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Biomedical subjects

E C Lai

Publications and source records attributed to E C Lai.

At least 19 recordsLinked to original sources
PubMed2006

The value of database controls in pilot or futility studies in ALS.

OBJECTIVE: To evaluate the use and reliability of database controls in place of a placebo group in pilot or "futility" ALS trials. METHODS: We compared the rates of disease progression in the placebo arm of the clinical phase III US Insulin-like Growth Factor-I Trial (n = 90) with the rates of disease progression of 207 patients with ALS selected from 1,600 ALS database patients using the same inclusion criteria. RESULTS: The mean rates of change in the Appel ALS (AALS) score were nearly identical in the placebo group (4.70 points/month) and in the database group (4.79 points/month). In addition, there was no significant difference in the median time to achieving a 20-point progression in AALS score: 143 days for database match vs 146 days for the placebo group (log rank p = 0.88). Furthermore, in the multivariate Cox analysis, both the rate at which the disease had progressed prior to first exam (preslope) (p < 0.001) and first exam AALS total score (p = 0.01) were shown to be covariates of subsequent rate of disease progression. CONCLUSION: The similarity in disease progression between placebo arm of clinical phase III trial and matched database group suggests the value of historical databases in futility trials. However, the proposed study design requires appropriate matching of study patients with database controls. Based on our results, we suggest matching by stage of the disease and rate of clinical decline in a contemporaneous ALS population.

Amyotrophic Lateral Sclerosis↗
PubMed2006

The ALSSQOL: balancing physical and nonphysical factors in assessing quality of life in ALS.

BACKGROUND: There is no generally accepted instrument for measuring quality of life (QOL) in patients with ALS. Current instruments are either too heavily weighted toward strength and physical function or useful for the evaluation of individuals but of less utility in assessing large samples. OBJECTIVE: To develop and evaluate the psychometric properties of an ALS-specific QOL instrument (the ALSSQOL) that would reflect overall QOL as assessed by the patient and would be valid and reliable across large samples. METHODS: The ALSSQOL is based on the McGill Quality of Life Questionnaire (MQOL), modified by changes in format and by adding questions on religiousness and spirituality, items derived from interviews with ALS patients, and items identified from open-ended questions administered during the MQOL. The psychometric properties of the ALSSQOL were assessed by a prospective multicenter study in which participants completed the ALSSQOL, other instruments measuring overall QOL, and instruments assessing religiousness, spirituality, and psychological distress. RESULTS: A 59-item ALSSQOL was developed; 342 patients evaluated its psychometric properties. Completion time averaged 15 minutes. Forty-six items loaded on six factors. The ALSSQOL demonstrated concurrent, convergent, and discriminant validity for the overall instrument and convergent validity for its subscales. Analysis of individual items permitted insight into variables of clinical importance. CONCLUSIONS: This new ALS-specific quality of life instrument is a practical tool for the assessment of overall quality of life in individuals with ALS and appears to be valid and useful across large samples. Validation studies of a shortened version are now under way.

Adjustment Disorders↗
PubMed2003

Quality of life in patients with amyotrophic lateral sclerosis: perceptions, coping resources, and illness characteristics.

OBJECTIVE: To assess and compare quality of life (QOL) for two groups of patients with amyotrophic lateral sclerosis (ALS): (1) those reporting a more positive quality of life and (2) those reporting a more negative quality of life. METHODS: One hundred patients with ALS participated in this cross-sectional, descriptive study conducted in an ALS clinic. Quality of life was graded in two ways: (1) a global question about present QOL, giving four choices (life could not be better, usually good, sometimes good, and not good) which the researchers divided into two groups: the more positive QOL and the more negative QOL and (2) patients' responses to a 25-item internally generated open-ended survey. The Appel ALS Rating Scale measured objective data for physical strength and functioning. RESULTS: One hundred patients (68 men and 32 women) with a mean age of 58.2 (range, 29-82) years participated in the study. The average disease duration was 1.9 (range, 0.08-15) years. Patients who reported the more positive QOL were younger, had a shorter disease duration, and experienced less disease severity (p < 0.05). Those endorsing the more positive QOL reported more adequate finances and less stress over disease characteristics (p < 0.05). CONCLUSIONS: Illness characteristics do influence QOL for patients with ALS, but they are not the only concerns. When measuring QOL in patients with ALS, the unique features of the psychosocial factors, personality traits, and spiritual factors, in addition to disease symptoms, need to be identified and discussed with patients and families throughout the illness.

