Coil embolization of a periprosthetic mitral valve leak associated with severe hemolytic anemia.
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Anemia, Hemolytic↗
Biomedical subjects
D M Williams
Publications and source records attributed to D M Williams.
Enhancing the catalytic repertoire of nucleic acids. II. Simultaneous incorporation of amino and imidazolyl functionalities by two modified triphosphates during PCR.
The incorporation of potentially catalytic groups into DNA is of interest for the in vitro selection of novel deoxyribozymes. We have devised synthetic routes to a series of three C7 modified 7-deaza-dATP derivatives with pendant aminopropyl, Z-aminopropenyl and aminopropynyl side chains. These modified triphosphates have been tested as substrates for Taq polymerase during PCR. All the modifications are tolerated by this enzyme, with the aminopropynyl side chain giving the best result. Most protein enzymes have more than one type of catalytic group located in their active site. By using C5-imidazolyl-modified dUTPs together with 3-(aminopropynyl)-7-deaza-dATP in place of the natural nucleotides dTTP and dATP, we have demonstrated the simultaneous incorporation of both amino and imidazolyl moieties into a DNA molecule during PCR. The PCR product containing the four natural bases was fully digested by XbaI, while PCR products containing the modified 7-deaza-dATP analogues were not cleaved. Direct evidence for the simultaneous incorporation during PCR of an imidazole-modified dUTP and an amino-modified 7-deaza-dATP has been obtained using mass spectrometry.
Binding Sites↗
Enhancing the catalytic repertoire of nucleic acids: a systematic study of linker length and rigidity.
The incorporation of potentially catalytic groups in DNA is of interest for the in vitro selection of novel deoxyribozymes. A series of 10 C5-modified analogues of 2'-deoxyuridine triphosphate have been synthesised that possess side chains of differing flexibility and bearing a primary amino or imidazole functionality. For each series of nucleotide analogues differing degrees of flexibility of the C5 side chain was achieved through the use of alkynyl, alkenyl and alkyl moieties. The imidazole function was conjugated to these C5-amino-modified nucleotides using either imidazole 4-acetic acid or imidazole 4-acrylic acid (urocanic acid). The substrate properties of the nucleotides (fully replacing dTTP) with TAQ polymerase during PCR have been investigated in order to evaluate their potential applications for in vitro selection experiments. 5-(3-Aminopropynyl)dUTP and 5-(E-3-aminopropenyl)dUTP and their imidazole 4-acetic acid- and urocanic acid-modified conjugates were found to be substrates. In contrast, C5-amino-modified dUTPs with alkane or Z-alkene linkers and their corresponding conjugates were not substrates. The incorporation of these analogues during PCR has been confirmed by inhibition of restriction enzyme digestion using XBAI and by mass spectrometry of the PCR products.
Catalysis↗
Unusual cause of extradural haemorrhage.
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Child↗
A polymeric system for the intra-oral delivery of an anti-fungal agent.
Oral candidal infections are often persistent and intractable and thus the aim of this study was to develop a polymeric sustained release device to improve the topical treatment of these infections. A self curing system based on poly(ethyl methacrylate) and tetrahydrofurfuryl methacrylate (PEM/THFM) was used with chlorhexidine diacetate (CX) added at levels between 0 and 12% w/w. Water uptake by the device was assessed gravimetrically and CX release measured by UV spectrometry. Anti candidal activity was established by culturing azole sensitive and resistant strains of Candida albicans in the presence of the polymeric delivery device with and without CX. Candidal growth was measured by turbidimetry or surviving colony-forming unit (CFU) formation. There was an initial high release of CX over 24 h followed by a slow diffusion up to 7 days. CX inhibited candidal growth and survival markedly in vitro, with the test samples showing less than 0.5 x 10(-7) CFU/ml compared to controls (3-4 x 10(-7) CFU/ml). These results indicate the potential of a chlorhexidine containing PEM/THFM polymeric system in the treatment of persistent candidal infections.
Administration, Oral↗
Kinase chips hit the proteomics era.
Protein kinase chips, in which kinases are tested for their ability to phosphorylate immobilized substrates, have been developed and used to evaluate the protein kinases encoded by the yeast genome. This new technology promises to be a valuable addition to the biochemists' and cell biologists' arsenal for evaluating the substrate selectivity and function of protein kinases in cell signaling.
Binding Sites↗
Bacterial endocarditis in a child with haemophilia B: risks of central venous catheters.
