Non-peptide cholecystokinin-B/gastrin receptor antagonists based on bicyclic, heteroaromatic skeletons

A series of potent and selective cholecystokinin-B/gastrin receptor antagonists based on the dibenzobicyclo[2.2.2]octane (BCO) skeleton which have recently been described were found to show species-dependent behavior when examined in rat and dog models. We now report the discovery of compounds in which the BCO skeleton has been replaced with bicyclic, heteroaromatic frameworks, such as a 5,6-disubstituted indole or benzimidazole. These new ligands maintain the affinity and selectivity profile of the previous compounds in vitro but show a much more consistent behavior pattern in vivo. Representative examples of this class of compound have been shown to inhibit pentagastrin-stimulated acid secretion when administered intravenously at doses of 0.1 mumol kg-1 or less.     

The role of nitric oxide in mechanisms of the nephrotoxic effect of verografin

A clinic based cross-sectional study was conducted at Immunoprophylaxis Clinic at Govt. Medical College, Nagpur. Mothers of 217 children were interviewed for infant feeding practices. In 62.67% of children, breast-feeding was initiated within 24 hrs. after birth. About 22% mother used prelacteal feed and 70% mothers preferred demand feeding. Prominent area of concern includes discarding of colostrum, low exclusive breast feeding rate, delayed weaning and early termination of breast feeding. Further improvement in present day infant feeding practices is possible by emphasising on the health education component of existing nutritional programmes.     

Increasing tidal volumes and pulmonary overdistention adversely affect pulmonary vascular mechanics and cardiac output in a pediatric swine model

OBJECTIVES: In a pediatric swine model, the effects of increasing tidal volumes and the subsequent development of pulmonary overdistention on cardiopulmonary interactions were studied. The objective was to test the hypothesis that increasing tidal volumes adversely affect pulmonary vascular mechanics and cardiac output. An additional goal was to determine whether the effects of pulmonary overdistention are dependent on delivered tidal volume and/or positive end-expiratory pressure (PEEP, end-expiratory lung volume). DESIGN: Prospective, randomized, controlled laboratory trial. SETTING: University research laboratory. SUBJECTS: Eleven 4- to 6-wk-old swine, weighing 8 to 12 kg. INTERVENTIONS: Piglets with normal lungs were anesthetized, intubated, and paralyzed. After median sternotomy, pressure transducers were placed in the right ventricle, pulmonary artery, and left atrium. An ultrasonic flow probe was placed around the pulmonary artery. MEASUREMENTS AND MAIN RESULTS: The swine were ventilated and data were collected with delivered tidal volumes of 10, 15, 20, and 25 mL/kg and PEEP settings of 5 and 10 cm H2O in a random order. Pulmonary overdistention was defined as a decrease in dynamic compliance of > or =20% when compared with a compliance measured at a baseline tidal volume of 10 mL/kg. At this baseline tidal volume, airway pressure-volume curves did not demonstrate pulmonary overdistention. Tidal volumes and airway pressures were measured by a pneumotachometer and the Pediatric Pulmonary Function Workstation. Inspiratory time (0.75 sec), FIO2 (0.3), and minute ventilation were held constant. We evaluated the pulmonary vascular and cardiac effects of the various tidal volume and PEEP settings by measuring pulmonary vascular resistance, pulmonary characteristic impedance, and cardiac output. When compared with a tidal volume of 10 mL/kg, a tidal volume of 20 mL/kg resulted in a significant decrease in dynamic compliance from 10.5 +/- 0.9 to 8.4 +/- 0.6 mL/cm H2O (p = .02) at a constant PEEP of 5 cm H2O. The decrease in dynamic compliance of 20% indicated the presence of pulmonary overdistention by definition. As the tidal volume was increased from 10 to 20 mL/kg, pulmonary vascular resistance (1351 +/- 94 vs. 2266 +/- 233 dyne x sec/cm5; p = .004) and characteristic impedance (167 +/- 12 vs. 219 +/- 22 dyne x sec/cm5; p = .02) significantly increased, while cardiac output significantly decreased (951 +/- 61 vs. 708 +/- 48 mL/min; p = .001). Each of these effects of pulmonary overdistention were further magnified when the tidal volume was increased to 25 mL/kg. The tidal volume-induced alterations in pulmonary vascular mechanics, characteristic impedance, and cardiac output occurred to a greater degree when the PEEP was increased to 10 cm H2O. Pulmonary vascular resistance and characteristic impedance were significantly increased and cardiac output significantly decreased for all tidal volumes studied at a PEEP of 10 cm H2O as compared with 5 cm H2O. CONCLUSIONS: Increasing tidal volumes, increasing PEEP levels, and the development of pulmonary overdistention had detrimental effects on the cardiovascular system by increasing pulmonary vascular resistance and characteristic impedance while significantly decreasing cardiac output. Delivered tidal volumes of >15 mL/kg should be utilized cautiously. Careful monitoring of respiratory mechanics and cardiac function, especially in neonatal and pediatric patients, is warranted.     

Tension-free hernioplasty: technical remarks and personal experience

The authors report their experience with 463 tension free hernioplasty procedures for inguinal and femoral hernias. The surgical technique included the insertion of both a polypropylene plug and a polypropylene mesh, and was carried out mostly in local anesthesia (84.2%) using bupivacaine 0.25% for ileoinguinal and ileohypogastric blockage and mepivacaine 0.5% for local infiltration. There was no major intraoperative complication; local postoperative complications were rare (10%) and easily managed; postoperative pain was frequently observed (66%), though mild and transient; resumption of working activity occurred within a month in 96.6% of cases; there were only 3 post-operative recurrences (respectively, at 1, 6 and 12 months). The authors conclude that the tension free hernioplasty is a simple, rapid, low-cost and effective technique, easily performed under local anesthesia.     

Electrodermal activity as a predictor of social functioning in female schizophrenics

Twenty-nine female schizophrenics and 20 female controls were presented with a series of moderately intense tones in a standard orienting habituation paradigm while skin conductance was monitored. Premorbid adjustment and symptoms were also rated, and the schizophrenics were observed 2 years later. The total schizophrenic group was divided into a good-outcome group and a poor-outcome group. Good social functioning outcome required both self-supporting ability in the job market and at least a minimal social life. The poor-outcome group had a significantly higher skin-conductance level and frequency of spontaneous skin-conductance fluctuations than the control group, whereas the few patients with good outcome did not differ from controls. These results are contrary to previous findings with a group of schizophrenic men in which poor social functioning was associated with low electrodermal activity. This discrepancy is discussed in terms of sex differences in schizophrenic disorder.     

Long-term remission of neutropenia in Felty''s syndrome after a short GM-CSF treatment

2-hydroxy-5-tert-butyl benzylalcohol and 2,6-bis(hydroxymethyl)-4-tert-butylphenol were identified as contact allergens in a phenolic resin used as a tackifier in the ink of a marking pen, which, after being used directly on the skin, caused an acute contact dermatitis on the hand of a 13-year-old boy. The patient also reacted to 4-tert-butylphenol-formaldehyde resin (BPF resin) 1% pet. included in the European standard series.