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Biomedical subjects

M Lam

Publications and source records attributed to M Lam.

At least 37 records · Page 2Linked to original sources

Compliance with recommendations in a geriatric outreach assessment service.

OBJECTIVES: to measure the extent to which the recommendations of a geriatric outreach assessment service were being followed, and to determine what patient-related factors were associated with compliance with assessment recommendations. METHODS: eighty-one eligible patients or caregivers who had an assessment in a geriatric outreach service participated in a telephone interview. The interview focused on the use of health services and compliance with assessment recommendations. Patient-related variables obtained from charts included demographics, caregiver support and stability, health status and assessment recommendations. RESULTS: overall compliance with recommendations from the geriatric outreach assessment service was 65%. Patients were less likely comply fully with recommendations if they had a high number of recommendations [odds ratio (OR) = 0.23; 95% confidence interval (CI) = 0.12-0.46; P = 0.0001], inadequate caregiver support (OR = 0.212; 95% CI = 0.04 to 1.02; P = 0.0523), or the ability to transfer themselves independently (OR = 0.12; 95% CI = 0.02-0.63; P = 0.0124). They were more likely to have full compliance if they had normal vision (OR = 6.67; 95% CI = 1.22-36.46; P = 0.0284). CONCLUSION: it is important to focus on key issues when developing service recommendations and on the role of the informal caregiver in facilitating compliance with them. Good communication between the patient or caregiver and the family physician and geriatric services can help to identify strategies which might improve acceptance of recommendations.

Aged↗

Predictors of hospitalization and death among pre-dialysis patients: a retrospective cohort study.

BACKGROUND: Although there is abundant research describing predictors of patient morbidity and mortality among dialysis patients, predictors of adverse clinical outcomes among pre-dialysis patients are less well defined. The purpose of this study was to identify baseline predictors of first non-elective hospitalization among a retrospective cohort of 362 pre-dialysis patients. METHODS: Univariate and multivariate Cox proportional hazard models were used to identify predictors of hospitalization prior to dialysis initiation, adjusted for baseline creatinine level. Dialysis initiation, loss to follow-up, and study conclusion were censored events. Secondary outcomes included cause-specific hospitalization and death. RESULTS: Univariate analysis indicated that advanced age (RR 1.026, CI 1.016-1.037), number of prescribed anti-hypertensive medications (RR 1.149, CI 1.019-1.296), history of myocardial infarction (RR 1.979, CI 1.339-2.926), congestive heart failure (RR 2.299, CI 1.616-3.270), angina (RR 2.289, CI 1.695-3.091), peripheral vascular disease (RR 1.841, CI 1.282-2.644), renal failure secondary to nephrosclerosis (RR 1.413, CI 1.033-1.933) or renal artery stenosis (RR 1.587, CI 1.036-2.430), lower baseline haemoglobin level (RR 0.986, CI 0.979-0.992), and baseline creatinine greater than 300 micromol/l (RR 1.636, CI 1.233-2.171) were predictors of hospitalization. Gender, diabetes, diastolic blood pressure, mean arterial pressure, history of stroke, and hypoalbuminaemia did not predict outcome. Multivariate analysis, adjusted for baseline creatinine level, selected advanced age (RR 1. 017, CI 1.006-1.027), angina (RR 1.893, CI 1.371-2.613), peripheral vascular disease (RR 1.545, CI 1.054-2.266), and haemoglobin level (RR 0.987, CI 0.944-0.979) as independent predictors of hospitalization. CONCLUSION: Advanced age, co-morbid cardiovascular illness and anaemia are independent predictors of non-elective hospitalization prior to dialysis initiation. Further study is needed to determine the extent to which aggressive pre-dialysis management of anaemia and cardiovascular disease can improve patient outcomes.

Aged↗

Effect of the factor V Leiden mutation on the clinical expression of severe hemophilia A.

