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Biomedical subjects

P Lim

Publications and source records attributed to P Lim.

At least 19 recordsLinked to original sources
PubMed2006

Treatment of schizophrenia with paliperidone extended-release tablets: a 6-week placebo-controlled trial.

BACKGROUND: Paliperidone extended-release tablet (paliperidone ER) is an investigational oral psychotropic developed for schizophrenia treatment. It utilizes OROS technology to provide a unique pharmacokinetic profile, eliminating the need for titration and potentially leading to improved tolerability. Furthermore, paliperidone undergoes limited hepatic metabolism. METHODS: The efficacy and safety of once-daily paliperidone ER (6 mg, 9 mg and 12 mg) were assessed versus placebo in 628 patients with acute schizophrenia in a 6-week, multicenter, double-blind, randomized, parallel-group study. RESULTS: All doses of paliperidone ER demonstrated significant improvement in PANSS score, all PANSS Marder factor scores (p<0.001) and personal and social functioning versus placebo (p<0.001). The PANSS total score also improved significantly in the olanzapine treatment arm. Significantly higher percentages of paliperidone ER patients demonstrated a > or =30% reduction in PANSS total score versus placebo (p<0.001). The incidence of movement disorder-related AEs and rating scales measurements were similar to placebo for the paliperidone ER 6 mg group and higher in the 9 mg and 12 mg groups. In the paliperidone ER groups there were no reports of glucose-related AEs or clinically relevant changes in plasma lipid levels and changes in mean bodyweight<1 kg. CONCLUSION: In this study, all doses of paliperidone ER were effective in significantly improving the symptoms of schizophrenia and personal and social functioning and were generally well tolerated. Paliperidone ER offers a distinctive treatment profile and may provide a valuable new treatment option for patients with schizophrenia.

Adult↗
PubMed2005

Assessment of left ventricular contraction by parametric analysis of main motion (PAMM): theory and application for echocardiography.

The computerized study of the regional contraction of the left ventricle has undergone numerous developments, particularly in relation to echocardiography. A new method, parametric analysis of main motion (PAMM), is proposed in order to synthesize the information contained in a cine loop of images in parametric images. PAMM determines, for the intensity variation time curves (IVTC) observed in each pixel, two amplitude coefficients characterizing the continuous component and the alternating component; the variable component is generated from a mother curve by introducing a time shift coefficient and a scale coefficient. Two approaches, a PAMM data driven and a PAMM model driven (simpler and faster), are proposed. On the basis of the four coefficients, an amplitude image and an image of mean contraction time are synthesized and interpreted by a cardiologist. In all cases, both PAMM methods allow better IVTC adjustment than the other methods of parametric imaging used in echocardiography. A preliminary database comprising 70 segments is scored and compared with the visual analysis, taken from a consensus of two expert interpreters. The levels of absolute and relative concordance are 79% and 97%. PAMM model driven is a promising method for the rapid detection of abnormalities in left ventricle contraction.

Algorithms↗
PubMed2005

Evidence for deletion of 9q as a two-step process in chronic myeloid leukemia.

Evidence for deletion of 9q as a two-step process in chronic myeloid leukemia. Chronic myeloid leukemia (CML) is characterized by the Philadelphia translocation t(9;22)(q34;q11) resulting in the BCR/ABL fusion gene. Submicroscopic deletion of the derivative chromosome 9 occurs in a subset of these patients and is associated with poor prognosis. In the current study, we present two unusual cases of CML selected from a series of 54 consecutive cases. A detailed study using classical cytogenetics and fluorescence in situ hybridization (FISH) analysis was done using dual color extra signal FISH and whole chromosome paint in order to elucidate the mechanism of 9q deletion. One case had two clones on interphase FISH, one with and one without chromosome 9q deletion. The other case had two clones on both cytogenetic and FISH analyses, one with and one without a marker chromosome carrying chromosome 9q sequences. In this latter case, the clone with deletion of the derivative chromosome 9 comprised 21.1% at diagnosis, increasing to 36.8% after 11 months, suggesting a growth advantage. We report here evidence that deletions on 9q in CML may occur through breakage and rearrangement of chromosomes resulting in derivative chromosomes and either a marker chromosome or fragment/episome, followed by loss of chromosome material from the cell.

