The aldosterone-to-renin ratio (ARR) has allowed the widespread screening for PA, but the exact cut-off values may vary in different population groups. All patients with hypertension and hypokalaemia, and young patients with hypertension, hypertension with an incidental adrenal mass, and severe or resistant hypertension should be screened. The use of the ARR to screen all hypertensives for PA is controversial as the test lacks specificity and many patients with false-positive tests will undergo complex and expensive testing to confirm the diagnosis. The fludrocortisone suppression test, the saline infusion test or 24-hour aldosterone excretion may be used to confirm PA in patients with a positive ARR. Adrenal venous sampling is the most reliable test to detect the presence of an aldosterone-producing adenoma, but spiral CT scan or adrenocortical scintigraphy may be useful in centres without facilities for adrenal venous sampling.
Spironolactone is emerging as an important antihypertensive agent in patients with resistant hypertension and aldosterone-related hypertension. The ARR may be a useful guide to drug selection in hypertensives patients, but further research is needed to make more definitive recommendations.
]]>Mucoepidermoid carcinoma (MEC) is the most common malignant primary salivary gland tumour. Little is known about cytokeratin expression in MEC or how it may relate to survival. In this study, the aim was to determine the extent of cytokeratin 5 (CK5) expression in intermediate- and high-grade MEC and correlate expression with survival.
Data on clinicopathological features including stage and survival outcome were collected on 29 patients with intermediate- or high-grade MEC that had follow-up for at least 4 years or until death. Staining with antibody to CK5 protein was carried out and tumour staining was stratified as 0–3 (0, no tumour cells staining; 1, 1–25% of tumour cells staining; 2, 26–75% of tumour cells staining; 3, >75% of tumour cells staining). Six patients had intermediate-grade tumours and 23 had high-grade tumours. The median patient follow-up was 33 months, and 11 patients were alive at the end of the study.
At the end of the study, 12/13 patients with the highest (>75%) CK5 expression were dead, while 6 of 18 patients with less than 75% expression were dead (p = 0.006, Fisher exact test). When compared with those patients whose tumours had less than 75% expression, patients whose tumours had greater than 75% CK5 expression had much poorer survival times (log-rank test; p <= 0.001).
The findings suggest that very high levels of CK5 expression may be a potential marker for worse outcome in intermediate- and high-grade MEC.
An evaluation of Chromogenic MRSA medium (CMRSA), MRSASelect (MRSAS) and Oxacillin Resistance Screening Agar (ORSA) was performed to determine the optimum medium providing a rapid and sensitive method for methicillin-resistant Staphylococcus aureus (MRSA) detection.
A total of 632 clinical specimens were cultured on the three media in first phase of the study, while 720 clinical specimens were cultured on CMRSA and ORSA in the second phase.
The sensitivity and specificity, respectively, of the media in the first phase were: CMRSA 88.9% and 98.45%; MRSAS 92.1% and 99.1%; ORSA (24 h incubation) 68.3% and 98.8%; and ORSA (48 h incubation) 85.7% and 96.3%. In the second phase the sensitivity and specificity, respectively, were CMRSA 91.2% and 98.6%; ORSA (24 h incubation) 58.9% and 98.2%; and ORSA (48 h incubation) 85.6% and 95.6%. The positive predictive values of the two chromogenic media were higher than that for ORSA. There were fewer false-positive results with the chromogenic media (1.4% for CMRSA and 0.8% for MRSAS) compared with ORSA (3.3%).
Performing latex agglutination tests on growth from chromogenic media provides results for 93.8% of MRSA isolates within 24 h. There is a small increase in cost of chromogenic media compared with ORSA (£28 for MRSAS, and £36 for CMRSA, per 1000 specimens) and direct agglutination tests (£80 per 1000 specimens). However early availability of MRSA screening results can reduce the burden of MRSA in hospitals because of early implementation of infection control measures.
Dysregulation of apoptosis is important in carcinogenesis.
To analyse the potential inactivation of the DAP kinase/p14/HDM2/p53/Apaf-1 pathway by aberrant promoter methylation in acute leukaemias.
