Radiolabeling and biological evaluation of DOTA-Ph-Al derivative conjugated to anti-EGFR antibody ior egf/r3 for targeted tumor imaging and therapy

An appropriate bifunctional chelating agent namely DOTA-Ph-Al was developed for the conjugation with biological vectors (anti EGFr antibody). We hereby report the synthesis of p-bromoacetamidobenzyl derivative of DOTA and its conjugation to monoclonal antibody anti-EGFR ior egf/r3. Immunoconjugate was prepared by conjugation of p-bromoacetamidobenzyl derivative of DOTA with ior egf/r3. Modified antibody was purified by size exclusion chromatography. DOTA-Ph-Al-ior egf/r3 exhibited quantitative 99mTc-labeling (>96%) with specific activity 10-20 mCi/mg of protein and 90Y-labeling with specific activity 2-5 mCi/mg. Immunoreactivity was determined by flow cytometry. Receptor ligand assay on murine cell line EAT and human tumor cell line U-87MG showed Kd = 2.87 nM and 4.86 nM respectively. The stability in serum indicated that 99mTc remained bound to antibodies up to 24h and 98% 90Y was associated with the mAb for five days. Biodistribution characteristics of Ab-conjugate radiolabeled to 99mTc and 90Y radionuclide was examined in BALB/c mice grafted with EAT and athymic mice with U-87MG cell line demonstrated high tumor uptake with 5.5 +/- 1.3 and 7.85 +/- 1.2%ID/g at four and 24 h for 99mTc- DOTA-Ph-AI-ior egf/r3 in EAT tumors after post injection respectively. Maximal radiotracer uptake peaked 17.6 +/- 2.5%ID/g in EAT tumor and 12.89 +/- 0.66% ID/g in U-87MG tumor at 48h for 90Y. The drug excreted through renal routes as the activity in the kidneys was 13.42 +/- 0.33%ID/g at 1 h and 4.51 +/- 1.2%ID/g at 4 h for 99mTc- DOTA-Ph-Al-ior egf/r3.     

Comparative study of perioperative infusion of diltiazem and nicorandil on myocardial protection during OPCAB surgery

We compared the effects of continuous intravenous infusions of nicorandil and diltiazem on left ventricular function, haemodynamics and as anti-ischaemic and anti-arrhythmic agents in 50 patients undergoing off pump coronary artery bypass surgery using arterial conduits. The patients were randomized into two equal groups to receive diltiazem or nicorandil. Both the drugs were given as a continuous infusion in the dose of 1microg/kg/min starting at induction and continued for 24 hours postoperatively. Haemodynamic parameters, cardiac enzyme levels and use of vasoactive agents were studied and compared using ANOVA, unpaired "t" and Fisher's exact tests. The two groups did not differ with respect to preoperative and operative data. Diltiazem group showed lower cardiac index (2.66+/-0.8 and 2.27+/-0.89 L/min/m2) as compared with nicorandil group (3.16+/-0.79 and 2.97+/-1.01 L/min/m2) during revascularisation of anterior (P=0.03) and inferior (P=0.01) circulation respectively. The systemic vascular resistance index was higher (2290+/-699 and 2545+/-911 dync.sec.cm-5.m2) in diltiazem group as compared with nicorandil group (1822+/-532 and 1877+/-548 dyne. sec.cm-5.m2) during revascularization of anterior (P=0.01) and inferior (P=0.002) circulation respectively. The mean pulmonary artery pressure was significantly higher in nicorandil group as compared with diltiazem group during revascularisation of anterior circulation (22.5+/-4.9 and 18.1+/-6.8 mmHg, P=0.01). The patients in the diltiazem group maintained a lower heart rate throughout the study period, but the difference was not statistically significant. None of the patients exhibited any arrhythmia except one in nicorandil group, who developed supraventricular arrhythmia 24 hours postoperatively. Cardiac enzyme levels were found to be similar in the two groups. The present study demonstrates that the anti-ischemic and antiarrythmic effects of diltiazem and nicorandil are comparable, but diltiazem causes a decrease in cardiac index and increase in systemic vascular resistance index during revascularization of anterior and inferior circulation.     

