Biomedical subjects

G Haddock

Publications and source records attributed to G Haddock.

At least 19 recordsLinked to original sources

PubMed2006

ADAMTS-1 and -4 are up-regulated following transient middle cerebral artery occlusion in the rat and their expression is modulated by TNF in cultured astrocytes.

ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) enzymes are a recently described group of metalloproteinases. The substrates degraded by ADAMTS-1, -4 and -5 suggest that they play a role in turnover of extracellular matrix in the central nervous system (CNS). ADAMTS-1 is also known to exhibit anti-angiogenic activity. Their main endogenous inhibitor is tissue inhibitor of metalloproteinases (TIMP)-3. The present study was designed to investigate ADAMTS-1, -4 and -5 and TIMP-3 expression after experimental cerebral ischaemia and to examine whether cytokines known to be up-regulated in stroke could alter their expression by astrocytes in vitro. Focal cerebral ischaemia was induced by transient middle cerebral artery occlusion in the rat using the filament method. Our results demonstrate a significant increase in expression of ADAMTS-1 and -4 in the occluded hemisphere but no significant change in TIMP-3. This was accompanied by an increase in mRNA levels for interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1ra) and tumour necrosis factor (TNF). ADAMTS-4 mRNA and protein were up-regulated by TNF in primary human astrocyte cultures. The increased ADAMTS-1 and -4 in experimental stroke, together with no change in TIMP-3, may promote ECM breakdown after stroke, enabling infiltration of inflammatory cells and contributing to brain injury. In vitro studies suggest that the in vivo modulation of ADAMTS-1 and -4 may be controlled in part by TNF.

ADAM Proteins↗

PubMed2006

Currarino triad: characteristic appearances on magnetic resonance imaging and plain radiography.

The Currarino triad is a complex anomaly consisting of an anorectal malformation, a sacral bone defect and a presacral mass. It was first described in 1981 and since then, approximately 250 cases have been reported. Radiology has an important part to play in the diagnosis of this entity, as the imaging features are characteristic. We report a case of Currarino triad in an infant who presented with intractable constipation and discuss relevant MRI and plain radiography findings.

Abnormalities, Multiple↗

PubMed2006

Upregulation of ADAM-17 expression in active lesions in multiple sclerosis.

ADAM-17, a disintegrin and metalloproteinase, is the major proteinase responsible for the cleavage of membrane-bound tumour necrosis factor (TNF) as well as being an active sheddase of other cytokines, cytokine receptors, growth factors and adhesion molecules. TNF is a major proinflammatory cytokine that has been identified as having a pathogenic role in inflammatory diseases within the CNS including multiple sclerosis (MS). Here we report the cellular origin and distribution of ADAM-17 expression within clinically and neuropathologically confirmed MS and normal control white matter, assessed by immunohistochemistry, western blotting and PCR. ADAM-17 expression was associated with the blood vessel endothelium, activated macrophages/microglia and parenchymal astrocytes in MS white matter. Increased levels of ADAM-17 immunoreactivity were displayed in active lesions with evidence of recent myelin breakdown. Further studies into the functional role of ADAM-17 in the pathogenesis of MS and other inflammatory conditions are required.

ADAM Proteins↗

PubMed2006

Expression of ADAMTS-1, -4, -5 and TIMP-3 in normal and multiple sclerosis CNS white matter.

ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) -1, -4 and -5 proteases have been identified in the CNS at the mRNA level. These glutamyl endopeptidases, inhibited by tissue inhibitor of metalloproteinases (TIMP)-3, are key enzymes in the degradation of the aggregating chondroitin sulphate proteoglycans (CSPGs), and may therefore play a role in CNS extracellular matrix (ECM) changes in multiple sclerosis (MS). We have investigated ADAMTS and TIMP-3 expression in normal and MS CNS white matter by real-time RT-PCR, western blotting and immunohistochemistry. We report for the first time the presence of ADAMTS-1, -4 and -5 in normal and MS white matter. Levels of ADAMTS-1 and -5 mRNA were decreased in MS compared to normal tissue, with no significant change in ADAMTS-4 mRNA levels. Protein levels of ADAMTS-4 were significantly higher in MS tissue compared to normal tissue. Immunohistochemical studies demonstrated that ADAMTS-4 was associated predominantly with astrocytes with increased expression within MS lesions. TIMP-3 mRNA was significantly decreased in MS compared to controls. These studies suggest a role for ADAMTS-4 in the pathogenesis of MS. Further studies on the activity of ADAMTS-4 will enable a better understanding of its role in the turnover of the ECM of white matter in MS.

