Cognitive impairment in coeliac disease improves on a gluten-free diet and correlates with histological and serological indices of disease severity.

BACKGROUND: Mild impairments of cognition or 'Brain fog' are often reported by patients with coeliac disease but the nature of these impairments has not been systematically investigated. AIM: This longitudinal pilot study investigated relationships between cognitive function and mucosal healing in people with newly diagnosed coeliac disease commencing a gluten-free diet. METHODS: Eleven patients (8 females, 3 males), mean age 30 (range 22-39) years, were tested with a battery of cognitive tests at weeks 0, 12 and 52. Information processing efficacy, memory, visuospatial ability, motoric function and attention were tested. Small bowel biopsies were collected via routine gastroscopy at weeks 12 and 52 and were compared to baseline Marsh scores. Cognitive performance was compared to serum concentrations of tissue transglutaminase antibodies, biopsy outcomes and other biological markers. RESULTS: All patients had excellent adherence to the diet. Marsh scores improved significantly (P = 0.001, Friedman's test) and tissue transglutaminase antibody concentrations decreased from a mean of 58.4 at baseline to 16.8 U/mL at week 52 (P = 0.025). Four of the cognitive tests assessing verbal fluency, attention and motoric function showed significant improvement over the 12 months and strongly correlated with the Marsh scores and tissue transglutaminase antibody levels (r = 0.377-0.735; all P < 0.05). However, no meaningful patterns of correlations were found for nutritional or biochemical markers, or markers of intestinal permeability. CONCLUSIONS: In newly diagnosed coeliac disease, cognitive performance improves with adherence to the gluten-free diet in parallel to mucosal healing. Suboptimal levels of cognition in untreated coeliac disease may affect the performance of everyday tasks.

Type II EATL (epitheliotropic intestinal T-cell lymphoma): a neoplasm of intra-epithelial T-cells with predominant CD8αα phenotype.

In this multicentre study, we examined 60 cases of Type II enteropathy-associated T-cell lymphoma (EATL) from the Asia-Pacific region by histological review, immunohistochemistry and molecular techniques. Patients were mostly adult males (median age: 58 years, male:female 2.6:1), presenting with abdominal pain (60%), intestinal perforation (40%) and weight loss (28%). None had a history of coeliac disease and the median survival was only 7 months. Histologically, these tumours could be divided into (i) central tumour zone comprising a monotonous population of neoplastic lymphocytes, (ii) peripheral zone featuring stunted villi and morphologically atypical lymphocytes showing epitheliotropism, and (iii) distant mucosa with normal villous architecture and cytologically normal intra-epithelial lymphocytes (IELs). Characterized by extensive nuclear expression of Megakaryocyte-associated tyrosine kinase (MATK) (87%) and usually a CD8(+)CD56(+) (88%) cytotoxic phenotype, there was frequent aberrant expression of CD20 (24%). T-cell receptor (TCR) expression was silent or not evaluable in 40% but of the remainder, there was predominant expression of TCRαß over TCRγδ (1.6:1). In keeping with the normal ratio of IEL subsets, CD8(+) cases showed predominant CD8αα homodimer expression (77%), regardless of TCR lineage. These tumours constitute a distinct entity from classical EATL, and the pathology may reflect tumour progression from IEL precursors, remnants of which are often seen in the distant mucosa.

The granzyme B inhibitor, PI-9, is differentially expressed during placental development and up-regulated in hydatidiform moles.

The intracellular serpin Proteinase Inhibitor-9 (PI-9) is a potent inhibitor of the cytotoxic lymphocyte (CL) proteinase granzyme B, a major effector molecule used by CLs to induce target cell apoptosis. PI-9 is produced by CLs to protect against mis-directed granzyme B. However, PI-9 expression has also been reported in immune privileged tissues. In the present study, cell-specific expression of PI-9 in placental tissue of various gestational ages was examined by immunohistochemistry. PI-9 is highly expressed by the extravillous trophoblasts that have invaded the decidua, and this high expression is maintained throughout pregnancy. Similar levels were also observed in proliferative villous cytotrophoblasts. Syncytial trophoblasts generally do not produce PI-9 to a significant level until the last few weeks of pregnancy. The villous stroma contains mixed populations of PI-9 positive and negative cells throughout pregnancy, with highest expression during the second trimester. Compared to first trimester placentas, syncytial trophoblasts of partial and complete hydatidiform moles showed marked up-regulation of PI-9. Examination of choriocarcinoma cell lines also demonstrated a very high level of PI-9 is produced by these cells, which may provide protection from granzyme B-mediated apoptosis. The cell-specific expression of PI-9 in the placenta is consistent with a function in the maintenance of immune privilege, and it is proposed that up-regulated expression of PI-9 in gestational trophoblastic diseases contributes to disease pathogenesis via immune evasion.

