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Biomedical subjects

S George

Publications and source records attributed to S George.

At least 91 records · Page 5Linked to original sources

Selective neuroprotective effects with insulin-like growth factor-1 in phenotypic striatal neurons following ischemic brain injury in fetal sheep.

Severe perinatal asphyxia can lead to injury and dysfunction of the basal ganglia. Post insult administration of insulin-like growth factor-1 is neuroprotective, particularly in the striatum. Insulin-like growth factor-1 is also known to be a neuromodulator of several types of striatal neurons. The striatum comprises various phenotypic neurons with a complex neurochemical anatomy and physiology. In the present study, we examined the specificity of neuronal rescue with insulin-like growth factor-1 on different striatal neurons. Bilateral brain injury was induced in near term fetal sheep by 30 min of reversible carotid artery occlusion. A single dose of 3 microg of insulin-like growth factor-1 was infused over 1 h into the lateral ventricle 90 min following ischemia. The histological and immunohistochemical outcome were examined after 4 days recovery using paraffin tissue preparations. Insulin-like growth factor-1 treatment (n = 11) significantly reduced the percentage of neuronal loss in the striatum compared with the vehicle treated group (n = 10, 28.3+/-5.1% vs 55.5+/-17.3%, P < 0.005). Immunohistochemical studies showed that ischemia resulted in a significant loss of calbindin-28kd, choline acetyltransferase, parvalbumin, glutamate acid decarboxylase, neuronal nitric oxide synthase and neuropeptide Y immunopositive neurons, compared with sham controls. Insulin-like growth factor-1 markedly prevented the loss of calbindin-28kd (n = 7, P < 0.05), choline acetyltransferase (n = 7, P < 0.05), neuropeptide Y (n = 7, P < 0.05), neuronal nitric oxide synthase (n = 8, P < 0.05) and glutamate acid decarboxylase (n = 9, P < 0.05) immunopositive neurons, but failed to protect parvalbumin (n = 6) immunopositive neurons. The present study indicates that the therapeutic effect of insulin-like growth factor-1 in the basal ganglia is selectively associated with cholinergic and some phenotypic GABAergic neurons. These data suggest a potential role for insulin-like growth factor-1 in preventing cerebral palsy due to perinatal asphyxia.

Animals↗

Flegel's disease treated with psoralen ultraviolet A.

Flegel's disease is an uncommon condition which causes asymptomatic keratotic papules on the limbs. It usually develops in the fourth or fifth decade. Therapeutic options are limited to emollients, topical 5-fluorouracil and retinoids, but none of these treatments is consistently helpful. We report a patient with Flegel's disease who responded to psoralen ultraviolet A treatment.

Female↗

Validation of the Frenchay Activities Index in a general population aged 16 years and older.

OBJECTIVES: To assess the validity and reliability of the Frenchay Activities Index (FAI) and to establish age and sex norms in people at or over the age of 16 years. DESIGN AND SETTING: Postal questionnaire survey to 1280 people randomly selected from 8 Health Authority patient registers in England. MAIN OUTCOME MEASURES: FAI scores, subscale scores by age and sex, health status, perceived level of activity, and subjects' opinions on how well the FAI reflected their activities. Test-retest reliability was measured in 1 Health Authority. RESULTS: The response rate was 49%. Men scored lower than women overall and on the domestic activities subscale. Respondents between the ages of 16 and 24 years and those over 85 years had the lowest FAI scores. FAI scores were related to self-reported health status, self-reported levels of activity, and presence of long-standing illness/disability. The FAI has high test-retest reliability. Qualitative data suggested that items such as sport, physical exercise, and caring for children should be included to make the FAI suitable for a wider age range. CONCLUSION: The FAI has good construct validity, particularly in middle-aged and elderly people, and is reliable. For the FAI to be valid in nonstroke populations, items specific to younger people must be incorporated into it. We have established preliminary age and sex norms that should be interpreted with caution, given the low response rate.

Activities of Daily Living↗

Evaluation of serum cystatin C and chromogranin A as markers of nephropathy in patients with type 2 diabetes mellitus.

