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Biomedical subjects

D C Smith

Publications and source records attributed to D C Smith.

At least 19 recordsLinked to original sources
PubMed2005

Dissolved oxygen saturation controls PAH biodegradation in freshwater estuary sediments.

Polycyclic aromatic hydrocarbons (PAHs) are common contaminants in terrestrial and aquatic environments and can represent a significant constituent of the carbon pool in coastal sediments. We report here the results of an 18-month seasonal study of PAH biodegradation and heterotrophic bacterial production and their controlling biogeochemical factors from 186 sediment samples taken in a tidally influenced freshwater estuary. For each sampling event, measurements were averaged from 25-45 stations covering approximately 250 km(2). There was a clear relationship between bacterial production and ambient temperature, but none between production and bottom water dissolved oxygen (DO) % saturation or PAH concentrations. In contrast with other studies, we found no effect of temperature on the biodegradation of naphthalene, phenanthrene, or fluoranthene. PAH mineralization correlated with bottom water DO saturation above 70% (r(2) > 0.99). These results suggest that the proportional utilization of PAH carbon to natural organic carbon is as much as three orders of magnitude higher during cooler months, when water temperatures are lower and DO % saturation is higher. Infusion of cooler, well-oxygenated water to the water column overlying contaminated sediments during the summer months may stimulate PAH metabolism preferentially over non-PAH organic matter.

Bacteria↗
PubMed2004

Does leucocyte depletion during cardiopulmonary bypass improve oxygenation indices in patients with mild lung dysfunction?

BACKGROUND: Leucocyte-depleting arterial line filters have not dramatically improved lung function after cardiopulmonary bypass (CPB), but patients with pre-existing lung dysfunction may benefit from their use. METHODS: We randomized 32 patients with mild lung dysfunction having elective first-time coronary revascularization to either a leucocyte depleting or a standard 40-mm arterial line filter during CPB. The alveolar arterial oxygenation index was calculated before and 5 min after CPB, then at 1, 2, 4, 8, and 18 h after surgery. Time to extubation on the ITU was recorded. Preoperative, immediate postoperative, and 24 h postoperative chest x-rays were scored for extravascular lung water. RESULTS: Postoperative alveolar-arterial oxygenation indices were better in the patients who received leucocyte depletion during CPB (1.65+/-0.96 in the study group vs 2.90+/-1.72 in the control group, P<0.05). The duration of postoperative mechanical ventilation was less in the leucocyte-depleted group (4.8+/-2.1 vs 8.3+/-4.7 h in the control group, P<0.05). The extravascular lung water scores immediately postoperatively were 13.0+/-8.6 in the study group vs 19.6+/-10.8 in the control group (P=0.04), and at 24 h postoperatively, 9.7+/-7.7 vs 15.2+/-9.9 for controls. CONCLUSIONS: For patients with mild lung dysfunction, a leucocyte-depleting arterial line filter improves postoperative oxygenation, reduces extravascular lung water accumulation, and reduces time on artificial ventilator after CPB. There may be an economic argument for the routine use of leucocyte-depleting filters for every patient during CPB.

Adolescent↗
PubMed2004

Poly(N-vinylpyrrolidone)-block-poly(D,L-lactide) as a new polymeric solubilizer for hydrophobic anticancer drugs: in vitro and in vivo evaluation.

