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Biomedical subjects

M Cole

Publications and source records attributed to M Cole.

At least 37 records · Page 2Linked to original sources
PubMed2001

OPEC/OJEC for stage 4 neuroblastoma in children over 1 year of age.

BACKGROUND: This paper reports the toxicity of OPEC/OJEC chemotherapy in stage 4 neuroblastoma patients over 1 year of age. PROCEDURE: Ninety-five patients with stage 4 neuroblastoma received alternating courses of OPEC/OJEC--vincristine 1.5 mg/m2 (O), cisplatin 80 mg/m2 (P), etoposide 200 mg/m2 (E), cyclophosphamide 600 mg/m2 (C), and carboplatin 500 mg/m2 (J), every 21 days if there was haematological recovery. RESULTS: Seventy out of ninety-five (74%) patients completed seven or more courses and were evaluable for toxicity. Of these 70 patients, 33% had more than three episodes of fever and sepsis, 35% required more than five blood or platelet transfusions, 36% had grade 2 or more gastrointestinal toxicity and 9% had neurotoxicity. There was a median reduction in GFR of 32 ml/min/1.73 m2 (-46 to 134) and there was one toxic death. CONCLUSIONS: OPEC/OJEC is a well-tolerated therapy for stage 4 neuroblastoma over 1 year of age.

3-Iodobenzylguanidine↗
PubMed2001

Oral immunoglobulin for preventing necrotizing enterocolitis in preterm and low birth-weight neonates.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common emergency of the gastrointestinal tract occurring in the neonatal period. There have been published reports which suggest that oral immunoglobulins IgA and IgG produce an immunoprotective effect in the gastrointestinal mucosa. This systematic review was undertaken to clarify the issue. OBJECTIVES: To assess whether oral immunoglobulin administered to preterm and low birth-weight neonates reduces the incidence of necrotizing enterocolitis without adverse effects. SEARCH STRATEGY: The databases MEDLINE, CINAHL, Embase and the Cochrane Controlled Trials Register were searched. The text words 'necrotising enterocolitis OR necrotizing enterocolitis' AND 'immunoglobulin' with constraints 'neonate OR infant' were used. Proceedings of the Perinatal Society of Australia and New Zealand were hand searched. The computer neonatal discussion site 'Nicu Net' was also used. Additionally, all references in the identified trials were checked and authors were contacted to request any additional published or unpublished data. SELECTION CRITERIA: All randomized or quasi-randomized controlled trials where oral immunoglobulins were used as prophylaxis against necrotizing enterocolitis in preterm (<37 weeks gestation) and/or low birth-weight (<2500 gms) neonates. DATA COLLECTION AND ANALYSIS: The procedures of the Cochrane Neonatal Review Group (CNRG) were used. The two reviewers independently assessed the trials for their methodological quality and subsequent inclusion in the review. Relative risk (RR), risk difference (RD), and number needed to treat (NNT) were used in the analysis. MAIN RESULTS: Five studies on oral immunoglobulin for the prevention of necrotizing enterocolitis were identified of which three met the inclusion criteria. In this review of the three eligible trials (including a total of 2095 neonates) the oral administration of IgG or an IgG/IgA combination did not result in a significant reduction in the incidence of definite NEC [RR 0.84 (95% CI 0.57, 1.25), RD -0.01 (95% CI -0.03, 0.01)], suspected NEC [RR 0.69 (95% CI 0.42, 1.13), RD -0.01 (95% CI -0.03, 0.00)], need for surgery [RR 0.21 (95% CI 0.02, 1.75), RD -0.03 (95% CI -0.06, 0.00)] or death from NEC [RR 1.10 (95% CI 0.47, 2.59), RD 0.00 (95% CI -0.01, 0.01)]. REVIEWER'S CONCLUSIONS: Based on the available trials, the evidence does not support the administration of oral immunoglobulin for the prevention of NEC. There are no randomised controlled trials of oral IgA alone for the prevention of NEC.

Administration, Oral↗
PubMed2001

A demographic study of the clinical significance of minimal residual disease in children with acute lymphoblastic leukemia.

