Induction of hypoxia in normal and malignant tissues by changing the oxygen affinity of hemoglobin--implications for therapy.

The drug BW12C, which increases the oxygen affinity of hemoglobin, reduces oxygen availability to tissues. This results in protection against radiation damage to the hemopoietic system and epidermal Langerhans cells in CBA mice. The drug also protects against beta-irradiation damage in pig epidermis. BW12C increases the hypoxic cell fraction in tumors and histological examination of an experimental T cell lymphoma shows that the induced hypoxia leads to tumor necrosis.

Demonstration of alpha-1-antitrypsin and alpha-1-antichymotrypsin in fibrous histiocytomas using the immunoperoxidase technique.

Until recently, the diagnosis and classification of malignant fibrous histiocytomas (MFH) has been based on light- and electron-microscopic appearances. Tissue culture studies have led to the suggestion that these tumors have a common histiocytic origin. Using the immunoperoxidase PAP technique, a variety of soft-tissue tumors have been stained for the histiocyte markers alpha-1-antitrypsin (A1AT), alpha-1-antichymotrypsin (A1ACT) and lysozyme. A1AT and A1ACT are found to be useful specific markers for tumors of the MFH group whereas lysozyme is not a reliable marker for such tumors. The presence of these substances within the tumors supports the theory that they share a common origin from tissue histiocytes. Only a proportion of superficial skin histiocytomas stain for A1AT and A1ACT, raising the possibility that these are a heterogeneous group and do not share a common histogenesis with MFH.

An immunohistochemical study of Whipple's disease using the immunoperoxidase technique.

Formalin-fixed, paraffin-embedded jejunal, lymph nodal, and splenic tissues were obtained from four patients with Whipple's disease. Using antisera to a variety of bacteria, sections were stained by the immunoperoxidase technique. Positive staining was obtained with antiserum to streptococcus group B in all tissues examined. The distinctive pattern of staining was similar to the findings of previous workers using fluorescein-labeled antibodies. However, when rigorous controls for specificity were applied in this study, it was not possible to confirm the presence of streptococcus B antigen in the tissues. The discrepancy between the specificity of the technique on control and test sections is interesting and emphasizes the need for adequate controls when the immunoperoxidase technique is used to look for microorganisms in tissues. It is suggested that the unknown microorganism observed in the macrophages of patients with Whipple's disease has been altered in some way to resemble streptococcus B antigenically or that it shares common antigens with streptococcus B.

Continuing medical education for pathologists: an evaluation of the Royal College of Pathologists' Wessex pilot scheme.

AIM: To discover the attitudes to continuing medical education (CME) of the Wessex pathologists who participated in the Wessex CME pilot scheme and to identify their preferences and difficulties in pursuing CME activities. METHOD: The views of pathologists in the scheme were collected during a period of one year using workshops and discussions. A confidential, anonymous postal questionnaire based on these issues was sent to the 103 pathologists in Wessex who participated in the pilot scheme. RESULTS: A 64% response rate was obtained. The respondents identified lack of time and funded study leave as major barriers to CME and highlighted the gap between CME activity and its recognition and funding by employers. They wanted a wide variety of locally based CME activities to be recognised, and they valued local activities that linked theory with practice. They believed that the college scheme tended to favour academic activities over more practical and locally based ones. They found the paired peer review process time consuming but valuable for identifying their learning needs in some cases, but demonstrated that they have mixed preferences about the way they do their CME. CONCLUSIONS: The Wessex pathologists believe that CME is important and have positive attitudes to it. Their attitudes to CME echo the current literature about what makes CME effective. Unless individuals' preferences and difficulties are taken into account, CME programmes in which they participate are not likely to succeed.

Mucosal prolapse syndrome--a unifying concept for solitary ulcer syndrome and related disorders.

Nineteen cases of classical solitary ulcer of the rectum syndrome (SURS) and sixteen examples of rectal mucosal prolapse are described. Similarities in the histological and histochemical features of the two groups lead us to suggest that the term "mucosal prolapse syndrome" be used to describe this group of disorders in which mucosal prolapse--overt or occult is the common underlying pathogenetic mechanism.

A clinicopathological survey of gallstones in the autopsy population.

This prospective study looked at the autopsy prevalence of gallstones and their relationship with symptoms and gallbladder pathology. Fifty consecutive autopsies were selected. The gallbladder was examined macroscopically and microscopically and gallstones were examined, cut and classified. Four females at autopsy had had previous cholecystectomies. Thirty three percent of patients had gallstones at post-mortem with a male to female ratio of 1:1.24. Histological features of the gallbladders were: normal 39.1%, cholecystitis 37.0%, hypertrophy 8.7% and fibrosis 15.2%. Increasing age was significantly associated with increasing common bile duct (CBD) circumference. Muscle hypertrophy and fibrosis may represent part of a spectrum of "burnt out" gallbladder disease. Fifteen percent of autopsy patients had calcular cholecystitis but were asymptomatic and the reason for this is unclear.

Will Rogers revisited: prospective observational study of survival of 3592 patients with colorectal cancer according to number of nodes examined by pathologists.