Prescribing and the epilepsy specialist nurse.

Increasingly, the epilepsy nurse specialist has become an integral part of the specialist epilepsy team. Nurse specialists, who practice at an advanced level, frequently advise patients on diagnosis and antiepileptic drug changes. The inclusion of antiepileptic drugs to the nurse Prescribing Formulary would allow specialist nurses to provide a more enhanced service to patients.

The granzyme B inhibitor, PI-9, is present in endothelial and mesothelial cells, suggesting that it protects bystander cells during immune responses.

Proteinase inhibitor 9 (PI-9) is a 42-kDa human intracellular serpin present in cytotoxic lymphocytes (CLs). PI-9 is an extremely efficient inhibitor of the pro-apoptotic CL granule proteinase granzyme B and is thought to function in the cytosol of CLs to protect against apoptosis induced by endogenously expressed or released granzyme B, particularly during target cell killing. Here we show by immunohistochemistry that PI-9 is also present in endothelial cells, in every tissue examined. Cultured endothelial cells express functional PI-9 (as assessed by binding to recombinant granzyme B) localized to the cytoplasm and nucleus. Immunohistochemistry also showed PI-9 in mesothelial cells, and this was confirmed by analysis of primary cells cultured from pleural and serous effusions. Granzyme B expression was not detected in either endothelial or mesothelial cells. In both cell types, PI-9 is up-regulated at the mRNA and protein level by exposure to the phorbol ester PMA, consistent with a response to inflammatory stimuli. We postulate that PI-9 is present in these lining cell types to protect against misdirected, free granzyme B released during a local immune response.

A histological study of Denonvilliers' fascia and its relationship to the neurovascular bundle.

OBJECTIVE: To evaluate the anatomical relationship between the nerves and fasciae at the site of dissection in a radical retropubic prostatectomy. MATERIALS AND METHODS: Eight adult male (autopsy) en bloc specimens of bladder and rectum were examined histologically after staining with either haematoxylin and eosin or S-100 protein (as a specific nerve stain). RESULTS: All specimens showed Denovilliers' fascia to have no clearly defined layers and no definable lateral edge. No distinct neurovascular bundle was seen but nerves were scattered throughout the fasciae, including medially towards the midline. CONCLUSION: In radical retropubic prostatectomy, a piece of Denonvilliers' fascia is taken with the specimen, thus removing these nerves. The loss of these nerve fibres may explain the significant rate of erectile dysfunction after 'nerve-sparing' surgery.

Candidal epididymo-orchitis: case report and review.

We describe a case of epididymo-orchitis with candiduria and histologically proven epididymal abscesses due to Candida albicans and review six previously reported cases. Candidal epididymo-orchitis occurs in patients with recognized risk factors for candidal infection, often after instrumentation of the urinary tract. Cases caused by both C. albicans and Candida glabatra have been described. Drainage or orchidectomy may be required for definitive diagnosis and treatment. Treatment with oral antifungals alone has been effective in two cases.

Utilizing Rogers' Theory of Self-Concept in mental health nursing.

The work of mental health nurse is interactive in nature, the priority of which is the effective development and maintenance of a therapeutic relationship with clients. This field of nursing bases its practice on theories from many schools of thought in order to provide clients with the highest quality of care. One such theory is that of Carl Rogers whose practice as a psychotherapist was based on his Theory of Self-Concept. This paper examines the development of the Theory of Self-Concept from the works of Cooley, Mead, Allport and Rogers and relates to the therapeutic alliance between a primary nurse and a client who has been medically diagnosed as being 'depressed'. The implications for practice are considered and some of the difficulties of utilizing Rogers' theory on an in-patient unit are explored. The paper emphasizes the need for nurses to be aware of the use of such theories in order to enrich the care that clients receive. It also highlights the need for nurses to be aware of their own 'self' when working with clients, a state that can only be achieved if the nurses themselves have adequate clinical supervision and an environment which is supportive of such work.