ADAM Proteins↗

PubMed2005

Differential expression of ADAMTS-1, -4, -5 and TIMP-3 in rat spinal cord at different stages of acute experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of inflammatory demyelination, a pathological event common to multiple sclerosis (MS). During CNS inflammation there are alterations in the extracellular matrix (ECM). A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS)-1, -4 and -5 are proteases present in the CNS, which are able to cleave the aggregating chondroitin sulphate proteoglycans, aggrecan, phosphacan, neurocan and brevican. It is therefore important to investigate changes in their expression in different stages of EAE induction. We have investigated expression of ADAMTS-1, -4, -5 and tissue inhibitor of metalloproteinase (TIMP)-3, by real-time RT-PCR. We have also examined protein expression of ADAMTS-1, -4 and -5 by western blotting and immunocytochemistry in spinal cord from animals at different stages of disease progression. Our study demonstrated a decrease in ADAMTS-4 mRNA and protein expression. TIMP-3 was decreased at the mRNA level although protein levels were increased in diseased animals compared to controls. Our study identifies changes in ADAMTS expression during the course of CNS inflammation which may contribute to ECM degradation and disease progression.

ADAM Proteins↗

PubMed2005

The reliability and validity of general psychotic rating scales with people with mild and moderate intellectual disabilities: an empirical investigation.

BACKGROUND: Whilst assessment tools have been developed to diagnose schizophrenia in people with mild intellectual disabilities (IDs), little attention has been paid to developing reliable and valid dimensional measures of psychotic experiences with this population. This study investigates the reliability and validity of two such measures developed for the general adult psychiatric population, the Positive and Negative Syndrome Scale (PANSS) and the Psychotic Symptom Rating Scales (PSYRATS), with a population of adults with mild IDs. METHOD: Sixty-two adults with mild IDs were interviewed using the PANSS and PSYRATS, and independently interviewed using the Psychiatric Assessment Schedule--Adults with Developmental Disability (PAS-ADD) to obtain psychiatric diagnoses to the criteria of the International Classification of Diseases--Tenth Revision (ICD-10). On the basis of ICD-10 diagnosis, participants were divided into three groups: psychosis (n=11); other mental health problem (n=14); no mental health problem (n=37). PANSS and PSYRATS subscale scores were compared across these three groups and were correlated with PAS-ADD symptom scores across a number of PAS-ADD symptom domains. RESULTS: All PANSS and PSYRATS subscales showed adequate internal reliability, largely good test-retest reliability, and logical inter-correlations between subscales. The PANSS positive symptoms and the PSYRATS auditory hallucinations subscales differentiated between the psychosis group and the other groups; the PANSS general symptoms subscale differentiated between the psychosis and no mental health problem groups; and the PANSS negative symptoms and the PSYRATS delusions subscales did not differentiate between the three groups. CONCLUSIONS: The PANSS and PSYRATS are promising measures for use with people with mild IDs and psychotic experiences, although further investigation of items relating to negative symptoms and delusions is warranted.

Adolescent↗

PubMed2004

The effects of emotional salience on thought disorder in patients with bipolar affective disorder.

BACKGROUND: This study aimed to explore the effects of emotionally salient material on thought disorder in patients with bipolar affective disorder. METHOD: Seventy-one participants (20 manic, 15 depressed, 16 currently well patients and 20 non-psychiatric-controls) were interviewed in two conditions: an emotionally salient interview and a non-salient interview. Speech samples were rated using the Scale for the Assessment of Thought, Language and Communication. RESULTS: Manic patients presented with significantly more thought disorder than any other group in both conditions and exhibited the greatest reaction to emotionally salient material. CONCLUSION: The effects of emotional salience on thought, language and communication are not unique to schizophrenic patients. The speech of manic patients is more affectively responsive than the speech of remitted, bipolar depressed and normal participants. The implications of these findings are discussed.

Adult↗

PubMed2004

The evolution of insight, paranoia and depression during early schizophrenia.

