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Biomedical subjects

John Webb

Publications and source records attributed to John Webb.

At least 19 recordsLinked to original sources

Percutaneous replacement of pulmonary valve using the Edwards-Cribier percutaneous heart valve: first report in a human patient.

We report on the use of the Edwards-Cribier percutaneous heart valve (PHV) in a stenotic right ventricle to pulmonary artery homograft in a 16-year old patient who underwent the Ross operation. Initially, the homograft was stented and at the same procedure, the PHV was deployed inside it. This is the first human case of the application of this valve in the pulmonary valve position.

Adolescent↗

Initial experience with a novel coronary rinsing and thrombectomy system: "Rinspiration".

BACKGROUND: Intracoronary thrombus is often problematic during percutaneous coronary intervention. Rinspiration is a new thrombectomy catheter system designed to mechanically disrupt and remove intravascular thrombus. METHODS: Rinspiration thrombectomy was performed in 15 patients with angiographically visible thrombus in native coronary arteries (10 cases) and in saphenous grafts (5 cases). Indications included acute myocardial infarction in 11 patients and postinfarction ischemia in 4 patients. RESULTS: The Rinspiration system appeared relatively simple to use. There were no device-related complications. Thrombectomy resulted in an improvement in thrombus grade from 3.8 +/- 1.6 to 2.5 +/- 1.7 (p = 0.02), and TIMI flow from 1.5 +/- 1.3 to 2.2 +/- 1.0 (p = 0.047). Stenting further improved thrombus grade to 0.8 +/- 1.6 and TIMI flow to 2.6 +/- 0.8. At 30-day follow up all patients remained free of repeat revascularization and reinfarction; 1 patient died from hemorrhagic stroke. CONCLUSIONS: The Rinspiration system appears capable of safely removing intracoronary thrombus and warrants further evaluation.

Aged↗

Distal microcirculatory protection during percutaneous coronary intervention in acute ST-segment elevation myocardial infarction: a randomized controlled trial.

CONTEXT: Atheromatous and thrombotic embolization during percutaneous coronary intervention (PCI) in acute myocardial infarction is common and may result in microcirculatory dysfunction, the prevention of which may improve reperfusion success, reduce infarct size, and enhance event-free survival. OBJECTIVE: To determine whether protection of the distal microcirculation from thromboembolic debris liberated during primary PCI results in improved reperfusion and decreased infarct size. DESIGN, SETTING, AND PATIENTS: Prospective randomized controlled trial at 38 academic and community-based institutions in 7 countries enrolling 501 patients aged 18 years or older with ST-segment elevation myocardial infarction (STEMI) presenting within 6 hours of symptom onset and undergoing primary PCI or rescue intervention after failed thrombolysis. INTERVENTIONS: Patients were randomized between May 20, 2002, and November 21, 2003, to receive PCI with a balloon occlusion and aspiration distal microcirculatory protection system vs angioplasty without distal protection. MAIN OUTCOME MEASURES: Coprimary end points were ST-segment resolution (STR) measured 30 minutes after PCI by continuous Holter monitoring and infarct size measured by technetium Tc 99m sestamibi imaging between days 5 and 14. Secondary end points included major adverse cardiac events. RESULTS: Among 252 patients assigned to distal protection, aspiration was performed in 97% (242/251), all angioplasty balloon inflations were fully protected in 79% (193/245), and visible debris was retrieved from 73% (182/250). Complete STR was achieved in a similar proportion reperfused with vs without distal protection (63.3% [152/240] vs 61.9% [148/239], respectively; absolute difference, 1.4% [95% confidence interval, -7.7% to 10.5%; P = .78]), and left ventricular infarct size was similar in both groups (median, 12.0% [n = 229] vs 9.5% [n = 208], respectively; P = .15). Major adverse cardiac events at 6 months occurred with similar frequency in the distal protection and control groups (10.0% vs 11.0%, respectively; P = .66). CONCLUSIONS: A distal balloon occlusion and aspiration system effectively retrieves embolic debris in most patients with acute STEMI undergoing emergent PCI. Nonetheless, distal embolic protection did not result in improved microvascular flow, greater reperfusion success, reduced infarct size, or enhanced event-free survival.

Aged↗

Percutaneous closure of a complex prosthetic mitral paravalvular leak using transesophageal echocardiographic guidance.

