Fat intolerance in developmentally impaired children with severe feeding intolerance

Children with a variety of genetic, metabolic, and neurologic disorders can suffer from severe feeding intolerance that is unresponsive to medical, surgical, and nutritional therapy. Developmentally disabled tube-fed children with severe upper gastrointestinal symptoms that persisted after fundoplication who were unresponsive to all medical, surgical, and nutritional interventions underwent a thorough gastrointestinal evaluation, including gastroscopy, pH-metry, upper gastrointestinal barium series, and gastric emptying studies. They were placed on a low-fat diet, and the symptoms before and after the diet were compared. The patients were then rechallenged with incremental increases in fat until the symptoms recurred or the patients reached their former fat concentration. Six children meeting the study criteria were evaluated. Four of these patients had a significant improvement in symptoms, oral intake and feeding tolerance with a decrease in fat intake, and relapse of symptoms when fat calories were increased. Improvement occurred in children who had been intolerant to duodenal feeding. We were subsequently able to wean two children from tube feeding. Dietary fat can provoke upper gastrointestinal symptoms in children with gastric and intestinal dysmotility. Short-term manipulation of dietary fat intake can improve tolerance to feeding.     

Functional disability after instrumented stabilization in lumbar degenerative spondylolisthesis: a follow-up study

Low back pain (LBP) is a widespread health problem and a major contributor to increasing health costs and lost work days. Different pathologies cause LBP and one of these is lumbar degenerative spondylolisthesis (SPL). There are no generally accepted and standardized methods for assessing the outcome of patients treated for degenerative lumbar SPL. This study aims to assess quality of life after surgery for lumbar degenerative SPL through the adoption of outcome measures. We studied 76 patients treated, for degenerative lumbar SPL, with spinal stabilization, decompression and bilateral dorsolateral fusion, followed up for at least two years. We used the Roland-Morris (RM) scale and the Oswestry Disability Index (ODI) to assess the quality of life of the patients before surgery and at follow up. Each patient was pre-operatively studied through standard and dynamic x-rays, CT scan and MRI of lumbar column. Relationships between clinical, radiological and disability scores, grouped by categories, were tested. The sample comprised 25 males and 51 females. Mean age was 59.6 years (SD 12.2). The mean duration of symptoms (from clinical onset to surgery) was 23.42 months (median 13, range 4-100 months). In about half of the cases, duration of symptoms before surgery was >12 months. At follow up, the fusion rate was 85.5%, and the ODI score was significantly reduced: an improvement of <20 points in 35.7% of patients, and of >20 points in 55.7%. On the RM scale, 59.4% of patients had a reduction >5 points, 13.1% a reduction of 2-4 points, and 27.5% an unchanged or worse score. There was no significant reduction in RM scale and ODI scores in patients with fusion versus pseudoarthrosis. Instrumental pedicle screw fixation and arthorodesis seem to be very effective in improving quality of life, as shown by the reduced disability scores at follow up.     

Regulation of insulin gene expression by cytokines and cell–cell interactions in mouse medullary thymic epithelial cells

Aims/hypothesis  

The expression of tissue-specific self-antigens in the thymus is essential for self-tolerance. Genetic susceptibility to type 1 diabetes correlates inversely with thymic insulin expression and, in mice, lowered levels of this expression result in T cell responses against insulin. This study was undertaken to examine whether thymic insulin expression is regulated by the same metabolic stimuli as in beta cells or by different inputs, possibly of an immune nature.     

Involvement of hippocampal PKCβI isoform in the early phase of memory formation of an inhibitory avoidance learning

Several evidences demonstrate that protein kinase C (PKC) is involved in hippocampal long-term potentiation (LTP) and in different forms of learning, including inhibitory avoidance training in rats. Here, we evaluated the levels of conventional PKC isozymes (α, βI, βII, γ) in synaptic plasma membrane (SPM) fractions isolated from hippocampus of rats subjected to a one-trial inhibitory avoidance paradigm. At 0, 30 and 120 min after training, there was a significant increase in the total amount of PKCβI. Densitometric analysis of the immunoblots showed an increase of 142±11% at 0 min, 193±16% at 30 min and 156±6% at 120 min after training relative to shocked control values. No changes were found in PKCβI levels in SPM fractions of the shocked animals relative to naive control values. No training-specific increments in the levels of PKCα, βII and γ were observed at any time point tested. However, an increase in PKCγ levels was found in trained and shocked animals sacrificed 120 min after each experimental procedure. In addition, bilateral microinjections of a fairly selective inhibitor of PKCβI isozyme into the CA1 of the dorsal hippocampus produced amnesia when given 10 min before training, or 50, 110, but not 170 min, after training. Thus, the present findings demonstrate the participation of PKCβI in the early synaptic events responsible for the acquisition and consolidation of an inhibitory avoidance learning, and suggest a putative role of this presynaptic isozyme on the enhanced PKC-dependent B-50/GAP-43 phosphorylation previously detected by us during this associative learning.     

