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Biomedical subjects

M R Conaway

Publications and source records attributed to M R Conaway.

At least 19 recordsLinked to original sources

Endoscopic ultrasound drainage of pancreatic pseudocyst: a prospective comparison with conventional endoscopic drainage.

BACKGROUND AND STUDY AIMS: Pancreatic pseudocysts are a complication in up to 20% of patients with pancreatitis. Endoscopic management of pseudocysts by a conventional transenteric technique, i. e. conventional transmural drainage (CTD), or by endoscopic ultrasound-guided drainage (EUD), is well described. Our aim was to prospectively compare the short-term and long-term results of CTD and EUD in the management of pseudocysts. PATIENTS AND METHODS: A total of 99 consecutive patients underwent endoscopic management of pancreatic pseudocysts according to this predetermined treatment algorithm: patients with bulging lesions without obvious portal hypertension underwent CTD; all remaining patients underwent EUD. Patients were followed prospectively, with cross-sectional imaging during clinic visits. We compared short-term and long-term results (effectiveness and complications) at 1 and 6 months post procedure. RESULTS: 46 patients (37 men) underwent EUD and 53 patients (39 men) had CTD. The mean age of the entire group was 50 +/- 13 years. There were no significant differences between the two groups regarding short-term success (93% vs. 94%) or long-term success (84% vs. 91%); 68 of the 99 patients completed 6 months of follow-up. Complications occurred in 19% of EUD vs. 18% of CTD patients, and consisted of bleeding in three, infection of the collection in eight, stent migration into the pseudocyst in three, and pneumoperitoneum in five. All complications but one could be managed conservatively. CONCLUSIONS: No clear differences in efficacy or safety were observed between conventional and EUS-guided cystenterostomy. The choice of technique is likely best predicated by individual patient presentation and local expertise.

Adult↗

Reduced expression of metastasis suppressor RhoGDI2 is associated with decreased survival for patients with bladder cancer.

PURPOSE: RhoGDI2 was recently shown to be a metastasis suppressor gene in models of bladder cancer. We sought to further understand its importance in human cancer by determining the level of its expression and the distribution of its encoded protein in normal human tissues and cell lines and to evaluate whether its protein expression is a determinant of human bladder cancer progression. EXPERIMENTAL DESIGN: RhoGDI2 mRNA and protein expression was evaluated in cell lines and human tissues using Affymetrix and tissue microarrays, respectively. Tissue microarrays represented most human normal adult tissues and material from 51 patients that had undergone radical cystectomy for bladder cancer. In these 51 patients, the chi(2) test was used to test for associations between RhoGDI2 and stage, grade of urothelial carcinoma, histological type, and disease-specific survival status. Cox proportional hazards regression analyses were used to estimate the effect of RhoGDI2 expression level on time to development of metastatic disease and disease-specific survival time, adjusting for grade, stage, and histological type. RESULTS: In normal tissues, there was strong RhoGDI2 protein expression in WBCs, endothelial cells, and transitional epithelium. RhoGDI2 mRNA expression was inversely related to the invasive and metastatic phenotype in human bladder cancer cell lines. In patients with bladder cancer, univariate analysis indicated that reduced tumor RhoGDI2 protein expression was associated with a lower actuarial 5-year disease-free and disease-specific survival (P = 0.01). In addition, patients with tumors that had low or absent RhoGDI2 had a shorter time to disease-specific death (P <or= 0.01). When tumor grade, stage, histological type, and RhoGDI2 staining level were examined using multivariate analysis, RhoGDI2 expression was found to be an independent predictive factor for disease-specific death (P = 0.03). CONCLUSIONS: These results suggest that RhoGDI2 is an independent predictor of prognosis for patients with bladder cancer and provide clinical evidence in support of its involvement in cancer metastasis.

Cell Line, Tumor↗

The use of dopamine enhancing medications with children in low response states following brain injury.

