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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.

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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.

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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.

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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.

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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.

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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.

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PURPOSE: To analyze the results of limited macular translocation (MT) and photodynamic therapy (PDT) in subfoveal choroidal neovascularization due to degenerative myopia, with a minimum follow-up of 12 months. METHODS: Retrospective review of 55 consecutive patients: 31 eyes were treated using PDT and 24 were operated on with the limited macular translocation technique with chorioscleral infolding described by de Juan. Before and after each treatment, a complete examination comprised visual acuity, fundus examination, fluorescein angiography, and optical coherence tomography. Mean follow-up was 14 months in the PDT group and 19 months in the MT group. RESULTS: The improvement in visual acuity was better in the MT group than in the PDT group and was correlated with younger age (p<0.001). At month 12, visual acuity improved by 3 ETDRS lines or more in 6 six eyes of the PDT group (19%), with no improvement over 6 lines. In the MT group, visual acuity improved by 3 lines in 14 eyes (58%) including 8 eight eyes (33%) with an improvement of 6 lines or more. Final visual acuity remain unchanged (+/-2 lines) in 16 eyes of the PDT group (66%) and 8 eight eyes of the MT group (33%), and decreased in 9 nine eyes in the PDT group (29%) versus 2 two eyes in the MT group (8%). Mean gain in visual acuity at 12 months was +3.5 ETDRS lines in the MT group and -0.1 line in the PDT group (p=0.001). The mean displacement of the fovea after translocation was 950 microm. The mMean number of PDT treatments was 2.3 during the 12-month follow-up. CONCLUSIONS: Limited macular translocation allowed provided a significant improvement in visual acuity in some eyes with subfoveal neovascularization in myopia, especially in young patients, and resulted in a moderate rate of complications. Longer follow-up and further controlled and randomized studies are required to confirm these encouraging findings.

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PURPOSE: A reliable classification of AMD subgroups is necessary prior to any genetic or clinical investigation. For this purpose, we evaluated a selected list of items for AMD based on color photographs of the fundus but also on fluorescein and ICG angiographies and OCT. The first step (SPA-1) is to evaluate the interobserver agreement for AMD precursors. METHODS: The 30 items for AMD precursors, choroidal neovascularization and atrophy, were chosen from the literature. We selected 20 eyes from 20 consecutive patients affected by various forms of these precursors from the prospective NAT-2 study. Grading was based on color photographs of fundus, red-free frames, and fluorescein angiography. For each eye, five grids were filled in by four independent, experienced readers from our reading center and one expert. Within-subject variance was studied. RESULTS: Within subject variance showed the greatest agreement between graders for drusenoid pigment epithelial detachment (variance=0.000). The worst value for within subject variance (0.255) was recorded for the item "intermediate drusen between 5 and 20." CONCLUSION: This evaluation of our first grid for AMD precursors shows high agreement between graders for most of the items. The item with the lowest agreement should be modified according to the comments of the physicians. This grid could be implemented for phenotypic classification of ARM and AMD in future clinical or genetic studies.

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PURPOSE: To investigate a viral etiology in certain chalazia. METHODS: A prospective study over 7.5 years of all newly presenting chalazia associated with diffuse follicular conjunctivitis but without any other aetiological factors. Patients were investigated for ocular or systemic infections by history, physical exam, slit-lamp exam, and/or histology of conjunctival biopsy (including transmission electron microscopy). RESULTS: A total of 27 patients developed follicular conjunctivitis without meibomian gland dysfunction, blepharitis, or sexually transmitted diseases. Evidence for a viral aetiology included: recent systemic viral illness (15/27), recent contact with subjects with chalazia or follicular conjunctivitis (5/27), preauricular lymphadenopathy (4/27), viral corneal disease (4/27), or viral particles by ultrastructure (4/4). CONCLUSIONS: Chalazia may be associated with viral conjunctivitis. Intralesional corticosteroids should be considered with great caution for viral-induced chalazia.

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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.

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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.

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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.

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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.

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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.

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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.

