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Biomedical subjects

Christopher Morris

Publications and source records attributed to Christopher Morris.

At least 19 recordsLinked to original sources
PubMed2026

Prophylactic antibiotics to prevent chest infections in children with neurological impairment: the PARROT RCT.

BACKGROUND: Improvements in neonatal and paediatric care in recent decades have increased the survival of children with non-progressive neurological impairment. Respiratory disease in children with neurological impairment is common, with symptoms difficult to manage and lower respiratory tract infection occurring frequently. To reduce these, prophylactic antibiotics are being increasingly used, but the type, duration and dose of antibiotics can vary considerably, and there is limited evidence about their effectiveness in children and young people. A joint United Kingdom and Australia multicentre, randomised, double-blind, placebo-controlled trial comparing 52 weeks of azithromycin to placebo in children and young people with neurological impairment at risk of lower respiratory tract infection (PARROT) was planned to address this gap. PARROT was a multicentre, parallel group, blinded, pragmatic randomised controlled trial of 52-week duration with a planned sample size of 500 (250 in each arm) participants with neurological impairment. The primary outcome was the proportion of children and young people hospitalised with lower respiratory tract infection over the 52-week period. RESULTS: In total, 90 children and young people (62 in Australia, 28 in the United Kingdom) aged 3-17 years, with a diagnosed non-progressive, non-neuromuscular neurological impairment, who had persistent respiratory symptoms were randomised (1 : 1) to receive azithromycin or placebo. Baseline demographic and clinical characteristics were relatively well balanced across the two treatment groups and countries. Overall, mean (standard deviation) age was 9.2 (4.4) years, with 64% of participants having cerebral palsy, 67% being non-ambulant and 54% being totally tube-fed. At baseline, mean (standard deviation) numbers of hospital admissions with lower respiratory tract infection in the preceding year were 1.8 (2.0)/year, and general practitioner attendances 3.3 (3.0)/year. The PARROT trial was closed early to recruitment due to challenges arising from the COVID-19 pandemic. Sixty-five (72%) participants (azithromycin n = 30, placebo n = 35) completed 52 weeks of treatment and were not withdrawn early from the trial. Regarding the primary outcome, 11 (36.7%) in the azithromycin group were hospitalised with lower respiratory tract infection and 9 (25.7%) in the placebo group [absolute risk reduction 0.11 (95% confidence interval -0.12 to 0.33), relative risk 1.43 (95% confidence interval 0.68 to 2.97)]. Analysis of secondary outcome data was limited by the number of missing data, but parent-reported quality of life for young person and parent, sleep amount/quality for young person and parent, and respiratory symptoms were similar between groups and countries. LIMITATIONS: As PARROT was stopped early and was consequently underpowered, it is not possible to say whether azithromycin prophylaxis is any more effective than placebo in reducing the proportion of children admitted to hospital with lower respiratory tract infection after a 52-week period. CONCLUSIONS AND FUTURE WORK: Although we cannot comment on the effectiveness of prophylactic antibiotics in this context, we can draw some useful conclusions from this trial. Thus, the importance placed by families on hospitalisation and its prevalence in both treatment groups, even during the pandemic, would suggest that this is an appropriate primary outcome measure for future trials in this high-risk group of children and young people. Furthermore, the high attrition rate and large numbers of missing data, specifically for questionnaire-based outcomes at later follow-up points, should encourage researchers to be mindful of minimising trial burden to families for any future trials wherever possible. FUNDING: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 16/17/01.

Humans↗
PubMed2007

Soluble cell adhesion molecules in late-life depression.

