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Sparing
Kinds of Sparing Terms modified by Sparing Selected AbstractsHippocampal lesions and discrimination performance of mice in the radial maze: Sparing or impairment depending on the representational demands of the taskHIPPOCAMPUS, Issue 2 2003Nicole Etchamendy Abstract The effects of ibotenate hippocampal lesions on discrimination performance in an eight-arm radial maze were investigated in mice, using a three-stage paradigm in which the only parameter that varied among stages was the way the arms were presented. In the initial learning phase (stage 1), animals learned the valence or reward contingency associated with six (three positive and three negative) adjacent arms of the maze using a successive (go/no-go) discrimination procedure. In the first test phase (stage 2), the six arms were grouped into three pairs, so that on each trial, the subject was faced with a choice between two adjacent arms of opposite valence (concurrent two-choice discrimination). In the second test phase (stage 3), the subject was faced with all six arms simultaneously (six-choice discrimination). Hippocampal-lesioned mice acquired the initial learning phase at a near-normal rate but behaved as if they had learned nothing when challenged with the two-choice discriminations at stage 2. In contrast, they behaved normally when confronted with the six-choice discrimination at stage 3. Detailed examination of within- and between-stage performance suggests that hippocampal-lesioned mice perform as intact mice when presentation of the discriminanda encourages the storage and use of separate representations (i.e., in initial learning and six-choice discrimination testing), but that they fail in test situations that involve explicit comparisons between such separate representations (two-choice discriminations), hence requiring the use of relational representations. Hippocampus 2003;13:197,211. © 2003 Wiley-Liss, Inc. [source] ORIGINAL ARTICLE: Sparing of the hippocampus and limbic circuit during whole brain radiation therapy: A dosimetric study using helical tomotherapyJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 4 2010JC Marsh Abstract Introduction:, The study aims to assess the feasibility of dosimetrically sparing the limbic circuit during whole brain radiation therapy (WBRT) and prophylactic cranial irradiation (PCI). Methods and Materials:, We contoured the brain/brainstem on fused MRI and CT as the target volume (PTV) in 11 patients, excluding the hippocampus and the rest of the limbic circuit, which were considered organs at risk (OARs). PCI and WBRT helical tomotherapy plans were prepared for each patient with a 1.0-cm field width, pitch = 0.285, initial modulation factor = 2.5. We attempted to spare the hippocampus and the rest of the limbic circuit while treating the rest of the brain to 30 Gy in 15 fractions (PCI) or 35 Gy in 14 fractions (WBRT) with V100 , 95%. The quality of the plans was assessed by calculating mean dose and equivalent uniform dose (EUD) for OARs and the % volume of the PTV receiving the prescribed dose, V100. Results:, In the PCI plans, mean doses/EUD were: hippocampus 12.5 Gy/14.23 Gy, rest of limbic circuit 17.0 Gy/19.02 Gy. In the WBRT plans, mean doses/EUD were: hippocampus 14.3 Gy/16.07 Gy, rest of limbic circuit 17.9 Gy/20.74 Gy. The mean V100 for the rest of the brain (PTV) were 94.7% (PCI) and 95.1% (WBRT). Mean PCI and WBRT treatment times were essentially identical (mean 15.23 min, range 14.27,17.5). Conclusions:, It is dosimetrically feasible to spare the hippocampus and the rest of the limbic circuit using helical tomotherapy while treating the rest of the brain to full dose. [source] Sparing of the substantia nigra in sporadic Creutzfeldt-Jakob disease presenting as an acute corticobasal syndromeMOVEMENT DISORDERS, Issue 11 2007Wim Vandenberghe [source] Cognitive visual dysfunctions in preterm children with periventricular leukomalaciaDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 12 2009ELISA FAZZI MD PHD Aim, Cognitive visual dysfunctions (CVDs) reflect an impairment of the capacity to process visual information. The question of whether CVDs might be classifiable according to the nature and distribution of the underlying brain damage is an intriguing one in child neuropsychology. Method, We studied 22 children born preterm (12 males, 10 females; mean age at examination 8y, range 6,15y; mean gestational age 30wks, range 28,36wks) with periventricular leukomalacia, spastic diplegia, normal intelligence (mean Full-scale IQ 84; mean Verbal IQ 97; mean Performance IQ 74), and normal visual acuity, focusing on higher visual functions. Brain magnetic resonance images (MRI) were analysed to establish the presence of lesions along the primary optic pathway, in the occipitoparietal and occipitotemporal regions. Results, Most children displayed an uneven cognitive profile, with deficits in visual object recognition, visual imagery, visual,spatial skills, and visual memory, and sparing of visual associative abilities, non-verbal intelligence, and face and letter recognition. Conventional brain MRI did not document major alterations of parietal and temporal white matter, or cortical alteration of areas involved in visual associative functions. Interpretation, We suggest a widespread involvement of higher visual processing systems, involving both the ventral and dorsal streams, in preterm children with periventricular leukomalacia. The lack of major alterations on conventional MRI does not exclude the possibility of malfunctioning of higher visual processing systems, expressing itself through discrete CVDs. Possible mechanisms underlying these neuropsychological deficits are discussed. [source] Acute encephalopathy with biphasic seizures and late restricted diffusion on MRI in a Japanese child living in the USADEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2008David E Traul MD PhD We report an 18-month-old Japanese female living in the USA whose clinical course and radiographic findings were consistent with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). She was initially diagnosed