Ultrasound detection of insulin-induced lipohypertrophy in Type 1 and Type 2 diabetes.

AIMS: To define standard criteria for the detection of lipohypertrophy using ultrasonography and to determine the accuracy of this method. METHOD: Individuals using insulin therapy for ≥2 years with unknown lipohypertrophy status were enrolled at a diabetes education centre. A team of diabetes educator nurses performed a clinical examination for evidence of lipohypertrophy and a separate team of ultrasonographers examined participants in a blinded fashion. RESULTS: The echo signature for lipohypertrophy consisted of location in the subcutaneous layer and lesions that were 1) well circumscribed either by hyperechoic foci with defined borders or a nodular shape with a hypoechoic halo, 2) heterogeneous in echotexture compared with surrounding tissue, 3) associated with distortion of surrounding connective tissue with 4) absence of vascularity and 5) absence of capsule. Ultrasonography identified individuals with lipohypertrophy significantly more frequently than inspection or palpation (P<0.0001). Inter-observer agreement was moderate (κ=0.50) and limited by the presence of subclinical lesions in 73% of the participants. CONCLUSIONS: The ultrasound detection of lipohypertrophy is consistent with clinical examination and is reproducible using a defined echo signature. (ClinicalTrials.gov registration no: NCT02348099).

Biofilm as a virulence marker in Candida species in Nosocomial blood stream infection and its correlation with antifungal resistance.

Nosocomial blood stream infections (BSI) due to fungi especially Candida is increasing steadily. A two year prospective study was conducted in the S.C.B. Medical College with an aim to evaluate the species distribution, antifungal susceptibility and biofilm formation of Candida spp. isolated from nosocomial BSIs. 34 Candida spp. were isolated from 359 blood cultures. Antifungal susceptibility was performed by microbroth dilution technique and both visual and spectrophotometric method were used for biofilm detection. C. tropicalis was the common spp. isolated followed by C. parapsilosis and others. Most (92%) of the isolates were susceptible to Amphoterecin-B and highest resistance was observed against Flucytosine (37%) and Fluconazole(35%). Biofilm production and antifungal resistance was observed more in nonalbicans Candida spp.

Role of azithromycin against clinical isolates of family enterobacteriaceae: A comparison of its minimum inhibitory concentration by three different methods.

PURPOSE: To determine the effect of azithromycin, a new azalide antibiotic, on clinical isolates of the family Enterobacteriaceae and to determine and compare its minimum inhibitory concentration (MIC) by disk diffusion, agar dilution and E-test methods. MATERIALS AND METHODS: One hundred fifty-nine bacterial strains belonging to the family Enterobacteriaceae, isolated from different clinical samples, were tested for their susceptibility to azithromycin by disk diffusion, agar dilution and E-test methods. The MIC values were analysed and the percentages of agreement between the different methods were mentioned. RESULTS: Of the 159 isolates of the family Enterobacteriaceae, 60.37% were E. coli followed by Klebsiella species 28.3%, Salmonella and Shigella species 3.77% and Enterobacter and Citrobacter species 1.88% each. Maximum isolates were obtained from urine 117/159 (73.58%). Azithromycin was found to be more active against Salmonella and Shigella species, showing 100% sensitivity the by E-test and 83.33% by the disk diffusion methods. In the agar dilution method, 83.33% of Salmonella and 66.66% of Shigella species were sensitive to azithromycin. The overall agreement between disk diffusion and agar dilution method was 96.8%, between agar dilution and E-test was 88% and between disk diffusion and E-test was 91.2%. CONCLUSION: Azithromycin may become an important addition to our antimicrobial strategies, especially for the treatment of bacterial diarrhoea and infections caused by Salmonella typhi.

Pretransplant HLA antibodies are associated with reduced graft survival after clinical islet transplantation.

Despite significant improvements in islet transplantation, long-term graft function is still not optimal. It is likely that both immune and nonimmune factors are involved in the deterioration of islet function over time. Historically, the pretransplant T-cell crossmatch and antibody screening were done by anti-human globulin--complement-dependent cytotoxicity (AHG-CDC). Class II antibodies were not evaluated. In 2003, we introduced solid-phase antibody screening using flow-based beads and flow crossmatching. We were interested to know whether pretransplant human leukocyte antigen (HLA) antibodies or a positive flow crossmatch impacted islet function post-transplant. A total of 152 islet transplants was performed in 81 patients. Islet function was determined by a positive C-peptide. Results were analyzed by procedure. Class I and class II panel reactive antibody (PRA) > 15% and donor-specific antibodies (DSA) were associated with a reduced C-peptide survival (p<0.0001 and p<0.0001, respectively). A positive T- and or B-cell crossmatch alone was not. Pretransplant HLA antibodies detectable by flow beads are associated with reduced graft survival. This suggests that the sirolimus and low-dose tacrolimus-based immunosuppression may not control the alloimmune response in this presensitized population and individuals with a PRA > 15% may require more aggressive inductive and maintenance immunosuppression, or represent a group that may not benefit from islet transplantation.

