Occupational stress in naval personnel

Introduction: Increased stress levels have been reported and it has been implicated for mental illness amongst service personnel. However no study has been reported among Indian naval sailors.     

How useful is computed tomography in the diagnosis and assessment of bronchiectasis?

A study was performed to determine the value of computed tomography (CT) in the diagnosis and assessment of cylindrical and mild varicose bronchiectasis. Fifteen patients, in whom bronchography had shown such bronchiectasis in 34 of 73 lobes that could be assessed, were examined by CT. A control group of 12 subjects in whom there was no clinical or plain radiographic suspicion of bronchiectasis was also studied. Computed tomography (CT) was considered to show bronchiectasis in 28 lobes, 27 of which were bronchiectatic as shown by bronchography. Of 45 lobes where CT was not thought to show bronchiectasis, bronchography demonstrated 38 normal and seven bronchiectatic lobes. All lobes in the control group were interpreted as normal. Using bronchography as the definitive investigation for cylindrical or mild varicose bronchiectasis, CT has a sensitivity of 79% and a specificity of 99% in the diagnosis of the disease. The high specificity indicates that a diagnosis of cylindrical or mild varicose bronchiectasis by CT is reliable but CT is too insensitive to be used as a screening test.     

Modulation of cellular annexin I in human leukocytes infiltrating DTH skin reactions.

Based on our previous studies showing endogenous annexin I being depleted from migrated neutrophils (PMN) in vitro, we have tested whether the levels of this glucocorticoid-regulated protein in PMN and mononuclear cells (PBMC) were modified after adhesion to endothelial monolayers in vitro and extravasation into skin blisters in vivo. In vitro, annexin I levels were depleted more significantly (-70%) in post-adherent PMNs than in monocytes (-25%) and lymphocytes (-50%, only in the positive fraction). In vivo, a significant time-dependent increase (approximately threefold, P < 0.05) in cell-associated annexin I was measured in PBMCs recovered from the blisters, whereas no significant changes were detected in extravasated PMNs. This was associated with annexin I release in the blister fluids (approximately 35 ng/mL), whereas no detectable protein was found in matched-paired plasmas. In conclusion, we report for the first time an activation of the annexin I pathway during an ongoing experimental inflammatory response in humans, which is differently regulated between PMNs and PBMCs.     

Lead generation using pharmacophore mapping and three-dimensional database searching: application to muscarinic M(3) receptor antagonists.

By using a pharmacophore model, a geometrical representation of the features necessary for molecules to show a particular biological activity, it is possible to search databases containing the 3D structures of molecules and identify novel compounds which may possess this activity. We describe our experiences of establishing a working 3D database system and its use in rational drug design. By using muscarinic M(3) receptor antagonists as an example, we show that it is possible to identify potent novel lead compounds using this approach. Pharmacophore generation based on the structures of known M(3) receptor antagonists, 3D database searching, and medium-throughput screening were used to identify candidate compounds. Three compounds were chosen to define the pharmacophore: a lung-selective M(3) antagonist patented by Pfizer and two Astra compounds which show affinity at the M(3) receptor. From these, a pharmacophore model was generated, using the program DISCO, and this was used subsequently to search a UNITY 3D database of proprietary compounds; 172 compounds were found to fit the pharmacophore. These compounds were then screened, and 1-[2-(2-(diethylamino)ethoxy)phenyl]-2-phenylethanone (pA(2) 6.67) was identified as the best hit, with N-[2-(piperidin-1-ylmethyl)cycohexyl]-2-propoxybenz amide (pA(2) 4. 83) and phenylcarbamic acid 2-(morpholin-4-ylmethyl)cyclohexyl ester (pA(2) 5.54) demonstrating lower activity. As well as its potency, 1-[2-(2-(diethylamino)ethoxy)phenyl]-2-phenylethanone is a simple structure with limited similarity to existing M(3) receptor antagonists.     

Forced vergence fixation disparity parameters with and without a central fusion lock

The effect of a central fusion lock on forced vergence fixation disparity curve parameters, that is, magnitudes of fixation disparity and associated phoria, curve type and the central slope of the curve, was studied in 84 subjects because of ambiguity in the previous studies. It was found that the magnitudes of exo fixation disparity and exo associated phoria decreased significantly when they were measured with the central fusion lock. The central lock had no noticeable effect on the type of the curve, although, the central slope of the curve was flatter in the presence of the central lock.