Thoracic causes of acute abdominal pain

The origin of abdominal pain may be extra-abdominal, caused by a thoracic illness. This article illustrates the various thoracic disorders that may present with acute abdominal pain. An erroneous focus on the abdomen alone can easily lead to misdiagnosis and incorrect treatment. In cases of unexplained acute abdominal pain, radiologists should be aware of also viewing beyond the borders of the abdomen. The key to most of these thoracic diagnoses is detection of pulmonary consolidation, pleural fluid or pericardial fluid.     

Prostaglandins are involved in acetylcholine- and 5-hydroxytryptamine-induced,nitric oxide-mediated vasodilatation in human forearm

Both acetylcholine (ACh) and 5-hydroxytryptamine (5HT) are used to examine nitric oxide (NO)-mediated vasodilatation in humans. Animal data suggest that both substances can also induce the release of prostacyclin (PGI ). This study was designed to investigate the role of the prostaglandin pathway in Ach- and 5HT-induced vasodilation in humans. The experiments were done in three groups of healthy male volunteers. In group 1 (n = 6), ACh (100-1,000 ng/kg/min) and sodium-nitroprusside (10-100 ng/kg/min) were infused into the brachial artery alone, together with a continuous infusion of indomethacin (1.3 micro g/kg/min) and during a combined infusion of indomethacin and the competitive NO synthase inhibitor N -monomethyl-l-arginine (l-NMMA; 30 micro g/kg/min). In group 2 (n = 5), 5HT (0.3-1.0 ng/kg/min) was infused alone and together with a continuous infusion of indomethacin and l-NMMA. In group 3 (n = 6), the synthetic prostaglandin analog iloprost (0.5-4.5 ng/kg/min) was infused together with a continuous infusion of saline, l-NMMA, and l-NMMA with indomethacin, respectively. The infusions of indomethacin and l-NMMA started 10 min before the infusion of ACh, 5HT, iloprost, and sodium nitroprusside. Forearm blood flow was measured using computerized venous occlusion plethysmography. Both the Ach- and 5HT-induced vasodilator responses were significantly attenuated by indomethacin (p < 0.05 for both), but not further influenced by a concomitant infusion of l-NMMA. The vasodilatation induced by iloprost was significantly inhibited by l-NMMA (p < 0.05) and not affected by indomethacin. The sodium nitroprusside-induced vasodilation was influenced by neither l-NMMA nor indomethacin. It is concluded that in the human forearm, the prostaglandin pathway is involved in both the Ach- and 5HT-induced NO-mediated vasodilatation.     

Mutations inducing divergent shifts of constitutive activity reveal different modes of binding among catecholamine analogues to the beta(2)-adrenergic receptor

1. We compared the changes in binding energy generated by two mutations that shift in divergent directions the constitutive activity of the human beta(2) adrenergic receptor (beta(2)AR). 2. A constitutively activating mutant (CAM) and the double alanine replacement (AA mutant) of catechol-binding serines (S204A, S207A) in helix 5 were stably expressed in CHO cell lines, and used to measure the binding affinities of more than 40 adrenergic ligands. Moreover, the efficacy of the same group of compounds was determined as intrinsic activity for maximal adenylyl cyclase stimulation in wild-type beta(2)AR. 3. Although the two mutations had opposite effects on ligand affinity, the extents of change were in both cases largely correlated with the degree of ligand efficacy. This was particularly evident if the extra loss of binding energy due to hydrogen bond deletion in the AA mutant was taken into account. Thus the data demonstrate that there is an overall linkage between the configuration of the binding pocket and the intrinsic equilibrium between active and inactive receptor forms. 4. We also found that AA mutation-induced affinity changes for catecholamine congeners gradually lacking ethanolamine substituents were linearly correlated to the loss of affinity that such modifications of the ligand cause for wild-type receptor. This indicates that the strength of bonds between catechol ring and helix 5 is critically dependent on the rest of interactions of the beta-ethanolamine tail with other residues of the beta(2)-AR binding pocket.     

