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Biomedical subjects

D Lewis

Publications and source records attributed to D Lewis.

At least 73 records · Page 4Linked to original sources
PubMed1999

Cats increase fatty acid oxidation when isocalorically fed meat-based diets with increasing fat content.

This study tested the hypothesis that sedentary cats have the ability to adapt to high-fat carnivore diets by increasing fat oxidation. Twenty-four hour indirect calorimetry was used to determine total energy expenditure (TEE) and macronutrient oxidation in six vasectomized male (VAS) and six ovariectomized female (OVX) cats isocalorically fed lower-fat (53% fat, 45% protein) and higher-fat (71% fat, 26% protein) meat-based diets at maintenance for 8 days. Fat oxidation increased linearly with fat intake with a mean slope of 0.91 g fat oxidized/g fat intake (P < 0.001), with no change in TEE. However, VAS male cats were able to more precisely match fat oxidation with fat intake than OVX female cats (P < 0.02). Body fat content did not significantly influence fat oxidation. These results demonstrate that cats maintain body weight during short-term isocaloric feeding of a high-fat carnivore-type diet in part by increasing fat oxidation commensurate with increases in fat intake. This ability may be an important mechanism underlying the resistance of cats to obesity, despite habitual consumption of high-fat diets.

Animals↗
PubMed1999

Characterization of ionotropic glutamate receptors in rat hypothalamus, pituitary and immortalized gonadotropin-releasing hormone (GnRH) neurons (GT1-7 cells).

Evidence from various sources suggested that the Gonadotropin-Releasing Hormone (GnRH) neuron does not contain glutamate receptors. Northern analysis of the hypothalamus showed the presence of NMDAR1, GluR1, GluR4 and GluR6 mRNA, while the pituitary showed the presence of NMDAR1, GluR1 and GluR6 mRNA. Western blot analysis also showed the presence of NMDAR1 and GluR1 protein. Since there are relatively few GnRH neurons in the hypothalamus, and GT1-7 cells have been considered to be a GnRH neuronal cell line, GT1-7 cells were studied in detail. GT1-7 cells contained NMDAR1 mRNA levels as shown by Northern analysis but did not contain GluR1, GluR4, or GluR6 mRNA. They did not show the presence of NMDAR1 and GluR1 protein by Western analysis. In addition, GT1-7 cells showed no NMDA receptor binding using the competitive inhibitor CGP-39563 and the noncompetitive inhibitor MK-801. Likewise, no binding was detected for kainate receptors. However, a small amount of binding for AMPA receptors was found in GT1-7 cells. GT1-7 cells did not exhibit glutamate toxicity and NMDA failed to elicit inward currents using patch-clamp techniques, although GABA did induce currents in the cells. As a whole, these studies suggest that GT1-7 cells lack or possess only low levels of ionotropic glutamate receptors.

Animals↗
PubMed1999

Safety and antitumor activity of recombinant soluble Apo2 ligand.

TNF and Fas ligand induce apoptosis in tumor cells; however, their severe toxicity toward normal tissues hampers their application to cancer therapy. Apo2 ligand (Apo2L, or TRAIL) is a related molecule that triggers tumor cell apoptosis. Apo2L mRNA is expressed in many tissues, suggesting that the ligand may be nontoxic to normal cells. To investigate Apo2L's therapeutic potential, we generated in bacteria a potently active soluble version of the native human protein. Several normal cell types were resistant in vitro to apoptosis induction by Apo2L. Repeated intravenous injections of Apo2L in nonhuman primates did not cause detectable toxicity to tissues and organs examined. Apo2L exerted cytostatic or cytotoxic effects in vitro on 32 of 39 cell lines from colon, lung, breast, kidney, brain, and skin cancer. Treatment of athymic mice with Apo2L shortly after tumor xenograft injection markedly reduced tumor incidence. Apo2L treatment of mice bearing solid tumors induced tumor cell apoptosis, suppressed tumor progression, and improved survival. Apo2L cooperated synergistically with the chemotherapeutic drugs 5-fluorouracil or CPT-11, causing substantial tumor regression or complete tumor ablation. Thus, Apo2L may have potent anticancer activity without significant toxicity toward normal tissues.

Animals↗
PubMed1999

Domiciliary dental care.

Domiciliary dental care is an important and growing area of treatment provision. However, adequate training is required in order to develop the knowledge and skills necessary to perform such care. This article draws attention to the likely increase in demand for domiciliary dental care services and the reasons for it; and highlights the issues and skills involved for dentists, hygienists and their teams in providing domiciliary dental care in order to facilitate quality of care and safe practice.

Delivery of Health Care↗
PubMed1999

Effect of ipratropium bromide treatment on oxygen saturation and sleep quality in COPD.