Cancer mortality in the European Union, 1970-2003, with a joinpoint analysis

Background: Cancer mortality peaked in the European Union (EU)in the late 1980s and declined thereafter. Materials and methods: We analyzed EU cancer mortality dataprovided by the World Health Organization in 1970–2003,using joinpoint analysis. Results: Overall, cancer mortality levelled off in men since1988 and declined in 1993–2003 (annual percent change,APC = –1.3%). In women, a steady decline has been observedsince the early 1970s. The decline in male cancer mortalityhas been driven by lung cancer, which levelled off since thelate 1980s and declined thereafter (APC = 2.7% in 1997–2003).Recent decreases were also observed for other tobacco-relatedcancers, as oral cavity/pharynx, esophagus, larynx and bladder,as well as for colorectal (APC = –0.9% in 1992–2003)and prostate cancers (APC = –1.0% in 1994–2003).In women, breast cancer mortality levelled off since the early1990s and declined thereafter (APC = –1.0% in 1998–2003).Female mortality declined through the period 1970–2003for colorectal and uterine cancer, while it increased over thelast three decades for lung cancer (APC = 4.6% in 2001–2003).In both sexes, mortality declined in 1970–2003 for stomachcancer and for a few cancers amenable to treatment. Conclusion: This update analysis of the mortality from cancerin the EU shows favorable patterns over recent years in bothsexes. Key words: cancer, European Union, mortality, trends Received for publication October 25, 2007. Revision received November 26, 2007. Accepted for publication December 14, 2007.     

CpG-C immunotherapeutic efficacy is jeopardized by ongoing exposure to stress: Potential implications for clinical use

Bi-directional influences between stress hormones and immune responses have been repeatedly documented, however, in the clinical setting they are rarely considered when immunotherapeutic approaches are used or studied in patients. As some immunotherapeutic treatments have shown great potential in animal models but have had limited success in patients, we hypothesize that ongoing psychological and physiological stress responses in patients, which do not characterize the setting of animal studies, contribute to this discrepancy. In the current study we examined the interaction between ongoing water stress and CpG-C immunotherapy to determine whether stress that precedes immunotherapy can modulate the efficacy of CpG-C immunostimulation. C57BL/6 mice were exposed to water stress or served as controls. Two hours following the commencement of the stress protocol animals were injected with CpG-C, non-CpG, or PBS, and sacrificed 1, 4 or 12 h thereafter. We found that in CpG-C-treated animals stress eliminated the elevation of plasma IL-12, and synergistically elevated corticosterone levels. Furthermore, stress markedly reduced the total number of myeloid (33D1⁺), plasmacytoid (mPDCA-1⁺) and plasmacytoid-derived (33D1⁺mPDCA-1⁺) dendritic cells in CpG-C-treated animals, as well as the numbers of these cell sub-types expressing CD11b, CD80 and CD69. These changes were more dramatic in the blood than in the spleen. Overall, these findings indicate that under no-stress conditions CpG-C induces a robust immune response, which is significantly diminished when immunostimulation is attempted during ongoing stress. If these findings hold in humans, potential prophylactic treatments should be found to limit the deleterious effects of ongoing stress on the efficacy of immunotherapy.     

Management of Anticoagulant Therapy for Patients with Prosthetic Heart Valves or Atrial Fibrillation

There is a wide array of recommendations for the management of anticoagulant therapy in patients with mechanical heart valves. Especially the optimal intensity of vitamin K antagonists (VKA) is a ongoing matter of debate. On the basis of several studies, recommendations for daily clinical practice can be made. In this review, we discussed the studies and the different guidelines. Guidelines for the prevention of thromboembolic complications in patients with atrial fibrillation are more stringent. VKA with a target INR between 2.0 and 3.0 is more effective in the prevention of stroke than aspirin, especially in the presence of riskfactors for thromboembolism (age above 65, previous thromboembolism, history of hypertension and diabetes, enlarged left atrial diameter and left ventricular dysfunction). In the absence of clinical or echocardiographical riskfactors for thromboembolism, patients may be safely treated with aspirin.