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D Smith

Publications and source records attributed to D Smith.

At least 37 records · Page 2Linked to original sources
PubMed1998

Quantification of ammonia in human breath by the selected ion flow tube analytical method using H30+ and 02+ precursor ions.

We show how our selected ion flow tube mass spectrometric technique for trace gas analysis can be used to determine the concentrations of ammonia in alveolar breath from single exhalations using both H30+ and 02+ precursor ions for chemical ionization. Thus, data are presented of the alveolar ammonia concentrations in the breath of six healthy volunteers following the ingestion of a liquid protein meal, which show that consistent values are obtained using these two precursor ions. Alveolar breath ammonia concentrations (which range from 200 to 1750 ppb in these individuals) are compared with those obtained from bag samples of breath from the same individuals.

Ammonia↗
PubMed1998

Clozapine use in Parkinson's disease: a retrospective analysis of a large multicentered clinical experience.

We conducted a multicentered, retrospective review of clozapine's (CZP) effects on a range of psychiatric, sleep, cognitive, motor, and sensory disorders in Parkinson's disease (PD). Therapeutic outcomes and adverse events were compared with varying prescribing practices at participating sites. The medical records of 172 consecutive PD patients treated with CZP at four movement disorder clinics were reviewed. Low-dose CZP improved psychiatric symptoms of psychosis, anxiety, depression, hypersexuality, sleep disturbance, and akathisia. Tremor, torticollis, limb dystonia, and pain showed modest rates of improvement. Twenty-three percent of patients withdrew as a result of adverse events or treatment failure. Inpatient CZP initiation did not improve therapeutic efficacy, or reduce adverse events or the withdrawal rate. Low-dose CZP in the outpatient setting is generally an effective and well-tolerated treatment for many of the psychiatric, sleep, motor, and sensory disturbances common to late-stage PD.

Aged↗
PubMed1998

Efficacy of succimer chelation for reducing brain Pb levels in a rodent model.

Increasing evidence indicates that early low-level lead (Pb) exposure produces enduring cognitive impairment in children, underscoring the need to develop improved therapeutic intervention. Although chelating agents have been shown to effectively reduce body Pb levels, it is not yet known whether this treatment ameliorates Pb-induced cognitive dysfunction. Clinical research in this area is hampered by the need to rely on reductions in blood Pb levels as the index of treatment efficacy, despite the fact that brain Pb level is the exposure parameter of greatest relevance to neurocognitive outcomes. The present studies were designed to provide information that will aid future research in this area in both human and animal models. The objectives of these studies were (1) to evaluate the efficacy of different doses and durations of succimer (meso-2,3-dimercaptosuccinic acid; DMSA) chelation for reducing brain and blood Pb levels and (2) to determine the extent to which blood Pb can serve as a surrogate of brain Pb following chelation. Long-Evans hooded rats were exposed to Pb from birth until day 31 (Study 1) or day 40 (Study 2) of life, followed by oral treatment with a vehicle or one of two succimer regimens for a duration of either 7 or 21 days. Results indicated that 7 days of succimer treatment produced a 1.5- to 2.5-fold greater reduction of Pb in blood than in brain, relative to time-matched vehicle groups. Prolonged treatment (21) days did not further reduce blood Pb levels (relative to 7-day succimer treatment), but did produce further reductions in brain Pb level compared to time-matched vehicle groups. Thus, chelation-mediated reductions in brain Pb did not parallel reductions in blood Pb over the course of treatment. While the relevance of these data to humans may be confounded by anatomical and physiological differences between rodents and primates, as well as differences in the metabolism of succimer (DMSA), they suggest that clinical studies should exercise caution when using blood Pb as an index of the efficacy of chelation treatment for reducing brain Pb levels.

Administration, Oral↗
PubMed1998

Investigation into the tensile properties of collagen/chondroitin-6-sulphate gels: the effect of crosslinking agents and diamines.

Artificial skin substitutes based on autologous keratinocytes are being developed for grafting onto burns patients. In order to be used successfully in the clinic, these skin substitutes need to have sufficient strength to allow ease of handling. This may be achieved by crosslinking the collagen substratum on which the cells are cultured. The influence of potential crosslinking agents on the tensile properties of acellular collagen gels has been investigated, including the glycosaminoglycan, chondroitin-6-sulphate (Ch6SO4), the water-soluble carbodiimide crosslinking agents 1-ethyl-3-(3-diaminopropyl) carbodiimide (EDAC), and 1,1-carbonyldiimidazole (CDI), and the polyamines, putrescine and diaminohexane. Values for Young's modulus, maximum load, stress, displacement and percentage strain at maximum load were generated by subjecting the samples to a tear propagation test. Incorporation of 20% Ch6SO4 into collagen gels caused a significant increase in the Young's modulus, maximum load and stress at maximum load. Crosslinking treatment with EDAC, CDI or polyamines had little further benefit, and in many cases resulted in a decrease in particular parameters. In terms of mechanical strength, the best crosslinking combination proved to be the combination of CDI and diaminohexane, with results either improved or maintained when compared with the control no treatment variants. However, previous experience suggests that the use of CDI as a crosslinking reagent may inhibit infiltration and proliferation of fibroblasts in the substratum and it may be necessary to reach a compromise to obtain the best combination of biological and mechanical properties for artificial skin substitutes.

