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Biomedical subjects

S Williams

Publications and source records attributed to S Williams.

At least 73 records · Page 4Linked to original sources

In vitro analysis of the wear, wear debris and biological activity of surface-engineered coatings for use in metal-on-metal total hip replacements.

Extremely low wear rates have been reported for metal-on-metal total hip replacements, but concerns remain about the effects of metal ion release, dissolution rates and toxicity. Surface-engineered coatings have the potential to improve wear resistance and reduce the biological activity of the wear debris produced. The aim of this study was to examine the wear and wear debris generation from surface-engineered coatings: titanium nitride (TiN), chromium nitride (CrN) and chromium carbon nitride (CrCN) applied to a cobalt-chrome alloy (CoCr) substrate. The coatings were articulated against themselves in a simple geometry model. The wear particles generated were characterized and the cytotoxic effect on U937 macrophages and L929 fibroblasts assessed. The CrN and CrCN coatings showed a decrease in wear compared to the CoCr bearings and produced small (less than 40 nm in length) wear particles. The wear particles released from the surface engineered bearings also showed a decreased cytotoxic effect on cells compared to the CoCr alloy debris. The reduced wear volumes coupled with the reduced cytotoxicity per unit volume of wear indicate the potential for the clinical application of this technology.

Cell Survival↗

Ethanol-induced mitogen activated protein kinase activity mediated through protein kinase C.

The aim of this study was to determine the pathway(s) by which ethanol activates mitogen-activated protein kinase (MAPK) signaling and to determine the role of Ca2+ in the signaling process. MAPK signaling was determined by assessing MAPK activity, measuring phosphorylated extracellular signaling-regulated kinase (pp 44 ERK-1 and pp 42 ERK-2) expression and ERK activity by measuring ERK-2-dependent phosphorylation of a synthetic peptide as a MAPK substrate in rat vascular smooth muscle cells. Ethanol activated extracellular signal-regulated kinase expression (ERK 1 and 2) could be observed when vascular smooth muscle cells (VSMCs) were stimulated for 5 min or less, but was inhibited when cells are treated for 10 min or more with 1-16 mM of ethanol. Maximum ethanol-induced MAPK activity was observed within 5 min with 4 or 8 mM. Ethanol stimulated MAPK activity was blocked by the protein kinase C (PKC) inhibitor (GF109203X) and epidermal growth factor (EGF) receptor antagonist (PD153035) by 41 +/- 24 and 34 +/- 12.3%, respectively. The calcium channel blocker, diltiazem and the chelating agent, BAPTA, reduced the activation of MAPK activity by ethanol, significantly. The data demonstrate that ethanol-stimulated MAPK expression is mediated partially through both the EGF-receptor and PKC intermediates and that activation through the PKC intermediate is calcium-dependent.

Animals↗

HPC2/ELAC2 polymorphisms and prostate cancer risk: analysis by age of onset of disease.

The candidate prostate cancer susceptibility gene HPC2/ELAC2 has two common coding polymorphisms: (Ser-->Leu 217) and (Ala-->Thr 541). The Thr541 variant in the HPC2/ELAC2 gene has previously been reported to be at an increased frequency in prostate cancer cases. To evaluate this hypothesis we genotyped 432 prostate cancer patients (including 262 patients diagnosed 55 years (OR=1.27, 95% CI 0.59-2.74). We conclude that any association between the Thr541 variant and prostate cancer is likely to be weak.

Adult↗

Spinal lipoma misinterpreted as a meningomyelocele on antenatal MRI scan in a baby girl.

INTRODUCTION: Antenatal screening for spina bifida with ultrasound and MR imaging is increasingly used. CASE REPORT: A baby girl's antenatal MRI examination showed features originally interpreted as a lumbar meningomyelocele. Repeat MRI examination soon after birth showed features of a spinal lipoma (lipomeningomyelocele). This was excised surgically and complete spinal cord untethering was achieved. CONCLUSION: As antenatal MR scanning is increasingly used, and fetal surgery is becoming more prominent, the correct interpretation of such images is crucial. We present a rare case of a misleading antenatal radiological diagnosis of spina bifida, which would have had severe implications if termination of the pregnancy or intra-uterine surgical repair had been considered.

