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Extracellular proteases of the matrix metalloproteinase (MMP) and serine protease families participate in many aspects of tumour growth and metastasis. Using quantitative real-time RT-PCR analysis, we have undertaken a comprehensive survey of the expression of these enzymes and of their natural inhibitors in 44 cases of human prostate cancer and 23 benign prostate specimens. We found increased expression of MMP10, 15, 24, 25 and 26, urokinase plasminogen activator-receptor (uPAR) and plasminogen activator inhibitor-1 (PAI1), and the newly characterised serine proteases hepsin and matriptase-1 (MTSP1) in malignant tissue compared to benign prostate tissue. In contrast, there was significantly decreased expression of MMP2 and MMP23, maspin, and the protease inhibitors tissue inhibitor of metalloproteinase 3 (TIMP3), TIMP4 and RECK (reversion-inducing cysteine-rich protein with Kazal motifs) in the cancer specimens. The expression of MMP15 and MMP26 correlated positively with Gleason score, whereas TIMP3, TIMP4 and RECK expression correlated negatively with Gleason score. The cellular localisation of the expression of the deregulated genes was evaluated using primary malignant epithelial and stromal cell cultures derived from radical prostatectomy specimens. MMP10 and 25, hepsin, MTSP1 and maspin showed predominantly epithelial expression, whereas TIMP 3 and 4, RECK, MMP2 and 23, uPAR and PAI1 were produced primarily by stromal cells. These data provide the first comprehensive and quantitative analysis of the expression and localisation of MMPs and their inhibitors in human prostate cancer, leading to the identification of several genes involved in proteolysis as potential prognostic indicators, in particular hepsin, MTSP1, MMP26, PAI1, uPAR, MMP15, TIMP3, TIMP4, maspin and RECK. [ABSTRACT FROM AUTHOR]

Background and Aim: Conventional banking of bone allografts has been well documented in the literature. It relies on standardised screening and providing a sterile storage facility. We report a new surgical technique of banking the femoral head in a surgically fashioned subperiosteal iliac pouch and its use for the donor's own surgery. Material and Methods: Thirteen patients with an average age of 60 years and a diagnosis of osteoarthritis of the hip with a contralateral symptomatic loose hip replacement were selected. The femoral head was harvested and banked. On retrieval, histological analysis was performed in four specimens with clinical and radiographic review of all subjects. Results: Radiographic results show good integration of the morselised femoral head bone graft in revision hip surgery. Histological results from four retrieved specimens show viability at eight years and eleven months from insertion into the pouch. Discussion: Autobanking of the patient's own femoral head is suitable in a select group of patients in whom a combined primary and contralateral revision total hip replacement poses an unacceptable anaesthetic risk. It has the advantage of providing a graft with osteoinductive potential and a reduced risk of infection. It eliminates the need for a storage facility and screening programme. It also provides a portable storage facility if the patient moves elsewhere. [ABSTRACT FROM AUTHOR]

It is proposed that atherosclerosis is a chronic inflammatory disease in which monocyte-derived macrophages are doing harm and smooth muscle cells are essentially reparative. Activities of macrophages that might be contributory to the development of atherosclerosis are tabulated. Observations and experiments are described that suggest macrophages may be contributing to lipoprotein oxidation within the plaque and that individual humans vary in their macrophage oxidative capacity. The possibility of intervention with antioxidants is discussed. [ABSTRACT FROM PUBLISHER]

Fifteen epididymectomies were performed on 10 patients with post-vasectomy pain and 12 specimens were available for histopathological review. The findings were compared with those in 2 groups in which epididymectomy was performed for chronic epididymo-orchitis and epididymal cysts. The results showed that 50% of the post-vasectomy group were cured by simple epididymectomy. Pathological findings revealed features of long-standing obstruction and interstitial and perineural fibrosis which may have accounted for the pain. It is important to recognise this late complication of vasectomy and, if surgery is to be performed, to include all of the distal vas and previous vasectomy site in the excision. [ABSTRACT FROM AUTHOR]

