Effect of suxamethonium, pancuronium, neostigmine and halothane on serum cholinesterase activity

Serum cholinesterase (Ch E) estimations were done in 30 healthy Nigerians scheduled for elective surgical procedures and were studied in two groups. Half of the patients were given general anesthesia using a muscle relaxant technique and the other half had halothane as the main anesthetic. Suxamethonium reduced Ch E by 9%, pancuronium by 25% and neostigmine by 58% compared to preinduction levels. Halothane reduced Ch E by 7% and 15% at 10 minutes and 24 hours postanesthetic respectively, compared to preinduction levels. The normal control value of Ch E in 30 healthy Nigerians was on the lower side of the normal range, observed mostly in Caucasians.     

DNA vaccine for rabies: relevance of the trans-membrane domain of the glycoprotein in generating an antibody response

Various studies have demonstrated the potential of immunization with DNA vaccines encoding the rabies virus glycoprotein (RV-G) to elicit humoral responses. In the present study, we have designed four constructs using a VR1020 vector, wherein the RV-G ectodomain has been cloned without the signal sequence (SS) and the trans-membrane domain (TD) (rGVR), without the SS but with the TD (rGVRt), with the SS but without the TD (rGVRs) and with the SS and the TD (rGVRst), under the control of a cytomegalovirus (CMV) promoter, and downstream of the tissue plasminogen activator (TPA) signal sequence. In addition, RV-G has been expressed as a His6 tag fusion protein, both in Escherichia coli as well as in baculovirus expression systems. Using a prime-boost strategy, BALB/cJ mice administered with the rGVRt construct either in saline (intramuscularly) or adsorbed onto gold microcarriers (delivered intradermally by gene gun) generated the highest rabies virus neutralizing antibody (RVNA) titers. Inclusion of the SS, in addition to the TD (rGVRst), led to a significant decrease in RVNA titers, compared to the rGVRt construct. The DNA vaccine construct lacking both the SS and the TD domain and the vaccine having only the SS generated lower antibody responses, compared to the rGVRt construct. After priming with DNA vaccine, boosting with both E. coli- as well as baculovirus-expressed rRV-G led to an increase in the RVNA titers. The present results demonstrate that a DNA vaccine encoding the full-length sequence of the ectodomain plus TD of the mature native RV-G is capable of expressing an 'ideal' immunogen to produce RVNA titers.     

Moraxella catarrhalis bacterium without endotoxin, a potential vaccine candidate

Lipooligosaccharide (LOS) is a major surface component of Moraxella catarrhalis and a possible virulence factor in the pathogenesis of human infections caused by this organism. The presence of LOS on the bacterium is an obstacle to the development of vaccines derived from whole cells or outer membrane components of the bacterium. An lpxA gene encoding UDP-N-acetylglucosamine acyltransferase responsible for the first step of lipid A biosynthesis was identified by the construction and characterization of an isogenic M. catarrhalis lpxA mutant in strain O35E. The resulting mutant was viable despite the complete loss of LOS. The mutant strain showed significantly decreased toxicity by the Limulus amebocyte lysate assay, reduced resistance to normal human serum, reduced adherence to human epithelial cells, and enhanced clearance in lungs and nasopharynx in a mouse aerosol challenge model. Importantly, the mutant elicited high levels of antibodies with bactericidal activity and provided protection against a challenge with the wild-type strain. These data suggest that the null LOS mutant is attenuated and may be a potential vaccine candidate against M. catarrhalis.     

CEACAM6 is a novel biomarker in pancreatic adenocarcinoma and PanIN lesions

OBJECTIVE: The purpose of this study was to test the hypothesis that CEACAM6 expression is an indicator of adverse pathologic features and clinical outcome in pancreatic adenocarcinoma. SUMMARY BACKGROUND DATA: Previously, we have demonstrated carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) to be an oncoprotein that plays an important role in the biology of pancreatic adenocarcinoma. Suppression of CEACAM6 expression reduces tumorigenesis and metastasis in vivo. METHODS: A tissue microarray was constructed using tumor specimens obtained from 89 consecutive patients who had undergone pancreatic resection for pancreatic adenocarcinoma with curative intent. A second microarray containing 54 pancreatic intraepithelial neoplasia (PanIN) lesions was constructed using tissues from a separate cohort of 44 patients. Both arrays were immunostained using a specific anti-CEACAM6 monoclonal antibody. Tumoral CEACAM6 expression was dichotomized into negative and positive immunoreactivity groups. The log-rank test was used to evaluate univariate associations of CEACAM6 expression with prognosis. Survival curves were derived using the Kaplan-Meier method. RESULTS: Tumoral CEACAM6 expression was detected in 82 (92%) pancreatic adenocarcinoma specimens. CEACAM6 expression was more prevalent in high-grade than in low-grade PanIN lesions (P = 0.0002). Negative tumoral CEACAM6 expression was associated with absence of lymph node metastases (P = 0.012), lower disease stage (P = 0.008), and longer postoperative survival (P = 0.047). CONCLUSIONS: CEACAM6 is a novel biomarker for pancreatic adenocarcinoma. CEACAM6 warrants further evaluation as both a prognostic factor and a therapeutic target in pancreatic cancer.     

