Fasting plasma triglycerides predict the glycaemic response to treatment of type 2 diabetes by gastric electrical stimulation. A novel lipotoxicity paradigm.

BACKGROUND: Non-stimulatory, meal-mediated electrical stimulation of the stomach (TANTALUS-DIAMOND) improves glycaemic control and causes modest weight loss in patients with Type 2 diabetes who are inadequately controlled on oral anti-diabetic medications. The magnitude of the glycaemic response in clinical studies has been variable. A preliminary analysis of data from patients who had completed 6 months of treatment indicated that the glycaemic response to the electrical stimulation was inversely related to the baseline fasting plasma triglyceride level. METHOD: An analysis of 40 patients who had had detailed longitudinal studies for 12 months. RESULTS: Twenty-two patients with fasting plasma triglycerides ≤ 1.7 mmol/l had mean decreases in HbA1c after 3, 6 and 12 months of gastric contraction modulation treatment of -15 ± 2.1 mmol/mol (-1.39 ± 0.20%), -16 ± 2.2 mmol/mol (-1.48 ± 0.20%) and -14 ± 3.0 mmol/mol (-1.31 ± 0.26%), respectively. In contrast, 18 patients with fasting plasma triglyceride > 1.7 mmol/l had mean decreases in HbA1c of -7 ± 1.7 mmol/mol (-0.66 ± 0.16%), -5 ± 1.6 mmol/mol (-0.44 ± 0.18%) and -5 ± 1.7 mmol/mol (-0.42 ± 0.16%), respectively. Pearson's correlation coefficient between fasting plasma triglyceride and decreases in HbA1c at 12 months of treatment was 0.34 (P < 0.05). Homeostasis model assessment of insulin resistance was unchanged during 12 months of treatment in patients with high baseline fasting triglycerides, while it progressively improved in patients with low fasting plasma triglycerides. Patients with low fasting plasma triglycerides had a tendency to lose more weight than those with high fasting plasma triglycerides, but this did not achieve statistical significance. CONCLUSIONS: The data presented suggest the existence of a triglyceride lipotoxic mechanism that interferes with gastric/neural mediated pathways that can regulate glycaemic control in patients with type 2 diabetes. The data suggest the existence of a triglyceride lipotoxic pathway that interferes with gastric/neural mediated pathways that can regulate glycaemic control.

[Efficacy and safety of Adalimumab in Crohn's disease]. / Indications et résultats de l'adalimumab au cours de la maladie de Crohn.

BACKGROUND: Adalimumab is the first subcutaneously self administered fully human anti-TNFa. AIM: To determine efficacy and safety of Adalimumab therapy in Crohn disease. METHODS: Literature review. RESULTS: Adalimumab has been evaluated for its effect in inducing and maintaining remission and its steroid-sparing effect of refractory Crohn's disease. In addition, it offers a significant treatment option in patients who have lost response to or become intolerant to Infliximab. Results also suggest efficacy of Adalimumab in fistulising Crohn's disease but more studies are needed. Adalimumab was well tolerated and studies show that all anti-TNF inhibitors have similar safety profiles.

Ultrahigh-Resolution X-ray Tomography.

Ultrahigh-resolution three-dimensional images of a microscopic test object were made with soft x-rays collected with a scanning transmission x-ray microscope. The test object consisted of two different patterns of gold bars on silicon nitride windows that were separated by approximately 5 micrometers. Depth resolution comparable to the transverse resolution was achieved by recording nine two-dimensional images of the object at angles between -50 and +55 degrees with respect to the beam axis. The projections were then combined tomographically to form a three-dimensional image by means of an algorithm using an algebraic reconstruction technique. A transverse resolution of approximately 1000 angstroms was observed. Artifacts in the reconstruction limited the overall depth resolution to approximately 6000 angstroms; however, some features were clearly reconstructed with a depth resolution of approximately 1000 angstroms.

Circadian patterns of gastric electrical and mechanical activity in dogs.

