Circulating vascular endothelial growth factor is not increased during relapses of steroid-sensitive nephrotic syndrome.
BACKGROUND: An uncharacterized circulating factor that increases vascular permeability has previously been described in childhood steroid-sensitive nephrotic syndrome (SSNS). The aim of this study was to determine whether this factor is vascular endothelial growth factor (VEGF), the recently described endothelial cell mitogen and enhancer of vascular permeability. METHODS: Plasma and urine VEGF levels were measured in children with SSNS in both relapse and remission and in normal age- and sex-matched controls. Semiquantitative reverse transcriptase-polymerase chain reaction studies investigating VEGF mRNA expression were performed on peripheral blood mononuclear cells isolated from children with SSNS in relapse and controls. In two experimental models (one-hour and three-day follow-up postinfusion), Sprague-Dawley rats were intravenously administered 50 microg rVEGF to determine whether this induced either proteinuria or glomerular histologic change. RESULTS: Plasma VEGF levels and urine VEGF/creatinine ratios were not elevated in SSNS relapse compared with remission and control samples. Peripheral blood mononuclear cell VEGF mRNA expression was no different in SSNS patients compared with controls. The administration of VEGF to rats induced an acute reversible fall in systemic blood pressure but did not result in the development of either proteinuria or glomerular histologic change. CONCLUSION: Increased circulating VEGF levels are not responsible for the proteinuria observed during relapses of SSNS. Further studies are warranted to investigate intrarenal VEGF expression. (+info)
Maternal adrenocortical hormones maintain the early development of pancreatic B cells in the fetal rat.
To investigate the effect of maternal adrenocortical hormones on the development of fetal pancreatic islet cells, pregnant rats were adrenalectomised on d 6 of gestation. On d 12-16 the growth patterns of fetal insulin-producing B cells, glucagon-producing A cells, and somatostatin-producing D cells were observed histometrically. Maternal adrenalectomy resulted in growth retardation of fetal B cells on d 12-15. Maternal corticosterone therapy prevented this retardation. Maternal adrenalectomy, however, did not affect the developmental patterns of A and D cells. By Western blotting and immunohistochemistry, glucocorticoid receptors were demonstrated to be present in the islet cells from d 12 to d 15. These results suggest that maternal adrenocortical hormones, glucocorticoids in particular, maintain the early development of fetal pancreatic B cells through their specific intracellular glucocorticoid receptor. (+info)
Herpetic keratitis. Proctor Lecture.
Although much needs to be learned about the serious clinical problem of herpes infection of the cornea, we have come a long way. We now have effective topical antiviral drugs. We have animal models which, with a high degree of reliability, clearly predict the effect to be expected clinically in man, as well as the toxicity. We have systemically active drugs and the potential of getting highly active, potent, completely selective drugs, with the possibility that perhaps the source of viral reinfection can be eradicated. The biology of recurrent herpes and stromal disease is gradually being understood, and this understanding may result in new and better therapy of this devastating clinical disease. (+info)
Idiopathic pulmonary haemosiderosis. Epidemiology, pathogenic aspects and diagnosis.
Idiopathic pulmonary haemosiderosis (IPH) is a rare clinical entity characterized by recurrent episodes of diffuse alveolar haemorrhage, often presenting with haemoptysis. Many patients have iron deficiency anaemia due to deposition of haemosiderin iron in the alveoli, and eventually develop moderate pulmonary fibrosis. Typically, intensive search for an aetiology ends up negative. There is no evidence of pulmonary vasculitis or capillaritis. The aetiology is obscure, but may be an immunological or toxic mechanism causing a defect in the basement membrane of the pulmonary capillary. IPH affects both children and adults. During an acute episode, a chest X-ray demonstrates bilateral, alveolar infiltrates. Sputum examination discloses haemosiderin-laden alveolar macrophages. Diagnosis is established by lung biopsy (fiber-optic or thoracoscopic), showing large numbers of haemosiderin-laden macrophages in the alveoli and without evidence of capillaritis or deposition of immunoglobulins. Corticosteroids and/or immunosuppressive drugs may be effective during an acute bleeding episode, and may in some patients improve symptoms and prognosis on the long-term, but the response to treatment displays great interindividual variation. (+info)
Pediatric renal transplantation under tacrolimus-based immunosuppression.
