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Biomedical subjects

J Evans

Publications and source records attributed to J Evans.

At least 91 records · Page 5Linked to original sources

Supported metallocene catalysts by surface organometallic chemistry. Synthesis, characterization, and reactivity in ethylene polymerization of oxide-supported mono- and biscyclopentadienyl zirconium alkyl complexes: establishment of structure/reactivity relationships.

The reactions of CpZr(CH(3))(3), 1, and Cp(2)Zr(CH(3))(2), 2, with partially dehydroxylated silica, silica-alumina, and alumina surfaces have been carried out with careful identification of the resulting surface organometallic complexes in order to probe the relationship between catalyst structure and polymerization activity. The characterization of the supported complexes has been achieved in most cases by in situ infrared spectroscopy, surface microanalysis, qualitative and quantitative analysis of evolved gases during surface reactions with labeled surface, solid state (1)H and (13)C NMR using (13)C-enriched compounds, and EXAFS. 1 and 2 react with silica(500) and silica-alumina(500) by simple protonolysis of one Zr-Me bond by surface silanols with formation of a single well-defined neutral compound. In the case of silica-alumina, a fraction of the supported complexes exhibits some interactions with electronically unsaturated surface aluminum sites. 1 and 2 also react with the hydroxyl groups of gamma-alumina(500), leading to several surface structures. Correlation between EXAFS and (13)C NMR data suggests, in short, two main surface structures having different environments for the methyl group: [Al](3)-OZrCp(CH(3))(2) and [Al](2)-OZrCp(CH(3))(mu-CH(3))-[Al] for the monoCp series and [Al](2)-OZrCp(2)(CH(3)) and [Al]-OZrCp(2)(mu-CH(3))-[Al] for the bisCp series. Ethylene polymerization has been carried out with all the supported complexes under various reaction conditions. Silica-supported catalysts in the absence of any cocatalyst exhibited no activity whatsoever for ethylene polymerization. When the oxide contained Lewis acidic sites, the resulting surface species were active. The activity, although improved by the presence of additional cocatalysts, remained very low by comparison with that of the homogeneous metallocene systems. This trend has been interpreted on the basis of various possible parameters, including the (p-pi)-(d-pi) back-donation of surface oxygen atoms to the zirconium center.

Journal Article↗

An investigation of the molecular basis for the synergistic interaction of tirapazamine and cisplatin.

PURPOSE: To determine if the observed tirapazamine (TPZ)-cisplatin synergistic cell kill was mediated at the cellular level by impairment of upregulation of key proteins involved in repair of DNA interstrand crosslinks. Cisplatin sensitivity has been shown to be dependent on the expression of the two DNA repair proteins ERCC1 and XPA. ERCC1 expression has also been shown to be upregulated by cisplatin exposure. Therefore, these studies were undertaken to determine if hypoxia-activated TPZ pretreatment inhibited the cells' normal protective response to cisplatin via inhibiting the upregulation of ERCC1 and/or XPA expression. METHODS AND MATERIALS: Two different cell lines, one cisplatin sensitive and one cisplatin resistant, were treated with TPZ, cisplatin, both drugs together (which results in additive cytotoxicity), or TPZ followed by cisplatin (which results in synergistic cytotoxicity). All cells were exposed to 1 h of hypoxia to bioactivate the TPZ. Expression of ERCC1 and XPA were evaluated at the mRNA and protein level at 24 or 48 h after drug exposure. RESULTS: In the cisplatin-sensitive non-small-cell lung cancer cell line, ERCC1 expression at the mRNA or protein level was not significantly altered in any of the treatment groups. In the cisplatin-resistant ovarian cancer cell line, ERCC1 expression was upregulated by TPZ, but not by cisplatin alone. The change in protein expression was less pronounced than the change in mRNA level. XPA expression was not significantly changed from baseline in either cell line at the mRNA or protein level. CONCLUSION: In contrast to reports in the literature, this study did not demonstrate cisplatin inducing its own repair by upregulating the DNA crosslink repair proteins ERCC1 or XPA. Therefore, the TPZ-cisplatin synergism cannot be mediated through hypoxia-activated TPZ inhibiting this cellular protective response. TPZ alone, however, was able to alter repair protein expression, which may play a role in mediating its cytotoxicity.