A 75-year-old man had a significant mitral paravalvular leak following unsuccessful mitral valve repair at age 71 years and mitral valve replacement two years later. He was referred for percutaneous closure, which was performed with an atrial septal defect occluder device. Subsequently, a small residual leak was closed with an embolization coil. A novel technique for identifying the paravalvular leak with simultaneous transesophageal and radiographic guidance is described.

Aged↗

Vascular responses at proximal and distal edges of paclitaxel-eluting stents: serial intravascular ultrasound analysis from the TAXUS II trial.

BACKGROUND: On the basis of brachytherapy experience, edge stenosis has been raised as a potential limitation for drug-eluting stents. We used serial intravascular ultrasound (IVUS) to prospectively analyze vessel responses in adjacent reference segments after implantation of polymer-controlled paclitaxel-eluting stents. METHODS AND RESULTS: TAXUS II was a randomized, double-blind trial with 2 consecutive patient cohorts that compared slow-release (SR) and moderate-release (MR) paclitaxel-eluting stents with control bare metal stents (BMS). By protocol, all patients had postprocedure and 6-month follow-up IVUS. Quantitative IVUS analysis was performed by an independent core laboratory, blinded to treatment allocation, in 5-mm vessel segments immediately proximal and distal to the stent. Serial IVUS was available for 106 SR, 107 MR, and 214 BMS patients. For all 3 groups, a significant decrease in proximal-edge lumen area was observed at 6 months. The decrease was comparable (by ANOVA, P=0.194) for patients in the SR (-0.54+/-2.1 mm2) and MR (-0.88+/-1.9 mm2) groups compared with the BMS (-1.02+/-1.9 mm2) group. For the distal edge, a significant decrease in lumen area was only observed with BMS (-0.91+/-2.0 mm2, P<0.0001); this decrease was significantly attenuated with SR (0.08+/-2.0 mm2) and MR (-0.19+/-1.7 mm2) stents (P<0.0001 by ANOVA). Negative vessel remodeling was observed at the proximal (-0.48+/-2.2 mm2, P=0.011) but not the distal edges of BMS and at neither edge of SR or MR stents. CONCLUSIONS: The marked reduction in in-stent restenosis with SR or MR stents is not associated with increased edge stenosis at 6-month follow-up IVUS. In fact, compared with BMS, there is instead a significant reduction in late lumen loss at the distal edge with TAXUS stents.

Coronary Restenosis↗

Damage to a covered stent by a thrombectomy device.

A 75-year-old with a history of coronary bypass grafting was found to have significant stenoses in a vein graft to the right coronary artery. Symbiot stents, with a polytetrafluoroethylene covering, were used to treat areas in the proximal and middle sections of the graft. The following day, she developed symptoms and signs consistent with an acute inferior infarction. The graft was found to be thrombosed. Thrombectomy was performed using an X-Sizer device, consisting of a helical cutter connected to a vacuum source. This resulted in damage to the stent lining, which led to jamming of the device and subsequent removal of a piece of the stent covering. Treatment was by way of deployment of a long stent within the damaged stent. Recovery was unremarkable. Caution or avoidance of this device appears warranted in the setting of covered stent procedures.

Aged↗

The NUGGET study: NIR ultra gold-gilded equivalency trial.

This study should clarify whether the gold-coated NIROYAL stent is equivalent to the stainless steel NIR stent. Patients were randomized to either NIR stent (n = 298) or a NIROYAL stent (n = 305). The primary endpoint was the minimum lumen diameter of the target lesion at 6 months postprocedure. Secondary endpoints focused on clinical events. At 30 days, adverse events were similar in both groups. At 6 months, the minimal lumen diameter was 1.83/1.64 mm (P < 0.001; 95% CI = 0.08-0.30) and the angiographic restenosis rate was 20.6%/37.7% (P < 0.001; 95% CI = -24.7 to -9.3) for NIR/NIROYAL. The 6-month MACE rates were NIR 7.4% and NIROYAL 10.5% (95% CI = -7.7 to 1.4). Compared to stainless steel stent, the NIROYAL stent demonstrated a smaller minimal lumen diameter, a higher late loss (i.e., higher neointimal hyperplasia in spite of a significantly better initial gain), with higher restenosis and similar MACE rates at 6 months.