BACKGROUND: Late-life depression has been associated with vascular diseases and with increases in circulating cytokines and cell adhesion molecules in the prefrontal cortex. We hypothesized that soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) would be increased in late-life major depression. METHODS: Serum levels of sICAM-1 and sVCAM-1 were measured in subjects over 60 with major depression (N = 23), subsyndromal depression (N = 20) and controls (N = 25). Depression severity was assessed using the Montgomery-Asberg (MDRS) and Geriatric Depression (GDS) rating scales. RESULTS: There was no significant increase in sICAM-1 (p = 0.240) or sVCAM-1 (p = 0.600) in depression nor was there any correlation of either molecule with depression severity. Adjusting for differences in cognitive impairment did not alter these findings. There was also no difference between subjects with an early onset of depression (before 60) and those with late-onset depression. CONCLUSIONS: These findings do not provide evidence that previously reported increases in serum cytokines in depression are due to peripheral vascular disease. Although we assessed subjects for vascular diseases it is possible that subtle but important differences between groups may still have been present and may have contributed to our negative findings. Our results suggest central nervous system mechanisms, such as related to HPA axis activation, may be responsible for the enhanced inflammatory response in depression.

Age of Onset↗
PubMed2006

Implications for clinical staging of metastatic cutaneous squamous carcinoma of the head and neck based on a multicenter study of treatment outcomes.

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) of the head and neck is a common cancer that has the potential to metastasize to lymph nodes in the parotid gland and neck. Previous studies have highlighted limitations with the current TNM staging system for metastatic skin carcinoma. The aim of this study was to test a new staging system that may provide better discrimination between patient groups. METHODS: A retrospective multicenter study was conducted on 322 patients from three Australian and three North American institutions. All had metastatic cutaneous SCC involving the parotid gland and/or neck and all were treated for cure with a minimum followup time of 2 years. These patients were restaged using a newly proposed system that separated parotid disease (P stage) from neck disease (N stage) and included subgroups of P and N stage. Metastases involved the parotid in 260 patients (149 P1; 78 P2; 33 P3) and 43 of these had clinical neck disease also (22 N1; 21 N2). Neck metastases alone occurred in 62 patients (26 N1; 36 N2). Ninety percent of patients were treated surgically and 267 of 322 received radiotherapy. RESULTS: Neck nodes were pathologically involved in 32% of patients with parotid metastases. Disease recurred in 105 (33%) of the 322 patients, involving the parotid in 42, neck in 33, and distant sites in 30. Parotid recurrence did not vary significantly with P stage. Disease-specific survival was 74% at 5 years. Survival was significantly worse for patients with advanced P stage: 69% survival at 5 years compared with 82% for those with early P stage (P = 0.02) and for those with both parotid and neck node involvement pathologically: 61% survival compared with 79% for those with parotid disease alone (P = 0.027). Both univariate and multivariate analysis confirmed these findings. Clinical neck involvement among patients with parotid metastases did not significantly worsen survival (P = 0.1). CONCLUSIONS: This study, which included a mixed cohort of patients from six different institutions, provides further information about the clinical behavior of metastatic cutaneous SCC of the head and neck. The hypothesis that separation of parotid and neck disease in a new staging system is supported by the results. The benefit of having subgroups of P and N stage is uncertain, but it is likely to identify patients with unfavorable characteristics that may benefit from further research.

Carcinoma, Squamous Cell↗
PubMed2006

Reliability of the manual ability classification system for children with cerebral palsy.

The aim of this study was to determine the reliability of family and professional assessment of manual ability using the Manual Ability Classification System (MACS) for children with cerebral palsy (CP) in the UK. Families who were taking part in a study measuring the activities and participation of children with CP were invited to classify their child's manual ability using the MACS. Postal surveys were conducted with the families and health professionals nominated by the families. Perfect agreement was assessed as a percentage; chance-corrected agreement was measured using Cohen's kappa (kappa), and reliability was determined using the intraclass correlation coefficient (ICC). Families of 91/128 (71%) children responded to the survey (53 males, 38 females; mean age 9y 11mo [SD 1y 11mo], range 6-12y) out of whom 88 indicated a single MACS level. Seventy-two children (82%) were classified with spastic CP, 12 (14%) with dyskinesia, two (2%) with ataxia, and two (2%) were not classified. There were 21, 27, 11, 10, and 19 children who were classified by their families in Gross Motor Function Classification System Levels I to V respectively; 14, 30, 18, 13, and 13 children classified by their families in MACS levels I to V. The survey of health professionals generated 60/71 (85%) responses from physiotherapists, 55/58 (93%) responses from paediatricians, and 21/24 (88%) responses from occupational therapists. There was perfect agreement between families and professionals for more than 50% of children; the indices of chance-corrected agreement ranged from kappa=0.3 to 0.5, and the reliability coefficients ranged from ICC 0.7 to 0.9. Indices of agreement and reliability between families and professionals were equivalent to those between different professionals. The MACS, therefore, offers a valid and reliable method for communicating about the manual ability of children with CP. Families and professionals may not always agree precisely on a MACS level, particularly if children's performance of manual tasks varies in different environments.