BACKGROUND: Minimal residual disease (MRD) detected during remission might predict outcome in children with acute lymphoblastic leukemia. No population-based studies have been carried out. We studied all children with ALL presenting over 5 years within a defined population to determine its clinical importance. PROCEDURE: Patients were investigated for the presence of unique clonal rearrangements of IgH and T-cell receptor genes. Unique patient specific probes were used to detect, by polymerase chain reaction, the presence of clonal markers indicating MRD in mononuclear cells obtained from marrow samples at 1, 3, 5, and 24 months. The effect of MRD on event-free survival was determined. RESULTS: Seventy-seven of 120 children with ALL had informative markers and samples of remission marrow suitable for testing. Presence or absence of MRD did not significantly affect outcome. Gender (P < 0.04) and white cell count (P < 0.04) were independent prognostic factors. Analysis of only those cases with detectable MRD showed that cases with one blast per 100 mononuclear cells, or more, 28 days after starting treatment did worse than those with lower levels (hazard ratio 7.77, P < 0.02). CONCLUSIONS: Mere presence or absence of MRD is probably too crude a measure to be useful and worse than other standard prognostic indicators. A threshold of 10(-2) blasts at 28 days might be discriminatory, but should not be over-interpreted. The number of patients available for this analysis (31) was small, the threshold and sampling points were arbitrary and any effects could be treatment regimen-specific. Large prospective studies are needed.

Adolescent↗
PubMed2001

Cyclophosphamide metabolism in children following a 1-h and a 24-h infusion.

PURPOSE: The pharmacokinetics and metabolism of cyclophosphamide (CPA) when given as a 1-h and a 24-h infusion to children were compared. METHODS: Thirteen children with a variety of different malignancies received an identical dose of cyclophosphamide as a 1- and 24-h infusion. In each case the concentration of CPA and its principal metabolites were measured by a thin-layer-chromatography-photographic-densitometry technique. RESULTS: Cyclophosphamide clearance was greater during the 24-h infusion, following time-dependent increases in the metabolism of the drug (autoinduction) (median 5.1 vs 3.1 l/h/m2: P = 0.037). Autoinduction was seen in five children (38%), producing a median end of infusion concentration of 49% (range 28-89%) of the maximum and was not accompanied by an increase in the production of the principal inactive metabolites carboxyphosphamide and dechloroethylcyclophosphamide. CONCLUSIONS: These results suggest potential benefits of prolonging the infusion of CPA in clinical practice.

Adolescent↗
PubMed2001

p53 cellular localization and function in neuroblastoma: evidence for defective G(1) arrest despite WAF1 induction in MYCN-amplified cells.

This study investigated the hypothesis that p53 accumulation in neuroblastoma, in the absence of mutation, is associated with functional inactivation, which interferes with downstream mediators of p53 function. To test this hypothesis, p53 expression, location, and functional integrity was examined in neuroblastoma by irradiating 6 neuroblastoma cell lines and studying the effects on p53 transcriptional function, cell cycle arrest, and induction of apoptosis, together with the transcriptional function of p53 after irradiation in three ex vivo primary, untreated neuroblastoma tumors. p53 sequencing showed five neuroblastoma cell lines, two of which were MYCN-amplified, and that all of the tumors were wild-type for p53. p53 was found to be predominantly nuclear before and after irradiation and to up-regulate the p53 responsive genes WAF1 and MDM2 in wild-type p53 cell lines and a poorly-differentiated neuroblastoma, but not a differentiating neuroblastoma or the ganglioneuroblastoma part of a nodular ganglioneuroblastoma in short term culture. This suggests intact p53 transcriptional activity in proliferating neuroblastoma. Irradiation of wild-type p53 neuroblastoma cell lines led to G(1) cell cycle arrest in cell lines without MYCN amplification, but not in those with MYCN amplification, despite induction of WAF1. This suggests MYCN amplification may alter downstream mediators of p53 function in neuroblastoma.

Apoptosis↗
PubMed2001

Agitation in demented patients in an acute care hospital: prevalence, disruptiveness, and staff burden.

