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Biomedical subjects

J Atkins

Publications and source records attributed to J Atkins.

At least 19 recordsLinked to original sources
PubMed2004

Phase I study pilot arms of radiotherapy and carmustine with temozolomide for anaplastic astrocytoma (Radiation Therapy Oncology Group 9813): implications for studies testing initial treatment of brain tumors.

PURPOSE: To determine the safety and toxicity of carmustine (BCNU) and temozolomide (TMZ) with radiotherapy (RT) in newly diagnosed anaplastic astrocytoma. METHODS AND MATERIALS: Patients >18 years old with anaplastic astrocytoma, a Karnofsky performance status score of > or =60, and adequate pulmonary function were eligible. All patients provided informed consent. Standard RT started within 5 weeks of diagnosis. In both arms, 150 mg/m(2) of TMZ was given on Days 1-5 of RT. In Arm 1, 200 mg/m(2) of carmustine was given on Day 1 of RT. In Arm 2, 150 mg/m(2) of carmustine was given on Day 5 of RT. After RT, TMZ and carmustine were repeated for a total of six cycles. RESULTS: A total of 15 and 14 patients were enrolled in the two pilot arms. Because of hematologic and pulmonary toxicities, dose reductions by the second cycle of therapy occurred in >70% of the patients in Arm 1 and >50% in Arm 2 despite a reduction in the carmustine dose. CONCLUSION: The results of these pilot studies have implications for the design of studies testing the initial treatment of brain tumors. Because of the poor tolerance of the combination, the multicooperative group Phase III study consists of two randomized arms of single-agent carmustine vs. single-agent TMZ.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Interprofessional education: effects on professional practice and health care outcomes.

BACKGROUND: As patient care becomes more complex, effective collaboration between health and social care professionals is required. However, evidence suggests that these professionals do not collaborate well together. Interprofessional education (IPE) offers a possible way forward in this area. OBJECTIVES: To assess the usefulness of IPE interventions compared to education in which the same professions were learning separately from one another. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialised register, MEDLINE (1968 to 1998) and Cinahl (1982 to 1998). We also hand searched the Journal of Interprofessional Care (1992 to 1998), the Centre for the Advancement of Interprofessional Education Bulletin (1987 to 1998), conference proceedings, the 'grey literature' held by relevant organisations, and reference lists of articles. SELECTION CRITERIA: Randomised trials, controlled before and after studies and interrupted time series studies of IPE interventions designed to improve collaborative practice between health/social care practitioners and/or the health/well being of patients/clients. The participants included chiropodists/podiatrists, complementary therapists, dentists, dietitians, doctors/physicians, hygienists, psychologists, psychotherapists, midwives, nurses, pharmacists, physiotherapists, occupational therapists, radiographers, speech therapists and/or social workers. The outcomes included objectively measured or self reported (validated instrument) patient/client outcomes and reliable (objective or validated subjective) health care process measures. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the eligibility of potentially relevant studies. MAIN RESULTS: The total yield from the search strategy was 1042, of which 89 were retained for further consideration. However none of these studies met the inclusion criteria. REVIEWER'S CONCLUSIONS: Despite finding a large body of literature on the evaluation of IPE, these studies lacked the methodological rigour needed to begin to convincingly understand the impact of IPE on professional practice and/or health care outcomes.

Attitude of Health Personnel↗
PubMed2001

The catalytic domain of human neuropathy target esterase mediates an organophosphate-sensitive ionic conductance across liposome membranes.

In humans and other vertebrates, reaction of organophosphates with a neuronal membrane protein, neuropathy target esterase (NTE), initiates events which culminate in axonal degeneration. The initiation process appears to involve modification of a property of the protein distinct from its esterase activity, subsequent to formation of a negatively charged adduct with the active site serine residue. Here, we show that membrane patches from liposomes containing NEST, a recombinant hydrophobic polypeptide comprising the esterase domain of human NTE, display a transmembrane ionic conductance with both stable and high-frequency flickering components. An asymmetric current-voltage relationship suggested that ion flow was favoured in one direction relative to the membrane and its associated NEST molecules. Flow of anions was slightly favoured compared with cations. The flickering current formed a much larger proportion of the overall conductance in patches containing wild-type NEST compared with the catalytically inactive S966A mutant form of the protein. The conductance across patches containing NEST, but not those with the S966A mutant, was significantly reduced after adding neuropathic organophosphates to the bathing medium. By contrast, non-neuropathic covalent inhibitors of the catalytic activity of NEST did not reduce NEST-mediated conductance. Future work may establish whether NTE itself mediates an organophosphate-sensitive ion flux across intracellular membranes within intact cells.

