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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 541 records · Page 30Linked to original sources

A clinical trial of a new dental implant.

This paper presents the results of a clinical trial of a new dental implant after two years of loading. The design and the technical details of the surgical and prosthodontic phases of treatment are discussed. The implant's success was measured using Health Canada (Health Protection Branch) criteria. Patients with less than optimal clinical situations were not excluded from the study. The study shows survival rates in the lower jaw of 85.6 per cent and in the upper jaw of 86.7 per cent. Bleeding and oral hygiene indices and bone loss (less than 0.2 mm/yr) all fall within generally accepted limits.

Adult↗

The selected ion flow tube (SIFT)--a novel technique for biological monitoring.

We describe the use of our selected ion flow tube (SIFT) technique for the rapid detection and quantification of trace gases in atmospheric air, with special reference to the analysis of human breath. It is based on the chemical ionization of the breath trace gases to the exclusion of the major breath gases, using 'soft' proton transfer from H3O+ ions. Breath samples can either be introduced into the SIFT from bags or by direct breathing into the apparatus, the advantage of the latter approach being that surface active gases such as ammonia and many organic vapours which adsorb onto bag surfaces can be more accurately quantified. We present examples of the analysis of laboratory air, the breath of a non-smoker and of a smoker taken from bag samples, and illustrate the rapid time response of the technique by showing the time profile of acetone on breath during direct breathing into the apparatus. The current partial pressure sensitivity of our SIFT method is within the range 30 ppb to in excess of 100 ppm, but with further development the device could be made more sensitive, 1 ppb being well within reach. A transportable SIFT device is under development which will have applications in environmental, medical and biological research, health and safety monitoring, and in clinical diagnosis.

Breath Tests↗

Intron-encoded endonuclease I-TevI binds as a monomer to effect sequential cleavage via conformational changes in the td homing site.

I-TevI, the intron-encoded endonuclease from the thymidylate synthase (td) gene of bacteriophage T4, binds its DNA substrate across the minor groove in a sequence-tolerant fashion. We demonstrate here that the 28 kDa I-TevI binds the extensive 37 bp td homing site as a monomer and significantly distorts its substrate. In situ cleavage assays and phasing analyses indicate that upon nicking the bottom strand of the td homing site, I-TevI induces a directed bend of 38 degrees towards the major groove near the cleavage site. Formation of the bent I-TevI-DNA complex is proposed to promote top-strand cleavage of the homing site. Furthermore, reductions in the degree of distortion and in the efficiency of binding base-substitution variants of the td homing site indicate that sequences flanking the cleavage site contribute to the I-TevI-induced conformational change. These results, combined with genetic, physical and computer-modeling studies, form the basis of a model, wherein I-TevI acts as a hinged monomer to induce a distortion that widens the minor groove, facilitating access to the top-strand cleavage site. The model is compatible with both unmodified DNA and glucosylated hydroxymethylcytosine-containing DNA, as exists in the T-even phages.

Base Sequence↗

Kinetic parameters of lymphocyte microsomal epoxide hydrolase in carbamazepine hypersensitive patients. Assessment by radiometric HPLC.

Idiosyncratic hypersensitivity reactions with carbamazepine have been postulated to be due to a deficiency of microsomal epoxide hydrolase (HYL1), although this is based on indirect evidence. Using 3H-cis stilbene oxide (0.5 Ci/mmol) as a substrate, we have developed a radiometric HPLC assay sensitive enough to measure the kinetic parameters of HYL1 in lymphocytes. The intra-assay coefficient of variation was 8%. Enzyme activity has been measured in lymphocytes from six carbamazepine hypersensitive patients, six patients on carbamazepine without any adverse effects, and twelve drug-naive healthy volunteers. No significant difference was observed in three kinetic parameters of the enzyme among these three groups. The values for Km, Vmax, and intrinsic clearance ranged from 6.1-89.9 microM, 3.0-23.2 pmoles diol formed/min/mg protein, and 0.147-0.493 microliter/min/mg protein. There was no difference in enzyme activity between patients currently on carbamazepine and healthy volunteers, indicating a lack of induction of lymphocyte HYL1 by carbamazepine. Co-incubation of lymphocytes with 1,1,1-trichloropropene oxide, an inhibitor of hepatic HYL1, resulted in an 82% inhibition of activity, similar to that observed with the hepatic enzyme. The healthy volunteers were genotyped as being either GSTM1 positive (n = 6) or GSTM1 negative (n = 6). This did not affect the kinetic parameters of lymphocyte microsomal epoxide hydrolase. Our results suggest that there is normal HYL1 activity in lymphocytes of hypersensitive patients using cis-stilbene oxide as a substrate.

