Antibody dependent cellular phagocytosis (ADCP) and antibody dependent cellular cytotoxicity (ADCC) of breast cancer cells mediated by bispecific antibody, MDX-210

Background: MDX-210 is a bispecific antibody (BsAb) with specificity for both the proto-oncogene product of HER-2/neu (c-erbB-2) and FcRI (CD64). HER-2/neu is overexpressed in malignant tissue of approximately 30% of patients with breast cancer, and FcRI is expressed on human monocytes, macrophages, and IFN- activated granulocytes. We investigated phagocytosis and cytolysis of cultured human breast cancer cells by human monocyte-derived macrophages (MDM) mediated by BsAb MDX-210, its partially humanized derivative (MDX-H210), and its parent MoAb 520C9 (anti-HER-2/neu) under various conditions.Materials and Methods: Purified monocytes were cultured with GM-CSF, M-CSF, or no cytokine for five or six days. Antibody dependent cellular phagocytosis (ADCP) and cytolysis (ADCC) assays were performed with the MDM and HER-2/neu positive target cells (SK-BR-3). ADCP was measured by two-color fluorescence flow cytometry using PKH2 (green fluorescent dye) and phycoerythrin-conjugated (red) monoclonal antibodies (MoAb) against human CD14 and CD11b. ADCC was measured with a non-radioactive LDH detection kit.Results: Both BsAb MDX-210 (via FcRI) and MoAb 520C9 (mouse IgG1, via FcRII) mediated similar levels of ADCP and ADCC. ADCP mediated by BsAb MDX-H210 was identical to that mediated by BsAb MDX-210. Confocal microscopy demonstrated that dual-labeled cells represented true phagocytosis. Both ADCP and ADCC were higher when MDM were pre-incubated with GM-CSF than when incubated with M-CSF.Conclusions: BsAb MDX-210 is as active in vitro as the parent MoAb 520C9 in inducing both phagocytosis and cytolysis of MDM. MDX-210 and its partially humanized derivative, MDX-H210, mediated similar levels of ADCP. GM-CSF appears to superior to M-CSF in inducing MDM-mediated ADCC and ADCP. These studies support the ongoing clinical investigations of BsAb MDX-210 and its partially humanized derivative.     

Randomized double-blind, placebo-controlled trial of oral atenolol in patients with unexplained syncope and positive upright tilt table test results

The objective of this investigation was the assessment of the response rate of oral atenolol in patients with vasovagal syncope after 1 month of treatment. We randomized into two groups all patients referred to our unit who had had at least one episode of syncope or two episodes of presyncope 1 month before presentation and had a positive isuprel Tilt Table Test (TTT). Group 1 (Gr 1) received oral atenolol, and group 2 (Gr 2) received placebo medication. After a 1-month period patients were reassessed for degree of their symptoms and underwent repeated TTT. Forty-two patients were enrolled in the study. Gr 1 and Gr 2 were comparable in age (38 ± 13 years vs 43 ± 14 years, p = 0.216 and sex (male/female = 6:15 vs 10:11, p = 0.204). The severity of attack was similar in both groups. Eight patients in Gr 1 and six patients in Gr 2 had mitral valve prolapse (p = 0.5). No significant differences were seen in systolic blood pressure (122 ± 17 vs 117 ± 16 mm Hg, p = 0.334), diastolic blood pressure (70 ± 11 vs 72 ± 11 mm Hg, p = 0.677), and heart rate (79 ± 12 vs 79 ± 13, p = 0.98) between the two groups. The response rates (negative TTT) after 1 month of treatment were 62% versus 5% (p = 0.0004) in the atenolol and control group, respectively. Moreover, patients who received atenolol reported feeling better compared with those who received placebo (71% vs 29%, p = 0.02). In conclusion, atenolol significantly improved symptoms of patients with vasovagal syncope. Patients who received atenolol were more likely to have negative isuprel TTT.     

Predicting fetal anemia by using reference centile charts for liver length, spleen perimeter and umbilical vein maximum flow velocity in Thai fetuses throughout gestation

AIM: To create reference centile charts for liver length, spleen perimeter and umbilical vein maximum flow velocity (UVVmax) in Thai fetuses in order to predict fetal anemia in Thai fetuses. METHODS: The study was a prospective, cross-sectional study, carried out at the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Faculty of Medicine, Siriraj Hospital, Mahidol University. A total of 780 pregnant women between 13 and 40 weeks' gestation, who attended the antenatal clinic at Siriraj Hospital, Mahidol University, Bangkok, were recruited. Each fetus was measured only once for the purpose of this study. The mean and standard deviation (SD) were estimated at each week of gestation using linear regression modeling. A total of 752 fetuses were measured for fetal liver length, spleen perimeter and UVVmax. Linear regression models were fitted to estimate the mean 95% confidence interval for liver length, spleen perimeter and UVVmax at each gestational age. The centile charts of those parameters were also presented. CONCLUSION: Reference centile charts for fetal liver length, spleen perimeter and UVVmax of Thai fetuses were created.     