Antineoplastic Agents↗

Theoretical perspectives on language and communication problems in mental retardation and developmental disabilities.

We argue that researchers interested in language and communication problems in mental retardation or any other developmental disorder should view such problems as emerging within the broader context of the behavioral profile, or phenotype, associated with a particular genetic condition. This will require understanding the direct and indirect effects of genes on the development of language and communication and thereby an understanding of the complex relations that exist between language and other dimensions of psychological and behavioral functioning as well as an understanding of the environments in which the developing person acts and is acted upon. We believe that the dominant model for understanding language and communication problems--the nativist approach, which emphasizes the child's innate capacity for acquiring language and characterizes language as consisting of a set of context-free deterministic rules that operate on abstract representations--is inconsistent with an emphasis on indirect genetic effects. We review recent evidence that undermines the nativist approach--evidence concerning the initial state of the language-learning child, the role of environmental input, the competence-performance distinction, and modularity. In place of nativism, we argue for Emergentism, which is a model in which language is seen to emerge from the interaction between the child's biological abilities to map statistical properties of the language input into a distributed representation and the characteristics of the language learning environment and for the purpose of engaging in real-time, meaningful language use.

Child↗

Glyceryl trinitrate vs. lateral sphincterotomy for chronic anal fissure: prospective, randomized trial.

INTRODUCTION: Glyceryl trinitrate has been shown to be an effective treatment for chronic anal fissure. It decreases anal tone and ultimately heals anal fissures. The aim of this trial was to compare glyceryl trinitrate with lateral sphincterotomy (current standard treatment) as definitive management for chronic anal fissure. METHODS: All patients with symptoms of chronic anal fissure were randomly assigned to one of two treatment arms. The glyceryl trinitrate group applied 0.2 percent paste to the perianal area three times a day for eight weeks. Patients in the lateral sphincterotomy group underwent surgery on the next available operating list. Patients were reviewed at two weekly intervals until the fissure healed. RESULTS: Sixty-five patients were enrolled in the trial, with 31 in the lateral sphincterotomy group and 34 in the glyceryl trinitrate group. Five patients were excluded after randomization. Twenty of 33 (60.6 percent) glyceryl trinitrate patients had healed fissures in eight weeks compared with 26 of 27 (97 percent) in the sphincterotomy group (P = 0.001). Twelve patients in the glyceryl trinitrate group had little improvement in their symptoms and underwent lateral sphincterotomy. Poor tolerance and poor compliance with treatment were important factors in patients whose fissures did not heal with glyceryl trinitrate. Fissures healed significantly faster after sphincterotomy compared with glyceryl trinitrate treatment (P = 0.0001). Nine of the 20 patients whose fissures healed with glyceryl trinitrate paste subsequently had a recurrence of their fissures. There were no long-term complications from lateral sphincterotomy. CONCLUSION: Glyceryl trinitrate paste heals the majority of chronic anal fissures. However, a significant minority have little improvement or develop side effects and require conventional surgical treatment. Poor compliance with prescribed treatment often contributes to nonhealing. In addition, some fissures which initially heal with glyceryl trinitrate paste recur and require further treatment. Glyceryl trinitrate treatment is labor intensive for patients and physicians and has not been shown to be superior to lateral sphincterotomy.

Administration, Topical↗

Characterisation of strains of enteroaggregative Escherichia coli isolated during the infectious intestinal disease study in England.