Adaptation, Psychological↗
PubMed2001

Clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma: a study of a prospective cohort.

PURPOSE: This study aims to clarify the clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: The clinicopathologic features of 5-year survivors and disease-free survivors were elucidated in a cohort of 230 patients prospectively observed for > 5 years (64 to 192 months) after curative resection of HCC. RESULTS: The incidence of 5-year overall and disease-free survivors were 37% (85 of 230) and 20% (45 of 230), respectively. Clinicopathologic features associated with 5-year survivors included female sex (P =.024), preoperative serum albumin > or= 40 g/L (P =.033), AST < 50 u/L (P =.001), tumor < 5 cm (P =.001), solitary tumor (P =.035), encapsulated tumor (P =.021), no venous invasion (P =.001), no microsatellite nodule (P =.001), and early pathologic tumor-node-metastasis (pTNM) stage (I or II, P <.001). Features favoring 5-year disease-free survivors were preoperative serum AST < 50 u/L (P =.007), tumor < 5 cm (P =.005), encapsulated tumor (P =.007), no venous invasion (P <.001), no microsatellite nodule (P =.001), and early pTNM stage (I or II, P <.001). By multivariate analysis, pTNM stage was the only significant predictive factor for both overall and disease-free survival. CONCLUSION: This study shows that long-term disease-free survival > 5 years after resection of HCC can be achieved in patients with favorable tumor characteristics. Early pTNM stage was the most reliable predictor of both long-term overall and disease-free survivors.

Adolescent↗
PubMed2001

Neuralized is essential for a subset of Notch pathway-dependent cell fate decisions during Drosophila eye development.

Neuralized (neur) is a neurogenic mutant of Drosophila in which many signaling events mediated by the Notch (N) receptor are disrupted. Here, we analyze the role of neur during eye development. Neur is required in a cell-autonomous fashion to restrict R8 and other photoreceptor fates and is involved in lateral inhibition of interommatidial bristles but is not required for induction of the cone cell fate. The latter contrasts with the absolute requirement for Suppressor of Hairless and the Enhancer of split-Complex for cone cell induction. Using gain-of-function experiments, we further demonstrate that ectopic wild-type and truncated Neur proteins can interfere with multiple N-controlled aspects of eye development, including both neur-dependent and neur-independent processes.

Animals↗
PubMed2001

neuralized functions cell-autonomously to regulate a subset of notch-dependent processes during adult Drosophila development.

neuralized (neu) represents one of the strong neurogenic mutants in Drosophila. Mutants of this class display, among other phenotypes, a strong overcommitment to neural fates at the expense of epidermal fates. We analyzed the role of neu during adult development by using mutant clonal analysis, misexpression of wild-type and truncated forms of Neu, and examination of genetic interactions with N-pathway mutations. We find that neu is required cell-autonomously for lateral inhibition during peripheral neurogenesis and for multiple asymmetric cell divisions in the sensory lineage. In contrast, neu is apparently dispensable for other N-mediated processes, including lateral inhibition during wing vein development and wing margin induction. Misexpression of wild-type Neu causes defects in both peripheral neurogenesis and wing vein development, while a truncated form lacking the RING finger is further capable of inhibiting formation of the wing margin. In addition, the phenotypes produced by misexpression of wild-type and truncated Neu proteins are sensitive to the dosage of several N-pathway components. Finally, using epitope-tagged Neu proteins, we localize Neu to the plasma membrane and reveal a novel morphology to the sensory organ precursor cells of wing imaginal discs. Collectively, these data indicate a key role for neu in the reception of the lateral inhibitory signal during peripheral neurogenesis.

Animals↗
PubMed2001

Endoscopic stenting for malignant biliary obstruction.

