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Biomedical subjects

S L Smith

Publications and source records attributed to S L Smith.

At least 37 records · Page 2Linked to original sources
PubMed2001

Radionuclide bone scintigraphy in the detection of significant complications after total knee joint replacement.

AIM: Post-arthroplasty knee pain is common and clinically it can be difficult to identify those patients with complications requiring active treatment. The aim of this study was to determine the usefulness of(99)Tc(m)-MDP bone scintigraphy. METHOD: A retrospective study of all patients having a(99)Tc(m)-MDP bone scintigram for a painful knee arthroplasty between 1993 and 1999 was performed. Bone scintigrams were classified as normal or abnormal by a single observer. The results of these investigations were correlated with clinical outcome. RESULTS: Seventy-five patients with painful knee arthroplasties were referred for investigation. A total of 80 bone scintigrams were performed. The average patient age was 66.2 years (42 female and 33 male). The mean time period between surgery and onset of knee pain was 3 years. A final clinical diagnosis based on arthroscopy, open surgery, and extended clinical follow-up was available for all patients. Forty-three (53.8%) of the scintigrams were normal and 37 (46.3%) abnormal. Two patients with a normal bone scintigram has loose prostheses. Thirteen patients with an abnormal study had normal prostheses on follow-up and these tended to be patients scanned less than a year after surgery. The sensitivity, specificity, positive predictive value and negative predictive value of an unequivocally normal or abnormal bone scintigram was 92.3, 75.9, 64.9 and 95.0%, respectively. The pattern of isotope uptake in the abnormal studies was not specific enough to reliably differentiate aseptic from septic loosening. CONCLUSION: Radionuclide bone scintigraphy is useful in the assessment of the painful knee arthroplasty. A negative bone scintigram is reassuring and makes loosening or infection unlikely.

Aged↗
PubMed2001

Does simple estimation of 131I-metaiodobenzylguanidine uptake in patients with neural crest tumours correlate with clinical outcome?

A retrospective study was undertaken in six patients (three male and three female) with neural crest tumours who received therapeutic doses of 131I-meta-iodobenzylguanidine (131I-MIBG) (6.7-10.5 GBq). The age range of the patients was 13-65 years (mean 36 years). Quantification of tumour uptake was obtained from images acquired with a large-field-of-view gamma camera on a single occasion between 2 and 10 days post-treatment. Tumour uptake was calculated to be 0.1% and 3.2% of the administered dose, corresponding to uptakes of 6.7-142.8 MBq. Tumour volume was assessed from computed tomography (CT) or magnetic resonance (MR) images and estimates of tumour dose made from the Medical Internal Radiation Dosimetry scheme (MIRD) tables. Estimated doses were between 7 and 113 Gy. Most significantly, our findings indicate that high tumour uptake did not always correlate with good clinical response.

3-Iodobenzylguanidine↗
PubMed2001

BTS 72664-- a novel CNS drug with potential anticonvulsant, neuroprotective, and antimigraine properties.

BTS 72664, (R)-7-[1-(4-chlorophenoxy)]ethyl]-1,2,4-triazolo(1,5-alpha)pyrimidine, was identified as a drug development candidate from a research program designed to discover novel, broad-spectrum, non-sedative anticonvulsant drugs. BTS 72664 antagonized bicuculline (BIC)- and maximal electroshock (MES)-induced convulsions with ED(50) values of 1.9 and 47.5 mg/kg p.o., respectively. In rodents, it has a wide spectrum of activity preventing seizures induced by picrotoxin, pentylenetetrazol, i.c.v. 4-aminopyridine or NMDA, and audiogenic seizures in DBA-2 mice and GEPR-9 rats. BTS 72664 was also effective in preventing convulsions in amygdala-kindled rats The lack of sedative potential was predicted on the basis of wide separation between ED(50) in anticonvulsant models and TD(50) for motor impairment in mice in rotating rod and inverted horizontal grid tests. BTS 72664 is likely to produce its anticonvulsant effect by enhancing chloride currents through picrotoxin-sensitive chloride channels, and by weak inhibition of Na(+) and NMDA channels. It does not act, however, at the benzodiazepine binding site. In addition to its potential use in the treatment of epilepsy BTS 72664 may be useful in the treatment of stroke. At 50 mg/kg p.o. x 4, given to rats at 12 hourly intervals, starting at 15 min after permanent occlusion of middle cerebral artery (MCA), it reduced cerebral infarct size by 31% (measured at 2 days after insult) and accelerated recovery in a functional behavioral model. BTS 72664 prevented increases in extraneuronal concentrations of glutamate, glycine and serine brain levels induced by a cortical insult to rats (cf. cortical spreading depression). It may, therefore, have also antimigraine activity.

