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Biomedical subjects

C A Young

Publications and source records attributed to C A Young.

At least 19 recordsLinked to original sources
PubMed2000

Development of a patient-specific dyspnoea questionnaire in motor neurone disease (MND): the MND dyspnoea rating scale (MDRS).

Motor neurone disease (MND) is a progressive, unremitting and fatal disease. Respiratory dysfunction is common and a significant cause of morbidity. The relationship between subjective dyspnoea and objective measures of lung function have been unexplored in MND. Increasing interest in the specific treatment of respiratory symptoms in MND has highlighted the need for simple, reliable and valid measures to quantify the degree of dyspnoea in this condition. Several generic questionnaires have been developed to rate subjective breathlessness but are inappropriate for use in MND patients as they often assess dyspnoea by exercise-limitation. As yet, there are no published disease-specific measures to assess dyspnoea in MND. In order to accurately and reproducibly measure the subjective experience of dyspnoea in this patient group, we have developed and validated a novel patient-specific dyspnoea questionnaire, the MND dyspnoea rating scale (MDRS). It comprises three domains covering dyspnoea, emotion and mastery and is valid for use in MND patients at all stages of disease progression. In our cohort of 40 unselected patients with MND we have shown that the patients subjective experience of dyspnoea is closely related to emotion and psychological control over the disease. Dyspnoea is not related to objective measures of lung function such as vital capacity, irrespective of limb or bulbar presentation. In conclusion, vital capacity, although useful prognostically, is only one aspect of respiratory function in MND. The MDRS is a reliable and valid tool to rate subjective dyspnoea in MND.

Adult↗
PubMed2000

Anti-spasticity agents for multiple sclerosis.

BACKGROUND: Spasticity is a common problem in MS patients causing pain, spasms, loss of function and difficulties in nursing care. A variety of oral and parenteral medications are available. OBJECTIVES: To assess the absolute and comparative efficacy and tolerability of anti-spasticity agents in multiple sclerosis (MS) patients. SEARCH STRATEGY: Randomised controlled trials (RCTs) of anti-spasticity agents were identified using MEDLINE, EMBASE, bibliographies of relevant articles, personal communication, manual searches of relevant journals and information from drug companies. SELECTION CRITERIA: Double-blind, randomised controlled trials (either placebo-controlled or comparative studies) of at least seven days duration. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data and the findings of the trials were summarised. Missing data were collected by correspondence with principal investigators. A meta-analysis was not performed due to the inadequacy of outcome measures and methodological problems with the studies reviewed. MAIN RESULTS: Twenty-three placebo-controlled studies (using baclofen, dantrolene, tizanidine, botulinum toxin, vigabatrin, prazepam and threonine) and thirteen comparative studies met the selection criteria. Only thirteen of these studies used the Ashworth scale, of which only three of the six placebo-controlled trials and none of the seven comparative studies showed a statistically significant difference between test drugs. Spasms, other symptoms and overall impressions were only assessed using unvalidated scores and results of functional assessments were inconclusive. REVIEWER'S CONCLUSIONS: The absolute and comparative efficacy and tolerability of anti-spasticity agents in multiple sclerosis is poorly documented and no recommendations can be made to guide prescribing. The rationale for treating features of the upper motor neurone syndrome must be better understood and sensitive, validated spasticity measures need to be developed.

Anti-Dyskinesia Agents↗
PubMed2000

Functional requirement of plant farnesyltransferase during development in Arabidopsis.

