Delayed eye and other consequences from exposure to methyl isocyanate: 93% follow up of exposed and unexposed cohorts in Bhopal.

A follow up study three years after exposure to methyl isocyanate in 93% of exposed survivors and "control" residents in 10 Bhopali communities showed an excess of eye irritation, eyelid infection, cataract, and a decrease in visual acuity among the exposed people. Breathlessness was twice as common in the heavily exposed clusters as those with lower exposure, a trend that could not be explained by different age or smoking patterns (OR 2.05, 95% CI 1.36-3.08). Case referent analysis of outpatient attendances at Bhopal Eye Hospital, considering patients with severe refractive errors and astigmatism as "controls," showed a 40% increased risk of trachoma, 36% increased risk of other lid infections, and 45% increased risk of irritant symptoms among previously exposed people. "Bhopal eye syndrome" may thus include full resolution of the initial interpalpebral superficial erosion, a subsequent increased risk of eye infections, hyperresponsive phenomena (irritation, watering, and phlyctens), and possibly cataracts. It remains to be confirmed whether this reflects a more generalised disease as a consequence of previous exposure to methyl isocyanate or whether it is only the eye that is affected.     

A numerical approach to resonance frequency analysis for the investigation of oral implant osseointegration

Experimental devices based on vibration testing are employed as non-destructive procedures for evaluating implants osseointegration. Their behaviour was evaluated considering the outcome of numerical analysis. The purpose was to use the finite element method for assessing the ability of frequency analysis in detecting the degree of oral implant osseointegration. A three-dimensional model of a mandible was obtained from tomographic survey. A single implant was considered in canine region. Two configurations were analysed, with and without a mass linked to the implant as a cantilever, reproducing experimental devices. Simulation consisted of analysing the response to impulse forces for different osseointegration levels, thus evaluating the biomechanical efficiency of the implant-bone compound. A good correlation between frequency response and osseointegration level was obtained. This was carried out by providing an impulse excitation of the implant that resulted in a vibration pattern. Within the limit of finite element analysis, the outcomes showed that numerical investigation provides understanding the behaviour of testing devices based on frequency measurements, confirming the potential of vibrations technique as non-invasive analysis for osseointegration process.     

Development and characterization of biodegradable nanospheres as delivery systems of anti-ischemic adenosine derivatives

We report a preliminary study concerning the encapsulation modalities in nanoparticles of the anti-ischemic drug N6-cyclopentyladenosine (CPA) and its pro-drug 5'-octanoyl-CPA (Oct-CPA). The release of these compounds and the related pro-drug stability effects in human whole blood have been tested. Moreover, the influence of the delivery systems on CPA interaction toward human adenosine A1 receptor has been analysed. The nanospheres were prepared by nanoprecipitation or double emulsion solvent evaporation method using poly(lactic acid) and recovered by gel filtration or ultracentrifugation or dialysis. Free and encapsulated Oct-CPA was incubated in fresh blood and its stability was analysed with HPLC. Quite spherical nanoparticles with mean diameters ranging between 210+/-50 and 390+/-90 nm were obtained. No encapsulation occurred when CPA was used. Satisfactory results concerning drug content (0.1-1.1% w/w) and encapsulation efficiency (6-56%) were achieved when Oct-CPA was employed. The controlled release of the pro-drug was achieved, being released within a range of 1-4 h, or very slowly, depending on nanoparticle preparations. The hydrolysis rate of Oct-CPA in human whole blood appeared stabilized in human whole blood with modalities related to the release patterns. The presence of all nanoparticle preparations did not interfere with CPA interaction at its action site.     

Evidence for the presence of N-formyl-methionyl-leucyl-phenylalanine (fMLP) receptor ligands in human amniotic fluid and fMLP receptor modulation by physiological labour

OBJECTIVES: The presence of amniotic binding sites for N-formyl-methionyl-leucyl-phenylalanine (fMLP), an inflammatory peptide, and its ability to induce prostaglandin E2 synthesis in the human amnion prompted us to investigate for: (1) the presence of fMLP receptor ligands (fMLPRL) in the amniotic fluid; (2) expression of the fMLP receptor in amniotic tissue; (3) the effect of amniotic fMLPRL on neutrophil cyclic AMP (cAMP) level and calcium concentration ([Ca2+]i) during physiological pregnancy and labour. METHODS: Binding assays were performed on neutrophils to determine the presence of fMLRL in the amniotic fluid at the 17th week of pregnancy, as well as at term, before and after the onset of labour. The expression of fMLP receptor mRNA was evaluated by RT-PCR, the cAMP level by a radiochemical assay, and the calcium concentration by Fura-2 AM fluorescence measurement. RESULTS: fMLPRLs were detectable in amniotic fluid throughout pregnancy, and their levels did not vary during gestation. Labour significantly increased both the amniotic fMLPRL level and the expression of fMLP receptor in amnion tissue. The increased amniotic fMLPRL concentration noted during labour significantly increased neutrophil cAMP level and [Ca2+]i. CONCLUSIONS: These findings demonstrate for the first time the presence of fMLP receptor ligands in amniotic fluid, and indicate a modulation of the fMLP system by the events of physiological labour.     

