Cronkhite-Canada syndrome six decades on : the many faces of an enigmatic disease

Cronkhite–Canada syndrome is a rare gastro-enterocolopathy of uncertain aetiology first described almost 60 years ago. It is characterised by diffuse gastrointestinal polyposis sparing only the oesophagus, ectodermal abnormalities and an unpredictable but often fatal clinical course. The disease may demonstrate extremely diverse clinical and endoscopic features, which often leads to a delay in diagnosis. A high index of suspicion and recognition of the characteristic histological findings frequently facilitate a correct diagnosis, but the distribution of the gastrointestinal pathology and its microscopic features may be atypical. The pathologist thus requires a thorough knowledge of both the typical and many atypical faces of this disease, for which various documented therapies often still prove ineffective. Close correlation with clinical findings, including any pertinent ectodermal abnormalities, and careful examination of biopsies derived from polypoid and endoscopically spared mucosa will ensure a timely and correct diagnosis in patients with this enigmatic syndrome.http://jcp.bmj.com/hb201

Antitumor activity and other biological actions of oligomers of ribonuclease A.

Dimers, trimers, and tetramers of bovine ribonuclease A, obtained by lyophilization of the enzyme from 40% acetic acid solutions, were purified and isolated by cation exchange chromatography. The two conformers constituting each aggregated species were assayed for their antitumor, aspermatogenic, or embryotoxic activities in comparison with monomeric RNase A and bovine seminal RNase, which is dimeric in nature. The antitumor action was tested in vitro on ML-2 (human myeloid leukemia) and HL-60 (human myeloid cell line) cells and in vivo on the growth of human non-pigmented melanoma (line UB900518) transplanted subcutaneously in nude mice. RNase A oligomers display a definite antitumor activity that increases as a function of the size of the oligomers. On ML-2 and HL-60 cells, dimers and trimers generally show a lower activity than bovine seminal RNase; the activity of tetramers, instead, is similar to or higher than that of the seminal enzyme. The growth of human melanoma in nude mice is inhibited by RNase A oligomers in the order dimers < trimers < tetramers. The action of the two tetramers is very strong, blocking almost completely the growth of melanoma. RNase A dimers, trimers, and tetramers display aspermatogenic effects similar to those of bovine seminal RNase, but, contrarily, they do not show any embryotoxic activity

Toothy craniopharyngioma : a literature review and case report of craniopharyngioma with extensive odontogenic differentiation and tooth formation

No abstract available.http://www.springerlink.com/content/100510

Endoscopic ultrasound guided fine needle aspiration allows accurate diagnosis of mycobacterial disease in HIV-positive patients with abdominal lymphadenopathy

BACKGROUND : Abdominal lymphadenopathy in HIV remains a challenge due to inaccessibility of lymph nodes and multitude of causes. The diagnostic yield of EUS FNA in HIV-infected patients with abdominal lymphadenopathy in the setting of high tuberculosis (TB) prevalence was assessed. METHODS : Prospective cohort study was conducted in tertiary referral centres recruiting symptomatic HIV+ patients (N=31, mean age 38.5 years, mean CD4 count 124 cells/μl, WHO stage 3-4 with abdominal lymphadenopathy. EUS was performed to assess lymph node characteristics and FNA aspirate subjected to cytological analysis, microbial culture and PCR. RESULTS : EUS appearance of lymph nodes was highly variable. Mycobacterial infections were the most common cause of lymphadenopathy in this cohort. Of the 31 patients 21/31 67.7 % had mycobacterial infections; 17 (80.9 %) of these were tuberculosis. Cytology failed to identify 23.8% and culture 38.1% of cases. PCR identified 16/17 (94.1%) of these cases. EUS-FNA altered the management of more than half of the patients. CONCLUSIONS : Mycobacterial disease was the commonest cause of lymphadenopathy in HIV but a third of patients had reactive lymphadenopathy. By combining the appearance of EUS FNA and cytological aspirate we could develop a diagnostic algorithm with a high PPV and NPV to identify patients in whom further analysis with PCR would be useful. PCR was highly accurate in confirming mycobacterial disease and determining genotypic drug resistance.South African Gastroenterological Society (SAGES)/Astra Zeneca Fellowship in Gastroenterologyhttp://www.journals.elsevier.com/ultrasound-in-medicine-and-biology/hb201

