Acquired circulating anticoagulants.

Acquired inhibitors of blood coagulation, which are pathologic circulating substances that directly inhibit clotting factors or their reactions, most commonly occur in patients with hereditary bleeding disorders. This article contains a discussion of acquired circulating anticoagulants that arise de novo in patients with previously normal hemostatic mechanisms. Pathogenesis and management are also discussed. Treatment of these patients poses a challenge for the hematologist because, unlike hereditary hemophiliacs who have learned to adjust their lifestyle, the acquired hemophiliac is unprepared for hemorrhagic episodes.     

Infection of the upper extremity byMycobacterium marinum in a 3-year-old boy — Diagnosis by 16S-rDNA analysis

Summary A 3-year-old boy developed several subcutaneous nodular lesions on his right arm. Based on the histological examination of one of these nodules furunculosis was suspected and cefuroxime was tentatively given. However, acid-fast bacilli were then detected in the tissue specimen and a few colonies of acid fast, gram-positive rods grew on blood agar. Definitive species diagnosis (Mycobacterium marinum) was rapidly achieved by automated sequencing of amplified 16S-rDNA and antimicrobial therapy was adjusted according to the available literature. After 3 weeks of treatment with clarithromycin, rifampicin and protionamid regression of the nodular lesions was evident.

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Infektion der oberen Extremität durchMycobacterium marinum — Diagnose mit Hilfe von 16S-rDNA Analyse

Zusammenfassung Wir berichten von einem 3-jährigen Jungen, der verschiedene subkutane Knoten im rechten Arm entwickelte. Nach histologischer Untersuchung wurde zunächst der Verdacht auf Furunkulose geäußert und eine vorläufige Therapie mit Cefuroxim begonnen. Es wurden dann jedoch säurefeste Stäbchen im entnommenen Gewebe nachgewiesen und eine Woche später auf Blutagar grampositive, säurefeste Stäbchen angezüchtet. Die definitive Speziesdiagnose (Mycobacterium marinum) wurde rasch mit automatischer 16S-rDNA Sequenzbestimmung erzielt und die Therapie entsprechend der verfügbaren Literatur korrigiert. Nach drei Wochen einer Behandlung mit Clarithromycin, Rifampicin und Protionamid war ein Rückgang der subkutanen Knoten erkennbar.

     

Comparison of chemical, histomorphometric, and absorptiometric analyses of bones of growing rats subjected to dietary calcium stress

Absorptiometric, histomorphometric, and chemical analyses of bones from growing rats fed diets with low (0.2%, w/w), marginal (0.4%, w/w), or adequate (0.8%, w/w) calcium (Ca) content with or without phytate were compared. Phytate was added to each diet in a molar ratio of 19:1 to calcium. Male weanling Sprague-Dawley rats were fed one of the six diets for 8 weeks. At the end of 8 weeks, rats were killed, and mandibles, femurs, and tibias were removed. Bone density profiles were determined on the mandibles and femurs using single photon absorptiometry. Femurs were also used for calcium and phosphorus analyses. Tibias were used for histomorphometric analyses. Bone density of the femurs and mandibles increased as dietary Ca increased. The only effect of phytate addition measured was in the 0.8% calcium diet, where density was lower in rats fed the phytate-containing 0.8% calcium diet. Femur calcium concentration also increased as dietary Ca increased and was unaffected by addition of phytate. Femur phosphorus concentration was unaffected by dietary Ca levels but was increased by 10% when phytate was added to the diet. Bone density values were highly correlated with bone calcium and phosphorus levels (r = 0.94). Rats fed the 0.2% calcium diets had 20% lower mineralized bone area and 20% larger medullary cavity area than rats fed the other diets. Bone densitometry appears to be useful for determining changes in bone occurring in growing rats fed low, marginal, and adequate levels of dietary Ca. Bone density values also correlated well with chemically determined calcium and phosphorus concentrations and with histomorphometric data.     

Cytokine networking in lung inflammation

The molecules that mediate normal events in the lung also regulate the development and ultimate resolution of pulmonary inflammation. And they can orchestrate such fulminant, life-threatening disorders as septic shock. Which cytokines are involved, and how may their physiologic roles be subverted? Interleukins and tumor necrosis factor-alpha are key players.     