Aptitude↗
PubMed2006

Do the abilities of children with cerebral palsy explain their activities and participation?

The aim of this study was to use family-assessed instruments and details of children's impairments to explore factors affecting the activities and participation of children with cerebral palsy (CP). A postal survey was conducted with families of a geographically defined population of children with CP aged 6 to 12 years. Family-assessed indices of children's activities and participation were the Activities Scale for Kids (ASK) and Lifestyle Assessment Questionnaire (LAQ-CP). Families also assessed children's abilities using the Gross Motor Function and Manual Ability Classification Systems (GMFCS; MACS). Details of children's impairments were available from the 4Child epidemiological database and used with the GMFCS and MACS as explanatory variables in multiple regression analyses to identify their effect on children's activities and participation. Families of 175/314 (56%) children returned an assessment using the GMFCS and 129 (41%) children participated fully by returning all the questionnaires. Full participants (72 males, 57 females) did not differ from those who did not take part by their age, sex, CP characteristics, or associated impairments: GMFCS Level I-25, Level II-43, Level III-15, Level IV-14, Level V-23; MACS Level I-14, Level II-30, Level III-18, Level IV-13, Level V-13. Scores for the ASK and LAQ-CP Physical Independence and Mobility domains were predicted well by children's movement, manual, and intellectual disability, and also, to some extent, by the presence of seizures or speech problems. LAQ-CP domains for Economic and Clinical Burden and Social Integration were not well explained by children's abilities and impairments. Family assessment, therefore, offers a useful method for measuring children's activities and participation; however, currently available instruments do not fully represent all the domains in the International Classification of Functioning, Disability and Health. Children's abilities only partially explain their activities and participation.

Aptitude↗
PubMed2006

The soybean isoflavone genistein induces differentiation of MG63 human osteosarcoma osteoblasts.

A soybean-rich diet was shown to reduce the incidence of osteoporosis in Eastern countries; its effect on bone metabolism was ascribed to the action of the soybean isoflavones such as genistein. Although many studies have shown isoflavone-induced osteoblast differentiation, its preventative action on bone mass loss has not been clarified. Here, the osteogenetic effects of genistein on human cell line MG63 osteoblasts were elucidated using a variety of approaches. In particular, phalloidin-rhodamine staining revealed that genistein-treated osteoblasts possessed a more organized cytoskeleton, and genistein's inhibitory effect upon cell proliferation was associated with exposure of phosphatidylserines on the external plasmalemma surface. Although this phosphatidylserine exposure is considered a typical apoptotic marker, scanning and transmission electron microscopy revealed that genistein-treated osteoblasts released matrix vesicles and showed no evidence of chromatin condensation. Assays, stainings, and scanning electron microscopy showed that genistein-treated osteoblasts synthesized relatively high levels of collagen and alkaline phosphatase and, even in a nonosteogenic growth medium, formed mineralized bone noduli. A clear pattern of genistein-induced osteoblast activation therefore emerges, in which all of the essential components required for the rapid production of mineralized bone extracellular matrix are stimulated by this soybean isoflavone.

Apoptosis↗
PubMed2005

The k variant of the butyrylcholinesterase gene is associated with reduced phosphorylation of tau in dementia patients.