Interobserver agreement of estimating the extent of intestinal metaplasia in patients with chronic atrophic gastritis

The extent of gastric intestinal metaplasia (GIM) can be used to determine the risk of gastric cancer. Eleven international gastrointestinal expert pathologists estimated the extent of GIM on haematoxylin and eosin (H&E)- and Alcian blue-Periodic acid Schiff (AB-PAS)-stained slides of 46 antrum biopsies in 5% increments. Interobserver agreement was tested with the intraclass correlation coefficient (ICC). Correlation between standard deviation and extent of GIM was evaluated with the Spearman correlation. The interobserver agreement was very good (ICC = 0.983, 95% confidence interval (CI) 0.975–0.990). The use of AB-PAS did not increase the agreement (ICC = 0.975, 95% CI 0.961–0.985). Cases with a higher amount of metaplastic epithelium demonstrated a higher standard deviation (rs = 0.644; p < 0.01), suggesting lower diagnostic accuracy in cases with extensive GIM. In conclusion, estimating the extent of GIM on H&E-stained slides in patients with chronic atrophic gastritis can be achieved satisfactorily with high interobserver agreement, at least among international expert gastrointestinal pathologists.Open access funding provided by Medical University of Graz.https://www.springer.com/journal/428am2023Anatomical Patholog

Polymerase chain reaction amplifying mycobacterial DNA from aspirates obtained by endoscopic ultrasound allows accurate diagnosis of mycobacterial disease in HIV-positive patients with abdominal lymphadenopathy

Abdominal lymphadopathy in Human Immunodeficiency Virus (HIV) infection remains a diagnostic challenge. We performed a prospective cohort study recruiting thirty-one symptomatic HIV+ patients with abdominal lymphadenopathy assessing diagnostic yield of endoscopic ultrasound (EUS) fine needle aspiration (FNA). Mean age was 38 years, 52% were female, mean CD4 count and viral load were 124 cells/pl, and 4 log respectively. EUS confirmed additional mediastinal nodes in 26 %. Porta- hepatis was the most common abdominal site. EUS FNA was subjected to cytology, culture and polymerase chain reaction (PCR) analysis. Mycobacterial infections were confirmed in 67.7% and 31% had reactive lymphadenopathy. Cytology and culture had low sensitivity whereas PCR identified 90% of mycobacterial infections. Combining appearance of EUS FNA and cytology a diagnostic algorithm was developed to indicate when analysis with PCR would be useful. PCR performed on an EUS guided aspirate was highly accurate in confirming mycobacterial disease and determining genotypic drug resistance.South African Gastroenterological Society (SAGES)/ Astra Zeneca Fellowship in Gastroenterology awarded to Schalk van der Merwehttp://www.journals.elsevier.com/ultrasound-in-medicine-and-biology/hb201

CD14+ macrophages that accumulate in the colon of African AIDS patients express pro-inflammatory cytokines and are responsive to lipopolysaccharide