Gastric motor function assessment, in humans and animals, is typically performed for short recording periods. The aim of this article was to monitor gastric electrical and motor activity in the antrum and fundus simultaneously, for long periods, using a new implantable system. Ten dogs were implanted with fundic and antral electrodes for assessment of impedance and electrical activity. Dogs were studied while in cages, for periods of 22-26 h. From late evening and until feeding on the next day, slow wave (SW) rhythm demonstrated a distinct pattern of intermittent pauses (mean duration = 22.8 +/-4.1 s) that delineated groups of SW's. Phasic increases in fundic tone were seen mostly in association with SW pauses, and were highly correlated with antral contractions, R(2) = 0.652, P < 0.05. The SW rate (events per minute) in the postprandial period, fasting and night time was 4.2 +/- 0.2, 5 +/- 0.2 and 4.7 +/- 0.3, respectively, P < 0.05 postprandial vs other periods. Antral and fundic mechanical activities were highly correlated during fasting, particularly at night. This novel method of prolonged gastric recording provides valuable data on the mechanical and electrical activity of the stomach, not feasible by current methods of recording. During fasting, fundic and antral motor activities are highly correlated and are associated with periodic pauses in electrical activity.

[Macular pigment and age-related macular degeneration. Clinical implications]. / Pigment maculaire et dégénérescence maculaire liée à l'âge. Implications cliniques.

The potential impact of macular pigment on the development of age-related macular degeneration (AMD) is currently a major research avenue. The role of oxidative damage in the pathogenesis of AMD has been recently confirmed by the results of a large randomized clinical trial, the AREDS (Age-Related Eye Disease Study). This study has established that high-dose supplementation with vitamins C and E, beta carotene, and zinc might prevent AMD progression and visual acuity loss in a large but determined subset of patients. Macular pigment components (mainly lutein and zeaxanthin) are highly resistant to free radicals. Moreover, extensive data from clinical, epidemiological and experimental studies suggest that lutein and zeaxanthin might protect against the development of AMD. Furthermore, an additional intake of lutein and/or zeaxanthin seems to induce an increase of the density of the macular pigment. However, a careful review of the available data suggest that only future randomized clinical trials will allow to determine the exact role of lutein and zeaxanthin in the prevention of AMD.

Discontinuing caffeine in preterm infants at 33-35 weeks corrected gestational age: Failure rate and predictive factors.

OBJECTIVE: To examine the success rate of our current practice of discontinuing caffeine at 33 0/7-35 6/7 weeks post menstrual age (PMA), as well as factors that predict the success or failure of discontinuation. STUDY DESIGN: A retrospective chart review of infants born before 34 weeks gestational age between 2006-2012. Data collected included demographics, and other comorbidities mainly complications of prematurity. RESULTS: 647 treated infants had caffeine discontinued at 33-35 PMA before discharge or transfer. 64 (10%) infants failed discontinuation and had caffeine restarted. Most (77%) of those who failed started having monitor alarms within 7 days of discontinuation. BPD and Hispanic ethnicity were predictive of weaning failure (p < 0.05). CONCLUSION: Caffeine can be discontinued at 33-35 weeks PMA with a failure rate of 10%. BPD and Hispanic ethnicity are predictive of failure. It is generally safe to discharge infants seven days after the caffeine was discontinued if no significant monitor events occur during that time.

Development and validation of a clinical score to estimate the probability of coronary artery disease in men and women presenting with suspected coronary disease.

PURPOSE: Guidelines for the management of patients with suspected coronary disease have emphasized stratification into groups with low, intermediate, and high probability of significant coronary disease. Previously derived clinical prediction rules have been difficult to apply in clinical settings. The purpose of this study was to develop and validate a clinical score that facilitates this stratification process. PATIENTS AND METHODS: We performed a retrospective analysis of prospectively acquired data from 915 patients with suspected coronary disease and normal resting electrocardiograms who presented for exercise testing at a university hospital. All patients subsequently underwent coronary angiography. Analysis included logistic regression with significant coronary disease (> or = 1 vessel with a > or = 50% lesion) presence as the dependent variable and clinical variables as independent variables. From this analysis, a coronary disease score was developed to estimate prevalence of coronary disease from clinical variables. Validation of this score was performed in a separate prospectively acquired cohort of 348 patients. RESULTS: For the entire validation group, the prevalence of significant coronary disease was 16% (10/63) in the low probability group, 44% (86/195) in the intermediate probability group, and 69% (62/90) in the high probability group. Both men and women were stratified equally well into the 3 probability groups. CONCLUSION: The clinical score is an easily memorized and accurate method for categorizing patients with suspected but not proven coronary disease and normal resting electrocardiograms into clinically meaningful probability groups upon which decisions concerning appropriate diagnostic test selection could potentially be based.

