Resistance of tumor interstitial pressure to the penetration of intraperitoneally delivered antibodies into metastatic ovarian tumors.

PURPOSE: Despite evidence that regional chemotherapy improves the treatment of metastatic peritoneal ovarian carcinoma, monoclonal antibodies have not shown significant success in i.p. delivery. The present study was designed to address the hypothesis that convective penetration of macromolecular antineoplastic agents depends on a positive pressure difference between the i.p. therapeutic solution and the tumor. EXPERIMENTAL DESIGN: Nude rats with human ovarian xenografts implanted in the abdominal wall were used in experiments to facilitate in vivo measurement of tumor pressure and the treatment of the tumor with i.p. solutions at high pressures. Penetration of (125)I-labeled trastuzumab was measured with quantitative autoradiography. RESULTS: Tumor pressure profiles showed peak pressures of 32 mm Hg with mean pressures (+/- SD, mm Hg) in 12 SKOV3 tumors of 9.7 +/- 8.3 and in 15 OVCAR3 tumors of 12.5 +/- 7.0. I.p. therapeutic dwells at 6 to 8 mm Hg (maximum feasible pressure) showed significantly less penetration of trastuzumab than in adjacent normal muscle. To establish a driving force for convection into the tumor, various maneuvers were attempted to reduce tumor pressure, including treatment with taxanes or prostaglandin E(1), elimination of tumor circulation, and removal of the tumor capsule. Tumor decapsulation decreased the pressure to zero but did not enhance the penetration of antibody. Binding to specific trastuzumab receptors on each tumor was shown to be not a significant barrier to antibody penetration. CONCLUSIONS: The results only partially support our hypothesis and imply that the microenvironment of the tumor is in itself a major barrier to delivery of charged macromolecules.     

Synthesis and Structure-Activity Relationships of Vasicine Analogues as Bronchodilatory Agents

The series of vasicine (1) analogues, an alkaloid from Adhatoda vasica Nees., were synthesized with changes in A, B or C rings. Compounds 13-19 were evaluated for in vitro bronchodilatory activity using isolated guinea pig tracheal chain. Compounds 3-8 were also synthesized in good yields using microwave-mediated synthesis under solvent free conditions. Compounds 5 and 8 with seven-member C ring were more active than etofylline and caused 100% relaxation of both the histamine and acetycholine pre-contracted guinea pig tracheal chain. The structure-activity relationship studies showed that the quinazoline and oxo functionalities were essential for activity. The compounds without C ring and instead having aliphatic and phenyl substitutions in B ring showed relaxation against histamine pre-contracted tracheal chain only, 2-methyl substituted analogues, 12 and 13, being most active with 100% relaxation effect.     

Accuracy of glycated haemoglobin in screening for pre‐diabetes in Asian Indians—a community survey: the Chandigarh Urban Diabetes Study (CUDS)

Aim To compare American Diabetes Association and International Expert Committee recommended cut‐off values of HbA_1c for detecting the presence of pre‐diabetes against plasma glucose values obtained from oral glucose tolerance tests in Asian Indians. Methods A cross‐sectional randomly sampled population survey involving 2368 adults, aged ≥ 20 years. HbA_1c was measured on a Bio‐Rad 10 system in 1972 subjects. Results Of the 1972 subjects studied, 329 were detected to have pre‐diabetes based on isolated impaired fasting glucose in 125 subjects (6.3%), isolated impaired glucose tolerance in 141 subjects (7.1%) and the presence of both in 63 subjects (3.2%). The HbA_1c cut‐off of 34 mmol/mol (5.7%), as recommended by the American Diabetes Association for detecting the presence of pre‐diabetes, showed sensitivity of 62%, specificity 77%, with a positive predictive value of 34.7%, a negative predictive value of 89.5% and accuracy of 67.8%; whereas the HbA_1c cut‐off recommended by the International Expert Committee of 42 mmol/mol (6%) had a sensitivity of 36%, specificity of 90%, positive predictive value of 42.7%, negative predictive of 85.4% and an accuracy of 77%. However, both these HbA_1c cut‐offs underdiagnosed the presence of pre‐diabetes in 38 and 64% of these subjects, respectively. Conclusions The American Diabetes Association and the International Expert Committee recommended HbA_1c cut‐off values and oral glucose tolerance tests identify different pre‐diabetes cohorts. Long‐term prospective studies are required to define the usefulness of one over the other.     

