Stephanie Fook-Chong

Evaluation of somnolence in Parkinson’s disease: Comparison with age- and sex-matched controls

Abstract—The authors found a significantly higher prevalence of daytime somnolence in 201 patients with PD compared with 214 age- and sex-matched healthy control subjects (Epworth Sleepiness Scale score 5.6 vs 4.6). The prevalence of “sleep attacks” (SA) was about seven times higher in patients with PD than in control subjects (13.9% vs 1.9%;p < 0.0005). Multivariate analysis demonstrated that a higher dose of levodopa and longer duration of disease significantly predicted for SA in patients with PD. Epworth Sleepiness Scale scores of ≥10 had 71.4% sensitivity and 88.4% specificity for SA.

Nasal-type extranodal natural killer/T-cell lymphomas: a clinicopathologic and genotypic study of 42 cases in Singapore

We studied the clinicopathologic features of 42 cases of nasal-type extranodal natural killer (NK)/T-cell lymphoma in Singapore and compared our findings with other series reported in the Asian and Western populations. A panel of immunohistochemical stains, which included CD2, CD3, CD4, CD8, CD56, T-cell intracellular Antigen-1 and granzyme B, and in situ hybridization for Epstein–Barr virus encoded RNA (EBER) were performed. Polymerase chain reaction for T-cell receptor-gamma gene rearrangement using both gel and capillary electrophoresis were evaluated to determine the proportion of tumors which are of true T-cell lineage. We also studied the functional status of the overexpressed p53 protein in these lymphomas by correlating p53 expression with its downstream target protein, p21. In all, 31 out of 42 cases presented in the upper aerodigestive tract. The other sites of involvement included gastrointestinal tract, skin, soft tissue, testis, liver, spleen, bone marrow and brain. The tumors displayed characteristic morphologic features. In situ hybridization for EBER was detected in 41 out of 42 cases (97.6%). The only significant adverse prognostic factor identified was an International Prognostic Index of two or more. A significantly higher proportion of the tumors (27%), compared to previous studies, demonstrated monoclonal T-cell receptor-gamma gene rearrangement. There was, however, no difference in survival or clinicopathologic features between the true NK-cell tumors and their T-cell counterparts. Overexpression of p53 was present in 40% of the cases, but no significant difference in survival rate was detected in patients with p53 overexpression and there was no association between p53 overexpression with large cell morphology, and advanced stage of disease. These findings suggest that molecular aberrations other than those of the p53 pathway may be operative in the pathogenesis of this malignancy.

Case-control study of diffusion tensor imaging in Parkinson’s disease

Background: Preliminary work has shown that diffusion tensor MRI (DTI) may contribute to the diagnosis of Parkinson’s disease (PD). Objectives: We conducted a large, prospective, case control study to determine: (1) if fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values on DTI in the basal ganglia and substantia nigra are different between patients with PD and healthy controls; and (2) the predictive value of these parameters and their clinical utility. Methods: DTI imaging was carried out in patients with PD and controls. FA and ADC values were obtained from various brain structures on the DTI scan using the diffusion tensor taskcard. The structures studied were: caudate, putamen, globus pallidus, thalamus and substantia nigra. Results: 151 subjects (73 PD patients, 41 men, 32 women; mean age 63.6 years) and 78 age and sex matched control subjects were studied. The FA value of the substantia nigra in patients with PD was lower compared with controls (0.403 vs 0.415; p = 0.001). However, no significant differences were demonstrated for FA or ADC values of other structures. Multiple regression analysis revealed that the clinical severity of PD correlated inversely with the FA value in the substantia nigra in patients with PD (regression coefficient −0.019). No single FA value had both a high positive and negative predictive power for PD. Conclusions: We demonstrated in a large, prospective, case control study that the FA value in the substantia nigra on DTI was lower in PD compared with healthy controls, and correlated inversely with the clinical severity of PD. Further longitudinal studies would be helpful to assess the clinical utility of serial FA measurements of the substantia nigra in objective quantification of disease progression and monitoring of the therapeutic response.

Dose-dependent protective effect of coffee, tea, and smoking in Parkinson's disease: a study in ethnic Chinese