Diagnosis, Differential↗

Hydration dynamics of human fingernails: an ellipsometric study.

We use spectroscopic ellipsometry to obtain the complex refractive index, ñ=n+ik, of human fingernails. By studying the change of ñ upon hydration and dehydration, we reveal three different time domains with typical time constants of 4, 150, and 3200 min. A simple model that takes into account the presence of one fast and one slow process is fully consistent with the observed hydration and dehydration dynamics. We attribute these processes to "free" water incorporated between the keratin filaments and water more tightly "bound" in keratin complexes, respectively. From our model we determine the hydration profiles of "free" and "bound" water during, both, hydration and dehydration.

Chemical Phenomena↗

Prevalence and numbers of Salmonella and Campylobacter spp. on raw, whole chickens in relation to sampling methods.

Salmonella and Campylobacter continue to be major foodborne pathogens and raw poultry is considered to be an important source of these bacteria. In this study, the prevalence and numbers of Salmonella and Campylobacter spp. in relation to isolation/sampling methods were determined in 241 whole raw chickens purchased from retail outlets in England during the winters of 1998/1999 (101 chickens) and 1999/2000 (140 chickens). The packaging of the 140 chickens was also examined for the presence of the above pathogens. The prevalence and numbers of enterococci were examined in 21 of the 101 chickens. In total, Salmonella and Campylobacter spp. were present in 25% and 83% of the chickens, respectively. Salmonella were isolated from a sample representing both the inside and outside of the packaging in 19% of the chickens, while the corresponding figure for Campylobacter spp. was 56%. Both of these pathogens were isolated from the outside of the packaging in 6% of the chickens. Salmonella was more frequently isolated from samples containing chicken skin in comparison with those containing carcass-rinse fluid only. Two chickens (0.8%) were positive for Salmonella by direct enumeration methods with contamination levels of log10 3.8 and 4.5 colony forming units (cfu) per carcass, respectively. The most prevalent serotypes were S. Hadar, S. Enteritidis and S. Indiana and two different serotypes were identified in 5/20 salmonella-positive chickens. Resistance to at least one antibiotic was found in 70% of the strains, 46% were multiresistant (resistant to > or = four drugs) and 52% showed a lowered susceptibility to ciprofloxacin. The likelihood of isolating Campylobacter spp. from neck-skin, carcass-rinse or carcass-rinse plus whole skin samples was similar, Campylobacter spp. were found in higher levels in carcass-rinse or carcass-rinse plus whole skin samples than in neck-skin. The log10 cfu of Campylobacter spp. were 2.70-4.99 in 18% of the chickens and 5.00-6.99 in 20%. Campylobacter isolates (425) comprised Campylobacter jejuni (98%) and C. coli (2%) and 98 different sero/phagetypes of these two species were identified. Resistance to at least one antibiotic was found in 73% of the strains and 13% were multiresistant. Thirteen percent of the strains showed lowered susceptibility to ciprofloxacin, while 4.9% were resistant to erythromycin. Vancomycin-resistant enterococci (VRE), able to grow on agar containing 15 mg l(-1) vancomycin (VRE15), were present in 19 chickens. The log10 cfu of VRE15 was 2.90-3.99 in 10 chickens and between 4.00 and 4.99 in two chickens. The data presented here contribute to risk assessment and highlight the need to continue to emphasise the safe handling of raw retail poultry.

Animals↗

PET imaging of brain acetylcholinesterase using [11C]CP-126,998, a brain selective enzyme inhibitor.

PET and [(11)C]CP-126,998, an N-benzylpiperidinebenzisoxazole, were used to image brain acetylcholinesterase (AChE) distribution in healthy controls before and after administration of 5 mg donepezil p.o., a reversible AChE inhibitor. Logan plots were used to compute distribution volumes (V(T)). The V(T) of [(11)C]CP-126,998 was highest in the basal ganglia and cerebellum and lowest in the cerebral cortex, thalamus, amygdala, and hippocampus. The regional V(T) values correlated well with AChE concentration measured in vitro. Donepezil, given 4 h before PET scanning, induced a substantial inhibition of [(11)C]CP-126,998 binding (43-62%) in all brain regions when compared to the baseline PET study. The results of this study indicate that PET imaging of [(11)C]CP-126,998 may be useful in quantifying the distribution of regional brain AChE. This new PET radiotracer may potentially be employed in the diagnosis and treatment of patients with disorders of cholinergic neurotransmission, such as Alzheimer's disease.

