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Alagille syndrome (ALGS) is an autosomal dominant, multisystem disorder which was first described in 1969 by Daniel Alagille as a constellation of clinical features in five different organ systems [1]. The diagnosis was based on the presence of intrahepatic bile duct paucity on liver biopsy in association with at least three of the major clinical features: chronic cholestasis, cardiac disease (most often peripheral pulmonary stenosis), skeletal abnormalities (typically butterfly vertebrae), ocular abnormalities (primarily posterior embryotoxon), and characteristic facial features. Advances in molecular diagnostics have enabled an appreciation of the broader disease phenotype with recognition of renal and vascular involvement [2, 3]. There is significant variability in the extent to which each of these systems is affected in an individual, if at all [4, 5]. ALGS was originally estimated to have a frequency of one in 70,000 live births, though this was based on the presence of neonatal cholestasis. However, this is clearly an underestimate as molecular testing has demonstrated that many individuals with a disease-causing mutation do not have neonatal liver disease and the true frequency is likely closer to one in 30,000 [5].
We present photo-ionization and morpho-kinematic analyses of the ejecta of novae. The sample consists of ten novae belonging to the Fe II, He/N and hybrid classes. The Fe II class of novae in the sample have bipolar cone-like structures, with or without equatorial rings with inclination angle in the range of 40°–60°. The He/N novae have bullet-nose curve along with bipolar cone-like structures and equatorial rings with an inclination angle of ~80°. The hybrid nova in the sample is a bipolar frustum of prolate spheroid along with bipolar cone-like structures and equatorial rings with an inclination angle of 63°.
Background: Post-craniotomy pain can be severe and undermanaged. While opioids are the mainstay treatment, they have the potential to interfere with neurological monitoring. The objectives of this review are: 1) to identify measures to provide opioid-free analgesia 2) to compare the effectiveness of non-opioid to opioid analgesia in post-craniotomy pain. Methods: A comprehensive search of EMBASE, MEDLINE, and the Cochrane Central Registry of Controlled Trials (CENTRAL) databases was conducted for RCTs evaluating the effect of opioid vs non-opioid pain control strategies in patients undergoing supratentorial craniotomy. Results: The literature search yielded 462 citations, 5 RCTs that met the inclusion criteria for a total of 250 patients. Scalp infiltration/block was found to provide equivalent analgesia to morphine1 and fentanyl.2 Morphine was associated with slightly higher postoperative nausea and vomiting. Paracetamol was less likely to induce nausea and vomiting,3,4 but provided inadequate pain relief compared to nalbuphine,3 tramadol,3 morphine4 and sufentanil.4 Dexmedetomidine5 provided similar analgesia to remifentanil but did delay the time to first dose of rescue analgesia with similar side effects. Conclusions: Based on the limited number of RCTs comparing opioid to non-opioid techniques, no definite recommendations can be made with regards to the optimal management of post-craniotomy pain. Considerations should be made for use of multimodal analgesia-including adjuvant analgesics.
The internal spinal cord blood flow was measured in dogs at the site of local cooling using hydrogen polarography. Blood flow decreased to 50% of the normothermic values during cooling of the cord to a central temperature of 16 degrees Celsius. Upon cessation of cooling internal blood flow rapidly returned to normal values. Implications of this finding for the treatment of spinal cord injury are discussed.
By
Binita M. Kamath, Department of Paediatrics, University of Toronto; Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada,
Nancy B. Spinner, Division of Genomic Diagnostics, and Evelyn Willing Bromley Chair of Pediatric Pathology, Department of Pathology Perelman School of Medicine at the University of Pennsylvania, Children’s Hospital of Pennsylvania, Pittsburgh, PA, USA,
David A. Piccoli, Division of Gastroenterology, Hepatology and Nutrition, Fred and Suzanne Biesecker Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Children’s Hospital of Pennsylvania, Philadelphia, PA, USA
Alagille syndrome (ALGS) is an autosomal dominant, multisystem disorder which was first described in 1969 by Daniel Alagille as a constellation of clinical features in five different organ systems [1]. The diagnosis was based on the presence of intrahepatic bile duct paucity on liver biopsy in association with at least three of the major clinical features: chronic cholestasis, cardiac disease (most often peripheral pulmonary stenosis), skeletal abnormalities (typically butterfly vertebrae), ocular abnormalities (primarily posterior embryotoxon), and characteristic facial features. Advances in molecular diagnostics have enabled an appreciation of the broader disease phenotype with recognition of renal and vascular involvement [2,3]. There is significant variability in the extent to which each of these systems is affected in an individual, if at all [4,5]. It was originally estimated that ALGS had a frequency of 1 in 70000 live births, although this was based on the presence of neonatal cholestasis. However, this is clearly an underestimate as molecular testing has demonstrated that many individuals with a disease-causing mutation do not have neonatal liver disease and the true frequency is likely closer to 1 in 30000 [5].
