PubMed Health⌕ Search

Biomedical subjects

R N Smith

Publications and source records attributed to R N Smith.

At least 19 recordsLinked to original sources

Pathological effects of alcohol septal ablation for hypertrophic obstructive cardiomyopathy.

BACKGROUND: The pathological effects and the mechanisms of action of intracoronary administration of ethanol for alcohol septal ablation (ASA) for the management of hypertrophic obstructive cardiomyopathy (HOCM) are unknown. METHODS: We examined surgical specimens and, in one case, autopsy specimens from four patients who underwent surgical septal myectomy 2 days to 14 months after unsuccessful ASA. RESULTS: Pathological examination early after ASA showed coagulative necrosis of both the myocardium and the septal perforator arteries. Affected arteries were distended and occluded by necrotic intraluminal debris, without platelet-fibrin thrombi. Late after unsuccessful ASA, excised septal tissue was heterogeneous, containing a region of dense scar, and adjacent tissue containing viable myocytes and interspersed scar. CONCLUSIONS: Intracoronary administration of ethanol in patients with HOCM causes acute myocardial infarction with vascular necrosis. The coagulative necrosis of the arteries, their distension by necrotic debris and the absence of platelet-fibrin thrombi distinguish ethanol-induced infarction from that caused by atherosclerotic coronary artery disease. The direct vascular toxicity of ethanol may be an important aspect of the mechanism of successful ASA.

Adolescent↗

Chronic antibody mediated rejection of renal allografts: pathological, serological and immunologic features in nonhuman primates.

The pathogenesis of late renal allograft loss is heterogeneous and difficult to diagnose. We have analyzed renal allografts in nonhuman primates to determine the relationship between alloantibodies and the graft pathology of late graft loss. Seventeen Cynomolgus monkeys were chosen from among those on several protocols for renal allotransplantation with mixed chimerism induction so that animals with and without alloantibodies were included. All animals received transient CD154 blockade and short-term cyclosporine treatment until day 28. Serial blood samples were tested for alloantibodies. Protocol biopsies and autopsy kidneys were scored for pathology and C4d deposition. Group 1, defined by complete lack of C4d deposition (24 tissue samples; 8 recipients), had no detectable alloantibodies (33 serum samples; 1-7 samples per recipient) and no evidence of chronic rejection. Three survived greater than 2 years with normal function and histology. Group 2, defined as having C4d deposition in peritubular capillaries, all made alloantibodies (100%), and most grafts later showed chronic allograft glomerulopathy (89%), and/or arteriopathy (89%). All grafts in Group 2 failed (3-27 months). Pathologic lesions of typical of chronic rejection in humans develop in monkeys, correlate with antecedent alloantibodies/C4d deposition and predict chronic rejection rather than durable accommodation.

Animals↗

A new technique for symmetry determination in tooth morphology using image analysis: application in the diagnosis of solitary maxillary median central incisor.

OBJECTIVE: To develop a new technique for determining symmetry in tooth morphology and to evaluate this in the investigation of a patient with a solitary maxillary median central incisor (SMMCI) and a control group. DESIGN: A 9-year-old Caucasian female presented with SMMCI. Clinically the tooth appeared symmetrical. Morphology measurements of the maxillary central incisor were made using an image analysis system. Symmetry was determined by outlining the tooth from labial and axial views. These images were block filled, duplicated, flipped horizontally and then superimposed on the original image. The coincident area and perimeter of the two images from both views were measured. The method was repeated for the maxillary central incisors of 20 sets of control study models for young adult patients from which reference intervals for comparison with the SMMCI case were prepared. RESULTS: From the labial view, the area and perimeter of the two images of the SMMCI tooth were 98.85% and 98.97% coincident, respectively. From the axial view the area of the two images was 96.17% coincident, while the perimeter was 99.03% coincident. In all but one comparison for coincidence the SMMCI was above the upper limit of the reference range from the control group. CONCLUSIONS: This new technique is a valid method of assessing symmetry and is a useful clinical tool in cases of SMMCI.

Adult↗

A digital SLR or intra-oral camera: preference for acquisition within an image analysis system for measurement of disclosed dental plaque area within clinical trials.

