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Biomedical subjects

M Sullivan

Publications and source records attributed to M Sullivan.

At least 55 records · Page 3Linked to original sources
PubMed2001

Endometrial bleeding in hormone replacement therapy users: preliminary findings regarding the role of matrix metalloproteinase 9 (MMP-9) and tissue inhibitors of MMPs.

OBJECTIVE: To establish the effect of hormone replacement therapy (HRT) on the expression of matrix metalloproteinase 9 (MMP-9) and the tissue inhibitor of MMPs, TIMP-1, in the endometrium of postmenopausal and perimenopausal women. DESIGN: Prospective observational study. SETTING: United Kingdom teaching hospital. PATIENT(S): Thirty-one perimenopausal and postmenopausal HRT recipients, with a control group of eight postmenopausal women not undergoing HRT. INTERVENTION(S): Prospective record of bleeding patterns and endometrial biopsy. MAIN OUTCOME MEASURE(S): Endometrial histology, bleeding patterns, MMP-9, and TIMP-1 expression. RESULT(S): MMP-9 and TIMP-1 are expressed in benign postmenopausal endometrium. Expression of both molecules is reduced in HRT recipients compared with non-HRT recipients. CONCLUSION(S): Exposure to HRT appears to alter endometrial expression of MMP-9 and TIMP-1 and also the local balance between these molecules. This alteration may promote breakdown of the endometrial extracellular matrix and blood vessels and hence bleeding.

Base Sequence↗
PubMed2001

Do SF-36 summary component scores accurately summarize subscale scores?

Standard scoring algorithms were recently made available for aggregating scores from the eight SF-36 subscales in two distinct, higher-order summary scores: Physical Component Summary (PCS) and Mental Component Summary (MCS). Recent studies have suggested, however, that PCS and MCS scores are not independent and may in part be measuring the same constructs. The aims of this paper were to examine and illustrate (1) relationships between SF-36 subscale and PCS, MCS scores, (2) relationships between PCS and MCS scores, and (3) their implications for interpreting research findings. Simulation analyses were conducted to illustrate the contributions of various aspects of the scoring algorithm to potential discrepancies between subscale profile and summary component scores. Using the Swedish SF-36 normative database, correlation and regression analyses were performed to estimate the relationship between the two components, as well as the relative contributions of the subscales to the components. Discrepancies between subscale profile and component scores were identified and explained. Significant correlations (r = -0.74, -0.67) were found between PCS and MCS scores at their respective upper scoring intervals, indicating that the components are not independent. Regression analyses revealed that in these ranges PCS primarily measures aspects of mental health (57% of variance) and MCS measures physical health (65% of variance). Implications of the findings were discussed. It was concluded that the current PCS MCS scoring procedure inaccurately summarizes subscale profile scores and should therefore be revised. Until then, component scores should be interpreted with caution and only in combination with profile scores.

Adolescent↗
PubMed2001

Symptom control may improve food intake, body composition, and aspects of quality of life after gastrectomy in cancer patients.

That severe malnutrition affects body function and psychological well-being is well documented. We addressed the question of whether quality of life relates to changes in variables such as food intake, body composition, and gastrointestinal symptomatology after gastrectomy for gastric cancer. Thirty-two patients undergoing gastric resection had their dietary intake, body composition, and specific and general aspects of quality of life determined preoperatively, at 12 months and, in the 15 surviving patients, several years after the operation. The patients lost 10% of their preoperative weight (mainly body fat) during the first year. Food intake did not correlate to changes in body composition or quality of life. Gastrointestinal symptoms adversely related to changes in lean body mass, meal size, and general aspects of quality of life for a long time after the operation. Gastrointestinal symptom control seems important to minimize impairment in quality of life, body composition, and eating after gastrectomy.

Adult↗
PubMed2001

Orchestrating anaphase and mitotic exit: separase cleavage and localization of Slk19.