with complex febrile seizures. However, on day 3 of admission, she had a cluster of complex partial seizures and the onset of a global developmental regression. In contrast to the normal magnetic resonance image of the brain obtained on admission, subsequent imaging demonstrated transient subcortical diffusion-weighted abnormalities in the white matter of the bilateral posterosuperior frontal, parietal, temporal, and occipital regions, with sparing of the perirolandic area. One year later, her developmental delay, although improved, persisted and she continued to experience sporadic seizures while being treated with topiramate monotherapy. Repeat imaging showed diffuse, poorly defined, increased T2 signals in the white matter of the posterosuperior frontal, parietal, temporal and occipital regions and diffuse cerebral volume loss. Previous reports of AESD have been limited to children aged under 4 years living in Japan. With the identification of this case, it is important that all physicians, not only those in Japan, who care for children with febrile seizures be aware of AESD and its associated neurological morbidity. [source] A unique case of limb-girdle muscular dystrophy type 2A carrying novel compound heterozygous mutations in the human CAPN3 geneEUROPEAN JOURNAL OF NEUROLOGY, Issue 7 2007E. Matsubara A unique sib pair afflicted by limb girdle muscular dystrophy type 2A (LGMD2A) is described showing a slowly progressive autosomal recessive type of muscular dystrophy with onset in the third and fourth decades. The patients had early asymmetric muscle involvement characterized by prominent biceps brachii atrophy with sparing of the knee extensors. Additional findings included elevation of serum creatine kinase level, myopathic EMG changes and dystrophic type of pathology on muscle biopsy. Asymmetrical wasting of muscles in the extremities exhibited uniform and highly selective CT imaging patterns. RNA and DNA analyses confirmed novel compound heterozygous mutations (R147X/L212F) in the human CAPN3 gene. [source] Neurocutaneous syndrome with mental delay, autism, blockage in intracellular vescicular trafficking and melanosome defectsEUROPEAN JOURNAL OF NEUROLOGY, Issue 8 2006S. Buoni We evaluated a 11-year-old male patient with mental delay, autism and brownish and whitish skin spots. The former resembled those of neurofibromatosis, the latter those of tuberous sclerosis. The patient received a complete clinical work-up to exclude neurofibromatosis, tuberous sclerosis, or any other known neurocutaneous disease, with biochemistry, chromosome analysis and analysis of skin specimens. Being all the other tests not significant, two main ultrastructural defects were observed. The first was a blockage in intracellular vescicular trafficking with sparing of the mitochondria; the second an aberrant presence of melanosomes in vacuoles of several cell lines and abnormal transfer of these organelles to keratinocytes. This patient presented with a unique clinical picture distinct from neurofibromatosis or tuberous sclerosis or any other known neurocutaneous disease. The ultrastructural abnormalities suggested a defect in cell trafficking involving several cell lines and compartments. [source] Flail arm syndrome: a clinical variant of amyotrophic lateral sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 8 2004A. Czaplinski We describe a case of a 65-year old patient diagnosed with amyotrophic lateral sclerosis. The clinical findings, with symmetric, predominantly proximal wasting and weakness of both arms (especially of the infra-, supraspinatus and deltoideus) leading to severe functional disability and contrasting with preserved independent ambulation and sparing of bulbar muscles, were consistent with the proposed criteria of the so-called flail arm syndrome. Based on our case we characterize the clinical features of flail arm syndrome and review the literature. [source] Nitric oxide synthase inhibition reduces O2 cost of force development and spares high-energy phosphates following contractions in pump-perfused rat hindlimb musclesEXPERIMENTAL PHYSIOLOGY, Issue 3 2006David J. Baker The purpose of the present experiments was to test the hypotheses that: (i) nitric oxide synthase (NOS) inhibition reduces the O2 cost of force development across a range of contractile demands; and (ii) this reduced O2 cost of force development would be reflected in a sparing of intramuscular higher energy phosphates. Rat distal hindlimb muscles were pump perfused in situ and electrically stimulated (200 ms trains with pulses at 100 Hz, each pulse 0.05 ms duration) for 1 min each at 15, 30 and 60 tetani min,1 and for 2 min at 90 tetani min,1 in three groups: 0.01 mm adenosine; 1 mm d -NAME and 0.01 mm adenosine (d -NAME); and 1 mm l -NAME and 0.01 mm adenosine (l -NAME). The gastrocnemius,plantaris,soleus muscle group was freeze clamped post-contractions for metabolite analyses. Force was 19% higher and oxygen uptake was 20% lower with l -NAME versus adenosine, and there was a 35% reduction in /time-integrated tension versus adenosine and 24% versusd -NAME that was independent of contraction frequency. l -NAME treatment produced a 33% sparing of muscle phosphocreatine (PCr), and intramuscular lactate was no different between groups. In contrast, d -NAME reduced force by 30%, by 29% and the O2 cost of force development by 15% compared with adenosine, but had no effect on the degree of intramuscular ATP and PCr depletion. These results show that NOS inhibition improved the metabolic efficiency of force development, either by improving the ATP yield for a given O2 consumption or by reducing the ATP cost of force development. In addition, these effects were independent of contraction frequency. [source] Comparative gene expression profiling of olfactory ensheathing glia and Schwann cells indicates distinct tissue repair characteristics of olfactory ensheathing gliaGLIA, Issue 12 2008Elske H.P. Franssen Abstract Olfactory ensheathing glia (OEG) are a specialized type of glia that support the growth of primary olfactory axons from the neuroepithelium in the nasal cavity to the brain. Transplantation of