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Biomedical subjects

J Pickard

Publications and source records attributed to J Pickard.

At least 19 recordsLinked to original sources

Monitoring emergence from coma following severe brain injury in an octogenarian using behavioural indicators, electrophysiological measures and metabolic studies: a demonstration of the potential for good recovery in older adults.

This case study describes a multi-disciplinary investigation of the emergence from coma of an 80-year old female (KE) following severe traumatic brain injury. The relationship between cognitive/behavioural ability and the integrity of cerebral function was assessed using neuropsychological measures, positron emission tomography, electroencephalography, somatosensory evoked potentials and trans-cranial magnetic stimulation. These investigations were performed as KE was beginning to emerge from coma (4 weeks) and, again, approximately 1 year following brain injury, when she was judged to have achieved her maximum level of recovery. Neuropsychological measures revealed improvement during the first year post-injury in KE's speed of information processing, memory and executive abilities. Electrophysiological and metabolic studies indicated a restoration of functional integrity that was consistent with the gradual recovery in higher brain function documented using behavioural procedures. This case study demonstrates the rehabilitation potential of pre-morbidly healthy older adults following severe traumatic brain injury.

Accidents, Traffic↗

Psychiatric, cognitive and behavioural outcomes following craniopharyngioma and pituitary adenoma surgery.

In order to determine the cognitive and behavioural changes in patients following craniopharyngioma surgery, all patients over the age of 16 years who had an operative intervention for craniopharyngioma between 1983 and 1998 were identified. Those consenting were interviewed using standardized instruments to assess for the presence of a psychiatric disorder, disturbance of behaviour or altered cognitive function. A control group of age- and sex-matched patients who had undergone pituitary adenoma excision were identically assessed. Eighteen people, of a total of 44, were interviewed. There were some differences in the subjective experience of appetite and the degree of control exercised over eating behaviour. Otherwise outcomes in cases and controls were similar. In the domains assessed, these two groups have similar outcomes from surgery.

Adenoma↗

Unilateral transplantation of human primary fetal tissue in four patients with Huntington's disease: NEST-UK safety report ISRCTN no 36485475.

OBJECTIVES: Huntington's disease (HD) is an inherited autosomal dominant condition in which there is a CAG repeat expansion in the huntingtin gene of 36 or more. Patients display progressive motor, cognitive, and behavioural deterioration associated with progressive cell loss and atrophy in the striatum. Currently there are no disease modifying treatments and current symptomatic treatments are only partially effective in the early to moderate stages. Neural transplantation is effective in animal models of HD and offers a potential strategy for brain repair in patients. The authors report a safety study of unilateral transplantation of human fetal striatal tissue into the striatum of four patients with HD. SUBJECTS AND METHODS: Stereotaxic placements of cell suspensions of human fetal ganglionic eminence were made unilaterally into the striatum of four patients with early to moderate HD. All patients received immunotherapy with cyclosporin A, azathioprine, and prednisolone for at least six months postoperatively. Patients were assessed for safety of the procedure using magnetic resonance imaging (MRI), regular recording of serum biochemistry and haematology to monitor immunotherapy, and clinical assessment according to the Core Assessment Protocol For Intrastriatal Transplantation in HD (CAPIT-HD). RESULTS: During the six month post-transplantation period, the only adverse events related to the procedure were associated with the immunotherapy. MRI demonstrated tissue at the site of implantation, but there was no sign of tissue overgrowth. Furthermore, there was no evidence that the procedure accelerated the course of the disease. CONCLUSIONS: Unilateral transplantation of human fetal striatal tissue in patients with HD is safe and feasible. Assessment of efficacy will require longer follow up in a larger number of patients.

Adult↗

Investigation into the tribological condition of acetabular tissue after bipolar joint replacement hip surgery.