Chondroitin Sulfates↗
PubMed1998

Oxidative DNA damage levels in blood from women at high risk for breast cancer are associated with dietary intakes of meats, vegetables, and fruits.

OBJECTIVE: We examined the relationship between intakes of specific foods--namely, meats, vegetables, and fruits--with levels of oxidative DNA damage in women consuming their own usual diet or a diet low in fat. DESIGN: Blood was obtained from women who had been assigned randomly to a low-fat or nonintervention diet for 3 to 24 months. Levels of 5-hydroxymethyluracil, a type of oxidative DNA damage, were determined. Diet data were obtained from 3-day food records. SUBJECTS/SETTING: The 21 women were participating in an outpatient clinic. All the women were healthy but had a first-degree relative with breast cancer. INTERVENTION: The intervention was a self-selected diet with a goal of 15% of energy from fat. MAIN OUTCOME MEASURES: Existing data on oxidative DNA damage levels were evaluated for possible relationships to foods eaten. Intakes of raw and cooked vegetables were examined separately. Meat intake was examined by type of meat (pork, beef, fish, chicken) and by cooking temperature. STATISTICAL ANALYSES: Initial univariate analyses relied on Spearman rank correlations of each food item with DNA damage. Further analyses of the data were performed with univariate and multivariate weighted least squares regression models. RESULTS: The model that best explained DNA damage levels was a bivariate regression model that included the intake of cooked vegetables and the sum of beef and pork intake. This model accounted for 85% of the variation in DNA damage levels among women. Preliminary results are suggestive of a positive association of DNA damage with beef and pork intake and a negative association with cooked vegetable intake. APPLICATION: These observations, if confirmed in larger studies, suggest specific dietary changes to reduce oxidative DNA damage levels and possibly cancer risk.

Adolescent↗
PubMed1998

The effects of diet and lovastatin on regression of fatty streak lesions and on hepatic and intestinal mRNA levels for the LDL receptor and HMG CoA reductase in F1B hamsters.

This study examined the effects of lovastatin supplementation (25 mg/kg per day) in conjunction with an atherogenic diet (10% coconut oil (w/w), 0.05% cholesterol) on regression of pre-existing foam cells and on hepatic and intestinal LDL receptor and HMG CoA reductase mRNA levels. F1B hamsters fed the atherogenic diet had significantly greater (p < 0.0002) foam cell accumulation (10078 +/- 1452 (S.E.M.) micron2) compared to those fed a low fat, no cholesterol chow diet (64 +/- 10 micron2) or the atherogenic diet supplemented with lovastatin (1621 +/- 132 micron2). Regression of fatty streak lesions was achieved by feeding either a chow diet or supplementing the atherogenic diet with lovastatin as evidenced by the significant (p < 0.0002) reduction in foam cell accumulation in the chow regression (94 +/- 55 micron2) and lovastatin regression (48 +/- 18 micron2) groups compared to the atherogenic diet group (10078 +/- 1452 micron2). Lovastatin supplementation of the atherogenic diet induced significant upregulation of both LDL receptor and HMG CoA reductase message levels in liver and intestine compared to the chow and atherogenic diet fed groups. These data demonstrate that lovastatin supplementation of an atherogenic diet decreases foam cell accumulation and induces upregulation of hepatic and intestinal LDL receptor and HMG CoA reductase mRNA levels. Furthermore, regression of pre-existing, diet-induced fatty streak lesions can be achieved by lovastatin supplementation of an atherogenic diet or by feeding a low fat, low cholesterol chow diet. The specific effects of lovastatin on foam cell accumulation and regression and messenger RNA levels are secondary to reductions in plasma total cholesterol concentrations and do not demonstrate a direct effect of lovastatin on atherosclerotic lesions.

Animals↗
PubMed1998

Tumor resistance to antimetabolites.

1. The inherent or acquired resistance of certain tumors to cytotoxic drug therapy is a major clinical problem. 2. Resistance to the chemotherapeutic antimetabolites (e.g., methotrexate, 5-fluorouracil, tomudex and gemcitabine) is no exception. 3. Mechanisms of resistance include mutations, amplification of target genes, altered drug transport, differences in nucleoside and nucleobase salvage pathways, DNA damage-response pathways and cell cycle control pathways.