BACKGROUND: How insight, paranoia and depression evolve in relation to each other during and after the first episode of schizophrenia is poorly understood but of clinical importance. METHOD: Serial assessments over 18 months were made using multiple instruments in a consecutive sample of 257 patients with first episode DSM-IV non-affective psychosis. Repeated measures of paranoia, insight, depression and self-esteem were analysed using structural equation modelling, to examine the direction of relationships over time after controlling for confounds. RESULTS: Depression was predicted directly by greater insight, particularly at baseline, and by greater paranoia at every stage of follow-up. Neither relationship was mediated by self-esteem, although there was a weak association of lower self-esteem with greater depression and better insight. Paranoia was not strongly associated with insight. Duration of untreated psychosis and substance use at baseline predicted depression at 18 months. CONCLUSIONS: In first-episode psychosis, good insight predicts depression. Subsequently, paranoia is the strongest predictor. Neither effect is mediated by low self-esteem. Effective treatment of positive symptoms is important in preventing and treating low mood in early schizophrenia.

Adult↗

PubMed2002

Randomised controlled trial of cognitive-behavioural therapy in early schizophrenia: acute-phase outcomes.

BACKGROUND: Cognitive-behavioural therapy (CBT) improves persistent psychotic symptoms. AIMS: To test the effectiveness of added CBT in accelerating remission from acute psychotic symptoms in early schizophrenia. METHOD: A 5-week CBT programme plus routine care was compared with supportive counselling plus routine care and routine care alone in a multi-centre trial randomising 315 people with DSM-IV schizophrenia and related disorders in their first (83%) or second acute admission. Outcome assessments were blinded. RESULTS: Linear regression over 70 days showed predicted trends towards faster improvement in the CBT group. Uncorrected univariate comparisons showed significant benefits at 4 but not 6 weeks for CBT v. routine care alone on Positive and Negative Syndrome Scale total and positive sub-scale scores and delusion score and benefits v. supportive counselling for auditory hallucinations score. CONCLUSIONS: CBT shows transient advantages over routine care alone or supportive counselling in speeding remission from acute symptoms in early schizophrenia.

Adult↗

PubMed2001

Schizophrenia and substance misuse problems: a comparison between patients with and without significant carer contact.

AIM: Many researchers and clinicians in the mental health field have given much attention over the last few years to patients with co-morbid problems of schizophrenia and substance use. This population is becoming a focus of attention for all service providers owing to the suggested increase in numbers of patients with these dual diagnoses and the observed negative effects on patients and costs to services. The advantages for providing family interventions in schizophrenia are now well established and increasingly these interventions are being evaluated for families of dual diagnosis patients. Many dually diagnosed patients do not, however, have a great deal of contact with a carer/relative. This paper looks at whether differences exist between patients with a dual diagnosis that have carer contact and those who do not have carer contact in terms of their illness history and type of substance use. For the purpose of this article 'carer' refers to an individual who is an informal carer or relative with whom the client has weekly contact of 10 h. Many of these carers provide the client with emotional, physical and material support. METHOD: The identification process for both'carer contact' and 'no carer contact' patients was conducted through the screening of the hospital's care programme approach (CPA) lists and through contact with care coordinators and consultants. Case notes of all patients identified were screened and information on demographic data, duration of illness, admissions and substance use was collected. RESULTS: Results indicated that the 'no carer contact' group was older and had significantly more days in hospital at last admission. CONCLUSIONS: It is possible that as patients get older their contact with significant others decreases, i. e. loss of contact with key relatives is due to age rather than severity of substance use. Furthermore, patients' reduced contact results in them having longer stays in hospital possibly because they will not receive additional support when discharged.

Adult↗

PubMed2001

Staff expressed emotion and causal attributions for client problems on a low security unit: an exploratory study.

This is an exploratory study that sought to investigate a number of measures of staff-patient relationships on a continuing care, low security inpatient facility for patients with severe mental illness. Twenty staff members were assessed for expressed emotion (EE) using the Camberwell Family Interview (CFI) in regard to a client for whom they were a designated key worker. Their spontaneous attributions for the patient's problems were also assessed, along with self-report staff and patient ratings of their expressed and perceived feelings and thoughts about their staff or patient counterpart. The study found that although none of the staff were rated as fulfilling criteria for high EE, there was evidence of some variability in the quality of staff-patient relationships as assessed from the subjective self-report scales of staff and patients. Patients seemed to be sensitive to staff feelings for them: patient ratings of perceived feelings and thoughts from staff were significantly correlated with staff expressed feelings both from the CFI EE ratings and the direct self-report staff measures. Staff tended to view the behaviors of patients they felt less positively disposed toward as more controllable, and this association between less benign explanations of behavior and a more critical attitude is consistent with the attribution research for familial caregivers. The more negatively perceived patient group was found to be more likely to have behavioral disturbances in the 7 months after the relationship ratings were made. This article discusses measurement issues in the assessment of formal caregiver-patient relationships in the light of this and previous studies.