UNLABELLED: BACKGROUND/LITERATURE REVIEW: The prevalence of agitated behaviors in different populations with dementia is between 24% and 98%. Although agitated behaviors are potentially disruptive, little research attention has been focused on the effects of these behaviors upon nursing staff. The objectives of this study of demented patients in long-term-care beds at an acute care community hospital were to determine the frequency and disruptiveness of agitated behaviors; to investigate the associations of patient characteristics and interventions with the level of agitation; and to explore the burden of these agitated behaviors on nursing staff. METHOD: The study sample comprised 56 demented patients in the long-term-care unit during the study period. Twenty-seven staff who cared for these patients during three shifts over a 2-week period were interviewed to rate the frequency and disruptiveness of agitated behaviors using the Cohen-Mansfield Agitation Inventory, and the burden of care using a modified version of the Zarit Burden Interview. Data on patient characteristics and interventions extracted from the hospital chart included scores on the Barthel Index and Mini-Mental State Examination, the use of psychotropic medication, and the use of physical restraints. RESULTS: Ninety-five percent of the patients with dementia were reported to have at least one agitated behavior; 75% had at least one moderately disruptive behavior. A small group of six patients (11%) had 17 or more disruptive behaviors. The frequency of most behaviors did not vary significantly by shift. Length of stay on long-term care, Barthel Index score, and the use of psychotropic medications were significantly associated with the number of agitated behaviors. The number of behaviors, their mean frequency, and their mean disruptiveness were all significantly correlated with staff burden. DISCUSSION: The prevalence of agitated behaviors in patients with dementia in long-term-care beds at an acute care hospital is similar to that reported in long-term-care facilities. These behaviors are associated with staff burden.

Aged↗
PubMed2001

Environmental risk factors for delirium in hospitalized older people.

OBJECTIVES: To evaluate the relationship of environmental risk factors in hospitals to changes over time in delirium symptom severity scores. DESIGN: Observational prospective clinical study with repeated measurements, several times during the first week of hospitalization and then weekly during hospitalization. SETTING: University-affiliated general community hospital. PARTICIPANTS: Four hundred forty-four patients age 65 and older admitted to the medical wards: 326 with delirium and 118 without delirium. Patients with prior cognitive impairment were oversampled. MEASUREMENTS: The severity of delirium symptoms was measured with the Delirium Index, a scale developed and validated by our group, based on the Confusion Assessment Method. Potential environmental risk factors assessed included isolation, hospital unit, room changes, levels of sensory stimulation, aids to orientation, and presence of medical (e.g., intravenous) or physical restraints. RESULTS: Controlling for initial severity of delirium and patient characteristics, variables significantly related to an increase in delirium severity scores included hospital unit (intensive care or long-term care unit), number of room changes, absence of a clock or watch, absence of reading glasses, presence of a family member, and presence of medical or physical restraints. CONCLUSION: The associations of intensive care and medical and physical restraints with severity of delirium symptoms may be due to uncontrolled confounding by indication. However, the other factors identified suggest potentially modifiable risk factors for symptoms of delirium in hospitalized older people.

Aged↗
PubMed2001

Applying social and behavioral theory as a template in containing and confining VRE.

Infection control professionals play several important roles--surveyors, educators, and ultimately change agents--in the identification and prevention of nosocomial infections in hospitals. The medical and surgical intensive care units (ICUs) in a large inner-city teaching hospital experienced an increased patient colonization rate with vancomycin-resistant enterococcus (VRE). Intervening in this problem required a multifaceted approach to control the spread of VRE and to change behavior by shifting social norms at multiple levels throughout the ICU community. The success of the interventions could be best explained by applying the use of several behavioral science models. The Ecological Model of Behavior Change, the Health Belief Model, and Social Cognitive Theory can be applied and are consistent with the successful interventions. This multifaceted approach to intervening in this problem consists of five levels of influence: (1) intrapersonal or individual factors, (2) interpersonal factors, (3) institutional factors, (4) community factors, and (5) public factors. We implemented educational inservices and developed references, policies, and programs directed at each of the five levels of influence. The Health Belief Model and Social Cognitive Theory were employed for intervention, and behavior change was based on modeling, observational learning, and vicarious reinforcement. Within six months of initial implementation, the number of positive VRE surveillance cultures and positive clinical isolates decreased significantly in both the medical and surgical ICUs. Two years later, there continues to be a marked reduction of VRE.

