Value of breast imaging in women with painful breasts. Women with severe problems must be seen in specialist breast clinics.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R Wilson.
Explore the source record for details and available documents.
The potential for health risks to humans exposed to the asbestos minerals continues to be a public health concern. Although the production and use of the commercial amphibole asbestos minerals-grunerite (amosite) and riebeckite (crocidolite)-have been almost completely eliminated from world commerce, special opportunities for potentially significant exposures remain. Commercially viable deposits of grunerite asbestos are very rare, but it can occur as a gangue mineral in a limited part of a mine otherwise thought asbestos-free. This report describes such a situation, in which a very localized seam of grunerite asbestos was identified in an iron ore mine. The geological occurrence of the seam in the ore body is described, as well as the mineralogical character of the grunerite asbestos. The most relevant epidemiological studies of workers exposed to grunerite asbestos are used to gauge the hazards associated with the inhalation of this fibrous mineral. Both analytical transmission electron microscopy and phase-contrast optical microscopy were used to quantify the fibers present in the air during mining in the area with outcroppings of grunerite asbestos. Analytical transmission electron microscopy and continuous-scan x-ray diffraction were used to determine the type of asbestos fiber present. Knowing the level of the miner's exposures, we carried out a risk assessment by using a model developed for the Environmental Protection Agency.
Explore the source record for details and available documents.
Unlike vertebrates, insects do not have an Ab-based nonself recognition system, and must rely totally on innate immunity to defend themselves from microbial invaders. The most likely candidates for recognizing foreign material in insects are the lectins, which have already been shown to be important in mammalian innate immunity. The hemolymph of the cockroach, Blaberus discoidalis, contains multiple lectins, designated BDL1, BDL2, BDL3, and GSL (beta-1,3-glucan-specific lectin), two of which, namely BDL1 and GSL, have close similarities to acute phase reactants. These endogenous molecules, as well as Con A, wheat germ agglutinin, and Helix pomatia agglutinin, have been shown to induce an enhanced phagocytic response by B. discoidalis plasmatocytes. This effect is related to the carbohydrates presented on the surface of the microorganism and to the sugar specificities of the lectins. Thus, the mannose-specific lectins, BDL1 and Con A, both increase the phagocytosis of baker's yeast and Escherichia coli, whereas the N-acetyl-D-glucosamine/N-acetyl-D-galactosamine-specific lectins, BDL2, wheat germ agglutinin, and H. pomatia agglutinin, induce the phagocytosis of Bacillus cereus and E. coli. GSL, specific for beta-1,3-glucan, and the N-acetyl-D-galactosamine-specific BDL3, only enhance the phagocytosis of yeast and B. cereus, respectively. Phenylthiourea, an inhibitor of the prophenoloxidase system, caused either total, partial, or no inhibition of the lectin-induced increase in phagocytosis, indicating that this immune enhancement results, in some cases, from at least two closely linked mechanisms. These results show that the endogenous lectins in the cockroach hemolymph are capable of acting as nonself recognition molecules for a wide range of microorganisms, and thus obviate the necessity of Abs in these animals.
The use of minimally invasive surgery for abdominal pathology, including malignancy, has increased significantly within the past decade. Despite the advances in radiographic imaging, the use of laparoscopy for diagnosing and staging abdominal malignancy has become an important tool in the overall care of these patients. A review of published series for a variety of abdominal malignancies is presented. With the growing experience in this technique, some preliminary conclusions and ongoing issues are discussed.
Competence is an active state that defines the way in which cells respond to an inductive signal. A challenge of developmental biology is to explain not just the nature of the signalling molecules that promote cell specification or differentiation, but also how cells acquire competence to respond to these signals and what that reflects in molecular terms. A recent paper by Carmena et al. has revealed how several signalling mechanisms are used sequentially and in specific combinations to specify two mesodermal lineages in Drosophila.
