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Biomedical subjects

D Thomas

Publications and source records attributed to D Thomas.

At least 127 records · Page 7Linked to original sources

The Heartmate II: design and development of a fully sealed axial flow left ventricular assist system.

Our group is developing the control and power transmission components required to implement a permanent and fully sealed left ventricular assist system (LVAS). Starting with the percutaneously powered HeartMate II blood pump, our development efforts are focused in the following areas: a complete redesign of the transcutaneous energy transmission system (TETS) to include a rectification network and autonomous voltage regulation within the secondary coil, a hermetically sealed electronics package containing a miniaturized implementation of the existing redundant drive and control electronics with several power-input options, an implanted rechargeable lithium ion battery pack capable of providing up to 1 h of untethered operation, implantable electrical connectors that allow components to be connected after placement in the body or to be replaced if needed, and a radio telemetry subsystem to transmit diagnostic information and to permit remote adjustment of selected parameters.

Electric Power Supplies↗

Evaluation of the contribution of isolation precautions in prevention and control of multi-resistant bacteria in a teaching hospital.

From February 1999 to January 2000, a control programme to prevent the spread multi-resistant bacteria (MRB) was implemented in a French teaching hospital. This programme focused on methicillin-resistant Staphylococcus aureus (MRSA) and Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBL), and was based on the application of barrier precautions (washing hands with antiseptic soaps, wearing disposable gloves and gowns, identifying MRB carriers). No changes in antibiotic policy occurred during the year. Our aim was to conduct an evaluation of this programme by measuring incidence rates. Concurrently, the effect of barrier precautions was estimated in an indirect way, by documenting the availability of barrier precautions in MRB carriers' rooms and by analysing the monthly correlation between the supply of such material and the theoretical cumulated length of MRB carriers' isolation in six randomized wards. All MRB isolated in hospitalized patients were recorded, and differentiated between acquisition in our hospital or from elsewhere. For the analysis of trends, the year was divided in three periods of four months. Over the year, the global MRB incidence was 1.26 per 1000 patient-days (PD) [95% confidence interval (95%CI)=1.16-1.36]. The MRSA incidence was 0.89 per 1000 PD (95%CI=0.81- 0.97) and the ESBL incidence was 0.38 per 1000 PD (95% CI=0.33-0.43). The MRB incidence decreased significantly in all types of specialties except for surgical wards. The incidence decreased by 17.9% for MRSA, 54.9% for ESBL and 34.8% for both MRB. Concurrently, the proportion of strains acquired in our hospital decreased for MRSA (P for trend > or = 0.05) and ESBL (P for trend > or = 0.01), whereas the incidence of imported strains increased slightly. The proportion of multiresistant strains in S. aureus (36.8%) and Enterobacter aerogenes (37.0%) remained similar throughout the year. Thus, the decrease of the incidence concerned both resistant and susceptible strains. The availability of antiseptic soaps increased significantly (P for trend > or = 0.01). The amount of antiseptic soap ordered and the theoretical lengths of isolation were correlated on a monthly basis (Spearman coefficient = 0.72; P > or = 0.02). These results shows the efficacy of such a programme of MRB containment in a large hospital, provided barrier nursing is instigated, together with the availability of such material as antiseptic soap, to allow implementation.

Bacterial Infections↗

Expression and immunolocalization of the aquaporin-8 water channel in rat gastrointestinal tract.

A remarkable amount, of water is transported in the gastrointestinal (GI) organs to fulfil the secretory and absorptive functions of the GI tract. However, the molecular basis of water movement in the GI epithelial barriers is still poorly known. Important clues about the mechanisms by which water is transported in the GI tract were provided by the recent identification of multiple aquaporin water channels expressed in GI tissues. Here we define the mRNA and protein expression and the cellular and subcellular distribution of aquaporin-8 (AQP8) in the rat GI tract. By semi-quantitative RT-PCR the AQP8 mRNA was detected in duodenum, proximal jejunum, proximal colon, rectum, pancreas and liver and, to a lesser extent, in stomach and distal colon. Immunohistochemistry using affinity-purified antibodies revealed AQP8 staining in the absorptive epithelial cells of duodenum, proximal jejunum, proximal colon and rectum where labeling was largely intracellular and confined to the subapical cytoplasm. Confirming previous results, AQP8 staining was seen at the apical pole of pancreatic acinar cells. Interestingly, both light and immunoelectron microscopy analyses showed AQP8 reactivity in liver where labeling was associated to hepatocyte intracellular vesicles and over the plasma membrane delimiting the bile canaliculi. A complex pattern was observed by immunoblotting with total membranes of the above GI organs incubated with affinity-purified anti-AQP8 antibodies which revealed multiple bands with molecular masses ranging between 28 and 45 kDa. This immunoblotting pattern was not modified after deglycosylation with N-glycosidase F except the 34-kDa band of liver that, as already reported, was partially down-shifted to 28 kDa. No bands were detected after preadsorption of the anti-AQP8 antibodies with the immunizing peptide. The cellular and subcellular distribution of AQP8 suggest physiological roles for this aquaporin in the absorption of water in the intestine and the secretion of bile and pancreatic juice in liver and pancreas, respectively. The large intracellular expression of AQP8 may indicate its recycling between the cytoplasmic compartment and the plasma membrane. The cytoplasmic localization observed may also relate to the involvement of AQP8 in processes of intracellular osmoregulation.