Acute suppressive effect of hydrocortisone on p47 subunit of nicotinamide adenine dinucleotide phosphate oxidase.

We have recently demonstrated that reactive oxygen species (ROS) generation by polymorphonuclear leukocytes (PMNL) and mononuclear cells (MNC) is inhibited following the intravenous administration of hydrocortisone. This is associated with a parallel decrease in intranuclear NFkappaB, known to modulate inflammatory responses including ROS generation. We have also shown that the plasma levels of interleukin-10 (IL-10), an anti-inflammatory and immunosuppressive cytokine produced by TH2 cells, are also increased after hydrocortisone administration. In this study, we have investigated the effect of hydrocortisone on p47(phox) subunit, a key component of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, in MNC and the pharmacodynamics of this effect with ROS generation and plasma IL-10 levels. p47(phox) subunit protein levels in MNC showed a progressive decrease after hydrocortisone administration. It reached a nadir at 4 hours and increased thereafter to a baseline level at 24 hours. ROS generation also decreased, reached a nadir between 2 and 4 hours, and returned to a baseline level at 24 hours. IL-10 concentrations increased, peaked at 4 hours, and reverted to the baseline levels at 24 hours. In conclusion, p47(phox) subunit suppression may contribute to the inhibition of ROS generation in MNC after hydrocortisone administration. This suppression occurs in parallel with the suppression of NFkappaB and an increase in IL-10 plasma levels. Therefore, it would appear that the decrease in intranuclear NFkappaB and an increase in IL-10 may cause the inhibitory modulation on p47(phox) subunit and ROS generation by MNC following hydrocortisone and other glucocorticoids.

Eligibility for treatment and angiographic features at the early stage of exudative age related macular degeneration.

AIMS: To determine the eligibility for laser photocoagulation treatment or for photodynamic therapy (PDT) with verteporfin in eyes at the earliest stage (first month of symptoms) of exudative age related macular degeneration (AMD) based on fluorescein angiographic (FA) features; to evaluate the potential contribution of indocyanine green angiography (ICG-A) for occult choroidal neovascularisation (CNV) at this stage. METHODS: Retrospective review of 252 consecutive patients (269 eyes) examined within the first month of symptoms of exudative AMD. RESULTS: On FA, 97 eyes (36%) had classic CNV alone. Occult CNV associated with fibrovascular retinal pigment epithelium detachments (PEDs) was observed in 71 eyes (26%) and without fibrovascular PED in 101 eyes (38%). 91 eyes (34%) met the Macular Photocoagulation Study criteria for laser photocoagulation. 53 eyes (20%) met the Verteporfin In PDT (VIP) or Treatment of AMD with PDT (TAP) studies criteria. By ICG-A, occult CNV was visualised as focal spots in 49% of eyes examined within 15 days v 32% of eyes examined between 16 and 30 days after the onset of symptoms (p=0.07). 8.5% of late staining plaques disclosed in eyes examined within 15 days were combined with focal spots v 36% in eyes examined between 16 and 30 days (p<0.01). CONCLUSIONS: Early examination of eyes with exudative AMD would allow the treatment of 47% of eyes. 60% of eyes with subfoveal CNV would be eligible for PDT with verteporfin. Up to half of eyes with occult CNV would be converted by ICG-A into well delineated focal spots.

Effect of cimetidine on healing and surgical treatment of gastric ulcers.

In this retrospective study, a cohort of gastric ulcer patients treated with antacids was compared with a well-matched group of patients treated with a combination of antacids and cimetidine. Cimetidine combined with antacids enhanced gastric ulcer healing, thereby significantly reducing the number of gastric ulcer operations. Cimetidine appears to act by providing a less acidic environment in which gastric ulcers can heal. The exact mechanism of cimetidine's action on gastric ulcers is not clear. Nonprophylactic administration of cimetidine apparently has no effect on the recurrence rate of gastric ulcers.

[Decompensation of a cirsoid aneurysm: a case report]. / Décompensation d'un anévrysme cirsoïde. A propos d'un cas.

We report a case of a 27-year-old woman with a cirsoid aneurysm, also called congenital arteriovenous communication of the retina. The cirsoid aneurysm, stage I according to Archer's classification, was revealed by a serous retinal detachment. The exudation resolved, and acuity was recovered after a short time, but exudation recurred during the 5 years of follow-up. Exudation of type I cirsoid aneurysm is rare. The clinical and pathogenic features are discussed.

