Biomedical subjects

J Richardson

Publications and source records attributed to J Richardson.

At least 19 recordsLinked to original sources

PubMed2001

Changes in physical functioning in institutionalized older adults.

PURPOSE: Chronic care and long-term care facilities have a responsibility to provide care that enables residents to attain or maintain their maximal functional capacity. This paper uses the Minimum Data Set (MDS) to examine changes in functional health. METHODS: One hundred and thirty-eight residents were assessed quarterly using the MDS over a 12 month period in a chronic care and long-term care institution. Physical functioning was conceptualized in two areas of physical limitations (e.g. bed mobility) and disability (e.g. dressing). RESULTS: Ten percent of the residents physical functioning improved. Gender, range of motion score at baseline, change in bed mobility and change in short term memory were strong independent predictors of changes in functional activity FL adjusted R2 = 0.23, F(5156) = 10.47, p<0.0001. The strongest independent predictors of change in ADL were gender, balance while standing at baseline, joint range of motion at baseline and change in depression scores, and weight loss, adjusted R2 = 0.24 , F(4157)= 13.38, p < 0.0001. CONCLUSIONS: Most residents' physical functioning showed a deterioration or remained stable. Impairments which best explained changes in functioning such as range of motion or balance in standing are modifiable and should be targeted in interventions by nursing and rehabilitation staff.

Activities of Daily Living↗

PubMed2001

Relation between childhood sexual and physical abuse and risk of revictimisation in women: a cross-sectional survey.

BACKGROUND: Women who are physically and sexually abused in childhood are at increased risk of victimisation in adulthood. Research has concentrated on sexual revictimisation, and has not included investigation of other abusive experiences, nor examination of prevalence and effects of abuse on adult revictimisation. We aimed to examine the relation between childhood trauma and adult revictimisation, and identify confounding factors. METHODS: We did a cross-sectional survey of 2592 women who were attending primary care practices in east London, UK, with self-administered anonymous questionnaires. We included questions on physical and sexual abuse in childhood; on domestic violence, rape, indecent assault, and other traumatic experiences in adulthood; and on alcohol and other drug abuse. We analysed associations between childhood and adulthood abuse with multiple logistic regression. FINDINGS: 1207 (55%) of 2192 eligible women were recruited and completed the questionnaire. Abusive experiences co-occurred in both childhood and adulthood. Repetition and severity of childhood abuse were independently associated with specific types of adult revictimisation. Unwanted sexual intercourse (<16 years) was associated with domestic violence in adulthood (odds ratio 3.54; 95% CI 1.52-8.25) and with rape (2.84; 1.09-7.35); and severe beatings by parents or carers with domestic violence (3.58; 2.06-6.20), rape (2.70; 1.27-5.74), and other trauma (3.85; 2.23-6.63). INTERPRETATION: Childhood abuse substantially increases risk of revictimisation in adulthood. Women who have experienced multiple childhood abuse are at most risk of adult revictimisation. Identification of women who have undergone childhood abuse is a prerequisite for prevention of further abuse.

Adolescent↗

PubMed2001

Dishevelled regulates the metabolism of amyloid precursor protein via protein kinase C/mitogen-activated protein kinase and c-Jun terminal kinase.

Alzheimer's disease (AD) is a disorder of two pathologies: amyloid plaques, the core of which is a peptide derived from the amyloid precursor protein (APP), and neurofibrillary tangles composed of highly phosphorylated tau. Protein kinase C (PKC) is known to increase non-amyloidogenic alpha-secretase cleavage of APP, producing secreted APP (sAPPalpha), and glycogen synthase kinase (GSK)-3beta is known to increase tau phosphorylation. Both PKC and GSK-3beta are components of the wnt signaling cascade. Here we demonstrate that overexpression of another member of this pathway, dishevelled (dvl-1), increases sAPPalpha production. The dishevelled action on APP is mediated via both c-jun terminal kinase (JNK) and protein kinase C (PKC)/mitogen-activated protein (MAP) kinase but not via p38 MAP kinase. These data position dvl-1 upstream of both PKC and JNK, thereby explaining the previously observed dual signaling action of dvl-1. Furthermore, we show that human dvl-1 and wnt-1 also reduce the phosphorylation of tau by GSK-3beta. Therefore, both APP metabolism and tau phosphorylation are potentially linked through wnt signaling.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Activated MEK5 induces serial assembly of sarcomeres and eccentric cardiac hypertrophy.