Anaphase in budding yeast is triggered by cleavage of the central subunit, Scc1, of the chromosomal cohesin complex by the protease separase. Here we show that separase also cleaves the kinetochore-associated protein Slk19 at anaphase onset. Separase activity is also required for the proper localization of a stable Slk19 cleavage product to the spindle midzone in anaphase. The cleavage and localization of Slk19 are necessary to stabilize the anaphase spindle, and we show that a stable spindle is a prerequisite for timely exit from mitosis. This demonstrates the cleavage of targets other than cohesin by separase in the orchestration of high-fidelity anaphase.

Amino Acid Sequence↗
PubMed2001

Treatment efficacy of intermittent claudication by invasive therapy, supervised physical exercise training compared to no treatment in unselected randomised patients II: one-year results of health-related quality of life.

OBJECTIVE: to compare the effectiveness of invasive therapy, supervised physical training and no treatment in terms of health-related quality of life (HRQL) in patients with intermittent claudication (IC). DESIGN: a prospective, randomised, controlled study. MATERIALS: a total of 253 unselected patients with stable IC were sequentially randomised into 3 balanced treatment groups. At 1 year follow-up data from a battery of generic and disease specific HRQL questionnaires, and global indices of quality of life and physical condition were available in 171 patients. RESULTS: compared with a non-diseased reference group, claudicants were substantially limited in daily physical functioning, but little affected regarding emotional, cognitive and social functioning, or well-being. Invasive therapy yielded significantly greater improvements in some aspects of physical functioning and walk-related symptoms than training. Training was not superior to invasive therapy on any HRQL dimension and superior to no treatment on only one dimension. Treatment effects, however, were generally small-to-moderate and levels of physical dysfunction in all groups remained higher than reference values. CONCLUSIONS: invasive therapy is more effective than supervised training in alleviating illness-specific symptoms and improving certain aspects of physical functioning - the primary HRQL domains impacted on by IC and the principal goals of its treatment. However, since treatment effect sizes were at most moderate and given that untreated claudicants reported at most small deterioration in HRQL, the level of evidence supporting invasive therapy is modest.

Activities of Daily Living↗
PubMed2001

Treatment efficacy of intermittent claudication by surgical intervention, supervised physical exercise training compared to no treatment in unselected randomised patients I: one year results of functional and physiological improvements.

OBJECTIVES: to compare the effect of surgery, exercise and simple observation on maximum exercise power in claudicants. DESIGN: prospective, randomised study. METHODS: a total of 264 unselected claudicants were randomised to supervised exercise training, invasive treatment (open surgical or endovascular procedures) or observation. One year treatment outcomes were analysed on an intention to-treat basis. RESULTS: invasively treated patients showed a significant improvement in maximum walking power, stopping distance, post-ischaemic blood flow and big toe pressure at one year. Patients randomised to physical exercise training or to the control group did not improve in any outcome measure. CONCLUSION: invasive treatment increased walking capacity, leg blood pressure and flow. Supervised physical exercise training offered no therapeutic advantage compared to untreated controls.

Adult↗
PubMed2001

A prospective study of quality of life in head and neck cancer patients. Part I: at diagnosis.

PURPOSE: A Swedish and Norwegian study was designed to examine health-related quality of life (HQL) in patients with head and neck cancer (head and neck) at diagnosis and during treatment and rehabilitation. The overall aim was to examine the impact on HQL at diagnosis depending on tumor location, stage, sex, and age (part I) and to describe HQL longitudinally and determine for which patients and during which period HQL deteriorated most (part II). This article presents the results at diagnosis. METHOD: Patients with head and neck cancer at five hospitals in Sweden and Norway were consecutively requested to participate. They were asked to answer the EORTC QLQ-C30 and QLQ-H&N35 (the European Organization for Research and Treatment of Cancer, Core 30 questionnaire and head and neck cancer module) repeatedly during 1 year. A total of 357 patients (mean age, 63 y; 72% males) were included. RESULTS: Patients with different tumor locations all had their special problems at diagnosis, for example, those with tumors in the larynx with communication, those with oral tumors with pain, and those with pharyngeal tumors with nutrition and pain. The patients with hypopharyngeal cancer reported the worst HQL. Stage appeared to have the strongest impact on HQL. Patients with a more advanced tumor stage reported significantly worse HQL scores for 24 of 32 variables reflecting functioning or problems. The females scored worse than the males for some areas, in particular, emotional functioning. The older patients scored significantly better for emotional and social functioning than patients <65 years but worse for physical functioning and various symptoms. The traditional way of grouping the tumor locations into oral, pharyngeal, laryngeal, and "other" tumors (salivary gland, sinus and nose, and unknown primary) was tested from a HQL point of view and found to be consistent. CONCLUSIONS: The chosen questionnaires differentiated between different sites of head and neck cancer at diagnosis. Tumor stage had the most powerful impact on HQL score.

