bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of blood culture reporting and clinical liaison on the empiric treatment of bacteraemia.
Authors: Cunney R J , McNamara E B , Alansari N , Loo B , Smyth E G
Published: June 2007

AIMS: To assess the impact of blood culture results and early clinical liaison on the treatment of patients with bacteraemia. METHODS: 123 patients with significant positive blood cultures were followed over a nine month period in a 620 bed teaching hospital. The impact of early blood culture reporting and clinical liaison on the cost and appropriateness of treatment was assessed. RESULTS: Empiric treatment was started before the Gram stain result in 107 (87%) patients. Treatment was altered on the basis of the Gram stain result in 39 (36%) of these patients, and on culture and sensitivity results in 53 (50%). The spectrum of antibiotic treatment was narrowed in 58 (54%) of these; 20 (19%) on Gram stain result alone. This resulted in a 42% reduction in daily antibiotic costs in patients who had received empiric treatment. Empiric treatment did not follow the hospital antibiotic policy in 49 (46%) of the patients treated. In patients where empiric treatment was not in accordance with hospital policy, 21 (44%) had an isolate resistant to the empiric treatment used; while in patients who received agents in accordance with hospital policy only one (1.7%) had a resistant isolate (p < 0.05). Patients who died (11 (9%)) were less likely to have received empiric treatment in accordance with the antibiotic policy, although this did not reach statistical significance (p = 0.1). CONCLUSION: Early reporting of Gram stain results from blood cultures, combined with early clinical liaison, results in more rational and cost effective treatment.
Resistance to ciprofloxacin in pathogenic Enterobacteriaceae in England and Wales in 1996.
Authors: Threlfall E J , Graham A , Cheasty T , Ward L R , Rowe B
Published: June 2007

In 1996, 6% of Escherichia coli from extraintestinal infections were resistant to ciprofloxacin with minimum inhibitory concentrations (MICs) > or = 2 mg/l (high level resistance). Low level resistance (MIC 0.125-1 mg/l) was also identified in 7% of Salmonella typhi, 4% of S paratyphi A, and 4% of non-typhoidal salmonellas. However, resistance to ciprofloxacin was rarely identified in shigellas. For E coli, physicians should be aware that treatment failures may occur when patients with invasive illness are treated with ciprofloxacin before the results of laboratory sensitivity tests are available. For salmonellas an increasing number of treatment failures have been recorded for patients infected with strains with low level resistance. Because of the increasing incidence of Enterobacteriaceae with low level resistance to ciprofloxacin, it is recommended that for this group of organisms a breakpoint of 0.125 mg/l should be included in laboratory sensitivity tests.
Cytokeratin 14 as a marker of squamous differentiation in transitional cell carcinomas.
Authors: Harnden P , Southgate J
Published: June 2007

The presence of squamous differentiation in transitional cell carcinomas has been variably related to prognosis and response to radiotherapy. This study sought to establish whether cytokeratin (CK) 14, normally expressed in the basal cells of squamous epithelium, could be used as a reliable marker of the emergence of a squamous phenotype in transitional cell carcinomas. In a series of 42 tumours, CK14 was expressed in areas of squamous morphology, whereas CK20 identified continuing urothelial differentiation. Furthermore, focal positivity for CK14 was present in a proportion of tumours with no morphological evidence of squamous differentiation, suggesting that it is a more sensitive marker of phenotypic switch. Investigation of CK subtypes may be more powerful than morphology alone in clinical studies of transitional cell carcinomas as CK expression profiles have been related to treatment response in other tumour types.
Pulmonary alveolar proteinosis: diagnosis using routinely processed smears of bronchoalveolar lavage fluid.
Authors: Mikami T , Yamamoto Y , Yokoyama M , Okayasu I
Published: June 2007

AIMS: For the diagnosis of pulmonary alveolar proteinosis from bronchoalveolar lavage specimens it is normally necessary to make an ultrastructural examination. However, this is thought to be impractical for bronchoalveolar lavage specimens that have been routinely fixed in ethanol. In the present study, bronchoalveolar lavage cytology smears on slide glasses were examined directly ultrastructurally to make a diagnosis of pulmonary alveolar proteinosis. METHODS: Bronchoalveolar lavage smears from three pulmonary alveolar proteinosis patients were stained with Papanicolaou and periodic acid-Schiff (PAS) for identification of amorphous globular structures. Subsequently, they were refixed with glutaraldehyde and osmium tetroxide, and embedded in epoxy resin. Ultrathin sections were cut and examined ultrastructurally. RESULTS: Papanicolaou stained specimens from pulmonary alveolar proteinosis patients contained scattered amorphous or granular globules, 20-50 microns in diameter, which were PAS positive. Ultrastructural examination of the globules revealed multilamellated structures, characteristic of pulmonary alveolar proteinosis, in all cases. CONCLUSIONS: In general, it is thought that the morphological diagnosis of pulmonary alveolar proteinosis from bronchoalveolar lavage specimens requires both cytological and ultrastructural examination. However, the amorphous globules evident on cytology smears proved to contain multilamellated structures so that they can themselves be used as diagnostic evidence.
Intestinal immune cells in Strongyloides stercoralis infection.
Authors: Trajman A , MacDonald T T , Elia C C
Published: June 2007