OBJECTIVES: The aim of this investigation was to compare the accuracy and reproducibility of images acquired from two types of camera (digital SLR camera, Kodak DCS410, KJP, UK and an intra-oral camera, Schick Technologies, UK) for application within an imaging system used for the quantification of disclosed dental plaque. METHODS: Subjects refrained from brushing their teeth for 24 h. Their teeth were then disclosed with Erythrosin FDC Red 3 and duplicate sets of images were obtained by each examiner of the upper central and lateral incisors. Images were then saved and measured for dental plaque area. These data were used to calculate reliability. RESULTS: No statistically significant bias in the measurements of plaque area was found. The reliability results showed the method was reliable. However, the image analysis system incorporating the 35 mm SRL camera was more reliable for both operators, as demonstrated by their intra-operator results. This was also collaborated by the inter-operator results. CONCLUSION: In this investigation the digital SLR camera combined with the image analysis system and frame permitted greater reliability of dental plaque surface area measurements than the digital intra-oral camera. This conclusion was derived both from the reliability data and from the perceived ease of use and flexibility of both camera types. When combined with the use of the custom-made frame, the images using the digital SLR camera were highly reproducible, confirming the systems application within clinical trials.

Adult↗

Prolonged survival of allogeneic islets in cynomolgus monkeys after short-term anti-CD154-based therapy: nonimmunologic graft failure?

Conventional drug therapy and several anti-CD154 mAb-based regimens were tested in the nonhuman primate (NHP) islet allograft model and found to be inadequate because islets were lost to rejection. Short-term therapy with an optimized donor-specific transfusion (DST) + rapamycin (RPM) + anti-CD154 mAb regimen enables immunosuppression drug-free islet allograft function for months following cessation of therapy in the NHP islet allograft model. After a substantial period of drug-free graft function, these allografts slowly and progressively lost function. Pathologic studies failed to identify islet allograft rejection as a destructive islet invasive lymphocytic infiltration of the allograft was not detected. To evaluate the mechanism, immunologic versus nonimmunologic, of the late islet allograft loss in hosts receiving the optimized therapeutic regimen, we performed experiments with islet autografts and studied islet function in NHPs with partial pancreatectomy. The results in both experiments utilizing autologous islet allografts and partially pancreatectomized hosts reinforce the view that the presence of a marginal islet mass leads to slowly progressive nonimmunological islet loss. Long-term clinically successful islet cell transplantation cannot be realized in the absence of parallel improvements in tolerizing regimens and in the preparation of adequate numbers of islets.

Animals↗

Measurement of stain removal in vitro: a comparison of two instrumental methods.

AIM: The aim of this study was to compare an established spectrophotometrical approach for the measurement of stain removal in vitro with a new digital image analysis system. METHOD: Eighteen acrylic blocks were stained by cycling them through human saliva (2 min), chlorhexidine (2 min) and tea (1 h), rinsed with deionized water and left to air dry. The absorbance of each block was then measured at 395 nm using a single-beam spectrophotometer. The lightness (L-value) of the stained blocks (after a baseline correction) was measured using digital image analysis. Image acquisition and L-values were obtained using Adobe Photoshop software. The stain removal ability of two whitening toothpastes and deionized water was tested by immersing each stained block in a test slurry (15 g paste/60 ml deionized water) for 1 min, rinsing and finally left to air dry. This cycle was repeated until the blocks had 5 min exposure to the slurry. Absorbance values from spectrophotometry and L-values by image analysis were obtained after each cycle. RESULTS: Fleiss' coefficient of reliability for intra-operator repeatability of the image analysis system and spectrophotometry was 0.999 for both methods which shows excellent reliability. Pearson's correlation coefficients for the two methods (stain build-up) were 0.976. Test products A, B and C gave correlations of 0.962, 0.998 and 0.817 respectively (stain removal), significant at the 0.01 level. CONCLUSION: The image system is a reliable alternative measurement method validated here against spectrophotometry for stain removal in vitro, and can provide full colour measurement.

Anti-Infective Agents, Local↗

Visual whiteness ranking of a Vitapan 3D Master shade guide by untrained assessors.