Aged↗
PubMed2001

Resolution of dysphagia following cricopharyngeal myectomy in six young dogs.

Six young dogs were presented with a history of dysphagia and nasal regurgitation since birth. Following cranial nerve examination and assessment of swallowing with fluoroscopy, a diagnosis of cricopharyngeal achalasia was made in each case. In four dogs, concomitant aspiration pneumonia was present. Sectioning and removal of part of the cricopharyngeal muscle resulted in immediate and continued resolution of all signs of dysphagia and nasal regurgitation over follow-up periods of two to eight years. Postoperative complications were not seen in any case. In five of the six dogs, the cricopharyngeal muscle was approached laterally, a technique not previously described.

Animals↗
PubMed2001

Molecular cloning, genomic positioning, promoter identification, and characterization of the novel cyclic amp-specific phosphodiesterase PDE4A10.

We describe the cloning and expression of HSPDE4A10, a novel long form splice variant of the human cAMP phosphodiesterase PDE4A gene. The 825 amino acid HSPDE4A10 contains a unique N terminus of 46 amino acids encoded by a unique 5' exon. Exon-1(4A10) lies approximately 11 kilobase pairs (kb) downstream of exon-1(4A4) and approximately 13.5 kb upstream of the PDE4A common exon 2. We identify a rat PDE4A10 ortholog and reveal a murine ortholog by nucleotide sequence database searching. PDE4A10 transcripts were detected in various human cell lines and tissues. The 5' sequence flanking exon-1(4A10) exhibited promoter activity with the minimal functional promoter region being highly conserved in the corresponding mouse genomic sequence. Transient expression of the engineered human PDE4A10 open reading frame in COS7 cells allowed detection of a 121-kDa protein in both soluble and particulate fractions. PDE4A10 was localized primarily to the perinuclear region of COS7 cells. Soluble and particulate forms exhibited similar K(m) values for cAMP hydrolysis (3-4 microM) and IC(50) values for inhibition by rolipram (50 nM) but the V(max) value of the soluble form was approximately 3-fold greater than that of the particulate form. At 55 degrees C, soluble HSPDE4A10 was more thermostable (T(0.5) = 11 min) than the particulate enzyme (T(0.5) = 5 min). HSPDE4A10 and HSPDE4A4B are shown here to be similar in size and exhibit similar maximal activities but differ with respect to sensitivity to inhibition by rolipram, thermostability, interaction with the SRC homology 3 domain of LYN, an SRC family tyrosyl kinase, and subcellular localization. We suggest that the unique N-terminal regions of PDE4A isoforms confer distinct properties upon them.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

Measurement of gastric P(CO2) as an index of tissue hypoxia during obstructive sleep apnea.