BACKGROUND: Strongyloides stercoralis can cause a wide spectrum of disease in man, ranging from a chronic asymptomatic infection to a hyperinfective, often fatal syndrome. In rodents, spontaneous expulsion of Strongyloides spp occurs after experimental infection. Mast cells, goblet cells, and eosinophils have been identified as possible effectors of this expulsion. AIMS: To investigate intestinal histopathology and mucosal immunity in immunocompetent patients with chronic S stercoralis infection. METHODS: Jejunal biopsies were performed in 19 immunocompetent patients with a positive stool examination for S stercoralis and few or no symptoms, and in seven healthy controls. Specimens were processed for histopathological analysis and stained by the immunoperoxidase technique, using the following monoclonal antibodies: CD2, CD3, CD4, CD8, anti-T cell receptor (TcR) gamma/delta, RFD1 and RFD7 (two different macrophage markers), Ki67+ (proliferating) cells, antihuman leucocyte antigen (HLA)-DR, and anticollagen IV. In addition, CD25+ cells, mast cells, IgE expressing cells, calprotectin containing cells, and neutrophil elastase positive cells were stained by the alkaline phosphatase method. RESULTS: Jejunal morphology and the numbers of different T cell subsets, mast cells, IgE expressing cells, eosinophils, and goblet cells were unaffected by S stercoralis infection. Conversely, the numbers of mature macrophages and dividing enterocytes in the crypts were reduced significantly. Crypt enterocytes did not express HLA-DR in both groups. The expression of HLA-DR by villus enterocytes was also comparable in patients and controls. There were no activated (CD25+) cells in the mucosa of either patients or controls. CONCLUSIONS: Compared with seven healthy uninfected volunteers, a group of 19 Brazilians with clinically mild strongyloides infection showed no abnormality of mucosal structure and no increase in non-specific inflammatory cells. Likewise, there was no increase in mucosal T cells or macrophages.
Evaluation of a new enzyme immunoassay for Clostridium difficile toxin A.
Authors: Vargas S O , Horensky D , Onderdonk A B
Published: June 2007

AIM: To evaluate a new enzyme immunoassay (EIA) method for detection of Clostridium difficile toxin by comparing it to cytotoxicity assay. To investigate the nature of false negative and false positive EIA results by evaluating clinical and therapeutic parameters. METHODS: 737 consecutive diarrhoeal specimens collected from patients clinically suspected of having C difficile colitis were tested for the presence of C difficile toxin by EIA for toxin A and by cytotoxicity assay. Clinical data were evaluated in all cases positive by either method. RESULTS: With the cytotoxicity assay as a gold standard, the specificity of EIA for toxin detection was 99.3% and the sensitivity was 62.2%. No false negative EIA specimens were obtained from patients already being treated for C difficile colitis. Among patients with cytotoxicity positive specimens, those with EIA positive samples had no clinical features distinguishing them from patients with EIA negative samples. CONCLUSIONS: Although specific, the new EIA method directed against toxin A lacks sensitivity compared to cytotoxicity. False negative EIA tests are not associated with concurrent treatment for C difficile colitis nor with any specific clinical features examined in our study.
Use of prototype automated blood culture system and gas-liquid chromatography for the analysis of continuous ambulatory peritoneal dialysis associated infection.
Authors: Catchpole C R , Macrae F , Brown J D , Palmer M , Healing D E , Richards N T , Elliott T S
Published: June 2007

AIMS: (1) To compare the recovery of organisms from continuous ambulatory peritoneal dialysis (CAPD) effluent fluid obtained from patients with clinical evidence of peritonitis, with an automated system (AS) and the Septichek blood culture system; (2) to evaluate the times to detection of organisms with the two systems; (3) to identify anaerobes from CAPD samples by extended anaerobic culture and gas-liquid chromatography (GLC). METHODS: 168 CAPD effluent fluid samples were studied, representing 157 episodes of peritonitis in 97 patients. CAPD samples were inoculated into two AS bottles-one anaerobic, one aerobic-and a Septichek bottle; samples were also examined for cell count, Gram stain, and direct culture. Culture bottles were then subcultured onto various media, and any organisms isolated were identified. After routine culture, GLC was performed on culture fluid in the anaerobic AS and Septichek bottles. When volatile fatty acids were detected, the broths were cultured anaerobically on specialised medium for a further five days. RESULTS: 147 organisms were isolated from the 168 samples: 96 (57%) yielded growth of significant organisms by direct culture, as compared to 129 (76.8%) by both AS and Septichek. There was no significant difference in isolation rates between AS and Septichek, but time to detection was more rapid with the AS system (p < 0.002). GLC showed volatile fatty acid in 15 specimens; of these, 14 subsequently grew anaerobic organisms. CONCLUSIONS: AS was comparable to Septichek for numbers of isolations. Speed to detection was faster with the AS, which may be an advantage in management of patients with CAPD peritonitis. GLC showed anaerobes in several cases which would not have been detected without prolonged anaerobic culture; thus anaerobic cultures are recommended for patients who are unresponsive to antimicrobials or who have evidence of bowel perforation.
Urethral malignant melanoma closely mimicking urothelial carcinoma.
Authors: Radhi J M
Published: June 2007

Primary malignant melanoma of the urethra is very rare. In the male, the distal urethra is the most common site. The histopathology does not usually differ from that of melanoma at other body sites. This report describes a case of urethral malignant melanoma which closely resembled urethral carcinoma. It showed both papillary and solid growth, and the diagnosis only became apparent from special stains. Pathologists should be aware of this rare occurrence.
Mucopolysaccharidosis type VII associated with hydrops fetalis: histopathological and ultrastructural features with genetic implications.
Authors: Molyneux A J , Blair E , Coleman N , Daish P
Published: June 2007