OBJECTIVE: This study was conducted to obtain the ranking order of a 29-tab (including three "bleaching tabs") Vita Shade Guide for perceived "whiteness" by untrained assessors, and to compare this ranking with both the shade guide manufacturer's rank order and a colorimetrically derived rank order. METHODOLOGY: A total of 85 people, not trained in color assessment by shade guides, were asked to rank order the tabs of a Vitapan 3D Master shade guide for perceived "whiteness" under standardized lighting conditions. A whiteness ranking was also obtained colorimetrically using a Minolta CM-2600d spectrophotometer calibrated to give CIE whiteness values. The data were analysed using means, standard deviations, and standard errors. RESULTS: The assessors varied more in their rankings for darker shades than the lighter ones. The order derived by the assessors and the colorimetry order did not match well with the manufacturer's order, especially toward the darker shades. CONCLUSION: For use in studies of whitening products, a new order of the Vitapan 3D Master shade guide tabs has been developed in relation to whiteness.

Adult↗

Tooth size in patients with supernumerary teeth and a control group measured by image analysis system.

OBJECTIVE: The aim of this study was to compare tooth size measurements between patients with supernumerary teeth and a control group. METHOD: The supernumerary group consisted of 56 subjects (21 females and 35 males) and the control group of 40 subjects (20 females and 20 males). All available permanent teeth on the dental casts were imaged and measured from both buccal and occlusal views using an image analysis system. Mesio-distal, bucco-lingual or occluso-gingival dimensions, area and perimeter were measured from each view. RESULTS: Supernumerary tooth patients tended to have larger tooth size measurements for almost all variables than controls. Significant differences (p<0.05) were found for the mesio-distal dimension of the upper and lower incisors and the bucco-lingual dimensions of the lower first premolars. CONCLUSIONS: The results are compatible with supernumerary teeth being a complex dental anomaly with a multifactorial aetiology in which both genetic and environmental factors are important. There is some evidence of a local effect with greater differences in tooth dimension adjacent to the site of the supernumeraries.

Adolescent↗

Quantification of dental plaque on lingual tooth surfaces using image analysis: reliability and validation.

AIM: The aim of this study was to increase the versatility and further validate the method reported by Smith et al. (2001) by testing the reliability of plaque measurement against two well-known dental plaque quantification methodologies using image analysis in a clinical trial. METHOD: The teeth of 40 subjects were disclosed before digital images of the labial and lingual surfaces of their upper and lower incisors were acquired. The amount of plaque present was quantified using a modification of the method described by Smith et al. (2001). The method was modified for obtaining images of the lingual surfaces by incorporating the use of orthodontic occlusal mirrors and 5-mm pieces of moistened blue articulating paper used to enable calibration. Plaque measurements were made from 320 upper and lower anterior teeth from the 40 subjects by two operators. Fliess' coefficient of reliability was used to assess intra- and inter-operator reliability and the independent sample t test was used to assess statistical significance between test and control groups after checking the data for normality. For validation, measurements were recorded using the Turesky et al. (1970) (modification of the Quigley & Hein (1962) plaque index and the Addy et al. (1983) plaque area index. The results were compared with the image analysis method using Pearson's correlation coefficient. RESULTS: The results for reliability were within Fliess' range of "excellent" for both intra-operator repeatability and inter-operator reproducibility. Pearson's correlation coefficients showed highly significant values indicating the close similarity between all three methods. CONCLUSIONS: This method for the measurement of dental plaque on lingual surfaces of anterior teeth proved reliable. The combined results from the labial and lingual surfaces of anterior teeth using image analysis produced trial conclusions comparable with the alternate plaque quantification methods used, with less clinician time and further producing a permanent database of images for future use.

Adult↗

The effect of an aldehyde biocide on the performance and characteristics of laboratory-scale rotating biological contactors.

The effect of an aldehyde biocide, glutaraldehyde, on the treatment efficiency of laboratory-scale rotating biological contactors (RBCs) as well as their component biofilms was studied. Biofilms were established on the RBCs and then exposed to 0-120 ppm glutaraldehyde at a flow rate of 2.5 l x h(-1). The results showed that glutaraldehyde up to 80 ppm did not cause any adverse effect on chemical oxygen demand (COD) removal of the RBC units, microbial activity (ATP content) of biofilms on the RBC disc and viability of the biofilms. Glutaraldehyde at 80 ppm could be almost totally removed by the units regardless of the presence of simple carbon sources. There was at least a fourfold difference in susceptibility of planktonic and sessile bacteria to glutaraldehyde. Cells acclimatized to glutaraldehyde did not increase their capability to degrade normal carbon sources or glutaraldehyde under the conditions used in this study.

