Nagy Mikhail

Gastrointestinal hemorrhage and intestinal ischemia associated with anticardiolipin antibodies

Two patients developed unusual causes of severe gastrointestinal hemorrhage associated with anticardiolipin antibodies. One patient bled from small bowel ischemia and mesenteric thrombosis. Another patient bled massively from an ulcer of the descending duodenum which was refractory to standard antiulcer therapy. Ischemia may have contributed to the atypical ulcer presentation in this second patient, which included atypical ulcer location, ulcer refractoriness to standard peptic ulcer therapy, and severe recurrent hemorrhage. In five previously reported cases intestinal infarction associated with anticardiolipin antibodies presented, as it usually presents in patients without anticardiolipin antibodies, as an acute abdomen without acute gastrointestinal bleeding. The current study demonstrates that intestinal ischemia due to thrombosis is in the differential diagnosis of gastrointestinal bleeding in the anticardiolipin antibody syndrome.

Binding of phycoerythrin-conjugated interleukin-6 to in vitro-activated human peripheral blood mononuclear cells : effect of immunosuppressive agents and of a calcium channel blocker

&NA; We studied the effect of cyclosporine A, prednisolone, and the Ca2+ channel blocker verapamil on interleukin-6 binding to mitogen-activated peripheral blood mononuclear cells, using a flow cytometric technique and phycoerythrin-conjugated IL-6. All mitogenic stimuli up-regulated IL-6 binding to a variable degree. PHA alone or in combination with PMA was the most effective stimulant in up-regulating IL-6 binding in all the experiments performed. The main changes in IL-6 binding were seen in the large cell cluster, which consisted mainly of lymphoblasts. PHA and PHA/PMA, however, also up-regulated the mean fluorescence intensity on the small cell cluster, which consisted mainly of quiescent lymphocytes. The overall effect of the three pharmacological agents on mitogen-up-regulated IL-6 binding was minimal; most significant were a down-regulation by all three agents of IL-6 binding by small lymphocytes in PHA/PMA cultures, a down-regulation of IL-6 binding by CsA in PHA/PMA-induced large PBMC, and an up-regulation by verapamil of PMA-induced IL-6 binding in large PBMC. Measurements of IL-2 binding and of IL-6 production in the same cultures showed a different pattern than that seen with IL-6 binding, as well as different CsA, prednisolone, and verapamil action.In conclusion, by using a new flow cytometric technique providing information both about the quantity of bound cytokine and about the proportion of IL-6-binding cells, we have demonstrated that IL-6 receptor expression in vitro by PBMC can be up-regulated by the use of stimulants differing in the signal transduction pathways they activate. In addition, by using different pharmacological agents and stimuli to dissect different activation pathways of the in vitro immune response, we conclude that IL-6R generation is regulated differently from IL-6 production. Furthermore, since CsA and prednisolone are known inhibitors of in vitro IL-2 production, our results indicate that IL-6R generation does not rely exclusively on the presence of IL-2.

Endoscopically identified pseudomelanosis duodeni: striking yet harmless

Melanosis and pseudomelanosis duodeni are benign processes that appear endoscopically as black tiger stripes. Histologically, aggregates of pigment-laden macrophages are observed in the lamina propria of the duodenal villi, most commonly within the apical tips. These pigments may include lipomelanin, ceroid, and iron sulfide. Results of iron staining with Prussian blue is characteristically variable. Pseudomelanosis duodeni may be associated clinically with hypertension, end stage renal disease, diabetes mellitus, and certain medications; for example, pigment deposition has been associated with absorption of cyclic compounds in antihypertensive medications. We report a case of an 80-year-old woman presenting with a brief history of vague abdominal pain. Endoscopic evaluation documented nonerosive gastritis and a darkly pigmented duodenal mucosa. Biopsy of the duodenum revealed subepithelial black pigment that was negative for stainable iron. These findings are consistent with pseudomelanosis duodeni, a benign duodenal mucosal pigmentation with variable iron staining results and specific clinical associations. Pseudomelanosis duodeni is relatively uncommon and is considered to be a benign condition, first described in 1976 by Bisordi and Kleinman. It usually is identified

Renal Pelviceal Keratinizing Squamous Metaplasia with Sparing of Pyramidal Zones

Metaplastic changes in the urothelium of the upper urinary tract are relatively infrequent. Metaplasia may present as either squamous or less often glandular differentiation. The process may be associated with chronic inflammation or associated chronic infections. There may be malignant transformation to either squamous cell carcinoma or adenocarcinoma. The demarcation of the metaplastic process in the minor calyces has not been well documented to date. We report the case of a 74-year-old female patient who presented with a history of chronic renal disease and acute pyohydronephrosis. The patient underwent a nephroureterectomy which revealed keratinizing desquamative squamous metaplasia throughout the renal pelvis and upper urinary tract with abrupt termination of metaplasia at the junction of the renal pelvis and the minor calyx (pyramidal zone). Immunohistochemical evaluation documents metaplastic urothelium stained positive for CK5, before converting sharply to simple cuboidal epithelium in the minor calyx (pyramidal zones) which stained positive CK7. At the junction of the metaplastic components and low cuboidal lined minor calyceal surfaces, the underlying stroma showed loss of ureteral muscularis mucosa with transition to renal parenchymal type stroma. We believe that this observation is unique and potentially relevant to the etiology and pathophysiology of pelviceal metaplasia.

Effect of verapamil on the IL-2 binding to its active receptor and on the release of IL-2 receptor by activated PBMC

In the present study we have examined the effect of a Ca2+ channel blocker (verapamil) on the binding of IL-2 to its biologically active receptor (IL-2R), as well as on the release of its soluble form (sIL-2R) by peripheral blood mononuclear cells (PBMC) stimulated by a variety of stimuli. In the same culture systems, cyclosporine A (CsA) was also used as an additional dissecting tool. PHA and the Ca2+ ionophore A23187 enhanced both the percentage of PBMC binding phycoerythrin-conjugated IL-2 (PE-IL-2) and the mean fluorescence intensity of this binding. A phorbol-ester (PMA), on the other hand, enhanced only slightly the proportion of PE-IL-2 binding cells. The two stimulatory combinations (PHA/PMA and A23187/PMA) also up-regulated the proportion of PE-IL-2 binding cells and the fluorescence intensity; the PHA/PMA combination was the most potent of all stimuli used. These two stimulatory combinations, and PHA alone, were also associated with maximal in vitro release of sIL-2R. Verapamil significantly down-regulated PE-IL-2 binding in all culture systems and it convincingly inhibited the release of sIL-2R. Furthermore, this mode of action of verapamil was concentration-dependent. CsA, on the other hand, inhibited the binding of PE-IL-2 to all stimulant-activated PBMC and had only a slight inhibitory effect on the in vitro release of sIL-2R. Our results indicate that there is a correlation between the binding of IL-2 to biologically active receptors on the surface of stimulant-activated PBMC and the release of the soluble form of IL-2R by the same cells.(ABSTRACT TRUNCATED AT 250 WORDS)