A case of mucopolysaccharidosis type VII (MPS VII, beta glucuronidase deficiency) causing fatal hydrops fetalis in the third trimester is presented. The diagnosis was suspected on histopathological examination by the presence of foam cells in many of the viscera and foamy change in the placental Hofbauer cells. Electron microscopy showed empty cytoplasmic inclusion bodies within macrophages and in the Hofbauer cells. Enzyme assay of cultured fibroblasts showed markedly deficient beta glucuronidase activity, thus confirming the diagnosis. A detailed and thorough histopathological examination of hydrops fetalis cases is important to detect subtle features of inherited metabolic disorders. Use of a structured necropsy protocol is recommended for cases of non-immune hydrops. Electron microscopy is a useful adjunct to light microscopy in cases where an inherited metabolic disorder is suspected. Precise necropsy diagnosis is important as there are implications for genetic counselling and possible prenatal diagnosis in subsequent pregnancies.
Hashimoto's thyroiditis associated with urticaria and angio-oedema: disappearance of cutaneous and mucosal manifestations after thyroidectomy.
Authors: Amoroso A , Garzia P , Pasquarelli C , Sportelli G , Afeltra A
Published: June 2007

A 60 year old woman affected by Hashimoto's thyroiditis presented with a history of recurring episodes of urticaria and angio-oedema. Clinical and laboratory evaluation of the patient excluded allergy to external agents, hereditary angio-oedema, and occult infections. A pathogenic relation between Hashimoto's thyroiditis and chronic urticaria/angio-oedema was suspected. However, treatment with L-thyroxine had no influence on the frequency and severity of the cutaneous and mucosal manifestations, which occurred almost daily and required repeated administration of steroids. The patient therefore underwent total thyroidectomy. Cytometric analysis of intrathyroidal lymphocyte subsets showed unusual abnormalities. Urticaria and angio-oedema completely remitted after surgery; 18 months postoperatively the patient was still asymptomatic.
Urinary tissue factor in glomerulonephritis: a potential marker of glomerular injury?
Authors: Lwaleed B A , Bass P S , Chisholm M , Francis J L
Published: June 2007

AIM: To investigate the significance of urinary tissue factor (uTF) concentrations in patients with glomerulonephritis. METHODS: Urine samples were collected from normal subjects (n = 57), patients with uncomplicated renal stones (n = 30), and patients with glomerulonephritis (n = 150). Samples were then centrifuged and the pellets solubilised in n-octyl-beta-glucopyranoside. uTF concentrations were determined using a one stage kinetic chromogenic assay. RESULTS: The uTF concentration was higher in patients with glomerulonephritis than in normal controls (p < 0.01) or in patients with renal stones (p < 0.05). uTF activity correlated with the protein creatinine index (PCI, r = 0.41, p < 0.001) and seven patients with glomerulonephritis and a PCI < or = 0.1 g/mmol had raised uTF. Glomerulonephritis patients were subdivided into two groups depending on the PCI: < 0.2 g/mmol creatinine (mild to moderate proteinuria, group I) and > or = 0.2 g/mmol creatinine (heavy proteinuria, group II). In group I, uTF concentrations were higher in patients with either immune complex (IC) glomerulonephritis (p < 0.01) or non-IC (p < 0.05) glomerulonephritis than in normal controls. In group II, the IC glomerulonephritis group had higher uTF concentrations than normal controls (p < 0.001) or patients with renal stones (p < 0.01); and non-IC glomerulonephritis patients had higher uTF than normal controls (p < 0.01). When the glomerulonephritis groups were divided into broad WHO subtypes, the significance level varied with the type of glomerulonephritis. CONCLUSIONS: uTF is increased in patients with glomerulonephritis, and its concentration may reflect the aetiopathogenesis of glomerulonephritis.
Effect of interferon alpha on high serum androgen concentrations in HIV positive men with Kaposi's sarcoma.
Authors: Christeff N , Gharakhanian S , Thobie N , Wirbel E , Dalle M T , Costagliola D , Nunez E A , Rozenbaum W
Published: June 2007

AIM: To measure serum androgen concentrations in men with HIV related Kaposi's sarcoma (KS) who had been treated with recombinant interferon (IFN) alpha-2a to determine the role of androgens on the development of KS lesions. METHODS: 32 men with HIV related KS who had been treated with IFN were studied: 24 men in complete KS remission and eight not in remission. Serum androgen concentrations were determined before, during, and after IFN treatment and correlated with clinical remission. RESULTS: All patients in complete KS remission had lower serum androgen concentrations following IFN treatment: -51% for dehydroepiandrosterone (DHEA) (p < 0.0001); -38% for DHEA sulphate (p < 0.002);-39% for androstenedione (p < 0.002); and -44% for testosterone (p < 0.007). These decreases brought the serum concentrations to about normal levels. However, IFN had varying effects on serum androgen concentrations in the men not in remission: a small decrease, a large increase in one androgen, or no change in serum androgens. CONCLUSIONS: The association between serum androgen levels and the progression or remission of HIV associated KS suggests that androgens affect the development of KS lesions. A clear understanding of the changes in the androgen environment may provide a sound basis for the development of new therapeutic strategies.
Late stage congestive gastropathy.
Authors: Leone O , Zanelli M , Piana S , Santini D , Marrano D
Published: June 2007

