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Biomedical subjects

C P Case

Publications and source records attributed to C P Case.

At least 19 recordsLinked to original sources
PubMed2004

Wear debris from hip or knee replacements causes chromosomal damage in human cells in tissue culture.

Wear debris was extracted from 21 worn hip and knee replacements. Its mutagenic effects were tested on human cells in tissue culture using the micronucleus assay and fluorescent in situ hybridisation. The extracted wear debris increased the level of micronuclei in a linear dose-dependent manner but with a tenfold difference between samples. The concentration of titanium +/- vanadium and aluminium within the wear debris was linearly related both to the level of centromere-positive micronuclei in tissue culture, indicating an aneuploid event, and to the level of aneuploidy in vivo in peripheral blood lymphocytes. The concentration of cobalt and chromium +/- nickel and molybdenum in the wear debris correlated with the total index of micronuclei in tissue culture, both centromere-positive and centromere-negative i.e. both chromosomal breakage and aneuploidy events. The results show that wear debris can damage chromosomes in a dose-dependent manner which is specific to the type of metal. The results from studies in vitro correlate with those in vivo and suggest that the wear debris from a worn implant is at least partly responsible for the chromosomal damage which is seen in vivo.

Adult↗
PubMed2003

Particulate debris from a titanium metal prosthesis induces genomic instability in primary human fibroblast cells.

Previous studies detected both lethal and cumulative chromosomal aberrations in bone marrow and peripheral blood of patients with worn hip and knee replacements. This study shows that wear debris from a worn titanium metal on high-density polyethylene hip replacement also produces chromosomal instability and reproductive failure in cell culture. The progeny of these treated cells also displayed chromosomal instability, mainly consisting of chromatid breaks and minutes, and reproductive failure as determined by clonogenic survival many generations postexposure. These delayed effects are similar to those caused by the heavy metals cadmium and nickel and to those seen for low-dose radiation. These findings may have important implications with regard to the long-term risks of joint replacement surgery. This highlights the need for long-term epidemiological studies of patients with surgical implants.

Cell Division↗
PubMed2001

Increased chromosome translocations and aneuploidy in peripheral blood lymphocytes of patients having revision arthroplasty of the hip.

The long-term biological effects of wear debris are unknown. We have investigated whether there is any evidence of cumulative mutagenic damage in peripheral blood lymphocytes of patients undergoing revision arthroplasty of predominantly metal-on-plastic total hip replacements compared with those at primary arthroplasty. There was a threefold increase in aneuploidy and a twofold increase in chromosomal translocations which could not be explained by the confounding variables of smoking, gender, age and diagnostic radiographs. In the patients with TiVaAl prostheses there was a fivefold increase in aneuploidy but no increase in chromosomal translocations. By contrast, in patients with cobalt-chrome prostheses there was a 2.5-fold increase in aneuploidy and a 3.5-fold increase in chromosomal translocations. In six patients with stainless-steel prostheses there was no increase in either aneuploidy or chromosomal translocations. Our results suggest that future epidemiological studies of the putative long-term risks of joint replacement should take into account the type of alloy used in the prosthesis.

Aged↗
PubMed2001

Development of a routine method for the determination of trace metals in whole blood by magnetic sector inductively coupled plasma mass spectrometry with particular relevance to patients with total hip and knee arthroplasty.

BACKGROUND: Joint-replacement surgery has revolutionized the treatment of osteoarthritis and is still the most effective therapy. A recent clinical trend reintroducing metal-on-metal bearing surfaces has in turn stimulated a requirement for accurate measurement of the concentrations of relevant metals in both pre- and postoperative patients. Thus, there is a need for cost-effective, multielement methods for trace metal analysis in whole blood to monitor possible increases in wear metal concentrations. METHODS: A method was developed to allow routine analysis of whole blood samples for molybdenum, cobalt, chromium, and nickel. Sample preparation consisted of a simple 1:10 dilution of whole blood with a solution of 10 mL/L Triton X-100, 0.0002 mol/L EDTA, and 0.01 mol/L ammonium hydroxide. Final determination was performed by a double-focusing magnetic sector inductively coupled plasma mass spectrometer operated in medium-resolution mode (resolution, 3400). Online addition of rhodium was used for internal standardization. RESULTS: Detection limits in whole blood were 0.06 microg/L for chromium, cobalt, and molybdenum and 0.30 microg/L for nickel. Base concentrations of 0.22, 0.17, 0.62, and 0.99 microg/L for chromium, cobalt, molybdenum, and nickel, respectively, in whole blood have been found. Polyatomic interferences on all four elements have been shown to be resolved from the analyte masses by use of a resolution of >3000. CONCLUSIONS: The simple, rapid method of sample preparation is effective in minimizing potential contamination and enables 60 samples (run time, 8 h) to be analyzed before cleaning the instrument is necessary. A resolution >3000 was sufficient to separate polyatomic interferences from the masses of interest. The method was used to analyze a large number of blood samples taken from primary patients awaiting total hip arthroplasty. The method is sensitive enough to provide base concentrations for chromium, cobalt, and molybdenum in whole blood. The results for nickel were compromised by high signals for blank samples.