PRIMARY OBJECTIVE: The study examines the possible relationship between dopamine-enhancing medications and improvement of arousal and awareness in children during persistent low response states (Rancho Los Amigos Levels I, II and III). RESEARCH DESIGN: A retrospective review was conducted of 10 children enrolled in an existing clinical protocol. The Kluge Children's Rehabilitation Center (KCRC) low response protocol provides a double baseline serial measure (A, A, B, B, B) design. Scores on the Western NeuroSensory Stimulation Profile (WNSSP) are the dependent variable. METHODS AND PROCEDURES: Ten children, mean age of 13.7 years low response state (30 days or more) who were treated with dopamine agonists. Co-morbid or iatrogenic influences were addressed or ruled out. Seven children had traumatic brain injury, one cerebral vascular accident, one anoxia and one encephalitis. EXPERIMENTAL INTERVENTION: On average, dopamine medications were started 52.9 days post-event. MAIN OUTCOMES AND RESULTS: Paired t-test of WNSSP scores before medications and on medications were significant at p = 0.03 (paired t-test). Also, the distributions of the slopes (rates of change of WNSSP scores over time) were significantly different in the pre-medication and medication phases (Paired T-test, p = 0.02). Random coefficient model comparison of individuals during pre- and medication phase response variability on WNSSP yielded F-test at p = 0.02. CONCLUSIONS: These results suggest a promising relationship between acceleration of recovery for some children in a low response state and administration of dopamine-enhancing medications.

Adolescent↗

Accelerated s-nitrosothiol breakdown by amyotrophic lateral sclerosis mutant copper,zinc-superoxide dismutase.

Mutations in copper,zinc-superoxide dismutase (SOD) have been implicated in familial amyotrophic lateral sclerosis (FALS). We have investigated the breakdown of S-nitrosothiols by wild-type (WT) SOD and two common FALS mutants, alanine-4 valine (A4V) SOD and glycine-37 arginine (G37R) SOD. In the presence of glutathione, A4V SOD and G37R SOD catalyzed S-nitrosoglutathione breakdown three times more efficiently than WT SOD. Indeed, A4V SOD catabolized GSNO more efficiently than WT SOD throughout the physiological range of GSH concentrations. Moreover, a variety of additional S-nitrosothiols were catabolized more readily by A4V SOD than by WT SOD. Initial rate data for fully reduced WT SOD and A4V SOD, and data using ascorbic acid as the reductant, suggest that FALS mutations in SOD may influence the efficiency of reduction of the copper center by glutathione. We have identified a potentially toxic gain of function of two common FALS mutations that may contribute to neurodegeneration in FALS.

Amyotrophic Lateral Sclerosis↗

Static magnetic fields for treatment of fibromyalgia: a randomized controlled trial.

OBJECTIVE: To test effectiveness of static magnetic fields of two different configurations, produced by magnetic sleep pads, as adjunctive therapies in decreasing patient pain perception and improving functional status in individuals with fibromyalgia. DESIGN: Randomized, placebo-controlled, 6-month trial conducted from November 1997 through December 1998. SETTING AND SUBJECTS: Adults who met the 1990 American College of Rheumatology criteria for fibromyalgia were recruited through clinical referral and media announcements and evaluated at a university-based clinic. INTERVENTIONS: Subjects in Functional Pad A group used a pad for 6 months that provided whole-body exposure to a low, uniform static magnetic field of negative polarity. Subjects in the Functional Pad B group used a pad for 6 months that exposed them to a low static magnetic field that varied spatially and in polarity. Subjects in two Sham groups used pads that were identical in appearance and texture to the functional pads but contained inactive magnets; these groups were combined for analysis. Subjects in the Usual Care group continued with their established treatment regimens. OUTCOME MEASURES: Primary outcomes were the change scores at 6 months in the following measures: functional status (Fibromyalgia Impact Questionnaire), pain intensity ratings, tender point count, and a tender point pain intensity score. RESULTS: There was a significant difference among groups in pain intensity ratings (p = 0.03), with Functional Pad A group showing the greatest reduction from baseline at 6 months. All four groups showed a decline in number of tender points, but differences among the groups were not significant (p = 0.72). The functional pad groups showed the largest decline in total tender point pain intensity, but overall differences were not significant (p = 0.25). Improvement in functional status was greatest in the functional pad groups, but differences among groups were not significant (p = 0.23). CONCLUSIONS: Although the functional pad groups showed improvements in functional status, pain intensity level, tender point count, and tender point intensity after 6 months of treatment, with the exception of pain intensity level these improvements did not differ significantly from changes in the Sham group or in the Usual Care group.