Arabidopsis era1 was identified as an abscisic acid-hypersensitive mutant caused by disruptions or deletions of the gene for the beta subunit (AtFTB) of farnesyltransferase (FTase). The heterodimeric enzyme catalyzes the covalent attachment of the 15-carbon farnesyl diphosphate to the C terminus of regulatory proteins and is essential for growth in yeast. The first disruption of FTB in a multicellular context revealed several developmental and growth regulatory processes that require the function of FTase. The lack of FTase activity in the Arabidopsis era1-2 FTB deletion mutant resulted in enlarged meristems and organs, supernumerary organs in floral whorls, arrested development of axillary meristems, late flowering, and homeotic transformations of flowers. Complementation of era1-2 with LeFTB, the tomato gene for the beta subunit of FTase, restored a normal phenotype and confirmed that the lesion is in AtFTB alone. The effect of this lesion on control of meristem size and on developmental processes suggests the involvement of regulatory proteins that require farnesylation for their function. At least three distinct processes that require the function of FTase were identified: regulation of cellular differentiation in the meristems, meristem maintenance, and regulation of flower development. Together, these results provide a basis for future studies on the involvement of FTase in specific developmental processes and for structure-function analysis of FTase in vivo.

Alkyl and Aryl Transferases↗
PubMed2000

The role of affect on the perception of disability in multiple sclerosis.

OBJECTIVE: To determine the prevalence of depression in multiple sclerosis in the community and to assess how the presence of depression affects patients' perception of their disability. DESIGN: Consecutive case series. SETTING: The study was carried out at a regional multiple sclerosis (MS) clinic. SUBJECTS: Eighty-eight patients with MS. MAIN OUTCOME MEASURES: Patients were asked to complete the following questionnaires: Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory (BDI), Rankin Scale of Disability/Handicap (completed by patient and physician to assess relative perceived disability) and two visual analogue scales (coping ability and perceived service adequacy). RESULTS: Thirty-nine per cent were case level for depression using the BDI criteria of Sullivan; 17% were case level for depression (34% borderline case) and 34% case level for anxiety on HADS. Depressed patients using both BDI and HADS criteria were three times more likely than nondepressed patients to perceive their disability as being greater than the physicians' perception (p < 0.001). CONCLUSION: Depression is common in MS and adversely affects patients' perception of their disability.

Affect↗
PubMed1999

Quality of life assessment in MND: development of a social withdrawal scale.

A scale to measure 'social withdrawal,' was developed specifically for use with MND patients. Scale design was based upon patient-focused interviews which were used to explore patients' concerns. The impact the condition had upon their social interactions with others was salient for all patients and affected their overall quality of life. Using issues raised by patients, a 23-item scale was generated to specifically and quantitatively measure social withdrawal and this scale was psychometrically evaluated. The scale was administered to a sample of 23 patients at varied stages of progression of MND, and to a control group of patients with arthritis with similar levels of physical disability. For MND patients withdrawal from the community was found to be closely related to severity of physical symptoms and depression. Specific patients were identified who are particularly susceptible to withdrawal and depression. Comparison of the pattern of withdrawal in the MND and arthritis patient groups suggested that there may be differences between the factors governing social withdrawal in different patient populations.

Adult↗
PubMed1998

Building a care and research team.

The provision of high quality care for people with Motor Neurone Disease (MND) is challenging. The physical and psychological health needs experienced in this progressively disabling disease necessitate input from many disciplines. In order to integrate the delivery of care, the preferred model for MND is a disease-specific team. Such teams can offer a coordinated range of skills, expertise and clinical experience in a setting of interprofessional support. Teams may adopt several formats; multidisciplinary, interdisciplinary and transdisciplinary. In multidisciplinary teams the different professions work to individually set goals and meet to discuss their progress. In interdisciplinary teams goals are first agreed by the team, whose members then coordinate their input to the common treatment plan. In transdisciplinary teams, not only goals but skills are shared. Teamwork allows the coordination of input and the sharing of skills and experience in solving complex clinical problems. Greater flexibility and integration of work make best use of resources. Disease-specific teams act as an educational resource and stimulate awareness of the condition. Teams should undertake clinical research, to strengthen their practice and demonstrate their effectiveness. Effective teamwork, whether in a clinical or research team, requires issues of responsibility, leadership, interprofessional rivalry and communication to be addressed.

Cooperative Behavior↗
PubMed1997

Structural plasticity of optic synapses in the rat suprachiasmatic nucleus: adaptation to long-term influence of light and darkness.