STUDY OBJECTIVES: Patients with COPD are at risk of experiencing a deterioration in arterial oxygen saturation (SaO2) during sleep, which is generally most pronounced during rapid eye movement (REM) sleep. Increased cholinergic tone has been suggested as a contributing factor to this decrease in SaO2. Therefore, we investigated whether 4-week treatment with ipratropium bromide inhalation solution 0.02% (qid) could improve sleep characteristics in COPD. DESIGN: Randomized, placebo-controlled, double-blind, two-arm parallel study of 4 weeks of treatment with ipratropium bromide solution or placebo. SETTING: Multicenter investigation. PATIENTS: Thirty-six patients with moderate-to-severe COPD (FEV1 < 65% of predicted). MEASUREMENTS AND RESULTS: Evaluation included polysomnographic, pulmonary function, and subjective quality of sleep (visual analog scale [VAS]) assessments. It was found that 4 week of treatment with ipratropium bromide solution in patients with COPD led to the following: (1) a significant (p = 0.05) improvement in mean nocturnal SaO2 with the more severe the nocturnal desaturation, the greater the improvement in SaO2; (2) significant (p = 0.03) improvement in perceived sleep quality (VAS: 5.5 +/- 0.5 after placebo; 7.2 +/- 0.5 after ipratropium); (3) a significant (p = 0.05) increase in REM sleep time (48.6 +/- 6.3 min after placebo; 66.5 +/- 6.4 min after ipratropium) with no effect on other sleep stages or total sleep time; and (4) a significant (p = 0.01) increase in pre-sleep FVC and flow rate at 50% of the vital capacity. CONCLUSIONS: These findings demonstrate that ipratropium bromide therapy can improve sleep SaO2 as well as sleep quality in patients with moderate-to-severe COPD.

Adult↗
PubMed1999

The detection of cocaine in hair specimens using micro-plate enzyme immunoassay.

The analysis of hair for drugs of abuse is becoming increasingly popular and is under consideration by the Division of Health and Human Services as a possible alternative or adjunct to urinalysis in workplace programs. The detection of cocaine in human hair using a commercially available micro-plate enzyme immunoassay is described for the first time. Sample size and incubation time were the major variables in the optimization of the method. In order to validate the procedure, the method was applied to 105 consecutive hair samples routinely received into our laboratory. The samples were simultaneously analyzed by the Micro-Plate immunoassay (EIA), as well as our current fluorescence polarization immunoassay (FPIA) procedure and gas chromatography-mass spectrometry (GC/MS). The sensitivity of the EIA and FPIA assays were 75% and 67.8% respectively; specificity 97.4% and 80.5% respectively; and efficiency 91.4 and 77.1% respectively. The Micro-Plate EIA was shown to be a valid alternative to other immunoassay screening methods for the detection of cocaine in hair by demonstrating increased sensitivity, specificity and efficiency over our current technique.

Cocaine↗
PubMed1999

The HIV patient in general dental practice.

General practitioners, especially those working in areas where there is a high incidence of HIV, will inevitably have to face patients who may or may not know that they are HIV antibody positive. This paper gives some guidelines on how to approach the problem, using two case scenarios.

Adult↗
PubMed1998

Determination of drugs of abuse in meconium.

Fetal exposure to drugs has many adverse effects upon the neonate including low birthweight, small head size and an increased risk of miscarriage and death. Correct diagnosis of drug use during pregnancy is essential if the child is to receive specialized treatment and care, which will aid in learning and behavioral development. Diagnosis will also help in the prevention of subsequent drug-exposed children being born to the same mother. Meconium is the first fecal material excreted by the newborn and is an excellent depository for drugs to which the fetus has been exposed. Its analysis is widely accepted in the scientific and medical communities since it has several advantages over urinalysis, including providing a longer historical record of drug exposure and easier collection. Various drugs and their metabolites have been detected in meconium, however, the metabolic profile of drugs in meconium differs from that of neonatal and/or maternal urine. This article addresses the determination of cocaines, amphetamines, opiates, cannabinoids, phencyclidine, nicotine and methadone in meconium using several analytical procedures including immunochemical and chromatographic methods.

Amphetamines↗
PubMed1998

Direct demonstration of Ca2+ binding defects in sarco-endoplasmic reticulum Ca2+ ATPase mutants overexpressed in COS-1 cells transfected with adenovirus vectors.