Synthetic vitreous fibers (SVFs) have been widely used as insulation material in places where asbestos was used many years ago and therefore the hazards have been compared. Since the three principal types of asbestos fibers types have caused lung cancer at high exposures, there is a widely held belief that all fibers are carcinogenic if inhaled in large enough doses. Hence, on a morphological basis, SVFs have been studied for their carcinogenic potential. However, there is considerable evidence that differences exist among fibers in their potency to produce a carcinogenic response. In this attempt to carry out a numerical risk assessment for the installers of blown glass wool (fiber) insulation, we start with a characterization of the material; then we review the exposures both in manufacturing and installation. Neither the epidemiological studies of human exposure nor the animal studies have shown a marked hazardous effect from glass wool and we can therefore be sure that any effect that might exist is small. But in this case, as in many other situations where there is a potential hazard, society desires further reassurance and therefore we have made a mechanistic calculation. There are good estimates of the risk associated with exposure to chrysotile asbestos at high exposures and doses. We have therefore taken these numbers and discussed how much less risky an exposure to glass wool fibers might be. We conclude that for a given fiber count, glass wool is five to ten times less risky (and of course the risk might be zero). The risk for a nonsmoking installer of glass wool fiber insulation who wears a respirator is about 6 in a million (and might be zero) per year. This means that out of a million installers there might be six lung cancers from this cause every year or out of 10,000 installers there might be one in 16 years. The low risk of 6 in a million per year of a worker blowing glass wool is consistent with the fact that no one has found any of cancer attributable to the manufacture or installation of glass wool fibers in spite of diligent searches. This is compared with several other occupational risks. Nonetheless common prudence suggests that any installer of blown glass wool fiber insulation wear a respirator.
OBJECTIVE: To determine whether the titer and avidity of the thyroid peroxidase antibody differs between pregnant women in their first trimester who have a history of recurrent miscarriage and whose pregnancies continue to term and those whose pregnancies fail again later in the first trimester. DESIGN: Controlled clinical study. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Pregnant women in their first trimester who had a history of recurrent miscarriage (> or = 3 miscarriages) and who were known to be positive for the thyroid peroxidase antibody. INTERVENTION(S): None of the patients received any medication. MAIN OUTCOME MEASURE(S): Thyroid peroxidase antibody titer and avidity (i.e., the net binding strength between antibody and antigen). RESULT(S): At the time of presentation, thyroid peroxidase antibody titer and avidity was significantly higher in those women who later miscarried compared with those whose pregnancies continued. In those whose pregnancies continued to term, titer and avidity declined as the pregnancy progressed. CONCLUSION(S): Autoimmunity plays a role in recurrent miscarriage. Among a group of patients who had had recurrent miscarriages, there appeared to be differences in the humoral response to the pregnancy between those whose pregnancies continued to term and those whose pregnancies failed again.
The GABA(B) receptor has been shown to consist of a heterodimer of two related 7-transmembrane receptors GABAB-R1 and GABA(B)-R2. These receptors share close homology to the Ca2+-sensing receptor and also to the metabotropic glutamate receptors, which have also been shown to respond to extracellular calcium. We show here that the GABA(B) receptor also has Ca2+ sensing properties. Ca2+ (0.001-1 mM) potentiated the GABA stimulation of [35S]GTPgammaS binding in membranes prepared from CHO cells stably expressing the GABA(B)-R1/R2 heterodimer. The GABA EC50 was reduced from 72 to 7.7 microM by addition of 1 mM Ca2+, with no change in the maximum response. A similar effect was observed in membranes from rat brain cortex. Ca2+ also potentiated GABA inhibition of forskolin-stimulated cAMP levels in the CHO cells and enhanced coupling to GIRK K+ channels in Xenopus oocytes. Other divalent cations were ineffective. The effects of Ca2+ were found to be agonist dependent with baclofen having a reduced sensitivity compared to GABA. Calcium appears to act allosterically to enhance GABA responses at the GABA(B) receptor, however, unlike the Ca2+-sensing receptor and some of the mGluR family, Ca2+ does not act as a ligand in its own right.
Explore the source record for details and available documents.
BACKGROUND: This study was undertaken to determine the frequency of skin colonization, hub colonization, and central venous catheter colonization in transparent hydrocolloid versus standard polyurethane dressings. METHODS: Adult patients requiring the insertion of a multilumen central venous catheter in an intensive care unit were randomized to receive either a standard polyurethane dressing or a transparent hydrocolloid dressing. Cultures were obtained from 125 skin insertion sites, 141 catheter hubs, 128 catheter tips, and blood samples from 132 patients. Extensive data on patient and catheter characteristics were collected. RESULTS: Skin and hub cultures revealed no significant difference in degree of colonization. However, the hydrocolloid group had a significantly higher level of catheter colonization than the polyurethane group (P =.048). Conversely, there was a significantly higher frequency of positive blood cultures in the polyurethane group (P =.03), although the majority were considered to be potential contaminants. There were only 6 cases in which the same species was simultaneously isolated from a positive blood culture and a colonized catheter, 5 from the hydrocolloid group and 1 from the polyurethane group. CONCLUSIONS: The results of this study suggest that an increased risk of catheter colonization is associated with the use of hydrocolloid dressings, despite previous research suggesting that they significantly reduce microbial growth compared with standard polyurethane. The clinical significance of increased numbers of positive blood cultures in the polyurethane group requires further examination, although distinguishing between contamination and true infection in intensive care settings continues to be methodologically challenging. Further studies are required to determine whether these findings are generalizable across different study settings and whether similar outcomes are obtained when different brands of hydrocolloid dressing are used.
