Search PubMed⌕ Search

Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 379 records · Page 21Linked to original sources
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

Retention of chylomicron remnants by arterial tissue; importance of an efficient clearance mechanism from plasma.

Atherosclerosis is thought to begin with the trapping of cholesterol rich lipoproteins within the intima of arterial vessels. Thereafter a complex inflammatory cascade involving recruitment and transformation of leukocytes, accumulation of sterols in macrophages and cellular proliferation, can lead to a progressive occlusion in blood flow, or an unstable arterial lesion prone to prothrombotic events. Primary intervention strategies aimed at reducing atherogenesis are designed to achieve reductions in sterol rich lipoproteins, primarily low density lipoproteins, given the hypothesis that decreased exposure will attenuate the rate of arterial cholesterol accumulation. Epidemiological evidence has clearly identified a positive relationship between poor dietary (fat) habits and the onset and progression of atherosclerosis. However lipoproteins which mediate the transport of dietary lipid, that is chylomicrons, are not normally considered to be directly involved in atherogenesis, because of their larger size and inability to efficiently penetrate arterial tissue. In contrast, this article reviews recent evidence which suggests that once chylomicrons are hydrolysed to their remnant form, the triglyceride depleted chylomicron remnants penetrate arterial tissue and moreover, become preferentially trapped within the subendothelial space as concentrated focii. Ongoing studies demonstrate that significant chylomicron remnant accumulation can occur in a number of primary and secondary lipid disorders and in normolipidemic subjects with coronary artery disease. Chylomicron remnant dyslipidemia in conditions prone to premature atherosclerosis is consistent with the putative atherogenicity of these particles and can be explained by increased arterial exposure to cholesterol rich chylomicron remnants.

Arteries↗
PubMed1998

Rothia dentocariosa endocarditis and aortic root abscess.

We report a case of endocarditis and associated paravalvular abscess due to Rothia dentocariosa which did not respond to antibiotic therapy. Nine case reports describing endocarditis caused by this organism, formerly thought to be non-pathogenic, have been recorded in the literature. The isolates were extremely sensitive to penicillin, and eight patients responded to this agent which, in most cases, was used in combination with an aminoglycoside. Surgery is recommended for an associated abscess, as the outcome in the two recorded cases has been fatal.

Abscess↗
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↗
PubMed1998

Pharmacological vasodilatation improves efficiency of rewarming from hypothermic cardiopulmonary bypass.

An afterdrop in core temperature after hypothermic cardiopulmonary bypass (CPB) is related to inadequate peripheral rewarming. We proposed that pharmacological vasodilatation during rewarming on bypass would improve peripheral rewarming and reduce the degree of afterdrop. Fifty-nine of 120 patients were randomized to receive a sodium nitroprusside (SNP) infusion during the rewarming stage of hypothermic CPB. Mean systemic vascular resistance (SVR) during the rewarming phase of CPB was 1129 dyne s-1 cm-5 in the control group and 768 dyne s-1 m-5 in the SNP group (P < or = 0.001). Patients receiving SNP rewarmed to 37.0 degrees C faster (299 min vs 376 min; P = 0.003) and were extubated earlier (490 min vs 621 min; P = 0.001). Patients receiving SNP had a warmer mean peripheral temperature (MPT) (32.9 degrees C vs 32.4 degrees C; P = 0.05) on termination of CPB. Postoperative core temperature fell less in the SNP group (35.6 degrees C vs 35.2 degrees C; P = 0.01) as did MPT (31.8 degrees C vs 31.2 degrees C; P = 0.004). SNP-induced vasodilatation during rewarming from hypothermic CPB improves peripheral rewarming, reduces the degree of postoperative core and peripheral hypothermia and reduces time to extubation.

Aged↗
PubMed1998

A comparative analysis of surveyors from six hospital accreditation programmes and a consideration of the related management issues.

PURPOSE: To gather data on how accreditors manage surveyors, to compare these data and to offer them to the accreditors for improvement and to the scientific community for knowledge of the accreditation process and reinforcement of the credibility of these processes. DATA SOURCE: The data were gathered with the aid of a questionnaire sent to all accreditors participating in the study. RESULTS: An important finding in this comparative study is the different contractual relationships that exist between the accreditors and their surveyors. CONCLUSION: Surveyors around the world share many common features in terms of careers, training, work history and expectations. These similarities probably arise from the objectives of the accreditors who try to provide a developmental process to their clients rather than an 'inspection'.

Accreditation↗