Quantitative assessment of circulating antigens in human lymphatic filariasis: a field evaluation of monoclonal antibody-based ELISA using blood collected on filter strips

objective   To quantify circulating antigens in individuals with lymphatic filariasis by means of an ELISA using blood on filter strips. method   Circulating antigens in filarial patients and normal individuals living in an area endemic for W. bancrofti infection in Madras, India were estimated using a monoclonal antibody-based ELISA. results   All microfilaraemics showed positivity to circulating antigens whereas people with chronic pathology and 80% of the endemic normals tested negative. The antigen levels in the blood collected in the night and during day time showed positivity and there was no difference in the antigen concentration. The results of the antigen levels collected onto filter strips correlated with their corresponding plasma antigen levels ( r = 0.83). In microfilaraemics, DEC treatment did not alter the levels of circulating antigens for up to one month. conclusions   We conclude that this monoclonal antibody-based ELISA using filter strips may be used in day time and replace the existing routine night blood surveys in our endemic area in India.     

Functional polymeric nanoparticles: an efficient and promising tool for active delivery of bioactives

Nanotechnology is a multidisciplinary field and has achieved breakthroughs in bioengineering, molecular biology, diagnostics, and therapeutics. A recent advance in nanotechnology is the development of a functional nanosystem by incorporation, adsorption, or covalent coupling of polymers, carbohydrates, endogenous substances/ligands, peptides, proteins, nucleic acids, and polysaccharides to the surface of nanoparticles. Functionalization confers a wide array of interesting properties such as stealth characteristics, a bioadhesive property, and that it prevents aggregation of nanoparticles, imparts biostability and solubility, reduces toxicity, and provides site-specific delivery. This makes the nanosystem an intelligent tool for diagnostics, prognostics, and controlled and sustained delivery of protein, peptide, pDNA, and other therapeutic agents to specific targets (tissue, cell, and intracellular). Various types of functional nanosystems, such as carbon nanotubes, quantum dots, polymeric micelles, dendrimers, metallic nanoparticles, and liposomes, are being extensively explored. However, high tissue accumulation of nonbiodegradable nanoparticles has caused toxicity problems and rendered them as not-so-popular therapeutic and diagnostic systems. The toxicity and safety of nonbiodegradable nanoparticles are subject to future research. Polymeric nanoparticles have offered attractive alternative modules due to biocompatibility, nonimmunogenicity, nontoxicity, biodegradability, simple preparation methods, high physical stability, possibility of sustained drug release, and higher probability for surface functionalization. Depending on properties that have been modified, polymeric nanoparticles can be grouped in to four classes, namely, stealth, polysaccharide decorated biomimetic, bioadhesive, and ligand-anchored functional polymeric nanoparticles (f-PNPs). This review explores the ligand-anchored f-PNP as a carrier for active delivery of bioactives, envisaged to date. This review also details the ligands available for conjugation, their method of coupling to nanoparticles, and applications of f-PNPs in anticancer drug delivery, oral delivery, gene delivery, vaccine delivery, and intracellular delivery; site-specific delivery to liver, macrophages, lymphatics, and brain; and miscellaneous applications. This review also addresses formidable challenges encountered, and proposes some future strategies for development of a promising site-specific active delivery system.     

Structure-based design of peptides that self-assemble into regular polyhedral nanoparticles

Artificial particulate systems such as polymeric beads and liposomes are being applied in drug delivery, drug targeting, antigen display, vaccination, and other technologies. Here we used computer modeling to design a novel type of nanoparticles composed of peptides as building blocks. We verified the computer models via solid-phase peptide synthesis and biophysical analyses. We describe the structure-based design of a novel type of nanoparticles with regular polyhedral symmetry and a diameter of about 16 nm, which self-assembles from single polypeptide chains. Each peptide chain is composed of two coiled coil oligomerization domains with different oligomerization states joined by a short linker segment. In aqueous solution the peptides form nanoparticles of about 16 nm diameter. Such peptide nanoparticles are ideally suited for medical applications such as drug targeting and drug delivery systems, such as imaging devices, or they may be used for repetitive antigen display.     

Palanivelu hydatid system for safe and efficacious laparoscopic management of hepatic hydatid disease

Background Hydatid disease, being endemic in several areas of the world, is of interest even to surgeons in non-endemic areas because they may encounter the disease due to ease and rapidity of travel as well as immigration. We describe a new device for laparoscopic management of hepatic hydatid disease. Methods The special trocar–cannula system—the Palanivelu hydatid system (PHS)—and the technique of operation are described. A total of 75 patients were operated on using this technique. Results In 83.3% of patients, only evacuation of the hydatid cyst by the PHS was done. In 13.7%, this was followed by left lobectomy because the cysts were large, occupying almost the entire left lobe of the liver. The remnant cavity was dealt with by omentoplasty. The average follow-up period was 5.9 years, during which there were no recurrences. Conclusions PHS is successful in preventing spillage, evacuating the contents of hydatid cysts, performing transcystic fenestration, and for dealing with cyst–biliary communications.     