Differential diagnosis,investigation, and current treatment of lower limb lymphedema

HYPOTHESIS: The causes and management of lower limb lymphedema in the Western population are different from those in the developing world. OBJECTIVE: To look at the differential diagnosis, methods of investigation, and available treatments for lower limb lymphedema in the West. DATA SOURCE: A PubMed search was conducted for the years 1980-2002 with the keyword "lymphedema." English language and human subject abstracts only were analyzed, and only those articles dealing with lower limb lymphedema were further reviewed. Other articles were extracted from cross-referencing. RESULTS: Four hundred twenty-five review articles pertaining to lymphedema were initially examined. This review summarizes the findings of relevant articles along with our own practice regarding the management of lymphedema. CONCLUSIONS: The common differential diagnosis in Western patients with lower limb swelling is secondary lymphedema, venous disease, lipedema, and adverse reaction to ipsilateral limb surgery. Lymphedema can be confirmed by a lymphoscintigram, computed tomography, magnetic resonance imaging, or ultrasound. The lymphatic anatomy is demonstrated with lymphoscintigraphy, which is particularly indicated if surgical intervention is being considered. The treatment of choice for lymphedema is multidisciplinary. In the first instance, combined physical therapy should be commenced (complete decongestive therapy), with surgery reserved for a small number of cases.     

The influence of peripheral vascular disease on the carotid and femoral wall mechanics in subjects with abdominal aortic aneurysm

AIM: Aortic and carotid stiffness is elevated in patients with abdominal aortic aneurysm (AAA). Peripheral vascular disease (PVD) frequently coexists with AAA and may further impair the arterial wall mechanics and increase the cardiovascular load. We therefore studied the elastic carotid and muscular femoral biomechanical properties and intima-media thickness (IMT) in this group of patients. METHODS: The elastic indices and IMTs of the common carotid and common femoral arteries were determined in 30 patients with AAA (15 with PVD) with a duplex scanner coupled with a wall tracking system. Fasting plasma creatinine level, glucose and lipid concentrations, and their physiologic variables known to influence the arterial wall mechanics were also assessed. RESULTS: Patients with AAA and PVD have significantly stiffer carotid (Petersen's elastic modulus, 2207 +/- 905 mm Hg versus 1268 +/- 432 mm Hg; P =.001; stiffness index, 22.73 +/- 9.63 versus 12.60 +/- 4.24; P =.001] and femoral (Petersen's elastic modulus, 4906 +/- 4057 mm Hg versus 2599 +/- 1169 mm Hg; P =.043; stiffness index, 49.02 +/- 40.04 versus 26.07 +/- 13.22; P =.044) arteries than subjects with AAA alone. Although patients with PVD have thicker carotid and femoral IMTs, no statistical difference was seen between the two groups. The subjects were matched for age, body mass index, heart rate, systolic and diastolic blood pressures, total vascular risk score, plasma creatinine level, and fasting lipid and glucose concentrations. CONCLUSION: Subjects with PVD and AAA have significantly stiffer carotid and femoral arteries, which may indicate increased cardiovascular load and may account for the highest mortality rate seen in these patients in the UK Small Aneurysm Trial. Therefore, treatment of associated cardiovascular risk factors is important and may have to be tailored on an individual basis according to the findings of the arterial wall mechanics.     

Neoral monitoring by limited sampling area under the concentration time curve in stable indian renal transplant recipients

The optimization of cyclosporine (CsA) immunosuppression remains a challenge because of the narrow therapeutic window and highly variable pharmacokinetics (PK). The highly variable PK were improved by the introduction of the current microemulsion preparation Neoral. However, the best clinical benefit of this CsA microemulsion can only be obtained by regular PK monitoring. During the past decade, various PK strategies have been proposed, such as C(0), C(2), level monitoring, abbreviated or limited sampling approach, and various prediction algorithms to replace the conventional area under the curve (AUC). In this study we evaluated the Neoral PK in stable Indian renal transplant recipients using a limited sampling approach. The C(0) (mean +/- SE) was 175 +/- 15 ng. mL(-1); C(max) 970 +/- 101 ng. mL(-1), and the AUC (0-4) 2734 +/- 258 ng. h. mL(-1). The C(0) showed a poor relationship to AUC (0-4) (r =.65) but high correlations were obtained with C(2) (r = 0.93) and C(3) (r =.96). Our finding suggest that stable Indian renal transplant recipients should either be monitored using C(2) or C(3).