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Biomedical subjects

M Sullivan

Publications and source records attributed to M Sullivan.

At least 145 records · Page 8Linked to original sources
PubMed1997

Prospective, longitudinal quality-of-life study of patients with head and neck cancer: a feasibility study including the EORTC QLQ-C30.

Despite modern advances in the treatment of head and neck cancer, the survival rate fails to improve. Considering the different treatment modalities involved, quality of life has been thought of as an additional end point criterion for use in clinical trials. A Nordic protocol to measure the quality of life of head and neck cancer patients before, during, and after treatment was established. Before the study, a pilot study was done with this protocol. The main purpose of this pilot study was to find out whether this cancer population would answer quality-of-life questionnaires repeatedly (six times) over a 1-year period and whether the chosen questionnaires-a core questionnaire (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30)), a tumor-specific questionnaire, and a psychological distress measure (Hospital Anxiety and Depression scale (HAD))-were sensitive for changes to functions and symptoms during the study year. The results presented in this article all refer to the pilot study. Forty-eight consecutive patients agreed to participate in the study. The most common tumor locations were the oral cavity (17) and the larynx (12). Almost all patients received combined treatment: 45 of 48 radiation therapy, 18 of 48 chemotherapy, and 17 of 48 surgery. After the primary treatment, 40 patients had complete tumor remission. Four of the 48 patients did not answer any questionnaires and were therefore excluded from the study. Of the remaining 44 patients, 3 died during the study year, and another 6 withdrew for various reasons. Thirty-five (85%) of the 41 patients alive at the 1-year follow-up answered all six questionnaires and thus completed the study. Mailed questionnaires were used throughout the study. All questionnaires were well accepted and found to be sensitive to changes during the study year. The greatest variability was found for symptoms and functions related specifically to head and neck cancer. The symptoms were swallowing difficulties, hoarse voice, sore mouth, dry mouth, and problems with taste. They all showed the same pattern, with an increase of symptoms during and just after finishing the treatment. The HAD scale revealed a high level of psychological distress, with 21% probable cases of psychiatric morbidity at diagnosis. In conclusion, it was shown that the study design and questionnaires were feasible for the forthcoming prospective quality-of-life assessment of Swedish and Norwegian head and neck cancer patients.

Adult↗
PubMed1997

A prospective quality of life study of patients with oral or pharyngeal carcinoma treated with external beam irradiation with or without brachytherapy.

The aim of this longitudinal quality of life (QL) study, was to study tumour-related symptoms and treatment side-effects of patients with oral or oropharyngeal cancer and to determine whether an increased local dose of irradiation (brachytherapy affected QL. The European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30), a tumour-specific Head and Neck questionnaire and the Hospital Anxiety and Depression scale (HAD) were used repeatedly during 1 year. There were 105 patients, with a cumulative response rate of 89%. Most symptoms and problems were at their peak 2 or 3 months after the start of treatment. Nutrition and pain were found to be the major problems, and as many as 19-40% reported psychiatric distress. Patients having received additional brachytherapy did not report any increase in QL problems (except for pain) compared with those having had external radiation only. Quality of life does not seem to be affected by the increased irradiation local dose given when brachytherapy is included in the treatment regimen.

Adult↗
PubMed1997

Spinal cord injuries: a shortened measure of function and mood.

A brief quality-of-life (QL) questionnaire was derived empirically from a cross-sectional study of 98 SCI-patients (83% men, median age 33.5 years, and median time after injury 2.3 years). A comprehensive general battery of well-established questionnaires (Sickness Impact Profile (SIP), Mood Adjective Check List (MACL), and Hospital Anxiety and Depression (HAD) scale) was combined with a study-specific set of questions to constitute patients' QL. A stepwise analysis model was used to define key areas and questions to be included in a brief SCI-adapted questionnaire. The central areas that independently mattered for SCI-patients' perception of good QL included mental health (no depressive feelings), physical and psychosocial dysfunction (no, or few and minor, limitations in mobility, body care and movement and social interaction), and SCI-related problems (no or little perceived difficulty with loss of independence due to injury). A 22-item questionnaire is suggested for routine clinical follow-up to assess more accurately when optimal treatment and services have been delivered.