Adolescent↗

Early childhood diarrhoea and helminthiases associate with long-term linear growth faltering.

BACKGROUND: Although the acute mortality from diarrhoeal diseases is well recognized, the potentially prolonged impact of early childhood diarrhoea on background growth and development is often overlooked. To examine the magnitude and duration of the association of early childhood enteric infections with growth faltering in later childhood, we investigated associations of early childhood diarrhoea (0-2 years) and intestinal helminthiases with nutritional status from age 2 to 7 years. METHODS: Twice-weekly diarrhoea surveillance and quarterly anthropometrics were followed from 1989 to 1998 in 119 children born into a Northeast Brazilian shantytown. RESULTS: Diarrhoea burdens at 0-2 years old were significantly associated with growth faltering at ages 2-7 years, even after controlling for nutritional status in infancy, helminthiases at 0-2 years old, family income, and maternal education by Pearson correlation, multivariate linear regression, and repeat measures analysis. The average 9.1 diarrhoeal episodes before age 2 years was associated with a 3.6 cm (95% CI : 0.6-6.6 cm) growth shortfall at age 7 years. Early childhood helminthiasis was also associated with linear growth faltering and a further 4.6 cm shortfall (95% CI : 0.8-7.9 cm) at age 7 years. CONCLUSIONS: Early childhood diarrhoea and helminthiases independently associate with substantial linear growth shortfalls that continue beyond age 6 years. Targeted interventions for their control may have profound and lasting growth benefits for children in similar settings.

Anthropometry↗

Ambulatory surgery: room air versus nasal cannula oxygen during transport after general anesthesia.

UNLABELLED: We compared outpatients transported to the postanesthesia care unit (PACU) while breathing room air to 2-4 L/min nasal cannula oxygen (O2) to test the hypothesis that routine supplemental O2 during transport is not required after general anesthesia in an ambulatory surgery center. We also examined whether the arbitrary arrival PACU O2 saturations of > 92% may be used to predict an infrequent incidence of subsequent significant desaturations (< 90%) in the PACU. One-hundred-ninety patients were randomized to receive either room air or 2-4 L/min nasal cannula for transport to PACU after receiving general anesthesia. O2 saturations were recorded before surgery, just before leaving the operating room, and upon arrival in the PACU. The lowest O2 saturation occurring in the PACU was also recorded. The mean arrival PACU O2 saturation was 95.0 in the Room Air group, compared with 97.2 for the Nasal Cannula (NC) group, a statistically significant difference (P < 0.001). In the Room Air group, 20% had arrival O2 saturations < or = 92%, and half of these (10%) had O2 saturations < 90%. In the NC group, 6% had O2 saturations < or = 92%, of which one third (2%) were < 90% on arrival in the PACU. All of these initial desaturations were easily corrected with face-tent O2 administration, deep breathing, or both. Subgroup analysis revealed that patients whose ages were 60 yr or older or those weighing 100 kg or more had lower arrival room air saturations than their younger or slimmer counterparts. In the Room Air group, only three (3.9%) of the patients that arrived in PACU with O2 saturations > 92% had subsequent desaturations < 90%, compared with seven (7.9%) in the NC group. We conclude that most adult patients undergoing ambulatory surgery can be transported safely to the PACU breathing room air after general anesthesia. However, patients whose age was > or = 60 yr or weight was > or = 100 kg, or for whom transient O2 desaturation on transport may be harmful, should be transported while breathing nasal O2 via nasal cannula. IMPLICATIONS: Most adult patients undergoing ambulatory surgery can be transported safely to the PACU breathing room air after general anesthesia. However, patients whose age was > or = 60 yr or weight > or = 100 kg, or for whom transient O2 desaturation on transport may be harmful, should be transported while breathing oxygen via nasal cannula.

Adult↗

Focal adhesion kinase, Rap1, and transcriptional induction of vascular endothelial growth factor.