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The intravenous use of positive inotropic agents, such as sympathomimetics and phosphodiesterase inhibitors, in heart failure is limited by pro-arrhythmic and positive chronotropic effects. Chronic use of these agents, while eliciting an improvement in the quality of life of patients with advanced heart failure, has been abandoned because of marked increase in mortality when compared to placebo. Nevertheless, patients with advanced heart failure can benefit from long-term positive inotropic support if the therapy can be delivered 'on demand' and in a manner that is both safe and effective. In this review, we will examine the use of a novel, non-stimulatory electrical signal that can acutely modulate left ventricular (LV) contractility in dogs with chronic heart failure in such a way as to elicit a positive inotropic support. Cardiac contractility modulation (CCM) with the Impulse Dynamic(trade mark) signal was examined in dogs with chronic heart failure produced by intracoronary microembolizations. Delivery of the CCM signal from a lead placed in the great coronary vein for periods up to 10 minutes resulted in significant improvements in cardiac output, LV peak+dP/dt, LV fractional area of shortening and LV ejection fraction measured angiographically. Discontinuation of the signal resulted in a return of all functional parameters to baseline values. In cardiomyocytes isolated from dogs with chronic heart failure, application of the CCM signal resulted in improved shortening, rate of change of shortening and rate of change of relengthening suggesting that CCM application is associated with intrinsic improvement of cardiomyocyte function. The improvement in isolated cardiomyocyte function after application of the CCM signal was accompanied by an increase in the peak and integral of the Ca(2+) transient suggesting modulation of calcium cycling by CCM application. In a limited number of normal dogs, intermittent chronic delivery of the CCM signal for up to 7 days showed chronic maintenance of LV functional improvement. In conclusion, pre-clinical results to date with the Impulse Dynamics CCM signal indicate that this non-pharmacologic therapeutic modality can provide short-term positive inotropic support to the failing heart and as such, may be a useful adjunct in the treatment of advanced heart failure. Additional, long-term studies in dogs with heart failure are needed to establish the safety and efficacy of this therapeutic modality for the chronic treatment of this disease syndrome.

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Heart failure is a highly prevalent disease in western society. Drug therapies aimed at increasing myocardial contractility have been associated with decreased survival. Several short and mid term clinical studies have suggested adjuvant or alternative therapies to congestive heart failure using modified pacing techniques that were aimed to increase contractility (e.g. Paired pacing) or restore synchrony of contraction (biventricular pacing). While delivery of paired pacing was abandoned during the early 70's, biventricular pacing has recently emerged as an adjuvant treatment to limited group of congestive heart failure patients with aberrant left ventricular conduction. In this brief review, we describe our initial safety and efficacy experience in patients with heart failure using a novel non-stimulatory electrical approach to the delivery of positive inotropic therapy to the failing myocardium. The study suggests that unlike modified pacing techniques, delivery of the signal to the left ventricle during the refractory period resulted in a rapid increase in myocardial contractility and improved hemodynamic performance. The near instantaneous contractility improvement achieved by this type of stimulus was shown to be safe and effective independently of the primary cause of heart failure or the function of the conduction system. Unlike pharmacologic treatments, which have a relatively constant effect, use of electrical stimuli may prove useful as a new therapeutic modality in the treatment of heart failure with which contractility can be improved when and as needed.

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Using concepts from the Precaution Adoption Process Model, we identified behavioral factors, sociodemographic and psychosocial variables, and beliefs about breast cancer that discriminated among women at different stages with regard to their intention to obtain mammography screening. An independent survey company conducted telephone interviews with 2,507 women aged 50 to 80 who were identified as underutilizers of mammography screening. Each underutilizer was assigned to one of three stages with regard to intention to get a mammogram: (a) definitely planning, (b) thinking about, and (c) not planning. Estimated actual risk of breast cancer, perceived risk to breast cancer, worry about breast cancer, and fear of learning from a mammogram that one has breast cancer were variables found to be significantly associated with intention to obtain a mammogram for several subgroups of underutilizing women. There are significant behavioral and psychosocial variables, beliefs and feelings about breast cancer, and demographic characteristics that distinguish underutilizing women at various stages with regard to intention to obtain mammography screening. Our findings provide new information that could help the health care professional motivate women who are not planning to utilize this preventive health measure to become regular utilizers.

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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.

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