PURPOSE: A large multicenter study has recently questioned the overall clinical efficacy of vena caval filters, especially when inserted prophylactically, because of the subsequent development of deep venous thrombosis (DVT) at the insertion site. We examined the incidence of this complication with newer, smaller diameter percutaneous devices. METHODS: We reviewed our vascular surgery and interventional radiology clinical registries to identify patients in whom a femoral percutaneous vena caval filter had been placed from 1993 to 1998. This list was cross referenced with patients who had undergone lower extremity venous ultrasound scan examinations for the diagnosis of DVT in the vascular laboratory within a 60-day period before and after the insertion of the filter device. RESULTS: A total of 35 patients during this 5-year period had timely follow-up venous duplex scan studies performed. The indications for filter placement were DVT in 16 patients (46%), pulmonary embolus in 13 patients (37%), DVT and pulmonary embolus in three patients (9%), and prophylactically in three patients (9%) at high risk for thromboembolization. Of the patients with documented thromboembolic events, 91% (29 of 32) had contraindications to anticoagulation therapy, and the remaining 9% (3 of 32) represented failure of anticoagulation therapy. A Greenfield filter was used in 13 patients (37%), a Simon Nitinol filter was used in 11 patients (31%), and a VenaTech filter was used in nine patients (26%). The other two patients (6%) had a Bird's Nest filter inserted. At a mean follow-up period of 12 +/- 2 days (median, 6 days), there was a 40% (14 of 35) incidence of proximal DVT in venous segments without evidence of thrombus before filter insertion. The majority (71%; 10 of 14) occurred in the common femoral vein, with three located in the superficial femoral vein and one in the external iliac vein. The lowest incidence of DVT was seen with the Greenfield and Bird's Nest filters as compared with the smaller Simon Nitinol and VenaTech filters (20% vs 55%; P < .05). The highest incidence of thrombosis occurred in patients with pre-insertion pulmonary emboli (50%; 8 of 16) as compared with those patients with DVT (38%; 6 of 16) and prophylactic insertion (0%; 0 of 3). However, the subgroups were too small to attain statistical significance. CONCLUSION: There is a continuing and significant incidence of new DVT development ipsilateral to the percutaneous femoral insertion site of vena caval filters. The smaller diameter filters are not associated with a lower incidence of femoral thrombosis.
Explore the source record for details and available documents.
The potential of the novel ketolide antimicrobial agents, HMR 3004 and HMR 3647, to antagonize the injurious effects of the bioactive phospholipids (PL), platelet-activating factor (PAF), lyso-PAF, and lysophosphatidylcholine (LPC) on the ciliary beat frequency and structural integrity of human ciliated respiratory epithelium in vitro was investigated, in the presence or absence of polymorphonuclear leukocytes (PMNL). The ciliary beat frequency of human nasal respiratory epithelium, obtained by nasal brushing of healthy volunteers, was measured using a photo-transistor technique, while superoxide generation by activated human PMNL and membrane-stabilizing activity were measured by lucigenin-enhanced chemiluminescence and haemolytic procedures, respectively. All three PL, at concentrations of 2.5 microg x mL(-1), caused significant (p<0.005) ciliary slowing and epithelial damage, while treatment of the epithelial strips with the ketolides, in particular HMR 3004, caused dose-related attenuation of these direct adverse effects of the PL on ciliated epithelium, apparently by a membrane-stabilizing mechanism. When epithelial strips were exposed to the combination of PMNL (1 x 10(6) cells x mL(-1)) and PAF (1 microg x mL(-1)), significant ciliary dysfunction and epithelial damage were also observed, which were mediated predominantly by neutrophil-derived oxidants. These injurious effects of PAF were antagonized by preincubation of the epithelial strips or the PMNL with HMR 3004 (10 microg x mL(-1)). The ketolide antimicrobial agents, in particular HMR 3004, antagonize the direct and polymorphonuclear leukocyte-mediated injurious effects of phospholipids on human ciliated epithelium and may have beneficial effects in inflammatory disorders of the airways, such as asthma, chronic bronchitis, diffuse panbronchiolitis and bronchiectasis.
