Skin epidermal thickness and vascular density in type 1 diabetes.

Epidermal skin thickness and vascular density were assessed in skin biopsies obtained from the dorsum of the foot in 28 Type 1 diabetic patients and 17 normal control subjects, matched for age. Epidermal skin thickness did not differ significantly between control subjects (74 +/- 4 (+/- SE) microns) and diabetic patients (78 +/- 4 microns). It was not related to the duration of diabetes and presence of complications. Neither small (capillary) nor large (arteriole/venule) vessel densities differed significantly between control subjects (59 +/- 6 mm-2 and 19 +/- 2 mm-2) and diabetic patients (65 +/- 4 mm-2 and 22 +/- 3 mm-2). Vessel densities were unrelated to the duration of diabetes and presence of complications.     

Approaches to integrating paediatric diabetes care and structured education: experiences from the Families, Adolescents, and Children's Teamwork Study (FACTS).

AIMS: The Families, Adolescents and Children's Teamwork Study (FACTS) is a family-centred structured education programme for children and adolescents with Type 1 diabetes. It aims to integrate group-based diabetes education into routine care, enhance parental responsibility for self management and improve glycaemic control. METHODS: A randomized wait-list control group study allocated participants to either the immediate (four educational sessions during year 1) or delayed intervention (four educational sessions during year 2). In both groups, glycated haemoglobin (HbA1c) was measured 3-monthly and participants completed the Paediatric Quality of Life Inventory (PedsQL), Problem Areas in Diabetes Scale (PAID) and Diabetes Family Responsibility Questionnaire (DFRQ) before and after the intervention. RESULTS: Intention-to-treat analysis showed no significant difference in HbA1c or parental responsibility between participants randomized to the immediate or delayed programme. However, during 12 months' follow-up, families who attended > or = 2 sessions reported increased parental involvement (P = 0.01), and in children/adolescents who attended > or = 2 sessions HbA1c fell by 0.29% compared with an increase of 0.11% in non-attenders (P = 0.04). CONCLUSION: This family-centred education programme has been integrated into paediatric diabetes care with potential benefits on parental involvement and glycaemic control, but further study is warranted before routine application into clinical care.     

The LDIflare: a novel test of C-fiber function demonstrates early neuropathy in type 2 diabetes

OBJECTIVE: The aim of this study was to evaluate a novel method for assessing the axon reflex and to determine its value in detecting neuropathy in type 2 diabetes. RESEARCH DESIGN AND METHODS: The neurogenic flare response to nociceptive stimuli is mediated by an axon reflex involving small unmyelinated C-fibers. We developed a method to assess this reflex involving skin heating to 44 degrees C to evoke the flare followed by scanning the site using a laser Doppler imager (LDI) to measure the area; we termed this method LDIflare. To confirm its neurogenic nature, we examined the LDIflare in eight healthy subjects before and after topical administration of anesthesia. We used this technique to detect C-fiber neuropathy in people with type 2 diabetes. A total of 36 subjects were studied: 12 subjects with neuropathy (group DN), 12 subjects without neuropathy (group DC), and 12 age- and sex-matched control subjects (group NC). For comparison, small-fiber function was also assessed using the Computer Aided Sensory Evaluator-IV (CASE IV) (WR Medical Electronics, Stillwater, MN). RESULTS: In the eight healthy control subjects, LDIflare was markedly reduced after topical administration of anesthesia (1.62 [1.45-1.72] vs. 5.2 cm2 [3.9-5.9], P <0.0001), confirming its neurogenic nature. Similarly, in neuropathic subjects, LDIflare was significantly smaller compared with normal and diabetic control subjects (LDIflare area: DN 1.3 cm2 [0.9-1.8], NC 5.5 cm2 [3.9-5.8], and DC 2.8 cm2 [2.5-3.8]; P <0.0001 and P=0.01, respectively). The group without neuropathy (DC) also demonstrated a reduced flare compared with the NC group (P=0.01). In contrast, C-fiber function assessed by evaluating the quantitative thermal thresholds (CASE IV) did not detect a difference between the latter two groups. CONCLUSIONS: This study confirms the neurogenic nature of the LDIflare and clearly demonstrates loss of C-fiber function in neuropathic subjects with type 2 diabetes. Moreover, it demonstrates C-fiber dysfunction before its detection by other currently available methods, including CASE IV. The LDIflare seems to be a simple objective method to detect early neuropathy and may be of value in assessing therapeutic interventions aimed at preventing or reversing C-fiber dysfunction.     

