Transposition of the great arteries and isolated origin of the sinus node artery

We report the cases of 2 newborns who underwent at 7 days of age an arterial switch operation for transposition of the great arteries with a rare coronary anomaly: the left and right coronary arteries originated with a single ostium from sinus 1 and the sinus node artery had an isolated origin from sinus 2. The sinus node artery was reimplanted into the new aorta in both patients. Both babies were discharged in sinus rhythm. Preserving the vascularization of the sinus node may avoid the occurrence of postoperative atrial rhythm disturbances.     

The significance of adult hematuria: 1,000 hematuria evaluations including a risk-benefit and cost-effectiveness analysis

Between March 1976 and June 1985, 1,000 consecutive adults with asymptomatic gross or microscopic hematuria in the absence of proteinuria were evaluated urologically. Lesions that could account for the hematuria were detected in 88.3 per cent of the patients. Life-threatening lesions were diagnosed in 9.1 per cent of the patients, while lesions requiring at least observation were present in 22.8 per cent. The incidence of life-threatening lesions increased with age, with a sharp increase after age 50 years. Life-threatening lesions were more common in men (13.6 per cent) than in women (4.9 per cent). In general, as the degree of hematuria increased so did the yield of life-threatening lesions; however, there was no "safe" lower limit of hematuria. Of the patients with life-threatening lesions 18.6 per cent had at least 1 urinalysis with less than 3 red blood cells per high power field within 6 months of the diagnosis. The direct medical cost of a hematuria evaluation was $777. The difference in direct medical costs to diagnose and treat localized versus metastatic genitourinary cancer was $48,070 in 3 matched pairs of patients. In this study group 77 of 84 patients (92 per cent) diagnosed with genitourinary cancer had localized disease. A hematuria evaluation was cost-effective for all groups studied. A literature-based estimate of the life-threatening risks of diagnostic studies applied to the study data resulted in a 1.1 per cent life-threatening risk per hematuria evaluation. For all categories studied, except for women less than 40 years old with microscopic hematuria, the risk of a hematuria evaluation was less than the incidence of life-threatening lesions discovered as a result of the evaluation. Asymptomatic hematuria, whether gross or microscopic, is a significant finding and warrants evaluation from a risk-benefit and cost-effectiveness standpoint.     

Increased elastin production in experimental granulomatous lung disease.

In the normal, healthy lung, elastin production is restricted to periods of development and growth. However, elastin expression in the adult lung has been observed in some forms of pulmonary injury, including pulmonary fibrosis. Here, we report that elastin production is significantly increased within precise interstitial compartments of the lung in an experimental model of granulomatous lung disease. An increase in the number and volume of elastic fibers within the alveolar walls was apparent on histological examination of Verhoeff-van Gieson-stained sections of silicotic rat lungs. Quantitation of mature elastin cross-links indicated that silicosis was accompanied by a 17-fold increase in lung elastin content when compared with values from saline-treated controls. In situ hybridization for tropoelastin mRNA revealed that elastin production was absent from granulomatous lesions yet was prominent at nonfibrotic alveolar septal tips, where a high density of elastic fibers is seen in the normal lung. Immunohistochemistry indicated tropoelastin was being expressed by alpha-smooth muscle actin-containing cells. Transforming growth factor-beta was immunolocalized to granulomatous regions of the silicotic lung but was absent from regions showing increased tropoelastin expression. These data indicate that the reinitiation of tropoelastin gene expression is associated with granulomatous lung disease, and this expression leads to the aberrant accumulation of mature elastin in the lung.     

NK-active cytokines IL-2, IL-12, and IL-15 selectively modulate specific protein kinase C (PKC) isoforms in primary human NK cells.