BACKGROUND: Signals from a cell's environment are sensed by receptors, which activate pathways that, in turn, transmit the signals to the nucleus, informing decisions on growth, angiogenesis, and other cell functions. Transcription of vascular endothelial growth factor (VEGF), a potent angiogenic factor, can be induced by cell-cell contact. In the current work, we sought to determine if this induction is dependent on transformation of cells to a malignant phenotype and subsequently to determine which signaling molecules mediate activation of VEGF transcription. METHODS: Normal and transformed prostate epithelial cell lines were examined at various cell densities to simulate the effect of increased cell contact on expression of VEGF messenger RNA. Transformed cells were also cotransfected with a VEGF promoter-reporter construct and with constructs that express dominant negative or activated versions of signal transduction proteins hypothesized to be involved in the cell-cell contact process, and reporter activity was assessed at various cell densities. All P values are two-sided. RESULTS: Direct cell-cell contact, but not extracellular matrix components, resulted in transcriptional activation of a VEGF promoter-reporter construct in malignant (P<.0001) but not in nonmalignant (P =.37) prostate cells. This process was mediated via a mitogen-activated protein kinase (MAPK); it required the activity of focal adhesion kinase (FAK), Rap1, and Raf and was Ras independent. In addition, transcriptional activation of a Ras-sensitive Elk-1 chimeric reporter by cell-cell contact suggests that Rap1 is a key factor in regulating the specificity of convergent MAPK-signaling pathways arising from different upstream extracellular stimuli. CONCLUSIONS: Cell contact induction of VEGF transcription via FAK and Rap1 provides a novel Ras-independent, but transformation-dependent, mechanism for stimulus-specific regulation of tumor VEGF expression via MAPK.

Blotting, Northern↗

Feasibility of gadodiamide compared with dilute iodinated contrast material for imaging of the abdominal aorta and renal arteries.

PURPOSE: To determine the quality of digital abdominal angiograms obtained with use of full-strength, intra-arterial gadodiamide compared with similar volumes of half-strength iodinated contrast material for evaluating the abdominal aorta and renal vessels. MATERIALS AND METHODS: Twenty-five consecutive patients underwent digital subtraction arteriography of the abdominal aorta performed with equal volumes (32 mL) of either half-strength (300 mg/mL iodine) iodinated contrast material or full strength gadodiamide (0.11-0.25 mmol/kg) to evaluate the abdominal aorta and renal arteries. The contrast agent used was not known to the image readers. The abdominal aorta, left and right renal main renal artery, and first and second order segmental branches were graded separately as diagnostic or nondiagnostic by four angiographers. RESULTS: Images of the abdominal aorta were diagnostic 100% of the time for iodine and gadodiamide, 76% and 80% diagnostic for iodine and gadodiamide in the left main renal artery, respectively; and 100% and 80% diagnostic for iodine and gadodiamide in the right main renal artery, respectively. The first order segmental branches of the right and left renal arteries were graded diagnostic 72% and 56% of the time, respectively, for dilute iodinated contrast material, and 40% and 28% of the time, respectively, for gadodiamide. The second order segmental branches of the right and left kidney were graded diagnostic 24% of the time for iodinated contrast and 8% and 4% of the time, respectively, for gadodiamide. CONCLUSION: Full-strength, intra-arterial gadodiamide at doses smaller than 0.3 mmol/kg can produce diagnostic images of the abdominal aorta and main renal arteries. However, images of the intrarenal branches are usually not diagnostic.

Adult↗

Responsiveness of fibromyalgia clinical trial outcome measures.

OBJECTIVE: To assess the responsiveness of the Fibromyalgia Impact Questionnaire (FIQ), patient ratings of pain intensity, number of tender points, and total tender point pain intensity score to perceived changes in clinical status in patients with fibromyalgia (FM). METHODS: Using data from a randomized placebo controlled study evaluating efficacy of magnetic therapy in patients with FM, the ability of primary outcomes to detect clinically meaningful changes over a 6 month period was assessed by: (1) degree of association between outcome change scores and patient global ratings of symptom change (Spearman rank-order correlations); (2) ability of these scores to discriminate among groups of patients whose perceived health status had changed to varying degrees (ANOVA); (3) ability of these scores, individually and jointly, to discriminate between patients who had reported improvement and those who did not (logistic regression); (4) effect size, standardized response mean, and Guyatt's statistic were calculated to quantify responsiveness. RESULTS: Correlations showed the outcome measures were moderately responsive to perceived symptomatic change. For FIQ, pain intensity ratings and number of tender points, differences in change scores between globally improved and unchanged groups and between globally improved and worsened groups were significant; for total tender point pain intensity, the globally improved differed from worsened group. FIQ outperformed the other measures in discriminating between patients who reported improvement from those who did not. Summary statistics were consistent with discriminatory analyses, indicating the measures were sensitive to improvement, but relatively unresponsive to decline. CONCLUSION: The FIQ was the most responsive measure to perceived clinical improvement and we recommend its inclusion as a primary endpoint in FM clinical trials.