To determine whether the factor V Leiden mutation is associated with decreased bleeding in individuals with severe hemophilia A, factor concentrate utilization, maximum annual number of bleeding episodes, and the prevalence of hemophilic arthropathy between carriers and non-carriers of the factor V Leiden mutation were compared. Heterozygosity for the factor V Leiden mutation was found in 6 of 137 subjects (4.4%). Carriers of the factor V Leiden mutation utilized less factor concentrate (geometric mean: 310 vs. 1185 units/kg/year) and had fewer bleeding episodes than non-carriers (proportion with 10 or fewer bleeding episodes in their worst year: 50 vs. 11%). However, the factor V Leiden mutation was not associated with the absence of arthropathy. The intron 22 inversion mutation of the factor VIII gene was tested for in a subgroup of 80 subjects, but it was not found to be a significant variable for any of the bleeding endpoints. The results of this small study are consistent with the hypothesis that the factor V Leiden mutation imparts a protective effect; however, a larger confirmatory study in which the factor VIII molecular defects can be controlled for is needed. Furthermore, most severe hemophiliacs who used fewer than 200 units/kg/year of factor concentrate or who had experienced 10 or fewer bleeding episodes per year did not carry the factor V Leiden mutation, suggesting that the proportion of severe hemophiliacs whose mild clinical course can be attributed to the factor V Leiden mutation is small.

Adolescent↗

Three different presentations of bulimia nervosa.

This case report describes the different presentations of three women with bulimia nervosa, all of whom demonstrated purging behaviour. Two of the patients also had hypokalaemia, whereas the third exhibited Russell's sign-that is, calluses on the dorsum of each hand. Drug treatment and psychosocial intervention improved the condition of all three patients. The report emphasises the need for both health care professionals and the public to recognise this potentially dangerous but treatable disorder.

Adolescent↗

Risk factors for amphotericin B-induced nephrotoxicity.

The association of amphotericin B with nephrotoxicity is well known, but risk factors for this complication are not well characterized. One hundred and seventy-eight patients who received > 3 days of intravenous amphotericin B and a minimal total cumulative dose > 100 mg were reviewed retrospectively. The mean age, average cumulative dose of amphotericin B and duration of therapy were 46 +/- 22 years, 536 +/- 547 mg and 16.6 +/- 8.2 days, respectively. Eighty-six percent of patients received amphotericin B for empirical therapy of febrile neutropenia. Various definitions of nephrotoxicity were used; these were as follows (the incidence of nephrotoxicity as determined by the given definition is given in parentheses): definition 1, a change in creatinine of > 46 mumol/L over baseline (50%); definition 2, a doubling of creatinine over baseline (49%); definition 3, a change in creatinine of > 92 mumol/L (29%); definition 4, a doubling and/or a change in creatinine of > 92 mumol/L (49%); definition 5, an increase in creatinine to > 230 mumol/L (8%). Multivariate analysis showed that nephrotoxicity was associated with a greater cumulative dose of amphotericin B and receipt of concomitant nephrotoxic drugs for all definitions (P < 0.05). In those patients who experienced severe nephrotoxicity (creatinine increased to > 230 mumol/L), cyclosporin therapy was the most significant risk factor (odds ratio 18.8, P = 0.022). Haemodialysis was necessary in one patient, but multiple concomitant risk factors for renal dysfunction were present. No patient experienced irreversible nephrotoxicity. These findings allow for stratification of patients at risk for amphotericin B-induced nephrotoxicity and rational use of alternative agents.

Adult↗

Cognitive functioning in schizophrenia: implications for psychiatric rehabilitation.

Research in psychopathology and the cognitive neurosciences suggests new applications in psychiatric rehabilitation. Analysis of performance deficits on laboratory tasks can contribute to treatment planning, individual and family counseling, and staff consultation, much like it does in cases of brain injury and other types of central nervous system neuropathology. Recognition of the nature of cognitive impairments in schizophrenia can inform design of psychosocial techniques such as social and living skills training. Cognitive impairments are increasingly seen as potential targets for pharmacological and psychosocial treatment and rehabilitation. In this article, three key issues for application of cognitive technology in psychiatric rehabilitation of schizophrenia and related disorders are formulated as straightforward, clinically relevant questions: (1) What is the prognostic significance of cognitive impairment in acute psychosis? (2) Can cognitive functioning improve in the chronic, residual course? (3) How does cognitive improvement benefit other aspects of recovery and rehabilitation? These questions are addressed through review of previous findings and new multivariate analyses of cognitive functioning in the acute, post-acute, and chronic residual phases of schizophrenia.