The aim of this research was to investigate the tribological condition of acetabular tissue before and after bipolar hip surgery. Articular cartilage was taken from the femoral head of patients undergoing primary joint replacement as a control. Tissue was also taken from the acetabular cups of patients undergoing revision hip surgery after primary bipolar surgery and compared with the control cartilage. The biomechanical characteristics of the two tissue types were tested using friction and compression tests. The friction tests were carried out on a sliding friction rig under nominal contact stresses of 0.5 and 4 MPa. The compression tests were carried out under a 0.8 MPa contact stress. The majority of the bipolar patients produced friction coefficients that were significantly higher than those produced by the control group, and the compression tests highlighted that the tissue from the bipolar patients produced a much greater rate of increase in displacement compared with the control cartilage. Histology showed major differences between the control cartilage and the bipolar tissue. The control cartilage showed a healthy collagen structure with a good distribution of proteoglycan whereas the majority of the bipolar tissue had lost tissue architecture and had a sparse fibrous structure. The high friction coefficients with the bipolar tissue imply that the frictional torque at the outer head of the bipolar prosthesis would be large compared with the inner bearing frictional torque. It was therefore predicted that the motion of the bipolar prosthesis should occur at the inner bearing.

Acetabulum↗

Non-random involvement of chromosome 13 in patients with persistent or relapsed disease after bone-marrow transplantation for chronic myeloid leukemia.

Chronic myeloid leukemia (CML) patients with persistent or relapsed disease following bone-marrow transplantation (BMT) usually show both clonal and non-clonal cytogenetic changes in addition to the Philadelphia (Ph) translocation. These changes are presumably due to conditioning prior to transplantation and are generally not thought to be of clinical significance. We have examined the additional cytogenetic changes found in Ph+ve cells after BMT in 47 CML patients. Forty patients showed clonal changes. The involvement of each chromosome was compared statistically with expected values assuming that further chromosome changes are random and related to chromosome size. In clones that comprised 50% or more of the Ph+ve metaphases, chromosome 13 was involved in 12 of 22 clones (55%); this was highly significant when compared with the theoretical expected value of 3.2 (14.5%) (P < 0.001). The chromosome 13 rearrangements comprised both translocations and deletions. By means of FISH with a panel of 13q YAC clones, the breakpoints in 6 of these patients were investigated, but no common site of translocation was identified. The YAC panel was then used on material from 6 patients with chromosomal deletions. A common region of deletion was identified at 13q12-14, suggesting the presence of one or more tumor suppressor genes. We conclude that chromosome 13 deletions are non-randomly overrepresented in Ph+ve metaphases following BMT for CML. Genes Chromosomes Cancer 27:278-284, 2000.

Bone Marrow Transplantation↗

Fusion of ETV6 to the caudal-related homeobox gene CDX2 in acute myeloid leukemia with the t(12;13)(p13;q12).

The t(12;13)(p13;q12) is a rare, recurrent translocation reported in a range of hematological malignancies. We have analyzed the molecular basis of this lesion in three patients with acute myeloid leukemia (AML), two of whom were known to have chromosome 12 breakpoints within the ETV6 gene. Fluorescence in situ hybridization (FISH) with ETV6 cosmids indicated that this gene was also disrupted in the third patient, while the normal ETV6 allele was retained. 3' rapid amplification of cDNA ends (RACE) polymerase chain reaction (PCR) from bone marrow mRNA of this individual identified a novel sequence fused to ETV6 that was homologous to a region just upstream of the mouse CDX2 homeobox gene, the human homologue of which has previously been mapped to chromosome 13q12. PCR primers designed to amplify an ETV6-CDX2 fusion identified two major transcripts from this patient. First, a direct in-frame fusion between exon 2 of ETV6 and exon 2 of CDX2, and second, a transcript that had an additional sequence of unknown origin spliced between these same exons. Surprisingly, apparently normal CDX2 transcripts, usually expressed only in intestinal epithelium, were also detectable in cDNA from this patient. Neither normal nor fusion CDX2 mRNA was detectable in the two other patients with a t(12;13), indicating that this translocation is heterogeneous at the molecular level. Reverse transcription-PCR analysis showed that CDX2 mRNA, but not ETV6-CDX2 mRNA, was strongly expressed in 1 of 10 patients with chronic myeloid leukemia in transformation, suggesting that deregulation of this gene may be more widespread in leukemia. CDX2 is known to regulate class I homeobox genes and its expression in hematopoietic cells may critically alter the balance between differentiation and proliferation.