Carboxylic Ester Hydrolases↗
PubMed2001

Encephalopathy associated with respiratory syncytial virus bronchiolitis.

Respiratory syncytial virus is an extremely common cause of childhood respiratory infections resulting in significant morbidity and mortality. Although apnea is a well-known complication in young infants with respiratory syncytial virus bronchiolitis, the encephalopathy associated with this infection is not well recognized. Our study reveals an incidence of encephalopathy of 1.8% in a total of 487 patients with respiratory syncytial virus bronchiolitis studied over a period of almost 4 years. Seizures were the presenting complication. Based on our study of a cohort of children with respiratory syncytial virus bronchiolitis, we believe that neurologic complications, although relatively uncommon, represent a significant component of this common childhood illness. Furthermore, respiratory syncytial virus has been shown to release several mediators that could directly or indirectly be neurotoxic and induce an encephalopathy associated with the respiratory illness.

Bronchiolitis, Viral↗
PubMed2000

Membrane association of and critical residues in the catalytic domain of human neuropathy target esterase.

Neuropathy target esterase (NTE) is an integral membrane protein in vertebrate neurons and a member of a novel family of putative serine hydrolases. Here we show that NEST, a recombinant polypeptide expressed in Escherichia coli, reacts with an ester substrate and covalent inhibitors in a manner very similar to NTE. NEST comprises residues 727-1216 of human NTE, and site-directed mutagenesis revealed that serine 966 and two aspartate residues, Asp(1086) and Asp(960), are critical for catalysis. The results of mutating the 11 histidines in NEST suggest that NTE does not use a conventional catalytic triad. By reacting NEST with [(3)H]diisopropyl fluorophosphate, Ser(966) was confirmed as the active-site serine, and evidence was obtained that an isopropyl group is transferred from the Ser(966) adduct to an aspartate residue. Detergent was required both for solubilization of NEST from lysates of E. coli and during purification procedures. Catalytic activity was lost in detergent extracts, but was restored when purified NEST was incorporated into dioleoylphosphatidylcholine liposomes. Hydropathy analysis did not indicate the presence of membrane-spanning segments within the NEST sequence. However, biochemical evidence including detergent-phase separation experiments and the resistance of liposome-incorporated NEST to proteolysis indicated that, unlike most eukaryotic serine hydrolases, the catalytic domain of NTE has integral membrane protein properties.

Amino Acid Sequence↗
PubMed1999

Molecular cloning of neuropathy target esterase (NTE).

Covalent modification of NTE, a neuronal protein with serine esterase activity, by certain organophosphates (OP) initiates degeneration of long axons in the peripheral and central nervous system. Simple inhibition of NTE esterase activity does not initiate neuropathy; the latter requires aging of the OP bound to the catalytic serine residue so that a negatively-charged species is left attached to the active site. This may indicate that a non-esterase function of NTE is important for axonal maintenance. We have recently cloned NTE and shown that it is unrelated to any known serine hydrolases but contains a novel C-terminal domain which is conserved from bacteria to man. Furthermore, the catalytic serine is located within this domain at the centre of a helical hydrophobic segment of the polypeptide's secondary structure. The integrity of NTE would be severely compromised by the presence of a negatively-charged organophosphate moiety at this site. Implications for possible higher-order structures and functions for NTE are discussed.

Binding Sites↗
PubMed1999

Characterization of the human endothelial nitric-oxide synthase promoter.

Understanding transcription initiation of the endothelial nitric-oxide synthase (eNOS) gene appears pivotal to gaining a comprehensive view of NO biology in the blood vessel wall. The present study therefore focused upon a detailed dissection of the functionally important cis-DNA elements and the multiprotein complexes implicated in the cooperative control of constitutive expression of the human eNOS gene in vascular endothelium. Two tightly clustered cis-regulatory regions were identified in the proximal enhancer of the TATA-less eNOS promoter using deletion analysis and linker-scanning mutagenesis: positive regulatory domains I (-104/-95 relative to transcription initiation) and II (-144/-115). Analysis of trans-factor binding and functional expression studies revealed a surprising degree of cooperativity and complexity. The nucleoprotein complexes that form upon these regions in endothelial cells contained Ets family members, Sp1, variants of Sp3, MAZ, and YY1. Functional domain studies in Drosophila Schneider cells and endothelial cells revealed examples of positive and negative protein-protein cooperativity involving Sp1, variants of Sp3, Ets-1, Elf-1, and MAZ. Therefore, multiprotein complexes are formed on the activator recognition sites within this 50-base pair region of the human eNOS promoter in vascular endothelium.

Animals↗
PubMed1999

Factors influencing enrollment in clinical trials for cancer treatment.

