation dominated these patterns, with concomitant regulation in both cell types being rare (<10%). β-Agonist evoked up- and downregulation of transcription factors, which was highly influenced by the proasthmatic condition, with little overlap of factors regulated by β-agonists under both conditions. Together, these results reveal complex, cell type-dependent networks of transcription factors in human airway epithelium and smooth muscle that are dynamically regulated in unique ways by β-agonists and inflammation. These factors may represent additional components in asthma pathophysiology or potential new drug targets.
Endoplasmic Reticulum Stress: Signaling the Unfolded Protein Response
Authors: Lai Elida , Teodoro Tracy , Volchuk Allen
Published: June 2007

The endoplasmic reticulum (ER) is the cellular site of newly synthesized secretory and membrane proteins. Such proteins must be properly folded and posttranslationally modified before exit from the organelle. Proper protein folding and modification requires molecular chaperone proteins as well as an ER environment conducive for these reactions. When ER lumenal conditions are altered or chaperone capacity is overwhelmed, the cell activates signaling cascades that attempt to deal with the altered conditions and restore a favorable folding environment. Such alterations are referred to as ER stress, and the response activated is the unfolded protein response (UPR). When the UPR is perturbed or not sufficient to deal with the stress conditions, apoptotic cell death is initiated. This review will examine UPR signaling that results in cell protective responses, as well as the mechanisms leading to apoptosis induction, which can lead to pathological states due to chronic ER stress.
G-Protein Coupled Receptor Signaling in Myocardium: Not for the Faint of Heart
Authors: Kang Misuk , Chung Ka Young , Walker Jeffery W.
Published: June 2007

Catecholamines, endothelin-1 and angiotensin II are among a diverse group of diffusible extracellular signals that regulate pump function of the heart by binding to G-protein coupled receptors (GPCR). When the body demands a temporary boost of power output or if temporary budgeting of resources is required, these signals can adjust heart rate and contractile strength to maintain continuous perfusion of all vascular beds with nutrient- and oxygen-rich blood. Given adequate time in the face of prolonged challenges, activation of GPCRs can also promote “remodeling of the heart” by increasing cell size, organ size, and chamber dimensions, or by varying tissue composition and altering the expression of protein isoforms controlling excitability and contractility. A common feature of heart disease is the state of chronic activation of GPCR signaling systems. Paradoxically, whereas acute activation is beneficial, chronic activation often contributes to further deterioration of cardiac performance. A better understanding of how chronic GPCR activation contributes to the development of heart disease is needed so that it can be translated into better prevention and therapeutic strategies in the clinic.
The Challenge of the Pentecostals in Asia Part Two: The Responses of the Roman Catholic Church
Authors: Prior John Mansford
Published: June 2007

Introduction by the Managing Editor: John Mansford Prior SVD wrote an essay for the Asian Convention of the Pontifical Council for Culture planned for Jogyakarta, Indonesia, in June 12-17, 2006. The essay starts with a survey of the Pentecostal and charismatic movements in five Asian countries. Subsequently Prior reviews a growing awareness of 'sects and new religious movements' in church documents. Then he looks at how social science understands the 'rise of the sects' before he takes up the pastoral challenge to link the dynamism of Pentecostal/charismatic movements with the social conscience of basic ecclesial communities. The editing board of Exchange was impressed by the content of the essay and considered it to be of great importance to the readership of the journal. However, the essay was too long to be published in one issue. Therefore it is decided to divide it into parts. The first part gives the overview of Pentecostal and charismatic movements in Asia and the second part deals with the reaction of the Asian mainline churches, in particular the Roman Catholic Church. Part one was published in the previous issue (pp. xx-xx).
HIV and AIDS, Stigma and Liberation in the Old Testament
Authors: Chitando Ezra , Gunda Masiiwa
Published: June 2007

As the HIV and AIDS pandemic continues to affect most parts of Sub-Saharan Africa, the church has attempted to mitigate its effects. Unfortunately, stigma has emerged as a major challenge. The church has been implicated in stigmatizing people living with HIV and AIDS. Some Christians have used the Bible to justify the exclusion of people living with HIV and AIDS. This article examines HIV and AIDS stigma. It highlights the various forms of stigma, alongside exploring the occurrence of stigma in the Hebrew Bible. The study calls for a re-reading of the Hebrew Bible in the context of HIV and AIDS stigma and discrimination. It argues that the theme of liberation that underpins the Hebrew Bible implies that stigma has no place in human relations. The paper draws attention to the need to bring liberation to the heart of mission in the light of HIV and AIDS in Africa.
Pharmacological Agents for the Treatment of Adult Attention Deficit Hyperactivity Disorder: A Review of the Literature
Authors: Sherwood Devon A. , Rey Jose A.
Published: June 2007

Adult attention deficit hyperactivity disorder (ADHD) has been an emerging area of psychiatry of particular interest over the past few years. Whether this attention is due to new medications prompting the issue (ie, FocalinTM, StratteraTM) or emerging awareness that an estimated 4.4% of adults suffer with this diagnosis, therapy is of a limited selection. Untreated symptoms can lead to several life problems, including work and school difficulties, personal relationship issues, low self-esteem, and an increased chance of tobacco use, alcohol abuse, or other substance abuse. This article is to serve as a general overview of the available information regarding adult ADHD and the pharmacologic therapies available to treat the disorder.
Integrating Innovative Technologies Into a Psychiatric Pharmacy Clerkship Rotation
Authors: Rappa Leonard , Larose-Pierre Margareth , McDonald Calandara , Massey Angela J. , Singh Angela
Published: June 2007

One quarter of the US population suffers from a diagnosable mental illness, and society is becoming more educated about these diseases and the medications used to treat them. Inasmuch as pharmacy is considered one of the most trusted professions, it is imperative that pharmacists have a good understanding of psychotropics to properly counsel their patients. However, psychopharmacology is often given disproportionate coverage in most pharmacy curricula considering the frequency of these illnesses. For future pharmacists to gain much-needed knowledge, a psychiatric pharmacy clerkship rotation can be instrumental in developing competence through patient consultations and in performing drug regimen reviews. Integrating simple technologies into a clerkship can greatly reduce the burden on the preceptor and provide a consistent and fulfilling experience for the student. Educators in nursing and medicine have used various technologies with much success, albeit in mostly a classroom environment. Applicable media include e-mail, the Internet, personal digital assistants, CD-ROM programs, and video teleconferencing. Various basic and advanced techniques, such as making monthly calendars and using CD-ROM media to free Web-based video teleconferencing, are described in detail to assist preceptors in using these technologies for their rotations. The future potential of the addition of technology into education is only limited by one's imagination and the tools available.