Validation of the bispectral index monitor for measuring the depth of sedation in children

The Bispectral Index (BIS) is an empirically calibrated number derived from adult electroencephalograph data that correlates with the depth of sedation in adults. We tested the hypothesis that the BIS score is a valid measure of the depth of pediatric sedation in a study designed to avoid limitations of a previously published report. BIS values from 96 healthy ASA physical status I-II children aged 1-12 yr undergoing sedation were continually recorded and electronically transferred to a computer. Two independent observers blinded as to BIS score evaluated sedation using the Observer's Assessment of Alertness/Sedation (OAA/S) and the University of Michigan Sedation Scale (UMSS) at 3-5 min intervals. There was a significant correlation between BIS and UMSS and between BIS and OAA/S by both the Spearman's rank correlation test and by prediction probability (P < 0.001). In children <6 yr, there was a significant correlation between BIS and the clinical sedation scores for subgroups undergoing invasive and noninvasive procedures (P < 0.001). There was also good agreement between the 2 independent observers who assessed clinical sedation scores (kappa = 0.51, P < 0.001). We conclude that the BIS monitor is a quantitative, nondisruptive and easy to use depth of sedation monitor in children.     

Modified Girdlestones-Taylor procedure for claw toes in spinal cord injury

STUDY DESIGN: A combination of review of case notes and outpatient follow-up. OBJECTIVE: To evaluate the effectiveness of the modified Girdlestones-Taylor procedure in patients with spinal cord injury (SCI). SETTING: Princess Royal Spinal Injuries Centre (PRSIC), Northern General Hospital, Sheffield, UK. METHODS: Nine patients with claw toe deformities to 27 toes were treated at the PRSIC from 1996 to 2005. After examination of their medical records, their toes were assessed for pain, residual deformity and stiffness. They were also asked to grade their satisfaction with the surgical outcome. The results were tabulated. RESULTS: The average age of our series of patients was 43.3 years. The mean time from injury to surgery was 20.4 years and the mean time from surgery to last follow-up was 37.3 months. All our patients had good to excellent results, with over 70% of the toes having excellent results. CONCLUSION: The modified Girdlestones-Taylor procedure for claw toe correction appears to be a safe and effective treatment for patients with SCI.     

CENTRAL PANCREATECTOMY FOR BENIGN PANCREATIC PATHOLOGY/TRAUMA: IS IT A REASONABLE PANCREAS‐PRESERVING CONSERVATIVE SURGICAL STRATEGY ALTERNATIVE TO STANDARD MAJOR PANCREATIC RESECTION?

BACKGROUND: The aim of this study was to assess the technical feasibility, safety and outcome of central pancreatectomy (CP) with pancreaticogastrostomy or pancreaticojejunostomy in appropriately selected patients with benign central pancreatic pathology/trauma. Benign lesions/trauma of the pancreatic neck and proximal body pose an interesting surgical challenge. CP is an operation that allows resection of benign tumours located in the pancreatic isthmus that are not suitable for enucleation. METHODS: Between January 2000 and December 2005, eight central pancreatectomies were carried out. There were six women and two men with a mean age of 35.7 years. The cephalic pancreatic stump is oversewn and the distal stump is anastomosed end-to-end with a Roux-en-Y jejunal loop in two and with the stomach in six patients. The indications for CP were: non-functional islet cell tumours in two patients, traumatic pancreatic neck transection in two and one each for insulinoma, solid pseudopapillary tumour, splenic artery pseudoaneurysm and pseudocyst. Pancreatic exocrine function was evaluated by a questionnaire method. Endocrine function was evaluated by blood glucose level. RESULTS: Morbidity rate was 37.5% with no operative mortality. Mean postoperative hospital stay was 10.5 days. Neither of the patients developed pancreatic fistula nor required reoperations or interventional radiological procedures. At a mean follow up of 26.4 months, no patient had evidence of endocrine or exocrine pancreatic insufficiency, all the patients were alive and well without clinical and imaging evidence of disease recurrence. CONCLUSION: When technically feasible, CP is a safe, pancreas-preserving pancreatectomy for non-enucleable benign pancreatic pathology/trauma confined to pancreatic isthmus that allows for cure of the disease without loss of substantial amount of normal pancreatic parenchyma with preservation of exocrine/endocrine function and without interruption of enteric continuity.     

Effect of vitamin E TPGS on immune response to nasally delivered diphtheria toxoid loaded poly(caprolactone) microparticles

The nasal mucosa has many advantages as a potential site for drug and vaccine delivery. The present study has sought to exploit this route of delivery using microparticles composed of D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a matrix material blended with poly(caprolactone) for nasal immunisation with diphtheria toxoid. Particles were prepared by a double emulsion method, followed by spray drying and the effect of TPGS on size, zeta potential, loading and release of antigen was assessed. Particles composed of TPGS-PCL blends were spherical, smooth and monodisperse, displaying increasing yields after spray drying with increasing concentrations of TPGS. The immune response to diphtheria toxoid loaded PCL-TPGS microspheres after nasal administration was shown to be higher than that achieved using PCL microspheres alone. We conclude that TPGS shows significant potential as a novel adjuvant either alone or in combination with an appropriate delivery system.