Use of endoscopic stents to manage patients with malignant obstructive jaundice is a well accepted measure. Interpretation of the results of endoscopic stenting must be made with reference to the level of the bile duct obstruction. Results were generally unsatisfactory for hilar lesions, especially when the intrahepatic ducts were segregated into multiple isolated systems. After deployment, stent dysfunction due to clogging by biliary sludge is apparently an inevitable process for the conventional plastic stent. Considerable efforts had been made to prolong the stent patency by changing its physical configuration, coating the inner lumen, and the choice of material but with little success. The development of a self-expandable metal stent is a major advance, but the benefits derived from a larger stent lumen are compromised by the initial expense and the tumor ingrowth through the wires for all models available commercially. Current data failed to substantiate the value of routine preoperative biliary decompression, as there is no reduction in the morbidity and mortality rates after surgery. Although biased patient selection may have resulted in the negative observations made, repeated clinical trials should probably focus on patients with distal bile duct tumors who are preparing for a major pancreatic resection. As a definitive palliative measure, endoscopic stenting is a more cost-effective option than surgery for patients with limited life expectancy based on data regarding plastic stents. The recommendations are evolving however, as there is progressive refinement of laparoscopic surgery techniques and designs of endoscopic stents.

Cholestasis, Extrahepatic↗
PubMed2001

Xenopus neuralized is a ubiquitin ligase that interacts with XDelta1 and regulates Notch signaling.

Notch signaling in Drosophila requires a RING finger (RF) protein encoded by neuralized. Here we show that the Xenopus homolog of neuralized (Xneur) is expressed where Notch signaling controls cell fate choices in early embryos. Overexpressing XNeur or putative dominant-negative forms in embryos inhibits Notch signaling. As expected for a RF protein, we show that XNeur fulfills the biochemical requirements of ubiquitin ligases. We also show that wild-type XNeur decreases the cell surface level of the Notch ligand, XDelta1, while putative inhibitory forms of XNeur increase it. Finally, we provide evidence that XNeur acts as a ubiquitin ligase for XDelta1 in vitro. We propose that XNeur plays a conserved role in Notch activation by regulating the cell surface levels of the Delta ligands, perhaps directly, via ubiquitination.

Amino Acid Sequence↗
PubMed2001

Drosophila neuralized is a ubiquitin ligase that promotes the internalization and degradation of delta.

The Drosophila gene neuralized (neur) has long been recognized to be essential for the proper execution of a wide variety of processes mediated by the Notch (N) pathway, but its role in the pathway has been elusive. In this report, we present genetic and biochemical evidence that Neur is a RING-type, E3 ubiquitin ligase. Next, we show that neur is required for proper internalization of Dl in the developing eye. Finally, we demonstrate that ectopic Neur targets Dl for internalization and degradation in a RING finger-dependent manner, and that the two exist in a physical complex. Collectively, our data indicate that Neur is a ubiquitin ligase that positively regulates the N pathway by promoting the endocytosis and degradation of Dl.

Animals↗
PubMed2001

Wheelchair use by patients with amyotrophic lateral sclerosis: a survey of user characteristics and selection preferences.

OBJECTIVES: To determine wheelchair types and features that are most beneficial to patients with amyotrophic lateral sclerosis (ALS), to ascertain at what stage of disease and disability patients benefit from wheelchair use, and to pinpoint the differences in patient characteristics between the users of manual and motorized wheelchairs. DESIGN: Internally generated questionnaire. SETTING: A neuromuscular clinic. PATIENTS: Forty-two patients (28 men, 14 women) with ALS who used wheelchairs and whose mean age was 53.9 years (range, 32-75yr). MAIN OUTCOME MEASURE: Wheelchair users completed a 39-item survey. RESULTS: At the time of the survey, the patients' mean Appel ALS rating scale total score was 84.5 (range, 48-138), indicating moderate disability. Forty-one patients reported that wheelchairs permitted them greater interaction in their communities; 33 were "very satisfied" with the positive impact of wheelchair use on their activity levels. Most users did not work and needed caregiver assistance for activities of daily living. The most desirable wheelchair features provide extra comfort (supports for the head, neck, trunk, extremities) and have improved maneuverability (lightweight frame, smaller wheelbase). Undesirable features are low sling backs and sling seats, nonremovable static leg rests, and large frames. No significant differences were reported between manual wheelchair users and motorized wheelchair users in terms of overall disease symptom severity, arm and leg strength, and bulbar function. However, motorized wheelchairs offer patients a greater sense of independence and an improved sense of well-being. CONCLUSION: Information obtained directly from wheelchair users with ALS provided first-hand experience concerning the most and least desirable features of wheelchairs and may help other ALS patients make informed decisions when purchasing a wheelchair.