Arthroplasty, Replacement, Hip↗
PubMed2000

Nerve injury-associated kinase: a sterile 20-like protein kinase up-regulated in dorsal root ganglia in a rat model of neuropathic pain.

Partial injury of the rat sciatic nerve elicits a variety of characteristic chemical, electrophysical and anatomical changes in primary sensory neurons and constitutes a physiologically relevant model of neuropathic pain. To elucidate molecular mechanisms that underlie the physiology of neuropathic pain, we have used messenger RNA differential display to identify genes that exhibit increased ipsilateral expression in L4/5 dorsal root ganglia, following unilateral partial ligation of the rat sciatic nerve. One set of partial complementary DNA clones identified in this screen was found to encode a protein kinase, nerve injury-associated kinase. Cloning of the full-length human nerve injury-associated kinase complementary DNA, together with recombinant expression analysis, reveal nerve injury-associated kinase to be a functional member of a subgroup of sterile 20-like protein kinases characterised by the presence of a putative carboxy terminal autoregulatory domain. Induction of nerve injury-associated kinase expression in dorsal root ganglia in the rat neuropathic pain model was confirmed by quantitative reverse transcription-polymerase chain reaction, and RNA in situ hybridization analysis revealed enhanced levels of nerve injury-associated kinase within neurons.Together, our data implicate nerve injury-associated kinase as a novel upstream component of an intracellular signalling cascade that is up-regulated in dorsal root ganglia neurons in response to sciatic nerve injury.

Amino Acid Sequence↗
PubMed2000

Identification of differentially expressed genes in dorsal root ganglia following partial sciatic nerve injury.

Partial sciatic nerve injury, a model of neuropathic pain, elicits a variety of neurochemical, electrophysiological and neuroanatomical changes in primary sensory neurons. We have used the technique of messenger RNA differential display to identify genes with altered expression in these neurons which may contribute to the development of aberrant sensation following such peripheral nerve damage. This approach identified 14 distinct complementary DNA clones, representing transcripts with increased ipsilateral expression in L4/5 dorsal root ganglia, two weeks after unilateral partial ligation of the rat sciatic nerve. Both Zucker diabetic fatty rats and their lean counterparts were used in this study but none of the transcripts identified showed an induction that was confined to one of the two groups. The majority of the clones did not show significant sequence similarity to previously reported genes and therefore may represent novel messenger RNA sequences or, alternatively, unknown regions of partially characterised messenger RNAs. Two of the clones represented transcripts for the known proteins muscle LIM protein and acidic epididymal glycoprotein, neither of which had previously been associated with expression in the nervous system. Reverse transcriptase-polymerase chain reaction analysis and in situ hybridization confirmed that the messenger RNA expression of both muscle LIM protein and acidic epididymal glycoprotein was induced in an ipsilateral-specific manner. Their localisations, examined with in situ hybridization in L5 dorsal root ganglia, were limited in each case to a sub-population of neuronal profiles. Those neuronal profiles that demonstrated muscle LIM protein hybridization were distributed across the profile size range, whereas the distribution of acidic epididymal glycoprotein-positive profiles appeared to be skewed towards smaller profiles. The induction of muscle LIM protein and acidic epididymal glycoprotein in dorsal root ganglia may play an important functional role in the adaptive response of primary sensory neurons following partial sciatic nerve injury.

Animals↗
PubMed2000

Changes in the proportions of peripheral blood lymphocytes in patients with worn implants.