Nephropathy is a significant cause of morbidity and mortality in patients with diabetes mellitus (DM). The condition is characterized by persistent albuminuria and years of progressive renal structural changes associated with decline in the glomerular filtration rate (GFR). This study evaluates whether serum concentrations of the endogenous markers of GFR, cystatin C and chromogranin A could be used as indicators of nephropathy in 77 patients with Type 2 DM. On the basis of early morning urine microalbumin:creatinine ratio, patients were divided into patients without diabetic nephropathy (DN) who were normoalbuminuric (n = 27) and patients with DN who were microalbuminuric (n = 8) or macroalbuminuric (n = 42). Patients with reduced GFR or elevated serum cystatin C did not show the expected increase in serum chromogranin A. Twenty-six percent of the patients with normoalbuminuria and 6% of those with DN had serum chromogranin A below the detection limit of the assay (< 2 U/L). In patients with DN, serum chromogranin A showed significant correlation with serum cystatin C, but not with serum creatinine and creatinine clearance. Serum cystatin C and creatinine showed poor correlation with duration of DM and HbA1c. Serum cystatin C and creatinine were significantly higher in patients with DN than in normoalbuminuric patients. Serum cystatin C showed significant correlation with serum creatinine (rs = 0.45, p = 0.002), but not with creatinine clearance (rs = 0.23, p = 0.17) in patients with DN. Four of nine patients with creatinine clearance between 50 and 80 mL/min had increased (> or = 1.4 mg/L) serum cystatin C compared with only two patients with increased serum creatinine concentration. Twenty of 50 (40%) patients with DN had elevated serum cystatin C compared with 6 of 50 (12%) with elevated serum creatinine. If microalbuminuria is regarded as the "gold-standard" test, serum cystatin C has a sensitivity of 40% and specificity of 100% for the detection of DN. However, further studies are required to confirm the usefulness of serum cystatin C estimation as a screening test and as an early indicator and predictor of the development of DN.

Biomarkers↗

Using amphetamine isomer ratios to determine the compliance of amphetamine abusers prescribed dexedrine.

The amphetamine isomer ratios (l-amphetamine/d-amphetamine) in 373 urine specimens submitted for analysis over a two-year period have been determined using a chiral derivatizing agent in conjunction with a gas chromatograph fitted with a nitrogen-specific detector. All of the specimens were collected from known or suspected amphetamine abusers, some of which were prescribed dexedrine for maintenance and detoxification. The mean (+/- 1 standard deviation [SD]) l/d-amphetamine isomer ratio for 147 specimens from compliant subjects prescribed dexedrine was 15.0% (+/- 4.9%). The mean (+/- 1 SD) l/d-amphetamine isomer ratio from 165 subjects abusing illicit amphetamine was 98.5 (+/- 27.5%). The calculation of l/d-amphetamine isomer ratios in urine has been found to be a rapid method for determining the compliance of subjects prescribed dexedrine and is therefore a useful technique for the continued management of amphetamine abusers. In addition, 17 specimens of illicit amphetamine powder (assumed to be a racemic mixture) were submitted to the laboratory for analysis. Using a combination of gas chromatography with and without chiral derivatization, the powders were found to have a mean l/d-amphetamine isomer ratio of 89.2% (range 72.2% to 98.3%) and mean purity (w/w) of 21.5% (range 3.4% to 71.0%) relative to pure dl-amphetamine substance.

Amphetamine-Related Disorders↗

Disabled people and professionals differ in their perceptions of rehabilitation needs.

BACKGROUND: This study set out to explore whether there are systematic differences in unmet needs for rehabilitation services and resources as identified by disabled people and nominated key professionals. METHODS: A cross-sectional interview survey of 87 pairs of community-dwelling disabled people (aged 16-65) and their nominated key professionals was conducted in southern England. The Southampton Needs Assessment Questionnaire (SNAQ) was used to examine unmet needs and the Office of Population Censuses and Surveys (OPCS) Disability and Severity Scale to examine level of disability. RESULTS: Eighty-seven pairs of disabled people and their nominated key professionals participated. People were severely disabled (median OPCS score 8; interquartile range 6-9). Disabled participants reported significantly more unmet needs than did professionals. There was zero concordance on identified unmet needs between disabled participants and professionals in 56 per cent of cases. Concordance between disabled participants and professionals was significantly better if the disabled participant had reported more unmet needs. There was a trend for general practitioners to be poorer at reporting disabled participants' needs than other professionals. There was fair agreement between disabled participants and professionals in five areas of unmet need only (in descending order): adaptations, physiotherapy, equipment, assistance with 'non-care' activities and the use of a day centre. In all the other areas of unmet need the agreement was poor. CONCLUSIONS: Needs for rehabilitation services and resources (for disabled people) are perceived differently by disabled people and professionals. Until we know who is right about rehabilitation needs, it is important to determine both users' and providers' views when planning and commissioning services.

Adolescent↗

The use of a classification approach to identify subgroups of patients with acute low back pain. Interrater reliability and short-term treatment outcomes.