Sunitinib reverses type-1 immune suppression and decreases T-regulatory cells in renal cell carcinoma patients

PURPOSE: Immune dysfunction is well documented in renal cell carcinoma (RCC) patients and likely contributes to tumor evasion. This dysfunction includes a shift from a type-1 to a type-2 T-cell cytokine response and enhanced T-regulatory (Treg) cell expression. Given the antitumor activity of select tyrosine kinase inhibitors such as sunitinib in metastatic RCC (mRCC) patients, it is relevant to assess their effect on the immune system. EXPERIMENTAL DESIGN: Type-1 (IFNgamma) and type-2 (interleukin-4) responses were assessed in T cells at baseline and day 28 of treatment with sunitinib (50 mg/d) by measuring intracellular cytokines after in vitro stimulation with anti-CD3/anti-CD28 antibodies. RESULTS: After one cycle of treatment, there was a significant increase in the percentage of IFNgamma-producing T cells (CD3(+), P < 0.001; CD3(+)CD4(+), P = 0.001), a reduction in interleukin-4 production (CD3(+) cells, P = 0.05), and a diminished type-2 bias (P = 0.005). The increase in type-1 response may be partly related to modulation of Treg cells. The increased percentage of Treg cells noted in mRCC patients over healthy donors (P = 0.001) was reduced after treatment, although not reaching statistical significance. There was, however, an inverse correlation between the increase in type-1 response after two cycles of treatment and a decrease in the percentage of Treg cells (r = -0.64, P = 0.01). In vitro studies suggest that the effects of sunitinib on Treg cells are indirect. CONCLUSIONS: The demonstration that sunitinib improved type-1 T-cell cytokine response in mRCC patients while reducing Treg function provides a basis for the rational combination of sunitinib and immunotherapy in mRCC.     

Oxidation of N-nitrosopiperidine in the udenfriend model system and its metabolism by rat-liver microsomes

The major product isolated from the oxidation of the carcinogen, N-nitrosopiperidine, by the ascorbic acid model system of Udenfriend et al. has been identified as N-nitroso-4-piperidone both by its spectral properties and by comparison with authentic material. On incubation of N-nitrosopiperidine with rat-liver microsomes in the presence of the appropriate co-factors, N-nitroso-4-hydroxypiperidine was the major metabolite. This was identified by comparison of its mass spectrum and chromatographic properties with those of N-nitroso-4-hydroxypiperidine obtained by nitrosation of 4-hydroxypiperidine. The significance of these products with respect to the mechanism of action of the parent carcinogen, N-nitrosopiperidine, is discussed.     

Robotic-assisted left atrial ligation for stroke reduction in chronic atrial fibrillation: a case report

Patients with atrial fibrillation are at significant risk for sustaining a thromboembolic stroke. More than 90% of thromboemboli form in the left atrial appendage. Ligation of the left atrial appendage to reduce the risk of stroke is often performed in connection with other cardiac surgical procedures. As a stand-alone procedure, however, left atrial ligation has generally been deemed too invasive and has gained little support as an alternative therapeutic option. We report a case of port-access robotic-assisted left atrial ligation as a stand-alone procedure in a patient with chronic atrial fibrillation in whom anticoagulation was a contraindication. To our knowledge, this is the first reported case of stand-alone robotic-assisted left atrial ligation in the literature.     

Three-dimensional mapping of gyral shape and cortical surface asymmetries in schizophrenia: gender effects

OBJECTIVE: People with schizophrenia exhibit abnormalities in brain structure, often in the left hemisphere. Disturbed structural lateralization is controversial, however, and effects appear mediated by gender. The authors mapped differences between schizophrenic and normal subjects in gyral asymmetries, complexity, and variability across the entire cortex. METHOD: Asymmetry and shape profiles for 25 schizophrenic patients (15 men) and 28 demographically similar normal subjects (15 men) were obtained for 38 gyral regions, including the sylvian fissure and temporal and postcentral gyri, by using magnetic resonance data and a novel surface-based mesh-modeling approach. Cortical complexity was examined for sex and diagnosis effects in lobar regions. Intragroup variability was quantified and visualized to assess regional group abnormalities at the cortical surface. RESULTS: The patients showed greater variability in frontal areas than the comparison subjects. They also had significant deviations in gyral complexity asymmetry in the superior frontal cortex. In temporoparietal regions, significant gyral asymmetries were present in both groups. Sex differences were apparent in superior temporal gyral measures, and cortical complexity in inferior frontal regions was significantly greater in men. CONCLUSIONS: Cortical variability and complexity show regional abnormalities in the frontal cortex potentially specific to schizophrenia. The results indicate highly significant temporoparietal gyral asymmetries in both diagnostic groups, contrary to reports of less lateralization in schizophrenia. Substantially larger study groups are necessary to isolate smaller deviations in surface asymmetries, if present in schizophrenia, suggesting their diagnostic value is minimal.