Synapses of optic afferents (optic synapses) in the suprachiasmatic nucleus of hooded rats were morphometrically evaluated after exposing the animals to 12 h, 14 days, 2 months, and 8 months of constant light (light rats) and darkness (dark rats). Compared with dark rats, optic synapses from light rats have larger boutons with larger mitochondria, more clear vesicles, fewer dense-core vesicles and front-line vesicles, smaller presynaptic dense projections, a smaller amount of postsynaptic density material, a smaller relative number of Gray-type I (asymmetric) junctions, a greater relative number of Gray-type II (symmetric) junctions, as well as more and larger mitochondria in the postsynaptic dendrites. Junctions of optic synapses are mostly straight, but the small number of positively curved contacts are more flattened in light rats than in dark rats. An age-related increase in the size of presynaptic dense projections was also observed. There are no changes in the sizes of clear and dense-core vesicles, in the size of synaptic junctions and their numerical density in area, and in the unspecific contact area between pre- and postsynaptic elements. The changes in optic boutons are characteristic for activated and relatively disused synapses with a slow, tonic firing rate. It appears that (1) the amount of postsynaptic density material is proportional to the strength of Gray-type I synapses, and that (2) some excitatory optic synapses become inhibitory after long-term activity, whereas some inhibitory synapses turn into excitatory contacts after long-term disuse.

Adaptation, Physiological↗
PubMed1997

Assessment of depression in patients with motor neuron disease and other neurologically disabling illness.

Motor neuron disease (MND) is a severely disabling, relentlessly progressive neurological condition with a marked reduction in life expectancy which might be expected to be associated with significant depression and psychological dysfunction following diagnosis. There is very little data on the incidence of depression in MND and most of the published evidence would suggest that depression is rare in patients with MND, especially when compared to other neurologically disabling illnesses. We have studied 40 patients with MND and compared them to a group of 92 patients with multiple sclerosis (MS) attending a neurology clinic. Depression was assessed using the Beck Depression Index (BDI) and the Hospital Anxiety and Depression Scale (HAD). There was no difference in incidence or severity of depression in these two patient groups. For the whole study group there was no difference in depression scores when compared by age, gender or marital status. Depression scores showed a weak association with increasing physical disability measured by the SF36 Physical Function scale for the MS group but there was no association between depression levels and SF36 physical function for the MND group. The MND group did, however, show a significant association between depression scores and pain measured by the SF36 scale. Anxiety levels (HAD scale) were shown to be significantly higher in females and married (versus single, widowed or divorced) subjects for the group as a whole. We conclude that depression is at least as common in MND patients as other neurologically disabled patients with MS and may often be associated with significant pain. Physicians and others involved in the care of patients with MND should be aware that depression and pain may be significant problems irrespective of the level of physical disability.

Aged↗
PubMed1997

Cryopreservation procedures for Day 7-8 equine embryos.

Larger grade 1 or 2 (1 = excellent,.... 4 = degenerate) equine embryos that ranged in diameter from 300 to 680 microm and were recovered from mares on Day 7 or 8 after ovulation, were randomly assigned to 3 widely divergent cryopreservation treatments. Treatment 1 consisted of cooling from -6 degrees C to -35 degrees C at 0.5 degrees C per min followed by plunging into liquid nitrogen, with a one-step addition and a 4-step removal of 1.0 M glycerol. Treatment 2 (step-down equilibration) consisted of a 2-step addition of glycerol to 4.0 M followed by a decrease to 2.0 M prior to freezing, with galactose present in the final step and in all glycerol removal steps and with a cooling protocol identical to Treatment 1. Treatment 3 was a standard vitrification protocol with step-wise addition of ethylene glycol up to 11.9 M, and step-wise removal of cryoprotectant with decreasing concentrations of galactose in the dilution medium. The cryoprotectants were removed at 20-21 degrees C. After the final dilution, the embryos were cultured in 5% CO2-in-air for 36 h at 38.5 degrees C on equine oviductal epithelial cell monolayers. Their morphology was then evaluated, their capsules were removed mechanically, and they were fixed prior to staining with 1% w:v orcein in 45% acetic acid to assess the morphology of their nuclei and cytoplasm. All 7 embryos in Treatment 1 degenerated during thawing or culture. Of the 6 embryos included in Treatment 2, 4 were graded 1, one was graded 2 and one graded 3 after culture in vitro. Of the 7 embryos in Treatment 3, one was graded 2, one was graded 3 and the remaining 5 were degenerate (P<0.01 among treatments). The average changes in initial diameter exhibited by the frozen/thawed embryos during culture after thawing were: Treatment 1, -91 microm; Treatment 2, +179 microm; Treatment 3, +20 microm (P<0.05). Two 26-day pregnancies were established following transfer of 6 Treatment 2 embryos (step-down equilibration method) to recipient mares.