Acetylcholinesterase↗

Imagery and psychotic symptoms: a preliminary investigation.

Recent cognitive accounts of psychotic symptoms have suggested that processes involved in the maintenance of emotional disorders may also be implicated in the maintenance of hallucinations and delusions, and particularly emphasise the appraisals of such symptoms as important. Imaginal appraisals have been identified in emotional disorders, and many studies have reported spontaneously occurring images in patients with anxiety disorders. Such images appear to be linked to affect, beliefs and memories. This study examined the occurrence of imagery, using a semi-structured interview, in 35 patients who were experiencing hallucinations and/or delusions and receiving cognitive therapy. The majority of patients (74.3%) reported images, and most of these were recurrent and associated with affect, beliefs and memories. Common themes included images about feared catastrophes associated with paranoia, traumatic memories, and images about the perceived source or content of voices. The theoretical and clinical implications of these findings are discussed and directions for further research considered.

Adolescent↗

Cobe Spectra is superior to Fenwal CS 3000 Plus for collection of hematopoietic stem cells.

One hundred and seventy-seven stem cell apheresis procedures performed on 91 patients using the Fenwal CS 3000 Plus cell separator and 61 procedures performed on 37 patients using the Cobe Spectra cell separator were studied to compare the CD34(+) cell collection efficiencies (CE; the proportion of the total CD34(+) cell content in the blood volumes processed that is harvested) of the two machines. The absolute peripheral blood CD34(+) cell count was comparable for the two groups (P = 0.27). A strong correlation was seen between the blood CD34(+) cell count and the total number of CD34(+) cells collected for the Spectra (r(2) = 0.59; P < 10(-6)) and for the CS 3000 Plus (r(2) = 0.60; P < 10(-6)). No significant correlation emerged between the peripheral blood CD34(+) cell count and the CE of either machine. The total number of CD34(+) cells collected per procedure was comparable (P = 0.51): median 113 x 10(6) for CS 3000 Plus and median 218 x 10(6)for Spectra. CE was significantly higher with the Spectra (median 45.7%, range 9.8-98.6%) than the CS 3000 Plus (median 30.3%, range 1.7-89.3%; P < 0.00001). We conclude that the CD34(+) cell CE of the Spectra is superior to that of the CS 3000 Plus. Therefore, under the usual clinical conditions, Cobe Spectra should be used preferentially for peripheral blood progentor cell collection to maximize the number of hematopoietic stem cells collected.

Blood Cell Count↗

Rarity of toxigenic Clostridium difficile infections after hematopoietic stem cell transplantation: implications for symptomatic management of diarrhea.

Diarrhea is a common complication of high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT). The frequent and prolonged use of multiple antibiotics in this setting can predispose to infection with toxigenic Clostridium difficile and the development of pseudomembranous colitis. Anti-motility agents are usually not administered in this setting until C. difficile infection has been excluded. The objective of this study was to determine the incidence of C. difficile toxin (CDT) positivity at the time of initial diarrhea in HSCT recipients, and to see if the practice of ensuring negative CDT assays prior to initiating symptomatic management of diarrhea needs modification. One hundred and nineteen patients with malignant diseases undergoing autologous or allogeneic HSCT were studied to determine the incidence of diarrhea and CDT positivity with initial diarrhea. One hundred and nine (91%) had diarrhea. Of these, only seven (6%) were CDT+ at the time of initial diarrhea. The median interval between onset of diarrhea and starting symptomatic anti-diarrheal therapy was 1 day. There were no significant differences between the patients with CDT+ diarrhea and the others in terms of timing or severity of diarrhea, number or duration of antibiotic usage, or leukocyte count. The infection resolved in all patients with metronidazole therapy. Our data suggest that the incidence of CDT+ diarrhea is low in HSCT recipients. Concern about C. difficile infection should not delay symptomatic therapy of initial diarrhea in HSCT recipients.