Strains of Escherichia coli, hybridising with a DNA probe for enteroaggregative E. coli (EAggEC), were isolated from patients with infectious intestinal disease (IID) or gastro-enteritis, and healthy controls during the study of IID in England. Of 3506 cases presenting with an IID, 160 (4.6%) had faecal EAggEC as compared with 46 (1.7%) of 2772 healthy controls, 53% of EAggEC isolated from each of the 'case' and the 'control' groups adhered in a 'stacked-brick' formation. Strains from cases and controls belonged to over 39 and 14 different serogroups respectively, and approximately half of the strains isolated did not react with antisera in the current somatic antigen serotyping scheme. Forty-nine cases with EAggEC (31%) had a known history of foreign travel. Over 50% of strains isolated from cases and controls were resistant to one or more of eight antimicrobials, and antimicrobial resistance was not statistically significantly more common among cases with a known history of foreign travel (p = 0.57). These data form part of the largest investigation carried out on these organisms in the UK to date and provide the most comprehensive analysis of strains of EAggEC isolated from the general population of England.

Case-Control Studies↗

Significance of histologic patterns of glomerular injury upon long-term prognosis in severe lupus glomerulonephritis.

BACKGROUND: Patients with systemic lupus erythematosus have a spectrum of glomerular disease, but the different patterns of glomerular injury identified within the general category of "severe" lupus glomerulonephritis are responsible for much of the morbidity and mortality in this disease. The glomerular injury patterns seen with severe lupus glomerulonephritis have been separated into distinct histopathologic groups to determine whether they can predict long-term patient outcome. METHODS: We analyzed the clinical follow-up of 85 patients participating in a controlled prospective therapeutic trial for the treatment of severe lupus glomerulonephritis conducted from April 1981 to December 1988, with an average follow-up of 10 years. Patients were classified according to the 1982 World Health Organization classification for lupus glomerulonephritis. RESULTS: During the course of follow-up [120 +/- 65 (SD) months], 60% of patients with category IV (diffuse proliferative glomerulonephritis) lesions entered a remission compared with only 38% of patients with category III (> or =50%, focal and segmental glomerulonephritis) lesions and 27% of patients with category Vc (> or =50%) and Vd (P < 0.05). Renal survival at 10 years was 75% for those with category IV lesions, 47% for patients with category Vc (> or =50%) and Vd, and 52% for patients with category III (> or =50%) lesions (P < 0.05). Based on multivariate analysis, patients with category III (> or =50%) or Vc (> or =50%) and Vd lesions had a relative risk of progression to end-stage renal disease 2.9 times that of category IV patients (P < 0.01), while the likelihood of entering a remission was 8.2 times greater for category IV patients (P = 0.0001). CONCLUSION: The histopathologic categorization among patients with severe lupus glomerulonephritis provides information relevant to their long-term outcome.

Adult↗

Effectiveness of beta-glucan collagen for treatment of partial-thickness burns in children.

BACKGROUND/PURPOSE: Beta glucan collagen matrix (BGC), which combines the carbohydrate beta-glucan with collagen, has been used as a temporary coverage for adult partial thickness burns with reported good results. Observed advantages of BGC coverage include reduction of pain, improved healing, and better scar appearance. Potentially even more important in children is the elimination of painful daily dressing changes to the burned epithelial surface, as well as decreased fluid loss. This report details the authors' 2-year experience with BGC in a pediatric burn center. METHODS: Retrospective chart review of 225 consecutive pediatric patients treated at our institution between 1997 and 1999 identified 43 patients (19%) with suspected partial thickness burns treated with BGC as the primary wound dressing. BGC was applied to a debrided burn wound and secured with steri-strips, kerlix, and an ace wrap. After 24 hours, adherence of the BGC was confirmed and then left open to air. RESULTS: The most common cause of burn injury was scald (61%), followed by flame (37%), and contact (2%). The average age of patients was 5.5 years (range, 6 weeks to 16 years) and mean percent total body surface area burned was 9.3% (1% to 35%). Thirty-four patients (79%) had the BGC remain intact while the wound healed underneath, with excellent cosmetic results, minimal analgesic requirements, and no need for repetitive dressing changes. Nine patients (21%) had the BGC removed before wound healing: 6 patients lost the BGC because of progression of the burn to full thickness, 2 had BGC nonadherence over a joint, and 1 had an unexplained nonadherence. CONCLUSIONS: Partial-thickness burns in children can be effectively treated with BGC with good results, even in infants and toddlers. BGC markedly simplifies wound care for the patient and family and seems to significantly decrease postinjury pain.