Mitogen-activated protein kinase (MAPK) pathways couple intrinsic and extrinsic signals to hypertrophic growth of cardiomyocytes. The MAPK kinase MEK5 activates the MAPK ERK5. To investigate the potential involvement of MEK5-ERK5 in cardiac hypertrophy, we expressed constitutively active and dominant-negative forms of MEK5 in cardiomyocytes in vitro. MEK5 induced a form of hypertrophy in which cardiomyocytes acquired an elongated morphology and sarcomeres were assembled in a serial manner. The cytokine leukemia inhibitory factor (LIF), which stimulates MEK5 activity, evoked a similar response. Moreover, a dominant-negative MEK5 mutant specifically blocked LIF-induced elongation of cardiomyocytes and reduced expression of fetal cardiac genes without blocking other aspects of LIF-induced hypertrophy. Consistent with the ability of MEK5 to induce serial assembly of sarcomeres in vitro, cardiac-specific expression of activated MEK5 in transgenic mice resulted in eccentric cardiac hypertrophy that progressed to dilated cardiomyopathy and sudden death. These findings reveal a specific role for MEK5-ERK5 in the induction of eccentric cardiac hypertrophy and in transduction of cytokine signals that regulate serial sarcomere assembly.

Animals↗

PubMed2001

Entorhinal cortex atrophy in epilepsy patients exhibiting normal hippocampal volumes.

OBJECTIVE: To determine whether MRI volumetric measurement of the entorhinal cortex could detect structural damage and lateralize the seizure focus in patients with temporal lobe epilepsy in whom no measurable hippocampal abnormalities were found. BACKGROUND: A reduction in the volume of the entorhinal cortex ipsilateral to the seizure focus in patients with intractable temporal lobe epilepsy and hippocampal atrophy was recently shown. METHODS: MRI volumetric analysis of the entorhinal cortex was performed using a T1-weighted three-dimensional gradient echo sequence in 24 control subjects and 22 patients with temporal lobe epilepsy and normal hippocampal volumes. Thirteen patients underwent surgery, with a mean postoperative follow-up of 36 months. RESULTS: Group analysis (multivariate analysis of variance) showed a reduction in the volume of the entorhinal cortex ipsilateral to the seizure focus in patients with left (p < 0.0001) and right temporal lobe epilepsy (p < 0.0001). Lateralization of the seizure focus could be done in 14 of 22 patients (64%) based on entorhinal cortex volumetry. CONCLUSION: Entorhinal cortex atrophy ipsilateral to the seizure focus supports the presence of structural damage in the mesial temporal lobe in patients with temporal lobe epilepsy and normal hippocampal volumes and emphasizes the participation of the entorhinal cortex in the pathogenesis of this disorder.

Adult↗

PubMed2001

A degradation signal located in the C-terminus of p21WAF1/CIP1 is a binding site for the C8 alpha-subunit of the 20S proteasome.

The cyclin-dependent kinase inhibitor p21WAF1/CIP1 is a key regulator of cell-cycle progression and its expression is tightly regulated at the level of transcription and by proteasome-dependent proteolysis. The turnover of p21WAF1/CIP1 by proteasomes does not always require the ubiquitylation of p21WAF1/CIP1 suggesting that there could be an alternative pathway into the proteasome. Here we show that the C8 alpha-subunit of the 20S proteasome interacts with the C-terminus of p21WAF1/CIP1 and mediates the degradation of p21WAF1/CIP1. A small deletion in this region that disrupts binding to C8 increased the half-life of p21WAF1/CIP1 expressed in vivo. In contrast a deletion that increased the affinity between C8 and p21WAF1/CIP1 significantly reduced the stability of the latter. These data suggest that interaction with a 20S proteasome alpha-subunit is a critical determinant of p21WAF1/CIP1 turn-over and show how non-ubiquitylated molecules might bypass the 19S regulator of the proteasome and become targeted directly to the 20S, core protease. Consistent with this, p21WAF1/CIP1 was degraded rapidly by purified 20S proteasomes in a manner that was dependent on the C8-interaction domain.

