Cellular retinoic acid- but not cellular retinol-binding protein is elevated in psoriatic plaques

Cellular retinoid binding proteins are thought to be involved in the molecular action of retinoids, a family of compounds successfully used in the treatment of psoriasis. Therefore, both cellular retinol (CRBP)- and retinoic acid (CRABP)-binding proteins were analyzed in psoriatic skin. Three facts emerged from our study: both CRABP and CRBP are detectable in the skin of psoriatic patients; qualitatively, they both appear similar to the corresponding proteins of normal human skin, in terms of their elution profile and apparent Kd; and quantitatively, only CRABP was found to be 3 times higher in psoriatic plaques as compared to either nonlesional skin of psoriatic patients or the skin of normal subjects. Since psoriatic plaques are particularly responsive to systemic retinoids, specifically to retinoic acid analogues, our results suggest for the first time a link between the levels of CRABP and the responsiveness of a nonneoplastic hyperproliferative tissue to systemic administration of retinoids in the human.     

The role of stress in interpreting the dexamethasone suppression test.

Stress has been implicated as a major confounding factor in the interpretation of Dexamethasone Suppression Test (DST) results. This study was designed to examine the effects of stress on DST results. Fifty patients with high levels of acute, chronic, and environmental stress participated in the study. Each patient was given a comprehensive psychiatric and psychological assessment, a routine administration of dexamethasone, and blood tests of cortisol values. The results indicate that the three measures of stress do not appear to affect levels of cortisol suppression, however, all three measures of stress predicted depression. As expected, DST cortisol levels were related to depression. Results are discussed in terms of their implications for understanding the associations among stress, depression and DST results.     

Effects of passive cardiac containment on left ventricular structure and function: verification by volume and flow measurements.

BACKGROUND: The cardiac support device (CSD, Acorn) is a compliant, textile-mesh graft placed around the ventricles to prevent further dilatation and to improve function in congestive heart failure. The aim of this study was to verify post-operative changes in left ventricular volumes, ejection fraction, blood flow, and myocardial mass. METHODS: Fourteen patients underwent contrast-enhanced, electrocardiography-triggered electron-beam computerized tomography before and 6 to 9 months after CSD implantation. We measured volume and flow using the slice-summation method and the indicator-dilution technique. RESULTS: We found significant changes for the following parameters: end-diastolic volume decreased from 382.9 +/- 140.2 ml to 311.3 +/- 138.7 ml, end-systolic volume from 310.4 +/- 132.4 ml to 237.4 +/- 133.8 ml, end-diastolic diameter from 75.3 +/- 7.8 mm to 70.7 +/- 11.6 mm, end-systolic diameter from 65.8 +/- 7.8 mm to 60.0 +/- 14.0 mm, and myocardial mass from 298.6 +/- 79.6 g to 263.1 +/- 76.8 g. Ejection fraction increased from 20.3% +/- 6.4% to 27.8% +/- 13.1%. We found no significant differences for stroke volume (from 72.5 +/- 24.6 ml to 73.8 +/- 23.6 ml), heart rate (from 80.5 +/- 11.0 beats per minute to 76.5 +/- 6.8 beats per minute), and total cardiac output (from 5.8 +/- 1.9 liter/min to 5.6 +/- 1.8 liter/min). Mitral regurgitation fraction decreased from 30.5% +/- 15.5% to 15.6% +/- 12.8%, increasing antegrade cardiac output from 3.8 +/- 0.9 liter/min to 4.7+/-1.5 liter/min. For most parameters, pre- and post-operative values in these patients differed significantly from those in an age- and gender-matched control group. In each patient, we observed a small hyperdense stripe along the pericardium after surgery, but we observed no local complications. CONCLUSION: Three-dimensional structural and functional data obtained by computerized tomography volume and flow measurements confirm the safety and efficacy of CSD implantation.     

Differences in T cell subsets between men and women with idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder, occurring predominantly in women. We studied by flow cytofluorimetry the T cell subsets in men and women with ITP and compared them with healthy sex-matched volunteers. In healthy controls, women were found to have higher proportions of T helper/inducer (Th/i) and lower T suppressor/cytotoxic (Ts/c) lymphocytes and consequently higher Th/i:Ts/c ratios than men. Accordingly, in clinical surveys, patients and controls should be matched for sex for proper comparisons. In patients with ITP in its active phase, an imbalance in T cell subsets was found in both sexes. The perturbation was more severe in women who had a marked decrease in number and proportion of Th/i lymphocytes and an increase in the proportion of Ts/c lymphocytes, whereas in men only, the proportion of Th/i lymphocytes was decreased. When patients with active disease were compared to those with ITP in remission, the decrease in Th/i subsets still persisted in both sexes but the Ts/c subset in women had returned to normal proportions. Therefore, the immune imbalance in ITP is more marked in women than men; imbalances in both Th/i and Ts/c are present in women while Ts/c appears not to be involved in men.     

Systematic mechanism-orientated approach to chronic pancreatitis pain

Pain in chronic pancreatitis(CP) shows similarities with other visceral pain syndromes(i.e.,inflammatory bowel disease and esophagitis),which should thus be managed in a similar fashion.Typical causes of CP pain include increased intrapancreatic pressure,pancreatic inflammation and pancreatic/extrapancreatic complications.Unfortunately,CP pain continues to be a major clinical challenge.It is recognized that ongoing pain may induce altered central pain processing,e.g.,central sensitization or pro-nociceptive pain modulation.When this is present conventional pain treatment targeting the nociceptive focus,e.g.,opioid analgesia or surgical/endoscopic intervention,often fails even if technically successful.If central nervous system pain processing is altered,specific treatment targeting these changes should be instituted(e.g.,gabapentinoids,ketamine or tricyclic antidepressants).Suitable tools are now available to make altered central processing visible,including quantitative sensory testing,electroencephalograpy and(functional) magnetic resonance imaging.These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes.The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved.Future research should address the circumstances under which central nervous system pain processing changes in CP,and how this is influenced by ongoing nociceptive input and therapies.Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy,leading to improved treatment of chronic pain in CP and other visceral pain disorders.