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Biomedical subjects

C A Graham

Publications and source records attributed to C A Graham.

At least 55 records · Page 3Linked to original sources
PubMed2000

Management of unexplained coma in children.

Coma in children is uncommon and can pose difficulties in diagnosis and management. Resuscitation should concentrate on management of the airway, breathing and circulation and on rapid exclusion of easily correctable conditions, e.g. hypoglycaemia. Common causes of coma are considered and the diagnostic evaluation of these children is discussed. A case of a toddler in coma is discussed from the perspective of the accident and emergency department to illustrate the management of these challenging but uncommon patients.

Anticonvulsants↗
PubMed2000

Effect of genotype on changes in intelligence quotient after dietary relaxation in phenylketonuria and hyperphenylalaninaemia.

BACKGROUND: Associations between genotype and intellectual outcome in patients with phenylketonuria are complicated because intelligence is influenced by many variables, including environmental factors and other genetic determinants. Intellectual changes with age, both on and after relaxation of diet, vary within the patient population. This study aims to determine whether a significant association exists between genotype and change in intelligence after relaxation of diet. METHODS: 125 patients with hyperphenylalaninaemia and phenylketonuria whose diet was relaxed after 8 years of age. Verbal, performance, and full scale intelligence quotients at 8, 14, and 18 years were expressed as standard deviation scores (IQ-SDS), and genotype as predicted residual enzyme activity (PRA) of phenylalanine hydroxylase. RESULTS: IQ-SDS at 8, 14, and 18 years were significantly below normal; no association was found between PRA and IQ-SDS. Significant reductions in verbal and full scale IQ-SDS occurred between 8 and 14 years and 8 and 18 years. There was a significant association between PRA and the reduction in verbal, performance, and full scale IQ between these years. Multiple regression analysis of 18 year results, using 8 year results as covariates, supported the association between PRA and IQ-SDS; after adjustment for phenylalanine control, both up to and after the age of 8 years, the full scale IQ-SDS at 14 and 18 years was 0.15 higher for each 10% increase in PRA. CONCLUSIONS: Genotype might be useful in predicting the likelihood of intellectual change in patients with hyperphenylalaninaemia and phenylketonuria whose diet is relaxed after the age of 8 years.

Adolescent↗
PubMed2000

Frozen chips: an unusual cause of severe frostbite injury.

A case of severe frostbite injury to the right foot is presented. This was caused by the inappropriate application of a bag of frozen chips to the foot in an attempt to ease non-specific pain. No specific acute traumatic injury was identified. As the patient was a teacher of physical education, the pain had initially been assumed to originate from a minor musculoskeletal injury. Full recovery ensued after surgical excision of necrotic tissue and split skin grafting. The danger of inappropriate overenthusiastic use of ice packs or other frozen material to treat soft tissue injuries is emphasised. The need for education to prevent similar future injuries is discussed.

Adult↗
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

Effects of treatment with growth hormone and somatostatin on efficacy of diammine [1,1-cyclobutane dicarboxylato (2-)-0,0']-(SP-4-2) in athymic rats with osteosarcoma.

OBJECTIVE: To determine the effect of exogenous growth hormone or somatostatin on chemotherapeutic efficacy in athymic (nude) rats with osteosarcoma. ANIMALS: 66 female athymic rats. PROCEDURE: Osteosarcoma was induced at an intratibial site. Rats were randomly allotted to 6 treatment groups. Rats were treated with saline (0.9% NaCl) solution alone, platinum, diammine [1,1-cyclobutane dicaboxylato (2-)-0,0']-(SP-4-2) (CBDCA; ie, carboplatin) plus saline solution, somatostatin alone, somatostatin plus CBDCA, growth hormone alone, or growth hormone plus CBDCA. Variables measured included estimated WBC count and percentage of neutrophils, plasma concentration of insulin-like growth factor I (IGF-I), body weight, tumor volume, weight of primary tumor, survival time, and distant metastasis at time of death. RESULTS: Tumors formed at the injection sites in all rats. Treatment with growth hormone increased, and treatment with somatostatin decreased, plasma IGF-I concentration. Treatment with growth hormone or somatostatin altered CBDCA efficacy, as determined by evaluation of mean and median survival times. Metastatic pulmonary disease developed in 63 of 64 rats. CONCLUSIONS AND CLINICAL RELEVANCE: The technique used here reliably induced local osteosarcomas and metastatic pulmonary disease. Treatment with growth hormone and CBDCA or somatostatin may improve chemotherapeutic efficacy without increasing toxic effects. IMPLICATIONS FOR HUMAN MEDICINE: Results reported here may be useful in the study of osteosarcoma in humans.

Animals↗
PubMed2000

Effects of fragrance on female sexual arousal and mood across the menstrual cycle.