Alagille syndrome is caused by mutations in JAGGED1 (JAG1), encoding a ligand Jagged1 in the Notch signaling pathway [6,7]. Mutations in JAG1 are identified in 94% of clinically defined probands [8]. Recently, mutations in NOTCH2 have been identified in a few patients with ALGS who do not have JAG1 mutations [9]. This exciting development has enhanced our understanding of the heterogeneity of this disorder, although much remains to be understood about the tremendous variability seen in affected individuals and the likely genetic modifiers involved.
The immunological responses in hamsters during treatment with mebendazole against Ancylostoma ceylanicum are studied. Indirect haemagglutination (IHA) counterimmunoelectrophoresis (CIEP), passive cutaneous anaphylaxis (PCA), foot pad swelling for immediate (ITH) and delayed (DTH) types of hypersensitivities were employed for measuring the responses. Serum antibody which was 1:32 before treatment increased to the maximim of 1:512 (control 1:128) on the 10th day and it declined subsequently. The CIEP test was positive for 10 days and then became negative. The PCA test was positive throughout the observation period both in the treated and untreated groups. Foot pad swelling for ITH and DTH responses were comparatively more prominent than in the untreated control up to the 20th day and then both decreased simultaneously. The immunological responses remained prominent for a longer period and decreased more slowly in the untreated control group.
Melioidosis is an infectious disease caused by a saprophytic bacterium, Burkholderia pseudomallei. It is endemic to Southeast Asia and Northern Australia. It may manifest as a pulmonary lesion, osteomyelitis, abscesses in soft tissue and various organs, or as septicaemia.
Case report:
We report a case of a 40-year-old, diabetic man who presented with a neck lump resulting from super-infection of a tuberculosis cavity with B pseudomallei. The patient was successfully managed by drainage along with meticulous excision of the capsule and prolonged antibiotic and anti-tubercular treatment.
Discussion:
Melioidosis may be confused diagnostically with tuberculosis, as both diseases are endemic in the same regions. Our patient was unfortunate to suffer from both endemic diseases simultaneously, perhaps representing the first such case in the world literature.
Conclusion:
Increased awareness of melioidosis is important as, although the organism is easy to culture, it may be dismissed as a contaminant.
By
Binita M. Kamath, M.B. B.Chir., Assistant Professor of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; Attending Physician, Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,
Nancy B. Spinner, Ph.D., Professor of Human Genetics in Pediatrics, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; Director, Cytogenetics Laboratory, Department of Pathology and Clinical Laboratories, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,
David A. Piccoli, M.D., Biesecker Professor of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; Chief, Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
Alagille syndrome (AGS) is a highly variable, multisystem, autosomal dominant disorder that primarily affects the liver, heart, eyes, face, and skeleton [1–3]. There is significant variability in the extent to which each of these systems is affected in an individual, if at all [4, 5]. AGS has traditionally been diagnosed based on the presence of intrahepatic bile duct paucity on liver biopsy in association with at least three of the major clinical features: chronic cholestasis, cardiac disease (most often peripheral pulmonary stenosis), skeletal abnormalities (typically butterfly vertebrae), ocular abnormalities (primarily posterior embryotoxon), and characteristic facial features [6]. It has an estimated frequency of 1 in 70,000 live births based on the presence of neonatal cholestasis. However, this is an underestimate as molecular testing has demonstrated that many individuals with a disease-causing mutation do not have neonatal liver disease.
Alagille syndrome is caused by mutations in Jagged1 (JAG1), a ligand in the Notch signaling pathway [7, 8]. JAG1 mutations are identified in more than 90% of clinically diagnosed probands [9]. Recently, mutations in Notch2 have been identified in a few patients with AGS who do not have JAG1 mutations [10]. This exciting development has enhanced our understanding of the heterogeneity of this disorder, though much remains to be understood about the tremendous variability seen in affected individuals and the likely genetic modifiers involved.
BILE DUCT PAUCITY
Bile duct paucity is present in a diverse group of metabolic, infectious, and inflammatory hepatic disorders in infancy.
Homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency may present with variable neurological manifestations. Radiological features include white matter changes (leukoencephalopathy). Clinical, biochemical, and radiological response to treatment may again be variable. Here we present a 12-year follow-up of two siblings on the same treatment regimen, with contrasting long-term findings. The first patient, a female presenting at 15 years, showed a good clinical response, substantial intellectual gain, and complete reversal of leukoencephalopathy. Her brother presented at 13 years 9 months and showed limited clinical and cognitive improvement with persistence of the leukoencephalopathy. Both siblings showed a partial biochemical response to treatment.
The oxidation resistance of ultrathin (5–15Å) thermally grown silicon nitride (Si3N4), in conditions relevant to the deposition/annealing of Tantalum Pentoxide (Ta2O5) in a Rapid Thermal Processing (RTP) environment, has been non destructively examined using X-Ray Photoelectron Spectroscopy (XPS). This has been carried out with a view to establishing a process window for the deposition of Ta2O5 on a Rapid Thermally Nitrided (RTN) Si(100) surface, with negligible oxidation of the Si(100) substrate. A physical model of the oxidation process of these films is also proposed.