Adolescent↗

Reassessing the definition of myeloid engraftment after autotransplantation: it is not necessary to see 0.5 x 10(9)/l neutrophils on 3 consecutive days to define myeloid recovery.

The time to myeloid recovery after autologous hematopoietic stem cell transplantation (HSCT) is usually defined as the first of 3 consecutive days with an absolute neutrophil count (ANC) of >or=0.5 x 10(9)/l (ANC500). Universal documentation of ANC500 for 3 consecutive days, historically required to ensure robust myeloid recovery, has become difficult with a trend towards early discharge and outpatient HSCT. We studied 90 autografted patients to see how frequently ANC declined after having reached >or=0.5 x 10(9)/l. ANC500 was documented on 2 and 3 consecutive days in 14 and 63 patients, respectively. ANC increased by a median of 213% from the 1st to the 2nd day (rise in 75 and unchanged in two), and by a median of 142% from the 2nd day to the 3rd (rise in 60, unchanged in one, and decline in two; higher than the 1st day in the latter three). The increase from the 1st to the 3rd day was 13-3433% (median, 557%). Thus, in all 63 patients, no decline below ANC500 was seen, and the first day with ANC500 was also the first of 3 consecutive days with ANC500. The remaining 13 patients had repeat counts 2-7 days after the 1st day with ANC500 documenting further increase in ANC with no evidence of failed engraftment. These data show that the first day with ANC500 is also consistently the first of 3 consecutive days with ANC500 in autografted patients. Therefore, the traditional definition of myeloid engraftment should be changed to consider the first day with ANC500 as the day of engraftment without necessarily documenting ANC500 on the subsequent 1-2 days. This simple change in definition has significant implications for how data are reported to transplant registries and how peer-review organizations such as the Foundation for the Accreditation of Hematopoietic Cell Therapy (FAHCT) define completeness of data.

Adolescent↗

Sociocultural aspects of areca nut use.

This paper aims to describe the sociocultural context of areca nut use through exploring people's norms and values and the meaning underlying a wide range of different practices. A historical review is followed by an examination of more recent evidence, including quantitative and qualitative research conducted in the United Kingdom. It is concluded that some reports involving the various uses of areca nut and the conclusions drawn are confusing and that future studies need to be more explicit. While a sound scientific background is required, important sociocultural and religious issues around areca nut use must also be understood if health promotion initiatives are to be considered.

Africa↗

An in vitro study of the reduction in wear of metal-on-metal hip prostheses using surface-engineered femoral heads.

Although the wear of existing metal-on-metal (MOM) hip prostheses (1 mm3/10(6) cycles) is much lower than the more widely used polyethylene-on-metal bearings, there are concerns about the toxicity of metal wear particles and elevated metal ion levels, both locally and systemically, in the human body. The aim of this study was to investigate the possibility of reducing the volume of wear, the concentration of metal debris and the level of metal ion release through using surface-engineered femoral heads. Three thick (8-12 microm) coatings (TiN, CrN and CrCN) and one thin (2 microm) coating (diamond-like carbon, DLC), were evaluated on the femoral heads when articulating against high carbon content cobalt-chromium alloy acetabular inserts (HC CoCrMo) and compared with a clinically used MOM cobalt-chromium alloy bearing couple using a physiological anatomical hip joint simulator (Leeds Mark II). This study showed that CrN, CrCN and DLC coatings produced substantially lower wear volumes for both the coated femoral heads and the HC CoCrMo inserts. The TiN coating itself had little wear, but it caused relatively high wear of the HC CoCrMo inserts compared with the other coatings. The majority of the wear debris for all half-coated couples comprised small, 30 nm or less, CoCrMo metal particles. The Co, Cr and Mo ion concentrations released from the bearing couples of CrN-, CrCN- and DLC-coated heads articulating against HC CoCrMo inserts were at least 7 times lower than those released from the clinical MOM prostheses. These surface-engineered femoral heads articulating on HC CoCrMo acetabular inserts produced significantly lower wear volumes and rates, and hence lower volumetric concentrations of wear particles, compared with the clinical MOM prosthesis. The substantially lower ion concentration released by these surface-engineered components provides important evidence to support the clinical application of this technology.

Carbon↗