Aldehydes↗

The effect of low versus high dose of streptozotocin in cynomolgus monkeys (Macaca fascilularis).

Streptozotocin (STZ) is often used to induce diabetes in animal models. However, morbidity associated with STZ and its ability to induce diabetes vary with different dosages among different animal species, including nonhuman primates. To find an optimal dose of STZ that would cause diabetes with minimal toxicity, we compared low and high doses of STZ. Male cynomolgus monkeys (3-6 years old) were given a single dose of 100 mg/kg (high dose, 4 animals) or 55 mg/kg (low dose, 20 animals) of STZ. Blood glucose levels, intravenous glucose tolerance test (IVGTT), pancreatic biopsies, liver function tests (LFTs), liver biopsies, kidney function tests, and kidney biopsies were performed periodically. Animals from both groups developed diabetes within 24 h after administration of STZ. Serum C-peptide levels in both groups decreased from 2 to 8 ng/mL before STZ to between 0.01 and 0.6 ng/mL after STZ. Animals with the high dose of STZ developed transient vomiting within minutes after injection. During the first week after STZ injection, high-dose animals developed elevated LFTs, BUN and creatinine. In contrast, low-dose animals had normal liver and kidney function tests. Histological analysis showed that animals given the high dose of STZ developed marked steatosis of the liver and tubular injury in the kidneys, whereas animals given the low dose of STZ had normal-looking liver and kidney histology. The pancreatic islets in both groups were indistinguishable by immunoperoxidase staining for insulin, and showed either no insulin-positive cells or rare insulin-positive cells. Glucagon staining was normal. Over time, low-dose diabetic monkeys remained persistently hyperglycemic with negligible C-peptide stimulation by intravenous glucose. We conclude that low-dose STZ at 55 mg/mL successfully induces diabetes in cynomolgus monkeys with minimal liver and kidney toxicity.

Animals↗

Effects of streptozotocin on autoimmune diabetes in NOD mice.

Non-obese diabetic (NOD) mice develop autoimmunity that destroys their native beta cells causing diabetes. Their autoimmunity will also destroy syngeneic transplanted islets and transfer both autoimmunity and diabetes via spleen cells to non-diabetic mice. In this report, we studied the effects of streptozotocin (STZ) on the autoimmune diabetes in NOD mice. We transplanted NOD.SCID islets into three groups of NOD mice: (1) spontaneously diabetic NOD mice (NOD-sp.); (2) prediabetic NOD mice made diabetic by streptozotocin (NOD-stz); and (3) diabetic NOD mice also treated with streptozotocin (NOD-sp./stz). In the first group, the transplants were rejected within 3 weeks. In the second and third groups, the transplants survived indefinitely. Alloxan, a drug similar to streptozotocin, did not have the same effect as streptozotocin. The ability of streptozotocin to prevent diabetes in young NOD mice was reversed by anti-CD8 antibody treatment but not by anti-CD4 treatment. Streptozotocin also made spleen cells from diabetic NOD mice less effective transferring diabetes. These results indicate that streptozotocin treatment both prevents and reverses the islet destructive autoimmunity in NOD mice. We postulate that the effects of streptozotocin treatment may be mediated in part by regulatory T cells.

Animals↗

The effect of a quaternary ammonium biocide on the performance and characteristics of laboratory-scale rotating biological contactors.

