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Biomedical subjects

A Green

Publications and source records attributed to A Green.

At least 19 recordsLinked to original sources
PubMed2008

Concurrent carbogen and radiation therapy in children with high-risk brainstem gliomas.

In an attempt to improve local control, we assessed the feasibility of the addition of 4 min of carbogen inhalation (as a radiosensitizer) to daily fractionated radiotherapy in pediatric patients with high grade and/or diffuse brainstem gliomas. Ten patients inhaled carbogen for >90% of the radiation treatments. Median survival time from start of therapy was 0.80 years. Carbogen inhalation did not appear to improve the dismal prognosis.

Administration, Inhalation↗
PubMed2006

Elevated serum angiogenin levels in ALS.

BACKGROUND: The role of hypoxia responsive genes in the pathogenesis of ALS was first suggested when deletions of the hypoxia-responsive element of vascular endothelial growth factor (VEGF) promoter caused a motor neuron disease phenotype in mice. The discovery of ALS-associated mutations in ANG, a hypoxia responsive gene coding for the protein angiogenin, has further supported this pathogenic mechanism in human ALS. In endothelium, angiogenin can regulate expression of VEGF. To date, the patterns of serum angiogenin expression among patients with ALS have not been assessed. METHODS: Serum angiogenin and VEGF levels were quantified at diagnosis in 79 patients with definite or probable ALS and 72 healthy controls, using a quantitative sandwich enzyme-linked immunoassay. RESULTS: Patients with ALS exhibited higher serum angiogenin (p = 0.006) but not VEGF (p = 0.55) levels than matched control subjects. Subgroup analysis showed a greater elevation in angiogenin levels for spinal- (p < 0.001) than bulbar- (p = 0.11) onset ALS vs controls. At 12 months, angiogenin levels remained elevated. No correlation was noted between angiogenin and VEGF levels (r = -0.08, p = 0.49) in ALS patient serum. CONCLUSION: These data suggest a modest elevation in serum angiogenin in ALS at diagnosis. Further investigation will be required to assess the utility of serum angiogenin as a biomarker for ALS and as a predictor of disease progression.

Amyotrophic Lateral Sclerosis↗
PubMed2006

Transcultural differences in suicide attempters: analysis on a high-risk population of patients with schizophrenia or schizoaffective disorder.

The aim of the study was to investigate transcultural differences between schizophrenia spectrum disorder patients who did or did not attempt suicide. DSM-IV schizophrenia (N=609) or schizoaffective disorder (N=371) patients who participated in the multicentre International Suicide Prevention Trial (InterSePT) were studied. Patients were sub-divided into 5 groups according to the different geographical regions of recruitment: North America (NA), Europe (EUR), East Europe (EEUR), South Africa (SAf), and South America (SA). The main lifetime clinical variables were compared, within each group, between attempters and non-attempters. The presence of comorbid substance abuse disorder and smoking was associated with suicide attempts in all the geographical groups considered (NA: chi(1)(2)=7.575, p<0.01 and chi(1)(2)=69.549, p<0.0001; EUR: chi(1)(2)=55.068, p<0.0001, and chi(1)(2)=48.431, p<0.0001; EEUR: chi(1)(2)=164.628, p<0.000, and chi(1)(2)=5.127, p<0.01; SA: chi(1)(2)=30.204, p<0.0001 and chi(1)(2)=11.710, p=0.001) except for SAf. For the other clinical variables various differences were found across the different groups. Variables related to suicide behavior were similar across the five groups investigated, with differences only in the age at the first suicide attempt (earlier in the NA sample) and the number of lifetime suicide attempts (higher in the NA sample). Results from this study show that, while some suicide-related clinical characteristics in schizophrenia patients are consistent worldwide suggesting the influence of stable biological traits, other variables may vary across different geographical areas suggesting environmental influences.

Adult↗
PubMed2006

CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease.

OBJECTIVES: To analyze the diagnostic sensitivity and specificity of various brain-derived proteins (14-3-3, Tau, neuron specific enolase [NSE], and S100b) in the CSF of patients with Creutzfeldt-Jakob disease (CJD) and to analyze biologic factors that modify these parameters. METHODS: CSF was tested for 14-3-3, Tau, NSE, and S100b in 1,859 patients with sporadic, genetic, iatrogenic, and variant CJD, and in 1,117 controls. RESULTS: The highest sensitivity was achieved for 14-3-3 and Tau in sporadic CJD (85% and 86%), and a combined determination of 14-3-3 and Tau, S100b, or NSE increased the sensitivity to over 93%. A multivariate analysis showed that the sensitivity of all tests was highest in patients with the shortest disease duration, age at onset >40 years, and homozygosity at codon 129 of the prion protein gene. In a group of patients with repeated lumbar punctures, a second test also increased the diagnostic sensitivity. CONCLUSIONS: The detection of elevated levels of brain-derived proteins in the CSF in patients with suspected Creutzfeldt-Jakob disease is a valuable diagnostic test. A second lumbar puncture may be of value in patients with atypical clinical course in whom the first test was negative.