Aged↗

Chromosomal breakage analysis in dyskeratosis congenita peripheral blood lymphocytes.

Dyskeratosis congenita (DC) is a rare inherited disorder characterized by reticulate skin pigmentation, nail dystrophy and mucosal leucoplakia. Bone marrow failure occurs in the majority of cases and there is a predisposition to malignancy. Following conflicting reports of increased spontaneous and induced chromosomal breakage in DC lymphocytes, we examined chromosomal breakage with and without clastogen treatment in 10 DC patients from six different families. Peripheral blood cultures were stimulated with phytohaemagglutinin and treated with three clastogenic agents and gamma-irradiation. There was no significant difference in the chromosomal breakage in DC lymphocytes with or without exposure to bleomycin, DEB, MMC or gamma-irradiation. DC can therefore be distinguished from Fanconi's anaemia in which lymphocytes show increased spontaneous and clastogen-induced chromosomal breakage.

Adolescent↗

Investigation into the effect of proteoglycan molecules on the tribological properties of cartilage joint tissues.

The aim of this research was to investigate the role of the hydrophilic properties of the proteoglycan molecules within the cartilage matrix, on the tribological properties of joint tissues in the mixed and boundary lubricating regime. Bovine articular cartilage, bovine meniscus and bovine cartilage that had been degraded to remove the chondroitin sulphate from its proteoglycans were studied in order to investigate differences in their friction and compression responses. The tissues were tested on a sliding friction rig under nominal contact stresses of 0.5 and 4 MPa. The compression tests were carried out under a 0.8 MPa contact stress. The compression tests showed the cartilage and meniscus deforming at the same rates, but the degraded cartilage deformed more quickly to reach its equilibrium position in a shorter period of time. The friction tests carried out at a constant load revealed the friction of the meniscus rising more rapidly with loading time than the cartilage. The degraded cartilage followed an almost identical curve as the untreated cartilage. Although the reduced proteoglycan content of the degraded cartilage substantially altered the biphasic compression response, it did not have an effect on the frictional properties of the tissue.

Animals↗

Guidelines for treatment of head injury in adults. Opinions of a group of neurosurgeons.

There are a number of parallel activities world wide to devise guidelines for the treatment of head injuries. A Group of neurosurgeons from various European countries worked on guidelines during three informal meetings, which may serve as a base for discussion of national or local protocols. Three levels of certainty were distinguished: Measures that must be taken which such a high degree of certainty, that they have not seriously been challenged-principles. Measures, that should be taken, as there is reasonable evidence in the literature about its efficacy-recommendations and measures that may be taken, but proof of its efficacy is lacking-optional measures. Protocols based on these guidelines are felt to help young neurosurgeons in training, define neurosurgical needs for other specialities and enhance the general efficacy of care for the head injured patient including multiple injuries.

Adult↗

Computerised transient hyperaemic response test--a method for the assessment of cerebral autoregulation.

A simple bedside test has been developed to assess the state of autoregulation in subarachnoid haemorrhage patients. Transcranial Doppler was used to measure blood flow velocity in the middle cerebral artery after a brief common carotid compression. Acceleration of blood flow postcompression was interpreted as evidence of intact cerebral autoregulation. A program using the Windows environment was designed for signal analysis of the transient hyperaemic response test (THRT). The flow velocity signal from the TCD was recorded, carotid compression and release automatically detected and the test results immediately displayed and stored in a database. The program was verified in 614 tests; 552 of them were analysed off-line using previously recorded data and 62 on-line during the examination. A significant correlation was found between the results of computerised testing and the patient's neurological state.

Adult↗