OEG in the injured spinal cord promotes sprouting of injured axons and results in reduced cavity formation, enhanced axonal and tissue sparing, remyelination, and angiogenesis. Gene expression analysis may help to identify the molecular mechanisms underlying the ability of OEG to recreate an environment that supports regeneration in the central nervous system. Here, we compared the transcriptome of cultured OEG (cOEG) with the transcriptomes of cultured Schwann cells (cSCs) and of OEG directly obtained from their natural environment (nOEG), the olfactory nerve layer of adult rats. Functional data mining by Gene Ontology (GO)-analysis revealed a number of overrepresented GO-classes associated with tissue repair. These classes include "response to wounding," "blood vessel development," "cell adhesion," and GO-classes related to the extracellular matrix and were overrepresented in the set of differentially expressed genes between both comparisons. The current screening approach combined with GO-analysis has identified distinct molecular properties of OEG that may underlie their efficacy and interaction with host tissue after implantation in the injured spinal cord. These observations can form the basis for studies on the function of novel target molecules for therapeutic intervention after neurotrauma. © 2008 Wiley-Liss, Inc. [source] Evaluation of patterns of failure and subjective salivary function in patients treated with intensity modulated radiotherapy for head and neck squamous cell carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2007Megan E. Daly BS Abstract Background. Our aim was to correlate patterns of failure with target volume delineations in patients with head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiation therapy (IMRT) and to report subjective xerostomia outcomes after IMRT as compared with conventional radiation therapy (CRT). Methods. Between January 2000 and April 2005, 69 patients with newly diagnosed nonmetastatic HNSCC underwent curative parotid-sparing IMRT at Stanford University. Sites included were oropharynx (n = 39), oral cavity (n = 8), larynx (n = 8), hypopharynx (n = 8), and unknown primary (n = 6). Forty-six patients received definitive IMRT (66 Gy, 2.2 Gy/fraction), and 23 patients received postoperative IMRT (60.2 Gy, 2.15 Gy/fraction). Fifty-one patients also received concomitant chemotherapy. Posttreatment salivary gland function was evaluated by a validated xerostomia questionnaire in 29 IMRT and 75 matched CRT patients >6 months after completing radiation treatment. Results. At a median follow-up of 25 months for living patients (range, 10,60), 7 locoregional failures were observed, 5 in the gross target or high-risk postoperative volume, 1 in the clinical target volume, and 1 at the junction of the IMRT and supraclavicular fields. The 2-year Kaplan,Meier estimates for locoregional control and overall survival were 92% and 74% for definitive IMRT and 87% and 87% for postoperative IMRT patients, respectively. The mean total xerostomia questionnaire score was significantly better for IMRT than for CRT patients (p = .006). Conclusions. The predominant pattern of failure in IMRT-treated patients is in the gross tumor volume. Parotid sparing with IMRT resulted in less subjective xerostomia and may improve quality of life in irradiated HNSCC patients. © 2006 Wiley Periodicals, Inc. Head Neck, 2007 [source] Particle beam radiotherapy for head and neck tumors: Radiobiological basis and clinical experienceHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2006Barbara Alicja Jereczek-Fossa MD Abstract Background. Head and neck tumors are often located near critical organs, making it impossible to deliver a dose of conventional radiotherapy high enough to eradicate the disease. Our aim was to review the potential benefits and available clinical experience of particle beam therapy (hadrontherapy) in the treatment of these tumors. Methods. A review of the literature was carried out through a MEDLINE search (publications between 1980 and 2005). Results. A review of the available clinical data shows that particle beam therapy can offer several radiobiological and physical advantages over conventional photon radiotherapy: improved dose distribution permits dose escalation within the target and optimal sparing of normal tissue. Preclinical and clinical studies suggest that there may be benefits to using hadrontherapy for tumors characterized by poor radiosensitivity and critical location. At present, the most used hadrons are protons and, as yet on an experimental basis, carbon ions. It is now well accepted that there are certain indications for using proton therapy for skull base tumors (chordoma and chondrosarcoma), paranasal sinus carcinomas, selected nasopharyngeal tumors, and neutron/ion therapy for salivary gland carcinomas (in particular, adenoid cystic tumors). Its viability in other cases, such as locally advanced squamous cell carcinoma, melanoma, soft tissue sarcoma, and bone sarcoma, is still under investigation. Conclusions. Hadrontherapy can be beneficial in the treatment of tumors characterized by poor radiosensitivity and critical location. Further clinical and radiobiological studies are warranted for improved selection of patient population. © 2006 Wiley Periodicals, Inc. Head Neck, 2006 [source] Effect of unitization on associative recognition in amnesiaHIPPOCAMPUS, Issue 3 2007Joel R. Quamme Abstract We examined how associative recognition performance in amnesic patients is mediated by use of a unitized (i.e., holistic) encoding strategy, and the degree to which the unitization effect is related to sparing of familiarity-based recognition. Participants studied word pairs as either separate lexical units in sentences (i.e., nonunitized) or as compounds (unitized). Under standard recognition instructions, normal controls and patients with left-temporal lobe damage (previously determined to have impairments in both recollection and familiarity) showed no difference for unitized and nonunitized pairs, whereas hypoxics (previously determined to have impaired recollection but relatively preserved familiarity) showed an