Animals↗
PubMed1996

The use of lexipafant in the treatment of acute pancreatitis.

The pathophysiology of systemic organ failure in acute pancreatitis has been the subject of debate for many years but there is growing evidence that increase production of pro-inflammatory cytokines plays an important role. from this work and from the results of studies in experimental pancreatitis there exists a rationale for the use of PAF antagonists in the treatment of acute pancreatitis. Two pilot studies have now demonstrated a beneficial effect of the PAF antagonist Lexipafant on acute pancreatitis which may lead to an important advance in the treatment of these patients. A multicentre trial aiming to recruit 300 patients with severe acute pancreatitis is now underway in the UK, the results of which will be awaited with interest.

Acute Disease↗
PubMed1996

Novel and complex chromosomal arrangement of Rhizobium loti nodulation genes.

A mutational and structural analysis of Rhizobium loti nodulation genes in strains NZP2037 and NZP2213 was carried out. Unlike the case with other Rhizobium strains examined to date, nodB was found on an operon separate from nodACIJ. Sequence analysis of the nodACIJ and nodB operon regions confirm that R. loti common nod genes have a gene organization different from that of other Rhizobium spp. At least 4 copies of nodD-like sequences were identified in R. loti. The complete nucleotide sequence of one of these, nodD3, was determined. A new host-specific nod gene, nolL, was identified adjacent to nodD3. NolL shares homology with NodX and other O-acetyl transferases. Mutational analysis of the nod regions of strains NZP2037 and NZP2213 showed that nodD3, nodI, nodJ, and nolL were all essential for R. loti strains to effectively nodulate the extended host Lotus pedunculatus, but were not necessary for effective nodulation of the less restrictive host, Lotus corniculatus. Both nodD3 and nolL were essential for R. loti strains to nodulate Leucaena leucocephala.

Acyltransferases↗
PubMed1995

Disease progression and perceptions of health in patients with motor neurone disease.

Motor neurone disease (MND) is a useful paradigm for many progressive disabling neurological disorders and serves as a particularly opposite model for the study of patients' responses to progressive and irreversible disability. We studied the progression of disability and the patients' perception of their health in a group of MND patients (n = 14) for 6 months from diagnosis or soon after. A comparison group of similar age, gender ratio and initial disability on Barthel index were Parkinson's disease (PD) patients, admitted because of poor response to outpatient drug therapy and increasing disability (n = 22). MND patients showed rapid deterioration in all aspects of self care and mobility, as assessed by Barthel Index. 32% PD patients showed a significant improvement in disability during their admission. For both groups, perception of their physical health on the SF36 was very poor at recruitment compared to age- and sex-matched population norms. However for patients in both groups the SF36 could not be used to monitor changes in perception of health because of floor effects. In those in whom change could be assessed, there was a trend for MND patients to deteriorate and PD patients to improve. We conclude that loss of independence in self care and failing mobility may occur more rapidly than current medical and social services can accommodate. There is a need for planning and proactive intervention to support patients and careers. The patients' perception of their physical health is poor from time of diagnosis as assessed by the SF36, but this scale cannot be used to monitor patients with MND or late stage PD over time.