Gastric mucosal abnormalities resulting from portal hypertension are defined as "congestive gastropathy". A case of congestive gastropathy with unusual features, in a 63 year old man with a history of excessive alcohol intake and cirrhosis, is described. The patient underwent a subtotal gastrectomy because of profuse bleeding from a gastric ulcer, providing a large surgical specimen for examination. Unusual gross and histological findings included prominent arterial intimal hyperplasia, and diffuse duplication and focal fragmentation of the internal lamina elastica. The differential diagnosis of this condition includes primary angiodysplastic gastropathy such as Dieulafoy's disease. The similarity with Dieulafoy-like angiodysplasia emphasises that clear cut criteria to define gastric vascular lesions do not yet exist.
Inflammatory pseudotumour of the liver.
Authors: Kafeel G , Telesinghe P U
Published: June 2007

Inflammatory pseudotumour is not a common lesion. The first series of 12 cases was described in 1986, to which 37 more cases have now been added. The histology, differential diagnosis, and prognosis of this lesion have been described in detail, but the aetiology is unknown and the mode of treatment remains controversial. A new case is presented and compared with the previously reported cases. Fine needle aspirate yielded a growth of klebsiella organisms. The possibility of this infection as an aetiological agent is considered.
Use of CHROMagar Candida for genital specimens in the diagnostic laboratory.
Authors: Houang E T , Chu K C , Koehler A P , Cheng A F
Published: June 2007

OBJECTIVE: To evaluate CHROMagar Candida (CA), a new yeast differential medium, for yeast isolation in a clinical laboratory for the routine examination of high vaginal swabs. METHODS: Results of high vaginal swab cultures processed in a standard manner on plates containing equal halves of Sabouraud dextrose agar (SDA) and CA were compared. Non-Candida albicans yeast isolates were further speciated with API 20C AUX or API 32C. To assess the ease of use of CA, laboratory staff lacking in experience of the medium were asked to identify 23 unlabelled yeast cultures on CA by referring to six labelled reference plates. RESULTS: Of the 1784 swab cultures processed, yeasts were isolated from 373 SDA and 368 CA. Of the 78 non-albicans isolates further speciated, CA identified correctly all cultures of C krusei and C tropicalis, and 82% of C glabrata. All the 38 inexperienced laboratory staff achieved 100% accuracy for C albicans and over 90% for C krusei and C tropicalis. CONCLUSIONS: CA is a satisfactory isolation medium for genital specimens, allowing immediate and correct identification of the commonly encountered yeasts and easy recognition of mixed cultures.
Cathepsin D detected by automated and quantitative immunohistochemistry in breast carcinomas: correlation with overall and disease free survival.
Authors: Charpin C , Garcia S , Bouvier C , Martini F , Lavaut M , Allasia C , Bonnier P , Andrac L
Published: June 2007

AIM: To determine the prognostic significance and clinical relevance of cathepsin D detected by immunocytochemical assays (ICAs) in breast carcinomas. METHODS: 151 patients presenting with palpable or impalpable breast carcinomas and who had not received any kind of adjuvant chemotherapy or endocrine therapy who were operated from January 1986 to May 1987 were studied. ICAs of tumour specimens were performed in optimal technical conditions (frozen sections, automated immunoperoxidase technique (Ventana), and computer assisted analysis of digitised coloured microscopic images (SAMBA)) to determine cathepsin D immunocytochemical expression. Results of quantitative ICAs were correlated with overall and disease free survival over 8.4 years of follow up in axillary lymph node positive and negative patients. RESULTS: Cathepsin D immunocytochemical expression in tumours of 15% or more was significantly associated with poor overall survival in the whole group and in node positive patients (Kaplan Meier, log rank test p = 0.003 and p = 0.007); however, it was not correlated with survival in node negative patients. Cathepsin D immunocytochemical expression (> 15%) correlated with short disease free (p = 0.015) and short recurrence free survival (p = 0.021) in the group as a whole but not when node positive and negative patients were evaluated separately. CONCLUSIONS: In optimal conditions (automated and quantitative ICAs on frozen sections) cathepsin D immunohistochemical expression is a significant prognostic indicator in terms of overall, disease free, and recurrence free survival; however, there is no correlation when node negative patients are considered separately.
Cytological and architectural heterogeneity in ductal carcinoma in situ of the breast.
Authors: Quinn C M , Ostrowski J L
Published: June 2007

AIM: The traditional architecture based classification system of ductal carcinoma in situ (DCIS) has been criticised on the grounds that individual lesions often show more than one pattern resulting in a large mixed category. New DCIS classification systems have emphasised the importance of cytological grade, which is reputed to be more uniformly expressed throughout a lesion. This study investigates the hypothesis that cytological heterogeneity is less common than architectural heterogeneity within DCIS lesions. METHODS: 121 cases of DCIS were graded as poorly, intermediately, or well differentiated according to a recently developed classification system that employs cytonuclear morphology as the major diagnostic criterion. Cases were categorised as pure when only one grade was present and as mixed if more than one grade was observed. Architecturally the cases were classified as solid, cribriform, micropapillary, or papillary and were described as pure if only one architectural pattern was present and as mixed if more than one pattern was seen. The incidence of cytological heterogeneity was compared with that of architectural heterogeneity. The presence of necrosis was assessed as an independent parameter and the relation to DCIS grade evaluated. RESULTS: Using the cytology based classification system 102 cases (84%) were classified as pure (65 poorly differentiated, 25 intermediately differentiated, and 12 well differentiated) and 19 cases (16%) as mixed. Extensive necrosis was observed in 61 (50%) cases and was closely correlated to DCIS grade. Architecturally 46 cases (38%) were classified as pure (38 solid, 5 cribriform, 2 micropapillary, and 1 papillary) and 75 (62%) as mixed. CONCLUSIONS: Cytological heterogeneity is much less common than architectural heterogeneity in DCIS lesions. The assessment of cytonuclear morphology is therefore likely to provide more consistent information about DCIS, particularly in small biopsy specimens where only part of the lesion may be available for examination.
Giant cells in pigmented villo nodular synovitis express an osteoclast phenotype.
Authors: Neale S D , Kristelly R , Gundle R , Quinn J M , Athanasou N A
Published: June 2007