Adult↗
PubMed2000

Long-term efficacy of posteroventral pallidotomy in the treatment of Parkinson's disease.

The authors describe results of unilateral posteroventral pallidotomy (PVP) in 89 patients with PD. At 3 months after surgery, 81.9% of the patients reported marked or moderate improvement in their parkinsonian symptoms. Postoperative Unified PD Rating Scale "off" state mean total motor score improved by 35.5% and the mean activities of daily living score by 33.7% (p <0.001). Improvements in parkinsonian symptoms were maintained in both"off" and "on" states in 62 patients at 12 months after PVP and in 41 patients who were followed for 18 months or longer (mean 26.6 months).

Adult↗
PubMed2000

Postural control in Parkinson's disease after unilateral posteroventral pallidotomy.

Postural control changes were studied in 27 patients with Parkinson's disease after unilateral posteroventral pallidotomy (PVP). Patients were evaluated before PVP and at 3, 6 and 12 months post-PVP, both 'off' and 'on' parkinsonian medications, with selected evaluation tools representing functional performance, functional balance and posturographic components of balance. The majority of variables in the 'off' state were significantly improved at 3 months post-PVP. Improvement was maintained at 6 months but had declined for some variables by the 12 month follow-up. Standing up from a chair (P = 0.009), the balance and gait sections of the Performance-Oriented Assessment (P < or = 0.0004), and the limits of stability (LOS) posturography variables (P < 0.0005) of the average time to reach a target, the number of targets missed and the initial excursion distance to the target (P = 0.029) retained significant improvement at the 12 month follow-up. When the patients were in the 'on' state, LOS posturography variables of average time to target, average path length deviation, and the number of targets missed were the only variables significantly improved at 3 months post-PVP (P = -0.013) and this improvement was maintained at 12 months post-PVP (P = 0.012-0.041). Unilateral PVP improves axial symptoms of Parkinson's disease involved in functional performance such as gait disturbance as well as improving postural stability in the 'off' state. Generally, the maximum improvement is seen at 3 months post-PVP with many variables remaining significantly improved at 12 months post-PVP. Axial dyskinesias in the 'on' state are also significantly reduced with the improvement maintained at 12 months post-PVP. These findings suggest that unilateral pallidotomy is not only effective in abolishing levodopa-induced dyskinesias, but that it also improves the axial signs of Parkinson's disease.

Aged↗
PubMed2000

Neuropsychological outcome after unilateral pallidotomy for the treatment of Parkinson's disease.

OBJECTIVE: To assess the long term cognitive outcome of unilateral posteroventral pallidotomy (PVP) and the overall efficacy of the surgery. METHODS: Forty two (29 left and 13 right PVP) patients with Parkinson's disease underwent neurological and neuropsychological testing before PVP and at 3 and 12 months after PVP. The neuropsychological testing battery emphasised measures of verbal learning and memory, visuospatial abilities, speed of information processing, executive functioning, and affective functioning. RESULTS: All patients demonstrated motor improvements after surgery during their off state, and 86% of patients also showed improvements in motor functioning in their on state. Repeated measures ANOVA showed significant improvements in confrontational naming, visuospatial organisation, and affective functioning 3 months and 12 months after surgery, with inconsistent improvements in executive functioning 12 months post-PVP. Patients demonstrated a transient impairment in verbal memory, with verbal learning performance returning to baseline 12 months post-PVP after a significant decline 3 months after PVP. When three patients with lesions extending outside of the PVP were excluded from the analysis, a decline in verbal fluency performance after PVP was not found to be significant. Differences due to side of lesion placement were not found on any of the cognitive measures. CONCLUSIONS: In the largest long term follow up study reported to date, the cognitive changes found up to a year after PVP are minimal compared with the robust improvements in motor function. The findings highlight the need to investigate the relation between the specific fibre tracts affected by the lesions and cognitive outcome.

Activities of Daily Living↗