Animals↗
PubMed2001

VibD and VibH are required for late steps in vibriobactin biosynthesis in Vibrio cholerae.

Vibrio cholerae synthesizes the catechol siderophore vibriobactin. In this report, we present the complete map of a vibriobactin gene region containing two previously unreported vibriobactin biosynthetic genes. vibD encodes a phosphopantetheinyl transferase, and vibH encodes a novel nonribosomal peptide synthase. Both VibD and VibH are required for vibriobactin biosynthesis.

Bacterial Proteins↗
PubMed2001

Location of death in Canada. A comparison of 20th-century hospital and nonhospital locations of death and corresponding population trends.

This report compares 20th-century Canadian hospital and nonhospital location-of-death trends and corresponding population mortality trends. One of the chief findings is a hospitalization-of-death trend, with deaths in hospital peaking in 1994 at 80.5% of all deaths. The rise in hospitalization was more pronounced in the years prior to the development of a national health care program (1966). Another key finding is a gradual reduction since 1994 in hospital deaths, with this reduction occurring across all sociodemographic variables. This suggests nonhospital care options are needed to support what may be an ongoing shift away from hospitalized death and dying.

Aged↗
PubMed2001

A five-station hip joint simulator.

A five-station hip joint wear simulator was designed and built which featured simplified motion and loading. An elliptical wear path was produced using approximately sinusoidal motion in the flexion/extension and internal/external rotation axes and the dynamic loading approximated to a square wave. Five 28 mm diameter zirconia femoral heads articulated against ultra-high molecular weight polyethylene acetabular cups in 25 per cent bovine serum for 5 x 10(6) cycles. Gravimetric wear measurement was used with moisture absorption compensation using a dynamically loaded soak control. With motion of physiological magnitude, the mean acetabular cup wear rate was 52.2 mm3/10(6) cycles which is comparable with a number of clinical studies.

Hip Prosthesis↗
PubMed2001

The effect of femoral head diameter upon lubrication and wear of metal-on-metal total hip replacements.

It has been found that a remarkable reduction in the wear of metal-on-metal hip joints can be achieved by simply increasing the diameter of the joint. A tribological evaluation of metal-on-metal joints of 16, 22.225, 28 and 36 mm diameter was conducted in 25 per cent bovine serum using a hip joint simulator. The joints were subject to dynamic motion and loading cycles simulating walking for both lubrication and wear studies. For each size of joint in the lubrication study, an electrical resistivity technique was used to detect the extent of surface separation through a complete walking cycle. Wear of each size of joint was measured gravimetrically in wear tests of at least 2 x 10(6) cycles duration. Joints of 16 and 22.225 mm diameter showed no surface separation in the lubrication study. This suggested that wear would be proportional to the sliding distance and hence joint size in this boundary lubrication regime. A 28 mm diameter joint showed only limited evidence of surface separation suggesting that these joints were operating in a mixed lubrication regime. A 36 mm diameter joint showed surface separation for considerable parts of each walking cycle and hence evidence of the formation of a protective lubricating film. Wear testing of 16 and 22.225 mm diameter metal-on-metal joints gave mean wear rates of 4.85 and 6.30 mm3/10(6) cycles respectively. The ratio of these wear rates, 0.77, is approximately the same as the joint diameters ratio, 16/22.225 or 0.72, as expected from simple wear theory for dry or boundary lubrication conditions. No bedding-in was observed with these smaller diameter joints. For the 28 mm diameter joint, from 0 to 2 x 10(6) cycles, the mean wear rate was 1.62 mm3/10(6) cycles as the joints bedded-in. Following bedding-in, from 2.0 x 10(6) to 4.7 x 10(6) cycles, the wear rate was 0.54 mm3/10(6) cycles. As reported previously by Goldsmith et al. in 2000 [1], the mean steady state wear rate of the 36 mm diameter joints was lower than those of all the other diameters at 0.07 mm3/10(6) cycles. For a range of joints of various diameters, subjected to identical test conditions, mean wear rates differed by almost two orders of magnitude. This study has demonstrated that the application of sound tribological principles to prosthetic design can reduce the wear of metal-on-metal joints, using currently available materials, to a negligible level.