Soft Tissue Reconstruction After Hemimandibulectomy in Oral Malignancies: A Retrospective Study

Aims  

The present study was under taken to evaluate the efficacy of various local and regional soft tissue flaps used for reconstruction after excision of various malignant lesions of the mouth and also to evaluate complications with length of hospital stay after the reconstruction.     

Measurement of multiple biomarkers in advanced stage heart failure patients treated with pulmonary artery catheter guided therapy

ABSTRACT: INTRODUCTION: This study was carried out to investigate the prognostic utility of biomarkers in advanced stage heart failure (HF) patients requiring ICU admission for pulmonary artery catheter (PAC) guided therapy. METHODS: Thirty patients admitted to an ICU for PAC guided HF therapy were enrolled; concentrations of soluble ST2 (sST2), highly sensitive troponin I, an experimental ultrasensitive troponin I, amino-terminal pro-B type natriuretic peptide, cystatin C, and myeloperoxidase were measured over the first 48 hours. Outcomes included response of filling pressures and hemodynamics to tailored therapy and 90-day event-free survival (death, left ventricular assist device implantation, transplant). RESULTS: Of the biomarkers evaluated, only sST2 concentrations were higher in those who failed to achieve goals for central venous pressure ((CVP), 225.3 versus 104.6 ng/mL; P = 0.003) and pulmonary capillary wedge pressure ((PCWP), 181.7 versus 88.2 ng/mL; P = 0.05). Only sST2 concentrations were associated with adverse events (186.7 versus 92.2 ng/mL; P = 0.01). In age-adjusted Cox proportional hazards analysis, an elevated sST2 during the first 48 hours following ICU admission independently predicted 90-day outcomes (Hazard Ratio = 5.53; P = 0.03) superior to the Simplified Acute Physiology Score for this application; in Kaplan-Meier analysis the risk associated with elevated sST2 concentrations was present early and sustained through the duration of follow-up (log rank P = 0.01). CONCLUSIONS: In patients undergoing HF therapy guided by invasive monitoring, sST2 concentrations were associated with impending failure to reduce filling pressures and predicted impending events. Elevated sST2 values early in the ICU course theoretically could assist therapeutic decision-making in advanced stage HF patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00595738.     

A low‐cost,mechanically simple apparatus for measuring eddy current‐induced magnetic fields in MRI

The fidelity of gradient waveforms in MRI pulse sequences is essential to the acquisition of images and spectra with minimal distortion artefacts. Gradient waveforms can become nonideal when eddy currents are created in nearby conducting structures; however, the resultant magnetic fields can be characterised and compensated for by measuring the spatial and temporal field response following a gradient impulse. This can be accomplished using a grid of radiofrequency (RF) coils. The RF coils must adhere to strict performance requirements: they must achieve a high sensitivity and signal‐to‐noise ratio (SNR), have minimal susceptibility field gradients between the sample and surrounding material interfaces and be highly decoupled from each other. In this study, an apparatus is presented that accomplishes these tasks with a low‐cost, mechanically simple solution. The coil system consists of six transmit/receive RF coils immersed in a high‐molarity saline solution. The sensitivity and SNR following an excitation pulse are sufficiently high to allow accurate phase measurements during free‐induction decays; the intrinsic susceptibility matching of the materials, because of the unique design of the coil system, results in sufficiently narrow spectral line widths (mean of 19 Hz), and adjacent RF coils are highly decoupled (mean S₁₂ of ?47 dB). The temporal and spatial distributions of eddy currents following a gradient pulse are measured to validate the efficacy of the design, and the resultant amplitudes and time constants required for zeroth‐ and first‐order compensation are provided. Copyright © 2013 John Wiley & Sons, Ltd.     

Door to balloon time in patients presenting with acute ST elevation myocardial infarction and time factors influencing it; an observational study from a tertiary care teaching hospital in India

The objective of this prospective observational study was to assess the door-to-balloon time (D2B), in acute ST-segment elevation myocardial infarction (STEMI) patients and the time factors influencing it. The following timeframes were measured during the study: ED to ECG time, ED to coronary care unit time (ED2CCU), consent time, post-consent to balloon time (POSTCONSENT2B) and D2B. Effective D2B was 54 ± 12.2 min. Of the dependent variables, D2B had a strong positive correlation (ρ = 0.903) with consent time. This study sheds light on consent time a previously unrecognized entity as a significantly influencing factor for the D2B time.