Behavior↗
PubMed2000

Prevalence and detection of delirium in elderly emergency department patients.

BACKGROUND: Delirium is a complex medical disorder associated with high morbidity and mortality among elderly patients. The goals of our study were to determine the prevalence of delirium in emergency department (ED) patients aged 65 years and over and to determine the sensitivity and specificity of a conventional clinical assessment by an ED physician for the detection of delirium in the same population. METHODS: All elderly patients presenting to the ED in a primary acute care, university-affiliated hospital who were triaged to the observation room on a stretcher because of the severity of their illness were screened for delirium by a research psychiatrist using the Mini-Mental State Examination and the Confusion Assessment Method. The diagnosis of "delirium" or an equivalent term by the ED physician was determined by 2 methods: completion of a mental status checklist by the ED physician and chart review. The prevalence of delirium and the sensitivity and specificity of the ED physician's clinical assessment were calculated with their 95% confidence intervals. The demographic and clinical characteristics of patients with detected delirium and those with undetected delirium were compared. RESULTS: A sample of 447 patients was screened. The prevalence of delirium was 9.6% (95% confidence interval 6.9%-12.4%). The sensitivity of the detection of delirium by the ED physician was 35.3% and the specificity, 98.5%. Most patients with delirium had neurologic or pulmonary diseases, and most patients with detected delirium had neurologic diseases. INTERPRETATION: Despite the relatively high prevalence of delirium in elderly ED patients, the sensitivity of a conventional clinical assessment for this condition is low. There is a need to improve the detection of delirium by ED physicians.

Age Factors↗
PubMed2000

Identification of members of the genera Panaeolus and Psilocybe by a DNA test. A preliminary test for hallucinogenic fungi.

Abuse of hallucinogens produced by the fungal genera Psilocybe and Panaeolus are a growing problem. Five species from each of the two genera were examined in this preliminary research and a method that will unambiguously identify fungal samples as being of one of these two genera has been developed. The method uses genus specific DNA sequences within the Internal Transcribed Spacer of the ribosomal gene complex. Amplification of a common DNA product and a genus specific product results in two identifiable products, which facilitates the unambiguous identification of material from these two fungi to generic level.

Agaricales↗
PubMed2000

Identification of hallucinogenic fungi from the genera Psilocybe and Panaeolus by amplified fragment length polymorphism.

Unambiguous identification of the hallucinogenic fungi of the genera Psilocybe and Panaeolus is required by national and international drug control legislation. We report on a DNA-based test using the technique of amplified fragment length polymorphism (AFLP). AFLP can differentiate species of the two genera Psilocybe and Panaeolus by using different primer sets. The identification of hallucinogenic fungi using a DNA-based test, which can be used in conjunction with morphological features, will assist in forensic investigations.

Agaricales↗
PubMed2000

Excessive ethanol drinking following a history of dependence: animal model of allostasis.

Alcohol withdrawal symptoms, particularly negative emotional states, can persist for months following the removal of alcohol. These protracted withdrawal symptoms have been implicated as an important trigger of relapse to excessive drinking in alcoholics and may represent a long lasting shift in affective tone as a result of chronic alcohol exposure. It was shown previously that ethanol-dependent rats increased their operant responding for ethanol when tested during the first 12 hr after withdrawal. The purpose of the present experiments was to determine the persistence of this finding by examining operant oral ethanol self-administration in rats with a history of physical dependence upon ethanol, detoxified and then allowed a two week period of protracted abstinence. The results of these experiments indicate that operant responding for ethanol was enhanced during protracted abstinence by 30-100% and remained elevated for 4-8 weeks post acute withdrawal. These results have important implications for understanding the characteristics and mechanisms underlying vulnerability to relapse.

Alcohol Drinking↗
PubMed2000

A long-term study of Rattus norvegicus in the London borough of Enfield using baiting returns as an indicator of sewer population levels.