Activities of Daily Living↗
PubMed1997

The efficacy of selective serotonin reuptake inhibitors for the management of chronic pain.

OBJECTIVE: To assess the effectiveness of selective serotonin reuptake inhibitors (SSRIs) in the management of chronic pain. METHODS: Randomized, controlled trials of SSRIs in the management of chronic pain were identified by searching MEDLINE from 1966 to 1997 and by contacting the manufacturers of SSRIs available in the United States. MAIN RESULTS: Nineteen studies were identified, including 10 on the treatment of headache, 3 on diabetic neuropathy, 3 on fibromyalgia, and 3 on mixed-chronic pain. SSRIs were consistently helpful for mixed-chronic pain. Results were conflicting for migraine headache, tension headache, diabetic neuropathy, and fibromyalgia. CONCLUSIONS: SSRIs appear to be beneficial for mixed-chronic pain. It is unclear, from the available evidence, whether SSRIs are beneficial for migraine headaches, tension headaches, diabetic neuropathy, or fibromyalgia. For those patients it may be reasonable to reserve SSRIs for those who fall to respond to other medications or who are intolerant of their side effects.

Chronic Disease↗
PubMed1997

The Balmain Hospital General Practice Casualty: an alternative model of primary health care provision.

The Balmain Hospital General Practice Casualty is a unique casualty style service, staffed and run by local general practitioners. It is a joint initiative of the Central Sydney Area Health Service and the Division of General Practice, Central Sydney Area, and is jointly funded by the Area Health Service and the Commonwealth. The casemix seen and type of services provided suggest that the service is intermediate between that provided by general practitioners and that provided by emergency departments. The service is well accepted by patients and local general practitioners. A number of benefits are seen by both service providers and users in terms of continuity of care and increased general practitioner skills.

Budgets↗
PubMed1997

Cognition and social functioning in schizophrenia.

This article reviews three studies investigating the relationship between information processing and social functioning in schizophrenia. The most consistent finding is the association between vigilance performance on a hybrid continuous performance/span of apprehension task and various indices of social functioning (e.g., ward behavior). However, the nature of the information processing-social functioning relationships is mutable and appears dependent on a number of factors (e.g., cross-sectional versus longitudinal designs). This article concludes with a discussion of treatment implications and future research directions.

Adolescent↗
PubMed1997

Doctors, diagnosis, and disability: a disastrous diversion.

Patients and third party payers expect physicians to identify damage or disease as the cause of pain and disability, but often there is no damage or disease that can be identified. The process of disability determination requires physicians to make determinations that cannot be based on medical science and for which they have no specialized training. The combination of pseudodiagnosis and pseudodisability is likely to bankrupt countries that do not recognize this folly and design more productive health and disability systems. Physicians need much more education about human behavior and the highly variable relationships among disease, distress, and disability.

Behavior↗
PubMed1997

Health-related quality of life after epilepsy surgery: a Swedish multicenter study.