The majority of novel anticancer drugs developed to date are intended for parenteral administration. Paradoxically, most of these drugs are water-insoluble, delaying their clinical development. A common approach to confering water solubility to drugs is to use amphiphilic, solubilizing agents, such as polyethoxylated castor oil (e.g., Cremophor EL, CrmEL). However, these vehicles are themselves associated with a number of pharmacokinetic and pharmaceutical concerns. The present work is aimed at evaluating a novel polymeric solubilizer for anticancer drugs, i.e., poly(N-vinylpyrrolidone)-block-poly(D,L-lactide) (PVP-b-PDLLA). This copolymer self-assembles in water to yield polymeric micelles (PM) that efficiently solubilize anticancer drugs, such as paclitaxel (PTX), docetaxel (DCTX), teniposide (TEN) and etoposide (ETO). A PM-PTX formulation was evaluated, both, in vitro on three different cancer cell lines and in vivo for its safety, pharmacokinetics, biodistribution and antitumor activity. In vitro, cytotoxicity studies revealed that the drug-loaded PM formulation was equipotent to the commercial PTX formulation (Taxol). In the absence of drug, PVP-b-PDLLA with 37% DLLA content was less cytotoxic than CrmEL. In vivo, acute toxicity was assessed in mice after a single injection of escalating dose levels of formulated PTX. PM-PTX was well tolerated and the maximum tolerated dose (MTD) was not reached even at 100 mg/kg, whereas the MTD of Taxol was established at 20 mg/kg. At 60 mg/kg, PM-PTX demonstrated greater in vivo antitumor activity than Taxol injected at its MTD. Finally, it was shown in mice and rabbits that the areas under the plasma concentration-time curves were inversely related to PM drug loading.

Animals↗
PubMed2004

Optical properties of mesoporous II-VI semiconductor compound films.

Direct liquid crystal templating from non-ionic polyoxyethylene surfactants has been utilised to produce well-defined birefringent films of nanostructured cadmium telluride films which displayed good optical properties as evidenced by UV/VIS reflectance spectroscopy.

Journal Article↗
PubMed2004

Does the use of leucocyte depletion during cardiopulmonary bypass affect exhaled nitric oxide production?

Fifty patients undergoing elective coronary revascularisation were prospectively randomised to receive either a leucocyte-depleting or a control filter inserted into the arterial line of the cardiopulmonary bypass (CPB) circuit. The concentration of exhaled nitric oxide (NO) was measured 15 min before and 30 min after CPB using a real-time chemiluminescence analyser (Logan Research, Northampton, UK). The baseline rate of exhaled NO production was 2.14 +/- 0.83 ppb/s in the control group, and 2.58 +/- 0.53 ppb/s in leucocyte-depleted group (p = 0.17). Following CPB, the mean rate of exhaled NO production in the control group had increased by 1.51 +/- 0.45 ppb/s to 3.65 +/- 0.81 ppb/s and in the leucocyte- depletion group had increased by 1.05 +/- 0.45 ppb/s to 3.64 +/- 0.62 ppb/s. The increase in exhaled NO production was significantly lower in the leucocyte depleted group (p = 0.002), indicating that leucocyte depletion suppressed the increase in exhaled NO production seen following CPB.

Aged↗
PubMed2003

RAPD markers linked to eastern filbert blight resistance in Corylus avellana.

A total of 1,110 decamer primers were screened for RAPD markers linked to a dominant allele in hazelnut ( Corylus avellana) that confers resistance to eastern filbert blight caused by Anisogramma anomala. Twenty RAPD markers linked in coupling, and five markers linked in repulsion, were found. A seedling population was used to construct a linkage map of the region flanking the resistance locus. The map spans 46.6 cM, with 14 markers on one side of the resistance locus and eight on the other side. Eleven markers showed less than 3% recombination with resistance, including three that showed no recombination. Seven of these 11 markers are sufficiently robust to allow their use in marker-assisted selection. These include AA12(850) which shows no recombination, and six markers on one side of the resistance locus: 173(500), 152(800), 122(825), 275(1130), H19(650) and O16(1250). Marker 268(580), which flanks the resistance locus on the other side, is also suitable for use in marker-assisted selection, but shows 5.8% recombination with resistance. Other markers are less suitable for marker-assisted selection because of sensitivity to changes in primer or MgCl(2) concentration, or the long time required for electrophoresis to separate bands of similar size. The 16 markers closest to the resistance locus were cloned and sequenced. The W07(365) marker, which showed no recombination with the resistance locus but is difficult to score, includes a CT microsatellite repeat. The sequence information will allow the design of SCAR primers and eventual map-based cloning of the resistance allele.

Base Sequence↗
PubMed2003

Catalogue of 45 reference Raman spectra of minerals concerning research in art history or archaeology, especially on corroded metals and coloured glass.