AIM: To determine the cytochemical and functional phenotype of multinucleated giant cells in pigmented villo nodular synovitis (PVNS). METHODS: Giant cells isolated from a patient with PVNS of the knee were assessed for a number of markers used to distinguish osteoclasts from macrophages/ macrophage polykaryons: evidence of tartrate resistant acid phosphatase (TRAP) activity; expression of CD11b, CD14, CD51, and calcitonin receptors; and the ability of the giant cells to carry out lacunar resorption. RESULTS: Isolated giant cells expressed an osteoclast antigenic phenotype (positive for CD51, negative for CD11b and CD14) and were TRAP and calcitonin receptor positive. They also showed functional evidence of osteoclast differentiation, producing numerous lacunar bone resorption pits on bone slices in short term culture. CONCLUSIONS: The giant cells in this case of PVNS express all the phenotypical features of osteoclasts including the ability to carry out lacunar resorption. This may account for the bone destruction associated with this aggressive synovial lesion.
Solitary cystic dilatation of the intrahepatic bile duct.
Authors: Ohmoto K , Shimizu M , Iguchi Y , Yamamoto S , Murakami M , Tsunoda T
Published: June 2007

A 31 year old man was hospitalised with general fatigue and epigastric pain. Abdominal ultrasonography, computed tomography, and magnetic resonance imaging showed a cystic lesion in the left lobe of the liver. Endoscopic retrograde cholangio-pancreatography and percutaneous trans-hepatic cholangiography revealed a localised dilatation of the intrahepatic bile duct without any obstruction. However, a large mass of mucinous material was noted in the saccular intrahepatic duct and the common bile duct. There was no evidence of a choledochal cyst, anomalous pancreaticobiliary ductal union, or congenital cystic change of the kidneys. A possible diagnosis of mucinous cystic neoplasm of the intrahepatic bile duct was made and a left hepatectomy performed. Cholangiography of the resected specimen showed a non-obstructive solitary cystic dilatation of the left hepatic duct. Histologically, the dilated duct was lined with columnar biliary epithelium without any papillary proliferation and/or atypia. Neither malignancy nor hepatic fibrosis was observed; the term "solitary cystic dilatation of the intrahepatic bile duct" perhaps is more descriptive and the concept easier to understand.
Clear cell mammary malignant myoepithelioma with abundant glycogens.
Authors: Kuwabara H , Uda H
Published: June 2007

Malignant myoepithelioma (myoepithelial carcinoma) of the breast is extremely rare. A case is reported of a 46 year old female with clear cell mammary malignant myoepithelioma that, on histological examination, was glycogen abundant clear cell carcinoma. Immunohistochemically, the clear cells showed myoepithelial differentiation--that is, they were a smooth muscle actin and S100 protein positive. This case shows that glycogen abundant clear cell carcinoma is a variant of malignant myoepithelioma of the breast.
Tumorous necrotic nodule in the liver: unexpected effect of the microwave tissue coagulator.
Authors: Mikami Y , Shimizu M , Manabe T
Published: June 2007

The microwave tissue coagulator (MTC) is used in hepatectomy because it provides excellent haemostasis during the procedure. A 59 year old man underwent partial hepatic lobectomy with MTC, for metastasis from colon cancer. A tumorous necrotic nodule was discovered in the liver. The nodule measured 2.5 cm at its largest diameter. Microscopically, it showed extensive coagulation necrosis and massive sinusoidal dilatation. To date, such a necrotic mass clinically mimicking neoplasm has not been reported as a complication of hepatectomy using MTC. Although it is unknown how the rounded necrotic nodule was formed in this case, clinicians should be aware of this phenomenon to avoid unnecessary operations. Likewise, pathologists should recognise such histological changes and review the clinical history of the patient when coagulation necrosis with massive sinusoidal dilatation is observed in a biopsy or hepatectomy specimen.
Hepatic histology of patients with HIV infection and chronic hepatitis C treated with interferon.
Authors: Boldorini R , Viganò P , Monga G , Nebuloni M , Cargnel A , Gubertini G , Migliaretti G , Costanzi G
Published: June 2007

AIMS: To evaluate the histological changes seen in liver biopsies after interferon (IFN) treatment in patients with chronic hepatitis C and human immunodeficiency virus (HIV) infection. METHODS: Twenty four intravenous drug users with chronic hepatitis C were investigated histologically before beginning a 12 month course of IFN treatment and 18 months later. Twelve were HIV positive, without opportunistic or other viral infections (group A), and 12 were HIV negative (group B). RESULTS: According to alanine amino-transferase concentrations, four sustained responders and eight non-responders were found in group A; six sustained responders, five relapsers, and one non-responder were found in group B. HCV RNA became negative in one sustained responder of group A and in the six sustained responders of group B. When histological findings of biopsies performed before therapy and 18 months later were compared, no significant changes in the mean value of Knodell's index and subindices were found in group A, whereas in group B Knodell's index, piecemeal necrosis, and focal hepatocellular necrosis decreased significantly. CONCLUSIONS: In chronic hepatitis C, coinfection with HIV showed a tendency towards a lower response to IFN, although this did not reach statistical significance; however, none of the HIV positive patients developed cirrhosis during the follow up and this should be considered in clinical management of such patients.
Detection of parvovirus B19 in macerated fetal tissue using in situ hybridisation.
Authors: Walters C , Powe D G , Padfield C J , Fagan D G
Published: June 2007

