Biomedical subjects

D M Williams

Publications and source records attributed to D M Williams.

At least 37 records · Page 2Linked to original sources

PubMed2001

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↗

PubMed2001

The cribriform features of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma: cytokeratin and integrin expression.

Cribriform areas are common features of both adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma. Both are malignant salivary gland tumors that share similar histologic patterns, but with marked distinct clinical behavior. This study was undertaken to improve the accuracy of the histopathology diagnostic process, using an immunohistochemical panel to differentiate adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma, with special concern to the common cribriform areas shared by these tumors. Three-microm serial sections of these tumors were submitted to the streptavidin-biotin peroxidase immunotechnique against the monoclonal antibodies anticytokeratins 7, 8, 14 and 19, and anti-integrins beta1, beta3, and beta4. In the neoplastic lobules of adenoid cystic carcinoma cribriform type, the spaces were mainly surrounded by cells negative for the cytokeratins and integrins studied. In the solid type of adenoid cystic carcinoma, the microcystic areas were caused by spaces lined by neoplastic luminal cells positive for cytokeratins and presenting integrins concentrated in the apical pole of these cells. The cribriform areas of polymorphous low-grade adenocarcinoma were composed of cords of luminal cells, positive for cytokeratins and showing integrins disposed in a bipolar pattern. We concluded that cribriform areas of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma are histologically similar, although not identical. Indeed, their cellular composition is distinct and can be distinguishable from one another by the proteins of the cytoskeleton, by the integrins, or both.

Adenocarcinoma↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2000

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↗

PubMed2000

Analysis of receptor/ligand interactions using whole-molecule randomly-mutated ligand libraries.

We report a novel method for the analysis of protein ligands using a whole molecule mutagenesis/phage display system. The cDNA for the inflammatory polypeptide C5a was used as template in a PCR reaction doped with mutagenic nucleoside triphosphates (dP and 8-oxo-2'deoxyguanosine (8-oxodG)) to allow introduction of mutations in a highly controlled manner throughout the cDNA. The resultant library of mutants was displayed on the surface of phage and functional polypeptides were selected by several rounds of selection against the cells bearing the receptor for C5a. Following selection only a limited number of residues in C5a were found to be mutated, suggesting that mutations in key residues involved in the maintenance of structure and in receptor binding had been eliminated. The selected C5a sequences had a higher affinity for receptor than wild type phage-C5a conjugates. As this method for analysing the functional characteristics of proteins does not rely on knowledge a priori of structure, it may be useful for affinity maturation or analysis in a wide range of protein ligand/receptor systems.

Amino Acid Sequence↗

PubMed2000

Assessment of the readability and comprehensibility of a CFC-transition brochure.

BACKGROUND: In anticipation of public confusion about the availability of medications during the metered-dose inhaler CFC phaseout period, a multidisciplinary effort has resulted in the development of a brochure designed to educate patients and health care providers about the health consequences of ozone depletion and the transition to CFC-free inhaled products. This brochure is the subject of this assessment. OBJECTIVES: The primary purpose of this study was to estimate the grade of reading difficulty of a brochure designed to educate patients about the change to CFC-free inhalation products. A secondary objective was to assess baseline knowledge of patients concerning CFC transition and their comprehension of this issue after reading the brochure. METHODS: Standard readability formulae were used to assess the grade level of the CFC transition brochure. In addition, baseline knowledge of the CFC transition process and comprehensibility of the brochure were measured via a 2-page questionnaire. RESULTS: The SMOG, Rix, and Flesch-Kincaid tests yielded readability at grade levels of 14, 10, and 10.4, respectively. The survey indicated that even after reading the brochure, many patients had concerns about the transition process. CONCLUSIONS: These results suggest that the readability of the brochure entitled Your Metered-Dose Inhaler Will Be Changing... Here Are the Facts...may not be appropriate for a large segment of the population for whom it is intended. Further, the comprehensibility assessment suggests that many patients are either unaware of or unable to understand the impending changes to their inhaled therapies.

Asthma↗

PubMed2000

BP1, a new homeobox gene, is frequently expressed in acute leukemias.