PURPOSE: To investigate health-related quality of life (HRQOL) in relation to seizure outcome as part of a multicenter follow-up of epilepsy surgery in Sweden. METHODS: A battery including the SF-36 Health Survey and the Hospital Anxiety and Depression scale (HAD) was distributed to all patients older than 16 years. Mean follow-up time was 4 years (range, 2-13 years) and response rate, 91% (103 of 113 patients). HRQOL data were related to seizure frequency and severity (Chalfont Seizure Severity Scale). RESULTS: Seventy-six percent considered their global health to be better than it was before surgery. Degree of improvement in seizure control correlated with improved satisfaction with health (Spearman's r = 0.44). Higher SF-36 scores (higher HRQOL ratings) correlated with percentage reduction of seizure frequency for all scales and was strongest for perception of general health (Spearman's r = 0.46). When the patients were divided into four categories [A, completely seizure free (n = 29); B, seizure free with aura (n = 18); C, > or =75% reduction in seizure frequency (n = 24); and D, <75% reduction in seizure frequency (n = 32)], a strong positive association was found between higher SF-36 scores (with the exception of physical functioning) and better seizure control. Health-related limitations in role performance differentiated best between the outcome categories. For patients with > or =75% reduction in seizure frequency, low seizure severity correlated with higher HRQOL ratings for scales measuring social function, vitality, and mental health. Depression levels (HAD scale scores) were on average low. Anxiety (HAD) increased significantly from A to D. CONCLUSIONS: HRQOL seems to be scored as a continuum in relation to seizure frequency. Seizure severity measures give complementary information.

Adaptation, Psychological↗
PubMed1997

Radiographic abnormalities in canine multicentric lymphoma: a review of 84 cases.

The thoracic and abdominal radiographs of 84 dogs with multicentric lymphoma were examined to identify the radiological abnormalities. The frequency of occurrence of individual changes, role of radiography in diagnosis, relationship of radiographic changes to hypercalcaemia and prognostic relevance of radiographic findings were assessed. Multiple abnormalities were more commonly seen than solitary changes. No radiographic abnormalities were seen in approximately one quarter of thoracic radiographs and one fifth of abdominal radiographs. Lymphoma could not be diagnosed on the basis of radiographs alone. Many of the features of lymphoma were non-specific, having numerous possible causes. Cranial mediastinal disease was neither a prerequisite for, nor a disproportionately common finding in, hypercalcaemic patients. The absence of radiological abnormalities may be a positive prognostic indicator for the individual patient. The differential diagnoses for the radiographic abnormalities seen in lymphoma are discussed.

Abdomen↗
PubMed1997

Protein model representation and construction.

Crystallographic studies play a major role in current efforts towards protein structure determination. However, despite recent advances in computational tools for molecular modeling and graphics, the task of constructing a protein model from crystallographic data remains complex and time-consuming, requiring extensive expert intervention. This paper describes an approach to automating the process of model construction, where a model is represented as an annotated trace (or partial trace) of the three-dimensional backbone of the structure. Potential models are generated using an evolutionary algorithm, which incorporates multiple fitness functions tailored to different structural levels in the protein. Preliminary experimental results, which demonstrate the viability of the approach, are reported.

Algorithms↗
PubMed1997

Pain and the choice to hasten death in patients with painful metastatic cancer.

Unrelieved pain has been cited as an important reason why cancer patients may seek to hasten their deaths. We interviewed 48 patients with painful metastatic cancer to ascertain their interest in various active and passive modes of hastening death. Ninety percent of these patients supported the general right of terminally ill patients to passive modes of hastening death and 80% supported the right to active modes such as assisted suicide and euthanasia. If they developed severe pain that could not be relieved, 80% would instruct their physician write a "do not attempt resuscitation" order, 40%-50% would want to receive suicide information or a lethal prescription from their physician, and 34% would request a lethal injection from their physician. Current pain and depression levels were not associated with interest in hastening death, but current somatic symptom burden was significantly associated with this interest.

Adult↗
PubMed1996

The human cyclic AMP-specific phosphodiesterase PDE-46 (HSPDE4A4B) expressed in transfected COS7 cells occurs as both particulate and cytosolic species that exhibit distinct kinetics of inhibition by the antidepressant rolipram.