AIMS: To compare the application of a non-radioactive in situ hybridisation (ISH) technique with an immunocytochemical technique for the detection of human parvovirus B19 in formalin fixed, paraffin wax embedded sections of macerated fetal tissue. METHODS: Archived samples of liver, lung or kidney from 19 human fetuses were investigated for parvovirus B19 using a full length digoxigenin labelled DNA probe of 5.5 kb; bound probe was detected using an anti-digoxigenin (alkaline phosphatase) conjugate and visualised using NBT/BCIP. Immunocytochemical detection of parvovirus B19 was performed using a monoclonal mouse antiparvovirus B19 antiserum, with a streptavidin-biotin complex (horse radish peroxidase) method. Cases were selected to provide a range of diagnostic certainty and a range of degrees of macerative degeneration. RESULTS: Parvovirus B19 was found in 15 of 19 cases using the B19 ISH technique compared with 8 of 19 cases using the immunocytochemical technique. The four negative cases were all controls known to be parvovirus B19 free. All ISH positive cases showed excellent staining with low background regardless of extent of maceration and tissue type. In comparison, sections stained by the immunocytochemical method showed considerable non-specific immunoreactivity in many cases, particularly with severe maceration. Kidney and lung tissues gave the cleanest results. CONCLUSIONS: ISH is more effective than the immunocytochemical technique for the detection of human parvovirus B19 in macerated fetal tissue. The lack of detectable background staining with the ISH technique led to easier interpretation suggesting that this technique should be the method of choice for the investigation of parvovirus B19 in macerated postmortem tissues.
Diagnostic distance of high grade prostatic intraepithelial neoplasia from normal prostate and adenocarcinoma.
Authors: Montironi R , Pomante R , Colanzi P , Thompson D , Hamilton P W , Bartels P H
Published: June 2007

OBJECTIVE: To develop a distance measure based methodology to support the morphological evaluation of high grade prostatic intraepithelial neoplasia (PIN), a direct precursor of prostate cancer. METHODS: Eight morphological and cellular features were analysed in 20 cases of high grade PIN found in radical prostatectomy specimens from patients with adenocarcinoma. The diagnostic distance was evaluated to measure the extent to which the feature outcomes of the individual high grade PIN cases differed from the expected outcome profile of normal prostate, low and high grade PIN, and cribriform and large acinar adenocarcinoma. The belief value for high grade PIN was evaluated with a Bayesian belief network (BBN). RESULTS: Complete separation existed between the cumulative absolute diagnostic distances of these 20 cases from the prototype feature outcomes of high grade PIN and normal prostate the values for which were < or = 3 (range 0 to 3) and > or = 9 (range 9 to 15), respectively. The distances from low grade PIN (range 3 to 9), cribriform adenocarcinoma (range 2 to 8), and large acinar adenocarcinoma (range 5 to 10) were intermediate and showed overlap in their distribution. When taking into consideration whether the severity of feature changes was increasing or decreasing in comparison with the category prototype outcomes, the cumulative directional diagnostic distances from high grade PIN ranged from -3 to +3. Positive distance values were seen relative to low grade PIN (range +3 to +9) and relative to normal prostate (range +9 to +15). Negative values were found relative to cribriform adenocarcinoma (range -8 to +2). The distance values from large acinar adenocarcinoma ranged from -2 to +4 and partly overlapped with those from the high grade PIN category. A bivariate scattergram derived from both diagnostic distance measures showed excellent separation between the groups' distances. BBN analysis confirmed the morphology based diagnosis. The distance evaluation resulted in 18 cases whose belief value for high grade PIN ranged from 0.60 to 0.87. In the remaining two cases the results of the BBN analysis showed a belief value of 0.50 and 0.57 for low grade PIN and of 0.49 and 0.38 for high grade PIN, respectively. CONCLUSIONS: Distance measure based methodology represents a useful diagnostic decision support tool for the accurate evaluation of high grade PIN.
Increased spontaneous tone in renal arteries of spontaneously hypertensive rats
Authors: Michel Frédéric S. , Man Ricky Y. K. , Vanhoutte Paul M.
Published: June 2007

The spontaneous tone of vascular smooth muscle is augmented in hypertension. The present study examined the role of nitric oxide (NO), cyclooxygenase (COX), thromboxane A2/prostanoid (TP) and PGE2/prostanoid (EP-1) receptors, reactive oxygen species, and large-conductance Ca2+-activated K+ (BKCa) channels in the regulation of spontaneous tone in renal arteries of young and mature Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Rings of arteries, with and without endothelium, were suspended in a myograph for isometric force recording. Spontaneous tone (increase above initial tension) was observed only in arteries of mature SHR and was greater in arteries without endothelium. Nω-nitro-l-arginine methyl ester (l-NAME, an inhibitor of NO synthases) induced larger contractions in arteries of SHR than WKY. Indomethacin (a COX inhibitor), SC-19220 (an EP-1 receptor antagonist), and terutroban (a TP receptor antagonist) reduced the l-NAME-evoked contractions. Tiron (a superoxide anion scavenger), catalase (an enzyme that degrades H2O2), and deferoxamine (a hydroxyl radical scavenger) augmented the l-NAME-induced contractions in arteries of mature SHR. Charybdotoxin (a BKCa channel blocker) caused contractions in arteries of mature SHR without endothelium and in arteries with endothelium incubated with l-NAME. A decreased protein level of endothelial NO synthase, an increased release of prostacyclin, and an increased expression of EP-1 receptors were observed in arteries of mature SHR. The present study suggests that spontaneous tone is precipitated by age and hypertension. The reduced production of NO, leading to decreased activation of BKCa channels, may leave the actions of endogenous vasoconstrictors unopposed. COX products that activate EP-1 and TP receptors are involved in the development of spontaneous tone.
Exercise training and β-blocker treatment ameliorate age-dependent impairment of β-adrenergic receptor signaling and enhance cardiac responsiveness to adrenergic stimulation
Authors: Leosco Dario , Rengo Giuseppe , Iaccarino Guido , Filippelli Amelia , Lymperopoulos Anastasios , Zincarelli Carmela , Fortunato Francesca , Golino Luca , Marchese Massimo , Esposito Giovanni , Rapacciuolo Antonio , Rinaldi Barbara , Ferrara Nicola , Koch Walter J. , Rengo Franco
Published: June 2007

