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Biomedical subjects

S Blair

Publications and source records attributed to S Blair.

At least 19 recordsLinked to original sources
PubMed2006

Convective flow effects on DNA biosensors.

We explore theoretic limits of convective flux effects, as a function of species concentrations and sample volume, in biosensing systems containing target species with differing affinities. A finite element method is used to simulate mass transport of DNA through a microfluidic chamber to the sensing surface where hybridization of DNA is modeled using the corresponding kinetic equations. Our results show enhancements due to convection are controlled by the concentration and sample volume of the lower affinity species, while the upper-limit of the enhancements are determined by the concentration and sample volume of the higher affinity species. Additionally, enhancements are controlled by the degree of competition between the two species, which is related to the total fraction of binding sites used.

Biosensing Techniques↗
PubMed2006

Competitive displacement of DNA during surface hybridization.

Using real-time dual-color fluorescence detection, we have experimentally tracked individual target species during competitive DNA surface hybridization in a two-component sample. Our experimental results demonstrate displacement of the lower affinity species by the higher affinity species and corroborate recent theoretical models describing competitive DNA surface hybridization. Competition at probe sites complementary to one of the two DNA species was monitored in separate experiments for two different target pairs. Each pair differs in sequence by a single nucleotide polymorphism, and one pair includes a folding target. We propose a mechanistic interpretation of the differences between hybridization curves of targets in multi-component and single-component experiments.

Binding, Competitive↗
PubMed2005

A competitive kinetic model of nucleic acid surface hybridization in the presence of point mutants.

Microarray analysis has become increasingly complex due to the growing size of arrays and the inherent cross-binding of targets. In this work, we explore the effects of matched and mismatched target species concentrations, temperature, and the time of hybridization on sensing specificity in two-component systems. A finite element software is used to simulate the diffusion of DNA through a microfluidic chamber to the sensing surface where hybridization of DNA is modeled using the corresponding kinetic equation. Comparison between a single-component system, where only one target is allowed to bind to a specific zone, and a two-component system, where more than one target can hybridize in a sensing zone, uncovers significant kinetic disparities during the transitory state; however, at thermodynamic equilibrium a modified Langmuir isotherm governs the bound amount of both species. The results presented suggest that it may be more appropriate to consider collective rather than quasi-independent interaction of targets in multicomponent systems.

Binding, Competitive↗
PubMed2005

Exposure to antineoplastic drugs in two UK hospital pharmacy units.

STUDY OBJECTIVES: To carry out an environmental and biological monitoring study in two UK hospital pharmacy units involved in the preparation of antineoplastic drugs. PARTICIPANTS AND METHODS: The two units studied used isolators for drug preparation. One used isolators operating at positive pressure relative to external atmospheric pressure, whereas the other used negative pressure isolators. Monitoring utilized the measurements of methotrexate, ifosfamide, cyclophosphamide and platinum reflecting the platino-coordinated drugs, such as cisplatin and carboplatin. Personal and static atmospheric and floor wipe samples were collected together with preshift and post-shift urine samples over a 4-day consecutive monitoring period. During the study period both units operated to their normal procedures. RESULTS: Measurable amounts of cytotoxic drugs were detected on the floors of both units and on the disposable gloves worn by staff preparing the drugs. There was also evidence in both units of some very low-level drug absorption from urine measurements, using the most sensitive analytical technique of platinum analysis. The absorption of platinum containing drugs in the unit using negative-pressure isolators was significantly higher, even though less platinum containing drug was prepared per day. Urine measurements in both units were below the detection limit for the other measured drugs. Although the unit using positive-pressure isolators handled daily approximately five times the drug quantities handled with the negative pressure unit, the general levels of external contamination and urine measurements did not reflect this difference. Comparison of the relative levels of glove and floor contamination between the two units was not clear-cut and appeared to depend on the specific cytotoxic drug being monitored. CONCLUSIONS: The levels of external contamination on the floor and gloves, and absorbed dose from urine measurements found in this study showed considerable improvement over many earlier, non-UK studies using comparable exposure measurements. These earlier studies were in facilities using laminar flow/microbiological safety cabinets and where staff were likely to be involved in both drug preparation and administration. Our data did not suggest that the differential pressure of the isolator to the pharmacy atmosphere was an overarching factor in the risk of operator exposure under normal operation. There remains a need to investigate the sources of the low-level drug contamination found in the pharmacies even when using isolators to prepare cytotoxic drugs. This study, and related studies of hospital oncology ward staff, appear to be the only recent UK studies of occupational cytotoxic drug exposure using environmental and biological monitoring techniques.