STUDY DESIGN: A prospective, consecutive, cohort study of patients with acute low back pain classified into subgroups based on examination data and treated with a specific treatment approach. OBJECTIVE: To calculated the interrater reliability of a classification system, and to compare initial patient characteristics and outcomes of physical therapy treatment when a classification approach is used. SUMMARY OF BACKGROUND DATA: Classification of patients with low back pain into homogeneous subgroups has been identified as a research priority. Identifying relevant subgroups of patients could improve clinical outcomes and research efficiency. METHODS: Consecutive patients referred to physical therapy for treatment of acute low back pain were evaluated and classified into one of four subgroups (immobilization, mobilization, specific exercise, or traction) before treatment. Physical therapy treatment was based on the patient's classification. The classifications were compared for initial patient characteristics, frequency and duration of physical therapy, and improvement in Oswestry scores. RESULTS: In this study, 120 patients were evaluated and classified. Analysis of interrater reliability showed a kappa value of 0.56. Differences were found among the classifications for age, initial Oswestry score, history of low back pain, symptom distribution, and average change in Oswestry score with treatment. CONCLUSIONS: Reaching a consensus regarding relevant patient subgroups requires data on the reliability and validity of existing classification systems. Further work is required to validate improvement in treatment outcomes using a classification approach.

Acute Disease↗

Xeroderma pigmentosum: the role of phototesting.

We report three patients newly diagnosed as having xeroderma pigmentosum (XP). Previous photobiological studies have implicated ultraviolet (UV) B as the activating waveband in XP, causing a delayed and prolonged erythemal response. This characteristic reaction pattern has been used as a quick screening test in patients suspected of having XP, while awaiting confirmatory DNA repair studies. Two of our patients showed no abnormal erythemal responses, and one showed severe photosensitivity from 330 to 400 nm but normal UVB responses, with a peak erythema at 24 h. We conclude that the erythemal responses in XP are highly variable and cannot be considered as a reliable screening test in the diagnosis of XP.

Child↗

Milk alkali syndrome-an unusual syndrome causing an unusual complication.

Milk alkali syndrome is rare and although pancreatitis secondary to hypercalcaemia is well recognised, there has only been one other reported case of pancreatitis secondary to the milk alkali syndrome. Such a case, caused by self medication of over the counter medication, is reported.

Acute Disease↗

The Southampton Needs Assessment Questionnaire (SNAQ): a valid tool for assessing the rehabilitation needs of disabled people.

OBJECTIVE: To validate the Southampton Needs Assessment Questionnaire (SNAQ) for use with disabled people during face-to-face interviews. DESIGN: The SNAQ was designed to be used in a cross-sectional survey of disabled people with a physical disability with a follow-up study one year later. Content and criterion validity was examined using 32 disabled people who took part in the pilot study. Construct validity and internal reliability was examined using data from 93 disabled people who took part in the main survey. Responsiveness of the questionnaire was evaluated using the data gathered during a follow-up study of 77 people had taken part in the original study. OUTCOME MEASURES: The OPCS Disability Severity Scales (OPCS) and the Functional Independence Measure (FIM) were used to measure level of disability of participants, the Nottingham Health Profile (NHP) and the UK version of the SF-36 to examine perceived health status. PARTICIPANTS: People with a primary physical disability, aged 16-65, randomly selected from two disability registers in southern England. MAIN RESULTS: Content and criterion validity were established. Construct validity and internal reliability of the SNAQ was good. Inter-rater reliability was not tested since only one researcher conducted the interviews. Test-retest reliability was not formally tested because of the probability that participants would learn from the first needs assessment questionnaire and that different results on a retest occasion could arise from this. The SNAQ was sensitive in picking up changes over time. CONCLUSION: The SNAQ has shown good validity (content, coverage and construct), internal reliability, sensitivity and responsiveness. Further studies are needed to define the consequences of meeting or not meeting the rehabilitation needs of disabled people. Inter-rater reliability remains to be established.

Adolescent↗

Simple high-performance liquid chromatographic method to monitor vigabatrin, and preliminary review of concentrations determined in epileptic patients.

A simple and rapid high-performance liquid chromatographic method has been developed for the determination of vigabatrin concentrations in plasma or serum. The assay uses only 100 microL of specimen and has been found to be linear over a concentration range of 1 to 50 mg/L. The limit of detection has been determined as 1 mg/L, and the between-batch coefficient of variation for the two internal quality controls routinely analysed (n = 33) has been found to be less than 5%. There was no evidence of interferences in the assay from other commonly prescribed anti-epileptic drugs. This method has been applied to routine clinical specimens to determine the concentration of vigabatrin in 47 patient specimens over a 12-month period. It was found that only 63% of the male group and 53% of the female group were within the proposed target concentration of 5 to 35 mg/L. In addition, it was found that 26% of the male group and 36% of the female group were found to have concentrations below 5 mg/L, which may indicate lack of compliance and/or lack of therapeutic efficacy of treatment.

Adolescent↗

Application and validation of a urinary methadone metabolite (EDDP) immunoassay to monitor methadone compliance.

A total of 1381 urine specimens were screened using a Microgenics CEDIA urinary primary methadone metabolite (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine; EDDP) immunoassay (cut-off calibrator concentration of 100 microg/L) in combination with a Dade Behring EMIT urinary methadone immunoassay (cut-off calibrator concentration of 300 microg/L). Of these, 642 (46%) were found to be positive using the EDDP assay but only 541 (39%) were found to be positive by the methadone assay. Out of the 108 specimens which were EDDP-positive but negative by the methadone assay, 47 (7%) could not be confirmed as positive using the routine in-house method of gas chromatography incorporating nitrogen-specific detection. Of these 47 results, 38 were re-screened using a more sensitive gas chromatography-mass spectrometry (GC-MS) technique, which demonstrated the presence of EDDP in every case. There was insufficient specimen to analyse the remaining nine samples. There were seven specimens which gave negative results by the EDDP and GC-MS assays but which had methadone concentrations ranging from 4000 to 37,500 microg/L. These were therefore presumed to be 'spiked' with methadone, i.e. to have had methadone added to the specimen to yield positive screening results and simulate compliance. It is concluded that the Microgenics CEDIA EDDP assay is a sensitive and reliable technique to determine the compliance of subjects prescribed methadone for opiate detoxification and maintenance.

Calibration↗

Ossifying pituitary gonadotroph adenoma: A case report.

BACKGROUND: Bone formation in pituitary adenomas is a rare finding. Only two previous cases were published, occurring in a prolactin- producing and a growth hormone- producing pituitary adenoma respectively, both in pre-menopausal women. CLINICAL MATERIAL: This is the third report of an ossified pituitary adenoma and the first report of a pituitary gonadotroph adenoma with bone formation occurring in an elderly man. MRI imaging revealed an unusual eggshell cap-like calcified structure surrounding the tumor. Histologically, the adenoma contained irregularly anastomosing trabecules with well formed lacunae and osteoblasts along the margins. CONCLUSIONS: Insufficient tumor blood supply may trigger proliferation of connective tissue that subsequently undergoes osteoid metaplasia. Pituitary adenoma with osteoid metaplasia should be included in the differential diagnosis of calcifying tumors in the sella region.

Adenoma↗

Spot urine concentrations of type I collagen cross-linked N-telopeptides and deoxypyridinoline in psoriatic arthritis.

The main objectives of this study were to investigate whether the spot urine concentrations of type I collagen cross-linked N-telopeptides (NTx) and deoxypyridinoline (Dpd) can be used to distinguish between active and suppressed disease in psoriatic arthritis (PsA) and to study the relationship between these markers of bone resorption and disease activity indices. Using enzyme-linked immunosorbent assays, concentrations of NTx and Dpd were estimated in spot urine samples from 25 patients with active disease, 10 patients with suppressed disease and 35 age- and sex-matched healthy control subjects. In patients with active disease, urine concentrations of NTx and Dpd were significantly elevated (p<0.001) compared with healthy controls and there were no significant differences (p>0.05) when compared with those with suppressed disease. In active disease, there was no significant positive correlation between urinary NTx and erythrocyte sedimentation rate (ESR) (r = 0.025, p>0.05) nor between Dpd and ESR (r = -0.208, p>0.05). In conclusion, NTx and Dpd concentrations in spot urine have no association with disease activity in patients with PsA.

Adolescent↗

Development of a disease specific quality of life (QoL) questionnaire module to supplement the EORTC core cancer QoL questionnaire, the QLQ-C30 in patients with pancreatic cancer. EORTC Study Group on Quality of Life.

There is overwhelming consensus that quality of life assessment is urgently required in pancreatic cancer, yet little research has been conducted. We report on the development of a disease specific questionnaire module to supplement the EORTC core cancer module, the QLQ-C30 in patients with pancreatic cancer, using EORTC quality of life study group guidelines for module development. Relevant QoL issues were generated from literature searches and interviews with health professionals and patients with pancreatic cancer. Issues were constructed into items and provisionally translated. The provisional module was pretested in patients in 8 European centres. The resulting module the QLQ-PAN26 includes 26 items related to disease symptoms, treatment side-effects and emotional issues specific to pancreatic cancer. This should ensure that the module will be sensitive to assess the small but important disease and treatment related QoL changes in pancreatic cancer. The use of the QLQ-C30 and QLQ-PAN26 will provide a comprehensive system of QoL assessment in international trials of pancreatic cancer.

Adult↗