The use of central venous catheters may be complicated by thrombosis and infection. We report a case of a needle-phobic 5-year-old boy with factor IX deficiency, in whom a portacath was inserted owing to poor compliance with prophylactic treatment. Within a week, he developed a Staphylococcus aureus line infection that was treated with a 2-week course of intravenous antibiotics. One month later he presented with nonspecific symptoms and blood cultures again grew S. aureus. An echocardiogram revealed a large vegetation adherent to the tricuspid valve, confirming the diagnosis of bacterial endocarditis. His clinical course was further complicated by the development of pulmonary emboli. Medical treatment with intravenous antibiotics led to a successful resolution of the endocarditis and pulmonary emboli with a favourable long-term outcome.
Catheterization, Central Venous↗
Diagnosis and endovascular treatment of iliocaval compression syndrome.
PURPOSE: The purpose of this study was to evaluate the clinical presentation, diagnosis, and endovascular treatment of iliocaval compression syndrome (ICS). PATIENTS AND METHODS: During a 3-year period, 18 patients (17 women, 1 man; mean age, 42 years) presented with clinical and imaging findings consistent with ICS. All patients were evaluated with venography and Doppler ultrasound (DUS), 13 of 18 with intravascular pressure measurements, 12 of 18 with intravascular ultrasound, 9 of 18 with air plethysmography (APG), and 4 of 18 with magnetic resonance venography. Seventeen patients were treated with endovascular stenting, one was treated with angioplasty alone, and six received adjunct thrombolysis. RESULTS: Despite the presence of stenosis or occlusion in all cases, APG indicated no iliac vein obstruction (outflow fraction > or = 40%) in nine patients. DUS revealed acute (6) or chronic (7) unilateral iliofemoral deep venous thrombosis in 13 of 18 patients, whereas the results of five of 18 DUS studies were normal. Recanalization and stent placement (n = 17) or angioplasty (n = 1) was achieved in all patients. The average pressure gradient was 5.6 mm Hg preprocedure and 0.6 mm Hg postprocedure. The primary patency rate demonstrated with DUS (n = 17) and venography (n = 7) at 6 months was 89%. The primary patency rate at 12 months was 79%. CONCLUSIONS: ICS often presents as sudden unilateral left lower extremity pain and swelling in young to middle-aged female patients after pregnancy, surgery, or a period of inactivity. Venography, intravascular ultrasound, and magnetic resonance venography demonstrate high sensitivity, whereas APG-outflow fraction demonstrates low sensitivity in the diagnosis of ICS. Endovascular stenting and angioplasty provide safe and effective early and intermediate-term treatment of symptomatic ICS.
Adult↗
Family carers and the adult head-injured: a critical review of carers' needs.
PRIMARY OBJECTIVE: To appraise recent literature on the topic of perceived needs of family carers of head-injured adult relatives. MEDLINE (1966-2000), EMBASE PSYCHIATRY (1987-1999), CINAHL (1982-January 2000) and PSYCHLIT (1967-1999) databases were searched. MAIN OUTCOMES AND RESULTS: A total of 13 papers were reviewed, of which six employed standardized research methods. The remainder used researcher developed questionnaires. Needs described by carers as important were predominantly related to information. Most unmet needs were linked to the provision of emotional support. There were significant differences in the perceived needs and their fulfilment between parental and spousal carers. In addition, unfulfilled needs could be predicted by behavioural problems in patients. CONCLUSIONS: The design and variation in methodology of most studies reviewed limits the generalization of reported data. Further research is required to fully identify both common and individual needs of family carers of the head-injured.
Adult↗
Selection of novel ligands from a whole-molecule randomly mutated C5a library.
Novel antagonists of the proinflammatory leukocyte chemoattractant C5a have been produced from a phage display library of whole-molecule random mutants. The cDNA for the inflammatory polypeptide C5adR(74) was used as template in a PCR reaction doped with the mutagenic nucleoside triphosphates dPTP [dP: 6-(2-deoxy-beta-D-ribofuranosyl)-3,4-dihydro-8H-pyrimido-[4,5-c][1,2]oxazin-7-one] and 8-oxodGTP (8-oxodG: 8-oxo-2'-deoxyguanosine) to allow the introduction of mutations in a highly controlled manner throughout the cDNA. The resultant library of mutants was displayed on bacteriophage M13 using a jun/fos linker sequence. Functional polypeptides were isolated by several rounds of selection against the receptor for C5a expressed on the surface of CHO cells. From this selection procedure, a limited number of variants of C5adR(74) were obtained. When expressed as free polypeptide, the binding affinities of the selected C5adR(74) sequences were increased 5-fold relative to wild-type protein. Site-directed mutagenesis of the C-terminus of these variants resulted in the production of antagonists of C5adR(74) activity.