advantage of unitized over nonunitized pairs. This effect was reproduced in normal healthy participants under instructions to restrict responses to judgments of familiarity. The results indicate that unitization may mediate the degree of associative recognition impairment exhibited by some amnesic patients, and that the effect is related to preserved familiarity capacity. The relevance of the results to the debate over the importance of the hippocampus in memory for associations is discussed. © 2007 Wiley-Liss, Inc. [source] Modulating tone: the overture of S1P receptor immunotherapeuticsIMMUNOLOGICAL REVIEWS, Issue 1 2008Hugh Rosen Summary: Modulation of complex functions within the immune system has proven to be surprisingly sensitive to alterations in the lysophospholipid sphingosine 1-phosphate (S1P) receptor-ligand rheostat. This has become increasingly evident from both chemical and genetic manipulation of the S1P system, with pharmacological effects upon lymphoid cells, dendritic cell function, as well as vascular interfaces. The integrated immune system, perhaps as a result of its relatively recent evolutionary ontogeny, has selected for a number of critical control points regulated by five distinct high affinity G-protein-coupled receptor subtypes with a shared ligand, with receptors distributed on lymphocytes, dendritic cells, and endothelium. All of these cellular components of the axis are capable of modulating immune responses in vivo, with the impact on the immune response being very different from classical immunosuppressants, by virtue of selective spatial and temporal sparing of humoral and myeloid elements of host defense. Pharmacological subversion of the S1P rheostat is proving to be clinically efficacious in multiple sclerosis, and both the scope and limitations of therapeutic modulation of the S1P axis in immunotherapy are becoming clearer as understanding of the integrated chemical physiology of the S1P system emerges. [source] Further experience with the use of 6-thioguanine in patients with Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 10 2008Azhar Ansari MD Abstract Background: 6-Thioguanine (6-TG) is efficacious in patients with Crohn's Disease (CD) failing conventional immunosuppression but there are reports of hepatotoxicity. We report our experience of the safety and efficacy of 6-TG in a series of patients with CD. Methods: A retrospective study of patients with CD who failed thiopurines ± methotrexate between 2001 and 2006 was performed. Indications for 6-TG were; active disease, to allow infliximab withdrawal, steroid sparing, or fistula closure. Patients underwent regular review and those treated longer than 1 year were advised to have liver magnetic resonance imaging (MRI) and liver biopsy. Results: All 30 patients treated with 6-TG during the period were included. The median dose and duration of 6-TG was 40 mg daily and 21.5 months, respectively. Initial clinical response was achieved in 18/30 (60%). Eleven of 29 (38%) (1 unrelated death) remained in remission at a median 44 months follow-up. Seven of 30 (23%) discontinued 6-TG due to adverse effects; 7/30 (23%) patients developed abnormal liver function tests (LFTs) during treatment, mostly transient and mild. One patient developed a portal hypertensive syndrome resolving on cessation of 6-TG. Of 11 liver biopsies, none showed nodular regenerative hyperplasia (NRH). The median red blood cell 6-thioguanine nucleotide (6-TGN) level was 807 pmol/108. Conclusions: 6-TG has good clinical efficacy for third-line immunosuppression in CD but hepatotoxicity remains a concern. However, previous reports of NRH in 6-TG-treated inflammatory bowel disease patients have not been substantiated by this cohort. (Inflamm Bowel Dis 2008) [source] Comparison of intensity modulated radiation therapy (IMRT) treatment techniques for nasopharyngeal carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 2 2001Jason Chia-Hsien Cheng M.D. Abstract We studied target volume coverage and normal tissue sparing of serial tomotherapy intensity modulated radiation therapy (IMRT) and fixed-field IMRT for nasopharyngeal carcinoma (NPC), as compared with those of conventional beam arrangements. Twelve patients with NPC (T2-4N1-3M0) at Mallinckrodt Institute of Radiology underwent computed tomography simulation. Images were then transferred to a virtual simulation workstation computer for target contouring. Target gross tumor volumes (GTV) were primary nasopharyngeal tumor (GTVNP) with a prescription of 70 Gy, grossly enlarged cervical nodes (GTVLN) with a prescription of 70 Gy, and the uninvolved cervical lymphatics [designated as the clinical tumor volume (CTV)] with a prescription of 60 Gy. Critical organs, including the parotid gland, spinal cord, brain stem, mandible, and pituitary gland, were also delineated. Conventional beam arrangements were designed following the guidelines of Intergroup (SWOG, RTOG, ECOG) NPC Study 0099 in which the dose was prescribed to the central axis and the target volumes were aimed to receive the prescribed dose ± 10%. Similar dosimetric criteria were used to assess the target volume coverage capability of IMRT. Serial tomotherapy IMRT was planned using a 0.86-cm wide multivane collimator, while a dynamic multileaf collimator system with five equally spaced fixed gantry angles was designated for fixed-beam IMRT. The fractional volume of each critical organ that received a certain predefined threshold dose was obtained from dose-volume histograms of each organ in either the three-dimensional or IMRT treatment planning computer systems. Statistical analysis (paired t -test) was used to examine statistical significance. We found that serial tomotherapy achieved similar target volume coverage as conventional techniques (97.8 ± 2.3% vs. 98.9 ± 1.3%). The static-field IMRT technique (five equally spaced fields) was inferior, with 92.1 ± 8.6% fractional GTVNP receiving 70 Gy ± 10% dose (P < 0.05). However, GTVLN coverage of 70 Gy was significantly better with both IMRT techniques (96.1 ± 3.2%, 87.7 ± 10.6%, and 42.2 ± 21% for tomotherapy, fixed-field IMRT, and conventional therapy, respectively). CTV