Aged↗
PubMed1995

Excess maternal history of diabetes in Caucasian and Afro-origin non-insulin-dependent diabetic patients suggests dominant maternal factors in disease transmission.

We examined the records of 2576 patients with non-insulin-dependent diabetes mellitus (NIDDM) and categorised them according to race and family history of diabetes. Family history of diabetes is known to play an important role in the development of NIDDM, and a maternal history is thought to be most influential. We found that a maternal history of diabetes was present in 60% of Caucasian and West Indian patients with a parental history of diabetes, whereas in Asian patients the figure was only 34%. Asian men were also more likely to have a father with diabetes. This anomaly may be due to cultural differences in the reporting of the disease. Our data support the dominant maternal role in the development of NIDDM in their offspring and suggest an under-reporting of NIDDM in Asian females.

Africa↗
PubMed1995

Elders' perceptions of the role of group psychotherapy in fostering self-transcendence.

Psychotherapeutic goals and interventions for older adults, like those for children and other age groups, need to be developmentally appropriate. Past clinical research has shown that self-transcendence is a resource for mental health in later life. The effectiveness of group psychotherapy in facilitating self-transcendence in elders was examined, applying a method of analysis in which a small, intact clinical sample could be used to generate data for research purposes. Results, based on a matrix analysis of group members' perceptions, indicated that group psychotherapy enhanced self-transcendence in various ways. Group psychotherapy may be used not only as a cost-effective treatment modality, but also as a theory-based intervention that is developmentally-appropriate for elders.

Adaptation, Psychological↗
PubMed1995

Central pontine myelinolysis: clinical and MRI correlates.

Central pontine myelinolysis (CPM) is a rare condition characterised by spastic tetraparesis, pseudobulbar palsy and the 'locked-in syndrome'. It is frequently fatal. We report a patient who developed CPM secondary to profound hyponatraemia and who recovered with no disability. Serial magnetic resonance imaging (MRI) demonstrated characteristic abnormalities within the pons at the onset of the disease, whereas computerised tomography was normal. Clinical improvement was followed six months later by progressive resolution of the MRI changes, with almost complete resolution after 18 months. Clinical and MRI findings correlate early in the course of CPM but clinical recovery predates MRI improvement by several months.

Adult↗
PubMed1994

Lymphocyte proliferation response to baker's yeast in Crohn's disease.

The etiology of Crohn's disease is still unknown. The present study served to test the hypothesis that baker's yeast (Saccharomyces cerevisiae) plays a role in Crohn's disease. Blood samples were obtained from 12 patients and 15 healthy controls. Peripheral blood leukocytes were isolated and incubated alone or with different concentrations of baker's yeast. After 3 days, the cultures were pulsed with tritiated thymidine. None of the lymphocyte cultures from healthy controls, including 3 bakers, proliferated in response to yeast. In striking contrast, all 9 patients with Crohn's disease in remission, on no medication, showed a threefold increase in their lymphocyte proliferation rate. Lymphocytes from 3 patients on 1.5 g of olsalazine maintenance therapy failed to respond. These results are consistent with previous findings that showed increased titers of IgG and IgA antibodies to baker's yeast in patients with Crohn's disease as compared to healthy controls. They confirm the suspicion that baker's yeast itself or a related antigen play a role in Crohn's disease and suggest that anti-inflammatory agents may act, in part, by inhibiting lymphocyte proliferation.

Crohn Disease↗
PubMed1993

Opsoclonus-myoclonus syndrome: an autopsy study of three cases.

Opsoclonus-myoclonus is a rare clinical syndrome. We report three patients who died with a pure opsoclonus-myoclonus syndrome. The presentation, management and associations of this distinctive condition are discussed, and the results of detailed pathological examination described. In each case the only abnormality was perivascular collections of lymphocytes widely distributed in the brain. This supports an immune-mediated rather than structural aetiology.

Aged↗