14-3-3 Proteins↗
PubMed2006

The incidence of inherited metabolic disorders in the West Midlands, UK.

BACKGROUND: Inherited metabolic disorders (IMDs) are a heterogeneous group of genetic conditions mostly occurring in childhood. They are individually rare but collectively numerous, causing substantial morbidity and mortality. AIMS: To obtain up-to-date estimates of the birth prevalence of IMDs in an ethnically diverse British population and to compare these estimates with those of other published population-based studies. METHODS: Retrospective data from the West Midlands Regional Diagnostic Laboratory for Inherited Metabolic Disorders (Birmingham, UK) for the 5 years (1999-2003) were examined. The West Midlands population of 5.2 million is approximately 10% of the UK population. Approximately 11% of the population of the region is from black and ethnic minority groups compared with approximately 8% for the the UK. RESULTS: The overall birth prevalence was 1 in 784 live births (95% confidence interval (CI) 619 to 970), based on a total of 396 new cases. The most frequent diagnoses were mitochondrial disorders (1 in 4929; 95% CI 2776 to 8953), lysosomal storage disorders (1 in 5175; 95% CI 2874 to 9551), amino acid disorders excluding phenylketonuria (1 in 5354; 95% CI 2943 to 9990) and organic acid disorders (1 in 7962; 95% CI 3837 to 17 301). Most of the diagnoses (72%) were made by the age of 15 years and one-third by the age of 1 year. CONCLUSIONS: These results are similar to those of the comparison studies, although the overall birth prevalence is higher in this study. This is probably due to the effects of ethnicity and consanguinity and increasing ascertainment. This study provides useful epidemiological information for those planning and providing services for patients with IMDs, including newborn screening, in the UK and similar populations.

Adolescent↗
PubMed2006

Nursing and midwifery: Millennium Development Goals and the global human resource crisis.

The World Health Organization Global Advisory Group for Nurses and Midwives and wider stakeholders met in May 2005 against a background of concern over the disappointing progress being made towards the Millennium Development Goals (MDGs). The meeting considered the urgent need to address human resource issues, particularly those related to nursing and midwifery, if the MDGs are to be achieved.

Forecasting↗
PubMed2005

Evaluation of urinary PrPSc as a diagnostic test for sporadic, variant, and familial CJD.

Previously collected urine specimens from 100 patients referred to the UK National CJD Surveillance Unit as suspected cases of Creutzfeldt-Jakob disease (CJD) were analyzed, testing for abnormal prion protein (PrP(Sc)). In this context, the test had a low sensitivity and was not completely specific for CJD. Additionally, the proteins detected by this assay were not PrP(Sc) but appeared to be immunoglobulins.

Antibody Specificity↗
PubMed2005

Awake stereotactic biopsy of brain stem lesions: technique and results.

BACKGROUND: Brain stem lesions are a heterogenous pathological group. In adults, pre-operative radiological diagnoses prove to be wrong in 10 to 20% of cases. It is therefore imperative to have a tissue diagnosis for appropriate therapeutic measures. Unless these lesions have a sizeable exophytic component, open biopsy and/or resection is marred by low diagnostic yield and prohibitive mortality/morbidity rates. METHODS: We describe our experience with awake stereotactic biopsy of brain stem lesions. Keeping the patient awake and monitoring clinically during the procedure allows us to make necessary changes in the trajectory of the biopsy probe to minimize the morbidity. A series of 13 brain stem lesions were stereotactically biopsied using CT guidance. Seven had midbrain lesions; four had pontine and two had Ponto-medullary lesions. A frontal, pre-coronal, transcortical trajectory was used in all patients. FINDINGS: Histological diagnosis was established in all but one patient. There was no procedural mortality, and morbidity was minimal and temporary, occurring in three patients. CONCLUSION: Awake stereotactic biopsy is a safe technique when combined with clinical monitoring.

Adolescent↗
PubMed2005

Hyperinsulinism in tyrosinaemia type I.

Tyrosinaemia type I (TT I) (McKusick 276700) is a heterogeneous disorder with a broad spectrum of clinical phenotypes. Although histological abnormalities of the pancreas are well recognized, there are only incidental reports of pancreatic dysfunction manifested as insulin-dependent diabetes mellitus. We report three subjects with TT I and acute liver dysfunction who had hyperinsulinism in early infancy. Hypoglycaemia persisted despite dietary treatment and one patient had inadequate lipolysis at the time of hypoglycaemia. All three patients were successfully treated with diazoxide (10 mg/kg per day) and chlorthiazide (35 mg/kg per day) and treatment was gradually withdrawn after 9, 13 and 34 months, respectively. The mechanism of pancreatic dysfunction in TT I is unknown but may be related to the toxic metabolites that accumulate in this condition. We conclude that hyperinsulinism is not a rare complication in TT I. In patients with persistent hypoglycaemia, C-peptide should always be measured. Treatment with diazoxide and chlorthiazide is highly effective, appears to be safe, and does not need to be continued lifelong.