Arthroplasty, Replacement, Hip↗
PubMed2001

An in vitro wear study of alumina-alumina total hip prostheses.

Four 28 mm diameter alumina-alumina hip prostheses were tested in the Mkll Durham hip simulator for 5 x 10(6) cycles using 25 per cent bovine serum as lubricant. Wear of the heads and cups was measured gravimetrically. The mean and standard deviation of the wear rate for the alumina cups was 0.097 +/- 0.039 mm3/10(6) cycles. The femoral heads produced such low wear that it could not be measured by weighing but could be detected byincreased surface roughness measurements. Such low wear rates represent about one-five-hundredthof the wear of ultra-high molecular weight polyethylene (UHMWPE) against ceramic in a similar test and supports work which indicates that fluid film lubrication exists in these joints.

Aluminum Oxide↗
PubMed2001

High efficiency electroporation of human umbilical cord blood CD34+ hematopoietic precursor cells.

Human umbilical cord blood provides an alternative source of hematopoietic cells for purposes of transplantation or ex vivo genetic modification. The objective of this study was to evaluate electroporation as a means to introduce foreign genes into human cord blood CD34+ cells and evaluate gene expression in CD34+/CD38(dim) and committed myeloid progenitors (CD33+, CD11b+). CD34+ cells were cultured in X-VIVO 10 supplemented with thrombopoietin, stem cell factor, and Flt-3 ligand. Electroporation efficiency and cell viability measured by flow cytometry using enhanced green fluorescent protein (EGFP) as a reporter indicated 31% +/- 2% EGFP+ /CD34+ efficiency and 77% +/- 3% viability as determined 48 hours post-electroporation. The addition of allogeneic cord blood plasma increased the efficiency to 44% +/- 5% with no effect on viability. Of the total CD34+ cells 48 hours post-electroporation, 20% were CD38(dim)/EGFP+. CD34+ cells exposed to interleukin-3, GM-CSF and G-CSF for an additional 11 days differentiated into CD33+ and CD11b+ cells, and 9% +/- 3% and 8% +/- 7% were expressing the reporter gene, respectively. We show that electroporation can be used to introduce foreign genes into early hematopoietic stem cells (CD34+/CD38(dim)), and that the introduced gene is functionally expressed following expansion into committed myeloid progenitors (CD33+, CD11b+) in response to corresponding cytokines. Further investigation is needed to determine the transgene expression in functional terminal cells derived from the genetically modified CD34+ cells, such as T cells and dendritic cells.

ADP-ribosyl Cyclase↗
PubMed2001

The mechanism of resveratrol-induced vasorelaxation differs in the mesenteric resistance arteries of lean and obese rats.