Cardiac β-adrenergic receptor (β-AR) signaling and left ventricular (LV) responses to β-AR stimulation are impaired with aging. It is shown that exercise and β-AR blockade have a favorable effect on cardiac and vascular β-AR signaling in several cardiovascular diseases. In the present study, we examined the effects of these two different strategies on β-AR dysregulation and LV inotropic reserve in the aging heart. Forty male Wistar-Kyoto aged rats were randomized to sedentary, exercise (12 wk treadmill training), metoprolol (250 mg·kg−1·day−1 for 4 wk), and exercise plus metoprolol treatment protocols. Ten male Wistar-Kyoto sedentary young rats were also used as a control group. Old trained, old metoprolol-treated, and old trained plus metoprolol-treated rats showed significantly improved LV maximal and minimal first derivative of the pressure rise responses to β-AR stimulation (isoproterenol) compared with old untrained animals. We found a significant reduction in cardiac sarcolemmal membrane β-AR density and adenylyl cyclase activity in old untrained animals compared with young controls. Exercise training and metoprolol, alone or combined, restored cardiac β-AR density and G-protein-dependent adenylyl cyclase activation in old rats. Although cardiac membrane G-protein-receptor kinase 2 levels were not upregulated in untrained old compared with young control rats, both exercise and metoprolol treatment resulted in a dramatic reduction of G-protein-receptor kinase 2 protein levels, which is a further indication of β-AR signaling amelioration in the aged heart induced by these treatment modalities. In conclusion, we demonstrate for the first time that exercise and β-AR blockade can similarly ameliorate β-AR signaling in the aged heart, leading to improved β-AR responsiveness and corresponding LV inotropic reserve.
Validity of a patient-derived system of tissue-specific human endothelial cells: interleukin-6 as a surrogate marker in the coronary system
Authors: Lehle Karla , Kunz-Schughart Leoni A. , Kuhn Peter , Schreml Stephan , Birnbaum Dietrich E. , Preuner Jürgen G.
Published: June 2007

The aim of our study was to evaluate the relevance of tissue- and species-specific endothelial cells (EC) to study EC-dependent mechanisms in inflammatory-mediated tissue injury. We established an isolation protocol for highly purified EC (pEC) preparations of different origin and compared EC-specific inflammatory responses. Fluorescence-activated cell separation was used to obtain pEC cultures from different human arterial (coronary artery, internal thoracic artery) and venous (umbilical vein, saphenous vein) vessels. All pEC were analyzed for growth kinetics, morphology, release of cytokines/chemokines, and expression of E-selectin. For all different EC cultures, purities of ≥99% were reproducibly achieved. The EC isolation did not affect EC growth, morphology, and function. However, characterization of pEC from different vessel materials revealed an intrinsic, tissue-specific functional heterogeneity of EC cultures. Despite an arterial and venous difference in the secretion of IL-8 and monocyte chemoattractant protein-1, especially EC from coronary arteries produced significantly more IL-6 compared with other EC types, independent of age, gender, and disease of the cell donors. In contrast, the expression of E-selectin was not affected. We conclude that the proposed isolation protocol allows the generation of a pEC bank, enabling us to study tissue-specific aspects at the level of the endothelium.
K+-Dependent Na+/Ca2+Exchangers: Key Contributors to Ca2+Signaling
Authors: Visser Frank , Lytton Jonathan
Published: June 2007

An elevation in cytosolic Ca2+is a universal signaling mechanism that controls a vast array of physiological processes. K+-dependent Na+/Ca2+exchangers are a newly identified family of Ca2+efflux transporters that play important and diverse roles in cellular Ca2+homeostasis.
The Value of Power Doppler Ultrasonography in Achilles Tendinopathy
Authors: de Vos Robert-Jan , Weir Adam , Cobben Lodewijk P. J. , Tol Johannes L.
Published: June 2007

Background

Neovascularization, detected with power Doppler ultrasonography (PDU), is thought by some to play a central role in pathogenesis of Achilles tendinopathy.

Hypothesis

Power Doppler ultrasonography neovascularization score is correlated with clinical severity at baseline and after conservative treatment.

Study Design

Cohort study (prognosis); Level of evidence, 2.

Methods

Seventy tendons from 58 patients with chronic midportion Achilles tendinopathy were included, and 63 symptomatic tendons were analyzed. All patients were prescribed a 12-week heavy-load eccentric training program and evaluated with PDU at baseline and 12 weeks. Patient satisfaction, Victorian Institute of Sports Assessment—Achilles (VISA-A) score, and mean visual analog scale (VAS) score were correlated with degree of neovascularization (5-grade scale).