Animals↗

Choice of opioid for initiation of combined spinal epidural analgesia in labour--fentanyl or diamorphine.

Sixty-two women requesting regional analgesia in labour were allocated to receive a 1.5 ml intrathecal injection as part of a combined spinal-epidural (CSE) analgesic technique. This contained either bupivacaine 2.5 mg plus fentanyl 25 microg (group F) or bupivacaine 2.5 mg plus diamorphine 250 microg (group D). Times of analgesic onset and offset were recorded, motor and proprioceptive assessments made and side-effects noted. Analgesic onset was not significantly different between the groups (group F, 8.0 min; group D, 9.5 min; P = 0.3) but time to first top-up request was significantly longer in the diamorphine group (group F, 73 min; group D, 101 min; P = 0.003). Motor loss, assessed by the modified Bromage score, was statistically but not clinically greater in the fentanyl group (P = 0.01). Maternal hypotension, pruritus, proprioceptive loss, nausea and fetal bradycardia were rare and not severe, and their incidences did not differ between groups. No respiratory depression was observed after CSE. This use of diamorphine was not associated with increased side-effects compared with fentanyl/bupivacaine, and it has a longer duration of action.

Analgesia, Epidural↗

Autologous blood transfusion in total knee replacement surgery.

We compared allogeneic blood usage for two groups of patients undergoing total knee replacement surgery (TKR). Patients were randomized to receive either their post-operative wound drainage as an autotransfusion (n=115) after processing or to have this wound drainage discarded (n=116). Allogeneic blood was transfused in patients of either group whose haemoglobin fell below 9 g dl(-1). Only 7% of patients in the autotransfusion group required an allogeneic transfusion compared with 28% in the control group (P<0.001). There was no hospital mortality and only 3% mortality from all causes at the study completion, which spanned 6 months to 3 yr. There was a higher incidence of infection requiring intervention in the allogeneic group (P<0.036). Total patient costs were Pound Sterling 113 greater in the autotransfusion group. We conclude that in this type of surgery post-operative cell salvage is a safe and effective method for reducing allogeneic blood use.

Adult↗

Tracheobronchopathia osteoplastica: incidental finding at tracheal intubation.

Subglottic papillomatous growths were observed on routine tracheal intubation for a scheduled colorectal procedure. Fibreoptic bronchoscopy revealed that the lesions extended down to the carina and into the main bronchi. The diagnosis of tracheobronchopathia osteoplastica was made after subsequent bronchoscopy and biopsy in the post-operative period. A brief review of this rare benign condition is given.

Aged↗

Overpassing an aberrant V(kappa) gene to sequence an anti-idiotypic abzyme with (beta)-lactamase-like activity that could have a linkage with autoimmune diseases.

A monoclonal antibody 9G4H9 that exhibits a beta-lactamase-like activity was previously obtained in accordance with the idiotypic network theory. This abzyme presents the most catalytic efficiency in amidase activity described in literature (kcat = 0.9 min-1). Some reports have demonstrated that functionality as complex as catalysis may be mimicked in this way. Comparison of the catalytic properties of both enzyme and abzyme previously allowed us to obtain better knowledge about 9G4H9 abzymatic machinery. In attempt to characterize this abzyme, the variable regions of kappa and heavy chain were cloned. We present a 'universal' method to clone the correct Vkappa gene to bypass aberrant Vkappa (abVkappa) produced by MOPC-21-derived hybridomas. Sequences obtained are compared in the GenBank database. The VH and Vkappa genes present some important sequence homology with autoantibodies suggesting a direct relationship between catalytic anti-idiotypic antibody and autoimmunity.

Amino Acid Sequence↗

Sleep disorders: a risk factor for pseudotumor cerebri?