The effects of fragrance on sexual response in women were investigated using subjective and physiological measures of sexual arousal and of mood. Responses were obtained from female participants in three different fragrance conditions (female fragrance, male fragrance, and a "blank" or neutral substance), as they viewed erotic and sexually neutral films, and fantasized about sexual situations. Each woman was tested twice: during the midfollicular and periovulatory phases of her menstrual cycle. Menstrual cycle phase effects were apparent; self-report data indicated greater sexual arousal and more positive mood during the periovulatory than during the follicular phase. Results demonstrated a positive effect of the male fragrance on genital arousal during erotic fantasy, but this finding was apparent only during the follicular phase testing session. This effect did not appear to be mediated by any effects of fragrance on mood.

Adult↗
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 study of the HLA-DR region in clinical subgroups of multiple sclerosis and its influence on prognosis.

OBJECTIVE: To investigate the HLA-DR associations in relapsing-remitting/secondary progressive multiple sclerosis (RR/SPMS) and primary progressive MS (PPMS). The HLA-DR2 allele (or its split, HLA-DRB1*15) is felt to be a risk factor for MS, rather than a genetic marker for the population of origin. Some studies have indicated a different HLA-DR antigen profile in PPMS patients compared with those having an initially relapsing-remitting course, only those with relapsing disease showing an increase in HLA-DR2. Association of PPMS with DR4 has been suggested. Several DR alleles have also been felt to influence the prognosis in MS. METHODS: Genomic DNA was prepared from peripheral blood of 202 RR/SPMS patients identified in a population-based prevalence study, 102 PPMS patients identified throughout Northern Ireland and 398 normal controls (Nor) matched for the postcode areas of those identified in the prevalence study. Samples were typed for the HLA-DR antigens using polymerase chain reaction (PCR) technology and sequence specific oligonucleotide probes (SSOP). RESULTS: A high incidence of HLA-DRB1*15 was found in each MS group - PPMS (63.73%), RR/SPMS (66.83%) - compared with normals (32.41%), (PPMS vs. Nor, P<0.0001: RR/SPMS vs. Nor, P<0.0001). HLA-DRB1*04 occurred at a lower incidence in both MS groups compared with controls - RR/SPMS (22%), PPMS (30%), Nor (35%). Overall, highly significant differences existed across the full HLA-DR allele distribution (RR/SPMS vs. Nor, P<0.0001, df=12: PPMS vs. Nor, P=0.0007, df=12). No significant differences existed between PPMS and RR/SPMS (P=0.47, df=12), and the allele distributions in benign and aggressive MS were similar. CONCLUSIONS: These data suggest that in this population, HLA-DRB1*15 is indeed associated with PPMS and that PPMS has a HLA-DR profile distinct from the normal population but not from those with an initially relapsing-remitting course. No single allele is associated with either a good or poor prognosis.

Adult↗
PubMed1999

Genetic association studies of tumour necrosis factor alpha and beta and tumour necrosis factor receptor 1 and 2 polymorphisms across the clinical spectrum of multiple sclerosis.

Allelic association studies with microsatellite markers around the tumour-necrosis factor (TNF) genes have demonstrated significantly different allele distributions of TNF markers (a and b) between relapsing-remitting/secondary progressive multiple sclerosis (MS) (RR/SPMS) patients and normal controls. Considering the suspected genetic and immunological heterogeneity in MS, we tested this association in primary progressive MS (PPMS) patients. Elevated levels of serum soluble TNF receptors (sTNF-R) are reported in patients with gadolinium enhancing lesions, and animal models suggest a possible therapeutic role of sTNF-RI in MS. Thus we performed similar association studies using markers for the TNF-R genes. Gene association studies were carried out on 199-216 normal controls, 174 RR/SPMS patients and 102 PPMS patients using polymorphic dinucleotide repeat TNF markers (a, b and d), and separate markers for TNF-RI and TNF-RII. Forward primers were fluorescently labelled, polymerase chain reaction (PCR) products were analysed on a fluorescent fragment analyser, and Genescan 672 software was used for allele sizing. Samples were typed for HLA-DR antigens using PCR technology and sequence-specific oligonucleotide probes. TNFa marker allele distributions differed significantly between PPMS patients and controls (P = 0.028), largely attributable to an increase in the 118-bp TNFa allele in PPMS patients (P = 0.00024). Allele distributions were similar in PPMS and RR/SPMS patients (P = 0.91). Logistic regression analysis, however, indicated that these associations were not independent of that with HLA-DRB1*15. For the TNFb marker, the 127-bp allele showed association with both patient categories (PPMS vs. controls, P = 0.010; RR/SPMS vs. controls, P = 0.027), whilst the 128-bp allele occurred more frequently in controls (PPMS vs. controls, P = 0.036: RR/SPMS vs. controls, P = 0.0009). As with the TNFa 118 bp allele, the association with TNFb was not independent of the HLA association. No association occurred with the TNFd marker, and there were also no significant differences in allele frequencies between MS groups and controls regarding the marker for TNF-RI or TNF-RII. In Northern Irish patients the TNF contribution to MS genetic susceptibility is therefore similar across the clinical spectrum of the disease but is not independent of the association with HLA-DRB1*15.