Adult↗
PubMed2005

The incidence and patterns of BCR/ABL rearrangements in chronic myeloid leukaemia (CML) using fluorescence in situ hybridisation (FISH).

INTRODUCTION: Chronic myeloid leukaemia (CML) is characterised by the formation of the BCR/ABL fusion gene, usually as a result of the Philadelphia (Ph) translocation between chromosomes 9 and 22. MATERIALS AND METHODS: The incidence of both typical and atypical BCR/ ABL gene rearrangements was determined in 110 patients suspected of CML using dual fusion fluorescence in situ hybridisation (DF-FISH) probes. RESULTS: Eighty-seven per cent of CML patients showed Ph translocation while 13% were negative for the Ph chromosome. About 71.9% of Ph-positive patients displayed the typical DF-FISH signal pattern. Atypical patterns among the Ph-positive patients included the concurrent loss of residual proximal 9q and distal 22q (10.4%), complex translocation with additional partners (9.4%), supernumerary Ph (3.1%), loss of residual 9q sequences proximal to breakpoint (3.1%), and deletion of distal derivative 22q signal (2.1%). Cryptic genetic alterations with loss of proximal 9q sequences were found in 13.5% of CML Ph-positive patients, which is associated with poor prognosis. Fusion signals were detected in 57.1% of CML Ph-negative patients, indicating cryptic BCR/ABL rearrangements (i.e., masked Ph). CONCLUSION: FISH is able to detect BCR/ABL fusion in CML with masked or variant Ph not apparent with conventional karyotyping. Establishment of signal patterns with FISH is important as atypical patterns may have clinical prognostic implications.

Gene Rearrangement↗
PubMed2005

[Echocardiography and mechanical complications of recent myocardial infarction].

The constantly advancing technology of echocardiography and its widespread usage in the intensive care unit has made it a routine examination in patients with acute myocardial infarction. It has become the reference method for diagnosis and monitoring of certain complications such as pericardial effusion, intra-ventricular thrombosis, ventricular aneurysm and mitral regurgitation. The echocardiographic description of these complications dates back to the 1980s during which prospective studies accurately described the principal abnormalities. These descriptions have not been much improved upon with the advent of new technology. On the other hand, the frequency of these complications assessed in an era when reperfusion by thrombolysis or primary angioplasty was much less common than today, has considerably decreased.

Echocardiography↗
PubMed2004

Radiation fields in gynecologic oncology: correlation of soft tissue (surgical) to radiologic landmarks.

OBJECTIVES: (1). To determine if radiation fields defined by bony structure landmarks correlate to anatomic boundaries of lymph node dissection marked intraoperatively; and (2). to determine if a patient's body mass index (BMI) correlates with these anatomic or radiographic boundaries. METHODS: One hundred patients undergoing exploratory laparotomy with pelvic and paraaortic lymph node dissection had three medium hemoclips placed at vascular junctions considered of clinical significance to lymph node dissection: insertion of the left ovarian vein into the renal vein, insertion of the right ovarian vein into the vena cava, inferior mesenteric artery (IMA), bifurcation of the aorta, bifurcation of the common iliacs (bilateral), and the insertion of the deep circumflex vein (DCV) in to the external iliac vein (bilateral). Postoperatively, an abdominal X-ray was obtained. Comparisons were made between these eight major vascular landmarks and radiographic bony landmarks that are used to define radiation field boundaries. The percentage of vascular landmarks that were encompassed or fell outside of traditional radiation fields was determined with a 1-cm margin considered an adequate boundary for radiation. These measurements were also compared to patient BMIs. RESULTS: Radiation fields defined by traditional bony landmarks would adequately encompass the paraaortic lymph nodes in the majority of patients (91%). For pelvic radiation fields, there was a significant "miss" (39%) of common iliac lymph nodes. Approximately one quarter (26%) of patients would receive inadequate coverage of one or both of the lateral boundaries of pelvic radiation. There was no apparent correlation of BMI to vascular or bony landmarks. CONCLUSIONS: Radiation fields determined by traditional bony landmarks do not adequately reflect the anatomic (surgical) landmarks associated with the lymphatic drainage of the female reproductive organs. Although the majority of tertiary care centers now use advanced imaging techniques (e.g. computed tomography) to plan their radiation treatments, the historical guidelines of radiographic landmarks are still used in smaller institutions and continue to be referenced in Gynecologic Oncology Group protocols. For centers still using radiographic landmarks, the application of hemoclips with X-ray identification is a low-cost modality that is easily reproducible and may be clinically useful in guiding treatment.