Results

Of the 63 symptomatic tendons, baseline neovascularization scores were 23 grade 0 (37% no neovessels), 18 grade 1, 8 grade 2, 8 grade 3, and 6 grade 4 (63% neovascularization grades 1-4). At baseline, neovascularization was not significantly correlated with the mean VAS score (r = .19, P = .131) and VISA-A score (r = —.23, P = .074). At 12-week follow-up, the neovascularization score significantly correlated with the mean VAS score (r = .43, P < .001) and VISA-A score (r = —.46, P < .001). No significant differences were found in improvement of VISA-A score after treatment between patients with neovessels (grades 1-4) or without neovessels (grade 0) at baseline.

Conclusion

Sixty-three percent of the symptomatic tendons were found to have neovessels at baseline. There was no significant correlation between neovascularization score and clinical severity at baseline, but at follow-up, there was a significant correlation. Neovascularization at baseline did not predict clinical outcome after conservative treatment.
Intranasal Zinc in the Management of the Common Cold
Authors: Augusto Laura Gianni
Published: June 2007

Because zinc ions may prevent rhinovirus from attaching to and infecting cells in the nasal cavity, it has been recently hypothesized that direct application of ionic zinc to the nasal mucosa would be effective in reducing the duration of rhinovirus-associated colds. Five studies that compare intranasal zinc to placebo were identified in the medical literature. These studies provide conflicting results and are reviewed in detail. In the clinical trials that found efficacy, intranasal zinc was administered within the first 24 to 48 hours of the onset of cold symptoms. Adverse effects reported in clinical trials include nasal stinging or burning, epistaxis, headache, dry nose, dry mouth, nasal irritation, throat irritation, and nasal pain. Also of importance, case reports of intranasal zinc—induced persistent anosmia (complete loss of the sense of smell) have been reported in the literature. It is important that pharmacists inform their patients who want to use intranasal zinc of this possible complication.
Design of a Proficiency-Based Skills Training Curriculum for the Fundamentals of Laparoscopic Surgery
Authors: Ritter E. Matt , Scott Daniel J.
Published: June 2007

Currently, no optimal curriculum exists for the Fundamentals of Laparoscopic Surgery (FLS) manual skills training program. The objective was to create a proficiency-based training curriculum that would allow both successful completion of the FLS manual skills exam and improved performance in the operating room. Two experienced laparoscopic surgeons performed 5 consecutive repetitions of all 5 FLS tasks. The mean performance times for both subjects were determined. Error parameters for each task were also recorded and used to establish a maximum allowable error parameter for each task. These data were used to create both error- and time-based proficiency levels for each task based on the importance of the task and the amount of resources consumed when practicing the task. This type of objective proficiency level was determined for each of the 5 FLS tasks. We have developed a proficiency-based training curriculum for the psychomotor skills portion of FLS. Work is under way to evaluate and validate this curricular design.
Hypoxic stress underlies defects in erythroblast islands in the Rb-null mouse
Authors: Spike Benjamin T. , Dibling Benjamin C. , Macleod Kay F.
Published: June 2007

Definitive erythropoiesis occurs in islands composed of a central macrophage in contact with differentiating erythroblasts. Erythroid maturation including enucleation can also occur in the absence of macrophages both in vivo and in vitro. We reported previously that loss of Rb induces cell-autonomous defects in red cell maturation under stress conditions, while other reports have suggested that the failure of Rb-null erythroblasts to enucleate is due to defects in associated macrophages. Here we show that erythropoietic islands are disrupted by hypoxic stress, such as occurs in the Rb-null fetal liver, that Rb−/− macrophages are competent for erythropoietic island formation in the absence of exogenous stress and that enucleation defects persist in Rb-null erythroblasts irrespective of macrophage function.
HIF–prolyl hydroxylase inhibition results in endogenous erythropoietin induction, erythrocytosis, and modest fetal hemoglobin expression in rhesus macaques
Authors: Hsieh Matthew M. , Linde N. Seth , Wynter Aisha , Metzger Mark , Wong Carol , Langsetmo Ingrid , Lin Al , Smith Reginald , Rodgers Griffin P. , Donahue Robert E. , Klaus Stephen J. , Tisdale John F.
Published: June 2007

The hypoxia-inducible factor (HIF) pathway is crucial in mitigating the deleterious effects of oxygen deprivation. HIF-α is an essential component of the oxygen-sensing mechanisms and under normoxic conditions is targeted for degradation via hydroxylation by HIF–prolyl hydroxylases. Several HIF–prolyl hydroxylase inhibitors (PHIs) induced erythropoietin (epo) expression in vitro and in mice, with peak epo expression ranging from 5.6- to 207-fold above control animals. Furthermore, several PHIs induced fetal hemoglobin (HbF) expression in primary human erythroid cells in vitro, as determined by flow cytometry. One PHI, FG-2216, was further tested in a nonhuman primate model without and with chronic phlebotomy. FG-2216 was orally bioavailable and induced significant and reversible Epo induction in vivo (82- to 309-fold at 60 mg/kg). Chronic oral dosing in male rhesus macaques was well tolerated, significantly increased erythropoiesis, and prevented anemia induced by weekly phlebotomy. Furthermore, modest increases in HbF-containing red cells and reticulocytes were demonstrated by flow cytometry, though significant increases in HbF were not demonstrated by high-pressure liquid chromatography (HPLC). HIF PHIs represent a novel class of molecules with broad potential clinical application for congenital and acquired anemias.