Transfection of COS7 cells with a plasmid encoding the human cyclic AMP-specific PDE4A phosphodiesterase PDE-46 (HSPDE4A4B) led to the expression of a rolipram-inhibited PDE4 activity, which contributed approximately 96% of the total COS cell PDE activity. A fusion protein was generated which encompassed residues (788-886) at the extreme C terminus of PDE-46 and was used to generate an antiserum that detected PDE-46 in transfected COS7 cells. Immunoblotting studies identified PDE-46 as a approximately 125-kDa species that was associated with both the soluble and particulate fractions. The relative Vmax of particulate PDE-46 was approximately 56% that of cytosolic PDE-46. Particulate PDE-46 was not solubilized using Triton X-100 or high NaCl concentrations. Immunofluorescence analysis by laser scanning confocal microscopy showed that PDE-46 was located at discrete margins of the cell, indicative of association with membrane cortical regions. The human PDE4A species, h6.1 (HSPDE4A4C), which lacks the N-terminal extension of PDE-46, was found as an entirely soluble species when expressed in COS7 cells. h6.1 was shown to have an approximately 11-fold higher Vmax relative to that of PDE-46. In dose-response studies rolipram inhibited particulate PDE-46 at much lower concentrations (IC50 = 0. 195 microM) than those needed to inhibit the cytosolic enzyme (IC50 = 1.6 microM). The basis of this difference lay in the fact that rolipram served as a simple competitive inhibitor of the cytosol enzyme (Ki = 1.6 microM) but as a partial competitive inhibitor of the particulate enzyme (Ki = 0.037 microM; Ki' = 2.3 microM). Particulate PDE-46 thus showed a approximately 60-fold higher affinity for rolipram than cytosolic PDE-46.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Comparison of circumsporozoite proteins from avian and mammalian malarias: biological and phylogenetic implications.

The circumsporozoite (CS) protein of malaria parasites (Plasmodium) covers the surface of sporozoites that invade hepatocytes in mammalian hosts and macrophages in avian hosts. CS genes have been characterized from many Plasmodium that infect mammals; two domains of the corresponding proteins, identified initially by their conservation (region I and region II), have been implicated in binding to hepatocytes. The CS gene from the avian parasite Plasmodium gallinaceum was characterized to compare these functional domains to those of mammalian Plasmodium and for the study of Plasmodium evolution. The P. gallinaceum protein has the characteristics of CS proteins, including a secretory signal sequence, central repeat region, regions of charged amino acids, and an anchor sequence. Comparison with CS signal sequences reveals four distinct groupings, with P. gallinaceum most closely related to the human malaria Plasmodium falciparum. The 5-amino acid sequence designated region I, which is identical in all mammalian CS and implicated in hepatocyte invasion, is different in the avian protein. The P. gallinaceum repeat region consists of 9-amino acid repeats with the consensus sequence QP(A/V)GGNGG(A/V). The conserved motif designated region II-plus, which is associated with targeting the invasion of liver cells, is also conserved in the avian protein. Phylogenetic analysis of the aligned Plasmodium CS sequences yields a tree with a topology similar to the one obtained using sequence data from the small subunit rRNA gene. The phylogeny using the CS gene supports the proposal that the human malaria P. falciparum is significantly more related to avian parasites than to other parasites infecting mammals, although the biology of sporozoite invasion is different between the avian and mammalian species.

Amino Acid Sequence↗
PubMed1996

Global mapping of structural solutions provided by the extended X-ray absorption fine structure ab initio code FEFF 6.01: structure of the cryogenic photoproduct of the myoglobin-carbon monoxide complex.