Small catalogues of reference Raman spectra of interest for analysing geomaterials or biomaterials of relevance to art history or archaeology are gradually being published by different research groups. However, except for some older catalogues, they are all concerned primarily with pigments, whether inorganic or organic. Here we present for the first time a catalogue of Raman spectra of minerals that may be found in corroded metal artworks or artefacts. At the same time we include some inorganic pigments that may be found in or on stained glass. Most of the minerals analysed came from the Gallery of Mineralogy at the Muséum National d'Histoire Naturelle and most were verified by X-ray diffraction in order to augment the confidence in the mineral identity (which is not the case with many other catalogues). A number of problems encountered with mineral terminology are discussed. Comments are made on the spectra where appropriate.

Archaeology↗
PubMed2003

Retrograde transport of toxins across the endoplasmic reticulum membrane.

Several protein toxins, including the A chain of the plant protein ricin (RTA), enter mammalian cells by endocytosis and catalytically modify cellular components to disrupt essential cellular processes. In the case of ricin, the process inhibited is protein synthesis. In order to reach their cytosolic substrates, several toxins undergo retrograde transport to the ER (endoplasmic reticulum) before translocating across the ER membrane. To achieve this export, these toxins exploit the ERAD (ER-associated protein degradation) pathway but must escape, at least in part, the normal degradative fate of ERAD substrates in order to intoxicate the cell. Toxins that translocate from the ER have an unusually low lysine content that reduces the likelihood of ubiquitination and ubiquitin-mediated proteasomal degradation. We have changed the two lysyl residues normally present in RTA to arginyl residues. Their replacement in RTA did not have a significant stabilizing effect on the protein, suggesting that the endogenous lysyl residues are not sites for ubiquitin attachment. However, when four additional lysyl residues were introduced into RTA in a way that did not compromise the activity, structure or stability of the toxin, degradation was significantly enhanced. Enhanced degradation resulted from ubiquitination that predisposed the toxin to proteasomal degradation. Treatment with the proteasomal inhibitor lactacystin increased the cytotoxicity of the lysine-enriched RTA to a level approaching that of wild-type RTA.

Endoplasmic Reticulum↗
PubMed2001

Phase I trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer.

PURPOSE: The primary objective of this phase I trial was to determine the maximum-tolerated dose of radiation that could be delivered to the primary tumor concurrent with full-dose gemcitabine in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Thirty seven patients with unresectable (n = 34) or incompletely resected pancreatic cancer (n = 3) were treated. Gemcitabine was administered as a 30-minute intravenous infusion at a dose of 1,000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. Radiation therapy was initiated on day 1 and directed at the primary tumor alone, without prophylactic nodal coverage. The starting radiation dose was 24 Gy in 1.6-Gy fractions. Escalation was achieved by increasing the fraction size in increments of 0.2 Gy, keeping the duration of radiation constant at 3 weeks. A second cycle of gemcitabine alone was intended after a 1-week rest. RESULTS: Two of six assessable patients experienced dose-limiting toxicity at the final planned dose level of the trial (42 Gy in 2.8-Gy fractions), one with grade 4 vomiting and one with gastric/duodenal ulceration. Two additional patients at this dose level experienced late gastrointestinal toxicity that required surgical management. CONCLUSION: The final dose investigated (42 Gy) is not recommended for further study considering the occurrence of both acute and late toxicity. However, a phase II trial of this novel gemcitabine-based chemoradiotherapy approach, at a radiation dose of 36 Gy in 2.4-Gy fractions, is recommended on the basis of tolerance, patterns of failure, and survival data.

Adenocarcinoma↗
PubMed2001

Chemotherapy in patients with prostate specific antigen-only disease after primary therapy for prostate carcinoma: a phase II trial of oral estramustine and oral etoposide.