BACKGROUND: Recruitment of cancer patients to clinical trials is an ongoing challenge. In this study, we assess factors that may influence enrollment in clinical trials for cancer treatment. METHODS: Between June 1997 and January 1998, data were collected on all adult cancer patients evaluated for enrollment in National Cancer Institute-sponsored clinical trials at 15 medical facilities in the southeastern United States. RESULTS: More than 2,300 cancer patients were evaluated; 7% were enrolled. Neither patient sex nor race predicted enrollment. Patients with fee-for-service coverage were more than twice as likely to be enrolled compared with patients with other types of coverage, including managed care. Patient refusal accounted for the nonenrollment of nearly 40% of those clinically eligible. CONCLUSIONS: Although multiple factors influence enrollment in clinical trials for cancer treatment, results suggest that insurance coverage plays a role. Patient refusal, a substantial reason for nonenrollment, points to the need for continued efforts to educate physicians and the public in the value of clinical trials.

Adult↗
PubMed1998

Adjuvant 5-fluorouracil and leucovorin with or without interferon alfa-2a in colon carcinoma: National Surgical Adjuvant Breast and Bowel Project protocol C-05.

BACKGROUND: National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol C-03 showed a benefit from leucovorin (LV)-modulated 5-fluorouracil (5-FU) adjuvant therapy (5-FU + LV) in patients with Dukes' stage B or C carcinoma of the colon. Preclinical and clinical phase I/II data suggested that interferon alfa-2a (IFN) enhanced the efficacy of 5-FU therapy. Accordingly, in NSABP protocol C-05, the addition of recombinant IFN to 5-FU + LV adjuvant therapy was evaluated. METHODS: Data are presented for 2176 patients with Dukes' stage B or C cancer entered onto protocol C-05 during the period from October 1991 through February 1994. Individuals with an Eastern Cooperative Oncology Group performance status of 0-2 (ranges from fully active to ambulatory and capable of self-care but unable to work), a life expectancy of at least 10 years, and curative resection were stratified by sex, disease stage, and number of involved lymph nodes and were randomly assigned to receive either 5-FU + LV or 5-FU + LV + IFN; the mean time on the study as of June 30, 1997, was 54 months. All statistical tests were two-sided. RESULTS: There was no statistically significant difference in either disease-free survival (5-FU + LV, 69%; 5-FU + LV + IFN, 70%) or overall survival (5-FU + LV, 80%; 5-FU + LV + IFN, 81%) at 4 years of follow-up. Toxic effects of grade 3 or higher were observed in 61.8% of subjects in the group treated with 5-FU + LV and in 72.1% of subjects in the group treated with 5-FU + LV + IFN; fewer patients in the latter group completed protocol-mandated 5-FU + LV therapy than in the former group (77.1% versus 88.5%). CONCLUSION: The addition of IFN to 5-FU + LV adjuvant therapy confers no statistically significant benefit, but it does increase toxicity.

Antimetabolites, Antineoplastic↗
PubMed1998

Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study.

BACKGROUND: The finding of a decrease in contralateral breast cancer incidence following tamoxifen administration for adjuvant therapy led to the concept that the drug might play a role in breast cancer prevention. To test this hypothesis, the National Surgical Adjuvant Breast and Bowel Project initiated the Breast Cancer Prevention Trial (P-1) in 1992. METHODS: Women (N=13388) at increased risk for breast cancer because they 1) were 60 years of age or older, 2) were 35-59 years of age with a 5-year predicted risk for breast cancer of at least 1.66%, or 3) had a history of lobular carcinoma in situ were randomly assigned to receive placebo (n=6707) or 20 mg/day tamoxifen (n=6681) for 5 years. Gail's algorithm, based on a multivariate logistic regression model using combinations of risk factors, was used to estimate the probability (risk) of occurrence of breast cancer over time. RESULTS: Tamoxifen reduced the risk of invasive breast cancer by 49% (two-sided P<.00001), with cumulative incidence through 69 months of follow-up of 43.4 versus 22.0 per 1000 women in the placebo and tamoxifen groups, respectively. The decreased risk occurred in women aged 49 years or younger (44%), 50-59 years (51%), and 60 years or older (55%); risk was also reduced in women with a history of lobular carcinoma in situ (56%) or atypical hyperplasia (86%) and in those with any category of predicted 5-year risk. Tamoxifen reduced the risk of noninvasive breast cancer by 50% (two-sided P<.002). Tamoxifen reduced the occurrence of estrogen receptor-positive tumors by 69%, but no difference in the occurrence of estrogen receptor-negative tumors was seen. Tamoxifen administration did not alter the average annual rate of ischemic heart disease; however, a reduction in hip, radius (Colles'), and spine fractures was observed. The rate of endometrial cancer was increased in the tamoxifen group (risk ratio = 2.53; 95% confidence interval = 1.35-4.97); this increased risk occurred predominantly in women aged 50 years or older. All endometrial cancers in the tamoxifen group were stage I (localized disease); no endometrial cancer deaths have occurred in this group. No liver cancers or increase in colon, rectal, ovarian, or other tumors was observed in the tamoxifen group. The rates of stroke, pulmonary embolism, and deep-vein thrombosis were elevated in the tamoxifen group; these events occurred more frequently in women aged 50 years or older. CONCLUSIONS: Tamoxifen decreases the incidence of invasive and noninvasive breast cancer. Despite side effects resulting from administration of tamoxifen, its use as a breast cancer preventive agent is appropriate in many women at increased risk for the disease.