Resveratrol has been shown to induce vasorelaxation. In this study, we investigated the mechanism(s) of resveratrol-induced vasorelaxation in resistance mesenteric arteries from male lean and dietary-induced obese rats. Compared with lean rats, arteries from dietary-obese rats showed significant (P<0.001) endothelial dysfunction, as indicated by a decrease (>20%) in maximal acetylcholine-induced vasorelaxation. Resveratrol (5-35 micromol/l) induced concentration-dependent relaxation of mesenteric arteries preconstricted with noradrenaline (8 micromol/l) or KCl (125 mmol/l) from both lean and dietary-obese rats. There were no significant differences between the two groups, achieving a maximum relaxation of >95% at a concentration of 35 micromol/l. In noradrenaline-preconstricted arteries from lean rats, N(G)-nitro-L-arginine methyl ester (L-NAME; 100 and 300 micromol/l) caused a significant (P<0.01) concentration-dependent rightward shift in reseveratrol activity, with no effect on maximal responses. However, L-NAME (100 and 300 micromol/l) did not alter the effects of reseveratrol on arteries from dietary-obese rats, giving superimposed concentration-responses curves. Indomethacin was also ineffective in altering resveratrol activity in arteries from both lean and dietary-obese rats. In noradrenaline-precontracted arteries from dietary-obese rats, responses to resveratrol were not attenuated by endothelial denudation, indicating an action independent of the endothelium. This study indicates that: (a) the maximal effects of resveratrol on resistance arteries from lean and dietary-obese rats are not effected by endothelial dysfunction, and (b) the effects of resveratrol in lean animals (where endothelial function is not impaired), but not in dietary-obese rats, are mediated via NO.

Acetylcholine↗
PubMed2001

Midsagittal facial tissue thicknesses of children and adolescents from the Montreal growth study.

Knowledge of changes in soft tissue depths during growth and development is important in applied contexts of forensics and dentistry as well as in growth research. In forensics, applications include facial reproductions, video superimpositions, and child aging/progressions. Garlie and Saunders (1) recently published radiographic data from the Burlington Canadian growth study; here, we present data from a mixed longitudinal sample of French-Canadian children and adolescents. Females (N = 159) range in age from 6 to 18 years: males (N = 129), from 6 to 19 years. Cephalometric measurements include nine soft tissue thicknesses, two hard tissue distances (sella-nasion and nasion-menton), and three measures of nasal projection. Several tissue thicknesses are moderately correlated with one another. The majority of thicknesses show significant sex differences by the time of adolescence; nasion and upper labial thicknesses are significantly different by sex at all ages from 6 to 18 years, as are the two hard tissue distances. However, thickness at nasion, as well as at glabella, changes little over time. Thickness at pogonion is variable and differs most between males and females at age 16; the length of the anterior inferior portion of the nose is significantly different between the ages of 6 and 12. Measurements display small and slow changes during development. The greatest average change per year (c. 2 mm/yr) is for a hard tissue measure, nasion-menton. The nasal and mid-philtrum regions have greater age changes than do other soft tissue variables. Much of the variation remains unexplained by changes with age or differences between sexes.

Adolescent↗
PubMed2000

Phase I and pharmacokinetic study of irofulven, a novel mushroom-derived cytotoxin, administered for five consecutive days every four weeks in patients with advanced solid malignancies.