BACKGROUND: Gastric mucosal ischemia develops in critically ill patients in a number of clinical settings due to diversion of blood flow from the splanchnic bed to more vital organs, and can be detected by the measurement of gastric intramucosal pH (pHi). STUDY OBJECTIVE: We hypothesized that similar changes would occur during obstructive sleep apnea (OSA) due to increased respiratory work during the periods of apnea. METHODS: Gastric P(CO2), pHi and arterial blood gases were measured during 3 conditions in 8 patients with severe OSA: at baseline awake, while asleep with > or = 30 obstructive apneas or hypopneas per hour, and asleep after elimination of apneas with continuous positive airway pressure (CPAP). RESULTS: Significant changes between the baseline and apnea conditions were detected using ANOVA for repeated measures for gastric P(CO2), 40.2 +/- 5.3 vs. 85.4 +/- 34.0 (p < 0.001), pHi, 7.41 +/- 0.06 vs. 7.11 +/- 0.17 (p < 0.005), and the gastric-arterial P(CO2) difference (D(CO2)), -2.3 +/- 5.5 vs. 44.3 +/- 36.21 (p < 0.006). Nasal CPAP returned all measures back to baseline values. CONCLUSIONS: Gastric tissue hypoxia develops in patients with severe OSA and may be a marker of disease severity. Treatment of OSA with CPAP eliminates the regional tissue hypoxia.

Acid-Base Equilibrium↗
PubMed2001

Researcher and researched--community perspectives: toward bridging the gap.

In the process of initiating a new community-based research project, the authors wanted to understand the experiences of community members and researchers in community-based research projects and to develop guidelines to improve future projects. They conducted qualitative, key informant interviews with 41 people involved at all levels of community-based research projects in Seattle. Respondents were identified using a snowball sampling technique. More problems than successes were discussed by informants, including dissatisfaction with the focus of research, which some said is marked by a lack of cultural appropriateness and relevance. Power imbalances, lack of trust, and communication difficulties impeded collaboration. According to respondents, many problems could be avoided if the community were involved from the beginning in setting research priorities and developing and implementing interventions. Meaningful collaboration between communities and researchers is characterized by early involvement of communities, power sharing, mutual respect, community benefit, and cultural sensitivity.

Attitude to Health↗
PubMed2001

Health-related quality of life in COPD: why both disease-specific and generic measures should be used.

Although research has consistently demonstrated that chronic obstructive pulmonary disease (COPD) impairs health-related quality of life (HRQL), little agreement has been evidenced regarding the factors identified as contributing to impaired HRQL. The aim was to study such factors using well established generic and specific HRQL instruments. The patients (n=68) were stratified by forced expiratory volume in one second (FEV1) to represent a wide range of disease severity. Pulmonary function, blood gases and 6-min walking distance test (6MWD) were assessed. HRQL instruments included: St George's Respiratory Questionnaire (SGRQ), Sickness Impact Profile (SIP), Hospital Anxiety and Depression Scale and Mood Adjective Check List. The strength of the impact of COPD on HRQL was represented along a continuum ranging from lung function, functional status (physical and psychosocial) to wellbeing. Although correlations between FEV1 versus SGRQ total and SIP overall scores (r=-0.42 and -0.32) were stronger than previously reported, multiple regression analyses showed that lung function contributed little to the variance when dyspnoea-related limitation, depression scores and 6MWD were included in the models. These three factors were important to varying degrees along the whole range of HRQL. Physiological, functional and psychosocial consequences of chronic obstructive pulmonary disease are only poorly to moderately related to each other. The present study concludes that a comprehensive assessment of the effects of chronic obstructive pulmonary disease requires a battery of instruments that not only tap the disease-specific effects, but also the overall burden of the disease on everyday functioning and emotional wellbeing.

Activities of Daily Living↗
PubMed2001

Obesity-related coping and distress and relationship to treatment preference.