L-arginine reverses the antinatriuretic effect of cyclosporin in renal transplant patients

BACKGROUND: Cyclosporin has been shown to facilitate renal vasoconstriction and to have an antinatriuretic effect. The existence of an interference of cyclosporin with the vasodilating properties of endothelium mediated by nitric oxide production could mediate these effects. On the other hand, the infusion of the nitric oxide precursor L-arginine has been shown to induce renal vasodilatation and to facilitate natriuresis in normal volunteers. We have investigated the renal effects of the administration of an infusion of L-arginine in renal transplant patients chronically treated with cyclosporin. To facilitate the analysis of the data the effects of the administration of a similar dose of cyclosporin on renal function during the infusion of a vehicle were also investigated during the administration of a vehicle of L-arginine. DESIGN: Ten male renal transplant patients, chronically treated with cyclosporin and with a stable renal function were studied during 2 consecutive days after the administration of the usual morning dose of cyclosporin. The first day they received an intravenous infusion of vehicle and the second the infusion of graded doses of L-arginine (50, 100, 150 mg/kg/h) during 3 consecutive h. RESULTS: The first day, after cyclosporin administration a significant fall (P < 0.01) was observed in natriuresis and kaliuresis in the absence of changes in renal plasma flow and glomerular filtration rate. After the administration of L-arginine significant (P < 0.01) increases of renal plasma flow, glomerular filtration rate, and natriuresis were seen. The increase in blood levels of cyclosporin after its administration did not differ between days 1 and 2. CONCLUSION: These results indicate that L-arginine facilitates renal vasodilatation and natriuresis in renal transplant patients. Furthermore, the observed increase in sodium excretion could indicate that L-arginine counteracts the antinatriuretic effect of cyclosporin.      

Lipoteichoic acid induces secretion of interleukin-8 from human blood monocytes: a cellular and molecular analysis.

Invasion by gram-positive and gram-negative bacterial organisms is characterized immunopathologically by the activation of mononuclear phagocytic cells, leading to the elaboration of macrophage-derived regulatory and chemotactic factors, and the resultant influx of inflammatory leukocytes. Little is known regarding the mechanisms by which gram-positive organisms initiate macrophage activation and subsequent inflammation. In this investigation, we postulated that lipoteichoic acid (LTA) purified from two different gram-positive bacterial species was an important signal for the expression of chemotactic cytokines from human peripheral blood monocytes (PBM). In initial experiments, we demonstrated that cell-associated interleukin-8 (IL-8) was expressed by mononuclear phagocytes present in inflamed areas of endocardium in cases of acute Staphylococcus aureus endocarditis. We next demonstrated that LTA purified from either Staphylococcus aureus or Streptococcus pyogenes induced the time- and dose-dependent expression of IL-8 mRNA and protein from human PBM. The expression of IL-8 mRNA from LTA- but not lipopolysaccharide (LPS)-treated PBM was superinduced by concomitant treatment with cycloheximide, indicating that the expression of IL-8 mRNA from LTA-treated PBM was negatively controlled by repressor proteins. Furthermore, mRNA stability studies indicated that IL-8 mRNA was less stable in the presence of LTA than in the presence of LPS. Our findings indicate that LTA can induce the secretion of the polymorphonuclear leukocyte chemotactic factor IL-8 and that LTA may be an important cellular mediator of inflammatory cell recruitment that characterizes immune responses to gram-positive bacterial infections.     

Regulation of human alveolar macrophage- and blood monocyte-derived interleukin-8 by prostaglandin E2 and dexamethasone.

Mononuclear phagocytes are important immune effector cells that play a fundamental role in cellular immunity. In addition to their antigen-presenting and phagocytic activities, monocytes/macrophages produce a vast array of regulatory and chemotactic cytokines. Interleukin-8 (IL-8), a potent neutrophil-activating and chemotactic peptide, is produced in large quantities by mononuclear phagocytes and may be an important mediator of local and systemic inflammatory events. In this investigation, we describe the effects of prostaglandin E2 (PGE2) and dexamethasone (Dex) on IL-8 mRNA and protein expression from lipopolysaccharide (LPS)-treated human peripheral blood monocytes (PBM) and alveolar macrophages (AM). We demonstrate the dose-dependent suppression of IL-8 from LPS-stimulated PBM by PGE2. Treatment of stimulated PBM with 10(-6) M PGE2 resulted in maximal inhibition, causing 60% suppression of both IL-8 mRNA and extracellular protein levels. In contrast, PGE2 (10(-6) to 10(-8) M) did not significantly alter IL-8 mRNA or protein expression from LPS-treated AM. Treatment of LPS-stimulated PBM and AM with Dex (10(-6) to 10(-8) M) resulted in 75% decline in IL-8 mRNA and extracellular protein from either cell population. Pretreatment of PBM with PGE2 or Dex 1 or 2 h before LPS stimulation caused a significant suppression of steady-state IL-8 mRNA levels; however, administration of either of these modulators 1 or 2 h after LPS stimulation failed to have an inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS)