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Biomedical subjects

P Gibson

Publications and source records attributed to P Gibson.

At least 19 recordsLinked to original sources

Aminophylline in undifferentiated out-of-hospital asystolic cardiac arrest.

PRIMARY OBJECTIVE: To determine if the introduction of intravenous aminophylline, a nonspecific adenosine receptor antagonist, into the resuscitation algorithm of asystole will increase return of spontaneous circulation when used in undifferentiated prehospital cardiac arrest. METHODS: An urban, prehospital, prospective, randomized, double-blind, placebo-controlled trial of nonpregnant normothermic adults suffering nontraumatic out-of-hospital asystolic cardiac arrest. Subjects were treated in accordance with published advanced cardiac life support guidelines and standard pharmacotherapy. They were randomly assigned to receive either placebo or aminophylline along with the initial boluses of atropine and epinephrine. Cardiac rhythms and carotid pulses were monitored throughout the resuscitation. RESULTS: Eighty-two patients were entered into the trial. Forty-five patients were assigned to the placebo group and 37 received aminophylline. Nine of 45 controls (20%; 95% CI 10-35%) achieved return of spontaneous circulation compared to ten of 37 (27%; 95% CI 14-44%) in the aminophylline group. CONCLUSIONS: We were not able to show a statistically significant improvement in return of spontaneous circulation when aminophylline was given during the early resuscitation phase of undifferentiated asystolic cardiac arrest in the prehospital setting with this sample size.

Aged

The characteristics of asthma education programs within New South Wales.

The aim of the study was to examine the characteristics of asthma education programs within NSW. A cross-sectional questionnaire survey concerning the aims and characteristics of 42 asthma education programs was administered to members of the Asthma Educators Association (AEA) of NSW. While most programs sought to improve asthma knowledge (78%), only a small number sought to improve asthma management skills (38%), asthma control (33%) and attitudes (10%). Most programs performed one-to-one (69%) education. Medical intervention was under-utilized by most programs and only 4% gave feedback to the referring doctor. Program evaluation was incompletely linked to program aims. There was incomplete evaluation of knowledge gain as an outcome. The study reviewed the characteristics of education programs within NSW Existing programs appropriately employ a variety of educational methods and target a broad range of people with asthma. There remains a need to use a combined approach utilizing education and medical management, and to employ methods to evaluate programs.

Adolescent

The C282Y mutation in the haemochromatosis gene (HFE) and hepatitis C virus infection are independent cofactors for porphyria cutanea tarda in Australian patients.

BACKGROUND/AIM: Whether mutations in the putative haemochromatosis gene (HFE) and hepatitis C virus act independently to precipitate porphyria cutanea tarda is unknown. The aim of the study was to investigate the relationship between mutations in HFE, hepatitis C and porphyria cutanea tarda. METHODS: The frequencies of the C282Y and H63D mutations in HFE were determined in 27 patients with porphyria cutanea tarda and compared with the reported control frequencies. In addition, the presence of hepatitis C virus infection was identified and related to the patients' HFE status. RESULTS: The C282Y mutation was found in 44.4% of patients compared with the control frequency of 12% (p<0.001). Three patients were homozygous for the C282Y mutation, two of whom did not meet current clinical diagnostic criteria for expressed haemochromatosis. The proportion of patients with the H63D mutation did not differ from the reported control frequency. The mean transferrin saturation and serum ferritin concentration were similar in porphyria cutanea tarda patients who were homozygous normal and heterozygous for the C282Y mutation, but greater in both groups than previously reported in healthy controls. Seven (25.9%) patients were anti-HCV IgG positive. None of these patients carried the C282Y mutation. Porphyria cutanea tarda patients heterozygous for the C282Y mutation and patients with anti-HCV antibodies had elevated transferrin saturations and serum ferritin concentrations. CONCLUSIONS: The raised frequency of the C282Y mutation in porphyria cutanea tarda indicates that this mutation is likely to be a predisposing factor. However, abnormalities of iron indices also exist in porphyria cutanea tarda patients without mutations in HFE. Hepatitis C virus infection is likely to be another common precipitating factor for porphyria cutanea tarda which acts independently of the C282Y mutation.

Adult

Adaptation and evaluation of the Liverpool Seizure Severity Scale and Liverpool Quality of Life battery for American epilepsy patients.