Aged↗

Direct stenting with TAXUS stents seems to be as safe and effective as with predilatation. A post hoc analysis of TAXUS II.

BACKGROUND AND METHOD: Although direct coronary stenting does not improve angiographic outcome, it makes sense by reducing procedure times, radiation exposure and costs. Other potential advantages of direct stenting may be a reduction of myocardial ischemia time, which could be clinically relevant in high-risk patients. With the introduction of drug-eluting stents, however, concern arose that direct stenting would possibly damage the polymer coating and change or diminish the efficacy of the programmed drug release. Also, concerns about safety by preventing optimal apposition of single stent struts developed. It is the purpose of this paper to retrospectively analyze the data from the TAXUS-II Trial (536 patients) regarding patients with and without direct stenting. While predilatation was recommended per protocol, direct stenting was not forbidden: thus, direct stenting was performed in 49 patients (TAXUS n = 23, control n = 26). RESULTS: In the TAXUS groups, there was no significant difference regarding major adverse cardiac events (MACE; 7.5% vs. 4.3%), angiographic restenosis in the analysis segment (4.8% vs. 4.3%), late loss (0.28 +/- 0.36 vs. 0.33 +/- 0.30 mm) or intravascular ultrasound-(IVUS-)measured volume obstruction (7.95 +/- 9.84% vs. 5.61 +/- 7.91%) at six months between the predilated and directly stented patients. The same was true for the patients receiving the control stent. Compared with the directly stented control group, the statistically significant positive effects of TAXUS direct stenting were maintained, regarding angiographic restenosis in the analysis segment (4.3% vs. 30.8%), late loss (0.33 +/- 0.30 vs. 0.80 +/- 0.62 mm) or IVUS-measured volume obstruction (5.61 +/- 7.91% vs. 22.50 +/- 21.62%) at six months. MACE was reduced from 19.2% to 4.3%; due to the small number of patients this trend did not reach statistical significance. After predilatation, all parameters were significantly improved by the TAXUS stent. CONCLUSION: Comparison of patients receiving TAXUS stents with or without predilatation revealed no differences in clinical, angiographic or IVUS parameters at six months. This suggests that direct stenting with the polymer-based paclitaxel-eluting TAXUS stent is feasible, safe and equally effective. Randomized trials comparing stenting after predilatation versus direct stenting with drug-eluting stents are warranted.

Angioplasty, Balloon, Coronary↗

Influence of trans-1,2-diaminocyclohexane structure and mixed carboxylic/phosphonic group combinations on samarium-153 chelation capacity and stability.

A simple procedure was developed to compare chelating agents for (153)Sm complexes as a preliminary step to synthesise bifunctional analogues. Several variables affecting the efficiency of complex stability were investigated, such as the pre-organisation concept, cavity size, and the nature of coordination sites. Four semi-rigid agents incorporating carboxylic and/or phosphonic groupings fixed at trans-1,2-diaminocyclohexane were evaluated for their (153)Sm chelation properties, and competition studies were performed. Data on the stability of the best chelating agent compound 3: trans-cyclohexane-1,2-bis(aminomethylphosphonic)-N,N'-bis(ethyl-2-iminodiacetic acid) in human serum are presented.

Carboxylic Acids↗

Formation of spherical iron(III) oxyhydroxide nanoparticles sterically stabilized by chitosan in aqueous solutions.

The interactions between the cationic polymer chitosan (Chit) and iron(III) were investigated. The solution properties were studied by pH-metry, viscometry and dynamic light scattering. Solid state iron(III)-Chit samples were also prepared and characterized by IR spectroscopy and electron microscopy. In aqueous solutions, the precipitation pH of the iron(III) oxyhydroxide (FeOOH) is significantly shifted towards the higher pH values in the presence of Chit indicating that some interaction takes place between the iron(III) and the polymer. However, the additivity of the pH-metric titration curves, the lack of variation both in the viscometric and IR spectra of Chit in the presence and absence of iron(III), indicate the lack of direct complexation between the Chit and ferric ions. Isolated FeOOH nanospheres of 5-10 nm diameter were observed on the transmission electron microscopic pictures of samples obtained from solutions containing iron(III) and Chit, while from DLS measurements hydrodynamic units with a few hundred nm in diameter were identified. Our data support that Chit acts as steric stabilizer and inhibits the macroscopic aggregation of the subcolloidal FeOOH particles. Thus the iron(III)-Chit interactions offer a simple and economic way to fabricate nanometric size FeOOH spheres, morphologically similar to the core of iron(III)-storage protein, ferritin.

