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101.
Willoughby CE Chan LL Herd S Billingsley G Noordeh N Levin AV Buys Y Trope G Sarfarazi M Héon E 《Investigative ophthalmology & visual science》2004,45(9):3122-3130
PURPOSE: Juvenile open-angle glaucoma (JOAG) differs from primary open-angle glaucoma in that it is usually a more severe phenotype and has an earlier age of onset. Optineurin was recently associated with a variant of POAG that is characterized by intraocular pressure within normal limits: normal-tension glaucoma. The present study tested whether OPTN sequence changes play a role in early-onset glaucoma characterized by elevated intraocular pressure. METHODS: Sixty-six patients with JOAG characterized by high intraocular pressure were screened for mutations. Mutational analysis was performed with a combination of restriction enzyme digestion, single-strand conformation polymorphism, and direct sequencing. The effects of select changes on exon splicing were assessed using bioinformatic modeling approaches and RT-PCR. RESULTS: Ten sequence changes were identified, of which H486R was strongly suggestive of pathogenicity. H486R represents the first reported OPTN mutation associated with JOAG. Also, L41L is proposed to confer an increased susceptibility to the development of JOAG. Most of the other sequence changes observed were not thought to be biologically significant. The frequency of the previously reported M98K allele was not increased in the JOAG population studied but showed the previously reported skewed distribution in the POAG study population. The changes identified were not shown to affect the splicing machinery. CONCLUSIONS: The results of this work support the hypothesis that mutations in OPTN are not specifically associated with low-pressure glaucoma, but can play a role in JOAG. 相似文献
102.
Grundt H Nilsen DW Hetland Ø Mansoor MA 《Clinical nutrition (Edinburgh, Scotland)》2004,23(4):491-500
BACKGROUND: Sustained effects following withdrawal of n-3 PUFAs are unknown. METHODS: Clinical outcome [cardiac death, resuscitation, recurrent myocardial infarction (MI) or unstable angina pectoris] was assessed after prolonged wash-out following randomised treatment with high-dosed n-3 PUFAs or corn oil for 12-24 months in 300 acute MI patients. Atherothrombogenic risk markers, serum glucose and markers of lipid peroxidation and inflammation were evaluated in 89 out of the 100 last included patients. RESULTS: After a total median observation period of 45 (range 0-53) months no intergroup difference in prognosis was observed for any of the cardiac events. Favourable effects on serum triglycerides and HDL-cholesterol by n-3 PUFAs were lost after washout, but triglycerides decreased in the corn oil as compared to the n-3 group, P < 0.001. The decline in total cholesterol after withdrawal was similar in both groups. No intergroup difference in the change in thiobarbituric acid-malondialdehyde, a marker of lipid peroxidation, ultrasensitive C-reactive protein, homocysteine, glucose or blood platelets was noted at sustained follow-up. CONCLUSION: Clinical outcome was similar in both patient groups, and the atherothrombogenic risk improvement by n-3 PUFAs was lost after prolonged wash-out. Withdrawal did not affect homocysteine, glucose or markers of lipid peroxidation or inflammation. 相似文献
103.
BACKGROUND: Parenteral nutrition (PN) is an essential component of neonatal care for those infants who are unable to tolerate adequate enteral feeding. Its use is not without complications such as biochemical derangements, sepsis, thrombosis, extravasation of fluid, and death. Such complications can be reduced by meticulous management of PN in response to biochemical abnormalities, nutrition teams, policies to reduce sepsis, and staff training to be more aware of pericardial and pleural effusions. We ascertained the current practices in PN administration and management of complications in all neonatal units with 6 or more intensive care cots in England, Scotland, and Wales. METHODS: Telephone survey of middle grade doctors (Specialist Registrars) working in all 57 neonatal units was conducted using a standard questionnaire. The questions were focused around practical issues and problems that are commonly encountered with PN practice, including composition, complications, and nutrition support. RESULTS: A response was obtained from 95% of the units contacted and a wide range of practices observed. Thirty-three percent of units delay protein (nitrogen) until > 48 hours after birth. Lipid infusions are stopped in proven or suspected sepsis in just over half of all units. In hyperglycemic preterm infants, 25 units decrease their glucose infusion, 21 commence insulin, and 8 have no policy. Two thirds of middle grade doctors had no idea of the amount of protein or nitrogen to prescribe for these infants, and only one-third involve a pharmacist in the PN prescribing. CONCLUSIONS: There is a diverse practice and knowledge with a concerning lack of education in nutrition among the middle grade doctors in England, Scotland, and Wales. The management of common complications such as sepsis and hyperglycemia are highly variable. Improved staff training and production of unified evidence-based guidelines need urgent consideration. 相似文献
104.