PURPOSE: To evaluate the toxicity and pharmacologic behavior of the novel mushroom-derived cytotoxin irofulven administered as a 5-minute intravenous (IV) infusion daily for 5 days every 4 weeks to patients with advanced solid malignancies. PATIENTS AND METHODS: In this phase I trial, 46 patients were treated with irofulven doses ranging from 1.0 to 17.69 mg/m(2) as a 5-minute IV infusion (two patients received a 1-hour infusion) daily for 5 days every 4 weeks. The modified continual reassessment method was used for dose escalation. Pharmacokinetic studies were performed on days 1 and 5 to characterize the plasma disposition of irofulven. RESULTS: Forty-six patients were treated with 92 courses of irofulven. The dose-limiting toxicities on this schedule were myelosuppression and renal dysfunction. At the 14.15-mg/m(2) dose level, renal dysfunction resembling renal tubular acidosis occurred in four of 10 patients and was ameliorated by prophylactic IV hydration. The 17.69-mg/m(2) dose level was not tolerated because of grade 4 neutropenia and renal toxicity, whereas the 14.15-mg/m(2) dose level was not tolerable with repetitive dosing because of persistent thrombocytopenia. Other common toxicities included mild to moderate nausea, vomiting, facial erythema, and fatigue. One partial response occurred in a patient with advanced, refractory metastatic pancreatic cancer lasting 7 months. Pharmacokinetic studies of irofulven revealed dose-proportional increases in both maximum plasma concentrations and area under the concentration-time curve, while the agent exhibited a rapid elimination half-life of 2 to 10 minutes. CONCLUSION: Given the results of this study, the recommended dose of irofulven is 10.64 mg/m(2) as a 5-minute IV infusion daily for 5 days every 4 weeks. The preliminary antitumor activity documented in a patient with advanced pancreatic cancer and the striking preclinical antitumor effects of irofulven observed on intermittent dosing schedules support further disease-directed evaluations of this agent on the schedule evaluated in this study.

Adult↗
PubMed2000

Dietary bioflavonoids induce cleavage in the MLL gene and may contribute to infant leukemia.

Chromosomal translocations involving the MLL gene occur in about 80% of infant leukemia. In the search for possible agents inducing infant leukemia, we identified bioflavonoids, natural substances in food as well as in dietary supplements, that cause site-specific DNA cleavage in the MLL breakpoint cluster region (BCR) in vivo. The MLL BCR DNA cleavage was shown in primary progenitor hematopoietic cells from healthy newborns and adults as well as in cell lines; it colocalized with the MLL BCR cleavage site induced by chemotherapeutic agents, such as etoposide (VP16) and doxorubicin (Dox). Both in vivo and additional in vitro experiments demonstrated topoisomerase II (topo II) as the target of bioflavonoids similar to VP16 and Dox. Based on 20 bioflavonoids tested, we identified a common structure essential for topo II-induced DNA cleavage. Reversibility experiments demonstrated a religation of the bioflavonoid as well as the VP16-induced MLL cleavage site. Our observations support a two-stage model of cellular processing of topo II inhibitors: The first and reversible stage of topo II-induced DNA cleavage results in DNA repair, but also rarely in chromosome translocations; whereas the second, nonreversible stage leads to cell death because of an accumulation of DNA damage. These results suggest that maternal ingestion of bioflavonoids may induce MLL breaks and potentially translocations in utero leading to infant and early childhood leukemia.

Adult↗
PubMed2000

Shape variation of the human pollical distal phalanx and metacarpal.

Human distal pollical phalanx form has been associated with tool manufacture, and the broad tuft of this bone in Neanderthals has been suggested to be a climatic adaptation and/or an aid to a tremendously powerful grip. A wide first metacarpal head has also been proposed to be useful in distinguishing tool-dependent hominids from those less reliant on tools. In order to contribute to an evaluation of these hypotheses variation in first metacarpal and distal phalanx shape is explored among samples of modern humans and compared to that of fossil hominids. Modern humans are from the Terry Collection, Larsen Bay, a Chinese-Alaskan cemetery, Egypt, and Sully and Mobridge. Hominid fossils include AL 333w-39, SKX 5016, SK 84, Stw 294, OH 7, several Neanderthals, Skhūl 4 and 5, and Predmostí 3. Analysis involves length-width ratios, regressions of distal phalanx tuft width on base width and of metacarpal head width on length, and pattern profiles based on Z-scores with reference to the Larsen Bay sample. Larsen Bay individuals are robust, while Terry "blacks," Egyptians, and Chinese-Alaskan males tend to be gracile. Fossil hominids are most distinctive for distal phalanx radioulnar tuft and mid-shaft widths relative to length. Security of grip is one plausible explanation. While most modern samples are positively allometric for tuft width relative to base width, the Larsen Bay and fossil hominid samples are not; thus caution is advised in accepting a base-tuft width comparison as a tool-dependence marker. Separation from modern humans is not easily achieved with metacarpal measures, but the Hadar metacarpal has distinctively narrow radioulnar head width ratios. While first metacarpal head expansion among hominids may plausibly be related to tool manufacture, other activities that place stress on the metacarpophalangeal joint should also be considered.