3T3 Cells↗

PubMed2001

Natural antisense transcripts are detected in different cell lines and tissues of cats infected with feline immunodeficiency virus.

Feline immunodeficiency virus (FIV) is a lentivirus inducing an AIDS-like disease in cats, thus providing an interesting model for AIDS study. FIV and HIV-1 possess a similar genomic arrangement of structural and non-structural genes, whose expression is regulated by related genetic mechanisms. On the DNA strand complementary to the HIV-1 envelope messenger, an open reading frame (ORF) has been identified which encompasses the Rev Responsive Element (RRE), a cis-acting element critical to HIV gene expression. This ORF was highly conserved among HIV-1 isolates and had the potential to encode a hydrophobic protein. A corresponding antisense transcript was detected in cells infected with HIV-1, and appeared to encode an antisense protein. In the present study, we have identified a well-conserved antisense ORF, also coincident with the RRE region, in the genome of 21 FIV isolates. The predicted protein, 103 amino acids in length, is highly hydrophobic, as is the case for that of HIV-1. In addition, we have shown that a corresponding transcript, complementary to the transmembrane sequence of the FIV envelope gene, was produced in different cellular and viral contexts, that is, ex vivo and in vivo in FIV infected cell lines and tissues of infected cats, respectively. Expression of antisense transcripts might therefore be of general importance in the natural history of retroviruses.

Amino Acid Sequence↗

PubMed2001

Incidence of the cblA major subunit pilin gene amongst Burkholderia species.

PCR-amplification has been used to screen 75 isolates of the Burkholderia cepacia complex for the cblA pilin gene. PCR-amplified products of the correct size (664 bp) were cloned and sequenced and the sequences compared. Apart from in the control, epidemic cystic fibrosis (CF)-associated B. cepacia lineage we also identified, for the first time, cblA genes in a unique, non-CF clinical isolate from France and a plant (onion) pathogenic isolate from Italy. The sequence of the cblA gene amplified from the clinical isolate was more diverged from the epidemic lineage than that amplified from the onion pathogenic isolate.

Amino Acid Sequence↗

PubMed2001

Pneumocystis carinii cytochrome b mutations are associated with atovaquone exposure in patients with AIDS.

This retrospective cohort study was conducted to determine whether Pneumocystis carinii cytochrome b gene mutations in patients with AIDS and P. carinii pneumonia (PCP) are associated with atovaquone exposure. Portions of the P. carinii cytochrome b genes that were obtained from 60 patients with AIDS and PCP from 6 medical centers between 1995 and 1999 were amplified and sequenced by using polymerase chain reaction. Fifteen patients with previous atovaquone prophylaxis or treatment exposure were matched with 45 patients with no atovaquone exposure. Cytochrome b coenzyme Q binding site mutations were observed in 33% of isolates from patients exposed to atovaquone, compared with 6% from those who were not (P=.018). There was no difference in survival 1 month after treatment between patients with or without cytochrome b mutations (P=.14). Thus, cytochrome b mutations are significantly more common in patients with AIDS and PCP with atovaquone exposure, but the clinical significance of these mutations remains unknown.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Nasogastric feeding in children and adolescents with eating disorders: toward good practice.

OBJECTIVE: This study aimed to provide an insight into the subjective experiences of nasogastric feeding from the perspective of patients with eating disorders and their parents. METHOD: A semistructured self-report questionnaire was completed by patients from two specialist eating disorders units who had received nasogastric feeding. Parents' views were also assessed via a similar self-report questionnaire. RESULTS: Diverse views were expressed by both patients and parents. Some regarded the experience of nasogastric feeding as wholly negative, but acknowledged the lack of suitable alternatives. Others had a more positive view and identified several helpful aspects. CONCLUSION: Reactions were generally more positive than had been anticipated. A number of useful suggestions were made regarding how to improve the procedure. These have informed the development of guidelines for good practice.

Adolescent↗

PubMed2001

Outcome in fracture healing: a review.