A number of nucleoside analogues, consisting of antiviral compounds and agents designed as adenosine A1 receptor agonists, were examined for nucleoside transporter affinity using an in vitro model of the blood-brain barrier (BBB), the rat brain endothelial cell line, RBE4. Structure-activity relationships (SAR) were also performed to identify the key structural requirements for transporter recognition and the suitability of these systems for carrier-mediated strategies to deliver therapeutics across the BBB. Adenosine receptor agonists did not show transport affinity for concentrative nucleoside carriers, but exhibited affinity for equilibrative systems (Ki=10.8-97.9 microM) within the range of Kms for natural substrates. However, none of the antiviral compounds tested in this study showed affinity for either class of nucleoside transporter. SAR studies suggest that the hydroxyl group located at the 3'-position of the ribose moiety is an essential requirement for transporter recognition. This may explain the inability of nucleoside derived anti-viral compounds to use these systems despite the significant structural homology with naturally occurring nucleosides. Sites have also been identified which accommodate structural additions with retention of carrier affinity, suggesting that compounds which fail to penetrate the BBB could be attached to these sites for carrier-mediated delivery using a prodrug strategy. 相似文献
105.
Lin P Bueso-Ramos C Wilson CS Mansoor A Medeiros LJ 《The American journal of surgical pathology》2003,27(8):1104-1113
Waldenstrom macroglobulinemia (WM) is a clinicopathologic syndrome in which a B-cell neoplasm involving the bone marrow, usually lymphoplasmacytic lymphoma (LPL), is associated with immunoglobulin M paraprotein in the serum. Extramedullary involvement occurs in a subset of patients and is infrequently examined histologically. The files of M.D. Anderson Cancer Center were searched for patients with WM who underwent biopsy of one or more extramedullary sites during the course of disease. Each biopsy specimen was classified using the criteria of the World Health Organization classification. The study group consisted of 44 patients (26 men and 18 women), with a total of 51 specimens obtained from lymph nodes (n = 36), soft tissue (n = 4), spleen (n = 3), skin (n = 2), lung (n = 2), tonsils (n = 1), colon (n = 1), liver (n = 1), and gallbladder (n = 1). Lymphoplasmacytic lymphoma was the most common histologic type, in 40 (78%) samples. This category was morphologically heterogeneous and was further subclassified as lymphoplasmacytic (n = 21), lymphoplasmacytoid (n = 18), and polymorphous (n = 1). Four of these LPL cases morphologically resembled marginal zone B-cell lymphoma. Four additional samples were involved by diffuse large B-cell lymphoma, probably transformed from LPL. Three more samples were involved by LPL with unusual features: two were CD5-positive and one was a composite tumor with classical Hodgkin's disease. Other categories of lymphoma in this group of patients with WM included small lymphocytic lymphoma/chronic lymphocytic leukemia (n = 2), mantle cell lymphoma (n = 1), and follicular lymphoma (n = 1). Waldenstrom macroglobulinemia is most commonly associated with LPL but can rarely occur with other types of B-cell lymphoma. Lymphoplasmacytic lymphoma in patients with WM is morphologically heterogeneous and can be indistinguishable from marginal zone B-cell lymphoma. CD5+ B-cell lymphomas with features otherwise typical of LPL are rare, and we think these tumors are part of the spectrum of LPL. 相似文献
106.
Abstract
The possibility of using quantitative motion analysis for objective assessment of simple surgical dexterity is investigated
using the Imperial College Surgical Assessment Device (ICSAD) with qualitative analysis undertaken by inspection. Bench-top
knot tying and suturing skills were performed and examined for the ability to discriminate between surgeons of varying experience.
These exercises were found to discriminate significantly between junior and senior surgeons in terms of both time taken and
the number of movements required. The relation between time and motion was found to be variable depending on what skill was
being undertaken: simple suturing, suturing at depth, or knot tying (1.71 vs. 1.86 vs. 2.36; p = 0.002 for 1 vs. 2; p < 0.001 for others). When the number of movements in a minute (standardized movements per minute) were considered, both groups
were found to work at a similar rate, depending on the task, implying that the more experienced surgeon is more economical,
performing the same exercise with fewer moves rather than with higher speed. Motion analysis exhibits face and construct validity
and is a reliable assessment of simple surgical dexterity. Its use for objective assessment of dexterity and competence should
be encouraged. 相似文献
107.