Activities of Daily Living↗

Spirometric correlates of improvement in exercise performance after anticholinergic therapy in chronic obstructive pulmonary disease.

We wished to determine which resting spirometric parameters best reflect improvements in exercise tolerance and exertional dyspnea in response to acute high-dose anticholinergic therapy in advanced COPD. We studied 29 patients with stable COPD (FEV(1) = 40 +/- 2% predicted [%pred]; mean +/- SEM) and moderate to severe chronic dyspnea. In a double-blind placebo-controlled cross-over study, patients performed spirometry and symptom-limited constant-load cycle exercise before and 1 h after receiving 500 micrograms of nebulized ipratropium bromide (IB) or saline placebo. There were no significant changes in spirometry, exercise endurance, or exertional dyspnea after receiving placebo. In response to IB (n = 58): FEV(1), FVC, and inspiratory capacity (IC) increased by 7 +/- 1%pred, 10 +/- 1%pred, and 14 +/- 2%pred, respectively (p < 0.001), with no change in the FEV(1)/FVC ratio. After receiving IB, exercise endurance time (Tlim) increased by 32 +/- 9% (p < 0.001) and slopes of Borg dyspnea ratings over time decreased by 11 +/- 6% (p < 0.05). Percent change (%Delta) in Tlim correlated best with DeltaIC%pred (p = 0.020) and change in inspiratory reserve volume (DeltaTLC%pred) (p = 0.014), but not with DeltaFVC%pred, DeltaPEFR%pred, or DeltaFEV(1)%pred. Change in Borg dyspnea ratings at isotime near end exercise also correlated with DeltaIC%pred (p = 0.04), but not with any other resting parameter. Changes in spirometric measurements are generally poor predictors of clinical improvement in response to bronchodilators in COPD. Of the available parameters, increased IC, which is an index of reduced resting lung hyperinflation, best reflected the improvements in exercise endurance and dyspnea after IB. IC should be used in conjunction with FEV(1) when evaluating therapeutic responses in COPD.

Administration, Inhalation↗

Improving access for Medicaid-insured children: focus on front-office personnel.

BACKGROUND: Access to dental services for low-income children is limited. Front-office personnel play a role regarding dentists' participation in the Medicaid program. METHODS: Subjects (N = 24) represented general dental offices in Spokane County, Wash., and included participants and nonparticipants in the Access to Baby and Child Dentistry, or ABCD, program, a dental society/community program aimed at expanding dental services provided to Medicaid-insured children. The authors stratified the participants according to the number of claims their practices submitted to Medicaid for ABCD children: non-ABCD, low-ABCD and high-ABCD. Five two-hour focus group sessions were conducted to determine participants' beliefs about, attitudes toward and experiences in serving this population. RESULTS: The authors' data analysis consisted of a comprehensive content review of participants' responses from transcripted audiotapes. They synthesized frequently mentioned concepts and ideas into relevant themes. The major factors affecting practices' participation in Medicaid were office policy on seeing Medicaid-insured patients; staff members' personal connection to Medicaid-insured patients; staff members' attitudes about Medicaid-insured patients; and staff members' perceptions of Medicaid-insured patients' barriers to care. CONCLUSIONS: The data suggest that factors affecting dentists' participation in the Medicaid program are more complex than the often-stated dissatisfactions with low reimbursement fees and hassles with paperwork. CLINICAL IMPLICATIONS: Efforts to increase dentist participation in serving Medicaid-insured patients will continue to be relatively ineffective until many of the concerns raised by this study's subjects are better understood and addressed.

Administrative Personnel↗

Regulation of Bcl-xl channel activity by calcium.