Adult↗
PubMed2003

Small-cell carcinoma of the cervix: fourteen years of experience at a single institution using a combined-modality regimen of involved-field irradiation and platinum-based combination chemotherapy.

PURPOSE: To determine the efficacy and toxicity of a combined-modality regimen of irradiation with platinum-based combination chemotherapy in small-cell carcinoma of the cervix (SCCC). PATIENTS AND METHODS: Thirty-four patients with SCCC were seen and treated at the British Columbia Cancer Agency between May 1988 and November 2002. Two protocols were used, SMCC (May 1988 to December 1995) and SMCC2 (January 1996 to November 2002). Both protocols used cisplatin, etoposide, and involved-field irradiation (essentially pelvis plus or minus para-aortics) with concurrent chemotherapy. In addition, SMCC2 included carboplatin and paclitaxel, and the para-aortics were irradiated routinely. RESULTS: Thirty-one patients received either SMCC (n = 17) or SMCC2 (n = 14), and three patients did not (disease too extensive, n = 1; patient refusal, n = 1; and alternative regimen, n = 1). For the 31 patients treated on one of the protocols, the 3-year overall and failure-free survival (FFS) rates were 60% and 57%, respectively. The results were equivalent for SMCC and SMCC2. Radiologic stage was the only independent predictor for FFS (80% at 3 years for stage I and II patients v 38% at 3 years for stage III and IV patients). Distant failure (28%) was the most common cause of failure, with local failure occurring in 13% of patients. The switch to SMCC2 did not improve efficacy but did lessen the toxicity. CONCLUSION: SCCC can be successfully treated in approximately 55% of patients with a combination of irradiation and platinum-based chemotherapy. Disease extent predicts for chance of curability.

Adult↗
PubMed2003

The atherogenic lipid profile is associated with type 2 diabetes and some of its treatment modalities.

BACKGROUND: Since diabetes is strongly linked to cardiovascular disease, we tested whether: 1) diabetic patients have a high prevalence of the atherogenic lipid profile and 2) the drugs used to treat hyperglycemia are related to the atherogenic lipid profile. METHODS: Seventy-two diabetic patients were retrospectively studied for lipids using the Lipid Research Clinic methods and LDL and HDL gel electrophoreses. RESULTS: Despite normal mean levels of total LDL- and HDL-cholesterol (HDL-c), diabetic patients had abnormal mean levels and an unusually high prevalence of lipid abnormalities not apparent on routine lipid blood tests. Thus, mean LDL peak particle diameter (PPD) was 258 +/- 11A and values < 263A occurred in 57% of diabetic patients; HDL2 < 40% in 61% and Lp(a) > 25 mg/dl occurred in 36% of patients, despite good glycemic control. Mean HbA1c [Diabetes Control and Complications Trial (DCCT) formatted] was 6.5 +/- 1.4%. In contrast to patients using sulfonylureas or metformin, diabetic patients using insulin had significantly larger mean LDL PPD (261 vs 254A, p < 0.006), lower triglycerides (115 vs 215 mg/dl,p < 0.0001), higher HDL-c (53 vs 40 mg/dl,p < 0.0001) and higher HDL2 levels (43 vs 29%, p < 0.0001). CONCLUSIONS: In this diabetic group, traditional guidelines fail to identify patients with high dyslipidemic prevalence rates (84%). Further, certain oral hypoglycemic treatments are associated with less favorable atherogenic lipid profiles when compared to insulin treatment.

Adult↗
PubMed2001

Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: a phase II study.