Changes in renal function after clinical islet transplantation: four-year observational study.

Tight glycemic control can reduce progression of diabetic nephropathy (DN) while the histological changes may regress after pancreas transplantation. Clinical islet transplantation (CIT) can restore euglycemia but the effects of CIT and concomitant immunosuppression on renal function are not known. Renal function (modification of diet in renal disease estimated glomerular filtration rate [GFR]) is reported in 41 type 1 diabetes subjects followed for 29.8 (6-57) months after CIT who received sirolimus and tacrolimus. HbA(1c) improved by 3 months (6.1 +/- 0.5 vs. 8.1 +/- 1.3%, p < 0.001) and was sustained. Over 4 years estimated GFR (eGFR) declined (repeated measures ANOVA: p = 0.0011). The median rate of change in eGFR was -0.39 mL/min/1.73 m(2)/month but was highly variable (range: +1.62 to -2.79 mL/min/1.73 m(2)/month). Progression of albuminuria was observed in ten individuals while regression of microalbuminuria was observed in only one (chi square = 22.51, df = 4, p = 0.0002). Despite improved glycemia, CIT and concomitant immunosuppression, was associated with a fall in eGFR and progression of albuminuria over 4 years of observation. The rate of decline in eGFR was extremely variable and difficult to predict. The risk of progressive nephrotoxicity with decline in eGFR should be discussed with prospective CIT candidates and the risk: benefit ratio carefully considered in individuals with pre-existing renal impairment.

Prevalence of autoimmune diseases in islet transplant candidates with severe hypoglycaemia and glycaemic lability: previously undiagnosed coeliac and autoimmune thyroid disease is identified by screening.

AIMS: Autoimmune diseases such as Addison's or coeliac disease can contribute to hypoglycaemia or malabsorption and are more common in Type 1 diabetes (T1DM). This brief report describes the prevalence of known and newly detected autoimmune disease in clinical islet transplant candidates with longstanding T1DM and severe hypoglycaemia and/or glycaemic lability who are routinely screened for coexisting autoimmune disease. METHODS: One hundred and twenty-four C-peptide negative T1DM subjects [77 (62%) female, mean age 44 +/- 9 years, diabetes duration 28 +/- 11 years, body mass index 24.9 +/- 3.5 kg/m(2)] with indications for clinical islet transplantation at the University of Alberta were screened for autoimmune disease by history and measurement of anti-transglutaminase antibodies (positive > 10 U/ml), 09.00 h cortisol (followed by adrenocorticotrophic hormone-stimulation if < 495 nmol/l) and thyroid-stimulating hormone to determine the prevalence of coeliac disease, Addison's disease and autoimmune thyroid disease, respectively. RESULTS: Forty per cent of subjects had one or more coexisting autoimmune disease. The prevalence of autoimmune disease was 35%, coeliac disease 8% and Addison's disease 1.6%. In 11 individuals (9%), one or more autoimmune disease were newly detected (seven coeliac disease and five thyroid disease). Seven of 10 cases of coeliac disease were newly detected. A gluten-free diet in individuals with newly diagnosed coeliac disease reduced gastrointestinal symptoms, but indications for clinical islet cell transplantation persisted. CONCLUSIONS: Coexisting autoimmune disease is common in candidates for clinical islet cell transplantation. Screening in this group identified a substantial number of previously unrecognized cases. Clinicians should consider the presence of autoimmune disease even in the absence of classical symptoms.

[Relationships between defense mechanisms and coping strategies, facing exam anxiety performance]. / Styles défensifs et stratégies d'ajustement ou coping en situation stressante.