Development of a HPLC method for the determination of cyclosporin-A in rat blood and plasma using naproxen as an internal standard 总被引:1,自引:0,他引:1
Zaghloul AA Hussain A Khan MA Ahsan F 《Journal of pharmaceutical and biomedical analysis》2003,31(6):1101-1107
An isocratic reversed phase high-performance liquid chromatographic (HPLC) method with ultraviolet detection at 205 nm has been developed for the determination of cyclosporin-A (CyA) in rat blood and plasma. Naproxen was successfully used as an internal standard. Blood or plasma samples were pretreated by liquid–liquid extraction with diethyl ether. The ether extract was evaporated and the residue was reconstituted in acetonitrile–0.04 M monobasic potassium phosphate buffer (pH 2.5) solvent mixture. After washing with n-hexane, 30 μl of the reconstituted solution was injected into HPLC system. Good chromatographic separation between CyA and internal standard peaks was achieved by using a stainless steel analytical column packed with 4 μm Nova-Pak Phenyl material. The system was operated at 75 °C using a mobile phase consisting of acetonitrile–0.04 M monobasic potassium phosphate (pH 2.5) (65:35 v/v) at a flow rate of 1 ml/min. The calibration curve for CyA in rat blood was linear over the tested concentration range of 0.0033–0.0166 M with a correlation coefficient of 0.989. For rat plasma, the range of the concentrations tested were between 0.002 and 0.0166 M and showed linearity with a correlation coefficient of 0.953. The intra- and inter-run precision and accuracy results were 1.24–21.87 and 3.1–12.23%, respectively. The low volume of blood or plasma needed (200 μl), simplicity of the extraction process, short run time (5 min) and low injection volume (30 μl) make this method suitable for quick and routine analysis. 相似文献
108.
PURPOSE: To prepare and evaluate a suppository dosage form of salbutamol sulfate. The prepared formulae with and without different concentrations of gels were tested for hardness, melting time, content uniformity, and drug release. The stability of some of the selected formulae was assessed. METHODS: Salbutamol sulfate was formulated as a rectal suppository with emulsifying fatty bases (suppocire and witepsol) and water-soluble bases (PEG) adopting the molding from a melt technique. Physical characteristics and dissolution profiles of the prepared formulations were determined as the responses. The effects of adding gels, methyl cellulose (MC), and Eudispert (Eud) and their concentrations (1, 3, and 6%) on these responses were also investigated. Formulations showing high rank order were scaled up for shelf-life stability study for one year. RESULTS: The results showed that all the investigated formulae have acceptable physical characteristics with respect to hardness, melting time (except F7), and uniformity of drug content. The amount of drug dissolved in 100 min of dissolution time was inversely affected by the melting point of the fatty base. The release from PEG bases was found to be molecular weight dependent. Addition of 1% MC or Eud gel increased the release from all the investigated formulae. Increasing gel concentration to 3% then to 6% showed different effects on the release. The degradation of salbutamol sulfate in the investigated formulae was found to be a first-order reaction. CONCLUSIONS: Rectal suppository of salbutamol sulfate could be prepared as an alternative to the oral dosage form to circumvent the first-pass metabolism. 相似文献
109.
PURPOSE: Infantile myofibromatosis is an uncommon tumor that occurs rarely in the periorbit and orbit. This article reports two cases of infantile myofibromatosis of the orbital adnexa and describes the associated clinical, histopathologic, and immunohistochemical findings. DESIGN: Two retrospective, interventional case reports with clinicopathologic correlation. INTERVENTION: Treatment consisted of excision of the tumors. MAIN OUTCOME MEASURES: Histologic and immunohistochemical evaluation and clinical evaluation for tumor recurrence. RESULTS: The first patient was a newborn male with a large tumor extending from his eyelid that was excised at day 2 of life. Histologic and immunohistochemistry analyses were used to make a diagnosis of infantile myofibromatosis. He remains disease free at age 7 years. The second case was a 6-year-old boy with a 1-month history of proptosis resulting from an orbital mass. Incisional biopsy revealed a tumor consistent with infantile myofibromatosis. He remains tumor free 12 months after complete gross surgical resection. CONCLUSIONS: Infantile myofibromatosis is an uncommon tumor that is rare in the orbit. Differential diagnosis can be difficult based solely on histologic analysis. Immunohistochemistry evaluation demonstrating cytoplasmic actin filaments within neoplastic spindle cells confirms the diagnosis. As soon as the diagnosis is made, chest and abdominal imaging is of value to define the prognosis and to direct further treatment. After the diagnosis of nonvisceral infantile myofibromatosis, complete gross resection, if possible, is the treatment of choice. 相似文献
110.
Several observations noted by early investigators supported the supposition that in most cases, congenital glaucoma is determined by genetic factors. The genetic heterogeneity of PCG was confirmed by genetic linkage studies conducted in the 1990s when the authors determined that CYP1B1 is the congenital glaucoma gene at the GLC3A locus. The coding sequence of CYP1B1 has been subjected to extensive screening in familial and sporadic cases of glaucoma from numerous countries and from a large number of ethnic groups. These studies have provided evidence for extensive allelic heterogeneity at the GLC3A locus. This article also discusses the molecular evidence for reduced penetrance in congenital glaucoma and the phenotypic heterogeneity of CYP1B1 mutations, mouse models of CYP1B1, and the biochemistry of CYP1B1. 相似文献