Air Pollution, Indoor↗
PubMed2003

Honey stimulates inflammatory cytokine production from monocytes.

Clinical observations indicate that honey may initiate or accelerate the healing of chronic wounds and has, therefore, been claimed to have anti-inflammatory properties. The aim of this study was to investigate the effects of honey on the activation state of immunocompetent cells, using the monocytic cell line, MonoMac-6 (MM6), as a model. We investigated the effect of each of the three honeys (manuka, pasture and jelly bush) on the release of important inflammatory cytokines from MM6 cells. These honeys, together with a sugar syrup control (artificial honey), were incubated with MM6 cells at a concentration of 1% (w/v) for 0-24h. Cell culture supernatants were tested using specific ELISA assays for tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta and IL-6. All honeys significantly increased the TNF-alpha, IL-1beta and IL-6 release from MM6 cells (and human monocytes) when compared with untreated and artificial-honey-treated cells (P<0.001). Jelly bush honey significantly induced the maximal release of each cytokine compared with manuka, pasture or artificial honeys (P<0.001). These results suggest that the effect of honey on wound healing may in part be related to the stimulation of inflammatory cytokines from monocytic cells. Such cell types are known to play an important role in healing and tissue repair.

Cell Line↗
PubMed2003

Evaluation of the mutagenicity of antimalarial products isolated from Solanum nudum (Solanaceae).

Diosgenone is a major component of the hexane extract from the plant Solanum nudum (Solanaceae). The products from degraded and acetylated diosgenone that showed in vitro antimalarial activity against the FCB-2 strain of Plasmodium falciparum and methanol, dichloromethane and ethereal extracts of Solanum nudum were tested for their mutagenic activity using the Ames test with the TA-97a, TA-98, TA-100 and TA-102 strains of Salmonella typhimurium. These compounds were not mutagenic at the tested concentrations.

Acetylation↗
PubMed2002

Antimalarial activity of neurolenin B and derivates of Eupatorium inulaefolium (Asteraceae).

Dried stems and leaves of Eupatorium inulaefolium (Austroeupatorium inulaefolium) (Asteraceae) were used to obtain four crude extracts (hexane, dichloromethane, methanol and ethanol). Two fractions were obtained from the hexane extract (S1 and S2) and three compounds (neurolenin B, lobatin A and lobatin B) from the dichloromethane extract. The ethanol, hexane, dichloromethane and methanol extracts, two fractions from the hexane extract (S1 and S2), and neurolenin B were evaluated in vitro against Plasmodium falciparum, FCB-2 strain. Two extracts (dichloromethane and methanol), the S2 fraction and neurolenin B showed statistically significant antiplasmodial activity.

Antimalarials↗
PubMed2001

Narrow-range optical pH sensors based on luminescent europium and terbium complexes immobilized in a sol gel glass.

The metal-based emission of a series of luminescent europium and terbium complexes incorporating an aromatic chromophore is rendered pH-dependent either through perturbation of the aryl singlet or triplet energy or by modulating the degree of quenching of the lanthanide excited state. Systems exhibiting each of these pathways have been incorporated in thin-film sol gel matrixes and evaluated as pH sensors in static and flow analyses at constant ionic strength. pH-dependent intensity or ratiometric methods, for emission or excitation spectra, have been defined for lanthanide complexes incorporating substituted phenanthridine (pK(a) from ca. 6.8 to 7.2) or 6-cyanophenanthridine-2-sulfonyl chromophores (pK(a) approximately 7.14 in human serum solution) (lambda(exc) 365 nm, phi H(2)O = 7.2%).

Journal Article↗
PubMed2001

Nonlinear Schrödinger equations with mean terms in nonresonant multidimensional quadratic materials.

We derive the asymptotic equations governing the evolution of a quasi-monochromatic optical pulse in a nonresonant quadratic material starting from Maxwell equations. Under rather general assumptions, equations of nonlinear Schrödinger (NLS) type with coupling to mean fields result (here called NLSM). In particular, if the incident pulse is polarized along one of the principal axes of the material, scalar NLSM equations are obtained. For a generic input, however, coupled vector NLSM systems result. Special reductions of these equations include the usual scalar and vector NLS equations. Based on results known for similar systems which arise in other physical contexts, we expect the behavior of the solutions to be characterized by a rather large variety of phenomena. In particular, we show that the presence of the coupling to the dc fields can have a dramatic effect on the dynamics of the optical pulse, and stable localized multidimensional pulses can arise through interaction with boundary terms associated to the mean fields.