The purpose of this study was to investigate the effect of the corticosteroid, fluticasone propionate (FP), on Pseudomonas aeruginosa infection of the respiratory mucosa of an organ culture model in vitro. Organ cultures infected with P. aeruginosa had significantly (p< or =0.05) elevated levels of mucosal damage and significantly (p< or =0.05) less ciliated cells compared to controls. Preincubation of tissue with FP (10(-6) or 10(-5) but not 10(-7) M) prior to P. aeruginosa infection significantly (p< or =0.05) reduced the bacterially induced mucosal damage in a concentration-dependent manner. FP (10(-5) M) also significantly (p< or =0.05) prevented loss of ciliated cells. FP did not alter the density of bacteria adherent to the different mucosal features of the organ cultures, but did reduce total bacterial numbers due to the reduced amount of damaged tissue, which is a preferred site of P. aeruginosa adherence. It has previously been shown that the long-acting beta2-agonist salmeterol (4 x 10(-7)M) also reduces the mucosal damage caused by P. aeruginosa infection, probably via elevation of intracellular cyclic adenosine monophosphate concentrations. Preincubation of tissue with both 10(-7)M FP and 10(-7)M salmeterol, concentrations at which they did not by themselves influence the effect of P. aeruginosa infection, significantly (p< or =0.05) reduced P. aeruginosa-induced loss of cilia. However, there was no additional benefit from adding 4 x 10(-7)M salmeterol to 10(-6)M FP. In conclusion fluticasone propionate reduced mucosal damage caused by P. aeruginosa infection in vitro and preserved ciliated cells. There was a synergistic action with salmeterol in the preservation of ciliated cells.
Arabidopsis thaliana has emerged as a model system for studies of plant genetics and development, and its genome has been targeted for sequencing by an international consortium (the Arabidopsis Genome Initiative; http://genome-www. stanford.edu/Arabidopsis/agi.html). To support the genome-sequencing effort, we fingerprinted more than 20,000 BACs (ref. 2) from two high-quality publicly available libraries, generating an estimated 17-fold redundant coverage of the genome, and used the fingerprints to nucleate assembly of the data by computer. Subsequent manual revision of the assemblies resulted in the incorporation of 19,661 fingerprinted BACs into 169 ordered sets of overlapping clones ('contigs'), each containing at least 3 clones. These contigs are ideal for parallel selection of BACs for large-scale sequencing and have supported the generation of more than 5.8 Mb of finished genome sequence submitted to GenBank; analysis of the sequence has confirmed the integrity of contigs constructed using this fingerprint data. Placement of contigs onto chromosomes can now be performed, and is being pursued by groups involved in both sequencing and positional cloning studies. To our knowledge, these data provide the first example of whole-genome random BAC fingerprint analysis of a eucaryote, and have provided a model essential to efforts aimed at generating similar databases of fingerprint contigs to support sequencing of other complex genomes, including that of human.
The laboratory mouse is the premier model system for studies of mammalian development due to the powerful classical genetic analysis possible (see also the Jackson Laboratory web site, http://www.jax.org/) and the ever-expanding collection of molecular tools. To enhance the utility of the mouse system, we initiated a program to generate a large database of expressed sequence tags (ESTs) that can provide rapid access to genes. Of particular significance was the possibility that cDNA libraries could be prepared from very early stages of development, a situation unrealized in human EST projects. We report here the development of a comprehensive database of ESTs for the mouse. The project, initiated in March 1996, has focused on 5' end sequences from directionally cloned, oligo-dT primed cDNA libraries. As of 23 October 1998, 352,040 sequences had been generated, annotated and deposited in dbEST, where they comprised 93% of the total ESTs available for mouse. EST data are versatile and have been applied to gene identification, comparative sequence analysis, comparative gene mapping and candidate disease gene identification, genome sequence annotation, microarray development and the development of gene-based map resources.
This paper reports on part of a national study conducted between 1994 and 1996, the overall aim of which was to examine the 'fitness for purpose' of the Project 2000 nursing education reforms. The study used multiple methods of data collection, including an individual and group interview study of nurse managers (n = 132) and a national survey of Project 2000 diplomates and traditionally prepared registered nurses (n = 5417). Findings in relation to the managers' expectations and experiences of diplomates are presented. This includes views on the level of skills achievement and skills acquisition of diploma level education. The qualities of the diplomates are discussed and this includes those areas where the skills of the diplomates are felt to achieve what is required of the role. Also included is an exploration of those skills which the managers felt fell short of expectations. Managers raised the long-standing concerns of clinical skills and competencies and discussed these in relation to the changing health care environment and the relative roles of other health care workers. The conclusions highlight the need to identify what could be seen as the 'core skills' required of a registered nurse and the need to explore the environment in which the diplomate takes up first appointment.