Aberrant expression of homeobox genes has been described in primary leukemia blasts. We recently cloned a new cDNA, BP1, which is a member of the homeobox gene family. BP1 expression was investigated in bone marrow samples from acute myeloid leukemia (AML), acute T cell lymphocytic leukemia (ALL) and pre-B cell ALL. Expression levels of two apparent isoforms of BP1, DLX7 and DLX4, were measured in the same samples. They are weakly if at all detectable in normal bone marrow, PHA-stimulated T cells or B cells. BP1 RNA was highly expressed in 63% of AML cases, including 81% of the pediatric and 47% of the adult cases, and in 32% of T-ALL cases, but was not found in any of the pre-B ALL cases. Coexpression of BP1, DLX7 and DLX4 occurred in a significant number of leukemias. Our data, including co-expression of BP1 with c-myb and GATA-1, markers of early progenitors, suggest that BP1 expression occurs in primitive cells in AML. Analysis of CD34+ and CD34- normal bone marrow cells revealed BP1 is expressed in CD34- cells and virtually extinguished in CD34+ cells. Ectopic expression of BP1 in the leukemia cell line K562 increased clonogenicity, consistent with a role for BP1 in leukemogenesis. The presence of BP1 RNA in leukemic blasts may therefore be a molecular marker for primitive cells and/or may indicate that BP1 is an important upstream factor in an oncogenic pathway.

Acute Disease↗

PubMed2000

The effect of sodium lauryl sulphate, triclosan and zinc on the permeability of normal oral mucosa.

OBJECTIVE: Sodium lauryl sulphate (SLS), an important component in many oral health products, is well established as a contact irritant in skin. Recent studies have suggested that it may also affect the structural integrity of oral mucosa. SLS is rarely used alone in dentifrices or mouthwashes and the aim of this study was to establish the effect of SLS both alone and in combination with Triclosan (TCN) and zinc (Zn) on the permeability barrier properties of normal human oral mucosa. METHOD: Ventral tongue mucosa was obtained from nine males and seven females within 60 h of death and stored frozen at -70 degrees C until use. The permeability of the tissue to tritiated water was measured after pretreatment for 15 min with SLS alone, SLS/TCN, SLS/Zn and a SLS/TCN/Zn mixture. Treatment with distilled water (DW) served as control. The histological appearance of the tissue before and after treatment was also examined by light microscopy. RESULTS: SLS treatment caused a significant increase in water permeability compared to control tissue (Kp = 11.7 +/- 1.00; 4.96 +/- 0.50 respectively; P < 0.005). Treatment with a SLS/TCN/Zn mixture, however, had no effect on the permeability to water (Kp = 5.5 +/- 0.56). Histological examination revealed that tissue exposed to SLS had a marked disruption of the epithelial surface whilst tissue treated with a SLS/TCN/Zn mixture was indistinguishable from controls. CONCLUSION: Although mucosa exposed to SLS alone showed an increase in permeability to water, the addition of TCN and Zn to SLS appeared to prevent this effect. As SLS is included in some dental products to solubilise compounds such as TCN, its presence may have no effect on the permeability barrier property of oral mucosa.

Adult↗

PubMed2000

Expression of the matrix metalloproteinase 9 in Hodgkin's disease is independent of EBV status.

BACKGROUND: In vitro the Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP-1) has been shown to upregulate expression of matrix metalloproteinase 9 (MMP-9), a member of a family of zinc dependent endopeptidases that is believed to facilitate tumour invasion and metastasis by degradation of the extracellular matrix. AIM: To test whether the expression of MMP-9 in Hodgkin's disease correlates with EBV status and survival and to investigate whether LMP-1 expression affects MMP-9 concentrations in the Hodgkin's disease cell line, L428. METHODS: MMP-9 expression was measured by means of immunohistochemistry in a series of Hodgkin's disease tumours and this expression was correlated with EBV status and survival. The influence of LMP-1 on MMP-9 expression was also investigated in the Hodgkin's disease cell line, L428. RESULTS: MMP-9 expression was demonstrated in the malignant Hodgkin and Reed-Sternberg cells of all (n = 86) formalin fixed, paraffin wax embedded Hodgkin's disease tumours examined. Although the intensity of MMP-9 immunostaining varied between cases, there was no correlation between MMP-9 expression and EBV status or survival. MMP-9 expression was also detected in a variety of non-malignant cells, including fibroblasts. MMP-9 was detected by zymography in the L428 and KMH2 Hodgkin's disease cell lines, whereas low or undetectable amounts of MMP-9 were found in the L591 Hodgkin's disease cell line. Induction of LMP-1 expression in the Hodgkin's disease cell line L428 did not result in a detectable increase in the values of MMP-9 as measured by zymography. CONCLUSIONS: These results demonstrate that MMP-9 is consistently expressed by the Hodgkin and Reed-Sternberg cells of Hodgkin's disease tumours and by the Hodgkin's disease cell lines, L428 and KMH2. However, this expression does not appear to be related either to LMP-1 values or to survival.

Biomarkers, Tumor↗