5'-Deoxy congeners of 9-(3-amido-3-deoxy-beta-D-xylofuranosyl)-N(6)-cyclopentyladenine: new adenosine A(1) receptor antagonists and inverse agonists

The synthesis and structure-activity relationship of N(6)-cyclopentyl-3'-substituted-xylofuranosyladenosine analogues with respect to various adenosine receptors were explored in order to identify selective and potent antagonists and inverse agonists for the adenosine A(1) receptor. In particular, the effects of removal of the 5'-OH group and introduction of selected substituents at the 3'-NH(2) position of 9-(3-amino-3-deoxy-beta-D-xylofuranosyl)-N(6)-cyclopentyladenine were probed. A solid phase-assisted synthetic approach was used to optimize the 3'-amide functionality. In view of the general concern of the presence of a 5'-OH moiety with regard to cellular toxicity, the present study describes 5'-deoxy compounds with reasonable affinity for the human adenosine A(1) receptor. Interestingly, this study shows that optimization of the 3'-"up" amide substituent can substantially compensate for the drop in affinity for the adenosine A(1) receptor, which is generally observed upon removal of the 5'-OH group. The fact that for several 3'-amido-substituted (5'-deoxy)-N(6)-cyclopentyladenosine derivatives, guanosine 5'-triphosphate-induced shifts in K(i) values were significantly lower than 1 implies that these analogues behave as inverse agonists. This is further supported by their 1,3-dipropyl-8-cyclopentylxanthine-like capacity to increase forskolin-induced adenosine cyclic 3',5'-phosphate production.     

Overexpression of corticotropin-releasing hormone in transgenic mice and chronic stress-like autonomic and physiological alterations

To gain a greater insight into the relationship between hyperactivity of the corticotropin-releasing hormone (CRH) system and autonomic and physiological changes associated with chronic stress, we developed a transgenic mouse model of central CRH overproduction. The extent of central and peripheral CRH overexpression, and the amount of bioactive CRH in the hypothalamus were determined in two lines of CRH-overexpressing (CRH-OE) mice. Furthermore, 24 h patterns of body temperature, heart rate, and activity were assessed using radiotelemetry, as well as cumulative water and food consumption and body weight gain over a 7-day period. CRH-OE mice showed increased amounts of CRH peptide and mRNA only in the central nervous system. Despite the presence of the same CRH transgene in their genome, only in one of the two established lines of CRH-OE mice (line 2122, but not 2123) was overexpression of CRH associated with increased levels of bioactive CRH in the hypothalamus, increased body temperature and heart rate (predominantly during the light (inactive) phase of the diurnal cycle), decreased heart rate variability during the dark (active) phase, and increased food and water consumption, when compared with littermate wildtype mice. Because line 2122 of the CRH transgenic mice showed chronic stress-like neuroendocrine and autonomic changes, these mice appear to represent a valid animal model for chronic stress and might be valuable in the research on the consequences of CRH excess in situations of chronic stress.     

Human papillomavirus 16 load in normal and abnormal cervical scrapes: an indicator of CIN II/III and viral clearance

The relation between human papillomavirus type 16 (HPV 16) viral load in cervical scrapes and development of high-grade cervical intraepithelial neoplasia (CIN II or III) was studied in a nested case-control study of women with normal cytology (group A) and in a cohort of women with abnormal cytology (group B). HPV 16 DNA load was determined using a quantitative real-time PCR assay. In group A, case women (women with CIN II/III, n = 12) had a significantly higher viral load than control women (women with CIN < or = I, n = 47). This resulted in an increased relative risk of women with the 50% highest viral load for development of CIN II/III (OR 7.7; CI 1.6-33). In group B, women with CIN II/III (n = 38) had a significantly higher viral load than women with CIN < or = I (n = 25). Women with the 50% highest viral load had an increased relative risk of CIN II/III (OR 3.2; CI 1.1-9.3) and a decreased chance of both viral clearance and cytologic regression. Our data suggest that in women with normal cytology an increased HPV 16 load confers an increased risk of developing a CIN lesion. A sustained high viral load is subsequently informative for progression to a high-grade CIN lesion.     

Evaluation of a commercial latex agglutination test for rapid detection of salmonella in fecal samples

A latex agglutination test for the detection of salmonella in feces was evaluated in comparison to direct culture and enriched culture using both artificially inoculated samples and clinical samples. In the samples inoculated artificially with different concentrations of salmonella (10¹ to 10⁵ per gram) the enriched culture performed better only at the 10² level in 0.4 g samples, whereas the latex test performed as well as the enriched culture at all levels in 4 g samples. In the tests using clinical samples, there was no significant difference between results of the latex test performed in 2283 samples and the enriched culture performed in 2072 samples. The sensitivity, specificity and negative and positive predictive values of the latex test were 88.2 %, 98 %, 97.5 % and 63 % respectively. The test provided results rapidly but yielded a number of false positive results.