Bandages↗

Self-expanding metal esophageal stent with anti-reflux mechanism.

BACKGROUND: When deployed across the gastroesophageal junction, self-expanding metal esophageal stents can predispose to gastroesophageal reflux. Our aim was to evaluate the efficacy of a self-expanding metal esophageal stent that was modified to prevent gastroesophageal reflux. METHODS: The polyurethane coating of a metal Z-stent was extended beyond its lower end to form windsock-type valve. The anti-reflux property of this stent was studied in vitro by submerging the stent under water and measuring the pressure required to invert the valve. Esophageal acid exposure time was measured in 5 dogs with a standard and the modified stent placed across the gastroesophageal junction. The modified stent was also placed in 11 patients with cancer of the gastroesophageal junction who were prospectively followed. RESULTS: The pressure required to invert the valve was directly proportional to the thickness of the valve membrane (48 +/- 0.4 cm water for a 0.0067-inch thick membrane). Esophageal acid exposure time was significantly less with the modified stent as compared with a standard stent (1% +/- 0.3%, 49% +/- 11%, respectively, p = 0.03). Dysphagia score in patients improved from 3.4 +/- 0.1 to 1.1 +/- 0.2 (p < 0.001). Daytime heartburn and regurgitation scores were less than 1 (score 10 = severe). No patient complained of nocturnal reflux symptoms. Karnofsky performance status scale did not improve significantly. CONCLUSIONS: The efficacy of the modified stent in relieving dysphagia is comparable with a standard stent. It also effectively prevents gastroesophageal reflux.

Aged↗

Comparison of pocket-computer memory aids for people with brain injury.

Two styles of pocket computer memory aid were compared as support for people who had sustained non-progressive, closed-head brain injury. A purpose-designed interface provided a diary with auditory alarms, a notebook and links between diary entries and specific notepages. One computer had a physical keyboard, the other did not. Twelve adult volunteers were loaned each computer for 2 months, with a 1 month gap between, in counterbalanced order. It was found that all participants could use the memory aids, and most (83%) found them useful. Little customizing was needed, but amount of use varied widely. Predictors of usage included use of other reminding systems before joining the project, and speed in calculator addition which may reflect working memory. High users preferred the computer with a physical keyboard; low users made more entries with the palm-size computer. These data highlight the need to distinguish ability to use from willingness to use.

Activities of Daily Living↗

Retirement intentions of doctors who qualified in the United Kingdom in 1974: postal questionnaire survey.

BACKGROUND: Medical workforce planning needs to be informed by knowledge about doctors' retirement intentions. Systematic information about retirement intentions, and factors that influence them, is sparse. METHODS: Postal questionnaires were sent to members of a cohort of medical qualifiers surveyed regularly since they qualified in 1974, with quantitative analysis of intentions about early retirement and qualitative analysis of reasons for wanting early retirement. RESULTS: A total of 1717 replies were received from 2217 traceable doctors (77.4 per cent). Of these, 1427 doctors worked in the NHS and answered the question about retirement: 14.8 per cent (211) said that they would definitely continue to normal retirement age and 20.1 per cent (287) probably would. Of those not definitely continuing to normal retirement age, 45.1 per cent had made financial provision to support early retirement, Seventy per cent cited reasons for considering early retirement: the main reasons were to reduce work-related pressure, increase leisure time, job dissatisfaction, disillusionment with the NHS, and wanting a healthy retirement. Doctors might be encouraged to stay by more flexible working patterns, a reduction in workload with increasing age, improved staffing levels, preservation of pension rights for part-time working, fewer NHS administrative changes, and greater professional freedom. CONCLUSION: The impact of early retirement on medical workforce supply may be considerable. Approaches to retirement policy need to shift away from the extremes of either full-time employment or total retirement.