Adult↗
PubMed1999

Intra-articular lignocaine versus Entonox for reduction of acute anterior shoulder dislocation.

We assessed, in a prospective randomised trial, the relative analgesic effects of Entonox and intra-articular lignocaine (IAL) in patients with acute anterior dislocation of the shoulder. A statistically significant reduction in pain scores was achieved with IAL (7.9 vs 5.2, P < 0.05), but the effect with Entonox was greater (7.8 vs 2.9, P < 0.001). We conclude that Entonox provides better analgesia than IAL in patients with acute anterior shoulder dislocation.

Acute Disease↗
PubMed1999

Mutation screening and genotype:phenotype correlation in familial hypercholesterolaemia.

The aim of this study was to develop a mutation screening protocol for familial hypercholesterolaemia (FH) patients and to assess genotype/phenotype effects in terms of pre-treatment lipid profiles and presentation of tendon xanthomata (TX). A total of 158 families with clinical definitions of possible (120) or definite (38) FH were studied using a tiered screening protocol. Mutations were identified in 52 families, 44 families showing 23 different LDLR gene defects and eight families showing the common Apo B100 gene defect R3500Q. LDLR defects were detected in various regions of the gene with 56% in the LDL binding domain (exons 2-6) and 37% in the EGF precursor homology domain (exons 7-14). The most common mutations were D461N(7), C210X(5), 932delA(5), and C163Y(4). Frameshift mutations accounted for 20% with nonsense 13%, mis-sense 35%, splice 3%, Apo B 13% and 2% large deletion, 13% of clinically definite FH remained undefined. In conclusion, DNA based diagnosis is possible in 79% (30/38) of clinically definite FH families and of the 120 possible FH families at the start of the screening program, 18% (22/120) now have defined mutations. Overall 60 families from the original 158 meet the clinical and/or genetic criteria for definite FH. Tendon xanthomata were present in only 58% (30/52) of genetically defined FH families, thus limiting its use as a strict diagnostic criteria. Families with low density lipoprotein receptor (LDLR) defects present with higher total and LDL cholesterol levels and a higher incidence of TX than do those with the common Apo B variant, and frameshift mutations appear to have the most severe presentation.

Electrophoresis, Agar Gel↗
PubMed1999

Appointment of a Resuscitation Training Officer is associated with improved survival from in-hospital ventricular fibrillation/ventricular tachycardia cardiac arrest.

OBJECTIVE: To determine if the appointment of a Resuscitation Training Officer improves survival to discharge from in-hospital ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest. DESIGN: A 22-month prospective study. SETTING: A 1100-bed teaching hospital. SUBJECTS: All inpatients suffering ventricular fibrillation or ventricular tachycardia cardiorespiratory arrests. INTERVENTIONS: Appointment of a Resuscitation Training Officer at start of study, who introduced coordinated resuscitation training for all staff. MAIN OUTCOME: Survival to discharge. RESULT: Improvement in survival to discharge of 20-75% (P<0.03, Spearman Rank Correlation test). CONCLUSION: Appointment of a Resuscitation Training Officer is associated with improved survival to discharge in ventricular fibrillation and ventricular tachycardia in-hospital cardiac arrest.

Cardiopulmonary Resuscitation↗
PubMed1999

Security of attachment and parenting: homeless and low-income housed mothers and infants.

A racially diverse sample of 112 low-income and homeless mothers of infants was examined for associations among housing status (homeless vs. housed), parenting practices, and infant attachment. Results demonstrated few effects of housing status on characteristics of parenting or security of attachment. Security of infant attachment was found to be related to parenting practices and parenting difficulties. Implications of the findings are discussed.

Adolescent↗
PubMed1999

'Popping': a cause of soft tissue sepsis in chronic drug abusers.

Septic complications arising from drug misuse are well documented. It is likely that most complications occur as a result of attempted intravenous (i.v.) injection. We report four cases of soft tissue infections where the patients were unable to obtain i.v. access and gave injections of drugs using a technique known as 'popping'. 'Popping' is the deliberate injection of drugs subcutaneously or intramuscularly when i.v. access is not possible. This practice is further discussed and the literature associated with soft tissue infections from drug misuse is reviewed.

Adult↗
PubMed1999

Major incidents: training for on site medical personnel.