Single mutations of specific amino acids within the membrane-bound region of the sarco-endoplasmic reticulum Ca2+ (SERCA)-1 ATPase interfere with Ca2+ inhibition of ATPase phosphorylation by Pi (1), suggesting that these residues may be involved in complexation of two Ca2+ that are known to bind to the enzyme. However, direct measurements of Ca2+ binding in the absence of ATP have been limited by the low quantities of available mutant protein. We have improved the transfection efficiency by means of recombinant adenovirus vectors, yielding sufficient expression of wild type and mutant SERCA-1 ATPase for measurements of Ca2+ binding to the microsomal fraction of the transfected cells. We find that in the presence of 20 microM Ca2+ and in the absence of ATP, the Glu771 --> Gln, Thr799 --> Ala, Asp800 --> Asn, and Glu908 --> Ala mutants exhibit negligible binding, indicating that the oxygen functions of Glu771, Thr799, Asp800, and Glu908 are involved in interactions whose single disruption causes major changes in the highly cooperative "duplex" binding. Total loss of Ca2+ binding is accompanied by loss of Ca2+ inhibition of the Pi reaction. We also find that, at pH 7.0, the Glu309 --> Gln and the Asn796 --> Ala mutants bind approximately half as much Ca2+ as the wild type ATPase and do not interfere with Ca2+ inhibition of the Pi reaction. At pH 6.2, the Glu309 --> Gln mutant does not bind any Ca2+, and its phosphorylation by Pi is not inhibited by Ca2+. On the contrary, the Asn796 --> Ala mutant retains the behavior displayed at pH 7.0. This suggests that in the Glu309 --> Gln mutant, ionization of acidic functions in other amino acids (e.g. Glu771 and Asp800) occurs as the pH is shifted, thereby rendering Ca2+ binding possible. In the Asn796 --> Ala mutant, on the other hand, the Glu309 carboxylic function allows binding of inhibitory Ca2+ even at pH 6.2. In all cases mutational interference with the inhibition of the Pi reaction by Ca2+ can be overcome by raising the Ca2+ concentration to the mM range, consistent with a general effect of mutations on the affinity of the ATPase for Ca2+.

Adenosine Triphosphate↗
PubMed1998

Liquid ventilation in an infant with pulmonary alveolar proteinosis.

Partial liquid ventilation (PLV) has been applied in various pulmonary diseases. We describe the use of partial liquid ventilation as a lavage method following normal saline (NS) lavage in an infant with pulmonary alveolar proteinosis (PAP) and severe hypoxemia. A 6 weeks old 3.4 kg former 36 weeks gestation boy on supplemental oxygen was transferred to our NICU with persistent tachypnea, dry cough, and increasing oxygen requirements. A lingular open lung biopsy revealed PAP. He developed progressive respiratory failure requiring ventilatory support, necessitating conventional NS lavage, followed by lung lavage with perflubron (LiquiVent; Alliance Pharmaceutical Corp. and Hoechst Marion Roussel) while on venovenous extracorporeal life support (ECLS). Lung lavage with NS and perflubron yielded minimal cloudy effluent. Gas exchange and pulmonary function deteriorated following NS lavage and attempts to discontinue ECLS were poorly tolerated. In contrast, tidal volume, PaO2, and pulmonary compliance increased after PLV, while the (A-a) D(O2) decreased to a point where ECLS was no longer required. Once perflubron was added repeatedly to the ventilator circuit to correct for evaporation over the 4 days of PLV. Cardiovascular status remained stable for several days; however, eventually he required reinitiation of ECLS and more mechanical ventilatory support with each trial off ECLS. He was maintained on high pressures and FiO2 without any possibility to wean him from mechanical ventilation. Life support was withdrawn 1 month after admission. The survival from PAP in infants remains dismal, even with total lung NS lavage. While both NS and perflubron lavage in this patient were not effective in removing the proteinaceous alveolar debris, PLV following NS lavage was associated with an improvement in gas exchange and lung compliance.

Bronchoalveolar Lavage↗
PubMed1998

Diminished expression of CD40 ligand may contribute to the defective humoral immunity in patients with MHC class II deficiency.

Major histocompatibility complex (MHC) class II deficiency (bare lymphocyte syndrome, BLS) is a rare primary immunodeficiency classified as a subgroup of severe combined immunodeficiency. We studied T and B lymphocyte function by examining the CD40 ligand/CD40 system in three BLS patients from two unrelated families. CD40 ligand expression by maximally activated BLS T cells was diminished. This abnormality may represent immunological naïveté rather than a general T cell defect, since expression of activation marker CD69 and proliferative responses to PHA or anti-CD3 were normal, and BLS T cells primed and restimulated in vitro expressed normal amounts of CD40 ligand. BLS B cells proliferated and produced IgE if stimulated with anti-CD40 or soluble CD40 ligand and IL-4. Activation of BLS B cells with soluble CD40 ligand and IL-4 induced normal expression of activation markers, although MHC class II expression remained absent. Depressed antibody titers, lack of amplification and failure to undergo isotype switching in response to immunization with bacteriophage phi x 174 demonstrated defective T cell help. We conclude that BLS B cells are functionally normal if appropriately stimulated, and that the defective humoral immunity observed may be related to diminished expression of CD40 ligand on BLS T cells.