OBJECTIVE: To determine whether sleep-related breathing disorders are common in patients with idiopathic intracranial hypertension. MATERIALS AND METHODS: Medical records of 53 patients with idiopathic intracranial hypertension from a tertiary center neuroophthalmology practice were reviewed. Thirty-seven patients were identified who had a history of snoring, difficulty sleeping, or daytime somnolence. The data from polysomnograms were tabulated to determine the frequency of apneas, hypopneas, and arousals. RESULTS: Fourteen of 37 patients with idiopathic intracranial hypertension and symptoms of sleep disturbance underwent polysomnography. There were two men and 12 women varying in age from 24 to 58 years (mean, 39.4 +/- 11.9). These patients were obese with body mass indexes varying from 33.0 to 63.2 (mean, 46.0 +/- 9.5). A diagnosis of sleep apnea was made in six and upper airway resistance syndrome in seven patients. CONCLUSIONS: Sleep-related breathing problems were common in our patients with idiopathic intracranial hypertension. Obesity was common in these patients and may be playing a causative role in sleep apnea and idiopathic intracranial hypertension. It is suggested that idiopathic intracranial hypertension patients who have symptoms of sleep disturbance should be further evaluated for the presence of sleep-related breathing problems.

Adult↗

Bargaining power within couples and use of prenatal and delivery care in Indonesia.

Indonesian women's power relative to that of their husbands is examined to determine how it affects use of prenatal and delivery care. Holding household resources constant, a woman's control over economic resources affects the couple's decision-making. Compared with a woman with no assets that she perceives as being her own, a woman with some share of household assets influences reproductive health decisions. Evidence suggests that her influence on service use also varies if a woman is better educated than her husband, comes from a background of higher social status than her husband's, or if her father is better educated than her father-in-law. Therefore, both economic and social dimensions of the distribution of power between spouses influence use of services, and conceptualizing power as multidimensional is useful for understanding couples' behavior.

Adolescent↗

Congestive heart failure: understanding the pathophysiology and management.

PURPOSE: To explain key concepts involved in the development and management of congestive heart failure (CHF). An overview of medications commonly used in the treatment of CHF is also presented. DATA SOURCES: Selected clinical articles, major research studies, and clinical guidelines. CONCLUSIONS: The prevalence of CHF continues to increase and in the United States alone accounts for more than two million outpatient clinic visits per year at a cost of more than $10 billion annually. With the growing number of people over age 65, coupled with the advances in medical technology, primary care providers are treating many more patients with CHF. IMPLICATIONS FOR PRACTICE: A thorough understanding of the pathophysiology, especially the compensatory neurohormonal systems and ventricular remodeling that are the hallmarks of CHF, is essential for consistent application of the principles of management of this complex condition. Multidisciplinary approaches led by advanced practice nurses have excellent outcomes and improve the quality of life of patients with CHF.

Aged↗

Structures of bacterial flagellar motors from two FliF-FliG gene fusion mutants.

Flagella purified from Salmonella enterica serovar Typhimurium contain FliG, FliM, and FliN, cytoplasmic proteins that are important in torque generation and switching, and FliF, a transmembrane structural protein. The motor portion of the flagellum (the basal body complex) has a cytoplasmic C ring and a transmembrane M ring. Incubation of purified basal bodies at pH 4.5 removed FliM and FliN but not FliG or FliF. These basal bodies lacked C rings but had intact M rings, suggesting that FliM and FliN are part of the C ring but not a detectable part of the M ring. Incubation of basal bodies at pH 2.5 removed FliG, FliM, and FliN but not FliF. These basal bodies lacked the C ring, and the cytoplasmic face of the M ring was altered, suggesting that FliG makes up at least part of the cytoplasmic face of the M ring. Further insights into FliG were obtained from cells expressing a fusion protein of FliF and FliG. Flagella from these mutants still rotated but cells were not chemotactic. One mutant is a full-length fusion of FliF and FliG; the second mutant has a deletion lacking the last 56 residues of FliF and the first 94 residues of FliG. In the former, C rings appeared complete, but a portion of the M ring was shifted to higher radius. The C-ring-M-ring interaction appeared to be altered. In basal bodies with the fusion-deletion protein, the C ring was smaller in diameter, and one of its domains occupied space vacated by missing portions of FliF and FliG.

Artificial Gene Fusion↗

Experimental preemptive immunotherapy of murine cytomegalovirus disease with CD8 T-cell lines specific for ppM83 and pM84, the two homologs of human cytomegalovirus tegument protein ppUL83 (pp65).