We compared the peripheral blood and periprosthetic tissues of 53 patients at revision arthroplasty with those of 30 patients at primary arthroplasty to determine whether there is a systemic difference in lymphocytes in patients with worn hip implants. The absolute number and relative proportion of lymphocytes bearing CD2, CD3, CD4, CD8, CD16, CD19, HLA-DR, kappa and lambda antigens were compared with the levels of IL-1beta, IL-6 and PGE2 in the pseudosynovial membrane as well as with a semiquantitative estimate of metal and polyethylene particles, necrosis and chronic inflammation and the total concentration of metals within the periprosthetic tissues. There was a significant increase in the relative proportion of CD2-positive T-cells and CD16-positive natural killer cells in the peripheral blood at revision arthroplasty compared with primary arthroplasty and an increased proportion of CD8-positive T-cells and a decreased ratio of CD4 to CD8 (helper inducer/suppressor cytotoxic cells). Three control patients, who went on to have revision surgery, had values at primary arthroplasty which were similar to those of patients at the time of revision surgery. These differences did not correlate with the local concentration of metal, plastic or cement or inflammatory response or the type of prosthesis. An inverse correlation was noted between the necrosis in the periprosthetic tissue and both the local production of IL-6 and the absolute numbers of T-cells in peripheral blood. We conclude that there may be several cell-mediated systemic immune responses to aseptic loosening, at least one of which may be directly related to events in the periprosthetic tissues. We cannot exclude the possibility that the changes in the proportion of CD8-positive cells reflected a predisposition, rather than a reaction, to loosening of the implant.

Aged↗
PubMed1998

Characterization of wear debris associated with aseptic loosening of a canine hip prosthesis.

A 12-month-old Golden Retriever bitch underwent unilateral hip arthroplasty following a diagnosis of coxofemoral osteoarthritis secondary to hip dysplasia. The hip prosthesis underwent aseptic loosening and was removed 6 months after implantation. Synovial biopsies taken at that time revealed scattered foci of granulomatous inflammation associated with intra-cytoplasmic and extracellular particulate material. Electron microscopical analyses demonstrated that this material contained cobalt, chromium, titanium and zirconium, which was probably wear debris from the loosened prosthesis. In human patients with hip arthroplasty, widespread dissemination of wear debris from loosened prostheses occasionally occurs, with an increased prevalence of neoplasia. A similar phenomenon may be predicted to occur with the increasing use of hip arthroplasty in the dog.

Animals↗
PubMed1997

Tumors around implants.

In 1989, A. G. Apley recommended cautious surveillance of malignant tumors that developed in association with orthopaedic implants. This retrospective review of the Bristol Bone Tumour Register between 1980 and 1992 reports on 240 malignant soft tissue sarcomas. Eighteen developed in the thigh region of patients more than 50 years old, and 4 of these developed in the soft tissues around a hip arthroplasty.

Aged↗
PubMed1996

Preliminary observations on possible premalignant changes in bone marrow adjacent to worn total hip arthroplasty implants.

Previous epidemiologic studies have suggested that there may be a risk of malignancy, especially lymphoma and leukemia, after joint replacement, but the followup has been relatively short. This is a preliminary study to see if there is any biologic basis for such a risk. Blood and bone marrow samples from 71 patients at revision arthroplasty of a loose or worn prosthesis and 30 control patients at primary arthroplasty were analyzed with cytogenetic techniques and molecular biology. There was a higher chromosomal aberration rate in cells adjacent to the prosthesis at revision surgery compared with iliac crest marrow from the same patients or with femoral bone marrow at primary arthroplasty. Clonal expansion of lymphocytes without a serum paraprotein was seen in 2 of 21 patients at revision arthroplasty performed more than 10 years after primary arthroplasty. The results of this preliminary study suggest that future epidemiologic studies should concentrate on patients with longer postoperative intervals to see if there is any risk that would be pertinent to a young patient at primary arthroplasty.

Aged↗
PubMed1995

Death after proximal femoral fracture--an autopsy study.

We reviewed 22,486 consecutive autopsy reports in a single District General Hospital, from 1953 to 1992. Five hundred and eighty-one patients with fractures of the proximal femur (hip fracture) were identified. Causes of death were correlated with timing of surgery and change of clinical practice. Thromboembolic and haemorrhagic potential were analysed. The principal causes of death after hip fracture were bronchopneumonia, cardiac failure, myocardial infarction and pulmonary embolism. Surgical intervention, within 24 h of injury significantly reduced death from bronchopneumonia and pulmonary embolism. Early mobilization reduced death from bronchopneumonia. Pulmonary embolism may be reduced by prophylactic anticoagulation, but 17 per cent of patients are at risk of haemorrhage, and mechanical methods seem safer in this population.

Aged↗
PubMed1995

Neurofibrillary tangles in Niemann-Pick disease type C.