BACKGROUND : Intestinal macrophages are key regulators of inflammatory responses to the gut microbiome and play a central role in maintaining tissue homeostasis and epithelial integrity. However, little is known about the role of these cells in HIV infection, a disease fuelled by intestinal inflammation, a loss of epithelial barrier function and increased microbial translocation (MT). METHODS : Phenotypic and functional characterization of intestinal macrophages was performed for 23 African AIDS patients with chronic diarrhea and/or weight loss and 11 HIV-negative Africans with and without inflammatory bowel disease (IBD). AIDS patients were treated with cotrimoxazole for the prevention of opportunistic infections (OIs). Macrophage phenotype was assessed by flow cytometry and immuno-histochemistry (IHC); production of proinflammatory mediators by IHC and Qiagen PCR Arrays; in vitro secretion of cytokines by the Bio-Plex Suspension Array System. Statistical analyses were performed using Spearman’s correlation and Wilcoxon matched-pair tests. Results between groups were analyzed using the Kruskal-Wallis with Dunn’s post-test and the Mann–Whitney U tests. RESULTS : None of the study participants had evidence of enteric co-infections as assessed by stool analysis and histology. Compared to healthy HIV-negative controls, the colon of AIDS patients was highly inflamed with increased infiltration of inflammatory cells and increased mRNA expression of proinflammatory cytokine (tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IFN-γ, and IL-18), chemokines (chemokine (C-C motif) ligand (CCL)2 and chemokine (C-X-C) motif ligand (CXCL)10) and transcription factors (TNF receptor-associated factor (TRAF)6 and T-box (TXB)21). IHC revealed significant co-localization of TNF-α and IL-1β with CD68+ cells. As in IBD, HIV was associated with a marked increase in macrophages expressing innate response receptors including CD14, the co-receptor for lipopolysaccharide (LPS). The frequency of CD14+ macrophages correlated positively with plasma LPS, a marker of MT. Total unfractionated mucosal mononuclear cells (MMC) isolated from the colon of AIDS patients, but not MMC depleted of CD14+ cells, secreted increased levels of proinflammatory cytokines ex vivo in response to LPS CONCLUSIONS : Intestinal macrophages, in the absence of overt OIs, play an important role in driving persistentinflammation in HIV patients with late-stage disease and diarrhea. These results suggest intensified treatmentstrategies that target inflammatory processes in intestinal macrophages may be highly beneficial in restoringthe epithelial barrier and limiting MT in HIV-infected patients.This research and selected researchers (EC, TR, PM, SM and CS) were funded in part by a grant from the Delegation of the European Union to South Africa: “Drug Resistance Surveillance and Treatment Monitoring Network for the Public Sector HIV Antiretroviral Treatment Programme in the Free State – Sante 2007/147-790” and by a grant from the National Research Council of South Africa, Unlocking the Future 61509.http://www.biomedcentral.com/bmcinfectdisam201

Prophylactic human papillomavirus vaccination against cervical cancer : a summarised resource for clinicians

No abstract available.http://www.sajgo.co.za/index.php/sajg

EMERALD and EMIT—worldwide computer aided education and training packages in medical physics

This paper describes the development of two web based education and training packages EMERALD and EMIT designed to meet the training needs of professional medical physicists. The program has been developed over a number of years by collaboration between hospitals and universities across Europe. The program concentrates on assisting competence development in five initial areas: diagnostic radiology; nuclear medicine; magnetic resonance tomography; ultrasound; and radiotherapy. Each of the topic areas includes around 50 training tasks in five hypertext workbooks, supplemented by a topical image database. The training materials have been extensively refereed during the development phase and are now in use in 65 countries across the globe. Initial evaluation has shown that the material enhances the training experience and produces a more consistent output

Diagnosis and predictive molecular analysis of non-small cell lung cancer in the Africa-Middle East region : challenges and strategies for improvement

The identification of tumor biomarkers provides information on the prognosis and guides the implementation of appropriate treatment in patients with many different cancer types. In nonesmall cell lung cancer (NSCLC), targeted treatment plans based on biomarker identification have already been used in the clinic. However, such predictive molecular testing is not currently a universally used practice. This is the case, in particular, in developing countries where lung cancer is increasingly prevalent. In September 2012 and November 2013, a committee of 16 lung cancer experts from Africa and the Middle East met to discuss key issues related to diagnosis and biomarker testing in NSCLC and the implementation of personalized medicine in the region. The committee identified current challenges for effective diagnosis and predictive analysis in Africa and the Middle East. Moreover, strategies to encourage the implementation of biomarker testing were discussed. A practical approach for the effective diagnosis and predictive molecular testing of NSCLC in these regions was derived. We present the key issues and recommendations arising from the meetings.Pfizer Inc.http://www.journals.elsevier.com/clinical-lung-cancer/hb201