Antimetabolites, Antineoplastic↗
PubMed1998

Destruxin-A4 chlorohydrin, a novel destruxin from fungus OS-F68576: isolation, structure determination, and biological activity as an inducer of erythropoietin.

In the course of screening for small-molecule modulators of erythropoietin gene expression, five destruxins were isolated from the fungal culture of OS-F68576. The structures were elucidated by extensive 1H and 13C NMR spectroscopy and by hydrolytic modification. One compound (destruxin-A4 chlorohydrin, 1) is a novel destruxin. All these compounds induced erythropoietin gene expression 5-fold at concentration of 0.2-2 microM.

Cell Line↗
PubMed1998

Accumulation of chylomicron remnants in homozygous subjects with familial hypercholesterolaemia.

BACKGROUND: Post-prandial lipoprotein kinetics were investigated in subjects who lack functioning low-density lipoprotein (LDL) receptors [homozygous familial hypercholesterolaemia (FH)]. METHODS: An oral fat load was given, and chylomicron plasma kinetics was determined by monitoring the clearance of triglyceride, retinyl palmitate and apolipoprotein B48, calculated as the area under the curve, for 7.5 h. In addition, the binding and uptake of chylomicron remnants by fibroblasts of FH and control subjects were assessed in vitro. RESULTS: Based on the plasma kinetics of chylomicron triglyceride, retinyl palmitate and apolipoprotein B48 after a lipid meal, chylomicron clearance was found to be substantially delayed compared with normolipidaemic control subjects. Consistent with involvement of the LDL receptor in chylomicron clearance, binding and uptake of chylomicron remnants by fibroblasts of FH subjects was found to be substantially less than in cells from control subjects. CONCLUSION: This study shows that, in addition to LDL, chylomicron metabolism is severely impaired in FH and that the LDL receptor is significantly involved in the clearance of post-prandial lipoproteins. Moreover, this study raises the possibility that in FH, and in other disorders in which LDL receptor expression is reduced, atherogenesis might be a post-prandial disease.

Adolescent↗
PubMed1998

Mosquito density, biting rate and cage size effects on repellent tests.

Mosquito biting rates and the mean duration of protection (in hours) from bites (MDPB) of Aedes aegypti and Anopheles quadrimaculatus, using the repellent 'deet' (N,N-diethyl-3-methylbenzamide) on a 50 cm2 area of healthy human skin, were observed in small (27 l), medium (approximately 65 l) and large (125 l) cages containing low, medium or high densities of mosquitoes: respectively, 640, 128 or 49 cm3 of cage volume per female. At the initial treatment rate of approximately 0.4 microliter/cm2 (1 ml of 25% deet in ethanol on 650 cm2 of skin), the MDPB for deet against Ae. aegypti ranged from 4.5 to 6.5 h and was significantly less (5.0 +/- 0.8 h) in large cages compared with medium (6.2 +/- 0.9 h) and small (6.2 +/- 0.8 h) cages, regardless of the density. Against An. quadrimaculatus the MDPB for deet 0.4 microliter/cm2 was 1.5-8.0 h, less in small (3.7 +/- 2.3 h) and large (2.2 +/- 1.1 h) cages at medium (3.7 +/- 2.3 h) and high (2.5 +/- 1.7 h) mosquito densities, and was longest in medium cages (6.2 +/- 2.6 h) at low mosquito densities (5.8 +/- 2.8 h). With equinoxial photoperiodicity (light on 06.00-18.00 hours) the biting rate was influenced by the time of observation (08.00, 12.00, 16.00 hours) for Ae. aegypti but not for An. quadrimaculatus. For both species, the biting rate was inversely proportional to mosquito density and the MDPB. The shortest MDPBs were obtained in large cages with high densities of mosquitoes and longest protection times occurred in medium sized cages with low mosquito densities.

Aedes↗
PubMed1998

The comparative anatomy of the pig middle ear cavity: a model for middle ear inflammation in the human?

This study was undertaken to develop a functional model of otitis media with effusion (OME) in the pig (Sus scrofa), with the purpose of investigating the origin of lymphocytes populating the middle ear during the course of an inflammatory process. The relevance of the model to the human condition of OME is to a large extent dependent on the anatomical and physiological similarities between the middle ear cavity and the pharyngeal lymphoid tissue of the pig and man. Anatomical specimens were collected from 7 young Large White pigs to determine the gross anatomy of the middle ear cavity and the histological characteristics of the middle ear mucosa. It was found that the anatomy of the 3 parts of the middle ear cavity in man and in the pig is broadly similar, although some minor differences were observed. The porcine eustachian tube was seen to be cartilaginous throughout its length in contrast to the part osseous, part cartilaginous structure found in man; the porcine ossicles were slightly different in shape to those of man and the air cell system was situated inferior to the tympanic cavity in the pig as opposed to posteriorly in man. This paper describes the structure and morphology of the pig middle ear cavity and compares and contrasts it with that of man. The minor differences observed are of anatomical importance but do not diminish the usefulness of the pig middle ear cleft as a potential model for human middle ear disorders.