Post-mortem neuropathological examination of five cases of Niemann-Pick disease type C revealed neurofibrillary tangles in many parts of the brain. Tangles were a consistent finding in the hippocampus, hypothalamus, substantia innominata, midbrain pons and medulla. Other regions of the brain in which tangles were present included neocortex, basal ganglia, thalamus, cerebellar cortex in one case, and dentate nucleus in another. The tangles were argyrophilic, fluoresced under ultraviolet light when stained with thioflavin S, and reacted strongly with antibody to tau protein. Some of the tangles could be immunostained for ubiquitin. Electron microscopy, performed in one of the cases, showed the tangles to consist of paired helical filaments ultrastructurally identical to those of Alzheimer's disease. The distribution of the tangles in the central nervous system as a whole and also within many individual neurons corresponded fairly closely with that of the abnormal storage material. Both the tangles and the storage material extended into, and distended, the proximal parts of many dendrites and axons. No A4/beta protein, either in the form of plaques or in the walls of blood vessels, was detected in any of the cases. Our findings suggest that neurofibrillary tangles are a common feature of Niemann-Pick disease type C and that their formation may be a reaction to the abnormal storage material.

Adolescent↗
PubMed1994

Ossifying fibromyxoid tumour of soft parts--a new tumour of the parotid/zygomatic arch region.

The ossifying fibromyxoid tumour of soft parts was first described as recently as 1989 by Enzinger has not been previously reported in the maxillofacial literature. This tumour has a proven record of recurrence and a potential in a few cases to become malignant and to metastasise. Being such a rare and relatively newly described tumour it has proved to be difficult to diagnose and manage. In order to illustrate these difficulties we describe a case in which such a tumour occurred in the parotid/zygomatic arch region and recurred three times following surgical removal over a period of 24 years. Since the tumour has a pseudo-capsule containing nests of tumour cells, we recommend that it could be removed from the head and neck region with a wide margin of excision.

Adult↗
PubMed1994

Widespread dissemination of metal debris from implants.

In a post-mortem study, we compared subjects with metal implants with and without visible wear with an age-matched control group to determine the extent and effects of dissemination of wear debris. In subjects with stainless-steel and cobalt-chrome prostheses metal was found in local and distant lymph nodes, bone marrow, liver and spleen. The levels were highest in subjects with loose, worn joint prostheses and the main source of the debris was the matt coating. Metal levels were also raised in subjects with implants without visible wear and, to a less extent, in those with dynamic hip screws. Necrosis of lymph nodes was seen in those cases with the most wear, and potential damage to more distant organs such as the bone marrow, liver and spleen in the long term cannot be discounted. The consequences for the immune system and the role of metal dissemination in the possible induction of neoplasia are discussed.

Aged↗
PubMed1993

Changing the light intensity of the visual environment results in large differences in numbers of synapses and in photoreceptor size in the retina of the young adult rat.

A quantitative light- and electron-microscopic study has been made of the retinae of rats which were exposed to different lighting conditions for between one and 15 weeks in young adulthood, having been reared in identical conditions during development. The width of the inner and outer segments of the photoreceptors and the width of the outer plexiform layer varied inversely with the light intensity under diurnal lighting conditions of 10 h light/14 h dark. Linear regression analysis showed that the widths were inversely related to the fourth root of the light intensity as measured in lux. Both central and peripheral areas of retina showed a similar change. No change was seen in the widths of the inner plexiform layer, or of the inner and outer nuclear cell layers. Nor was there a difference in the packing density or size of the nuclei in the nuclear cell layers. The number of ribbon synapses in the outer plexiform layer also varied inversely with the intensity of diurnal light. Linear regression analysis showed that the number of synapses was inversely correlated with the fourth root of the light intensity and was positively correlated with the width of the outer plexiform layer. The number of ribbon synapses was increased by up to two and a half times in constant darkness compared to diurnal light of 35 lux. The increase was present but not maximal after one week of exposure. The length of synaptic ribbons was unchanged. The nerve terminals forming such synapses were increased in size but not in number. After one week, there was little or no additional change in the retinal widths and number of synaptic ribbons with time. However, there was a progressive increase with time in nerve terminal size (two-fold in area) in constant darkness. There was some evidence of a slight decrease in nerve terminal number and increase in size of retinal nuclei with age. It is concluded that the adult retina responds to a different lighting environment by a relatively rapid change in the size of photoreceptor segments, by a progressive and large change in number of ribbon synapses and by a slower progressive and large change in the size of photoreceptor nerve terminals. The response is quantitatively determined by the strength of the stimulus but not in a linear fashion. These results are compared with the effects of environmental stimulation of other areas of the nervous system.

Animals↗