Natural killer (NK) cell function is largely modulated by growth factors and cytokines. In particular, interleukin (IL)-2, IL-12, and IL-15 have major effects on the proliferative and cytotoxic activities of NK cells against tumor and virus-infected cells. It is thought that the members of the protein kinase C (PKC) family of serine/threonine kinases play an important role in mediating the pleiotropic effects of cytokines on their target cells. We have investigated the downstream effects generated in purified human NK cells by IL-2, IL-12, and IL-15 on PKCalpha and PKCepsilon--a canonical and a novel isoform of PKC, respectively. By means of Western blotting, PKC activity assays, and immunofluorescence performed on highly purified preparations of primary human NK cells, we demonstrate that: 1) the three cytokines have similar effects on PKCalpha and PKCepsilon activities; 2) whereas PKCepsilon activity is induced by cytokine stimulation, PKCalpha activity is inhibited; and 3) both the induction of PKCepsilon and the inhibition of PKCalpha functional activity are relatively early events in NK cells, while longer cytokine stimulations do not generate significant variations in enzyme activity, suggesting that the activation of both the canonical and novel isoforms of PKC are events required in the early phases of cytokine-induced NK cell stimulation.     

Experimental model for studying the effects of 2-ethylhexyl-phthalate and dialysate on connective tissue

In order to have a model for studying the possible implications of 2-ethylhexyl-phthalate and dialysate on connective tissue, we evaluated their direct effects on the air pouch lining tissue and on fibroblast cultures. Air pouches were formed on the backs of 60 ten-week-old Wistar rats by subcutaneous injections of 10 ml sterile air. On the tenth day 2 ml sterile air, or 2 ml 5 microg/L or 2 ml 10 microg/L 2-ethylhexyl-phthalate in olive oil, or 2 ml olive oil alone, or 2 ml 5 mg/ml or 12 mg/ml lyophilized dialysate were injected into the air pouches. After sampling at seven or twenty-one days, the rats were killed. The biochemical data showed an increase in sulphated glycosaminoglycans with 2-ethylhexyl-phthalate and dialysate. Electron microscopy findings revealed cellular alterations such as vacuolation and cell remnants with 2-ethylhexyl-phthalate, while the cells of the air pouches treated with dialysate showed regular organelles with increased and dilated cisternae of rough endoplasmic reticulum. Moreover, an increase in collagen fibres surrounding the damaged zones was noticed in 2-ethylhexyl-phthalate and dialysate treated rats. The glycosaminoglycan modifications and collagen fibre increase seem to suggest that the morphological changes, with the features of fibrosis, could be the result of 2-ethylhexyl-phthalate and dialysate action on connective tissue. Moreover, the air pouch technique can be considered a good model for studying the direct effects of 2-ethylhexyl-phthalate and other substances, such as uremic toxins, on connective tissue.     

Immunohistochemical evidence for epinephrine-containing retinal amacrine cells

The enzyme for the synthesis of epinephrine, phenylethanolamine-N-methyltransferase, has been localized, by an indirect immunofluorescent staining method, to a subpopulation of amacrine cells in the rat retina. The immunoreactive cells are located primarily in the inner nuclear layer and send a single process to the inner plexiform layer. Most of the immunoreactivity is found in the center of the inner plexiform layer. A small percentage of immunoreactive cell bodies were found in the inner plexiform layer and occasionally cells were observed in the ganglion cell layer. These epinephrine-containing amacrine cells are morphologically distinct from the dopamine-containing amacrine cells previously described by formaldehyde fluorescence and we speculate from reports in the literature that epinephrine-containing amacrine cells may play a role in modulating the activity of dopamine-containing amacrine cells.     

Diltiazem impairs maturation and functions of human dendritic cells

The aim of this study was to define the effects of diltiazem, a calcium antagonist drug used in cardiology and in clinical transplantation, on the differentiation and maturation of human dendritic cells (DC). Herein, we demonstrate that diltiazem, in association with granulocyte macrophage-colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), induces monocytes to differentiate into cells with many of the characteristic of DC. However, diltiazem-induced DC express high levels of mannose receptor and Fc gamma RII and, consequently, manifest a higher endocytic activity compared with GM-CSF+IL-4-induced DC. Importantly, diltiazem-induced DCs have an impaired responsiveness to lipopolysaccharide and CD40 ligand because they produce decreased levels of IL-12 and reveal a reduced ability to stimulate alloreactive T-cell responses as well as in inducing interferon-gamma producing Th1 cells. These effects may contribute to a decreased DC-dependent T-cell activation and may help to explain the immunoregulatory function of diltiazem and its effectiveness in preventing transplant rejection.