INTRODUCTION Few studies have examined the relationship of coffee and tea in Parkinsons disease (PD). The potential protective effect of coffee intake and risk of PD has not been studied in a Chinese population. There is a high prevalence of caffeine takers among Chinese in our population. OBJECTIVE We undertook a case control study to examine the relationship between coffee and tea drinking, cigarette smoking, and other enviromental factors and risk of PD among ethnic Chinese in our population. METHODS AND RESULTS 300 PD and 500 population controls were initially screened. Two hundred case control pairs matched for age, gender, and race were finally included in the analysis. Univariate analysis revealed significant association of PD with coffee drinking (p<0.0005), tea drinking (p=0.019), alcohol drinking (p=0.001), cigarette smoking (p<0.0005), and exposure to heavy metals (p=0.006). Conditional logistic regression analysis demonstrated that amount of coffee drunk (OR 0.787, 95%CI 0.664-0.932, p=0.006), amount of tea drunk (OR 0.724, 95%CI 0.559-0.937, p=0.014), number of cigarettes smoked (OR 0.384, 95%CI 0.204-0.722, p=0.003), history of heavy metal and toxin exposure (OR 11.837, 95%CI 1.075-130.366, p=0.044), and heart disease (OR 5.518, 95%CI 1.377-22.116, p=0.016) to be significant factors associated with PD. One unit of coffee and tea (3 cups/day for 10 years) would lead to a 22% and 28% risk reduction of PD. One unit of cigarette smoke (3 packs/day for 10 years) reduced the risk of PD by 62%. CONCLUSIONS We demonstrated a dose-dependent protective effect of PD in coffee and tea drinkers and smokers in an ethnic Chinese population. A history of exposure to heavy metals increased the risk of PD, supporting the multifactorial etiologies of the disease.

Hormone Receptor and c-ERBB2 Status in Distant Metastatic and Locally Recurrent Breast Cancer Pathologic Correlations and Clinical Significance

Estrogen receptor (ER), progesterone receptor (PR), and c-ERBB2 (HER2/neu) are therapeutically and prognostically important markers in the management of breast carcinoma. They are not always analyzed in distant metastatic and locally recurrent breast cancers. We compared immunohistochemical expression in a series of primary breast carcinomas with their distant metastases (n = 72) and local recurrences (n = 45) and analyzed the impact of any changes on survival. Discordance rates between primary and metastatic and between primary and locally recurrent lesions, respectively, were 18% (13/72) and 13% (6/45) for ER, 42% (30/72) and 33% (15/45) for PR, and 7% (5/72) and 2% (1/45) for c-ERBB2. There was statistically significant discordance between primary and metastatic PR status (P = .017; kappa = 0.201). Among locally recurrent tumors, 15 (33%) of 45 revealed discordance for PR (P = .006; kappa = 0.366). We observed a trend for shorter survival among women with ER- metastatic and locally recurrent tumors regardless of the primary tumor ER status. Our findings suggest a benefit for routine evaluation of ER, PR, and c-ERBB2 status in distant metastatic and locally recurrent breast cancer for therapeutic and prognostic purposes.

Case Control Polysomnographic Studies of Sleep Disorders in Parkinson's Disease

Background The relationship between a number of primary sleep disorders and Parkinsons disease (PD) is still debated. There are limited case control polysomnographic studies in PD and most of these study sample sizes are small. Methodology/Findings We conducted one of the largest case-control studies involving overnight polysomnographic evaluation, with prospective recruitment of unselected Parkinsons disease patients and healthy controls from an Asian population. The cases were recruited from the specialized movement disorder outpatient clinics in a tertiary referral center, and controls from the same geographical locations. All subjects underwent an overnight polysomnographic study and a multiple sleep latency test. A total of 124 subjects including 56 patients and 68 controls frequency-matched for age and sex were included. Multivariate analysis revealed that patients had significantly shorter total sleep time than controls (p = 0.01), lower sleep efficiency (p = 0.001) and increased REM latency (p = 0.007). In patients, multivariate analysis showed that reduced total sleep time was significantly associated with increased age (p = 0.001) and increased levodopa dose (p = 0.032). The mean Insomnia Severity Index was higher in PD patients (9.0±7.1) compared to controls (3.3±3.9, p<0.001). The mean Epworth Sleepiness Scale score was higher in PD patients (9.3±5.9 vs. 5.7±4.8, p<0.001). Nocturnal arousals, obstructive sleep apnea, periodic leg movements and objective abnormal sleepiness were not increased in our patients. Conclusions/Significance Our case-control polysomnographic study, the first-ever performed in an Asian population, revealed altered sleep architecture and reduced sleep in PD patients compared to controls. Reduced total sleep time was associated with increased age and levodopa dose. However, nocturnal arousals, primary sleep disorders and abnormal sleepiness were not increased in our PD patients suggesting that ethnic/genetic differences may be a factor in the pathophysiology of these conditions.

The feasibility and accuracy of sentinel lymph node biopsy in clinically node‐negative patients after neoadjuvant chemotherapy for breast cancer—a systematic review and meta‐analysis

The sentinel lymph node biopsy (SLNB) is now an accepted alternative to the axillary lymph node dissection for pathologic evaluation of the axilla in patients with early breast cancer. The use of SLNB after neoadjuvant chemotherapy (NAC) is controversial. This meta‐analysis aims to determine the feasibility and the accuracy of SLNB in the population of patients who are clinically node‐negative after NAC for breast cancer. J. Surg. Oncol. 2011;104:97–103.