PURPOSE: To evaluate the efficacy of carboplatin plus paclitaxel in primarily advanced or recurrent endometrial cancers. PATIENTS AND METHODS: Four distinct patient groups received carboplatin (area under the curve, 5 to 7) plus paclitaxel 175 mg/m(2) for 3 hours at 4-week intervals: group 1 (n = 21), patients with primarily advanced, nonpapillary serous cancers; group 2 (n = 20), the same as group 1 but with papillary serous cancers; group 3 (n = 18), recurrent, nonpapillary serous cancers; and group 4 (n = 4), recurrent, papillary serous cancers. Involved-field irradiation was used in groups 1 and 2 for those with radioencompassable disease. RESULTS: Sixty-three patients were treated. Response rates to chemotherapy in the assessable patients in the four groups were 78% (95% confidence interval [CI], 51% to 100%); 60% (95% CI, 35% to 85%), 56% (95% CI, 34% to 78%), and 50%, respectively. Nineteen patients (90%) in group 1 also were irradiated, and the median failure-free survival time for all 21 patients was 23 months, with a 62% 3-year overall survival rate. Eleven patients (55%) in group 2 were irradiated, and the median failure-free survival time for all 18 patients was 18 months, with a 39% 3-year overall survival rate. The median failure-free interval in the patients in group 3 was 6 months, with a 15-month median overall survival time. Toxicity was manageable, reversible, and predominantly hematologic. Two patients developed neutropenic fever, and three patients, including these two, were hospitalized for complications. CONCLUSION: Carboplatin-paclitaxel is an efficacious, low-toxicity regimen for managing primarily advanced or recurrent endometrial cancers.

Adult↗
PubMed2001

Early stage uterine papillary serous carcinoma of the endometrium: effect of adjuvant whole abdominal radiotherapy and pathologic parameters on outcome.

BACKGROUND: Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer, behaving like ovarian epithelial cancers and having a predilection for transperitoneal relapse. Within this subtype of uterine cancers, predictors of outcome and the role of adjuvant therapies have not been firmly established, to the authors' knowledge. METHODS: Between 1985-1995, 78 patients who had International Federation of Gynecology and Obstetrics (FIGO) Stage I, II, or IIIa UPSC (based on positive washings only) were seen at the British Columbia Cancer Agency. During this time, the authors had a policy of offering adjuvant pelvic, paraaortic and whole-abdominal radiotherapy (WART) to these patients. Fifty-eight patients received adjuvant WART, and 20 received lesser or no adjuvant therapy. The authors undertook a retrospective analysis of pathology with quantification of the percentage of papillary serous component (% PSC) and p53 expression. Pathology was retrieved and reviewed on 62 patients; p53 staining was performed on blocks from the hysterectomy specimen in 46 cases. Pathologic parameters, stage, and adjuvant therapy were correlated with clinical outcome in a multivariate analysis. RESULTS: Median follow-up was 52 months (3-139 mos) and the 5-year disease-specific survival rate was 66.2%. The 58 patients who received adjuvant WART had a significantly better 5-year disease-specific survival than those 20 patients who did not, 74.9% versus 41.3% (P = 0.04). Multivariate analysis showed that % PSC and p53 were not significant predictors of outcome for early stage UPSC. Of the factors examined, only FIGO stage and WART significantly predicted improved outcome (P = 0.02 and 0.04, respectively). CONCLUSIONS: The current study demonstrated a significant difference in the outcomes of patients who had FIGO Stage I compared with Stage II UPSC. In the current series of patients, the authors were not able to predict outcome based on % PSC or p53 expression. The current study results with WART were promising, and WART merits further study.

Adult↗
PubMed2000

Effects on serum lipid profiles of continuous 17beta-estradiol, intermittent norgestimate regimens versus continuous combined 17beta-estradiol/norethisterone acetate hormone replacement therapy.