Recent studies have demonstrated that the anti-apoptotic proteins, Bcl-2 and Bcl-xl, with the carboxyl-terminal hydrophobic domain removed, form cation-selective channels in the lipid bilayer reconstitution system. However, the regulatory properties of these channels are unknown. In this study, we investigated the ion-conducting properties of full-length Bcl-xl in the lipid bilayer reconstitution system. Our findings indicate that Bcl-xl forms a cation-selective channel that conducts sodium but not calcium and that Bcl-xl channel activity is reversibly inhibited by luminal calcium with a half-dissociation constant of approximately 60 microM. This calcium-dependent regulation of the Bcl-xl channel provides new insights into the roles of calcium and Bcl-2-related proteins in the programmed cell death pathway.

Apoptosis↗

A method for assaying intestinal brush-border sucrase in an intact intestinal preparation.

Small intestinal brush-border hydrolases usually are assayed in intestinal mucosal homogenates resuspended in solutions of unphysiological ionic composition. Thus, extrapolation of measured Vmax values (maximal reaction rates at high substrate concentrations) to in vivo conditions, hence comparison with physiological substrate loads, is uncertain. We therefore have developed a sucrase assay in an intact preparation of mouse small intestine, an everted intestinal sleeve incubated in a physiological Ringer's solution. As in homogenate studies, sucrase is assayed by glucose production measured colorimetrically, but uptake of liberated glucose into the intestinal sleeve is prevented by the transport inhibitor phlorizin. The coefficient of variation of Vmax is 16% for sleeves from the same mouse and 8% for mean values from different mice. Sleeve sucrase activity is abolished by the inhibitor castanospermine. Activity in sleeves and homogenates proves to be the same when measured under identical solution conditions, but variations in assay conditions cause large activity changes from values measured in physiological solutions.

Animals↗

Glucose uptake in dilated small intestine.

BACKGROUND/PURPOSE: The development of dilated small intestine in patients with short bowel syndrome results in increased mucosal surface area. This study examines whether the incremental increase in surface area leads to a proportional increase in absorptive function of the small intestine. METHODS: Partial obstruction of the small intestine was created in rats by placing an intussusception valve in the proximal jejunum. Rats that underwent sham operations served as controls. One week postoperatively, the small intestine proximal and distal to the valve was removed. The intestinal diameter proximal and distal to the obstruction was measured. The rate of glucose uptake was measured by the everted sleeve technique. The results were analyzed by analysis of variance (ANOVA). RESULTS: The intestine proximal to the valve was significantly dilated and thickened when compared with the intestine distal to the valve. The wet mass per centimeter of the dilated segment was 2.5 times that of the control group (P<.001). The glucose uptake capacity of the dilated segment was slightly higher than that of the control group (540 v 420 nmol/min/cm, P<.05). However, the specific glucose uptake rate was reduced significantly in the intestine proximal to the valve (247 v 335 nmol/min/cm2, P<.01). CONCLUSIONS: Although the partial obstruction of small intestine resulted in a substantial increase in the intestinal surface area, the absorptive capacity of the dilated intestine per unit surface area was decreased significantly. This translated ultimately into a slight increase in the overall functional absorptive capacity of glucose in the small intestine. These results suggest that dilated small intestine may not enhance mucosal absorption.

Analysis of Variance↗

Measurement of symptoms, lung hyperinflation, and endurance during exercise in chronic obstructive pulmonary disease.