This editorial reviews outcome measures in fracture healing. Individually radiological and clinical methods are inaccurate, but together provide a good indicator in clinical practice when a fracture has healed. Other quantitative methods are not practical. Vibrational analysis of fracture healing is complex and limited to research at present. Indirect fracture stiffness measurement is possible and has been used in clinical trials. Pin loosening reduces accuracy. The measurement of direct fracture stiffness has been validated and using this a decrease in re-fracture rate and a reduction of time to independent weight bearing (on average 3 weeks) was found. The system is accurate and simple to use in the clinical setting and allows the rate of healing to be monitored in fractures. Studies using poor outcome measures should be interpreted with care. The study of healing fractures is no exception.

Biomechanical Phenomena↗

PubMed2001

The use of coated paramagnetic particles as a physical label in a magneto-immunoassay.

An ideal label for use in an immunoassay would require no further chemical or electromagnetic stimulation prior to its detection and would be free from interference from the sample matrix. Micron sized paramagnetic particles are able to perturb magnetic fields. This perturbation can be directly detected using a suitable electronic device and is independent of the sample matrix. In this study coated paramagnetic particles were used as a physical label in a non-competitive solid phase "sandwich" assay for the detection of human transferrin. The transferrin acted as a "biological bridge" allowing a dose dependant immobilization of the paramagnetic particles to a polyethylene terephthalate solid phase. Quantitation of the paramagnetic label was achieved using an electronic detection system allowing a linear dose response with a femtomolar detection limit (260 fmol).

Animals↗

PubMed2001

A novel measuring system for the determination of paramagnetic particle labels for use in magneto-immunoassays.

Coated micrometer-sized paramagnetic particles (PMPs) are readily available and widely used in immunoassays, mainly for separation and as a solid phase. We have described in a separate paper a model sandwich assay in which approximately 1 x 10(5) to 1 x 10(6) PMPs (2.8 microm diameter) are immobilised on a plastic strip at the end of the assay. In this paper, we describe the design of an instrument that is capable of determining the number of PMPs on the plastic strip. The paper also describes a method of making standard plastic strips with known numbers of PMPs on them. A strip, when placed in a coil of wire in parallel with a capacitor, causes the resonant frequency of the coil to decrease because of the presence of the PMPs. The decrease in frequency relates directly to the number of PMPs on the strip. A circuit based on a voltage-controlled oscillator and a phase-locked loop is used to accurately measure the resonant frequency of the coil. The instrument is capable of detecting at least 1 x 10(5) PMPs immobilised on a plastic strip and has a linear response (r=0.99) for up to at least 3.33 x 10(6) PMPs. In terms of the iron content of the PMPs, the detection limit is approximately equal to 1.2 microg Fe in the paramagnetic particles and the sensitivity is approximately equal to 3 Hz per microg of Fe. The instrument is small and compact and together with a suitable magneto-immunoassay will have many applications, including near-patient monitoring.

Biosensing Techniques↗

PubMed2001

EMG biofeedback: the effects of CRF, FR, VR, FI, and VI schedules of reinforcement on the acquisition and extinction of increases in forearm muscle tension.

Biofeedback was used to increase forearm-muscle tension. Feedback was delivered under continuous reinforcement (CRF), variable interval (VI), fixed interval (FI), variable ratio (VR), and fixed ratio (FR) schedules of reinforcement when college students increased their muscle tension (electromyograph, EMG) above a high threshold. There were three daily sessions of feedback, and Session 3 was immediately followed by a session without feedback (extinction). The CRF schedule resulted in the highest EMG, closely followed by the FR and VR schedules, and the lowest EMG scores were produced by the FI and VI schedules. Similarly, the CRF schedule resulted in the greatest amount of time-above-threshold and the VI and FI schedules produced the lowest time-above-threshold. The highest response rates were generated by the FR schedule, followed by the VR schedule. The CRF schedule produced relatively low response rates, comparable to the rates under the VI and FI schedules. Some of the data are consistent with the partial-reinforcement-extinction effect. The present data suggest that different schedules of feedback should be considered in muscle-strengthening-contexts such as during the rehabilitation of muscles following brain damage or peripheral nervous-system injury.