BACKGROUND: A Phase II study was initiated to evaluate the effectiveness of an oral regimen of etoposide and estramustine in patients with early recurrent prostate carcinoma. METHODS: Patients with early recurrent prostate carcinoma as indicated by an increasing prostate specific antigen (PSA) level and without any evidence of metastatic disease were treated with oral etoposide 50 mg/m2/day and estramustine 15 mg/kg/day in divided doses for 21 days, followed by a 7-day rest period. Patients received a maximum of four cycles. RESULTS: Eighteen patients were entered in this study. The median serum PSA was 3.1 (range, 0.3-30.3) at the time of entry into the trial. Sixteen patients were assessable for response. Serum PSA declined to undetectable levels in 13 patients with 2 additional patients meeting the criteria for partial response; the median duration of response was 8.5 months (range, 1-18 months). Most patients developed gastrointestinal, cardiac, or hematologic complications. Grade 3 toxicities included neutropenia (one patient), deep venous thrombosis (three patients), and chest pain (one patient). One patient developed acute myelogenous leukemia (French-American-British, acute myelogenous leukemia M5) 23 months after initiating the chemotherapy. CONCLUSIONS: The combination of oral etoposide and oral estramustine resulted in a high rate but only a short duration of response in patients with early recurrent prostate carcinoma. The regimen was poorly tolerated, and the toxicity was significant. This regimen should not be considered standard therapy for the treatment of early recurrent prostate carcinoma, but further exploration of treatment in this setting is warranted.

Administration, Oral↗
PubMed2001

Combination paclitaxel, carboplatin, and gemcitabine is an active treatment for advanced urothelial cancer.

PURPOSE: To determine the efficacy and toxicity of the drug combination of carboplatin, paclitaxel, and gemcitabine in patients with advanced urothelial carcinoma. PATIENTS AND METHODS: Patients eligible included those with advanced urothelial malignancy of any histology, no previous chemotherapy for metastatic disease, Southwest Oncology Group performance status of 2 or less, serum creatinine levels of 2 mg/dL or less, and adequate bone marrow and hepatic function. Treatment consisted of paclitaxel 200 mg/m2, carboplatin (target area under the curve = 5) on day 1, and gemcitabine 800 mg/m2 on days 1 and 8, repeated every 21 days. RESULTS: Forty-nine patients (44 men and five women) were enrolled; the patients' median age was 63 years, and their median creatinine clearance was 78 mL/min (range, 26 to 165 mL/min). Forty-three patients had transitional cell carcinoma, and six had squamous cell carcinoma or mixed histology. Ten patients had metastases to lymph nodes only, six had locally advanced disease, four had locally recurrent disease, 24 patients had visceral metastases, and five had soft tissue metastases. Twenty-one patients had disease in one site, 16 in two sites, and 12 in three sites. A total of 272 cycles were administered (median, six cycles; range, 1 to 15 cycles). Major toxicities were grade 3 and 4 neutropenia in 17 and 19 patients, respectively; grade 3 and 4 thrombocytopenia in 15 and six patients, respectively; grade 3 and 4 anemia in 10 and two patients, respectively; grade 3 neuropathy in four patients; and diarrhea in two patients. The incidence of febrile neutropenia was 1.4%; no patients died of drug toxicity. Forty-seven of the 49 patients were assessable for response. Fifteen (32%) patients experienced a complete response, and 17 (36%) patients experienced a partial response (32 of 47 patients, 68%; 95% confidence interval, 56.27 to 82.86). Responses were seen in all sites, including 15 (68%) of 22 patients with visceral metastases. The median survival was 14.7 months, with a 1-year survival of 59%. CONCLUSION: Combination paclitaxel, carboplatin, and gemcitabine is active; an encouraging number of patients with advanced urothelial carcinoma treated with this regimen experienced complete remission.

Adult↗
PubMed2001

A novel tandem quadrupole mass spectrometer allowing gaseous collisional activation and surface induced dissociation.