Magnetic resonance imaging abnormalities in right ventricular outflow tract tachycardia and the prediction of radiofrequency ablation outcome

BACKGROUND: Recent reports have shown abnormalities on cardiac magnetic resonance imaging (MRI) in patients with right ventricular outflow tract (RVOT) tachycardia. Objectives: Objectives of this study were to demonstrate abnormalities on MRI and signal-averaged ECG (SAECG) in patients with RVOT tachycardia and their correlation with the outcome of radiofrequency (RF) ablation. METHODS: We studied 41 patients with symptomatic RVOT tachycardia and 15 controls. SAECG and cardiac MRI were performed on every subject. An evaluation of structural abnormality, chamber size, function, and wall motion abnormality of the left and right ventricle was performed by MRI. Focal wall thinning was evaluated by the black blood technique and fatty infiltration was evaluated by the T1 image with and without fat suppression. RESULTS: MRI abnormalities were demonstrated in 24 (58.5%) patients with RVOT tachycardia. The abnormalities included localized wall bulging in 22 (53.7%), focal wall thinning in 10 (24.4%), and fatty replacement in 9 (22%) patients. MRI abnormality was found in only one patient in the control group (P < 0.001). Late potentials from SAECG were demonstrated in six (10.7%) patients but none in the controls (P = 0.117). Among 29 patients who underwent RF ablation, 3 patients had a failed procedure and 3 having arrhythmia recurrence needed repeated ablation. MRI abnormalities and late potentials were associated with an unfavorable outcome of RF ablation. CONCLUSIONS: MRI abnormalities were frequently found in patients with RVOT tachycardia. MRI abnormalities and late potentials can predict outcomes of RF ablation.     

Kratom Abuse in Ramathibodi Poison Center,Thailand: A Five-Year Experience

Abstract

Kratom (Mitragyna speciosa Korth), a native tree in Southeast Asia, is misused as an abuse drug and becomes legally widespread to several countries. Currently, it is available through the online market or by some shops. The clinical manifestations of Kratom's effects are not well-defined and the clinical studies are limited. This study was designed to identify the characteristics of Kratom poisoning and withdrawal cases from Kratom exposure cases in Ramathibodi Poison Center (RPC), Thailand, during a five-year period. We used a retrospective review of Kratom exposure cases from the RPC toxic surveillance system. A total of 52 Kratom exposure cases were identified. The trend of case consultations has been increasing. There were Kratom poisoning cases (76.9%) and withdrawal cases (23.1%). Common presenting symptoms in the poisoning group were palpitation (22.5%), followed by seizure (17.5%). For the withdrawal group, the common presenting symptoms were myalgia (33.3%), insomnia (16.67%), fatigue (16.67%), and chest discomfort (16.67%). There was a baby with withdrawal symptoms who was delivered from a chronic Kratom-abusing mother, suggesting possible exposure via the transplacental route. There were no deaths in either group. Kratom abuse can cause either poisoning or withdrawal. Most cases in both groups had good prognostic outcome.     

Electrocardiographic predictors of long-term outcomes after radiofrequency ablation in patients with right-ventricular outflow tract tachycardia.

AIMS: The objectives of this study were to identify electrocardiographic (ECG) predictors of long-term outcomes after radiofrequency (RF) ablation in patients with right-ventricular outflow tract (RVOT) tachycardia. METHODS AND RESULTS: We correlated ECG characteristics with RF ablation outcomes in 144 patients with RVOT tachycardia who underwent RF ablation for >1 year. Unfavourable RF ablation outcomes were predefined as unsuccessful RF ablation or recurrence of tachycardia requiring repeated ablation. RF ablation was not successful in 11 (7.6%) patients and 16 (12%) patients had arrhythmia recurrence requiring repeated ablation. Average follow-up time was 72.2+/-28.4 months. Selected parameters from univariate analysis included number of RF applications, pacemapping, application of bonus burn, procedure time, monophasic R-wave in lead I, QS pattern in leads I and aVL, QRS duration in leads II and V(2), and right axis deviation, in ventricular tachycardia. From logistic regression analysis, only monophasic R-wave in lead I remained in the final equation (P=0.004, odds ratio 12.9). CONCLUSION: Monophasic R-wave in lead I during RVOT tachycardia is associated with unfavourable outcomes after RF ablation. This finding may help clinicians in the selection of patients for RF ablation and for the prediction of RF ablation outcome.     