CD8 T cells are the principal antiviral effectors controlling cytomegalovirus (CMV) infection. For human CMV, the virion tegument protein ppUL83 (pp65) has been identified as a source of immunodominant peptides and is regarded as a candidate for cytoimmunotherapy and vaccination. Two sequence homologs of ppUL83 are known for murine CMV, namely the virion protein ppM83 (pp105) expressed late in the viral replication cycle and the nonstructural protein pM84 (p65) expressed in the early phase. Here we show that ppM83, unlike ppUL83, is not delivered into the antigen presentation pathway after virus penetration before or in absence of viral gene expression, while other virion proteins of murine CMV are processed along this route. In cytokine secretion-based assays, ppM83 and pM84 appeared to barely contribute to the acute immune response and to immunological memory. Specifically, the frequencies of M83 and M84 peptide-specific CD8 T cells were low and undetectable, respectively. Nonetheless, in a murine model of cytoimmunotherapy of lethal CMV disease, M83 and M84 peptide-specific cytolytic T-cell lines proved to be highly efficient in resolving productive infection in multiple organs of cell transfer recipients. These findings demonstrate that proteins which fail to prime a quantitatively dominant immune response can nevertheless represent relevant antigens in the effector phase. We conclude that quantitative and qualitative immunodominance are not necessarily correlated. As a consequence of these findings, there is no longer a rationale for considering T-cell abundance as the key criterion for choosing specificities to be included in immunotherapy and immunoprophylaxis of CMV disease and of viral infections in general.

Adoptive Transfer↗

EAU Guidelines on benign prostatic hyperplasia (BPH).

OBJECTIVE: To establish guidelines for the diagnosis, treatment, and follow-up of BPH. METHODS: A search of published work was conducted using Medline. In combination with expert opinions recommendations were made on the usefulness of tests for assessment and follow-up: mandatory, recommended, or optional. In addition, indications and outcomes for the different therapeutic options were reviewed. RESULTS: A digital rectal examination is mandatory in the assessment for the diagnosis of BPH. Recommended tests are the International Prostate Symptom Score, creatinine measurement (or renal ultrasound), uroflowmetry, and postvoid residual urine volume. All other tests are optional. The aim of treatment is to improve patients' quality of life, and it depends on the severity of the symptoms of BPH. The watchful waiting policy is recommended for patients with mild symptoms, medical treatment for patients with mild-moderate symptoms, and surgery for patients who failed medication or conservative management and who have moderate-severe symptoms, and/or complications of BPH which require surgery. Regarding non-surgical treatments, transurethral microwave thermotherapy is the most attractive option. These treatments should be reserved for patients who prefer to avoid surgery or who no longer respond favourably to medication. Finally, recommendations for follow-up tests and a recommended follow-up time schedule after BPH treatment are provided. CONCLUSIONS: Recommendations for assessment, possible therapeutic options, and follow-up of patients with BPH are made.

Follow-Up Studies↗

Disaggregation of in vitro preformed platelet-rich clots by abciximab increases fibrin exposure and promotes fibrinolysis.

The glycoprotein IIb/IIIa receptor inhibitor abciximab has been shown to facilitate the rate and the extent of pharmacological thrombolysis with recombinant tissue plasminogen activator (rtPA) in patients with acute myocardial infarction. However, the underlying mechanisms remain not fully determined. We sought to demonstrate that this facilitating effect of abciximab could be related to its potential to modify the clot architecture and the clot physical properties. Compared with fibrin-rich clots, platelets dramatically modified the in vitro properties of the fibrin network, leading to a significant increase of the permeability (K(s)) and the viscoelasticity (G') indexes but also leading to the appearance of platelet aggregates (surface area [S.ag]). These modifications resulted in a 2.6-fold decrease of the fibrinolysis rate when rtPA (1 nmol/L) was added before the initiation of clotting. Adding aspirin (100 microgram/mL) or abciximab (0.068 micromol/L) before the clotting of platelet-rich clots (PRCs) lowered K(s) by 50% and 70%, respectively (P<0.01), G' by 41% and 66%, respectively (P<0.01), and S.ag by 32% and 61%, respectively (P<0.01). As a consequence, the lysis speed was increased by 21% with aspirin (P<0.01) and 45% with abciximab (P<0.01). However, unlike aspirin, permeation of preformed PRCs with abciximab (0.068 micromol/L) decreased G' (37%, P<0.01), K(s) (35%, P<0.001) and S.ag (25%, P=NS) and resulted in a 27% (P<0.01) increase of the lysis speed when abciximab and rtPA (0.2 micromol/L) were simultaneously permeated. This effect was found to be time dependent and was observed only with early permeation, starting within the first 10 minutes of clotting. These changes in the physical properties of the PRC architecture suggest that fibrin is removed from the platelet-fibrin aggregates and reexposed into the surrounding fibrin network, increasing rtPA access to fibrin and therefore the fibrinolysis rate. The superiority of abciximab over aspirin in accelerating fibrinolysis of forming and preformed PRCs is related to its ability to modulate the interactions of fibrinogen and fibrin with platelets. These findings provide new mechanistic information on reperfusion therapy.