[Age-related macular degeneration and apoptosis]. / Dégénérescence maculaire liée à l'âge et apoptose.

Several studies suggest that apoptosis might play a major role in age-related macular degeneration. Apoptosis in retinal pigment epithelium cells undergoing severe oxidative stress has been reported and could therefore be involved in the pathogenesis of AMD. The processes of drusen formation seem to be similar to the processes described in apoptosis. Moreover, apoptosis appears to be involved in the early outgrowth of choroidal neovascular membranes as well as in the development of fibrotic scars at a later stage. Targeting apoptotic pathways should therefore be considered as a possible treatment approach for AMD.

[Alternative therapies for choroidal neovessels resulting from age-related macular degeneration]. / Thérapeutiques alternatives des néovaisseaux choroïdiens de la dégénérescence maculaire liée à l'âge.

Classic neovessels (CNVs) identified on fluorescein angiography may benefit from thermal laser photocoagulation when sparing the fovea. If they extend into it, photodynamic therapy may halt the natural progression to a central scotoma. Occult CNVs, when subfoveal, may benefit from photodynamic therapy when isolated (not associated with classic CNV or with a pigment epithelium detachment). A number of therapeutic approaches are being evaluated in order to diversify the therapeutic choices available for treatment of CNVs. Transpupillary thermotherapy, which causes a limited increase in retinal temperature, could produce a sclerosis of occult isolated CNV. This approach has shown interesting results in pilot studies but also carries a risk for iatrogenic effects. The American randomized clinical trial currently under way will provide an evaluation of this treatment. An antiangiogenic therapy currently in progress is studying anecortave acetate and another is investigating anti-VEGF compounds. Anecortave acetate, which demonstrated its angiostatic activity in experimental models as well as in a phase II study, is now in a worldwide randomized clinical trial. The anti-VEGF molecules (antibodies and oligonucleotides) have shown very interesting preliminary results and are being evaluated in a large number of patients. Finally, a preventive therapy consisting of oral supplementation with antioxidants (vitamins C, E, and A) and zinc is a major step forward, providing the possibility of a real and effective prevention of the complications of age-related maculopathy.

Giant cell tumour of tendon sheath: experience with 52 cases.

INTRODUCTION: The aim of this retrospective study was to study the clinical presentation, investigations, histopathological findings, and the best ways of treatment of the giant cell tumour of the tendon sheath (GCTTS). METHODS: The medical records of all patients diagnosed to have GCTTS during the period 1994-2001 were reviewed, and follow-up was for three to ten years. RESULTS: The total number of patients was 52, of whom 36 were females, and the mean age was 32.4 years. All the tumours except one were located in the hand and wrist area, with the thumb being the most affected finger. Painless swelling was the most common presentation. All of them were treated surgically and the recurrence rate was 24 percent. CONCLUSION: After reviewing the literature and comparing with our results, we conclude that GCTTS is a true benign tumour with local aggressive behaviour in some cases, and the best way of treatment is wide local excision.

The use of gastric electrical signals for algorithm for automatic eating detection in dogs.

Food ingestion increases fundic impedance (FI) and reduces antral slow wave rate (SWR). Our aim was to determine if such changes can be integrated into an algorithm for automatic eating detection (AED). When incorporated in implantable medical devices, AED can time treatment to food intake without need for patient input. Four dogs were implanted with fundic and antral electrodes, connected to an implantable recording device. Changes in FI and SWR induced by fixed meals of different weights were determined, and were used to build an AED algorithm. Its performance was then tested on the same animals given an ad libitum access to food. The effects of gastric balloon distension and nitroglycerin on SWR and FI were also tested. Fixed meals reduced SWR in a weight-dependent manner, R(2) = 0.936, P < 0.05 baseline compared to 50, 100, 200 and 400 g. Meals increased FI above baseline in a weight-dependent manner; R(2) = 0.994, P < 0.05 baseline compared to 200 and 400 g. During ad libitum intake, the AED algorithm detected 86% of all meals > or =15 g. Gastric distension reduced SWR and increased FI. Nitroglycerin reduced SWR. AED, using changes in FI and gastric SWR is feasible. Changes in FI and SWR are induced primarily by the presence of food in the stomach.