One-year outcome after radiofrequency catheter ablation of symptomatic ventricular arrhythmia from right ventricular outflow tract

Although ventricular premature complexes (VPCs) in patients without structural heart disease are benign, many patients experience disabling symptoms. Many patients need long-term medication, which is often ineffective and may have adverse effects. Radiofrequency catheter ablation (RFCA) may be an alternative treatment. RFCA was performed in 33 patients with severely symptomatic VPCs that were refractory to medication. Mean VPCs were 23,987 +/- 2,077 beats/24 hours. Twenty-four-hour ambulatory electrocardiographic monitoring, quality of life, and symptoms were assessed at a screening visit and 1 and 12 months after RFCA. RFCA was successfully performed in 32 patients (97%). This resulted in a significant improvement in symptoms, severity of ventricular arrhythmia, and quality of life at 1 and 12 months after the procedure. There were no major complications related to the procedure. Eight patients (24%) had residual arrhythmia. Five of them underwent repeated ablation with successful results. Thus, catheter ablation is a safe and effective treatment for symptomatic ventricular arrhythmia from the right ventricular outflow tract. It also improves the quality of life. Catheter ablation is a viable alternative to drugs in the presence of disabling symptoms.     

Effect of atenolol on symptomatic ventricular arrhythmia without structural heart disease: a randomized placebo-controlled study

Background Ventricular arrhythmia (VA) from the right ventricular outflow tract (RVOT) is a common problem. Symptomatic patients are usually treated with β-blockers. There is little data on the systematic evaluation of the efficacy of β-blocker. We determine the efficacy of atenolol in the treatment of symtomatic VA from RVOT compared with placebo. Methods and Results This was a randomized, double-blinded, placebo-controlled study. We prospectively studied 52 consecutive patients with symptomatic VA. Severity of symptoms, 24-hour ambulatory monitoring (AECG) and quality of life (QOL) were assessed at baseline and 1 month after atenolol. Exercise testing was performed at baseline. Average premature ventricular complex (PVC) count at baseline was 21,407 ± 1740 beats per 24 hours, and 19% had ventricular tachycardia as measured by AECG. Results of this study showed that atenolol significantly decreased symptom frequency (P = .03), PVC count (P = .001) and average heart rate (P < .001) measured by AECG, whereas placebo significantly decreased symptom frequency (P = .002) but had no effect on PVC count (P = .78) or average heart rate (P = .44). Neither atenolol nor placebo had an effect on QOL. Conclusions Atenolol improves symptoms and decreases PVC count from ambulatory monitoring. Placebo improved symptoms to the same extent as atenolol but had no effect on severity of VA. This might be the so-called placebo effect, which is a concern when treating patients or doing research on the effects of a drug. (Am Heart J 2002;144:e15.)     

Underlying pathology of women with "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion" smears, in a region with a high incidence of cervical cancer

AIM: To evaluate the histopathology of women who had "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions" (ASC-H) on cervical cytology in a region with high incidence of cervical cancer. METHODS: This study was conducted at Chiang Mai University Hospital, Chiang Mai, Thailand. All women with ASC-H, who had undergone colposcopic and histolopathologic evaluation between October 2004 and January 2007, were recruited. Similar cohorts with other squamous cell abnormalities on a Pap-smear, who had undergone colposcopy during the same period, were included as comparative groups. RESULTS: During the study period, 85 women who had ASC-H smears underwent colposcopic and histopathologic evaluation. The mean age was 45.3 years (range, 20-64 years). The histopathologic results of these 85 women were as follows: cervical intraepithelial neoplasia (CIN) II-III, 52 (61.2%); invasive cancer, 7 (8.2%); CIN I, 6 (7.1%); and no lesions, 20 (23.5%). The incidence of underlying CIN II or higher in an ASC-H smear (69.4%) was intermediate between atypical squamous cell of undetermined significance (22.7%), low-grade squamous intraepithelial lesion (44.7%) and high-grade squamous intraepithelial lesion (90.5%) smears. There was no statistically significant difference in the incidence of CIN II or higher between women who were 40 years old or more and those who were younger (68.7% and 71.4%, respectively, P=0.81), or between pre-menopausal and post-menopausal women (71.4% and 63.6%, respectively, P=0.49). CONCLUSION: Reporting ASC-H cytology in our population is strongly associated with significant cervical pathology, particularly invasive cancer that is possibly at a rate higher than previously reported. Women who have ASC-H smears should therefore be referred for immediate colposcopy regardless of age and menopausal status.