Adult↗

PubMed2001

Randomized controlled trial of motivational interviewing, cognitive behavior therapy, and family intervention for patients with comorbid schizophrenia and substance use disorders.

OBJECTIVE: Comorbidity of substance abuse disorders with schizophrenia is associated with a greater risk for serious illness complications and poorer outcome. Methodologically sound studies investigating treatment approaches for patients with these disorders are rare, although recommendations for integrated and comprehensive treatment programs abound. This study investigates the relative benefit of adding an integrated psychological and psychosocial treatment program to routine psychiatric care for patients with schizophrenia and substance use disorders. METHOD: The authors conducted a randomized, single-blind controlled comparison of routine care with a program of routine care integrated with motivational interviewing, cognitive behavior therapy, and family or caregiver intervention. RESULTS: The integrated treatment program resulted in significantly greater improvement in patients' general functioning than routine care alone at the end of treatment and 12 months after the beginning of the study. Other benefits of the program included a reduction in positive symptoms and in symptom exacerbations and an increase in the percent of days of abstinence from drugs or alcohol over the 12-month period from baseline to follow-up. CONCLUSIONS: These findings demonstrate the effectiveness of a program of routine care integrated with motivational interviewing, cognitive behavior therapy, and family intervention over routine psychiatric care alone for patients with comorbid schizophrenia and alcohol or drug abuse or dependence.

Adolescent↗

PubMed2001

The effect of introducing a dedicated emergency theatre and altering consultant on-call commitments in a large children's hospital.

BACKGROUND: Two recommendations of NCEPOD were the introduction of dedicated emergency theatres and a higher level of consultant involvement in emergency cases. In May 1998 a dedicated emergency theatre was introduced in the Royal Hospital for Sick Children, Glasgow. At the same time the on-call rota of the Consultant Paediatric Surgeons was changed from days on-call to a period of one week, during which elective commitments were cancelled. METHOD: A retrospective audit was conducted for the 12-month periods before and after these changes. Start times of emergency cases and grades of surgeons were obtained from the theatre database. RESULTS: The proportion of emergency operations carried out during on call periods (weekends and weekdays after 5 pm) decreased for general paediatric and neonatal surgery (OR = 0.7, p < 0.01). There was an increase in the proportion of daytime emergency cases performed before 1 pm (OR = 0.28, p < 0.01). The Consultant Paediatric Surgeons were involved in more emergency cases (OR = 0.60, p < 0.01). CONCLUSIONS: The provision of a dedicated emergency theatre increased the proportion of emergency cases performed during normal working hours, particularly before 1 pm. Cancelling elective commitments for Consultant Paediatric Surgeons ensured higher levels of consultant input into daytime emergency cases.

Consultants↗

PubMed2000

Patch incorporation in diaphragmatic hernia.

BACKGROUND/PURPOSE: Biomaterial insertion often is required for closure of congenital diaphragmatic hernia (CDH). The optimal biomaterial remains uncertain. This study was designed to compare a commonly used patch (polytetrafluoroethylene) with a recently available fabric, fluorinated polyester. The aim of this study was to determine the clinical performance, histological tissue-polymer interaction, bacterial adhesion, and shrinkage rates of biomaterial inserted endoscopically into a CDH lamb model. METHODS: Polytetrafluoro-ethylene (PTFE) and fluorinated polyester (FP) were randomised for laparoscopic patch insertion into 12 lambs. All lambs (age <4 weeks) underwent 3-port laparoscopy, surgical creation of diaphragmatic hernia, and sutured patch placement. Two PTFE and 2 FP lambs were killed at 1-, 3-, and 6-month intervals postoperatively. Postmortem examination histopathology, electron microscopy, and specific bacterial broth immersion (Escherichia coil, Staphylococcus aurens, and epidermidis) were performed. RESULTS: All 12 lambs completed the study with intact patches that were fully peritonised. One abdominal adhesion was noted in a FP lamb at 6 months. FP was comparatively easier to insert, manipulate, and suture endoscopically. Histopathology findings showed that PTFE patches created a strong peripheral foreign body reaction with dystrophic calcification, whereas FP was well incorporated with intrapatch fibroblastic activity and neovascularsation. No significant difference in resistance to bacterial adhesion of relevant organisms was noted between the materials. Graft shrinkage for FP was 7% in one direction only, evident by 3 months. CONCLUSIONS: Fluorinated polyester has advantages in this laparoscopic lamb model. It shows rapid and sustained incorporation with intrapatch neovascularisation when compared with polytetrafluoro-ethylene's significant foreign body reaction. It was preferred for its endoscopic handling and suturing properties. The laparoscopic techniques used may contribute to the general lack of adhesions, and insufficient data are available to comment on the comparative effect of the materials on adhesion formation. No difference was demonstrated in resistance to bacterial adherence in the harvested materials.