Accumulating evidence suggests that butyrylcholinesterase (BuChE) plays an important role in the progression of cognitive deficits and Alzheimer-type pathology in dementia patients. We examined the relationship between the K variant of BuChE and the severity of deposits of amyloid (Abeta(1-42)) and phosphorylated tau in the temporal cortex (BA36) of 30 prospectively studied autopsy-diagnosed dementia (Alzheimer's disease and dementia with Lewy bodies) patients. There was 42% less phosphorylated tau in BA36 in cases with > or =1 K compared with those with wild-type BuChE alleles (t = 2.2, p = 0.039), but no difference in the extent of Abeta(1-42) deposition. BuChE may play this role in the phosphorylation of tau, relevant to therapeutic inhibition of the enzyme.

Aged↗
PubMed2005

In vitro assessment of the osteointegrative potential of a novel multiphase anodic spark deposition coating for orthopaedic and dental implants.

Hydroxyapatite coatings have been proven to improve the osteointegration of metal implants through a tight binding to the bone mineral phase as well as through favorable osteoblast adhesion and proliferation onto the implant surface. However, hydroxyapatite coatings are not stable and they tend to delaminate from the metal surface when challenged by the mechanical stresses experienced by the implant. Recently, a new multiphase anodic spark deposition (ASD) method has been optimized where the formation of a thick oxide film is followed by the deposition of a calcium phosphate mineral phase and its etching by alkali. The data in this paper demonstrate that this novel type of coating, BioSpark, improves the material osteointegration potential when compared to conventional ASD while offering more mechanical stability. A faster mineralization was obtained by incubation in simulated body fluids and osteoblasts showed better adhesion, proliferation, differentiation, and collagen production. These performances were related to the surface morphology, to the film calcium/phosphate ratio and its surface oxygen content, as well as to a preferential binding of structural proteins such as fibronectin.

Adsorption↗
PubMed2005

Angiotensin converting enzyme insertion/deletion polymorphisms in vasovagal syncope.

UNLABELLED: Recent studies suggest vasovagal syncope (VVS) has a significant heritable component (crude estimate sibling relative risk (lambda(s)): 1080) indicating that at least some forms of VVS may have a genetic cause. Here we present the first study examining a potential genetic abnormality in VVS. METHODS: DNA was collected from consecutive patients attending our unit with head up tilt confirmed VVS (n=165). One hundred and fourteen affected and unaffected first-degree relatives of those with a definitive diagnosis of VVS and positive family history also provided DNA. RESULTS: DNA from 165 VVS index cases was genotyped for the ACE insertion/deletion polymorphism. Mean+/-SD age of cases was 56+/-19 years (103 (62%) females). There was no significant difference in distribution of ACE insertion or deletion gene frequencies in cases compared with a large (>6000 subjects) national control population. No preferential transmission of alleles in families was identified using tests of association (P=0.1789) CONCLUSION: We have shown using both a case control and a small family based association study that polymorphisms of ACE alone are not associated with increased risk of VVS. Further studies are planned to clarify the genotype/phenotype relationship in VVS and examine other candidate genes.

Case-Control Studies↗
PubMed2005

Increase in interleukin-1beta in late-life depression.

OBJECTIVE: Depression has been associated with increases in circulating cytokines in younger adults, and there is evidence for prefrontal inflammation in late-life depression. The authors tested the hypothesis that levels of cytokine interleukin-1beta (IL-1beta) would be higher in subjects with late-life major depression. METHOD: Serum levels of IL-1beta were measured in three groups of subjects who were older than 60: 19 subjects with major depression, 20 subjects with subsyndromal depression, and 21 healthy comparison subjects. The Montgomery-Asberg Depression Rating Scale and the Geriatric Depression Scale were used to assess severity of depression. RESULTS: Compared with healthy subjects, those with major depression had significantly higher levels of IL-1beta (170%); the higher levels of IL-1beta strongly correlated with current depression severity. There were no significant differences between subjects with subsyndromal depression and the other two groups. CONCLUSIONS: These findings support the existence of an inflammatory response, which may be state dependent, in late-life depression.

Age Factors↗
PubMed2004

Gross Motor Function Classification System: impact and utility.