Indian experience with a single long-acting vaginal suppository for the termination of pregnancies.

The Indian Council of Medical Research conducted a multicentric trial with a single vaginal suppository containing 3 mg 15-Me-PGF2 alpha for terminating pregnancies. Success rate in the 290 women investigated was 79.2 per cent at 30 hours observation. The mean induction-abortion interval was 14.7 hours and the incidence of complete abortions was 58.3 per cent. Vomiting and diarrhoea were the most common side-effects noted. Vomiting was experienced by 72.3 per cent women and diarrhoea by 76.8 per cent. Although the vaginal route for administering 15-Me-PGF2 alpha is simple and the induction-abortion interval short, it is suggested that the combination of a vaginal suppository and prostaglandins intra-muscularly may lead to higher percentage of complete abortions.     

Adolescent onset of adult metabolic diseases

There has been a significant rise in many adult diseases linked with obesity like insulin resistance, type 2 diabetes, hypertension, coronary artery disease, hyperlipidaemia and stroke. These diseases have been shown to have their origin in adolescence, specially in children who are getting bulkier relative to themselves. Thus it is important that an individual child is monitored with regular weight and/or serial BMI measurements. Creating a healthy environment specially in schools which include increased physical activity would probably be the best intervention strategy to check undue weight gain in adolescents.     

A need for reevaluation of sports participation recommendations for children with a solitary kidney

PURPOSE: We sought to evaluate the incidence and outcome of blunt renal injury in children by mechanism of injury. These data could then be used to provide the basis for more rational recommendations to parents and physicians regarding participation in sporting activities. MATERIALS AND METHODS: We analyzed data on 49,651 pediatric trauma cases collected by 92 trauma centers as part of the National Pediatric Trauma Registry from 1995 to 2001. Cases involving renal injury were isolated and the data were stratified according to age, sex and injury, as well as procedures required for treatment and outcomes. RESULTS: Of 49,651 pediatric trauma patients 813 incurred renal injury. There were 516 males and 291 females, and sex was not documented in 6 children. Average age was 10.6 years. There were no reports of a solitary kidney. In the sports group there were 4 nephrectomies, which were associated with sledding (2), skiing (1) and rollerblading (1), and 2 deaths related to skiing (1) and jet skiing (1). All 3 nephrectomies in the nonsports/other group were associated with equestrian activities, and 1 death occurred in this population. The nonsports/other group includes minor sports that are outlined by the American Academy of Pediatrics Committee on Sports Medicine and Fitness. CONCLUSIONS: The majority of renal injuries in children associated with kidney loss (21 of 28) occurred as a result of motor vehicle accidents, pedestrians being struck by a vehicle or other object, and falls. There were no kidneys lost in any contact sport. Sledding, skiing and rollerblading resulted in kidney loss. Current recommendations of the American Academy of Pediatrics Committee on Sports Medicine and Fitness prohibiting children with a solitary kidney from participating in contact sports appear to be overly protective and need to be reevaluated. In some instances activities listed as limited contact sports resulted in renal loss, showing that the risk associated with these activities has been underestimated.     

Biomarker profiling for cancer diagnosis, prognosis and therapeutic management

The basis of cancer treatment has come a long way since the days of the the classical TNM staging. Identification of novel biomarkers for various cancers and their specific correlations with prognosis have increased our understanding of carcinogenesis and tumour progression on the molecular level. Recent advances in technologies for simultaneous detection of multiple biomarkers have opened up new avenues for multimarker profiling on a more individual scale. We summarize the key molecular determinants and their prognostic role in various cancers, and examine the available techniques for analysing biomarker panels that can have a major impact on cancer diagnostics and therapeutics.     

Psoriatic nephropathy--does an entity exist?

Psoriasis is an immune-mediated chronic inflammatory disorder of the skin. Association with kidney disease has been debated for a long time. Secondary renal amyloidosis in psoriatic arthropathy and drug-induced renal lesions secondary to methotrexate or cyclosporine are accepted accompaniments of psoriasis. IgA nephropathy is also known to occur in psoriatics. We report three interesting cases of renal involvement in long-standing established psoriasis on topical therapy alone. The patients presented with hypertension, significant proteinuria, hypoalbuminemia, and dyslipidemia. Kidney biopsies revealed "mesangioproliferative glomerulonephritis with IgA nephropathy," "focal proliferative glomerulonephritis," and "membranous glomerulonephropathy." The former two had marked active urinary sediment. Patients improved on prednisolone and angiotensin-converting enzyme inhibitors. Contrary to the belief that renal involvement in psoriasis is coincidental, we propose that kidney disease may be a common accompaniment of psoriasis, which may be labeled as "psoriatic nephropathy" or "psoriatic kidney disease." The exact mechanism of this entity is yet to be elucidated.