Blood Glucose↗
PubMed2005

Factors affecting the outcome of stem cell transplantation from unrelated donors for childhood acute lymphoblastic leukemia in third remission.

Between July 1990 and March 2002, 35 consecutive children with ALL in third complete remission (CR3) underwent stem cell transplantation (SCT) from unrelated donors (UD). All patients received CAMPATH-1M 5-20 mg daily for 5 days. Grafts were T-cell depleted in 30 patients, 29 by CAMPATH antibodies and one by CD34 selection. Median follow-up was 3.8 years (0.3-9.3). Event-free survival (EFS) at 3 years was 35% (SE 8%); relapse rate and transplant-related mortality (TRM) at 3 years was 42 and 23%. Short first complete remission (CR1) <2.5 years was associated with lower EFS (P=0.001), higher TRM (P=0.019) and higher relapse rate (P=0.023). Short second complete remission (CR2) <2.5 years was associated with lower EFS (P=0.003) and higher TRM (0.009). Higher relapse rate and lower EFS were associated with isolated first extramedullary relapse (P=0.019, 0.012). There was no significant difference in outcome between mismatched unrelated donor stem cell transplantation (MMUD-SCT) and matched unrelated donor stem cell transplantation (UD-SCT). We conclude that UD-SCT is an effective treatment of ALL in CR3. The outcome remains limited by TRM and a high relapse rate. Short duration of CR1 and of CR2 and extramedullary site at first relapse are particularly adverse. MMUD should also be considered in high-risk patients, since the outcome of MMUD appears similar to MUD.

Alemtuzumab↗
PubMed2005

Validation of a food-frequency questionnaire assessment of carotenoid and vitamin E intake using weighed food records and plasma biomarkers: the method of triads model.

BACKGROUND: Reliability or validity studies are important for the evaluation of measurement error in dietary assessment methods. An approach to validation known as the method of triads uses triangulation techniques to calculate the validity coefficient of a food-frequency questionnaire (FFQ). OBJECTIVE: To assess the validity of an FFQ estimates of carotenoid and vitamin E intake against serum biomarker measurements and weighed food records (WFRs), by applying the method of triads. DESIGN: The study population was a sub-sample of adult participants in a randomised controlled trial of beta-carotene and sunscreen in the prevention of skin cancer. Dietary intake was assessed by a self-administered FFQ and a WFR. Nonfasting blood samples were collected and plasma analysed for five carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene) and vitamin E. Correlation coefficients were calculated between each of the dietary methods and the validity coefficient was calculated using the method of triads. The 95% confidence intervals for the validity coefficients were estimated using bootstrap sampling. RESULTS: The validity coefficients of the FFQ were highest for alpha-carotene (0.85) and lycopene (0.62), followed by beta-carotene (0.55) and total carotenoids (0.55), while the lowest validity coefficient was for lutein (0.19). The method of triads could not be used for beta-cryptoxanthin and vitamin E, as one of the three underlying correlations was negative. CONCLUSIONS: Results were similar to other studies of validity using biomarkers and the method of triads. For many dietary factors, the upper limit of the validity coefficients was less than 0.5 and therefore only strong relationships between dietary exposure and disease will be detected.

Adult↗
PubMed2005

Developmental delay: when to suspect and how to investigate for an inborn error of metabolism.

The purpose of this review is to provide a practical guideline on the suspicion and investigation of inborn errors of metabolism (IEMs) as cause of developmental delay. Developmental delay is a common paediatric problem. Inborn errors of metabolism are a rare cause of developmental delay. However, it is important to detect IEMs for several reasons: accurate counselling may be given regarding recurrence risk; metabolic decompensation may be avoided; and specific treatments may be available. Certain clinical situations are more likely to point to an IEM as the cause of developmental delay. This review highlights the risk factors in the history, the important examination findings, and the appropriate biochemical investigation of the child with developmental delay. Following these guidelines makes "missing" an IEM unlikely.

Biomarkers↗
PubMed2004

A novel candidate region for ALS on chromosome 14q11.2.

Sequence variations with biologic effect in ALS have been identified in the gene for vascular endothelial growth factor (VEGF). The gene for a related protein, angiogenin, lies on chromosome 14q11.2. Analysis of the angiogenin (ANG) gene in the authors' population has demonstrated a significant allelic association with the rs11701 single nucleotide polymorphism (SNP) and identified a novel mutation in two individuals with sporadic ALS that potentially inhibits angiogenin function. These observations propose a candidate region for ALS on chromosome 14q11.2 and suggest that other genes with similar function to VEGF may be important in the pathogenesis of ALS.

Aged↗