A novel tandem quadrupole mass spectrometer is described that enables gaseous collision-induced dissociation (CID) and surface-induced dissociation (SID) experiments. The instrument consists of a commercially available triple quadrupole mass spectrometer connected to an SID region and an additional, orthogonal quadrupole mass analyser. The performance of the instrument was evaluated using leucine-enkephalin, allowing a comparison between CID and SID, and with previous reports of other SID instruments. The reproducibility of SID data was assessed by replicate determinations of the collision energy required for 50% dissociation of leucine-enkephalin; excellent precision was observed (standard deviation of 0.6 eV) though, unexpectedly, the reproducibility of the equivalent figure for CID was superior. Several peptides were analysed using SID in conjunction with liquid secondary-ion mass spectrometry or electrospray; a comparison of the fragmentation of singly protonated peptide ions and the further dissociation of y-type fragments was consistent with the equivalence of the latter fragments to protonated peptides. Few product ions attributable to high-energy cleavages of amino acid side-chains were observed. The SID properties were investigated of a series of peptides differing only in the derivatization of a cysteine residue; similar decomposition efficiencies were observed for all except the cysteic acid analogue, which demonstrated significantly more facile fragmentation.

Amino Acid Sequence↗
PubMed2001

Adjuvant and neoadjuvant therapy in prostate cancer.

While surgery and radiation therapy remain the only definitive treatments for prostate cancer, single modality therapy has been associated with high failure rates in patients with aggressive disease. Although hormonal therapy has been effective in cases of metastatic disease, the timing of treatment with respect to definitive therapy remains controversial. This review will explore the efficacy of hormonal and chemotherapy in both the adjuvant and neoadjuvant settings. A MEDLINE search was performed to identify pertinent articles regarding both adjuvant and neoadjuvant therapy in prostate cancer. Articles of historical relevance in addition to those using large patient numbers with a randomized design were reviewed preferentially. Since hormonal therapy has been considered standard treatment at the time of cancer progression after definitive therapy, many of the randomized trials essentially compared adjuvant therapy to delayed therapy. Historical trials using adjuvant hormonal therapy have been limited due to difficulties in clinical staging, as well as toxicities attributed to the formulations used. More recently, hormonal therapy has been found to delay disease progression, increase disease-free survival, and decrease mortality when given immediately after prostatectomy or radiation therapy in selected patients. Neoadjuvant hormonal therapy can improve disease-free survival and local control when given before radiation therapy; it has only decreased positive surgical margins when given prior to radical prostatectomy. Although hormonal therapy given immediately after either radical prostatectomy or radiation therapy is highly effective, the side effects of persistent long-term use must be weighed for each patient. While the use of chemotherapy has been limited by the lack of active agents, newer combinations have shown effectiveness in patients with hormone refractory disease, raising the possibility of their use in the adjuvant setting.

Antineoplastic Agents↗
PubMed2001

Angioplasty or stent placement in the proximal common iliac artery: is protection of the contralateral side necessary?

PURPOSE: To determine if protection of the contralateral common iliac artery is necessary when performing angioplasty or stent placement in a proximal common iliac artery. MATERIALS AND METHODS: A retrospective review of all patients undergoing endovascular treatment for unilateral common iliac artery stenosis or occlusion from 1979 to 2000 was performed. All angiograms were reviewed independently by three experienced vascular interventional radiologists who evaluated both common iliac arteries before and after angioplasty or stent placement. RESULTS: The medical records or angiograms of 514 patients were located. Of these, complete records and angiograms were found for 175 patients who underwent proximal (within 2 cm of its origin) common iliac artery angioplasty or stent placement without treatment or protection of the contralateral common iliac artery. Treatment of proximal common iliac stenosis in 160 patients resulted in luminal compromise of the contralateral common iliac in two patients (17% and 24% reduction in luminal diameter). No contralateral compromise was noted in 15 patients treated for iliac occlusion. CONCLUSION: The data reported herein suggest that protection of the contralateral common iliac artery during angioplasty or stent placement in a proximal common iliac artery is not mandatory.

Angioplasty, Balloon, Coronary↗
PubMed2001

Sheathless technique of Ash Split-Cath insertion.

A novel technique for insertion of the Ash Split-Cath without a peel-away sheath to decrease the potential for air embolism is described. A retrospective review of 62 attempted Ash Split-Cath insertions at three hospitals was made. Conversion to the usual technique using a sheath was necessary in four cases, mostly because of extensive scarring from previous catheters. There was no air embolus, hematoma, or immediate catheter malfunction. The authors believe that the occurrence of air embolism during placement of Ash Split-Cath may be lessened by eliminating the use of a peel-away sheath.

Catheterization, Central Venous↗