In summary, the GMFCS has had, and continues to have, a major effect on the health care of children with CP. The number of citations of the GMFCS has been increasing every year, and the classification system has had good uptake internationally and across the spectrum of health professionals for use in research design and clinical practice by providing a system for clearly communicating about children's gross motor function. The utility of diagnostic labels such as diplegia has been questioned. However, although by definition CP is a disorder of posture and movement, the movement disability is often only one of the neurodevelopmental problems for many children with CP. When a complete description of a child's clinical presentation is required we recommend that the GMFCS be used together with the Surveillance of Cerebral Palsy in Europe classification indicating the type and topography of movement impairment. When appropriate the clinical profile will similarly be enhanced with details of other impairments and disabilities such as epilepsy or sensory, learning, feeding, or emotional disturbance. The observations in this annotation are constrained by the amount of information in the public domain. Although these sources adequately represent the effect of the GMFCS on research design, they are less likely to inform us of how the GMFCS is being used in administration, clinical practice, or education. It is not yet clear whether information is being used for these purposes or in assisting with case load management, as intended by the developers. By its localized nature, such information might remain difficult to gauge. We would therefore be interested to hear from others who are using the system for these or any other purposes.

Cerebral Palsy↗
PubMed2004

Reliability of family report for the Gross Motor Function Classification System.

The aim of this study was to determine the reliability of family reports for the Gross Motor Function Classification System (GMFCS), a condition-specific discriminative measure of severity of movement disability for children with cerebral palsy (CP). We conducted a cross-sectional survey using a short questionnaire with families of children with CP for whom we already had ratings of GMFCS level made by a health professional. We assessed the potentially confounding effect of whether the family had discussed the GMFCS with a professional. Two hundred and one questionnaires were posted to families of which 97 (48%) were completed and returned. Mean age of the children (53 males, 40 females) was 9 years 5 months (SD 1 year 1 month), range 6 to 11 years. Children of the families who responded encompassed the spectrum of types and distribution of impairment and severity of movement disability. The intraclass correlation coefficient (ICC) of agreement between professionals and families who had discussed their child's GMFCS level with a health professional (n=35) was 0.97 (95% confidence interval [CI] 0.96 to 0.98); for those who had not (n=52) the ICC was 0.92 (95% CI 0.91 to 0.93); and for the whole sample (n=93) the ICC was 0.94 (95% CI 0.90 to 0.96). Stability between ratings made by health professionals for children when they were in the 4 to 6 year age band of the GMFCS and ratings made by families for the same children when they were in the 6 to 12 year age band (n=35) was ICC=0.96 (95% CI 0.95 to 0.97). The excellent agreement demonstrated in this study suggests that family reports of the GMFCS made by using our questionnaire provide a reliable method for measuring gross motor function in children between 6 and 12 years old. This might be more efficient for observational studies of large populations, experimental research, or community health administration than direct observation, particularly when professional assessment is not feasible.

Adult↗
PubMed2003

Neck level-specific nodal metastases in oropharyngeal cancer: is there a role for selective neck dissection after definitive radiation therapy?

PURPOSE: To determine the extent of the required neck dissection for patients with persistent lymphadenopathy after definitive radiation therapy for oropharyngeal cancer. If feasible, a conservative approach using selective neck dissection would likely minimize the extent of neck fibrosis and other adverse sequelae. METHODS: Analysis of pretreatment and posttreatment radiologic scans and pathology reports of 76 patients with oropharyngeal carcinoma (35 tonsil; 41 base of tongue), who had radiologic evidence of persistent nodal disease for level-specific involvement. Patients were treated with twice-daily fractionations of external-beam radiation therapy (median dose, 76.8 Gy to the primary tumor) and planned neck dissection (levels I-V) for bulky nodes (N2-3) or salvage neck dissection for N1 disease. RESULTS: The distribution of clinical nodal disease by neck level on the basis of pretreatment and posttreatment radiologic scans indicated levels II and III to be most commonly involved. The false-negative rate for the restaging radiologic scans for each neck level was as follows: level I, 0%; level II, 8%; level III, 6%; level IV, 5%; and level V, 1.5%. Of the eight hemi-necks found to contain positive pathologic nodes in a neck level judged to be negative on the basis of restaging scans, five of the patients subsequently had disease recurrence in the primary site. Patients who had evidence of residual neck disease had a significantly lower rate of locoregional control (77% vs 100%, p =.0005). CONCLUSIONS: The extent of neck dissection for patients with nodal disease associated with oropharyngeal cancer treated with radiation therapy should include levels II-IV. It is reasonable to spare levels I and V in patients without radiologic and clinical evidence of positive nodes in levels I and V.