OBJECTIVE: To assess the present levels of training for the medical incident officer (MIO) and the mobile medical team leader (MMTL) throughout the UK. METHOD: Postal questionnaire to consultants in charge of accident and emergency (A&E) departments seeing more than 30,000 patients a year. Information regarding MIO staffing and training and MMTL training and provision requested. RESULTS: A&E provides the majority of both MIOs and MMTLs in the event of a major incident. Virtually all MIOs are consultants or general practitioners. However, 63% of MMTLs are from hospital training grade staff. One third of hospitals required their designated MIO to have undertaken a Major Incident Medical Management and Support course and a quarter had no training requirement at all. Two thirds of MMTLs were expected to have completed an Advanced Trauma Life Support course, but in 21% there was no minimum training requirement. Training exercises are infrequent, and hence the exposure of any one individual to exercises will be minimal. CONCLUSION: There has been some improvement in major incident training and planning since 1992, but much remains to be done to improve the national situation to an acceptable standard.

Ambulances↗
PubMed1999

Lack of association of transforming growth factor (TGF)-beta 1 and beta 2 gene polymorphisms with multiple sclerosis (MS) in Northern Ireland.

OBJECTIVE: To examine the influence of TGF-beta genes on MS susceptibility. BACKGROUND: TGF-beta, of which three homologous isoforms exist (1, 2 and 3), is a strongly immunosuppressive cytokine-inhibiting expression of pro-inflammatory cytokines and blocking cytokine induction of adhesion molecules. TGF-beta delays onset of EAE and TGF-beta 1 gene knockout mice develop fatal multifocal inflammatory disease. High TGF-beta levels exist during MS remission whilst E-selectin, whose expression is inhibited by TGF-beta, is found at higher levels in primary progressive disease (PPMS) and it is postulated that the unremitting course of PPMS may be due to low levels of TGF-beta. METHODS: Gene association studies using separate polymorphic microsatellite markers for TGF-beta 1 and TGF-beta 2 were performed, incorporating 151 relapsing-remitting or secondary progressive MS (RR/SPMS) patients, 104 PPMS patients and 159 normal controls (Nor). Forward primers were 5' end-labelled with 6-Fam, PCR products were analysed on an Applied Biosystems 373A fluorescent fragment analyser and Genescan 672 software was used for allele sizing. RESULTS: No significant differences existed in allele frequencies between either MS group and controls regarding the TGF-beta 1 marker: RR/SPMS vs Nor (P = 0.48, df = 8); PPMS vs Nor (P = 0.34, df = 8). Similarly there were no associations demonstrated with the TGF-beta 2 marker: RR/SPMS vs Nor (P = 0.24, df = 2); PPMS vs Nor (P = 0.53, df = 2). CONCLUSION: These data indicate that TGF-beta 1 and beta 2 genes are not loci influencing MS susceptibility, either RR/SPMS or PPMS, in this population.

Alleles↗
PubMed1999

Relationship between tumour necrosis factor-alpha (TNFalpha) production and a specific multiple sclerosis (MS) associated TNF gene haplotype.

OBJECTIVE: To determine if monocyte TNFalpha production from patients homozygous for a specific MS associated TNF gene haplotype is different from that produced in patients either heterozygous for, or without this haplotype. BACKGROUND: The balance between pro- and anti-inflammatory cytokines is important in the clinical outcome of inflammatory reactions. Levels of TNFalpha, a pro-inflammatory cytokine, is raised in MS as well as being found in acute and chronic MS lesions. A previous population based study in Northern Ireland with polymorphisms spanning the TNF gene region identified a conserved MS associated haplotype in relation to three markers (130: 118: 127 TNF d:a:b) for which 19 MS patients were homozygous. METHODS: Venous blood collected in EDTA to give a concentration of 10(-3) M was drawn from 16 patients with the conserved MS associated haplotype, 19 patients heterozygous for the haplotype and 17 patients without the haplotype. Mononuclear cells were separated and cultured by standard techniques and levels of TNFalpha and of TNF binding proteins I and II were determined by commercial enzyme-linked immunosorbent assays. RESULTS: There were no significant differences in TNFalpha production in the 3 h (P = 0.28) or 24 h cultures (P = 0.18) or following stimulation with interferon-gamma (P = 0.17) between the group positive for the conserved haplotype and the group negative for this haplotype. There was also no significant difference when compared to the heterozygote group. No association was found between the MS associated haplotype and levels of either TNF binding protein. A greater proportion of patients with the conserved haplotype had a benign clinical course (P = 0.06). CONCLUSION: We conclude that whilst a trend exists, we have found no significant association between peripheral TNFalpha production and a specific MS associated TNF haplotype in this population. Paradoxically this haplotype may also predict a more favourable clinical course.

Cells, Cultured↗