Animals↗

PubMed2000

Neonatal head injuries.

A retrospective case note review of head injuries in neonates admitted to the Neonatal Surgical Unit in Glasgow between 1990 and 1996 (n=25) was carried out. Most injuries were caused by a fall (68%) and resulted in scalp haematomata and associated skull fractures in the majority of patients. Three neonates were involved in high speed road traffic accidents, and these infants all had intracranial pathology identified by computed tomography. Isolated skull fractures were common and did not appear to be associated with any neurological deficit. Nonaccidental injury was uncommon in this age group. Outcome was excellent in the majority of patients (92%).

Chi-Square Distribution↗

PubMed2000

Pancreatic trauma in Scottish children.

BACKGROUND: Trauma is the leading cause of death in children. Abdominal trauma is common, but there is little information on pancreatic injuries in UK children. The aim of this study was to investigate the clinical course of children suffering pancreatic trauma in Scotland. METHODS: All children admitted to the three major Scottish paediatric surgery centres with evidence of pancreatic injury were identified. A retrospective case note review of these children was performed using a structured proforma. RESULTS: 16 patients (11 males and 5 females), median age 7 years (range 1-11 years) were identified. The commonest mechanism of injury was the typical bicycle handlebar injury (10/16, 62%). Delays in definitive diagnosis were common due to subtle clinical signs. Increased serum amylase levels upon admission were not necessarily diagnostic for pancreatic injury. The diagnosis was confirmed by ultrasound scanning and/or computerised tomography in all patients. Ten patients (62%) developed pseudocysts and, in seven cases, they settled with non-operative management. There were no deaths and no long-term complications. CONCLUSION: Pancreatic injury in children is rare, and a high index of suspicion is required to make the diagnosis. The commonest mechanism of injury is a direct impact to the epigastrium, typically the bicycle handlebar injury. Presentation and diagnosis are frequently delayed. The incidence of pseudocysts is high, but most can be managed conservatively.

Acute Disease↗

PubMed1999

A pilot study evaluating the effectiveness of individual inpatient cognitive-behavioural therapy in early psychosis.

BACKGROUND: Recent research indicates that cognitive-behaviour therapy (CBT) can be effective in ameliorating persistent positive symptoms in chronic psychotic patients. The effectiveness of CBT in acute and recent-onset psychosis has been little explored, although a recent pilot study indicated that CBT could significantly improve recovery in acutely psychotic inpatients. METHOD: Short-term individual CBT was compared to supportive counselling/psychoeducation (SC) as an adjunct to standard inpatient hospital care and medication in 21 inpatients experiencing a recent-onset acute schizophrenic episode. RESULTS: Both groups showed significant reductions in Brief Psychiatric Rating Scale (BPRS) scores following treatment, although there were no group differences. Time to discharge did not differ significantly between the groups, although there was a greater variance for the SC patients. Two-year follow-up showed no significant differences between the groups, although the number of patients who relapsed, the number of relapses and the time to recurrence of psychotic symptoms was lower in the CBT group than the SC group. Interestingly, the time to readmission was shorter in the CBT group. CONCLUSIONS: CBT and SC are acceptable treatments for recent-onset acutely psychotic inpatients. A larger randomised controlled trial over multiple hospital sites is warranted.

Acute Disease↗

PubMed1999

Separation of renal fragments by a urinoma after renal trauma: percutaneous drainage accelerates healing.

BACKGROUND: Two boys suffered blunt abdominal trauma resulting in renal injury. In both cases the damaged kidney was fractured through its mid-portion, and the upper and lower fragments of the kidney became widely separated by a urinoma. MATERIALS AND METHODS: US-guided drainage of the urinoma resulted in immediate apposition of the renal fragments. The drains were left on free drainage by gravity for 1 week before removal. RESULTS: The urinomas did not reaccumulate and follow-up DMSA scans showed good residual function. CONCLUSION: We suggest that drainage of urinomas that separate renal fragments should be considered since this may accelerate healing and help preserve renal function.

Accidental Falls↗