The Liverpool Seizure Severity Scale (LSSS) and the Liverpool Quality of Life (LQOL) battery were developed in Great Britain to assess the severity of seizure symptoms and the impact of epilepsy on patients' quality of life. The scales have been validated on British patients, but have not been validated for use with American patients. The objectives of this study were to adapt the scales to the American population and to evaluate their reliability and validity. After modifications recommended by focus groups with patients and epilepsy specialists, the scales were administered to a sample of 90 epilepsy patients who had experienced seizures within the previous 4 weeks. Comparisons of patients with generalized tonic-clonic seizures (n = 58) and partial seizures (n = 32) revealed significant differences on 9 of the 20 items on the LSSS as well as the total score. None of the six LQOL subscales (negative drug effects, positive drug effects, affect balance, sense of mastery, life fulfilment and impact of epilepsy) distinguished patients with different seizure types but five of the six subscales were significantly correlated with seizure severity. The internal consistency and test-retest reliability were adequate for both the LSSS and LQOL. Finally, five of the six LQOL scales were significantly correlated with independent measures of mental health, physical health and role functioning.

Adult

Adaptation and evaluation of the Liverpool Seizure Severity Scale and Liverpool Quality of Life battery for American epilepsy patients.

The Liverpool Seizure Severity Scale (LSSS) and the Liverpool Quality of Life (LQOL) battery were developed in Great Britain to assess the severity of seizure symptoms and the impact of epilepsy on patients' quality of life. The scales have been validated on British patients, but have not been validated for use with American patients. The objectives of this study were to adapt the scales to the American population and to evaluate their reliability and validity. After modifications recommended by focus groups with patients and epilepsy specialists, the scales were administered to a sample of 90 epilepsy patients who had experienced seizures within the previous 4 weeks. Comparisons of patients with generalized tonic-clonic seizures (n = 58) and partial seizures (n = 32) revealed significant differences on 12 of the 20 items on the LSSS as well as the total score. None of the six LQOL subscales (negative drug effects, positive drug effects, affect balance, sense of mastery, life fulfillment and impact of epilepsy) distinguished patients with different seizure types but five of the six subscales were significantly correlated with seizure severity. The internal consistency and test-retest reliability were adequate for both the LSSS and LQOL. Finally, five of the six LQOL scales were significantly correlated with independent measures of mental health, physical health and role functioning.

Adult

Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis.

A reliable predictor of benefit from corticosteroid treatment in patients with chronic airflow limitation is needed. In a single-blind, sequential crossover trial of placebo and prednisone (30 mg/day) treatment, with each given for 2 wk, we investigated whether an increased proportion of sputum eosinophils (>= 3%) predicts a beneficial effect of prednisone in smokers with severe obstructive bronchitis. Patients were seen before and after each treatment. Clinical measurements were made blind to the laboratory findings and vice-versa. Eighteen of 20 patients completed the study. Eight had sputum eosinophilia and similar clinical and physiologic characteristics to those of 10 patients without a finding of sputum eosinophilia. Only in patients with sputum eosinophilia did prednisone, as compared with placebo, produce a statistically significant and clinically important mean effect on effort dyspnea of 0.8 (95% confidence interval [CI]: 0.3 to 1.2), p = 0.008, and in quality of life of 1.96 (95% CI: 0.5 to 3.3), p = 0.01, associated with a small improvement in FEV1 of 0.11 L (95% CI: - 0.04 to 0.23 L), p = 0.05. In these patients, prednisone also produced a significant decline in the median sputum eosinophil percentage, from 9.7% to 0.5% (p = 0.002), eosinophil cationic protein (ECP), from 6, 000 microgram/L to 1,140 microgram/L (p < 0.001), and fibrinogen, from 25. 3 mg/L to 5.4 mg/L (p < 0.001). These findings indicate that in smokers with severe airflow limitation, sputum eosinophilia predicts a beneficial effect of prednisone treatment. Improvement in FEV1, after prednisone treatment in this population, is small, and may not be appreciated in clinical practice.

Adult

Adenosine receptor antagonism in refractory asystolic cardiac arrest: results of a human pilot study.

PRIMARY OBJECTIVE: To determine if adenosine receptor antagonism has any beneficial impact on victims of asystolic cardiac arrest and whether or not it warrants further clinical study as a treatment for cardiac asystole. MATERIALS AND METHODS: A 6-month prospective, randomized, double-blinded, placebo-controlled trial, set in an urban emergency medical services system, in adults with nontraumatic asystolic out-of-hospital cardiac arrest. Patients in whom standard advanced cardiac life support pharmacotherapy failed were randomized to receive placebo or aminophylline, a nonspecific competitive adenosine receptor antagonist. Rhythms were recorded before and after intervention. RESULTS: Twenty-two patients were appropriately entered into the trial. Eight patients served as controls and 14 patients received aminophylline. The groups were similar in all measured parameters except for initial rhythm. None of the patients in the placebo group responded to the intervention. Half of the patients in the treatment group had return of organized cardiac electrical activity. CONCLUSION: Our results suggest that adenosine receptor antagonism may have a role in the treatment of cardiac asystole. Further clinical studies to validate these findings and clarify the appropriate use of adenosine receptor antagonists in cardiac asystole may be justified.