coverage of 60 Gy was also significantly better with the IMRT techniques. Parotid gland sparing was quantified by evaluating the fractional volume of parotid gland receiving more than 30 Gy; 66.6 ± 15%, 48.3 ± 4%, and 93 ± 10% of the parotid volume received more than 30 Gy using tomotherapy, fixed-field IMRT, and conventional therapy, respectively (P < 0.05). Fixed-field IMRT technique had the best parotid-sparing effect despite less desirable target coverage. The pituitary gland, mandible, spinal cord, and brain stem were also better spared by both IMRT techniques. These encouraging dosimetric results substantiate the theoretical advantage of inverse-planning IMRT in the management of NPC. We showed that target coverage of the primary tumor was maintained and nodal coverage was improved, as compared with conventional beam arrangements. The ability of IMRT to spare the parotid glands is exciting, and a prospective clinical study is currently underway at our institution to address the optimal parotid dose-volume needs to be spared to prevent xerostomia and to improve the quality of life in patients with NPC. © 2001 Wiley-Liss, Inc. [source] Xeroderma pigmentosum with limited involvement of the UV-exposed areas: a case reportINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 4 2003Mostafa Mirshams-Shahshahani MD A 21-year-old woman with skin type IV, who had developed photophobia and brown, spotty, hyperpigmented lesions on her face from early childhood, presented to our center for treatment of her facial lesions. Examination on admission revealed numerous, freckle-like, hyperpigmented macules and actinic keratoses over the central part of the face, with sparing of the forehead, chin, and peripheral area (Fig. 1). The area involved was approximated to be around 2% of the total body surface. The dorsal parts of the hands showed no lesions (Fig. 2), but guttate hypomelanotic lesions were apparent on both forearms. Figure 1. Limitation of xeroderma pigmentosum lesions to the center of the face Figure 2. Hands are devoid of any lesions Histologic examination of biopsies from four different facial lesions revealed them to be keratoacanthoma (1.5 × 2.5 cm ulcerative nodule on the right cheek), sclerosing basal cell epithelioma (nasal lesion), lentigo simplex, and hypertrophic actinic keratosis. Corneal clouding, conjunctival injection, loss of lashes, and atrophy of the lids were apparent on ophthalmologic examination. Other parts of the physical examination, including examination of the oral cavity, were nonsignificant. In addition, except for the presence of mild eczema in a sibling, the patient's family history regarding the presence of any similar problem and also any other important dermatologic or general disorder was negative. [source] Putting a Human Face on DevelopmentINTERNATIONAL SOCIAL SCIENCE JOURNAL, Issue 166 2000Rubens Ricupero The century is ending with failure to solve two major threats to the future: mass unemployment and growing inequality. Furthermore, in the poor parts of the world, the very possibility of sustainable development has been questioned by the economic crisis that started in Asia two years ago. This monetary and financial crisis truly deserved to be called a "crisis of development", for three main reasons. First, it hit almost exclusively most of the developing countries, at the same time sparing and even benefitingthe industrial economies. Second, paradoxically, it was much more destructive in the most advanced of the developing nations. Third, it has created uncertainties and questions regarding the possibility of regaining the previous levels of economic performance that characterised "the Asian tigers". Competition is very analogous to games. Both need fair rules and impartial arbiters. Governments and trade negotiators think that these are sufficient, forgetting a third and fundamental element. To play a game, you have to learn how to play it; through education and time to train. A key to success will be access to information. [source] Characterizing the nutritional strategy of incubating king eiders Somateria spectabilis in northern AlaskaJOURNAL OF AVIAN BIOLOGY, Issue 6 2008Rebecca L. Bentzen We measured plasma concentrations of variables associated with lipid metabolism (free fatty acids, glycerol, triglyceride, and ,-hydroxybutyrate), protein metabolism (uric acid), and baseline corticosterone to characterize the nutritional state of incubating king eiders Somateria spectabilis and relate this to incubation constancy at two sites, Kuparuk and Teshekpuk, in northern Alaska. King eiders at both sites appeared to employ a partial-income incubation strategy, relying on both endogenous and exogenous energy resources. Females maintained high invariant levels of free fatty acids, ,-hydroxybutyrate, and glycerol throughout incubation, indicating that fat reserves were a major energy source, and not completely depleted during incubation. Similarly, uric acid did not increase, suggesting effective protein sparing or protein ingestion and adequate lipid reserves throughout incubation. Baseline corticosterone and triglyceride levels increased during incubation, indicative of an increase in foraging during late stages of incubation. Incubating females at Kuparuk had higher triglyceride concentrations but also had higher ,-hydroxybutyrate concentrations than females at Teshekpuk. This dichotomy may reflect a short-term signal of feeding overlaying the longer-term signal of reliance on endogenous lipid reserves due to higher food intake yet higher metabolic costs at Kuparuk because of its colder environment. Incubation constancy was not correlated with plasma concentrations of lipid or protein metabolites. [source] Necrolytic acral erythema without hepatitis C infectionJOURNAL OF CUTANEOUS PATHOLOGY, Issue 3 2009Yu-Hung Wu Necrolytic acral erythema is a newly described entity characterized by sharply demarcated scaly plaques on the dorsum of the hands and feet. More than 30 patients have been reported since 1996, all of whom had anti-hepatitis C virus antibody. A 32-year-old Taiwanese woman had been diagnosed with and treated for systemic