OBJECTIVES: The primary purpose was to define obesity-related strategies for coping with psychological problems connected with obesity. We also wanted to identify obesity-related distress and explore the effect of coping on distress. Thirdly, we wanted to investigate differences in coping and distress related to choice of surgery or conventional treatment. DESIGN: Cross-sectional data from patients in the Swedish Obese Subjects (SOS) intervention study. METHODS: An obesity-related questionnaire concerning coping and distress was created and evaluated in 2510 patients from the SOS study, using multitrait, exploratory and confirmatory factor analysis procedures. RESULTS: Three coping factors were defined. Social Trust and Fighting Spirit were problem-focused, whereas Wishful Thinking was emotion-focused. Surgical candidates displayed lower levels of problem-focused and higher levels of emotion-focused coping. We also identified two distress factors: Intrusion and Helplessness. Wishful Thinking was positively related to distress, and Social Trust and Fighting Spirit were inversely related, thus explaining the higher levels of distress reported by the surgical candidates. CONCLUSIONS: In our sample, emotion-focused coping proved maladaptive and was associated with increased distress. Problem-focused coping, however, was adaptive and associated with reduced distress. These findings partly explain psychological morbidity and should be taken into consideration in the treatment of obese people.

Adaptation, Psychological↗
PubMed2001

Treatment of dysthymia and minor depression in primary care: a randomized trial in patients aged 18 to 59 years.

OBJECTIVE: The researchers evaluated the effectiveness of paroxetine and Problem-Solving Treatment for Primary Care (PST-PC) for patients with minor depression or dysthymia. STUDY DESIGN: This was an 11-week randomized placebo-controlled trial conducted in primary care practices in 2 communities (Lebanon, NH, and Seattle, Wash). Paroxetine (n=80) or placebo (n=81) therapy was started at 10 mg per day and increased to a maximum 40 mg per day, or PST-PC was provided (n=80). There were 6 scheduled visits for all treatment conditions. POPULATION: A total of 241 primary care patients with minor depression (n=114) or dysthymia (n=127) were included. Of these, 191 patients (79.3%) completed all treatment visits. OUTCOMES: Depressive symptoms were measured using the 20-item Hopkins Depression Scale (HSCL-D-20). Remission was scored on the Hamilton Depression Rating Scale (HDRS) as less than or equal to 6 at 11 weeks. Functional status was measured with the physical health component (PHC) and mental health component (MHC) of the 36-item Medical Outcomes Study Short Form. RESULTS: All treatment conditions showed a significant decline in depressive symptoms over the 11-week period. There were no significant differences between the interventions or by diagnosis. For dysthymia the remission rate for paroxetine (80%) and PST-PC (57%) was significantly higher than for placebo (44%, P=.008). The remission rate was high for minor depression (64%) and similar for each treatment group. For the MHC there were significant outcome differences related to baseline level for paroxetine compared with placebo. For the PHC there were no significant differences between the treatment groups. CONCLUSIONS: For dysthymia, paroxetine and PST-PC improved remission compared with placebo plus nonspecific clinical management. Results varied for the other outcomes measured. For minor depression, the 3 interventions were equally effective; general clinical management (watchful waiting) is an appropriate treatment option.

Adolescent↗
PubMed2001

Nephron-sparing surgery for small incidental renal cell carcinoma.

BACKGROUND: Nephron-sparing surgery is currently an accepted treatment for renal cell carcinomas in patients with bilateral tumours, solitary kidneys and when overall renal function is impaired or at risk from medical disease. Its role in patients with a normal contralateral kidney remains controversial. METHODS: The authors' experience in 23 patients undergoing partial nephrectomy for small peripheral lesions between 1995 and 2000 is reported here. RESULTS: Twenty-three patients (13 men and 10 women) with a mean age of 56 years underwent partial nephrectomy. All but three of these patients had a normal contralateral kidney. Mean operating time was 141 min with a mean reduction of haemoglobin of 28 g/dL. Three patients required transfusion. Serum creatinine did not change significantly between preoperative and postoperative values. Two JJ stents were placed prophylactically during surgery to minimize urinary leak. There were no intraoperative or early postoperative deaths and at mean follow up of 16 months there was no evidence of recurrent tumour in 23 patients. Seventeen per cent of lesions removed were benign. CONCLUSIONS: Partial nephrectomy for small peripheral lesions is a safe procedure with low morbidity. No definite recurrences are evident at an early stage of follow up, although longer review (probably more than 10 years) will be required to assess cancer-specific survival following this procedure.