Adult

Comparison of sputum processing techniques in cystic fibrosis.

Sputum analysis is a useful technique for the study of airway inflammation. In asthma, dithiothreitol (DTT) is used to disperse cells from surrounding mucus; however, the applicability of these processing methods to cystic fibrosis (CF) sputum is unknown. In order to compare two methods for processing sputum of patients with CF, sputum was obtained from 11 subjects with CF (8 female, aged 9-21 years). The sample was split into 2 portions and sputum dispersal using DTT was compared with an enzyme mixture (E) of deoxyribonuclease, hyaluronidase, and galactosidase. Outcomes assessed were sample quality, cell viability (percent cells excluding trypan blue), total cell count (TCC), neutrophil count, and elastase immunoreactivity (percent cells positive). Sample quality (enzymes vs. DTT, 8.3 +/- 0.3 vs 7.6 +/- 0.4, mean +/- SEM) and cell viability (enzymes vs. DTT, 75.0% vs. 68.0%, median) were similar for both methods. Sputum total cell count (20.5 x 10(6)/ml vs. 12.0 x 10(6)/ml, median; P = 0.01) and neutrophil count (13.4 x 10(6)/ml vs. 5.5 > 10(6)/ml, median; P = 0.02) were significantly higher with E. Elastase immunoreactivity was lost after processing with E (19.0% vs. 39.5%, median; P = 0.04). When purified peripheral blood neutrophils were incubated with DTT and E, there was no reduction in neutrophil viability, suggesting that the reduced neutrophil number in CF sputum was not due to a toxic effect of DTT but rather incomplete dispersal. We conclude that published sputum processing methods for asthma using DTT give false results when applied to CF sputum, which should be processed using an enzyme mixture.

Adolescent

Effect of food on the comparative pharmacokinetics of modified-release morphine tablet formulations: Oramorph SR and MST Continus.

The relative bioavailability and pharmacokinetic profiles of Oramorph SR (OSR) and MST Continus (MST), were evaluated by a randomized, four-way cross-over study in 24 healthy, male volunteers given single oral (30 mg) doses whilst fasting or after a high-fat breakfast. Mean Cmax, tmax, AUC (0,24h), AUC and tlag were significantly greater in fed compared with fasting subjects. Overall relative bioavailability of the two formulations (log AUC), was within the acceptable 80-125% limits for bioequivalence both fed and fasting. Mean fasting Cmax for OSR was greater than MST (P < 0.05) but there was no difference between formulations in mean fed Cmax. No statistically significant difference between OSR and MST was found for other parameters nor in the incidence of adverse events. These results suggest that OSR and MST are bioequivalent and that if patients were to transfer between formulations, dosage adjustment would be unnecessary, irrespective of their meal schedules or food intake.

Adolescent

Open fractures of the tibia in children.

The results of the treatment of open tibial fractures in 58 children aged between 3 and 15 years are reviewed. There were 25 Gustilo Type I, 22 Type II and 10 Type III fractures. At operation 37 wounds were closed primarily and 21 wounds were left open. Of these 21, 13 healed by secondary intention and eight required split skin grafting or soft tissue flap coverage. Stable fractures were immobilized in an above-knee plaster in 48 cases (83 per cent) and six fractures treated with external fixation (10 per cent). Two patients (3.5 per cent) had cast immobilization of the tibial fracture and traction for an ipsilateral femoral fracture. Two patients (3.5 per cent) with Gustilo Type IIIc injuries required an amputation, one 'de novo' as the limb was not salvageable and one 4 days after failed vascular reconstruction. All fractures healed primarily without bone grafting, although there were three cases of delayed union and seven cases of malunion. Six children had superficial wound infections but there were no cases of deep infection or osteomyelitis. There was one case of compartment syndrome.

Adolescent

Heat-stroke: a review of rapid cooling techniques.

Patients with prolonged hyperpyrexia due to heat-stroke have a poor outcome. Thus, the most important feature in the management of heat-stroke is rapid cooling. There are several methods of cooling available, such as fan therapy, cold water immersion, iced baths and evaporative cooling. Based on military and civilian experiences worldwide the development of protocols based on evaporative cooling is advocated as the most efficient.

Baths

Colonic epithelium is diffusely abnormal in ulcerative colitis and colorectal cancer.