Adolescent↗

Failure of 29Si NMR to detect increased blood silicon levels in silicone gel breast implant recipients.

We have compared directly the results of atomic absorption (AA) spectroscopy and a 29Si magic angle spinning (MAS) nuclear magnetic resonance (NMR) technique reported in the literature by Garrido et al. (Garrido, L.; et al. Magn. Reson. Med. 1994, 31, 328-330) for analyzing blood silicon levels in control patients versus patients with silicone gel breast implants. AA spectroscopy yielded blood silicon levels in the nanogram per milliliter range for control patients, while somewhat higher values were found in patients with implants. The 29Si MAS NMR technique applied to the identical blood samples was unable to detect silicon in any of the samples. Sensitivity calculations demonstrate that 29Si MAS NMR should not be expected to detect silicon at the levels determined by AA spectroscopy under the spectroscopic conditions employed and that the concentration of silicon-containing compounds would need to 10(4) times the level detected by AA in order to be detected by this NMR method.

Breast Implants↗

ICAAC's small advances.

Explore the source record for details and available documents.

AIDS-Related Opportunistic Infections↗

Secondary organ allografting after a primary "bridging" xenotransplant.

It remains uncertain whether xenotransplantation can sensitize the recipient to alloantigens, rendering subsequent allotransplantation unsuccessful. This is of considerable importance if a xenograft is to be used as a "bridge" to support the patient until a suitable allograft becomes available. When sera from 9 baboons that had received pig or African green monkey heart or liver xenografts were tested against a panel of lymphocytes from 5 or 6 potential donor baboons, positivity was seen in only 1 baboon (and then to only 2 of the potential 5 donors). In 4 baboons that had undergone previous xenotransplants (1 from this series of 9 baboons and 3 others), subsequent organ allografting was not followed by hyperacute, antibody-mediated, or accelerated cellular rejection. We conclude that organ xenotransplantation using discordant or concordant donor species does not prohibit subsequent allotransplantation.

Animals↗

Auxiliary liver allografting and xenografting in the nonhuman primate.

Auxiliary liver transplantation has been performed in the baboon using allografts (n = 8) and concordant xenografts from donor African green monkeys (n = 8). The native portal vein was ligated in all cases and the native common bile duct was ligated in 5 cases. The immunosuppressive therapy used was identical in both the allografts and xenografts and consisted of triple drug therapy (cyclosporine, cyclophosphamide, and methylprednisolone), all at dosages consistent with clinical use. During the determination of the surgical technique to be applied, there were 5 early failures (3 allografts, 2 xenografts), and 2 deaths at 10 and 20 days from multiorgan failure and sepsis, respectively (xenografts). The remaining 9 baboons (5 allografts, 4 xenografts) were electively euthanized at 16-62 days (allografts) and 35-120 days (xenografts). Hyperacute rejection or antibody-mediated rejection was not seen in the grafted livers. Episodes of acute cellular rejection occurred in the majority of animals within the first 30 days and recurred in the longer-term survivors, but could be controlled by bolus therapy with intravenous methylprednisolone. Satisfactory donor liver function was confirmed using a number of tests, including scintigraphy in 3 cases. We conclude that auxiliary liver transplantation using a closely related donor species is feasible in baboons and might be extended to humans with terminal liver failure. A baboon-to-man auxiliary liver graft may serve as a "bridge" until either a human cadaver donor liver became available or native liver function recovers in patients with fulminant hepatic failure.

Animals↗

Voltage-sensitive adenylyl cyclase activity in cultured neurons. A calcium-independent phenomenon.

Catalytic subunits of mammalian adenylyl cyclases have been proposed to contain 12 transmembrane domains, a property shared with some voltage-sensitive ion channels. Here we report that adenylyl cyclase activity in cerebellar neurons is synergistically stimulated by depolarizing agents and beta-adrenergic receptor activation. This phenomenon is Ca(2+)-independent and not attributable to Ca(2+)-stimulated adenylyl cyclase activity. Cholera toxin and forskolin also synergistically stimulate adenylyl cyclase activity in combination with depolarizing agents. We hypothesize that conformational changes in the catalytic subunit of the enzymes caused by changes in the membrane potential may enhance stimulation of adenylyl cyclases by the guanylyl nucleotide stimulatory protein. This novel mechanism for regulation of adenylyl cyclases generates robust cAMP signals that may contribute to various neuromodulatory events including some forms of neuroplasticity.

