Migration of Langerhans Cells from Carcinogen-Treated Sheep Skin

To define the mechanism(s) of carcinogen depletion of Langerhans cells (LC) from skin, the migration of LC from the skin to the regional lymph node was examined in carcinogen-treated, antigen-treated, and control sheep. This was assessed by cannulation of afferent lymphatic vessels that drain the treated areas of skin or the efferent lymphatic draining the regional lymph node. Cells draining from test or control skin were continuously collected and enumerated by indirect immunofluorescence and flow cytometry using specific anti-CD1 monoclonal antibodies. There was a marked increase in the rate of LC migration in the 8h following the application of the contact sensitizing antigen trinitrochlorobenzene (TNCB). The chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) triggered a tenfold-greater migration of LC compared with TNCB—with the peak response at 5 d. After DMBA treatment LC were also detected in the efferent lymph of the regional lymph node. It is concluded that the depletion of LC from carcinogentreated skin is due to the increased LC migration and not carcinogen-induced cell death

Diagnostic accuracy study of anorectal manometry for diagnosis of dyssynergic defecation

OBJECTIVE: The diagnostic accuracy of anorectal manometry (AM), which is necessary to diagnose functional defaecatory disorders (FDD), is unknown. Using blinded analysis and standardised reporting of diagnostic accuracy (STARD), we evaluated whether AM could discriminate between asymptomatic controls and patients with functional constipation (FC). DESIGN: Derived line-plots of anorectal pressure profiles during simulated defaecation were independently analysed in random order by 3 expert observers blinded to health status in 85 women with FC and 85 age-matched asymptomatic healthy volunteers (HV). Using accepted criteria, these pressure profiles were characterized as normal (i.e. increased rectal pressure coordinated with anal relaxation) or types I-IV dyssynergia. Inter-observer agreement and diagnostic accuracy were determined. RESULTS: Blinded consensus-based assessment disclosed a normal pattern in 16/170 (9%) of all participants and only 11/85 (13%) HV. The combined frequency of dyssynergic patterns (I-IV) was very similar in FC (80/85 [94%]) and HV (74/85 [87%]). Type I dyssynergia (‘paradoxical’ contraction) was less prevalent in FC (17/85 [20%] than HV (31/85 [36.5%], p=0.03). After statistical correction, only type IV dyssynergia was moderately useful for discriminating between FC (39/85 [46%] and HV 17/85 [20%], p=0.001, PPV=70.0%, positive LR=2.3). Inter-observer agreement was substantial or moderate for identifying a normal pattern, dyssynergia types I and IV, and FDD, and fair for types II and III. CONCLUSIONS: While the interpretation of AM patterns is reproducible, nearly 90% of HV have a pattern that is currently regarded as “abnormal” by AM. Hence AM is of limited utility for distinguishing between FC and HV