To investigate the relationship between survival in colorectal cancer patients and the number of lymph nodes examined by a pathologist, previously attributed to stage migration, we used data from a cohort of 5174 colorectal cancer patients recruited between September 1991 and August 1994, and followed-up for 5 years. We selected cases with data present on all prognostic variables, and stratified them into three groups by number of nodes examined. We made a multivariate survival comparison using a Cox regression model. In all, there were 3592 cases with data present on all prognostic variables. Patients who had >10 nodes identified had a significant survival advantage over those who had 5-10 identified, who had in turn a similar advantage over those with 0-4 identified (P<0.001). This effect was present in the whole group and at all Dukes' stages, although statistically significant only in stages B (P=0.004) and C (P=0.019). The effect remained after adjustment in a Cox regression model in which the mean number of nodes taken out by each surgical firm did not predict survival. In a sub-group with data on lymphocytic infiltration into the primary tumour a survival advantage was noted in those with prominent rather than mild infiltration (P<0.001): the former also tended to have more nodes found (P=0.015). Stage migration alone cannot explain these results, as survival advantages are noted across the whole population independent of stage. Lymphocytic infiltration into the primary tumour is prognostically important, and is associated with the number of nodes found. Reactive enlargement of lymph nodes in the mesentery may make them easier to find, reflect immune response to the tumour, and thus indirectly impact upon survival.

Immunohistochemistry of soft tissue tumours: a review.

The diagnosis and classification of soft tissue sarcomas can pose difficult problems for the histopathologist. Many sarcomas are too poorly differentiated to exhibit morphological features specific enough to define their histogenesis. Using the immunoperoxidase technique with commercially available antisera as a routine adjunct to other diagnostic aids, it is possible to arrive at more accurate diagnoses on which treatment protocols can be based. In addition a better understanding of mesenchymal neoplasms and their origins can be obtained by functional immunohistochemical studies.

Demonstration of fibronectin in soft tissue tumours using the immunoperoxidase technique.

A variety of reactive, benign and malignant soft tissue lesions have been stained for fibronectin using the immunoperoxidase technique. Two patterns of mesenchymal staining have emerged. The first has a diffuse stromal collagen and basement membrane distribution within normal and neoplastic mesenchyme and the second a more specific intracytoplasmic granular staining pattern. The latter is seen only in lesions derived from fibrous-histiocytic and synovial cells, a finding which may be of diagnostic use. The possible significance of intracellular fibronectin in neoplastic mesenchyme is discussed.

Carcinoma of the oesophagus with spindle cell features.

There is considerable confusion surrounding the histogenesis and nomenclature of squamous cell carcinomas of the oesophagus with spindle cell elements. These tumours, many of which are polypoid, have been variously called carcinosarcoma, pseudosarcoma and polypoid carcinoma of the oesophagus. A study of three recent cases strongly supports the theory that these tumours are squamous cell carcinomas with spindle cell metaplasia. They are not necessarily polypoid and adenocarcinomatous elements may also be present.

'Nodular necrobiosis': a new cutaneous manifestation of Crohn's disease?

A skin lesion previously unassociated with Crohn's disease is described. Although superficially resembling erythema nodosum it runs a different clinical course and has different histological appearances, the central feature being necrobiotic collagen. The term ;nodular necrobiosis' is suggested.

The clinical skills resource: a review of current practice.

This review is based on the findings of the Southampton Clinical Skills Project, which was a needs assessment and feasibility study to consider the development of a multiprofessional Clinical Skills Resource at Southampton. The project spanned a period of 18 months and used a range of methods of data collection, including visits to 12 clinical skills facilities in the UK. Most existing clinical skills centres have developed in response to changing healthcare policy, curricular initiatives and increasing emphasis on the quality of assessments and competencies. There is also increasing recognition that clinicians are no longer able to teach effectively all skills to students in the traditional ways, and that clinical skills training and assessment, particularly for undergraduates, is an area of deficiency. The potential scope of clinical skills centres is broad and encompasses not only clinical and communication skills but medical informatics, computer assisted learning, multiprofessional learning and assessment. Skills centres can also promote self directed and lifelong learning methods. The planning of skills centres involves a variety of stakeholders and users, including undergraduates, postgraduates, acute and community Trusts, Postgraduate Deans and medical schools. A successful skills centre needs to be flexible in its design, integral to the curriculum and relevant to educational and training requirements. This requires planning, organization and resources. Different organizational models can be used, depending on local factors. The management of skills centres involves consideration of issues such as security, safety, supervision of learners and staff development, informed by a network of experts and everyday users. The development of skills centres should include ongoing educational evaluation of outcomes and educational research. The use of a clinical skills centre has potential benefits for staff and students, including the provision of a safe environment in which to learn and practise skills before using them in the real clinical setting. This can reduce anxiety in students and protect patients from novice practice. Clinical skills centres provide a setting for structured learning with feedback as well as assessment of competence. The limitations of a skills centre are that it can only provide simulated experiences which are an adjunct to, but can never replace real clinical experience.

A case of ovarian fibromatosis with disseminated intra-abdominal fibromatosis.

A case of bilateral ovarian fibromatosis and massive oedema with subsequent intra-abdominal fibromatosis which underwent an aggressive and fatal course is described. This is the first report of co-existence of these two conditions and the possible relationship between them is discussed.

A histopathological study of the appendix at autopsy and after surgical resection.

In a study of 101 autopsy appendices and over 3000 surgically resected appendices the range of histopathological features seen in each group is described. Fibrosis and faecoliths were more common in the older autopsy group than in the younger surgically resected group. The high incidence of fibrosis in the autopsy group suggests that this is an age-related change, although some may be due to previous inflammation. The low incidence of faecoliths in the surgically resected group does not support the hypothesis that they are a major cause of appendicitis.