Adult↗
PubMed2000

Treatment of dysthymia and minor depression in primary care: A randomized controlled trial in older adults.

CONTEXT: Insufficient evidence exists for recommendation of specific effective treatments for older primary care patients with minor depression or dysthymia. OBJECTIVE: To compare the effectiveness of pharmacotherapy and psychotherapy in primary care settings among older persons with minor depression or dysthymia. DESIGN: Randomized, placebo-controlled trial (November 1995-August 1998). SETTING: Four geographically and clinically diverse primary care practices. PARTICIPANTS: A total of 415 primary care patients (mean age, 71 years) with minor depression (n = 204) or dysthymia (n = 211) and a Hamilton Depression Rating Scale (HDRS) score of at least 10 were randomized; 311 (74.9%) completed all study visits. INTERVENTIONS: Patients were randomly assigned to receive paroxetine (n = 137) or placebo (n = 140), starting at 10 mg/d and titrated to a maximum of 40 mg/d, or problem-solving treatment-primary care (PST-PC; n = 138). For the paroxetine and placebo groups, the 6 visits over 11 weeks included general support and symptom and adverse effects monitoring; for the PST-PC group, visits were for psychotherapy. MAIN OUTCOME MEASURES: Depressive symptoms, by the 20-item Hopkins Symptom Checklist Depression Scale (HSCL-D-20) and the HDRS; and functional status, by the Medical Outcomes Study Short-Form 36 (SF-36) physical and mental components. RESULTS: Paroxetine patients showed greater (difference in mean [SE] 11-week change in HSCL-D-20 scores, 0.21 [0. 07]; P =.004) symptom resolution than placebo patients. Patients treated with PST-PC did not show more improvement than placebo (difference in mean [SE] change in HSCL-D-20 scores, 0.11 [0.13]; P =.13), but their symptoms improved more rapidly than those of placebo patients during the latter treatment weeks (P =.01). For dysthymia, paroxetine improved mental health functioning vs placebo among patients whose baseline functioning was high (difference in mean [SE] change in SF-36 mental component scores, 5.8 [2.02]; P =. 01) or intermediate (difference in mean [SE] change in SF-36 mental component scores, 4.4 [1.74]; P =.03). Mental health functioning in dysthymia patients was not significantly improved by PST-PC compared with placebo (P>/=.12 for low-, intermediate-, and high-functioning groups). For minor depression, both paroxetine and PST-PC improved mental health functioning in patients in the lowest tertile of baseline functioning (difference vs placebo in mean [SE] change in SF-36 mental component scores, 4.7 [2.03] for those taking paroxetine; 4.7 [1.96] for the PST-PC treatment; P =.02 vs placebo). CONCLUSIONS: Paroxetine showed moderate benefit for depressive symptoms and mental health function in elderly patients with dysthymia and more severely impaired elderly patients with minor depression. The benefits of PST-PC were smaller, had slower onset, and were more subject to site differences than those of paroxetine.

Aged↗
PubMed2000

Vacuum disk and facet phenomenon in a dog with cauda equina syndrome.

A 7-year-old castrated male Rottweiler was evaluated for an 18-month history of bilateral hind limb lameness, signs of pain on rising, and mild ataxia. A gas-filled lumbosacral disk space (vacuum disk phenomenon) was revealed by use of computed tomography. Additional smaller gas bubbles were in the periphery of the disk and between the degenerated L5-L6 dorsal articular facets (vacuum facet phenomenon). Vacuum disk and facet phenomena have been described in humans with degenerative disk and vertebral articular facet joint disease; gas attracted from surrounding tissues accumulates within clefts of the degenerated disk or in unstable facet joints. Vacuum disk phenomenon has been reported in dogs and indicates degenerative disk disease. The phenomenon is more commonly observed by use of computed tomography, compared with conventional radiography, and can be elicited by hyperextension of the vertebral column.

Animals↗