X-ray methods based on synchrotron technology have the promise of providing time-resolved structural data based on the high flux and brightness of the X-ray beams. One of the most closely examined problems in this area of time-resolved structure determination has been the examination of intermediates in ligand binding to myoglobin. Recent crystallographic experiments using synchrotron radiation have identified the protein tertiary and heme structural changes that occur upon photolysis of the myoglobin--carbon monoxide complex at cryogenic temperatures [Schlichting, I., Berendzen, J., Phillips, G., & Sweet, R. (1994) Nature 371, 808--812]. However, the precision of protein crystallographic data (approximately 0.2 A) is insufficient to provide precise metrical details of the iron--ligand bond lengths. Since bond length changes on this scale can trigger reactivity changes of several orders of magnitude, such detail is critical to a full understanding of metalloprotein structure--function relationships. Extended X-ray absorption fine structure (EXAFS) spectroscopy has the potential for analyzing bond distances to a precision of 0.02 A but is hampered by its relative insensitivity to the geometry of the backscattering atoms. Thus, it is often unable to provide a unique solution to the structure without ancillary structural information. We have developed a suite of computer programs that incorporate this ancillary structural information and compute the expected experimental spectra for a wide ranging series of Cartesian coordinate sets (global mapping). The programs systematically increment the distance of the metal to various coordinating ligands (along with their associated higher shells). Then, utilizing the ab initio EXAFS code FEFF 6.01, simulated spectra are generated and compared to the actual experimental spectra, and the differences are computed. Finally, the results for hundreds of simulations can be displayed (and compared) in a single plot. The power of this approach is demonstrated in the examination of high signal to noise EXAFS data from a photolyzed solution sample of the myoglobin--carbon monoxide complex at 10 K. Evaluation of these data using our global mapping procedures placed the iron to pyrrole nitrogen average distances close to the value for deoxymyoglobin (2.05 +/- 0.01 A), while the distance from iron to the proximal histidine nitrogen is seen to be 2.20 +/- 0.04 A. It is also shown that one cannot uniquely position the CO ligand on the basis of the EXAFS data alone, as a number of reasonable minima (from the perspective of the EXAFS) are observed. This provides a reasonable explanation for the multiplicity of solutions that have been previously reported. The results presented here are seen to be in complete agreement with the crystallographic results of Schlichting et al. (1994) within the respective errors of the two techniques; however, the extended X-ray absorption fine structure data allow the iron--ligand bond lengths to be precisely defined. An examination of the available spectroscopic data, including EXAFS, shows that the crystallographic results of Schlichting et al. (1994) are highly relevant to the physiological solution state and must be taken into account in any attempt to understand the incomplete relaxation process of the heme iron for the Mb*CO photoproduct at low temperature.

Animals↗
PubMed1996

The relationship of social cognition to ward behavior in chronic schizophrenia.

The relationship between social cognition (i.e., cognition for social stimuli) and ward behavior among individuals with chronic schizophrenia was investigated. Twenty-seven inpatients completed a battery of cognitive and social-cognitive tasks and were rated by staff on various indices of ward behavior. Overall, there was a relationship between the measures of social cognition and behavior on the ward. Social cognition contributed unique variance beyond cognition to maladaptive behavior on the ward (i.e., irritability). Implications for assessment and future research are discussed.

Adult↗
PubMed1996

Criterion-based validation of the EORTC QLQ-C36 in advanced melanoma: the CIPS questionnaire and proxy raters.

An extensive quality of life (QOL) investigation of the effects of chemotherapy in patients with generalized malignant melanoma included a validation study of involved questionnaires. The QOL domains of the three basic quality of life questionnaires, the EORTC QLQ-C36 (European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire), a study-specific malignant melanoma (MM) module and the Hospital Anxiety and Depression (HAD) scale vs. the Cancer Inventory of Problem Situations (CIPS) were validated by correlation analyses. The value of using attending nurses and/or next of kin to assess the patients situation was also examined. Functional and symptom scales of the C36 and the subscales of the HAD showed appropriate convergent and discriminant validity when compared with the CIPS. The subscales of the MM module had less clear relationships, probably due to lack of accordance in the CIPS. Assessments of attending nurses revealed very low correlations with the patients' measures. They underestimated significantly series of specific symptoms and overestimated nausea and the overall quality of life of the patients. However, assessments of close relatives, mostly spouses, showed moderate to high correlations and no significant difference. These results further strengthen the overall validity of the modular approach of the EORTC QLQ technique. In this context of active chemotherapy in patients with advanced cancer disease, relatives seem to be better surrogates than the attending nurses in assessing the patients' quality of life.

Activities of Daily Living↗