Changes in lung hyperinflation, dyspnea, and exercise endurance are important outcomes in assessing therapeutic responses in chronic obstructive pulmonary disease (COPD). Therefore, we studied the reproducibility of Borg dyspnea ratings, inspiratory capacity (IC; to monitor lung hyperinflation), and endurance time during constant-load symptom-limited cycle exercise in 29 patients with COPD (FEV1 = 40 +/- 2% predicted; mean +/- SEM). Responsiveness was also studied by determining the acute effects of nebulized 500 micrograms ipratropium bromide (IB) or saline placebo (P) on these measurements. During each of four visits conducted over an 8-wk period, spirometry and exercise testing were performed before and 1 h after receiving IB or P (randomized, double-blinded). Highly reproducible measurements included: endurance time (intraclass correlation R = 0.77, p < 0.0001); Borg ratings and IC at rest, at a standardized exercise time (STD), and at peak exercise (R > 0.6, p < 0.0001); and slopes of Borg ratings over time, oxygen consumption (V O2), and ventilation (R > 0.6, p < 0.0001). Responsiveness was confirmed by finding a significant drug effect for: change (Delta) in endurance time (p = 0.0001); DeltaBorgSTD and DeltaBorg-time slopes (p < 0.05); and DeltaIC at rest, at STD, and at peak exercise (p = 0.0001). With all completed visits, DeltaBorgSTD correlated better with DeltaICSTD than any other resting or exercise parameter (n = 115, r = -0.35, p < 0.001). We concluded that Borg dyspnea ratings, and measurements of IC and endurance time during submaximal cycle exercise testing are highly reproducible and responsive to change in severe COPD.

Aged↗

Confirmatory factor analysis of the nurses' observation system for geriatric referrals.

The Nurses' Observation System for Geriatric Referrals is a 30-item observational scoring system for geriatric inpatients. As constructed, it is scored into six subscales of five items each; however, these six factors have not been empirically validated. A confirmatory factor analysis, performed on a sample of 218 completed forms for 218 geriatric inpatients, did not support the six original factors. Exploratory factor analysis gave a five-factor solution that partially replicated the scale's original factors but which also indicated important differences for interpretation and clinical use.

Aged↗

Can different types of retinal emboli be reliably differentiated from one another? An inter- and intraobserver agreement study.

OBJECTIVE: To determine whether ophthalmologists can agree on the qualitative assessment of visible retinal emboli. DESIGN: Inter- and intraobserver agreement study. SETTING: The retina and vitreous subspecialty session at the 1996 Canadian Ophthalmological Society meeting. SUBJECTS: A total of 42 observers, of whom 30 were retinal specialists. OUTCOME MEASURES: The observers viewed 17 fundus photographs of 11 patients with embolic acute retinal artery occlusion and classified the visible retinal emboli into one of three groups: cholesterol, calcific or other. RESULTS: Overall, there was slight agreement for the 17 observations (mean kappa = 0.063). The kappa statistic for all cases ranged from slight to fair agreement. Slight interobserver agreement for the six unique photographs was observed (mean kappa = 0.073). Slight intraobserver agreement was found for the three photographs that were shown in different orientations (mean kappa = 0.041) and for the two photographs shown with differing magnification (mean kappa = 0.102). CONCLUSIONS: Overall both intraobserver and interobserver agreement on the qualitative assessment of retinal emboli was poor. With only slight agreement on the classification of emboli, systemic evaluation of acute retinal artery occlusion should not be based on qualitative assessment of retinal emboli.

Calcinosis↗

Comparison of PRA-STAT, sHLA-EIA, and anti-human globulin-panel reactive antibody to identify alloreactivity in pretransplantation sera of heart transplant recipients: correlation to rejection and posttransplantation coronary artery disease.