Adult↗

Recruiting cancer patients to participate in motivating their relatives to quit smoking. A cancer control study of the Cancer and Leukemia Group B (CALGB 9072).

BACKGROUND: A diagnosis of cancer provides a teachable moment in which a physician can counsel or teach the patient. The Cancer and Leukemia Group B hypothesized that this teachable moment could also be used to encourage counseling of the patients' relatives who smoke. The authors' first study sought to determine the feasibility of such an intervention, the cooperation of the patients, and the compliance of relatives who were smokers. The long-range goal is to recruit by mail a large population of adult smokers into an intervention program and to assist them in quitting cigarette smoking. METHODS: Oncologists and their clinical research associates asked recently diagnosed cancer patients to identify their relatives who were smokers and assist in persuading them to quit. Consenting patients spoke to relatives and mailed them a personalized motivational leaflet along with a list of the benefits of quitting smoking. Intervention was continued only with relatives who were contacted in this manner. The participating physicians then wrote to the smokers, advising them to quit; enclosed with each physician's letter were the National Cancer Institute booklet "Clearing the Air," which is about quitting smoking, and a questionnaire determining "stage of change" (the stage of the smoker's inaction or action regarding quitting smoking). After 6 months, a postintervention questionnaire was mailed to the relatives. RESULTS: Written consent was obtained from 89% of 144 eligible patients solicited. Eighty percent of patients involved in the study contacted relatives. Sixty-three percent of contacted relatives returned the first questionnaire and 40% answered the second. Nine percent of all contacted relatives reported having quit smoking after the intervention. CONCLUSIONS: The intervention proved to be feasible and will lead to the next study, which will randomize relatives who smoke within a more intensive intervention over 12 months and compare the results with nonintervention controls.

Adult↗

Anthropometric risk factors for prostate cancer.

Cancer of the prostate is the leading cancer among American men, yet few risk factors are known. Anthropometry may help uncover potential risk factors for prostate cancer, since fat distribution, skeletal structure, and musculature may differ between men with this hormonally linked cancer and those without it. A case-control study was undertaken to determine whether anthropometric differences exist between prostate cancer cases and controls and whether such differences are associated with specific hormonal profiles. The study accrued 315 men stratified for race, age, and case/control status. Weight, height (sitting/standing), skinfold thicknesses (triceps, biceps, subscapular, suprailiac, thigh), circumferences (midarm, waist, hip, thigh), breadths (elbow, biacromial, biiliac), hormonal levels (total and free testosterone, dihydrotestosterone, sex hormone-binding globulin), bone density, and body composition were measured. Measures of upper body robustness [i.e., biacromial breadth-to-height ratio (p = 0.02) and biacromial (p = 0.05) and bideltoid (p = 0.04) breadths] were greater among controls. Strong negative associations were found uniformly between sex hormone-binding globulin levels and measures of body adiposity and musculature. Data show that prostate cancer cases exhibit a propensity toward a slight upper body skeleton, which may in itself serve as a risk factor or provide a benchmark of past nutritional and/or hormonal status and help elucidate the etiology of this disease.

Aged↗

Reduced rates of metabolism and decreased physical activity in breast cancer patients receiving adjuvant chemotherapy.

Weight gain, a common side effect among breast cancer patients receiving adjuvant chemotherapy, may decrease quality of life and impair survival. Weight gain during treatment is a well-known problem and has been studied by many investigators. However, few controlled studies have been conducted to determine reasons to explain this apparent energy imbalance. An exploratory study was undertaken to quantitate potential changes in energy intake and specific components of energy expenditure in breast cancer patients receiving adjuvant chemotherapy. The research hypothesis was that a reduction in resting metabolic rate (RMR) would be observed during the period in which women received adjuvant chemotherapy. Twenty premenopausal patients with stage I or II breast cancer and receiving cyclophosphamide+doxorubicin+5-fluorouracil; cyclophosphamide +methotrexate+5-fluorouracil+/-doxorubicin; doxorubicin +cyclophosphamide+/-leucovorin; or methotrexate+5-fluorouracil +leucovorin chemotherapy were recruited. RMR, diet-induced thermogenesis, energy intake, physical activity, and body composition were assessed before the initiation and throughout the course of therapy. Complete data on 18 subjects suggest that RMR decreased significantly from baseline to midtreatment (P = 0.02) and rebounded to levels similar to those at baseline on completion of chemotherapy. Overall, levels of physical activity and energy intake also decreased significantly during treatment compared with baseline levels (P = 0.04 and P = 0.03, respectively). These findings suggest that chemotherapy provokes many significant changes in body composition and metabolic requirements. Additional research in this area will provide valuable insight into creating optimal interventions to curb weight gain in women with breast cancer.

Adult↗

Pain during mammography: characteristics and relationship to demographic and medical variables.

Reports of pain during mammography show that there is great variability in both the incidence of reported pain (0.2-62%) and the intensity of that pain. Much of that variability may be due to the measures used to rate mammography pain. This is the first study that has examined the incidence, quality and intensity of mammography pain using a variety of pain measures. A sample of 119 women undergoing screening mammography was studied using four pain scales, three well-validated measures frequently used in the pain research literature as well as a pain/discomfort measure frequently reported in the radiology literature. A large proportion (up to 91%) of women report having some degree of pain during mammography. The intensity of that pain was typically in the low to moderate range, but a small proportion of women (< 15%) reported intense pain. The incidence of reported pain was related to the pain measure used. Pain measures that provided a woman with many options for reporting pain were associated with a higher incidence of pain than a scale that provided only one or two options. Thus, some of the variability in reported incidence of pain during mammography can be explained by the pain scale used in the study. Demographic and medical variables could explain 18-20% of the variance in mammography pain. Two of the variables that were shown to consistently predict a painful mammographic experience were (1) average pain at the last mammogram and (2) breast density. This study demonstrated that the pain measure selected for use in a particular study may depend on the population being studied. A college education was found to be an important predictor of pain scores on the McGill Pain Questionnaire. Thus, this pain measure may be of limited usefulness in studying a population of women with little formal education.

Female↗

Factors contributing to patient satisfaction with breast reconstruction using silicone gel implants.

Recently, concerns have been raised about risks and benefits of silicone gel implants for breast reconstruction. Using a survey conducted during the silicone controversy that began in 1990, this study examines patient satisfaction in 174 women with silicone breast implants. Overall satisfaction was high; 43 percent indicated complete satisfaction, and only 3 percent stated they were "not at all" satisfied. Satisfaction was correlated with each woman's assessment of how reconstruction met her expectations, particularly expectations about clothes fitting better, feeling whole, looking normal, and having similar-appearing breasts. Higher levels of satisfaction also were associated with lower body mass index and absence of medical problems. While patients appeared satisfied with their reconstructions, 34 percent said they would be completely unlikely to choose silicone implants today. Further research is needed to understand the impact of the silicone breast implant debate on women who have had or may consider breast reconstruction.

Adult↗

Designs for phase II trials allowing for a trade-off between response and toxicity.

In this paper we propose methods for designing phase II trials that allow for a trade-off between treatment safety and antitumor activity, where safety and antitumor activity are measured as binary endpoints. The designs can be carried out either in a single stage or can be conducted in two stages, with an interim analysis to assess whether the treatment appears sufficiently safe and effective to warrant continuing. The emphasis is on the derivation of stopping rules for phase II trials that require the enrollment of a small number of patients and are based on enumerating the exact distribution of the proposed test statistic. We illustrate the methods with a recent study that required the use of a group sequential design to monitor antitumor activity and toxicity.

Antineoplastic Agents↗