BACKGROUND: Defence mechanisms and coping strategies rely on different theoretical backgrounds and describe distinct psychological processes. Cramer has based a distinction on the following dimensions: conscious processes vs. not; intentionality vs. not; hierarchical conception vs. not. On the contrary to these distinctions, the two notions of defense mechanisms and coping strategies are defined as similar in the Diagnostical and Statistical Manual (DSM IV). This assimilation between coping and defenses in the DSM IV is not confirmed by some researches, namely the one by Callahan and Chabrol. It indeed proves a relationship between adaptive coping and mature defenses, as well as between maladaptive coping and immature defenses. Similarly, Plutchik offered theoretical correspondences between eight defense mechanisms and eight coping strategies: (a) Defenses: repression, isolation, introjection and Coping escape; (b) Defense denial and Coping minimalization; (c) Defense undoing and coping substitution; (d) Defenses: regression, acting out and coping social support; (e) Defenses: compensation, identification, fantasy and coping replacement; (f) Defenses: intellectualization, sublimation, annulation, rationalisation and coping: planification; (g) Defense projection and coping blame; (h) Defense: reactional formation and coping inversion. GOAL: this research aims at testing the relations observed by Callahan and Chabrol and some theoretical correspondences proposed by Plutchik between defences and coping strategies in a population of students similar to the one used by Callahan and Chabrol. It also aims at studying the relationships between coping strategies and conscious derives of defense mechanisms, such as defined by Bond (1995). Defenses were evaluated the first day of the examination week. POPULATION: the population includes 184 women students in human sciences (sociology and psychology). INSTRUMENTS: defenses were evaluated with the Defense Style Questionnaire by Bond (DSQ 40). Its French version is made of 40 items and validated by Guelfi et al. It explores 20 defense mechanisms, as well as 3 defense styles: (1) a "mature style", composed by 4 defenses: sublimation, humor, anticipation, repression; (2) a "neurotic style", composed by 4 defenses: annulation, reactional formation, altruism and idealization; (3) an "immature style", composed by 12 defenses. Coping strategies were measured by the French version of the Way of Coping Check-List-Revised, (WCC-R) by Lazarus and Folkman, validated by Graziani et al. It evaluates 10 factors: 1) Problem solving; 2) Evasion; 3) Social support; 4) Self-control; 5) Escape; 6) Responsabilization-Replanification; 7) Resignation; 8)Diplomacy; 9) Confrontation; 10) Personal evolution. RESULTS: Our results confirm partially Callahan and Chabrol's conclusions in favour of existing relationships between adaptive coping strategies and mature defenses, as well as between maladaptive coping strategies and immature defenses. They demonstrate three positive relationships: 1) a relation between Problem solving resolution coping and two mature defenses (Sublimation, Anticipation); 2) a relation between Evasion coping and nevrotic and immature defenses; 3) a relation between Escaping coping and immature defenses. The correspondences between defense mechanisms and coping strategies, such as proposed by Plutchik psycho-evolutionist emotional model are partly validated. Some links were indeed validated in this research, between: a) Defense Undoing and Escaping or Evasion coping; b) Defense Fantasy and Responzabilization coping, c) Defense Sublimation and Problem solving resolution coping; d) Defense Sublimation and Responsabilization coping or Problem solving resolution coping; e) Défense Annulation and Responzabilisation coping.

Prevention of bleeding after islet transplantation: lessons learned from a multivariate analysis of 132 cases at a single institution.

Islet transplantation is being offered increasingly for selected patients with unstable type 1 diabetes. Percutaneous transhepatic portal access avoids a need for surgery, but is associated with potential risk of bleeding. Between 1999 and 2005, we performed 132 percutaneous transhepatic islet transplants in 67 patients. We encountered bleeding in 18/132 cases (13.6%). In univariate analysis, the risk of bleeding in the absence of effective track ablation was associated with an increasing number of procedures (2nd and 3rd procedures with an odds ratio (OR) of 9.5 and 20.9, respectively), platelets count <150,000 (OR 4.4), elevated portal pressure (OR 1.1 per mm Hg rise), heparin dose > or =45 U/kg (OR 9.8) and pre-transplant aspirin (81 mg per day) (OR 2.6, p = 0.05). A multivariate analysis further confirmed the cumulative transplant procedure number (p < 0.001) and heparin dose > or =45 U/kg (p = 0.02) as independent risk factors for bleeding. Effective mechanical sealing of the intrahepatic portal catheter tract with thrombostatic coils and tissue fibrin glue completely prevented bleeding in all subsequent procedures (n = 26, p = 0.02). We conclude that bleeding after percutaneous islet implantation is an avoidable complication provided the intraparenchymal liver tract is sealed effectively.

Inhibitory effects of immunosuppressive drugs on insulin secretion from HIT-T15 cells and Wistar rat islets.

Until recently, islet allotransplantation for type 1 diabetic patients has been largely unsuccessful. Previous pharmacologic studies of single drugs have suggested that one factor contributing to this poor success is toxicity of immunosuppressive drugs on transplanted islets. However, no comprehensive study of agents currently used for islet transplantation has been previously reported. Consequently, we exposed HIT-T15 cells and Wistar rat islets to various concentrations of five immunosuppressive agents for 48 and 24 hr, respectively, and measured glucose-stimulated insulin secretion during subsequent static incubations. Results are expressed as percent reduction of insulin secretion at the lower and upper limits, respectively, of plasma drug concentrations used in clinical transplantation compared with control (no drug exposure). Insulin secretion from HIT-T15 cells was significantly inhibited by 74% and 90% after exposure to methylprednisolone (P<0.05), 11% and 24% after exposure to cyclosporine (P<0.01), 60% and 83% after exposure to mycophenolate (P<0.05), 56% and 63% after exposure to sirolimus (P<0.001), and 10% and 20% after exposure to tacrolimus (P<0.001). Insulin secretion from Wistar rat islets was reduced by 0% and 48% after exposure to mycophenolate (P<0.001) and 20% and 31% after exposure to tacrolimus (P<0.05). No reduction in insulin secretion was observed from either HIT-T15 cells or rat islets after exposure to daclizumab. The results support the hypothesis that toxicity of certain immunosuppressive drugs on beta-cell function plays a role in the poor success of islet allotransplantation. This is especially true of intrahepatically transplanted islets, which are exposed to higher portal concentrations of immunosuppressive agents. These findings support the use of low-dose immunosuppressive drug protocols in clinical islet transplantation.