BACKGROUND: Screening pretransplantation recipient sera for percent panel reactive antibodies (%PRA) by an anti-human globulin (AHG) assay may identify recipients who are at risk for graft rejection or development of posttransplantation coronary artery disease. However, the pretransplantation AHG-%PRA does not always correlate with the occurrence of graft rejection or coronary artery disease. METHODS: We compared the predictive capacity of the AHG-%PRA with that of an enzyme-linked immunoassay (EIA)-based PRA assay that identifies immunoglobulin G bound to soluble human leukocyte antigen (sHLA) class I molecules from pooled platelets of 240 random donors (sHLA-EIA), and that of an EIA-based assay that detects immunoglobulin G anti-HLA class I antibodies bound to sHLA derived from individual HLA-typed cell cultures (PRA-STAT). The pretransplantation sera from 130 cardiac allograft recipients were comparatively tested and results evaluated. RESULTS: Although AHG-%PRA- and sHLA-EIA-determined PRA results were comparable, neither assay discriminated potential recipients at risk for rejection or coronary artery disease. However, cardiac allograft recipients with pretransplantation PRA-STAT sera > 10% were at risk for (1) graft rejection (77% vs 56%, p < .05); (2) more rejections/recipient (1.9 vs 1.0, p < .02); (3) graft rejection within 30 days (92% vs 38%, p < .001); or (4) development of coronary artery disease (48% vs 23%, p < .05) than recipients with pretransplantation PRA-STAT sera < 10%. CONCLUSIONS: PRA-STAT analysis of pretransplantation sera from potential cardiac allograft recipients may be more clinically informative about HLA alloimmunity and a better predictor of adverse clinical events than either AHG-%PRA- or sHLA-EIA-determined PRA.

Antibody Specificity↗

Maintenance of calcium homeostasis in the endoplasmic reticulum by Bcl-2.

The oncogene bcl-2 encodes a 26-kD protein localized to intracellular membranes, including the ER, mitochondria, and perinuclear membrane, but its mechanism of action is unknown. We have been investigating the hypothesis that Bcl-2 regulates the movement of calcium ions (Ca2+) through the ER membrane. Earlier findings in this laboratory indicated that Bcl-2 reduces Ca2+ efflux from the ER lumen in WEHI7.2 lymphoma cells treated with the Ca2+-ATPase inhibitor thapsigargin (TG) but does not prevent capacitative entry of extracellular calcium. In this report, we show that sustained elevation of cytosolic Ca2+ due to capacitative entry is not required for induction of apoptosis by TG, suggesting that ER calcium pool depletion may trigger apoptosis. Bcl-2 overexpression maintains Ca2+ uptake in the ER of TG-treated cells and prevents a TG-imposed delay in intralumenal processing of the endogenous glycoprotein cathepsin D. Also, Bcl-2 overexpression preserves the ER Ca2+ pool in untreated cells when extracellular Ca2+ is low. However, low extracellular Ca2+ reduces the antiapoptotic action of Bcl-2, suggesting that cytosolic Ca2+ elevation due to capacitative entry may be required for optimal ER pool filling and apoptosis inhibition by Bcl-2. In summary, the findings suggest that Bcl-2 maintains Ca2+ homeostasis within the ER, thereby inhibiting apoptosis induction by TG.

Animals↗

Expression of a defective mouse mammary tumor virus envelope glycoprotein precursor which binds stably to GRP78 within the lumen of the endoplasmic reticulum is associated with decreased glucocorticoid-induced apoptosis in mouse lymphoma cells.

Viral proteins inhibit apoptosis in host cells by a variety of mechanisms. This report proposes an additional mechanism, based on the interaction of a mutant mouse mammary tumor virus (MMTV) envelope glycoprotein precursor, Pr74, with the stress protein GRP78 (BiP) within the lumen of the endoplasmic reticulum (ER) (J. Biol. Chem. 268 7482-7488, 1993). We show that WEHI7.2 (W7.2) mouse lymphoma cells, which do not express Pr74, are more sensitive to cell death induction by the glucocorticoid hormone dexamethasone (dex), than W7MG1 cells, which were derived by infecting W7.2 cells with MMTV and therefore express Pr74 under control of the glucocorticoid-inducible MMTV promoter. Moreover, W7-ENV/N cells, derived by stably transfecting W7.2 cells with a constitutively expressed cDNA encoding mutant Pr74, were less sensitive to dex-induced cell death than control transfectant W7-ENV/- cells. Among multiple W7-ENV/N subclones, susceptibility to dex-induced cell death was inversely related to the level of Pr74 synthesis. The interaction of Pr74 with GRP78 induces an increase in GRP78 synthesis. Thus, the repression of cell death associated with Pr74 expression may be secondary to elevated synthesis of GRP78, a stress protein previously implicated in protection against cell death.

Journal Article↗