Alaska↗
PubMed2000

A tribological study of UHMWPE acetabular cups and polyurethane compliant layer acetabular cups.

A novel design of polyurethane compliant layer acetabular cup has been developed through a series of friction, creep and wear tests. Friction tests were initially conducted on ABG standard form, polyurethane acetabular cups and an ABG standard form, UHMWPE acetabular cup for comparison. The polyurethane cups showed lower friction than the UHMWPE cup with maximum friction factors between 0. 008 and 0.02 compared with 0.035 for the UHMWPE cup. This indicated that, in the polyurethane cups, more of the load across the joint was carried by the fluid entrapped in the joint space rather than with asperity contact, compared with the UHMWPE cup. The inherent compliance of the polyurethane is used to promote elasto-hydrodynamic lubrication. However, this compliance raised concerns over excessive creep, which may in turn adversely affect tribological performance. Therefore, creep tests were undertaken on the ABG standard form, polyurethane acetabular cups followed by further friction tests. Small amounts of creep occurred in the polyurethane cups at ambient temperature, which reduced the friction slightly (maximum friction factors of 0.009) due to increased conformity between the head and the cup. However, at 37 degrees C, greater creep occurred causing pinching of the femoral head by the acetabular cup resulting in lubricant starvation and higher friction (maximum friction factors of 0.035). The design of the polyurethane cups was subsequently modified to incorporate a flared rim to eliminate the possibility of fluid starvation through pinching. Creep in polyurethane acetabular cups is also affected by the method of fixation of the cups, due to the conformity with and the stiffness of the cup backing. Hence, a one-million-cycle wear test was performed on five ABG flared form, polyurethane acetabular cups on the Mk. I Durham Hip Joint Wear Simulator to evaluate the best method of fixation for the polyurethane cups. The smallest amount of penetration, due to creep and wear, was found with cement fixation (0.30 mm penetration with cement fixation, 0.44 mm with polyethylene holder mounting, and 0.52 mm with metal shell mounting). A 4. 25-million-cycle wear test was then conducted on a further five ABG flared form, polyurethane acetabular cups with cement fixation. Five ABG standard form, UHMWPE acetabular cups were also wear-tested to 5. 0-million cycles. The mean and standard error of the wear rate for the polyurethane cups were 14.1 +/- 4.3 mg/10(6) (12.0 +/- 3.6 mm(3)/10(6)), cycles compared with 44.8 +/- 3.4 mg/10(6) (48.2 +/- 3. 7 mm(3)/10(6)), cycles for the UHMWPE cups. This study showed that the novel polyurethane-compliant layer acetabular cup with cement fixation was tribologically superior to the ABG standard form UHMWPE design currently being used clinically.

Biocompatible Materials↗
PubMed2000

Complement system of bony and cartilaginous fish.

Accumulating evidence indicates that the complement system experienced a discontinuous development at an early stage of vertebrate evolution. Invertebrates such as echinoderms and ascidians, and the most primitive extant vertebrates, the cyclostomes, seem to have a primitive complement system equipped only with the alternative and lectin pathways. In contrast, cartilaginous fish and higher vertebrates seem to have a modern complement system which has two additional pathways, namely the classical and lytic pathways. Recent molecular analyses of the complement system of bony and cartilaginous fish have not only confirmed the above conclusion, but also revealed a unique characteristic of the complement system of fish, where certain key component genes are duplicated. The complement system seems to play a more pivotal role in body defence in fish, whose adaptive immunity is considered to be at a relatively undeveloped state.

Amino Acid Sequence↗