A case of an 84 year old man presenting with obstruction of the superior vena cava caused by an intimal sarcoma of the right brachiocephalic vein is reported. The tumour morphology was similar to intimal sarcomas arising in major arteries, a more common primary site, and showed malignant fibrous histiocytoma-like features. Immunohistochemistry was suggestive of myofibroblastic differentiation. [ABSTRACT FROM PUBLISHER]

Describes the case of a man with systemic lupus erythematosus (SLE) affecting the testis. Medical treatment and clinical history of the patient; Classification criteria for SLE; Role of vasculitis in a lupus-like disease.

Presents a letter to the editor commenting on degenerative changes in patients with primary hip replacement.

Aim: To highlight some problems that may occur when investigating clozapine-associated deaths including (i) that death may be related to gastrointestinal hypomotility and (ii) that post-mortem blood clozapine and norclozapine concentrations may not reflect ante-mortem concentrations., Case Reports: A 41-year-old male died 40 min after admission to hospital as a result of aspiration complicating severe, clozapine-induced constipation. At post-mortem the small bowel was dilated and contained bloodstained mucus, particularly within the jejunum. The large bowel was considerably dilated and contained large quantities of foul-smelling, bloodstained fluid and a small amount of stool. Its lining was focally congested, but there was no other obvious abnormality. Analysis of serum obtained on admission revealed clozapine and norclozapine concentrations of 0.56 and 0.43 mg/L, respectively, whereas post-mortem femoral whole blood obtained <34 h after death showed clozapine and norclozapine concentrations of 3.73 and 1.75 mg/L, respectively. In 6 out of a further 12 clozapine-associated deaths investigated 2002-9 there were reports of gastrointestinal tract problems of varying severity., Conclusions: Severe constipation or paralytic ileus in clozapine-treated patients may lead to intestinal necrosis and/or perforation, or pulmonary aspiration. In some such cases the immediate cause of death may be obvious, but in others only careful assessment of the clinical course of the terminal illness may reveal gastrointestinal hypomotility as a likely underlying cause of death., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Intra-operative assessment of the sentinel lymph node (SLN) status may allow the surgeon to complete the breast cancer surgery in most patients in one sitting. We have studied the role of imprint cytology in the assessment of SLN status., Patients and Methods: Imprint cytology of the SLN in 132 patients with invasive breast carcinoma was correlated with the histopathological assessment of the SLN and overall axillary nodal status. In 26 patients, the cytology was reported intra-operatively., Results: Imprint cytology reflected the status of the parent node well (sensitivity 86%, specificity 97%, positive predictive value (PPV) 92%, negative predictive value (NPV) 93%). Its ability to reflect the axillary status was also good (sensitivity 70%, specificity 97%, PPV 95% and NPV 83%) but somewhat diminished by the relatively high number of false-negative SLN in the study. Intra-operative assessment (sensitivity 86%, specificity 100%, PPV 100% and NPV 95%) did not reduce the accuracy of imprint cytology in predicting the SLN status and took a mean of 24.5 min., Conclusions: Imprint cytology is an accurate and relatively simple method for the assessment of the SLN and can be a useful intra-operative tool.

The development locally of a malignant neoplasm after total hip arthroplasty is rare but increasingly recognized. Its significance is unclear. The association could be fortuitous. If not, the rarity of the complication argues that constitutional factors are likely to be important in pathogenesis. We describe a case of disseminated osteosarcoma of the hip developing 6.5 years after total hip arthroplasty and review the related literature.

Urethral melanoma is very rare and pathological diagnosis is important. The prognosis remains poor irrespective of the treatment modality. Rare cases of long-term survival have been reported, one of them following conservative management. An initial attempt at conservative resection is worth considering to offer a better quality of life to the patient for as long as possible. We describe a technique of organ-sparing resection in the management of urethral melanoma along with the follow-up protocol that we adapted., (Copyright 2001 The British Association of Plastic Surgeons.)

