Non-invasive techniques for imaging in-vivo human corneal sub basal nerve mapping and migration rate in diabetic neuropathy

Purpose Corneal confocal microscopy (CCM) is a rapid non-invasive ophthalmic technique, which has been shown to diagnose and stratify the severity of diabetic neuropathy. Current morphometric techniques assess individual static images of the subbasal nerve plexus; this work explores the potential for non-invasive assessment of the wide-field morphology and dynamic changes of this plexus in vivo. Methods In this pilot study, laser scanning CCM was used to acquire maps (using a dynamic fixation target and semi-automated tiling software) of the central corneal sub-basal nerve plexus in 4 diabetic patients with and 6 without neuropathy and in 2 control subjects. Nerve migration was measured in an additional 7 diabetic patients with neuropathy, 4 without neuropathy and in 2 control subjects by repeating a modified version of the mapping procedure within 2-8 weeks, thus facilitating re-identification of distinctive nerve landmarks in the 2 montages. The rate of nerve movement was determined from these data and normalised to a weekly rate (µm/week), using customised software. Results Wide-field corneal nerve fibre length correlated significantly with the Neuropathy Disability Score (r = -0.58, p < 0.05), vibration perception (r = -0.66, p < 0.05) and peroneal conduction velocity (r = 0.67, p < 0.05). Central corneal nerve fibre length did not correlate with any of these measures of neuropathy (p > 0.05 for all). The rate of corneal nerve migration was 14.3 ± 1.1 µm/week in diabetic patients with neuropathy, 19.7 ± 13.3µm/week in diabetic patients without neuropathy, and 24.4 ± 9.8µm/week in control subjects; however, these differences were not significantly different (p = 0.543). Conclusions Our data demonstrate that it is possible to capture wide-field images of the corneal nerve plexus, and to quantify the rate of corneal nerve migration by repeating this procedure over a number of weeks. Further studies on larger sample sizes are required to determine the utility of this approach for the diagnosis and monitoring of diabetic neuropathy.

Exploring Retinal Markers of Diabetic Neuropathy

Purpose : To investigate the application of retinal nerve fibre layer (RNFL) thickness as a marker for severity of diabetic peripheral neuropathy (DPN) in people with Type 2 diabetes. Methods : This was a cross-sectional study whereby 61 participants (mean age 61 [41-75 years], mean duration of diabetes 14 [1-40 years], 70% male) with Type 2 diabetes and DPN underwent optical coherence tomography (OCT) scans. Global and 4 quadrant (TSNI) RNFL thicknesses were measured at 3.45mm around the optic nerve head of one eye. Neuropathy disability score (NDS) was used to assess the severity of DPN on a 0 to 10 scale. Participants were divided into three age-matched groups representing mild (NDS=3-5), moderate (NDS=6-8) and severe (NDS=9-10) neuropathy. Two regression models were fitted for statistical analysis: 1) NDS scores as co-variate for global and quadrant RNFL thicknesses, 2) NDS groups as a factor for global RNFL thickness only. Results : Mean (SD) RNFL thickness (µm) was 103(9) for mild neuropathy (n=34), 101(10) for moderate neuropathy (n=16) and 95(13) in the group with severe neuropathy (n=11). Global RNFL thickness and NDS scores were statistically significantly related (b=-1.20, p=0.048). When neuropathy was assessed across groups, a trend of thinner mean RNFL thickness was observed with increasing severity of neuropathy; however, this result was not statistically significant (F=2.86, p=0.065). TSNI quadrant analysis showed that mean RNFL thickness reduction in the inferior quadrant was 2.55 µm per 1 unit increase in NDS score (p=0.005). However, the regression coefficients were not statistically significant for RNFL thickness in the superior (b=-1.0, p=0.271), temporal (b=-0.90, p=0.238) and nasal (b=-0.99, p=0.205) quadrants. Conclusions : RNFL thickness was reduced with increasing severity of DPN and the effect was most evident in the inferior quadrant. Measuring RNFL thickness using OCT may prove to be a useful, non-invasive technique for identifying severity of DPN and may also provide additional insight into common mechanisms for peripheral neuropathy and RNFL damage.

Young people and citizenship-delayed, diminished and empty?

This paper is presented in workshop format in order to meet the style and themes of the conference, and seeks to explore as fully as possible with participants issues, concerns and proposals around the discourse of young people and citizenship. This paper takes the position that the relationship between young people and citizenship is complex and in places contradictory, and while Ruth Lister (1998), argues for an 'inclusionary potential', a central concern is that the citizenship that young people get is as Hartley Dean (1997), suggests, at best 'ambiguous', and at its worst, 'diminished'. Under not so new Labour, the term has according to Gail Lewis (1998) re-emerged as a 'category of political articulation', imbued with the pronouncements of Charles Murray (1995) on the underclass, and Amitai Etzioni (1996), on the virtues of Communitarianism and the central assertion that in relation to young people and certain communities, 'rights have exceeded responsibilities'. This body of opinion has proved to be seductive to a government dedicated to joined up solutions in the battle against social exclusion and to the reconfiguration of the welfare state to place the onus for welfare and social provision on to individuals and communities. Those who work with young people and young people themselves may wish to be proactive in asserting the kind of citizenship they require, rights-based, expansive and supportive, rather than accept an imposed version devoid of rights but full to the brim of authoritarian measures, vindictive proposals and narrow horizons. This paper will engender debate and reflection and offer a context of the erosion of young people's rights over the last 20 years, Hartley Dean (1996), and will consider the work of T.H. Marshall (1950) in dividing citizenship into three elements: the civil element, the political element, and the social element. The paper will explore in workshop tradition, strategies and proposals for action relevant to practitioners and academics, such as the reduction in the voting age to 16.