Adolescent↗

PubMed2001

A single-injection, multi-segmental paravertebral block-extension of somatosensory and sympathetic block in volunteers.

BACKGROUND: It is our experience that a deposition of an anesthetic solution in the ventral area of the paravertebral space near the parietal pleura and the sympathetic trunk produces extended unilateral block. Because sympathetic block effects in this extended paravertebral block are not reported yet, we undertook this singly blinded, controlled study on the sympathetic change in volunteers. METHODS: A total of 22 ml 1% lidocaine was injected at the T11 level into the ventral area of the right-sided paravertebral space in 16 volunteers. The distribution of analgesia, heart rate, blood pressure and body temperature (measured by 12 skin sensors) was monitored. On a later occasion the volunteers underwent a control injection of saline. RESULTS: Unilateral analgesia (with no contralateral element) was induced in every subject injected with lidocaine, contrasted with no block induction with saline. Loss of pin-prick sensation was observed within 10 min after injection and involved a mean of 12 (range 8-13) dermatomes. A sympathetic block was indicated by cutaneous temperature increase within at least 6 dermatomes. Increase of arterial blood pressure was obtained in all volunteers with no change in pulse rate. No side effects or complications occurred. Epidural spread of the local anesthetic was unlikely because of the absence of contralateral cutaneous analgesia and temperature increase. CONCLUSION: One-sided extended analgesia (sensory loss) follows the paravertebral injection of lidocaine. A large ipsilateral sympathetic block is observed without change in pulse rate and with no hypotension. These are all characteristics of an optimal regional block.

Adult↗

PubMed2001

Negative pressure pulmonary oedema after cryotherapy for tracheal obstruction.

We report a patient who suffered negative pressure pulmonary oedema because of tracheal obstruction after cryotherapy to granulation tissue in the trachea. The pathophysiology and clinical course of negative pressure pulmonary oedema is described. Though there are reports of negative pressure pulmonary oedema after airway obstruction, to our knowledge this is the first case reported after cryotherapy.

Aged↗

PubMed2001

Spinal endoscopy in chronic low back pain with radiculopathy. A prospective case series.

All 38 patients listed for day-case spinal endoscopy over a 12-month period (April 1998 - April 1999), who had chronic severe low back pain with a radiculopathic element, were studied prospectively. The mean [range] pain duration before treatment was 10.9 [2-26] years and 50% had failed back surgery syndrome. In all patients in whom treatment was completed (n = 34), the pain-generating nerve roots were located through symptom interaction with the patient. All had epidural scar tissue, 14 (41%) having dense adhesions. Mobilisation of adhesions around the nerve root (neuroplasty) was performed so that a pocket was formed for the subsequent placement of bupivacaine, Depomedrone and clonidine. No intra-operative complications occurred and side-effects were minimal. Follow-up over a 12-month period showed statistically significant reductions in pain scores and disability. Spinal endoscopy may be the diagnostic method of choice for epidural fibrosis. It has substantial therapeutic and research potential. Prospective randomised studies are required.

Ambulatory Surgical Procedures↗

PubMed2001

Developing and evaluating complementary therapy services: Part 1. Establishing service provision through the use of evidence and consensus development.

The integration of complementary therapies within the British National Health Service (NHS) in the context of limited evidence of effectiveness has been much debated, as has the need for the provision of health services to be more evidence-based. In June 1994, a project was launched within a South-East London NHS Hospital Trust to introduce complementary therapy (acupuncture, homeopathy, and osteopathy), in the context of an evaluation program. This followed approximately 4 years of working toward raising the profile of complementary therapies within the hospital through study days, workshops, and providing a massage and osteopathic service for staff. A survey of local general practitioners highlighted areas of complementary therapy provision and interest in referring patients to a hospital-based service. A steering group was established to draw together a proposal for funding the service. Evidence for the effectiveness of acupuncture, homeopathy, and osteopathy was presented at a multidisciplinary seminar. A consensus development process, using a modified Delphi technique to establish referral indicators followed this. This study provides a useful model of service development in the absence of good quality evidence for the effectiveness of clinical interventions.

Attitude of Health Personnel↗