This is a long-term study that investigates the dynamics of a population of Rattus norvegicus (Berk) inhabiting a sewerage system in London. Thirteen years (1986/7-1998/9) of data from sewer baiting records were analysed (a total of 35,478 records). Manholes were baited with the anticoagulant Brodifacoum (0.005%) on a pinhead oatmeal bait base. Time series analysis was conducted on the data set to determine the underlying trend of the data and the population fluctuations about this trend. An exponential curve was found to give an accurate and realistic fit to the data and indicated that the rat population had decreased over the study period. Decomposition analysis indicated a 5-year cycle best described fluctuations around this trend.

Animals↗
PubMed2000

Tracking cognitive decline in Alzheimer's disease using the mini-mental state examination: a meta-analysis.

OBJECTIVES: To estimate the annual rate of change scores (ARC) on the Mini-Mental State Examination (MMSE) in Alzheimer's disease (AD) and to identify study or population characteristics that may affect the ARC estimation. METHODS: MEDLINE was searched for articles published from January 1981 to November 1997 using the following keywords: AD and longitudinal study or prognosis or cognitive decline. The bibliographies of review articles and relevant papers were searched for additional references. All retrieved articles were screened to meet the following inclusion criteria: (a) original study; (b) addressed cognitive decline or prognosis or course of AD; (c) published in English; (d) study population included AD patients with ascertainable sample size; (e) used either clinical or pathological diagnostic criteria; (f) longitudinal study design; and (g) used the MMSE as one of the outcome measures. Data were systematically abstracted from the included studies, and a random effects regression model was employed to synthesize relevant data across studies and to evaluate the effects of study methodology on ARC estimation and its effect size. RESULTS: Of the 439 studies screened, 43 met all the inclusion criteria. After 6 studies with inadequate or overlapping data were excluded, 37 studies involving 3,492 AD patients followed over an average of 2 years were included in the meta-analysis. The pooled estimate of ARC was 3.3 (95% confidence interval [CI]: 2.9-3.7). The observed variability in ARC across studies could not be explained with the covariates we studied, whereas part of the variability in the effect size of ARC could be explained by the minimum MMSE score at entry and number of assessments. CONCLUSIONS: A pooled average estimate of ARC in AD patients was 3.3 points (95% CI: 2.9-3.7) on the MMSE. Significant heterogeneity of ARC estimates existed across the studies and cannot be explained by the study or population characteristics investigated. Effect size of ARC was related to the initial MMSE score of the study population and the number of assessments.

Aged↗
PubMed2000

Expression and proteolysis of vascular endothelial growth factor is increased in chronic wounds.

Degradation of angiogenic mediators might be an underlying cause of chronic wounds. To test this hypothesis, we evaluated the expression and integrity of vascular endothelial growth factor, a potent angiogenic mediator, and its receptors, Flt-1 and KDR, in chronic venous leg ulcerations. Immunohisto- chemical, in situ hybridization, and semiquantitative reverse transcriptase polymerase chain reaction analyses all indicate that expression of vascular endothelial growth factor is elevated in ulcerative tissue, with vascular endothelial growth factor mRNA being especially pronounced in the hyperplastic epithelium of the wound margin. Flt-1 and KDR protein and mRNA were detected in the papillary vessels in close vicinity to the lesional epithelium of chronic wounds. Although increased expression of vascular endothelial growth factor protein was detected in the epidermis, the intensity of this staining was weak compared with the epidermal staining in psoriatic lesions and compared with the strong vascular endothelial growth factor mRNA signal in chronic wounds and psoriasis. To analyze whether this apparent decrease in immunoreactivity could be the result of degradation of vascular endothelial growth factor by proteolytic activities from the wound environment, we examined the stability of recombinant vascular endothelial growth factor in wound fluid from chronic leg ulcers. As demonstrated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, incubation of rVEGF165 with chronic, but not acute, wound fluid resulted in rapid proteolytic degradation of rVEGF165. Protease inhibitor studies indicate that serine proteases, such as plasmin, are involved in this degradation. Together, our data show that, although vascular endothelial growth factor expression is elevated in chronic wounds, increased proteolytic activity in this environment results in its degradation, which may contribute to an impaired wound healing response.

Chronic Disease↗