A tissue-engineered humanised xenograft model of human breast cancer-induced bone metastasis and bone colonisation

This thesis focuses on the development of a humanised mouse model to investigate human breast cancer metastasis to bone, an incurable disease presenting a major medical challenge in our society. The method is based on tissue-engineered constructs with human cells that generate a human bone-like organ within mice. This novel platform is further applied to mimic human-specific mechanisms of breast cancer metastasis and growth in human bone, and in particular the role of specific cell adhesion molecules in this process is closely investigated.

Glutathione transferase activities in renal carcinomas and adjacent normal renal tissues : factors influencing renal carcinogenesis induced by xenobiotics

In general, the biological activation of nephrocarcinogenic chlorinated hydrocarbons proceeds via conjugatiton with glutathione. It has mostly been assamed that the main site of initial conjugation is the liver, followed by a mandatory transfer of intermediates to the kidney. It was therefore of interest to study the enzyme activities of subgroups of glutathione transferases (GSTs) in renal cancers and the surrounding normal renal tissues of the same individuals (n = 21). For genotyping the individuals with respect to known polymorphic GST isozymes the following substrates with differential specificity were used: 1-chloro-2,4-dinitrobenzene for overall GST activity (except GST θ); 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole for GST α; 1,2-dichloro-4-nitro-benzene for GST μ; ethacrynic acid and 4-vinylpyridine for GST π; and methyl chloride for GST θ. In general, the normal tissues were able to metabolize the test substrates. A general decrease in individual GST enzyme activities was apparent in the course of cancerization, and in some (exceptional) cases individual activities, expressed in the normal renal tissue, were lost in the tumour tissue. The GST enzyme activities in tumours were independent of tumour stage, or the age and gender of the patients. There was little influence of known polymorphisms of GSTM1, GSTM3 and GSTP1 upon the activities towards the test substrates, whereas the influence of GSTT1 polymorphism on the activity towads methyl chloride was straightforward. In general, the present findings support the concept that the initial GST-dependent bioactivation step of nephrocarcinogenic chlorinated hydrocarbons may take place in the kidney itself. This should be a consideration in toxicokinetic modelling.

Dapsone-induced agranulocytosis. The role of xenobiotic-metabolizing enzymes demonstrated by a case report [Dapson-induzierte Agranulozytose]

A 34-year-old female patient with a three year history of generalized granuloma annulare was treated systemically with dapsone (DADPS). Six weeks after the onset of treatment, the patient developed an extensive tonsillitis of the base of the tongue with fever and malaise. Routine laboratory work showed a leukocytopenia with agranulocytosis. Further investigation revealed a marked decrease of the enzyme activity of N-acetyltransferase 2, which plays an important role in dapsone metabolism. Treatment included the cessation of dapsone, antibiotic coverage, and G-CSF leading to the rapid improvement of symptoms and normalization of leukocyte counts. Dapsone-induced angina agranulocytotica is a rare event and is interpreted as an idiosyncratic reaction. Depending on genetic polymorphisms of various enzymes, dapsone can be metabolized to immunologically or toxicologically relevant intermediates. Because of the risk of severe hematologic reactions, dapsone should only be employed for solid indications and with appropriate monitoring. [Article in German]

Primary and substance-induced psychotic disorders in methamphetamine users

This study investigates the rates of primary psychotic disorders (PPD) and substance induced psychotic disorders (SIPDs) in methamphetamine (MA) users accessing needle and syringe programs (NSPs). The aim was to determine if there are systematic differences in the characteristics of MA users with PPDs and SIPDs compared to those with no psychotic disorder. Participants were 198 MA users reporting use in the previous month. Diagnosis was determined using the Psychiatric Research Interview for DSM-IV Substance and Mental Disorders (PRISM-IV). Current psychiatric symptoms and substance use were also measured. Just over half (N=101) of participants met DSM-IV criteria for a lifetime psychotic disorder, including 81 (80%) with a SIPD and 20 (20%) with a PPD. Those with a younger age of onset of weekly MA use were at increased risk of a lifetime SIPD. A current psychotic disorder was found in 62 (39%), comprising 49 SIPDs (79%) and 13 PPDs (21%). MA users with a current PPD were more likely to have received psychiatric treatment in the past month than those with a current SIPD, despite a similar level of psychotic symptom severity. A high proportion of MA users accessing NSPs have psychotic disorders, the majority of which are substance-induced.

BOSTER : an efficient algorithm for mining frequent unordered induced subtrees

Extracting frequent subtrees from the tree structured data has important applications in Web mining. In this paper, we introduce a novel canonical form for rooted labelled unordered trees called the balanced-optimal-search canonical form (BOCF) that can handle the isomorphism problem efficiently. Using BOCF, we define a tree structure guided scheme based enumeration approach that systematically enumerates only the valid subtrees. Finally, we present the balanced optimal search tree miner (BOSTER) algorithm based on BOCF and the proposed enumeration approach, for finding frequent induced subtrees from a database of labelled rooted unordered trees. Experiments on the real datasets compare the efficiency of BOSTER over the two state-of-the-art algorithms for mining induced unordered subtrees, HybridTreeMiner and UNI3. The results are encouraging.