Chitin↗

Contribution of Raman spectroscopy to identification of biominerals present in teeth of Acanthopleura rehderi, Acanthopleura curtisiana, and Onithochiton quercinus.

Raman spectroscopic investigations of the major lateral teeth of the chitons Acanthopleura rehderi and Acanthopleura curtisiana indicate that, in addition to the magnetite of the cutting surface and a carbonated hydroxyapatite in the central tooth core, these species deposit limonite in place of the lepidocrocite reported for other members of the genus Acanthopleura. A comparison of the spectra from these species with those of Onithochiton quercinus, which also deposits limonite, indicates that the current assignment of these species to Acanthopleura may not be appropriate. Biomineralization of the major lateral teeth may be a useful parameter to include in the taxonomic classification of chiton species.

Animals↗

Sensitivity of different thalassaemia genotypes to food mutagens in the Comet assay.

Thalassaemia is a heterogeneous group of inherited anaemias, characterised by a reduction or total absence of one or more of the globin chains of haemoglobin. Individuals with thalassaemia major require regular blood transfusions in order to maintain their haemoglobin concentration at an appropriate level. An essential treatment in parallel with transfusions is iron chelation therapy to remove excess iron deposited in tissues from the transfused blood. The high iron levels in these patients make free oxygen radicals accessible, for example, through Fenton-type chemistry, and generate superoxide and hydroxyl radicals. Increased oxygen radical capacity is known to be associated with cancer and ageing. In a previous study, it has been shown that peripheral blood lymphocytes isolated from a sickle/beta thal double heterozygote-sickle phenotype thalassaemia patient, who was not undergoing chelation therapy, showed increased sensitivity to the effects of oxygen radicals and iron salts by comparison with lymphocytes from normal controls. Furthermore, in a later study, this patient also showed increased sensitivity to the dietary food mutagen 3-amino-1-methyl-5H-pyridol(4,3-b)indole (Trp-P-2) when compared to the control. The present study, therefore, investigated whether the above observation could be duplicated using different food mutagens in different thalassaemia genotypes. The effect of the food mutagens 2-amino-2-methylimidazolo(4,5-f)quinolone (IQ) and 2-amino-1-methyl-6-phenylimidazol(4,5-b)pyridine (PhIP) on lymphocytes of three different thalassaemia patients, a beta-thalassaemia major, a beta-thalassaemia/Hb E, and an alpha-thalassaemia trait with a 3.7-kb deletion, who were not undergoing chelation therapy were investigated using the Comet assay. All three thalassaemia genotypes showed increased sensitivity to both IQ and PhIP in comparison to the control, although with PhIP at the highest two concentrations (50 and 75 microM) the differences monitored with the alpha-thalassaemia trait were found not to be statistically significant (P > 0.05).

Child, Preschool↗

Modulation by flavonoids of the effects of a food mutagen in different thalassaemia genotypes in the Comet assay.

Thalassaemia is an inherited group of disorders caused by a reduction or total absence of one or more of the globin chains of the haemoglobin molecule. It has been shown that lymphocytes isolated from a sickle/beta thal double heterozygote-sickle phenotype patient showed increased sensitivity to the dietary food mutagen 3-amino-1-methyl-5H-pyridol(4,3-b)indole (Trp-P-2) when compared to the control. Furthermore, when a combination of Trp-P-2 with either quercitin or kaempferol was compared, the responses to Trp-P-2 were reduced to untreated control levels at the highest doses of quercitin and kaempferol. It has now been shown that using the food mutagens 2-amino-2-methylimidazolo(4,5-f)quinolone (IQ) and 2-amino-1-methyl-6-phenylimidazol(4,5-b)pyridine (PhIP) on lymphocytes of three different thalassaemia patients, a beta-thalassaemia major, a beta-thalassaemia/Hb E, and an alpha-thalassaemia trait with a 3.7-kb deletion, similar increased sensitivity could also be demonstrated. The present study investigated whether the modulatory effects of the flavonoids could be demonstrated in lymphocytes isolated from a beta-thalassaemia major and a beta-thalassaemia/Hb E patient. Lymphocytes from both a beta-thalassaemia major and beta-thalassaemia/Hb E patient showed increased sensitivity to PhIP when compared to the normal control. When a combination of PhIP and either quercitin or kaempferol was used, a reduction in the responses was seen, and at the highest doses of quercitin and kaempferol the responses were reduced to near untreated control levels and were significantly different when compared to PhIP alone (P < 0.05). It was concluded that lymphocytes from different thalassaemia genotypes showed increased sensitivity to different dietary food mutagens compared to normal lymphocytes and that flavonoids such as quercitin and kaempferol modulated the effects of these food mutagens in an antigenotoxic/antioxidant manner.