Restored hypoglycemic counterregulation is stable in successful pancreas transplant recipients for up to 19 years after transplantation.

BACKGROUND: Pancreas transplantation has been shown to fully restore glucagon response and partially restore epinephrine response to hypoglycemia during the first few years after transplantation in patients with type 1 diabetes. However, prior studies have not examined hypoglycemic counterregulation in any pancreas transplant recipient of more than 6 years' duration. METHODS: To determine whether restoration of hypoglycemic counterregulation is maintained over a prolonged period after transplantation, we studied counterregulatory responses and symptom recognition in two groups of pancreas transplant recipients using a stepped hypoglycemic, hyperinsulinemic clamp. Group 1 consisted of 11 successful transplant recipients of 11 to 19 years' duration (mean+/-SE, 13.9+/-0.7 years). Group 2A consisted of seven successful pancreas transplant recipients of 5 to 11 years' duration (mean+/-SE, 8.7+/-0.9 years) who had been studied approximately 5 years earlier using the same stepped, hypoglycemic clamp technique. RESULTS: Both groups had significant rises in plasma glucagon during the hypoglycemic clamp similar to that seen in short-term recipients and normal controls. Both groups also had significant increases in plasma epinephrine responses similar to that seen in short-term transplant recipients but less than that of normal control subjects. The mean symptom scores of group 1 were significantly less than those of the control group at glucose levels of 60 and 50 mg/dL but not at 40 mg/dL. The mean symptom scores of group 2A were not significantly different than that of control subjects. CONCLUSION: These results indicate that the restoration of hypoglycemic counterregulation by pancreas transplantation remains stable in successful pancreas transplant recipients for up to 19 years after transplantation.

Managing myocardial infarction in the diabetic patient.

Myocardial infarction is the leading cause of death among persons with diabetes. Recent advances in the understanding and treatment of cardiovascular disease in diabetes have made it increasingly important to tailor therapy when treating this high-risk population. Because patients with diabetes are at significantly higher risk for complications and death from MI, these patients are most likely to benefit from early and aggressive therapeutic intervention. Strong recommendations can be given for the use of beta-blockers, ACE inhibitors, and thrombolysis when indicated in the management of acute MI in the diabetic patient. Acetylsalicylic acid is also likely to be beneficial with little risk of adverse events in this setting. In the absence of more definitive data, cautious use of mechanical intervention in diabetic patients is recommended. The use of intravenous insulin therapy may benefit diabetic patients during the acute phase of MI, but more definitive studies are required before it can be recommended for broad use.

The development of gender schemata about heterosexual and homosexual others during adolescence.

Perceptions of heterosexual and homosexual individuals were investigated among 12-, 16-, and 20-year-old French adolescents. Participants described heterosexual and homosexual males and females with typical masculine and feminine personality traits. Overall, they perceived heterosexual males as having more masculine traits than homosexual males. The 16- and 20-year-olds perceived homosexual males as more feminine than heterosexual males, whereas the reverse was observed in 12-year-olds. Furthermore, the 12-year-olds perceived heterosexual females as more feminine than homosexual females, a difference that disappeared in the older age groups. Results support the view of early adolescence as a crucial period in the development of gender schemata about sexually significant others.

Colonic carcinoma in two adult cystic fibrosis patients.

Two adult women with cystic fibrosis (CF) who developed colonic carcinoma, both at age 31, are described. In both patients the carcinoma occurred in the midtransverse colon. The diagnosis had not been suspected, partly because of the patients' relatively young age. In case 1, the symptoms also mimicked the distal intestinal obstruction syndrome. At diagnosis she was shown to have metastases to the regional lymph nodes. In case 2, despite a long history of chronic pulmonary and sinus disorders, CF was not diagnosed until the patient was 36 years old. The incidence of gastrointestinal malignancies has been shown to be significantly increased in patients with CF. As the life expectancy of the CF population increases, vigilance for gastrointestinal cancers in CF patients is important, as illustrated by these two cases.