Evidence of increased odds of essential tremor in Parkinson's disease

In a case control study using a standardized protocol, 600 subjects were evaluated for essential tremor (ET). We demonstrated that ET was significantly more frequent in patients with Parkinsons disease (PD) (12/204, 5.9%) compared to diseased controls (2/206, 1%) and healthy controls (1/190, 0.5%). A regression analysis with ET as outcome and group (either PD or healthy controls or diseased controls) as independent variable (adjusting for age and sex) revealed that PD had higher odds of having ET than diseased controls (OR = 5.43, 95% CI = 1.16, 25.39, P < 0.001) and healthy controls (OR = 10.87, 95% CI = 1.39, 85.15, P < 0.001). The low frequency of ET in our controls was further confirmed in a follow‐up study in a group of age and gender matched general medical patients who attended an outpatient clinic (0% frequency). Eight of 204 PD (3.9%) compared to none of diseased (0%) (P = 0.004) and healthy controls (0%) (P = 0.008) had a prior diagnosis of ET. The duration of ET symptoms in patients with PD was 25.1 ± 19.6 (range 3–60) years. A multivariate analysis demonstrated that a lower dose of levodopa (OR = 0.993, 95%CI for OR = 0.988, 0.997, P < 0.001) and a higher age of onset of disease (OR = 1.108, 95%CI for OR = 1.035, 1.187, P < 0.001) were associated with increased odds of PD with ET, compared to patients with PD without ET. In our Asian population, patients with PD were 5 to 10 times more likely to have ET compared to diseased and healthy controls, suggesting that the association of ET and PD is unlikely to be ethnicity‐specific.

Immunohistochemical expression of hormone receptors in invasive breast carcinoma: correlation of results of H-score with pathological parameters.

Summary The results of H‐scores of oestrogen and progesterone receptor (ER and PR) expression in 150 invasive breast cancers were correlated with conventional pathological prognostic parameters: tumour size, histological grade and subtype, lymph node status, lymphovascular invasion, Nottingham Prognostic Index (NPI) and pathological stage. ER and PR status was determined by immunohistochemical staining of sections cut from archival paraffin‐embedded tissue blocks. We defined positive receptor expression as a H‐score of 50 and above. Our findings revealed ER and PR positivity in 98 (65%) and 52 (35%) cases, respectively. Fiftyone (34%) ER‐positive cases also showed PR expression, while 51 (34%) tumours were negative for both ER and PR. Positive expression for ER and PR was significantly correlated with histological grade (P < 0.0005), mitotic score (P < 0.05) and nuclear pleomorphism (P < 0.05). When we used the relatively simpler method of a cut off of at least 10% tumour cell nuclear staining of moderate or greater intensity as positive receptor status, we found that it agreed well with results of the H‐score, a more quantitative method of assessment.

Bioresorbable adhesion barrier facilitates early closure of the defunctioning ileostomy after rectal excision: a prospective, randomized trial.

INTRODUCTION A temporary loop ileostomy is often created to minimize the impact of peritoneal sepsis from an anastomotic dehiscence after a coloanal or low colorectal anastomosis. Such a stoma is usually closed after 6 to 12 weeks when the intestinal edema is reduced and the peristomal adhesions are less dense. This period is three to four times longer than necessary for assurance of anastomotic healing, which is usually achieved by the second week after surgery. With the use of a bioresorbable membrane to minimize the formation of peristomal adhesions, earlier closure is hypothetically possible at three weeks. METHODS Patients undergoing creation of a defunctioning ileostomy were randomized in Phase I either to have an adhesion barrier membrane wrapped around the limbs of the ileostomy, with closure at three weeks, or to the control group, with no barrier membrane and closure after more than six weeks. In the subsequent Phase II, the efficacy of the barrier membrane was compared in a similar manner with a control group at ileostomy reversal after three weeks. Peristomal adhesions at the time of stomal mobilization were scored in a blinded manner. RESULTS In Phase I, no statistically significant differences were noted in the mean adhesion scores between the two groups (7.42 vs. 7.28). However, in Phase II, when peristomal adhesions at closure were compared at three weeks for both groups, with and without adhesion barrier placement, there was a significant reduction in the overall mean adhesion scores (5.81 vs. 7.82, respectively). The number of patients with dense adhesions was also reduced in the adhesion barrier group. There was no significant difference in the time taken and the difficulty encountered during ileostomy closure in the two groups. A tendency to easier closure, as evidenced by a lower incidence of perioperative complications, was noted in the adhesion barrier group. CONCLUSION An adhesion barrier membrane placed around the limbs of a defunctioning loop ileostomy reduces peristomal adhesion and facilitates early closure at three weeks with minimal complications.