Child, Preschool↗

T-bet/GATA-3 ratio as a measure of the Th1/Th2 cytokine profile in mixed cell populations: predominant role of GATA-3.

The differentiation of naive T-helper (Th) cells towards Th1 or Th2 cells is regulated by the transcription factors T-box expressed in T-cells (T-bet) and GATA-binding protein-3 (GATA-3). In the present study, the gene expression of T-bet and GATA-3 was measured by semi-quantitive reverse transcription polymerase chain reaction (RT-PCR) in Th1 and Th2 cells derived from purified splenic CD4+ T cells from DO11.10/Rag2(-/-) transgenic mice and control BioBreeding (BBc) Wistar rat splenic T cells stimulated under Th1 or Th2 conditions. In both sets of experiments, changes in the ratio of expression of T-bet and GATA-3 reflected changes in the Th1-specific cytokine interferon-gamma (IFN-gamma) and Th2-specific cytokine interleukin (IL)-4. T-bet gene expression was not maintained in fully polarized rat Th1 cells whereas GATA-3 gene expression was maintained in long-term polarized rat Th2 cells, indicating that maintenance of Th1/Th2 status occurred more as a result of altered GATA-3 mRNA expression than T-bet. These transcription factors are up-regulated in several cells that produce type 1 and type 2 cytokines and can be analyzed readily by RT-PCR using total RNA isolated from mixed cell populations or cultured splenocytes thereby providing a surrogate marker of Th1/Th2 cytokine balance under a variety of conditions.

Animals↗

A novel protein tightly bound to bacterial magnetic particles in Magnetospirillum magneticum strain AMB-1.

Magnetic bacteria synthesize magnetite crystals with species-dependent morphologies. The molecular mechanisms that control nano-sized magnetite crystal formation and the generation of diverse morphologies are not well understood. From the analysis of magnetite crystal-associated proteins, several low molecular mass proteins tightly bound to bacterial magnetite were obtained from Magnetospirillum magneticum strain AMB-1. These proteins showed common features in their amino acid sequences, which contain hydrophobic N-terminal and hydrophilic C-terminal regions. The C-terminal regions in Mms5, Mms6, Mms7, and Mms13 contain dense carboxyl and hydroxyl groups that bind iron ions. Nano-sized magnetic particles similar to those in magnetic bacteria were prepared by chemical synthesis of magnetite in the presence of the acidic protein Mms6. These proteins may be directly involved in biological magnetite crystal formation in magnetic bacteria.

Amino Acid Sequence↗

A new biomineral identified in the cores of teeth from the chiton Plaxiphora albida.

The hydrated iron(III) oxide limonite is reported for the first time as a biomineral. In situ laser Raman spectra of the tooth cores from major lateral teeth of the chiton Plaxiphora albida are compared with those of synthetic and mineral iron phosphates and iron oxides. Raman spectra measured on iron phosphate and iron oxide standard materials are shown to be easily distinguishable from one another. The central tooth cores of mature P. albida teeth do not show any evidence for the presence of a separate iron phosphate mineral. Rather, in each tooth a narrow band of the hydrated iron(III) oxide limonite is shown to separate the magnetite of the tooth surface from a central core region comprising both lepidocrocite and limonite. The high concentration of phosphorus in P. albida tooth cores, previously observed by energy dispersive spectroscopy, is not associated with a separate iron phosphate mineral, indicating that this element may be adsorbed onto the surface of the iron oxide minerals present. The failure to detect a separate iron(III) phosphate is discussed with reference to other chiton species that display high levels of iron and phosphorus in the cores of their mature major lateral teeth.

Animals↗