lupus erythematosus with lupus nephritis about 10 years earlier. Soon thereafter, she noted several well-demarcated keratotic plaques with erythematous borders on her feet, with sparing of the soles. Histopathology showed diffuse parakeratosis with a neutrophil infiltrate, hypogranulosis, pale upper keratinocytes, scattered and grouped dyskeratotic cells, psoriasiform hyperplasia and a mild lymphocytic infiltrate in the upper dermis. The diagnosis was made after three biopsies. The lesions regularly worsened just before and during menstruation, but patch and intradermal tests for progesterone and estrogen were negative. There was no evidence of either hepatitis B or hepatitis C infection. The lesions did not respond to treatment with zinc. The rash regressed spontaneously when corticosteroids were stopped and recurred when they were restarted, finally resolving completely after she was treated with high-dose pulse steroids for her lupus. [source] Minocycline neuroprotects, reduces microgliosis, and inhibits caspase protease expression early after spinal cord injuryJOURNAL OF NEUROCHEMISTRY, Issue 5 2006Barry W. Festoff Abstract Minocycline, a clinically used tetracycline for over 40 years, crosses the blood,brain barrier and prevents caspase up-regulation. It reduces apoptosis in mouse models of Huntington's disease and familial amyotrophic lateral sclerosis (ALS) and is in clinical trial for sporadic ALS. Because apoptosis also occurs after brain and spinal cord (SCI) injury, its prevention may be useful in improving recovery. We analyzed minocycline's neuroprotective effects over 28 days following contusion SCI and found significant functional recovery compared to tetracycline. Histology, immunocytochemistry, and image analysis indicated statistically significant tissue sparing, reduced apoptosis and microgliosis, and less activated caspase-3 and substrate cleavage. Since our original report in abstract form, others have published both positive and negative effects of minocycline in various rodent models of SCI and with various routes of administration. We have since found decreased tumor necrosis factor-,, as well as caspase-3 mRNA expression, as possible mechanisms of action for minocycline's ameliorative action. These results support reports that modulating apoptosis, caspases, and microglia provide promising therapeutic targets for prevention and/or limiting the degree of functional loss after CNS trauma. Minocycline, and more potent chemically synthesized tetracyclines, may find a place in the therapeutic arsenal to promote recovery early after SCI in humans. [source] Magnetic Resonance Analysis of Postsurgical Temporal LobectomyJOURNAL OF NEUROIMAGING, Issue 3 2001Taoufik M. Alsaadi MD ABSTRACT Background and Purpose. The effect of temporal lobe transection area, volume of postoperative gliosis, and surgical technique on patients' seizure-free outcome is unknown. The authors studied the effects of these variables on patients' seizure-free outcome. Methods. A retrospective review of magnetic resonance imaging examinations acquired 3 to 18 months after temporal lobe resection was carried out for 18 patients with intractable temporal lobe seizures and known postsurgical outcomes for more than 2 years. The total volume of radiologically probable gliosis evident on axial proton-density-weighted images was calculated for each patient using software on an independent console. The total area of temporal lobe surface transected by the scalpel was calculated as well, using sagittal T1-weighted images. The total volume of gliosis, the total area of transected temporal lobe, and the specific type of surgery (sparing vs no sparing of the superior temporal gyrus) were then correlated with the postsurgical outcome of the patients. An examiner with no prior knowledge of the patients' postsurgical outcomes carried out the above calculations and measurements. The patients' postoperative outcome was defined using Engel classifications, and patients were divided into two groups: group A with Engel class 1 (n= 9) and group B with Engel classes 2,4 (n= 9). Results. The mean volumes of postoperative gliosis were not significantly different between group A (3592.3 mm3) and group B (4270 mm3). The mean area of transected temporal lobe was also similar between group A (1865.2 mm2) and group B (1930 mm2). With regard to surgical technique, there were 5 subjects who had the superior temporal gyrus resected and 13 who did not. Eighty percent of patients with the superior temporal gyrus resected were Engel class 1 or 2, whereas only 20% were of Engel class 3 or 4. Conclusion. The authors found no clear association between postoperative outcome and residual temporal lobe gliosis, the surgical technique, or the total area of temporal lobe transected by the scalpel. [source] Overexpression of Bcl-XL in human neural stem cells promotes graft survival and functional recovery following transplantation in spinal cord injuryJOURNAL OF NEUROSCIENCE RESEARCH, Issue 14 2009Seung I. Lee Abstract Transplantation of neural stem cells (NSCs) has shown promise for improving functional recovery after spinal cord injury (SCI). The inhospitable milieu of injured spinal cord, however, does not support survival of grafted NSCs, reducing therapeutic efficacy of transplantation. The present study sought to examine whether overexpression of antiapoptotic gene Bcl-XL in NSCs could promote graft survival and functional recovery following transplantation in rat contusive SCI model. A human NSC line (HB1.F3) was transduced with a retroviral vector encoding Bcl-XL to generate Bcl-XL -overexpressing NSCs (HB1.F3.Bcl-XL). Overexpression of Bcl-XL conferred resistance to staurosporine-mediated apoptosis. The number of HB1.F3.Bcl-XL cells was 1.5-fold higher at 2 weeks and 10-fold higher at 7 weeks posttransplantation than that of HB1.F3 cells. There was no decline in the number of HB1.F3.Bcl-XL cells between 2 and 7 weeks, indicating that Bcl-XL overexpression completely blocked cell death occurring between these two time points. Transplantation of HB1.F3.Bcl-XL cells improved locomotor scores and enhanced accuracy of hindlimb