We have studied the thermal growth chemistry and bonding structure of three promising ultrathin (5–20Å), nitrogen rich passivation layers on Si(100), namely-Si3N4, NO/Si(100) grown oxynitride and NO annealed SiO2. These films are intended to serve as substrates with excellent diffusion barrier/interface properties during deposition of high- K dielectrics such as Ta2O5, with tSiO2 equivalent <30Å for ULSI applications. In this paper we show that it is possible to form films with a tailored composition and nitrogen profile using techniques that can easily be integrated with existing silicon processing technology. Alternating growth and surface analysis by X-Ray Photoelectron Spectroscopy (XPS) is used to non destructively characterize the growth.
Historical records suggest dyskinesia was observed in severely ill institutionalised patients with schizophrenia in the pre-neuroleptic era More recent work has not found dyskinesia in never-medicated younger and middle aged patients. The present study complements this recent work and avoids the confounders of severity of illness and institutionalism by examining elderly patients in a wide variety of community settings.
Method
Movement disorders were examined in 308 elderly individuals in Madras, India, using the Abnormal Involuntary Movements Scale, the Simpson and Angus Parkinsonism Scale and the Barnes Akathisia Scale. Patients' mental state was assessed by the Positive and Negative Syndrome Scale.
Results
Dyskinesia was found in 15% of normal subjects (n=101, mean age 63 years), 15% of first degree blood relatives of younger schizophrenic patients (n=103, mean age 63 years), 38% of never medicated patients (n=21, mean age 65 years) and 41 % of medicated patients (n=83, mean age 57 years). The respective prevalences for Parkinsonism were 6%, 11 %, 24% and 36%; and for akathisia 9%, 5%, 21 % and 23%. Dyskinesia was associated with negative schizophrenic symptoms.
Conclusions
Dyskinesia in elderly schizophrenic patients is an integral part of the illness and not associated with antipsychotic medication.
Photoconductivity in photocrosslinkable second-order nonlinear optical (NLO) polymeric materials and photovoltage generation in a poled guest-host polymer are reported. These NLO polymers have been functionalized with crosslinkable cinnamoyl groups and show relatively stable second-order optical nonlinearities at room temperature when poled and crosslinked. Without introducing any photosensitizer or charge carrier transport agents, photoconductivity was obtained in these polymer systems. Optical excitations of the NLO chromophores lead to photocarrier generation and it is conjectured that these NLO chromophores also play a role in the carrier transport. In addition to photoconductivity, photovoltage generation was observed in the dye doped polymer upon poling. This poled polymer also exhibits a polarization dependent photovoltage when illuminated by light in the absorption region of the NLO chromophore.
Residual stresses present in thin films evaporated on ceramic substrates, can lead to loss of adhesion of the metal features to the ceramic, or, between metal films in multi-level stacks. If the adhesion is good, ceramic cracking may occur around the metal features. Long term one must avoid stress corrosion cracking in the ceramic. These residual stresses are generated by a variety of causes. In general, defect incorporation during the deposition process and thermal expansion mismatch between thin film and substrate play major roles.
In this paper, we describe a method for determining the residual stresses that may be detrimental, or more accurately, the residual stress induced load that may cause reliability problems. This method involves evaporating metal pads or various thicknesses onto the ceramic to the point of failure, and measuring the residual stress loading on the substrate. A direct measure of this loading is the stress intensity factor which takes into account both the residual stress and pad or film thickness. Thus, a critical “load” or stress intensity at which substrate cracking or thin film delamination occurs can be estimated. This approach can be used to select the optimum metal-thickness combination for various substrates.
The polycation conducting polymers, oxidized polypyrrole and polyalkylthiophene, possess the ability to form complexes with polyanionic DNA molecules through largely electrostatic interactions. This study demonstrated the solution uptake and binding of 32p radiolabeled DNA by conducting polymer thick films (50–100μm). Polypyrrole (PPy) was synthesized by electrochemical methods and poly(3-hexylthiophene) (PHT) and poly(3-undecylthiophene) (PUT) were synthesized by chemical methods. The DNA binding rates on PPy films were affected by DNA concentration and the oxidation state (measured as conductivity). The DNA kinetics support a diffusion limited model for binding. We measured DNA binding levels onto all three polymer films; PUT, PHT, and PPy. The binding levels increased in the same order as the conductivities of the polymer films. DNA binding onto oxidized PPy film was diminished upon electrochemical reduction. These observations showed, therefore, the binding may be linked with the positive charge sites responsible for conduction in the polymer films.
Type I collagen in a porous sponge form attracts fibroblasts in culture and accelerates repair of animal wounds. This study examines the effect of type I collagen sponge and flakes on healing of chronic skin ulcers. Patients included in this study had skin ulcers.
Patients included in this study had skin ulcers characterized by loss of dermis and epidermis without exposure of muscle, tendon or bone. Patients showing evidence of systemic infection or patients with ulcers that decreased in area during an initial three week observation period were excluded.
Three out of seven patients treated with a collagen sponge and twelve out of fourteen patients treated with collagen flakes showed a 40% decrease in wound area after six weeks of treatment. In comparison, eighteen control patients showed no change in wound area over the same time interval. These results suggest that collagen flakes are effective in initiating healing of chronic skin ulcers.
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