Amino Acid Sequence↗
Head injury and family carers: a critical appraisal of case management programmes in the community.
The objective of this review was to identify the available support systems for family carers of head-injured people within the community. The following databases were searched: MEDLINE, EMBASE PSYCHIATRY, CINAHL and PSYCHLIT (years 1987-1999). Only seven papers were identified. Programmes varied from behavioural to cognitive interventions to help carers adjust to particular problem behaviours in their injured relatives. All programmes were professionally led. Most of the data presented was on primary caregivers related to the head-injured person. Only one study used standard assessment tools. The remainder used a variety of methods including self-report measures and interviews. All interventions were reported as beneficial to carers. Overall these studies were found to be limited by biased sampling, nonstandardized outcome measures using subjective methodologies and a lack of control samples. Most studies did not reveal pertinent information regarding the degree and type of head injury or rehabilitation history. There is an outstanding requirement for large randomized controlled studies using standardized methodologies to identify efficacious carer programmes.
Adaptation, Psychological↗
Multiphase-multistep gadolinium-enhanced MR angiography of the abdominal aorta and runoff vessels.
RATIONALE AND OBJECTIVES: To optimize three-dimensional gadolinium magnetic resonance angiography (3D-Gd-MRA) of the aorta and runoff vessels by addressing fundamentally different requirements for temporal and spatial resolution in a single semiautomated examination. METHODS: The technique was designed to obtain pure arterial-phase 3D-Gd-MR angiograms with adequate spatial resolution for each station while avoiding incomplete enhancement due to delayed filling vessels as well as venous overlay. During gadolinium-chelate infusion, a breath-held multiphase 3D-Gd-MRA scan was initiated in the aorta by automatic triggering, followed by automatic table movement. The acquisition was tailored to the vessels of interest by tilting of the 3D volumes. A spatial resolution of 1.7 x 1.2 x 0.8 mm in the calves was achieved by use of elliptical-centric k-space reordering. Signal-to-noise ratio was maximized with a 12-element peripheral vascular coil. Twelve patients with peripheral vascular disease were studied. RESULTS: In cases of aortic occlusive disease (n = 2), dissections (n = 3), or aneurysms (n = 4), substantially delayed fill-in of reconstituted arteries, false lumens, or aneurysmal segments occurred, which was detected only on the later 3D-Gd-MRA phase. High-resolution arterial-phase scans in the calves were obtained, with only one case of substantial venous overlay. Correlation to digital subtraction angiography revealed excellent agreement of pathological findings. CONCLUSIONS: Multiphase-multistep 3D-Gd-MRA reduces the limitations of standard 3D-Gd-MRA techniques with respect to anatomic coverage, spatial resolution, and nonuniform arterial vessel enhancement.
Adult↗
Ulcerlike lesions of the aorta: imaging features and natural history.
PURPOSE: To document the natural history of ulcerlike aortic lesions and determine whether any computed tomographic (CT) features predict outcome. MATERIALS AND METHODS: CT scans from 1994 to 1998 that depicted an ulcerlike aortic lesion were retrospectively evaluated. Features evaluated included lesion and aortic size and intramural hematoma. Initial CT findings were correlated with clinical data and subsequent CT findings. RESULTS: There were 56 lesions in 38 patients. Follow-up (mean, 18.4 months) CT scans were available for 33 lesions. Stability of the lesion and adjacent aorta was noted in 21 lesions. Two lesions were unchanged, although associated intramural hematoma regressed over 1-2 months. Ten lesions showed mild to moderate increase in aortic diameter (mean follow-up, 19.8 months) either with (seven lesions) or without (one lesion) increase in size of the lesion or with incorporation of the lesion into the aortic wall contour (two lesions). Of all 56 lesions, 37 were clinically stable, two were associated with recurrent chest and/or back pain, eight underwent surgical resection or stent placement, and two were in patients who died. Seven lesions were in patients lost to follow-up. No initial CT feature was predictive of CT outcome, although lack of pleural effusion correlated with clinical stability. CONCLUSION: Most ulcerlike aortic lesions are asymptomatic and do not enlarge. About one-third of lesions progress, generally resulting in mild interval aortic enlargement.
Aged↗
Clinical considerations in the use of inhaled corticosteroids for asthma.