Antibodies, Viral↗
PubMed1998

An ultrastructural investigation into proteoglycan distribution in human corneas.

PURPOSE: We report an investigation into the distribution of proteoglycans (PGs) in normal, organ-cultured and dextran-treated human corneas. METHODS: Immunogold labeling was carried out at the electron microscope level to localize keratan sulphate (KS), chondroitin sulphate (CS), and heparan sulphate (HS) PGs. RESULTS: High levels of labeling for CS was found in the epithelium, endothelium, and keratocytes, with light labelling present in the basement membranes and the corneal stroma. Labeling for HS was present in the epithelium, endothelium, and keratocytes, with intense labeling present at the endothelium/Descemet's membrane interface and the epithelium/Bowman's layer interface. Large filaments were also observed in these regions in cuprolinic blue-stained specimens. Keratan sulphate was present at high levels in the stroma and the basement membranes with low levels present within the keratocytes, epithelium, and endothelium. The pattern of KS labeling along the collagen fibrils in the stroma sometimes showed evidence of periodicity. Organ-cultured corneas had extensive collagen-free "lakes," the interior of which immunolabeled positively for KS and showed staining with cuprolinic blue. The lakes were greatly reduced in the dextran-treated samples. CONCLUSION: This investigation determined the ultrastructural distribution of KS, CS, and HS PGs in human cornea and showed that organ culture is associated with a change in distribution of stromal PGs.

Chondroitin Sulfates↗
PubMed1998

Cell-specific promoter in adenovirus vector for transgenic expression of SERCA1 ATPase in cardiac myocytes.

Adenovirus-mediated transfer of cDNA encoding the chicken skeletal muscle sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA1) yielded selective expression in cultured chick embryo cardiac myocytes under control of a segment (-268 base pair) of the cell-specific cardiac troponin T (cTnT) promoter or nonselective expression in myocytes and fibroblasts under control of a constitutive viral [cytomegalovirus (CMV)] promoter. Under optimal conditions nearly all cardiac myocytes in culture were shown to express transgenic SERCA1 ATPase. Expression was targeted to intracellular membranes and was recovered in subcellular fractions with a pattern identical to that of the endogenous SERCA2a ATPase. Relative to control myocytes, transgenic SERCA1 expression increased up to four times the rates of ATP-dependent (and thapsigargin-sensitive) Ca2+ transport activity of cell homogenates. Although the CMV promoter was more active than the cTnT promoter, an upper limit for transgenic expression of functional enzyme was reached under control of either promoter by adjustment of the adenovirus plaque-forming unit titer of infection media. Cytosolic Ca2+ concentration transients and tension development of whole myocytes were also influenced to a similar limit by transgenic expression of SERCA1 under control of either promoter. Our experiments demonstrate that a cell-specific protein promoter in recombinant adenovirus vectors yields highly efficient and selective transgene expression of a membrane-bound and functional enzyme in cardiac myocytes.

Adenosine Triphosphate↗
PubMed1998

Gaining strength: supplements revised.

Responding to concerns for weight loss and nutritional status of its patients, a Transitional Care Unit (TCU) began an intensive Medication Pass Supplement Program. It involves nurses administering a dietitian-reviewed and approved nutritional supplement for specified residents with every medication pass. As a result, 94% of discharged patients lost less than 5% of their admission weight.

Dietary Supplements↗
PubMed1998

Health years equivalents as a measurement of preferences for dental interventions.

OBJECTIVE: To test the feasibility and importance of measuring preferences among treatment choices using Healthy Years Equivalents (HYE). DESIGN: Development of scenarios for alternative approaches to caries treatment. Completion of category rating and standard gamble questions elicited in personal interviews. SETTING: The provision of dental care to children in a public-funded dental health clinic. PARTICIPANTS: Random sample of the adult population of Hamilton, Ontario. MAIN OUTCOME MEASURES: The percentage of the sample unable to complete the interviews, time taken to perform interviews, ease of understanding of interviews, correlation between rank ordering and HYE scores. RESULTS: Ninety-six per cent of the sample were able to complete the HYE exercise. Inconsistencies between HYE scores and rank orders implying preference reversal occurred in 6% of those completing HYE scores for the two scenarios. The additional time taken by the HYE was of the order of 17 minutes but increased with the age of the subject. Where problems occurred, they were related to the method of measurement or the sensitivity of the chosen scale as opposed to additional requirements of the HYE. There was some evidence that HYEs and QALYs produced different scores even in the context of chronic constant health states. CONCLUSIONS: HYEs are a feasible and important practical method of measuring preferences among interventions. Alternative utility-based approaches, such as willingness to pay, may be required to detect differences in modest improvements in temporary health states.

Adult↗