The hypothesis that the colonic epithelium is diffusely abnormal in ulcerative colitis was examined by comparing disease related responses in expression of markers of differentiation by colonic crypt cells to culture with and without butyrate. Cells were isolated from patients with normal colon (15), cancer (24), ulcerative colitis (19), or Crohn's disease (16). Alkaline phosphatase activities were measured in cell homogenates and the rate of glycoprotein synthesis assessed at the end of 24 hours of culture and expressed relative to the rate of protein synthesis as the G:P ratio. Alkaline phosphatase activities, but not G:P ratios, differed across the groups before and after 24 hour culture (p < 0.05), activities being lowest in the cancer group and highest in inflammatory bowel disease groups. Butyrate (1 mM) suppressed alkaline phosphatase activities in the cancer group by mean (SEM) of 17 (4) (p = 0.006) compared with no change in the other groups. Butyrate suppressed G:P ratios only in the cancer (6 (3)%, p = 0.03) and ulcerative colitis groups (5 (3)%, p = 0.04) and the changes in both were different (p < 0.05) from those in normal cells (increase of 10 (7)%). Changes in ulcerative colitis were different from those in Crohn's disease (p = 0.029). Responses were independent of the presence or absence of mucosal inflammation. These data confirm the diffuse nature of epithelial abnormalities in colorectal cancer. In ulcerative colitis, a different pattern of abnormality occurs, supporting the notion that the epithelium is also diffusely abnormal independent of mucosal inflammation.

Adult

Interleukin 8 secretion by colonic crypt cells in vitro: response to injury suppressed by butyrate and enhanced in inflammatory bowel disease.

Epithelia from several sites exhibit inducible secretion of interleukin 8 (IL-8). This study aimed to characterise secretion of IL-8 by colonic epithelial cells in vitro. Colonic crypt cells were isolated enzymatically from resected colon and the IL-8 content of culture supernates was measured by ELISA. The rate of secretion of IL-8 accelerated and levels of IL-8 transcripts increased appreciably during culture. Exposure to tumour necrosis factor alpha (TNF alpha) failed to increase secretion further. Secretion was not induced by the enzymatic digestion or by serum used in the culture medium but was significantly inhibited by butyrate, by a mean of 23%. Control experiments indicated that colonic crypt cells were the likely source. The secretion of IL-8 over 24 hours by cells from uninflamed mucosa of patients with ulcerative colitis or Crohn's disease was more than twofold that from normal cells, while that from cancer bearing colons was normal. TNF alpha (10 mM) significantly suppressed IL-8 secretion only in the ulcerative colitis group and the change was different to those in the normal (p = 0.007) and Crohn's disease groups (p = 0.012). Cells from inflamed areas secreted more IL-8 than those from autologous uninflamed areas (p = 0.009) but responses to modulating factors were no different. The induction of IL-8 secretion by colonic crypt cells in vitro is probably a response to injury associated with isolation and culture. It is suppressed by butyrate and increased in inflammatory bowel disease independently of the presence of mucosal inflammation. Whether epithelial derived IL-8 plays a part in the pathogenesis of inflammatory bowel disease is not yet clear.

Adolescent

The effect of allowing clinical discretion in ordering biochemical tests. Evaluation by complementary methods.

We describe the effects on costs, working patterns, and clinical behavior of installing a DAX "discretionary" biochemistry analyzer. Use of the new analyzer encouraged doctors to be more specific in requesting biochemical tests, which substantially reduced the number of tests requested and slightly reduced overall costs. Doctors preferred being able to order tests in this more specific way.

Autoanalysis

Serum free medium increases expression of markers of differentiation in human colonic crypt cells.

In colitis, colonic epithelial cells have a shortened life span but show normal or increased expression of phenotypic markers of differentiation. This study examined the effect of differing culture conditions on the expression of such markers in colonic crypt cells. Crypt cells were enzymatically isolated from macroscopically normal large bowel mucosa resected because of neoplasia, inflammatory bowel disease or non-neoplastic non-inflammatory conditions. Cells cultured in the presence of serum exhibited a doubling of the rate of protein synthesis (measured by 14C-leucine uptake; p < 0.001) compared with autologous cells cultured in the absence of serum without evidence of loss of cell viability (assessed by 51Cr release from prelabelled cells) or of change in the rate of cell proliferation (assessed by total DNA content and 3H-thymidine uptake). Irrespective of the underlying colonic disease, crypt cells cultured in the absence of serum exhibited increased expression of phenotypic markers of differentiation compared with those cultured with serum: the rate of glycoprotein synthesis relative to that of protein synthesis increased by a mean of 59% and the cellular expression of brush border glycoproteins, alkaline phosphatase, and carcinoembryonic antigen significantly increased. The effects seen could not be mimicked by addition of dexamethasone or insulin to serum free medium. Thus, under less optimal (serum free) culture conditions, colonic crypt cells express phenotypic markers of differentiation at an accelerated rate suggesting that unfavourable microenvironmental conditions themselves are probably in part responsible for the normal or increased expression of such markers in colitis.

Alkaline Phosphatase