Attitude of Health Personnel↗

Lyme disease.

Lyme disease is the most common tick-borne disease in the United States, and the number of reported cases has increased steadily since 1992. Coinfection of ticks with Borrelia burgdorferi and Ehrlichia phagocytophila did not appear to affect the transmission of the other agent. Serologic evidence of exposure to Babesia microti did not significantly impact the clinical course of Lyme disease. Two clinical studies indicated that the long-term outcome of Lyme disease is good. Results are pending of chronic Lyme disease studies funded by the US National Institutes of Health. A better understanding of the pathogenesis of Lyme disease provided clues about possible mechanisms for persistent symptoms. Use of the current method of diagnosis by the two-step approach has proven to be reliable, but new methods are under investigation. Treatment guidelines were published recently. OspA vaccination of children aged 2 to 5 years was shown to be safe and immunogenic.

Anti-Bacterial Agents↗

Enhancing an appointment diary on a pocket computer for use by people after brain injury.

People with memory loss resulting from brain injury benefit from purpose-designed memory aids such as appointment diaries on pocket computers. The present study explores the effects of extending the range of memory aids and including games. For 2 months, 12 people who had sustained brain injury were loaned a pocket computer containing three purpose-designed memory aids: diary, notebook and to-do list. A month later they were given another computer with the same memory aids but a different method of text entry (physical keyboard or touch-screen keyboard). Machine order was counterbalanced across participants. Assessment was by interviews during the loan periods, rating scales, performance tests and computer log files. All participants could use the memory aids and ten people (83%) found them very useful. Correlations among the three memory aids were not significant, suggesting individual variation in how they were used. Games did not increase use of the memory aids, nor did loan of the preferred pocket computer (with physical keyboard). Significantly more diary entries were made by people who had previously used other memory aids, suggesting that a better understanding of how to use a range of memory aids could benefit some people with brain injury.

Appointments and Schedules↗

Neurocognitive correlates of helplessness, hopelessness, and well-being in schizophrenia.

Persons with schizophrenia are widely recognized to experience potent feelings of hopelessness, helplessness, and a fragile sense of well-being. Although these subjective experiences have been linked to positive symptoms, little is known about their relationship to neurocognition. Accordingly, this study examined the relationship of self-reports of hope, self-efficacy, and well-being to measures of neurocognition, symptoms, and coping among 49 persons with schizophrenia or schizoaffective disorder. Results suggest that poorer executive function, verbal memory, and a greater reliance on escape avoidance as a coping mechanism predicted significantly higher levels of hope and well being with multiple regressions accounting for 34% and 20% of the variance (p < .0001), respectively. Self-efficacy predicted lower levels of positive symptoms and greater preference for escape avoidance as a coping mechanism with a multiple repression accounting for 9% of the variance (p < .05). Results may suggest that higher levels of neurocognitive impairment and an avoidant coping style may shield some with schizophrenia from painful subjective experiences. Theoretical and practical implications for rehabilitation are discussed.

Adaptation, Psychological↗

Muscle glycogen supercompensation is enhanced by prior creatine supplementation.