Endogenous human cytomegalovirus gB is presented efficiently by MHC class II molecules to CD4+ CTL

Human cytomegalovirus (HCMV) infects endothelial, epithelial, and glial cells in vivo. These cells can express MHC class II proteins, but are unlikely to play important roles in priming host immunity. Instead, it seems that class II presentation of endogenous HCMV antigens in these cells allows recognition of virus infection. We characterized class II presentation of HCMV glycoprotein B (gB), a membrane protein that accumulates extensively in endosomes during virus assembly. Human CD4+ T cells specific for gB were both highly abundant in blood and cytolytic in vivo. gB-specific CD4+ T cell clones recognized gB that was expressed in glial, endothelial, and epithelial cells, but not exogenous gB that was fed to these cells. Glial cells efficiently presented extremely low levels of endogenous gB--expressed by adenovirus vectors or after HCMV infection--and stimulated CD4+ T cells better than DCs that were incubated with exogenous gB. Presentation of endogenous gB required sorting of gB to endosomal compartments and processing by acidic proteases. Although presentation of cellular proteins that traffic into endosomes is well known, our observations demonstrate for the first time that a viral protein sorted to endosomes is presented exceptionally well, and can promote CD4+ T cell recognition and killing of biologically important host cells.     

Social Isolation,Impulsivity and Depression as Predictors of Aggression in a Psychiatric Inpatient Population

Aggressive behavior among psychiatric inpatients remains an issue of concern for staff, families and patients themselves. At the present time, studies examining prediction of aggression among psychiatric inpatients have focused mainly on diagnostic or demographic risk factors. Unfortunately little is known about specific social functioning and personality risk factors that may help identify specific individuals at risk for aggressive behavior. Given that many individuals who have engaged in violent criminal behavior have been observed to experience a combination of social isolation, depression and impulsiveness, it is possible that this same combination of traits may function as a predictor of aggression among psychiatric inpatients. The current study examines whether psychiatric inpatients with a combination of social isolation, depression and impulsivity are significantly more likely to become aggressive than other psychiatric inpatients without that combination of factors. Results indicated that impulsivity functioned as a positive predictor of aggression, whereas depression acted as a protective factor. Perceived social support did not appear to relate strongly to aggression. Further, physicians ratings of hostility were more predictive of aggressive incidents than were self-reports of hostility. Clinical implications of these findings are discussed.     

Perforated acute appendicitis in a term neonate

Acute appendicitis is rare in term neonates. In most of the reported cases, it is seen as a complication of necrotizing enterocolitis, Hirschsprung’s disease, cystic fibrosis, meconium plug, inguinal hernia, umbilical hernia, Group B Streptococcal septicemia and chorioamnionitis. A surviving term male newborn with isolated acute appendicitis with perforation is reported. A high index of suspicion of acute appendicitis, early surgery and the importance of a thorough search for a perforation in cases of neonatal acute abdominal distention is stressed. Literature of this rare condition is reviewed briefly     

Central giant cell granuloma in child: a case report

The central giant cell granuloma or CGCG is a benign intraosseous lesion of the jaw. It is found predominantly in children and young adults. A case of 10 year old male child with CGCG in mandible is presented.     

Tuberous sclerosis: a case report

A case of tuberous sclerosis (TS) with classic triad of seizures, mental deficiency and angiofibromas is presented. The child also presented with self-mutilating behavior, which resulted in the fracture of her anterior teeth. A comprehensive treatment was rendered to the patient under general anesthesia and a mouth guard was given to prevent further trauma to the teeth.     

Vulval lipoma: a rare occurrence

Case report. An extremely rare case of vulval lipoma is being reported for its rarity and brief review discussed.