We report a case of long-standing SLE which presented with symptomatic muscle vasculitis on a background of photosensitivity, arthralgia and myalgia. The diagnosis was complicated by cardiomyopathy, nephrotic syndrome and diabetes. We highlight the benefits of aggressive treatment in severe disease and the importance of recognising and treating comorbidity especially ih relation to atherosclerosis.

A 68-year-old man presented with obstructive and irritative lower urinary tract symptoms and microscopic hematuria. Cystourethroscopy showed a circumferential stricture in the bulbar urethra that bled easily on contact. Biopsy revealed malacoplakia. There was also focal nonspecific cystitis. The patient improved symptomatically, but the microscopic hematuria persisted. Follow-up biopsies showed persistent urethral malacoplakia and stricture. Malacoplakia of the male urethra is exceptionally rare, this being the second reported case.

An elderly woman presenting with a perforated benign gastric peptic ulcer was found to have widespread dissemination of breast carcinoma. Several small discrete metastases were present within a large benign ovarian fibroma. The rare phenomenon of tumor-to-tumor metastasis is discussed in the context of ovarian pathology.

The bcl-2 proto-oncogene, which inhibits programmed cell death (apoptosis), has recently been found to be cyclically expressed in human endometrium. In order to investigate its role in endometrial hyperplasia and neoplasia, bcl-2 expression was studied in 25 cases of endometrial carcinoma and 20 cases of endometrial hyperplasia (eight simple, two complex, and ten atypical hyperplasias). Uniform intense cytoplasmic bcl-2 expression was found in all cases of non-atypical hyperplasia, and less strong positivity in eight out of ten cases of atypical hyperplasia. In well-differentiated carcinomas, nine out of ten showed weak to moderate bcl-2 expression, whereas six out of seven poorly differentiated carcinomas were bcl-2-negative. Moderately differentiated tumours were an intermediate group, with six out of eight being positive. Widespread localization of bcl-2 protein to the chromosomes of dividing cells was also demonstrated, regardless of cytoplasmic bcl-2 expression, with rare staining of interphase nuclei. Our findings suggest a role for bcl-2 in the natural history of endometrial neoplasia and studies are needed to determine its usefulness as a prognostic marker. The finding of bcl-2 localization to chromosomes has important implications for its mode and site of action.

Sections of human atherosclerotic lesions of different stages show that, in early lesions, the acellular lipid core is usually immediately adjacent to the deepest edge of a collection of macrophage foam cells. Advanced lesions with a large lipid core have variable numbers of macrophage foam cells, close to the lateral edges, or shoulders, of the core. In both early and advanced lesions, some of the macrophages nearest the core appear to be dying. Lipid cores contain two materials which in earlier lesions are found only in macrophages, namely ceroid and CD68 antigen, but do not contain recognisable smooth muscle cell actin. It is concluded that death of macrophage foam cells contributes to the origin and slow enlargement of the lipid core. The cause of macrophage death is not yet certain, but is under investigation.

Immunohistochemical studies to localise collagen IV, laminin, fibronectin and tenascin were undertaken in 59 bladder biopsies. These were non-neoplastic or contained foci of flat dysplasia or of transitional cell neoplasia. Collagen IV and laminin were reliably demonstrated in basement membranes but focal loss of reactivity for collagen IV was found in the urothelial basement membrane in some cases of inflammation, dysplasia, and non-invasive papillary transitional cell tumour. Basement membranes were rarely demonstrated around invasive transitional cell carcinomas. Fibronectin and tenascin were found in the sub-urothelial lamina propria and in some urothelial basement membranes. The stroma of invasive tumours reacted strongly for both. Increased numbers of sub-urothelial capillaries were present in association with some cases of cystitis, flat dysplasia or non-invasive transitional cell neoplasia suggesting an angiogenic stimulus in these circumstances. Immunohistochemical staining of basement membrane components is unlikely to be of value in the routine histopathological assessment of transitional cell neoplasms of the bladder.