Adult↗
PubMed2003

Prognostic factors in allogeneic transplantation for patients with high-risk multiple myeloma after reduced intensity conditioning.

OBJECTIVES: The aim of this study was to identify prognostic factors for outcome of high-risk patients with multiple myeloma after allogeneic transplantation prepared by reduced intensity conditioning (RIC). MATERIALS AND METHODS: Data from 45 consecutive patients (median age 52 years, range 38-68), who received grafts from a sibling (n = 34) or unrelated donor (n = 11) were analyzed. Fourteen patients received an RIC allotransplant while chemosensitive (>/=partial remission [PR]), whereas 31 chemoresistant patients (<PR) had either relapsed (n = 28) or were refractory (n = 3) after one or more autografts; of these 28 patients, 4 had secondary myelodysplasia concurrent with relapse. Of the 14 chemosensitive patients, 12 received an RIC allotransplant as consolidation after an autotransplant (AT). RESULTS: Twenty-nine (64%) were in a complete remission (CR) or near CR, 5 were in PR, and 5 had progressive disease. Twenty-five patients died, 17 of transplant-related complications, 7 of progressive disease, and 1 of a nontransplant-related cause. With a median follow-up of 15 months, the following factors were significantly associated with a better event-free survival (EFS) probability at 3 years: chemosensitive disease (64% vs 12%), pretransplant performance score (PS, Zubrod) </=2 (36% vs 0%), CR + near CR post transplant (36% vs 0%), and presence of chronic graft-vs-host disease (GVHD; 29% vs 0%). The same factors and absence of grade III to IV acute GVHD (52% vs 0%) were significant for a better overall survival (OS). On multivariate analysis including only pretransplant factors, both chemosensitive response and PS </=2 were significant for overall survival and event-free survival (p < 0.01). When response to RIC allotransplant and GVHD were added to the model, chronic GVHD was significant for better event-free survival, with an odds ratio of 1.5 (p < 0.01). CONCLUSIONS: Our data suggest that although RIC allotransplant induces high rates of CR and near CR, even in refractory disease, it appears to result in a durable response only if it is applied early in the disease in high-risk patients, when they still are chemosensitive and have an adequate PS.

Adult↗
PubMed2003

Prognostic impact of cytogenetic and interphase fluorescence in situ hybridization-defined chromosome 13 deletion in multiple myeloma: early results of total therapy II.

Cytogenetic abnormalities of chromosome 13 (CA 13) and those detected by fluorescence in situ hybridization (FISH 13) have both been associated with poor prognosis in multiple myeloma (MM) patients. The prognostic implications of CA, FISH 13 and other standard laboratory parameters were examined in the first 231 patients enrolled in Total Therapy II, an intensive cytotoxic chemotherapy programme with tandem autotransplants. Three-year projections of event-free survival (EFS) and overall survival (OS) were 71% and 77% respectively. CA 13 was detected in 14% and significantly correlated with FISH 13 (present in 51%), tumour burden, proliferative activity and lactic dehydrogenase (LDH). Both EFS and OS were significantly shorter in patients with CA 13, FISH 13, LDH >or= 190 U/l, beta2 microglobulin >or= 4 mg/l and C reactive protein >or= 4.0 mg/l; other CA was an additional risk factor for OS. Two-thirds of CA 13 patients were identified by FISH 13 and plasma-cell-labelling index (PCLI) >or= 0.4%; however, PCLI failed to identify additional risk groups in FISH subsets. Although present in considerably fewer patients, CA 13 imparted more rapid relapse (61% at 3 years) and death (43% at 3 years) than FISH 13 (38% and 35%; P = 0.02 and 0.1 respectively) and should be part of the initial work-up of patients with MM.

Aged↗