Abciximab↗

Calcium puffs are generic InsP(3)-activated elementary calcium signals and are downregulated by prolonged hormonal stimulation to inhibit cellular calcium responses.

Elementary Ca(2+) signals, such as "Ca(2+) puffs", which arise from the activation of inositol 1,4,5-trisphosphate receptors, are building blocks for local and global Ca(2+) signalling. We characterized Ca(2+) puffs in six cell types that expressed differing ratios of the three inositol 1,4,5-trisphosphate receptor isoforms. The amplitudes, spatial spreads and kinetics of the events were similar in each of the cell types. The resemblance of Ca(2+) puffs in these cell types suggests that they are a generic elementary Ca(2+) signal and, furthermore, that the different inositol 1,4,5-trisphosphate isoforms are functionally redundant at the level of subcellular Ca(2+) signalling. Hormonal stimulation of SH-SY5Y neuroblastoma cells and HeLa cells for several hours downregulated inositol 1,4,5-trisphosphate expression and concomitantly altered the properties of the Ca(2+) puffs. The amplitude and duration of Ca(2+) puffs were substantially reduced. In addition, the number of Ca(2+) puff sites active during the onset of a Ca(2+) wave declined. The consequence of the changes in Ca(2+) puff properties was that cells displayed a lower propensity to trigger regenerative Ca(2+) waves. Therefore, Ca(2+) puffs underlie inositol 1,4,5-trisphosphate signalling in diverse cell types and are focal points for regulation of cellular responses.

Adenosine Triphosphate↗

Women's health and pregnancy outcomes: do services make a difference?

We use data from the Indonesia Family Life Survey to investigate the impact of a major expansion in access to midwifery services on health and pregnancy outcomes for women of reproductive age. Between 1990 and 1998 Indonesia trained some 50,000 midwives. Between 1993 and 1997 these midwives tended to be placed in relatively poor communities that were relatively distant from health centers. We show that additions of village midwives to communities between 1993 and 1997 are associated with a significant increase in body mass index in 1997 relative to 1993 for women of reproductive age, but not for men or for older women. The presence of a village midwife during pregnancy is also associated with increased birthweight. Both results are robust to the inclusion of community-level fixed effects, a strategy that addresses many of the concerns about biases because of nonrandom program placement.

Adult↗

Surveillance of sexually transmitted infections in England and Wales.

Surveillance of sexually transmitted infections (STIs) in England and Wales has, in the past, relied principally on aggregated statistical data submitted by all genitourinary medicine clinics to the Communicable Disease Surveillance Centre, supplemented by various laboratory reporting systems. Although these systems provide comparatively robust surveillance data, they do not provide sufficient information on risk factors to target STI control and prevention programmes appropriately. Over recent years, substantial rises in STIs, the emergence of numerous outbreaks of STIs, and changes in gonococcal resistance patterns have necessitated the introduction of more sophisticated surveillance mechanisms. This article describes current STI surveillance systems in England and Wales, including new systems that have recently been introduced or are currently being developed to meet the need for enhanced STI surveillance data.

Chlamydia Infections↗

HIV clinical trials in correctional settings: right or retrogression?

The right of incarcerated prison and jail inmates to health care is protected by the 8th and the 14th amendments of the Constitution, respectively. Does the right to health care include access to clinical trials? At the time of this writing, clinical trials have become part of the fabric of HIV/AIDS care, allowing patients to participate in studies of new and often lifesaving treatments. Participation in trials can also be dangerous, as illustrated by the recent death of a subject in a gene therapy trial. This danger is compounded by ethical dilemmas that can arise from the large amount of financial support for clinical trials (greater than 75%) that is derived from for-profit corporations. Indeed, clinical trials are the subject of grave concern on the part of the United States Government, which has recently taken steps to shore up human subject safeguards. Following a conference on the conduct of clinical trials in correctional settings, the Office for Human Research Protections suspended prison research conducted by 4 prestigious academic institutions.

Anti-HIV Agents↗