Of five leukaemic lines examined, p14 was unmethylated in Raji, HL60 and U937, but completely deleted in Jurkat and NB4. DAP kinase was totally methylated in Raji and NB4, but unmethylated in HL60, Jurkat and U937. Apaf-1 was unmethylated in all the lines. At diagnosis, DAP kinase methylation occurred in eight (25%) APL patients and none of the other AML patients (8/32 vs 0/50, p = 0.001). DAP kinase methylation was detected in four (16%) ALL patients. p14 and Apaf-1 methylation was not detected in any of the 32 cases of acute promyelocytic leukaemia (APL), 50 cases of other subtypes of acute myeloid leukaemia (AML), and 25 cases of acute lymphoblastic leukaemia.
Among AML subtypes, DAP kinase is preferentially hypermethylated in APL.
To establish the most frequent pathological findings encountered at postmortem examination during the investigation of a fatality with a history of cocaine abuse.
Autopsied deaths investigated by the coroner for the Eastern district of London, between 2004 and 2007, in which the decedent had positive toxicology for cocaine were identified (n = 28). The autopsy records and histology of tissue taken at autopsy were retrieved and reviewed. Pathological findings (gross and microscopic, including cardiac, pulmonary, gastrointestinal, hepatobiliary, renal and neurological) were collated.
The main pathological findings at autopsy occurring in this cohort (comprising predominantly men, mean age 31 years), were cardiovascular: left ventricular hypertrophy (46%), multifocal myocardial fibrosis (21%), coronary artery disease (29%), cerebrovascular disease (36%) and pulmonary oedema (71%). Hepatic steatosis (29%) and gastrointestinal haemorrhage (18%), due mostly to gastric erosions/ulceration, were also frequent findings.
During a coroner’s autopsy of a cocaine user, a thorough cardiac examination combined with cardiac tissue sampling for histology, are valuable investigations, which are most likely to help show pathology relevant to the cause of death.
Odontogenic tumours are often biphasic, consisting of epithelial and interstitial components, with an origin that is not well understood. Odontogenic fibromas are rich in mesenchymal component, but also have many epithelial nests.
To investigate the origin of this tumour by immunohistochemistry.
The expression of several odontogenic and epithelial markers, including amelogenin, was investigated by immunofluorescent studies.
Immunohistochemical analysis showed that epithelial nests exhibited E-cadherin expression, but not amelogenin. Amelogenin positive cells were scattered in the fibrous tissue, which did not exhibit epithelial marker expression except for epithelial membrane antigen. In one case that had received a test biopsy before whole resection of tumour, amelogenin positive cells were distributed in the regenerating mucosal epithelium or subepithelial tissue.
Results indicate that amelogenin positive cells of odontogenic fibromas have an epithelial origin and may have the potential for epithelial mesenchymal transition, which has not to date been investigated in benign tumours.
Changes in junctional catenin expression may compromise cadherin-mediated adhesion, increasing cell malignant properties such as invasive and metastatic abilities. Altered expression of -, β-, - and p120-catenin has been reported to be associated with E-cadherin loss or decreased expression, in both breast carcinomas and breast cancer cell lines.
To investigate the expression and subcellular localisation of p120- and β-catenin in a series of human invasive breast carcinomas, and correlate it with biological markers and clinicopathological parameters.
Both catenins frequently exhibited a reduced membranous or cytoplasmic staining pattern. These alterations were significantly correlated with lack of both E-cadherin and oestrogen receptor- expression. It was possible to associate the expression of β-catenin with histological grade, tumour size and nodal status, suggesting a relevant role for this catenin as a prognostic factor. The majority of E- and P-cadherin co-expressing tumours were related to cytoplasmic expression of p120-catenin; in this group of breast carcinomas, patient survival was poor.
Results indicate that p120-catenin cytoplasmic accumulation may play an important role in mediating the oncogenic effects derived from P-cadherin aberrant expression, including enhanced motility and invasion, particularly in tumours which maintain E-cadherin expression.