Adult↗
PubMed1996

Doctors leaving the training grades in obstetrics and gynaecology: a study of the years 1985 to 1988.

OBJECTIVES: To determine the numbers of doctors leaving the specialty after obtaining the Membership of the Royal College of Obstetricians and Gynaecologists (MRCOG), and the factors influencing their decisions to seek alternative career paths. DESIGN: Retrospective postal questionnaire based survey. PARTICIPANTS: One hundred and sixty-eight doctors who had passed the MRCOG examination between 1985 and 1988 but were not known to have achieved Consultant or Senior Registrar status in the British Isles by 1993. RESULTS: The response rate was 80%. The crude leaving rate was 31%, although 7.5% had never intended to seek consultant appointment in the specialty in the UK. The majority left shortly after obtaining the Part 2 MRCOG examination, 75% within the first two years thereafter. The perception of the lifestyle of a consultant and poor job prospects were commonly seen as the critical factors causing trainees of both sexes to leave the specialty, although hours of work was the single most commonly cited factor among female trainees. CONCLUSIONS: A consistently high rate of loss from the specialty of obstetrics and gynaecology has been demonstrated in surveys covering the period 1978 to 1988. Approximately one-quarter of this loss reflects trainees who had never intended to pursue consultant appointment in the specialty in the British Isles, half reflects factors which may improve with the implementation of the recommendations contained in the New Deal and the 'Calman' report, and one-quarter reflects loss for inevitable reasons. Loss of trainees for these reasons is therefore a crucial element in manpower calculations.

Career Mobility↗
PubMed1996

Rehabilitation of the shoulder.

Rehabilitation of the shoulder has undergone significant changes during the past few years due to many clinical and basic science projects that have taught us about biomechanics of the shoulder. The athlete's shoulder is a particularly good model to allow us an understanding related to rehabilitation for treatment of injuries, injury prevention and performance enhancement. A comprehensive rehabilitation program for athletes can be based on these clinical and basic science principles to aid in our understanding of rehabilitation for shoulders in general.

Athletic Injuries↗
PubMed1993

Rehabilitation for the overhead athlete.

Rehabilitation of the shoulder of the overhead athlete has undergone significant changes during the past few years. This article illustrates shoulder problems related to repetitive overhead activities, such as throwing. Additionally, we present basic science contributions in this area, principles of shoulder rehabilitation, and a comprehensive rehabilitation program for the symptomatic or asymptomatic athlete based on these principles.

Adult↗
PubMed1993

External rhinoplasty. Comparison of two approaches.

This paper compares two different techniques of external rhinoplasty, in which the lower lateral cartilages are either elevated with the columellar skin (i.e., Gillies-Meyer approach) or left attached to the main body of the nose (i.e., Rethi-Sercer approach). Both techniques give good access and exposure, but we found the Gillies-Meyer approach somewhat easier to perform. It can also be used to provide extended access if difficulty is experienced during a closed rhinoplasty operation.

Humans↗
PubMed1991

Facial nerve monitoring in acoustic tumor surgery.

Anatomic and functional preservation of the facial nerve during acoustic tumor surgery remains a primary goal. Intraoperative electromyographic facial nerve monitoring with auditory feedback has enabled the surgeon to more readily achieve this goal. We compared a group of monitored translabyrinthine acoustic tumor removals (N = 89) to a similar unmonitored group (N = 155) in regard to facial nerve function. Function was assessed immediately postoperatively, at time of discharge, and at 1 year postoperatively using the House six-point scale. Results were grouped as satisfactory, intermediate, or poor and were analyzed by tumor size. Facial nerve results were better at all time intervals in the monitored groups, although the difference was not statistically significant at the 1-year interval. There was no difference between monitored and unmonitored patients in the subgroups with tumors smaller than 2.5 cm in diameter. This study supports the usefulness of intraoperative facial nerve monitoring in improving facial nerve results, particularly in larger tumors.

Adult↗