OBJECTIVE: To compare the effects of a daily oral 1-mg dose of continuous 17beta-estradiol (E2) plus intermittent (3 days off, 3 days on) norgestimate (NGM) 90 microg (n = 221), an oral 2-mg dose of continuous E2 plus intermittent NGM 180 microg (n = 219), and an oral 2-mg dose of continuous E2 plus continuous norethisterone acetate (NETA) 1 mg (n = 217) on blood lipids and lipoproteins in postmenopausal women. BACKGROUND: The present study was undertaken because some progestins have adverse effects on lipid profiles, thereby negating the favorable effects of estrogens. METHODS: This was a multicenter, randomized, parallel-group trial that focused primarily on the 2 marketed regimens--E2 1 mg/NGM 90 microg and E2/NETA. Both subjects and investigators were blinded to the intermittent regimens; the continuous combined regimen was administered open-label. After a minimum 12-hour overnight fast, blood samples were collected at baseline and during months 7 and 12 to determine lipid and lipoprotein concentrations using validated methods. RESULTS: E2 1 mg/NGM 90 microg was associated with significant (ie, the 95% CI did not include 0) increases in high-density lipoprotein cholesterol (HDL-C) (6.8% [95% CI = 4.7%, 9.0%] and 4.8% [2.3%, 7.2%] at months 7 and 12, respectively) and high-density lipoprotein 2 cholesterol (HDL2-C) (10.8% [6.2%, 15.3%] and 24.1% [18.9%, 29.4%]) concentrations, and decreases in total cholesterol (-7.7% [-9.0%, -6.3%] and -9.2% [-10.5%, -7.9%]), low-density lipoprotein cholesterol (-14.3% [-16.3%, -12.4%] and -14.9% [-16.7%, -13.2%]), and lipoprotein(a) (-30.6% [-41.4%, -20.0%] at month 12) concentrations. A significant difference (P < 0.001 by analysis of variance) between the E2 1-mg/NGM 90-microg and NETA regimens was seen for HDL-C and HDL2-C concentrations, which were elevated in subjects receiving E2 1 mg/NGM 90 microg but reduced (-9.1% [-11.1%, -7.1%] and -12.3% [-14.3%, -10.3%] for HDL-C at months 7 and 12, respectively; -14.2% [-18.0%, -10.4%] and -2.5% [-7.8%, +2.8%] for HDL2-C at months 7 and 12, respectively) in those receiving E2/NETA. CONCLUSIONS: In the present study, continuous E2 1 mg/NGM 90 microg was associated with beneficial effects on lipids and lipoproteins in healthy postmenopausal women, effects that were greater at least for HDL-C and HDL2-C than those observed with continuous combined E2/NETA. The applicability of the study results to women with preexisting cardiovascular disease or dyslipidemia, or those who are overweight, remains to be investigated.

Administration, Oral↗
PubMed1999

A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Topiramate YL Study Group.

OBJECTIVE: To evaluate the efficacy and safety of topiramate as adjunctive therapy for Lennox-Gastaut syndrome in a multicenter, double-blind, placebo-controlled trial. BACKGROUND: Conventional antiepileptic drugs are frequently ineffective against multiple-seizure types of Lennox-Gastaut syndrome. METHODS: Ninety-eight patients >1 year to <30 years of age, with slow spike-and-wave patterns on EEG, seizure types including drop attacks, and either a history of or active atypical absence seizures, were assigned to an 11-week, double-blind treatment phase with either topiramate or placebo. Topiramate was titrated to target doses of approximately 6 mg/kg/d. RESULTS: For drop attacks, the most severe seizures associated with this syndrome, the median percentage reduction from baseline in average monthly seizure rate was 14.8% for the topiramate group and -5.1% (an increase) for the placebo group (p = 0.041). Topiramate-treated patients demonstrated greater improvement in seizure severity than did placebo-treated patients based on parental global evaluations (p = 0.037). The percentage of patients with a > or = 50% reduction from baseline in major seizures (drop attacks and tonic-clonic seizures) was greater in the topiramate group (15/46 or 33%) than in the control group (4/50 or 8%; p = 0.002). The most common adverse events in both groups were CNS related; there were no discontinuations from topiramate therapy due to adverse events. CONCLUSIONS: Topiramate adjunctive therapy was effective in reducing the number of drop attacks and major motor seizures and in improving seizure severity as determined by parental global evaluation.

Adolescent↗