Journal Article↗
PubMed2001

Second-line chemotherapy for non-small-cell lung cancer with monthly docetaxel and weekly gemcitabine: a phase II trial.

BACKGROUND: Docetaxel and gemcitabine are active against chemotherapy-pretreated non-small-cell lung cancer (NSCLC). The purpose of this phase II study was to evaluate the efficacy and safety of monthly docetaxel combined with weekly gemcitabine in NSCLC patients failing one prior regimen. PATIENTS AND METHODS: Forty patients were enrolled. Prior chemotherapy was a platinum-based combination in 36 patients, using vinorelbine in 26 patients and etoposide in 10 patients. The other four patients had prior single agents. Tumors were refractory or resistant to front-line therapy in 80% of patients. Treatment was gemcitabine 800 mg/m2 days 1, 8, 15 and docetaxel 100 mg/m2 day 1, with cycles repeated every four weeks. RESULTS: Thirteen patients responded (32.5%; 95% confidence interval (CI): 19%-49%), including one complete and 12 partial responses. Responses were observed at all metastatic sites, with similar response frequencies in platinum-sensitive and platinum-resistant/refractory tumors. The median time to progression for responders was nine months, with two responses lasting longer than a year. Median survival was 8.1 months. Hematologic toxicities included grade 4 neutropenia in 23 patients, with 4 episodes of febrile neutropenia, grade 3-4 thrombocytopenia in 9 patients, and anemia requiring red cell transfusions in 9 patients. With the exception of asthenia, severe non-hematologic toxicities were infrequent. CONCLUSIONS: Monthly docetaxel, combined with weekly gemcitabine, is an active and safe second-line therapy for NSCLC patients.

Adult↗
PubMed2001

Effect of Solanum nudum extracts on the liver of mice infected with Plasmodium berghei.

The plant Solanum nudum has been used by the community of Tumaco (Nariño, Colombia) as a cure for malaria. Our group has confirmed the in vitro antimalarial activity against the strain of Plasmodium falciparum FCB-2. During our in vivo studies on the therapeutic effect of Solanum nudum extracts on mice infected with Plasmodium berghei, we observed yellowish tint in the palms of mice treated with the aqueous extract via i.p. at a concentration of 2.4% w/vol. This finding suggested the need to carry out a histology study of the liver. Plasmodium berghei infection produces liver changes such as the deposit of pigment in sinusoids, leucocytes infiltration, esteatosis and necrosis of hepatocytes. These changes were also observed when the mice were treated with methane and hexane extracts from Solanum nudum; however necrosis of hepatocytes in mice infected with malaria decreased 47-65% when they were administered either with aqueous extract, or tumacoside A and degraded diosgenone, compounds from methane and hexane extracts of Solanum nudum respectively.

Animals↗
PubMed2001

[Resistance of Plasmodium falciparum to 3 antimalarials in Turbo (Antioquia, Colombia), 1998].

In 1998 we determined in vivo and in vitro the frequency and the degree of resistance of Plasmodium falciparum to the three antimalarials (chloroquine, amodiaquine, and sulfadoxine/pyrimethamine) most utilized in the municipality of Turbo (in the area of Urabá, Antioquia, Colombia), in a sample representative of the population with malaria. We carried out clinical and parasitological analyses over a 14-day period using the standard test recommended by the World Health Organization. In vivo, P. falciparum showed resistance to chloroquine, amodiaquine, and sulfadoxine/pyrimethamine, with a frequency of 97%, 7%, and 13%, respectively. In vitro, the corresponding figures were 21%, 23%, and 9%, respectively. For chloroquine the level of agreement between the in vivo and in vitro results was 23%.

Adolescent↗
PubMed2001

Determination of gamma-hydroxybutyrate in water and human urine by solid phase microextraction-gas chromatography/quadrupole ion trap spectrometry.

A simple method of detection was developed for gamma-hydroxybutyrate (GHB). The method involves the derivatization of GHB using a hexyl-chloroformate procedure in aqueous media (such as water or urine), extraction of the derivatization product directly from the sample using solid-phase microextraction, and subsequent separation and detection with gas chromatography quadrupole ion trap mass spectrometry. The deuterated form of GHB (GHB-D6) is used as an internal standard for quantitation. The method was linear for GHB-spiked pure water samples from 2 to 150 microg/mL GHB with a detection limit of 0.2 microg/mL. Spiked urine samples showed linearity from 5 to 500 microg/mL GHB with a detection limit of 2 microg/mL. The SPME-GC/MS method is applied to actual case samples, and the results are compared to those values obtained using a conventional GC/MS method. Sensitivity and linearity are comparable to those seen using traditional methods of separation, yet the SPME method is superior due to the simplicity, speed of analysis, reduction in solvent waste, and ability to differentiate between GHB and gamma-butyrolactone (GBL).