PURPOSE: Recently, it was shown that glycogen supercompensation tended (P = 0.06) to be greater if creatine and glycogen were loaded simultaneously. Because the authors suggested that creatine loading increased cell volumes and, therefore, enhanced glycogen supercompensation, we decided to determine whether an enhanced glycogen supercompensation could be realized if the glycogen loading protocol was preceded by a 5-d creatine load. METHODS: Twelve men (19-28 yr) performed two standard glycogen loading protocols interspersed with a standard creatine load of 20 g.d(-1) for 5 d. The vastus lateralis muscle was biopsied before and after each loading protocol. RESULTS: The initial glycogen loading protocol showed a significant 4% increase (P < 0.05) in muscle glycogen (Delta upward arrow 164 +/- 87 mmol.kg(-1) d.m.), and no change (P > 0.05) in total muscle creatine. Biopsies pre- and post-creatine loading showed significant increases in total muscle creatine levels in both the left leg (Delta upward arrow 41.1 +/- 31.1 mmol.kg(-1) d.m.) and the right leg (Delta upward arrow 36.6 +/- 19.8 mmol.kg(-1) d.m.), with no change in either leg's muscle glycogen content. After the final glycogen loading, a significant 53% increase in muscle glycogen (Delta upward arrow 241 +/- 150 mmol.kg-1 d.m.) was detected. Finally, the postcreatine load total glycogen content (694 +/- 156 mmol.kg(-1) d.m.) was significantly (P < 0.05) greater than the precreatine load total glycogen content (597 +/- 142 mmol.kg(-1) d.m.). CONCLUSION: It is suggested that a muscle's glycogen loading capacity is influenced by its initial levels of creatine and the accompanying alterations in cell volume.

Adult↗

Surgical management of clinoidal meningiomas.

OBJECTIVE: Surgical outcome has been less than desirable in the management of patients with clinoidal meningiomas in the past, and little attention has been directed at improving their visual function. The purpose of this article is to advocate an available cranial base technique for removing these difficult tumors and to delineate the technique's advantages that aid in achieving an improved extent of tumor resection and enhancing the patients' overall outcome, particularly their visual outcome. METHODS: A retrospective analysis was performed on 15 consecutive patients with clinoidal meningiomas (including a patient with hemangiopericytoma) who underwent surgical resection at the Cleveland Clinic Foundation between June 1995 and January 2000. A cranial base technique consisting of extradural anterior clinoidectomy, coupled with optic canal unroofing and optic sheath opening, was used in 13 patients, and standard pterional craniotomy was used in 2. Eight of 15 patients had significant visual deficits preoperatively. All patients had thorough preoperative and postoperative ophthalmological evaluations. The follow-up period ranged from 6 to 60 months (mean, 37.2 mo). RESULTS: Total resection was achieved in 13 (86.7%) of the 15 patients in this series, and the majority of the patients with preoperative visual impairment experienced significant improvement (6 of 8 patients; 75%). CONCLUSION: In the majority of patients with clinoidal meningiomas, total resection may be achieved with minimal complications. For large tumors encasing the optic nerve and internal carotid artery, or for those tumors causing preoperative visual impairment, use of the cranial base technique delineated in this study may lead to significant improvement in the patients' visual and overall outcomes.

Adolescent↗

Controversies in the diagnosis and management of hypotension in the newborn infant.

Although close to half of the newborns admitted to neonatal intensive care units receive treatment for "hypotension," the normal physiologic blood pressure range ensuring appropriate organ perfusion in the neonate is unknown. Thus, the decision to treat hypotension in the newborn is based on statistically defined gestational and postnatal age-dependent normative blood pressure values and physicians' beliefs rather than on data bearing physiologic reference. Dopamine is the most widely used sympathomimetic amine in the treatment of neonatal hypotension, and it is more effective than dobutamine in raising blood pressure. Volume administration is less effective in the immediate postnatal period, and its extensive use is associated with significant untoward effects, especially in preterm infants. During the course of their disease, some of the sickest hypotensive newborns become unresponsive to volume and pressor administration. This phenomenon is caused by the desensitization of the cardiovascular system to catecholamines by the critical illness and relative or absolute adrenal insufficiency. The findings that steroids rapidly up-regulate cardiovascular adrenergic receptor expression and serve as hormone substitution in cases of adrenal insufficiency explain their effectiveness in stabilizing the cardiovascular status and decreasing the requirement for pressor support in the critically ill newborn with volume-and pressor-resistant hypotension. Finally, despite recent advances in our understanding of the pathophysiology and management of neonatal hypotension, there are few data on the impact of the treatment on organ blood flow and tissue perfusion and on neonatal morbidity and mortality.

Blood Pressure↗