placement in a grid walk. Approximately 10% of surviving NSCs differentiated into oligodendrocytes. Surviving NSCs produced brain-derived neurotrophic factor (BDNF), and the level of BDNF was significantly increased only in the HB1.F3.Bcl-XL group. Transplantation of HB1.F3.Bcl-XL cells reduced cavity volumes and enhanced white matter sparing. Finally, HB1.F3.Bcl-XL grafts enhanced connectivity between the red nucleus and the spinal cord below the lesion. These results suggest that enhancing graft survival with antiapoptotic gene can potentiate therapeutic benefits of NSC-based therapy for SCI. © 2009 Wiley-Liss, Inc. [source] Pivotal role of early B-cell factor 1 in development of striatonigral medium spiny neurons in the matrix compartmentJOURNAL OF NEUROSCIENCE RESEARCH, Issue 10 2008Mary Kay Lobo Abstract The mammalian striatum plays a critical function in motor control, motor and reward learning, and cognition. Dysfunction and degeneration of the striatal neurons are implicated in major neurological and psychiatric disorders. The vast majority of striatal neurons are medium spiny neurons (MSNs). MSNs can be further subdivided into distinct subtypes based on their physical localization in the striatal patch vs. matrix compartments and based on their axonal projections and marker gene expression (i.e., striatonigral MSNs vs. striatopallidal MSNs). Despite our extensive knowledge on the striatal cytoarchitecture and circuitry, little is known about the molecular mechanisms controlling the development of the MSN subtypes in the striatum. Early B-cell factor 1 (Ebf1) is a critical transcription factor implicated in striatal MSN development. One study shows that Ebf1 is critical for the differentiation of MSNs in the matrix, and our separate study demonstrates that Ebf1 is selectively expressed in the striatonigral MSNs and is essential for their postnatal differentiation. In the present study, we further validate the striatonigral MSN deficits in Ebf1,/, mice using multiple striatonigral MSN reporter mice. Moreover, we demonstrate that the striatonigral MSN deficits in these mice are restricted to those in the matrix, with relative sparing of those in the patch. Finally, we demonstrate that Ebf1 deficiency also results in reduced expression of another striatonigral-specific transcription factor, zinc finger binding protein 521 (Zfp521), which is a known Ebf1 functional partner. Overall, our study reveals that Ebf1 may play an essential role in controlling the differentiation of the striatonigral MSNs in the matrix compartment. © 2008 Wiley-Liss, Inc. [source] Fasting is neuroprotective following traumatic brain injury,JOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2008Laurie M. Davis Abstract To determine the neuroprotective effect of fasting after traumatic brain injury (TBI) and to elucidate the potential underlying mechanisms, we used a controlled cortical impact (CCI) injury model to induce either a moderate or a severe injury to adult male Sprague Dawley rats. Tissue-sparing assessments were used to determine the level of neuroprotection of fasting, hypoglycemia (insulin 10 U), or ketone (1.66 mmoles/kg/day or 0.83 mmoles/kg/day; D-beta-hydroxtbutyrate) administration. Mitochondrial isolation and respiratory studies were utilized to determine the functionality of mitochondria at the site of injury. We also investigated biomarkers of oxidative stress, such as lipid/protein oxidation, reactive oxygen species (ROS) production, and intramitochondrial calcium load, as a secondary measure of mitochondrial homeostasis. We found that fasting animals for 24 hr, but not 48 hr, after a moderate (1.5 mm), but not severe (2.0 mm), CCI resulted in a significant increase in tissue sparing. This 24-hr fast also decreased biomarkers of oxidative stress and calcium loading and increased mitochondrial oxidative phosphorylation in mitochondria isolated from the site of injury. Insulin administration, designed to mimic the hypoglycemic effect seen during fasting did not result in significant tissue sparing after moderate CCI injury and in fact induced increased mortality at some injection time points. However, the administration of ketones resulted in increased tissue sparing after moderate injury. Fasting for 24 hr confers neuroprotection, maintains cognitive function, and improves mitochondrial function after moderate (1.5 mm) TBI. The underlying mechanism appears to involve ketosis rather than hypoglycemia. © 2008 Wiley-Liss, Inc. [source] Cerebellar cortical abiotrophy in Lagotto Romagnolo dogsJOURNAL OF SMALL ANIMAL PRACTICE, Issue 8 2007T. S. Jokinen This case report documents two pathological variations of potentially inherited, cerebellar cortical abiotrophy in two unrelated Lagotto Romagnolo breed dogs. The first dog had an atypical lesion in the cerebellar cortex with depletion of cerebellar granular cell layer and sparing of the Purkinje cell layer. The second case had degenerative changes in both Purkinje and granular cell layers. The clinical picture was similar in both cases presented, although the severity of the signs of cerebellar dysfunction varied. [source] Combining etanercept with traditional agents in the treatment of psoriasis: a review of the clinical evidenceJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2010PA Foley Abstract Psoriasis is a chronic, systemic inflammatory disorder manifesting primarily in skin and potentially in joints, frequently necessitating treatment with conventional systemic therapies, phototherapy or biological agents. Patients with moderate to severe disease suffer a diminished quality of life, experience significant comorbidities and have a higher mortality. Although traditional treatments are effective in the short-term, their use is often limited by concerns over long-term toxicity, including end-organ damage and risk of malignancy. Combination therapy is a commonly used approach and is often more effective than any single agent. Lower doses of two treatments in combination can also minimize potential side effects from a single agent at higher doses. Etanercept is a recombinant human tumour necrosis factor (TNF), receptor (p75) protein fused with the Fc portion of IgG1 that binds to TNF,. This article reviews the evidence on the efficacy and safety of etanercept in combination with methotrexate, acitretin, narrowband UVB and cyclosporin. The largest body of evidence assesses the combination with methotrexate, although evidence is available for the other combinations. Data suggest that although highly effective as monotherapy, etanercept in combination with a conventional systemic agent can enhance efficacy and allow drug sparing. Potentially, the combination may also result in faster treatment responses and permit safe transitioning from one systemic agent to another. Evidence to date suggests that these benefits can be achieved without significant additional toxicity, although long-term data on the efficacy and safety of the combination in psoriatic populations is limited and further evaluation is warranted. [source] Systematic review: steroid withdrawal in anti-TNF-treated patients with inflammatory bowel diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010E. Bultman Aliment Pharmacol Ther 2010; 32: 313,323 Summary Background, The increasing awareness of increased risk for opportunistic infections when combining several immunosuppressant drugs led to new treatment goals for inflammatory bowel disease including limited use of steroids. Aim, To conduct a systematic review to establish figures for steroid withdrawal in anti-TNF treated inflammatory bowel disease-patients. Methods, Medline was searched using the search-terms Ulcerative Colitis (UC) [Mesh], Crohn Disease (CD) [Mesh], IBD [Mesh], crohn, colitis, IBD and steroid sparing, all combined with infliximab and adalimumab. We selected English-language publications that addressed the effect of anti-TNF on steroid withdrawal. Studies had to assess patients with luminal CD or UC. Numbers of patients who were able to withdraw steroids were calculated. Results, Six studies could be included; five reporting on infliximab and one on adalimumab. Studies were heterogeneously designed. Overall, in the adult population, up to 38% of the patients were able to withdraw corticosteroids during infliximab therapy. In the paediatric population, up to 75% of the patients were able to withdraw corticosteroids during infliximab therapy. Conclusions, Although a consensus on the definition of steroid-sparing is lacking, approximately two-thirds of the inflammatory bowel disease-patients are unable to withdraw corticosteroid treatment during anti-TNF therapy. [source] Preclinical pharmacology of robenacoxib: a novel selective inhibitor of cyclooxygenase-2JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2009J. N. KING This manuscript reports the results of preclinical studies in the rat with robenacoxib, a novel selective cyclooxygenase (COX)-2 inhibitor. Robenacoxib selectively inhibited COX-2 in vitro as evidenced from COX-1:COX-2 IC50 ratios of 27:1 in purified enzyme preparations and >967:1 in isolated cell assays. Binding to COX-1 was rapid and readily reversible (dissociation t1/2 << 1 min), whilst COX-2 binding was slowly reversible (t1/2 = 25 min). In vivo, robenacoxib inhibited PGE2 production (an index of COX-2 inhibition) in lipopolysaccharide (LPS)-stimulated air pouches (ID50 0.3 mg/kg) and for at least 24 h in zymosan-induced inflammatory exudate (at 2 mg/kg). Robenacoxib was COX-1 sparing, as it inhibited serum TxB2 synthesis ex vivo (an index of COX-1 inhibition) only at very high doses (100 mg/kg but not at 2,30 mg/kg). Robenacoxib inhibited carrageenan-induced paw oedema (ID50 0.40,0.48 mg/kg), LPS-induced fever (ID50 1.1 mg/kg) and Randall,Selitto pain (10 mg/kg). Robenacoxib was highly bound to plasma protein (99.9% at 50 ng/mL in vitro). After intravenous dosing, clearance was 2.4 mL/min/kg and volume of distribution at steady-state was 306 mL/kg. Robenacoxib was preferentially distributed into inflammatory exudate; the AUC for exudate was 2.9 times higher than for blood and the MRT in exudate (15.9 h) was three times longer than in blood (5.3 h). Robenacoxib produced significantly less gastric ulceration and intestinal permeability as compared with the reference nonsteroidal anti-inflammatory drug (NSAID), diclofenac, and did not inhibit PGE2 or 6-keto PGF1, concentrations in the stomach and ileum at 30 mg/kg. Robenacoxib also had no relevant effects on kidney function at 30 mg/kg. In summary, results of preclinical studies in rats studies suggest that robenacoxib has an attractive pharmacological profile for potential use in the intended target species, cats and dogs. [source] Adalimumab for Crohn's disease with intolerance or lost response to infliximab: a 3-year single-centre experienceALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2009A. OUSSALAH Summary Background, Adalimumab is effective in inducing clinical remission in patients with Crohn's disease who lost response or became intolerant to infliximab. Aim, To evaluate long-term efficacy and safety of adalimumab as a second line therapy in luminal and fistulizing Crohn's disease. Methods, We report our single-centre experience in 53 patients. We evaluated maintenance of clinical response defined as the absence of adverse events leading to drug withdrawal, no major abdominal surgery and no loss of clinical response in initial responders. Major abdominal surgery, steroid sparing, complete fistula closure and safety were also assessed. Results, The probability of maintaining clinical response was 77.2%, 67.8% and 50.8% at 26, 52 and 130 weeks respectively. The probability of remaining major abdominal surgery-free was 82.3% at 26, 52 and 130 weeks. Complete fistula closure occurred in six of 10 patients, and eight of 10 patients were able to taper steroid therapy. Adverse events occurred in 31 patients (58.5%) leading to adalimumab withdrawal in nine patients (17%). Conclusion, Adalimumab therapy may be effective in the long term in both luminal and fistulizing Crohn's disease in infliximab-failure patients, half of patients maintaining clinical response and potentially avoiding major abdominal surgery in 80% of cases. [source] | ||||||||||||||||||||||||||||||||||||||||