Adenylyl Cyclases↗

Measurement of absolute epicardial coronary artery flow and flow reserve with breath-hold cine phase-contrast magnetic resonance imaging.

BACKGROUND: Noninvasive measurement of absolute coronary arterial flow and coronary flow reserve would be of considerable use in the diagnosis and management of patients with coronary artery disease. Phase-contrast magnetic resonance imaging (MRI) has been used to measure flow in a variety of vessels. The goal of the present study was to determine if MRI measurements of coronary artery flow in a single breath-hold can be used to determine flow reserve and the severity of pericardial stenosis. METHODS AND RESULTS: In eight mongrel dogs, a closed chest model of partial left anterior descending coronary artery (LAD) occlusion was created. Coronary flows in the left circumflex artery (LCx) and LAD were measured at rest and during adenosine infusion using velocity-encoded, breath-hold MRI and perivascular ultrasound (US) flowmeters. MRI measurements of absolute coronary flow and coronary flow reserve were highly correlated with US (r = .96 and .94, respectively). Flow reserve measured in the constricted LAD was significantly lower than that in the unconstricted LCx by both US (P = .002) and MRI (P = .011). CONCLUSIONS: MRI measurements of coronary flow and flow reserve were in good agreement with US measurements. In addition, MRI measurements of coronary flow reserve successfully discriminated stenotic from normal vessels. These results indicate that MRI is a useful method for the noninvasive assessment of coronary flow and stenosis.

Adenosine↗

Adults with a history of child sexual abuse: evaluation of a pilot therapy service.

OBJECTIVE: To evaluate a pilot service offering therapy specifically to adults with a history of child sexual abuse. DESIGN: Questionnaire survey. SETTING: Specialised therapy unit, Breakfree, which offers care, therapy, and support. SUBJECTS: 116 clients presenting to the service who were offered therapy. MAIN OUTCOME MEASURES: Scores from three psychological questionnaires--the social activities and distress scale, the general health questionnaire, and the delusions, symptoms, and states inventory--and from questionnaires about the clients' abuse, previous use of health services, and opinion of the Breakfree service. RESULTS: Clients had received previous help from health services and other agencies without apparent effect; they were highly distressed according to their psychological scores; and they were very frequent users of the health services. The clients showed significant improvement in their psychological scores (Wilcoxon's matched pairs signed ranks test): social activities and distress scale, z = -3.3, P = 0.001; general health questionnaire, z = -5.8, P < 0.00001; delusions, symptoms, and states inventory, z = -4.8, P < 0.00001). This was most pronounced for those who had completed therapy by the end of the study. Whereas 82/88 clients had a score for the general health questionnaire that indicated clinical distress at the start, only 28/58 did so at the end of the study (only 17/35 among those who had finished therapy). CONCLUSIONS: This group of adults with a history of child sexual abuse were highly disturbed and previous high users of the health service. The specialist service Breakfree was effective in the short term and, if the benefits are sustained, would yield a net cost saving to the health service.

Adult↗

Lovastatin inhibits diet induced atherosclerosis in F1B golden Syrian hamsters.

3-Hydroxy-3-methylglutaryl-CoA (HMG CoA) reductase inhibitors are the drugs most commonly prescribed in the US to lower blood cholesterol. Previous studies have shown their efficacy in reducing plasma low density lipoprotein (LDL) cholesterol. However, little is known about their effects on preventing diet induced atherosclerosis. We have investigated the changes in lipoprotein profiles and extent of atherogenesis in hamsters (F1B strain) consuming an atherogenic diet with and without lovastatin. Thirty-six animals were randomized into 3 groups of 12 animals each, with similar plasma cholesterol levels. One group of animals received a basal chow diet, and the other two groups a basal diet plus 10% (w/w) coconut oil and 0.05% cholesterol. After 2.5 weeks, one of the groups received the latter diet supplemented with lovastatin (25 mg/kg/day). A second study was carried out in which animals received the same diets, but lovastatin was given during the 10 week period at a dose of 12.5 mg/kg/day. At the end of the experimental period, animals were sacrificed and lipoprotein cholesterol, liver enzymes, and aortic foam cell development were determined. Animals fed the high fat diet plus lovastatin had significantly lower levels of non-high density lipoprotein (HDL) cholesterol than those fed the unsupplemented high fat diet. No differences were observed in mean levels of this parameter between animals fed the low fat diet and those receiving lovastatin. The amount of aortic lipid staining was significantly less in the lovastatin and low fat groups when compared to the unsupplemented high fat groups. These results indicate that lovastatin can prevent diet induced aortic lipid deposition in this animal model.

Analysis of Variance↗