Animals↗
PubMed1998

Impact of etiology of secondary ureteropelvic junction obstruction on outcome of endopyelotomy.

Endopyelotomy for secondary ureteropelvic junction obstruction (UPJO) is a highly effective procedure. However, the impact of the etiology of the obstruction on the outcome of an endopyelotomy has not been defined. Herein, we review the success rates with endopyelotomy for secondary UPJO after failure of open pyeloplasty or endopyelotomy. Thirty-five adult patients with both objective and subjective follow-up were identified retrospectively who had endopyelotomy for secondary UPJO. Twenty-four patients had failed a previous open reconstruction (23) or laparoscopic Foley Y-V plasty (1). Eleven patients had failed a prior endopyelotomy. Retrograde endopyelotomy was performed using the Acucise device in 11 patients, and antegrade endopyelotomy was performed in 24 patients. Objective follow-up was obtained with diuretic renal scintigraphy (mean 14.1 months) and subjective follow-up by analog pain scales (mean 27.8 months). Objective success was defined as no obstruction on renal scintigraphy, while subjective success was used to describe a minimum of 50% resolution of symptoms. The subjective success rate of secondary endopyelotomy in the open-pyeloplasty group was 88% v 71% in the prior endopyelotomy group (P = 0.20). The objective success rate in the failed-pyeloplasty group was 71% v 55% in the prior endopyelotomy group (P = 0.40). Endopyelotomy for secondary UPJO has a good success rate. Success rates tend to be higher in patients who have failed an open pyeloplasty; however, a statistically significant difference was not seen between the two groups.

Adult↗
PubMed1998

CD31 immunoreactivity in carcinomas and mesotheliomas.

CD31 is a specific and sensitive marker of endothelial differentiation. Previous reports have described its immunoreactivity in large series of soft tissue neoplasms, as well as its comparison with other available and commonly used endothelial markers. CD31 reactivity in carcinomas or mesotheliomas has been incompletely addressed, however. Hence, we applied anti-CD31 (JC70/A, DAKO, Carpinteria, Calif) to 290 previously characterized neoplasms by using a modified avidin-biotin-peroxidase complex technique following microwave epitope retrieval. Seven carcinomas showed plasmalemmal-based immunoreactivity (2 papillary thyroid carcinomas, 2 mucoepidermoid salivary gland carcinomas, 1 cutaneous adnexal tumor, 1 cutaneous squamous cell carcinoma, and 1 esophageal squamous cell carcinoma); the remaining 283 lesions were negative for this marker. We conclude that anti-CD31 immunostaining in carcinomas and mesotheliomas is rare. These findings support the concept that CD31 is a reliable marker of endothelial differentiation and should be included in diagnostic immunohistochemical panels when vascular tumors enter the differential diagnosis.

Adenocarcinoma↗
PubMed1998

Haemodynamic responses to extubation after cardiac surgery with and without continued sedation.

We studied the haemodynamic response to cessation of mechanical ventilation and removal of the tracheal tube in 84 patients after coronary artery bypass grafting. Patients were sedated on the ICU with propofol 1-3 mg kg-1 h-1, and randomly allocated to extubation while awake or while still sedated. Systolic and diastolic blood pressures and heart rate increased significantly faster in the awake group as mechanical ventilation was stopped; systolic blood pressure 6.1 (3.0) vs 0.7 (1.8) mm Hg min-1, diastolic blood pressure 2.1 (1.6) vs 0.2 (0.9) mm Hg min-1, heart rate 2.1 (1.7) vs 0.2 (0.5) beats min-2; P < 0.01 in each case. Treatment was required for systolic hypertension during discontinuation of mechanical ventilation in 20 patients (53%) in the awake group and in three patients (7.5%) in the sedated group (P < 0.001). No patient in the sedated group had any new ischaemic ECG changes. Significant new ST segment changes did not occur in the sedated group but were present in five patients in the awake group (P = 0.013), one of whom suffered a perioperative myocardial infarction. Removal of the tracheal tube while patients are still sedated after coronary artery bypass grafting is safe, and reduces the incidences of haemodynamic disturbance and myocardial ischaemia during extubation.

Procedural Sedation↗