AIMS: To study the effect of a quaternary ammonium biocide, didecyldimethylammonium chloride (DDAC), on the treatment efficiency of laboratory-scale rotating biological contactors (RBCs) as well as their component biofilms. METHODS AND RESULTS: Biofilms were established on the RBCs and then exposed to 0-160 mg l(-)1 (p.p.m.) DDAC at a flow rate of 2.5 l h(-1). The treatment efficiency of the RBC and the microbial activity of the biofilms were markedly decreased when 40 mg l(-1) DDAC or greater were applied to the units. However, DDAC had no effect on the number of viable bacteria in the biofilms when DDAC concentrations up to 80 mg l(-1) were applied to the RBCs. No viable bacteria could be detected in the biofilm when DDAC was applied at 160 mg l(-1). Extended observation over a further 40 d with 20 and 80 mg l(-1) DDAC showed similar results in terms of chemical oxygen demand removal, ATP content and viability of biofilms compared with those values over the first 12 d of exposure. CONCLUSIONS: There was at least a fourfold difference in the susceptibility of planktonic and sessile bacteria to DDAC. Cells acclimatized to DDAC did not increase their capability to degrade normal carbon sources or DDAC under the conditions used in this study. SIGNIFICANCE AND IMPACT OF THE STUDY: The results show that RBCs can be used to treat effluents containing DDAC at concentrations up to 20 mg l(-1) and that 160 mg l(-1) of DDAC was required to eliminate cells in established biofilms.

Animals↗

Further studies of a model for the etiology of anomalies of tooth number and size in humans.

A multifactorial model based on an underlying continuous distribution of tooth size, with thresholds determining hypodontia and supernumeraries, has been proposed [1]. Our aim is to investigate this model by comparing tooth morphology of affected patients and their first degree relatives with normal controls. An image analysis system [2] was used to measure teeth on study models of controls, patients with hypodontia of varying degrees and location, first-degree relatives of hypodontia index cases, and patients with supernumerary teeth in the maxillary incisor region. Mesio-distal crown size in hypodontia patients was smaller than controls, and this difference was significant for all tooth types. There was a general pattern: the more severe the hypodontia, the smaller the size of the tooth formed. Patients with supernumerary teeth had permanent maxillary central and lateral incisors and canines that were significantly larger in mesio-distal width than controls. The maxillary central incisors also differed in taper in supernumerary patients compared to controls. Hypodontia prevalence was higher in first-degree relatives (22%) of hypodontia index cases than in the general population (4.4%), and unaffected relatives had smaller teeth than controls. Thus, there were generalized and localized effects within the dentition, and these findings are compatible with the statistical expectations of the proposed multifactorial model.

Adult↗

Long-term islet allograft function in the absence of chronic immunosuppression: a case report of a nonhuman primate previously made tolerant to a renal allograft from the same donor.

UNLABELLED: Development of mixed chimerism by donor bone marrow transplantation (DBMT) has led to long-term tolerance of solid organ allografts in nonhuman primates. As an initial attempt to extend this approach to cellular transplant, islet transplant from the same donor was attempted in the recipient previously made tolerant to a kidney allograft. METHODS: After the conditioning with ATG, total body irradiation, thymic irradiation, and splenectomy, DBMT was performed followed by 4 weeks of cyclosporine. Kidney transplantation and native nephrectomies were subsequently performed on day 89. After 2.8 years of DBMT, diabetes was induced by streptozocin (STZ) and islets from bone marrow and kidney donor were transplanted without immunosuppression. RESULTS: After DBMT, the recipient developed chimerism and no evidence of kidney rejection for more than 1000 days. STZ induced diabetes was reversed after the islet transplantation. Islet biopsies demonstrated insulin staining without rejection. Although the recipient became diabetic 300 days after islet transplantation, viable transplanted islets were found in the liver and under the kidney capsule without any evidence of rejection. CONCLUSION: Tolerance with a nonmyeloablative conditioning can allow successful pancreatic islet transplantation without immunosuppression. Because no histological evidence of rejection was identified, recurrent diabetes is presumed to be inadequate islet mass.

ABO Blood-Group System↗

Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants.