Inhaled corticosteroids are the most potent and effective therapy for treating asthma. They exert their pharmacologic action through activation of the glucocorticoid receptor, which helps regulate gene transcription. Corticosteroids also directly inhibit several inflammatory mediators involved in the pathophysiology of asthma. In randomized, controlled clinical trials, inhaled corticosteroids, as monotherapy, are superior to other therapies in improving lung function and clinical outcomes in patients with asthma. However, the use of inhaled corticosteroids is limited by concerns of dose-related adverse effects, including growth suppression and decreased bone density. Combination regimens with these agents and other long-term therapies are beneficial in maintaining asthma control while minimizing dose-related toxicities. Several inhaled corticosteroid products are available in the United States. They differ in potency; however, clinical efficacy is similar when equipotent doses are administered. A variety of factors influence product selection and patient response, including the therapeutic ratio, pharmacokinetic properties, and the inhalation delivery device. In addition, adherence to therapy and the patient's skill in administering the inhaled drug contribute to the therapeutic outcome.
Administration, Inhalation↗
Aortic dissection: CT features that distinguish true lumen from false lumen.
OBJECTIVE: The purpose of this study was to determine which CT findings are reliable indicators of the true or false lumen in an aortic dissection. CONCLUSION: The beak sign and a larger cross-sectional area were the most useful indicators of the false lumen for both acute and chronic dissections. Features generally indicative of the true lumen included outer wall calcification and eccentric flap calcification. In cases showing one lumen wrapping around the other lumen in the aortic arch, the inner lumen was invariably the true lumen.
Adult↗
Permeability barrier properties of oral keratinocyte cultures: a model of intact human oral mucosa.
OBJECTIVES: The aim of this study was to establish whether an in vitro model of human oral mucosa had similar permeability characteristics to normal oral mucosa. Such a model would have considerable value as an alternative to the use of mucosal biopsies in studies of transmucosal drug delivery. MATERIALS AND METHODS: Keratinocytes obtained from buccal mucosa, hard palate and abdominal skin were seeded onto inert collagen membranes (Cellagen Discs) or dead de-epidermised dermis (DDED) and grown either as submerged or air-liquid interface cultures. Subsequently the ultrastructural characteristics, permeability to water and barrier lipid content of the epithelial cultures were assessed and compared with samples of intact mucosa and skin. RESULTS: All the cultures stratified into multilayered epithelia and displayed features of differentiation including tonofilaments, desmosomes and membrane coating granules. The permeability characteristics and barrier lipid content of the oral mucosal cultures resembled those of intact mucosa. By contrast, epidermal keratinocytes failed to produce a permeability barrier comparable with that of skin and had low levels of barrier associated lipids. CONCLUSIONS: Cultures of human oral mucosal keratinocytes obtained from healthy adults develop similar permeability properties and barrier lipid composition to their site of origin. This model system may be useful for the evaluation of local and systemic oral mucosal drug delivery.
Adult↗
The impact of the maquiladoras on health and health policy along the U.S.-Mexico border.
Over the last three and one-half decades, the development of twin industrial plants, maquilas, along the U.S.-Mexico border has resulted in industrialization of the northern tier of Mexican states and rapid population growth on both sides of the border. Maquilas have been responsible for some environmental contamination and may contribute to changes in family cohesiveness. At the same time they have not supported the needed expansion of public infrastructure. These are major public health consequences that must be considered by both countries. Solutions will require better cooperative efforts than have occurred in the past.
Economic Competition↗
Chemical rescue of a mutant protein-tyrosine kinase.
Protein-tyrosine kinases contain a catalytic loop Arg residue located either two or four positions downstream of a highly conserved Asp residue. In this study, the role of this Arg (Arg-318) in the protein-tyrosine kinase C-terminal Src kinase (Csk) was investigated. The observed k(cat) for phosphorylation of the random copolymer poly(Glu,Tyr) substrate by Csk R318A is approximately 3000-fold smaller compared with that of wild type Csk, whereas the K(m) values for ATP and poly(Glu,Tyr) are only mildly affected. The k(cat) value for poly(Glu,Tyr) phosphorylation by the Csk double mutant A316R,R318A is 100-fold greater than the k(cat) value for the single R318A mutant, suggesting that an Arg positioned at the alternative location fulfills a similar function as in wild type. Csk R318A kinase activity can also be partially recovered by several exogenous small molecules including guanidinium and imidazole. These molecules contain key features whose roles in catalysis can be rationalized from a known x-ray structure of the insulin receptor tyrosine kinase. Imidazole is the best of these activators, enhancing phosphorylation rates by Csk R318A up to 100-fold for poly(Glu,Tyr) and significantly stimulating Csk R318A phosphorylation of the physiologic substrate Src. This chemical rescue of mutant protein kinase activity might find applications in cell signal transduction experiments.
Amino Acid Sequence↗