Anesthetics, Intravenous↗
PubMed2001

Evaluation of mutagenic activity of several antimalarial extracts from Eupatorium inulaefolium.

Eupatorium inulaefolium is used as an antimalarial agent by traditional healers of the Tumaco region (Nariño-Colombia). Several extracts of this plant have been tested by our laboratory and in vitro antimalarial activity against the FCB-2 strain of Plasmodium falciparum has been confirmed. For this reason, the mutagenic effect of the methanol, dichloromethane, and hexane extracts of Eupatorium inulaefolium (number 83377 university of Antioquia herbarium) were evaluated using the Ames test. None of the extracts evaluated had mutagenic effects on TA-98 or TA-100 strains of Salmonella typhimurium.

Animals↗
PubMed2000

Transanal excision for low rectal cancers is curative in early-stage disease with favorable histology.

Controversy still exists as to the optimal treatment of early-stage low rectal cancers. Standard resections such as abdominal perineal resections or low anterior resection with coloanal anastomosis can be associated with significant morbidity. Local excision has been considered as a potentially far less morbid option for these patients. We identified 20 patients from our prospective tumor registry database that underwent transanal resection of early rectal cancers between 1988 and 1998. Five patients had carcinoma in situ, and 15 patients had T1 lesions. All T1 lesions were well or moderately well differentiated, and none had lymphovascular invasion. The mean tumor size was 2.65 cm, and the average distance from the anal verge was 4.55 cm. One patient required temporary colostomy because of postoperative complications. Four patients had postoperative adjuvant therapy (radiation alone, two; radiation and chemotherapy, two) for close margins after they refused an abdominal perineal resection. With a median follow-up of 60 months there were no recurrences and no cancer-related deaths. This series suggests that transanal excision is a safe and effective treatment for selected early low rectal cancers with favorable histology.

Adenocarcinoma↗
PubMed1997

Prevention of hepatic tumor metastases in rats with herpes viral vaccines and gamma-interferon.

Previous studies showed that gammaIFN decreases metastatic hepatic tumor growth by stimulating Kupffer cells (KC). The present studies examine whether lymphocyte stimulation via cells engineered to secrete GM-CSF or IL-2 decreases hepatic tumor growth, and whether stimulation of both macrophages and lymphocytes is more effective than either individually. Rats were immunized with irradiated hepatoma cells transduced by herpes viral amplicon vectors containing the genes for GM-CSF, IL-2 or LacZ. On day 18, half of each group was treated with 5 x 10(4) U gammaIFN, or saline intraperitoneally for 3 d. On day 21, all rats received 5 x 10(5) hepatoma cells intrasplenically. On day 41, rats were killed and tumor nodules were counted. Separate rats underwent splenocyte and KC harvest for assessment of lymphocyte- and macrophage-mediated tumor cell kill in vitro. GM-CSF or IL-2 vaccines or gammaIFN decreased tumor nodules significantly (GM-CSF 13+/-4, IL-2 14+/-6 vs. control 75+/-24, P < 0.001). Combination therapy was more effective, and completely eliminated tumor in 4 of 12 IFN-GM-CSF and 8 of 11 IFN-IL-2 animals. Additional rats underwent partial hepatectomy, an immunosuppressive procedure known to accelerate the growth of hepatic tumor, following tumor challenge. Therapy was equally effective in this immunosuppressive setting. Vaccination is associated with enhancement of splenocyte-mediated tumoricidal activity, whereas the effect of gammaIFN is mediated by KC. GM-CSF and IL-2 vaccine therapy and pretreatment with gammaIFN represent effective strategies in reducing hepatic tumor. Combination therapy targets both lymphocytes and macrophages, and is more effective in reducing tumor than either therapy alone.

Animals↗
PubMed1997

Chronic illness in adolescents: transfer or transition to adult services?

It is widely believed that the improved survival of young people with chronic diseases will be associated with the development of appropriate services within the adult healthcare domain. There is, however, little evidence to suggest that this is happening at a rate commensurate with clinical requirements. This paper highlights the multiplicity of barriers that impede the development of transition services to facilitate the transfer of medical care from the paediatric to the adult domain. Different models of transition care are described, and the terms 'transfer' and 'transition' are differentiated. The clinical demand for service development is highlighted, as well as the need for specific research in this area of healthcare delivery.

Adolescent↗