Mouse-to-rat cardiac transplants survive long term after transient complement depletion by cobra venom factor and T cell immunosuppression by cyclosporin A. Expression of heme oxygenase-1 (HO-1) by the graft vasculature is critical to achieve graft survival. In the present study, we asked whether this protective effect was attributable to the generation of one of the catabolic products of HO-1, carbon monoxide (CO). Our present data suggests that this is the case. Under the same immunosuppressive regimen that allows mouse-to-rat cardiac transplants to survive long term (i.e., cobra venom factor plus cyclosporin A), inhibition of HO-1 activity by tin protoporphyrin, caused graft rejection in 3--7 days. Rejection was associated with widespread platelet sequestration, thrombosis of coronary arterioles, myocardial infarction, and apoptosis of endothelial cells as well as cardiac myocytes. Under inhibition of HO-1 activity by tin protoporphyrin, exogenous CO suppressed graft rejection and restored long-term graft survival. This effect of CO was associated with inhibition of platelet aggregation, thrombosis, myocardial infarction, and apoptosis. We also found that expression of HO-1 by endothelial cells in vitro inhibits platelet aggregation and protects endothelial cells from apoptosis. Both these actions of HO-1 are mediated through the generation of CO. These data suggests that HO-1 suppresses the rejection of mouse-to-rat cardiac transplants through a mechanism that involves the generation of CO. Presumably CO suppresses graft rejection by inhibiting platelet aggregation that facilitates vascular thrombosis and myocardial infarction. Additional mechanisms by which CO overcomes graft rejection may involve its ability to suppress endothelial cell apoptosis.

Acute Disease↗

Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia.

Low folate intake as well as alterations in folate metabolism as a result of polymorphisms in the enzyme methylenetetrahydrofolate reductase (MTHFR) have been associated with an increased incidence of neural tube defects, vascular disease, and some cancers. Polymorphic variants of MTHFR lead to enhanced thymidine pools and better quality DNA synthesis that could afford some protection from the development of leukemias, particularly those with translocations. We now report associations of MTHFR polymorphisms in three subgroups of pediatric leukemias: infant lymphoblastic or myeloblastic leukemias with MLL rearrangements and childhood lymphoblastic leukemias with either TEL-AML1 fusions or hyperdiploid karyotypes. Pediatric leukemia patients (n = 253 total) and healthy newborn controls (n = 200) were genotyped for MTHFR polymorphisms at nucleotides 677 (C-->T) and 1,298 (A-->C). A significant association for carriers of C677T was demonstrated for leukemias with MLL translocations (MLL+, n = 37) when compared with controls [adjusted odd ratios (OR) = 0.36 with a 95% confidence interval (CI) of 0.15-0.85; P = 0.017]. This protective effect was not evident for A1298C alleles (OR = 1.14). In contrast, associations for A1298C homozygotes (CC; OR = 0.26 with a 95% CI of 0.07--0.81) and C677T homozygotes (TT; OR = 0.49 with a 95% CI of 0.20--1.17) were observed for hyperdiploid leukemias (n = 138). No significant associations were evident for either polymorphism with TEL-AML1+ leukemias (n = 78). These differences in allelic associations may point to discrete attributes of the two alleles in their ability to alter folate and one-carbon metabolite pools and impact after DNA synthesis and methylation pathways, but should be viewed cautiously pending larger follow-up studies. The data provide evidence that molecularly defined subgroups of pediatric leukemias have different etiologies and also suggest a role of folate in the development of childhood leukemia.

Adolescent↗

The quantification of dental plaque using an image analysis system: reliability and validation.

AIM: Established clinical indices used to measure dental plaque have limitations. The aim of this study was to develop and evaluate a new method of quantitative plaque measurement, with increased sensitivity and reproducibility, using a purpose designed image analysis system. METHOD: After plaque disclosure, the patient was positioned in a cephalometric head holder mounted in a custom-built frame with standard lighting and camera position. A 32-bit Digital Camera grabbed the image of the patient's teeth, which was analysed using Adobe Photoshop (V5.02, Adobe Systems Ltd, Europe) and Image Pro Plus software (V4.0, Media Cybernetics, USA). Measurements were made on 120 incisors in 15 patients and reproducibility was assessed using Fliess' Coefficient of Reliability. Sensitivity was assessed by comparison of results of treatment effects from a clinical trial involving 30 patients. Analysis of covariance was used to compare the image analysis system with the Turesky modification of the Quigley and Hein plaque index and the Addy plaque area index. RESULTS: The results were within the 'Excellent Reliability' category, for inter-operator reproducibility and intra-operator repeatability. CONCLUSIONS: This new system provided accurate quantitative measurements of dental plaque and labial tooth surfaces and was shown to have increased sensitivity when compared with the Turesky modification of the Quigley and Hein plaque index and the Addy plaque area index. The stored images can be re-measured for reliability and comparability between studies.

Analysis of Variance↗