BACKGROUND: Tacrolimus has been used as a primary immunosuppressive agent in adult and pediatric renal transplant recipients, with reasonable outcomes. Methods. Between December 14, 1989 and December 31, 1996, 82 pediatric renal transplantations alone were performed under tacrolimus-based immunosuppression without induction anti-lymphocyte antibody therapy. Patients undergoing concomitant or prior liver and/or intestinal transplantation were not included in the analysis. The mean recipient age was 10.6+/-5.2 years (range: 0.7-17.9). Eighteen (22%) cases were repeat transplantations, and 6 (7%) were in patients with panel-reactive antibody levels over 40%. Thirty-four (41%) cases were with living donors, and 48 (59%) were with cadaveric donors. The mean donor age was 27.3+/-14.6 years (range: 0.7-50), and the mean cold ischemia time in the cadaveric cases was 26.5+/-8.8 hr. The mean number of HLA matches and mismatches was 2.8+/-1.2 and 2.9+/-1.3; there were five (6%) O-Ag mismatches. The mean follow-up was 4.0+/-0.2 years. RESULTS: The 1- and 4-year actuarial patient survival was 99% and 94%. The 1- and 4-year actuarial graft survival was 98% and 84%. The mean serum creatinine was 1.1+/-0.5 mg/dl, and the corresponding calculated creatinine clearance was 88+/-25 ml/min/1.73 m2. A total of 66% of successfully transplanted patients were withdrawn from prednisone. In children who were withdrawn from steroids, the mean standard deviation height scores (Z-score) at the time of transplantation and at 1 and 4 years were -2.3+/-2.0, -1.7+/-1.0, and +0.36+/-1.5. Eighty-six percent of successfully transplanted patients were not taking anti-hypertensive medications. The incidence of acute rejection was 44%; between December 1989 and December 1993, it was 63%, and between January 1994 and December 1996, it was 23% (P=0.0003). The incidence of steroid-resistant rejection was 5%. The incidence of delayed graft function was 5%, and 2% of patients required dialysis within 1 week of transplantation. The incidence of cytomegalovirus was 13%; between December 1989 and December 1992, it was 17%, and between January 1993 and December 1996, it was 12%. The incidence of early Epstein-Barr virus-related posttransplant lymphoproliferative disorder (PTLD) was 9%; between December 1989 and December 1992, it was 17%, and between January 1993 and December 1996, it was 4%. All of the early PTLD cases were treated successfully with temporary cessation of immunosuppression and institution of antiviral therapy, without patient or graft loss. CONCLUSIONS: These data demonstrate the short- and medium-term efficacy of tacrolimus-based immunosuppression in pediatric renal transplant recipients, with reasonable patient and graft survival, routine achievement of steroid and anti-hypertensive medication withdrawal, gratifying increases in growth, and, with further experience, a decreasing incidence of both rejection and PTLD. (+info)
Disseminated nocardiosis in a bone marrow transplant recipient with chronic GVHD.
We describe a case of disseminated nocardiosis in a 53-year-old male allogeneic marrow recipient with chronic GVHD, 15 years post BMT. Six months prior to admission he was treated for recurrent chronic GVHD with corticosteroids with a good response. He deteriorated subsequently while still on steroids requiring admission for fever, anorexia, weight loss, productive cough and progressive dyspnoea. On admission he had multiple nodular lesions on chest roentgenogram and subsequently grew Nocardia farcinica in blood culture. N. farcinica is rare post BMT, has a high mortality, is resistant to various antibiotics and needs prolonged antimicrobial therapy. We report the successful management of our patient with single agent trimethoprim-sulphamethoxazole. (+info)
Intravenous immune globulin (i.v.IG) therapy in steroid-resistant atopic dermatitis.
Many trials have been done on steroid-resistant atopic dermatitis. Recently, intravenous immune globulin (i.v.IG) was reported to be effective in the treatment of steroid-dependent atopic dermatitis. The aim of this study was to clarify whether i.v.IG therapy is effective in steroid-resistant atopic dermatitis. Forty-one steroid-resistant atopic dermatitis patients were tested in this study. Patients who weighed less than 30 kg were administered 500 mg/kg of i.v.IG. Patients who weighed 30 kg or more were administered 15 g of i.v.IG. Patient evaluations and laboratory tests with peripheral bloods such as eosinophil percentages and serum IgE levels were performed at days 0, 1, 7, and 21. In the present study, patients who responded to i.v.IG therapy were classified as Group A. Twelve patients who showed transient effects with lower clinical significance were classified as Group B (29.3%). Remaining 12 patients (29.3%) in Group C showed no improvement at all. Serum IgE levels and blood eosinophil percentages were markedly decreased in Group A. I.v.IG therapy may be recommended in the treatment of atopic dermatitis with extremely high serum IgE levels. (+info)
Antioxidant effects of aminosalicylates and potential new drugs for inflammatory bowel disease: assessment in cell-free systems and inflamed human colorectal biopsies.
BACKGROUND: The therapeutic efficacy of 5-aminosalicylic acid in inflammatory bowel disease may be related to its antioxidant properties. AIM: To compare in vitro the antioxidant effects of conventional drugs (5-aminosalicylic acid, corticosteroids, metronidazole), with new aminosalicylates (4-aminosalicylic acid, balsalazide) and other potential therapies (ascorbate, N-acetylcysteine, glutathione, verapamil). METHODS: Compounds were assessed for efficacy in reducing the in vitro production of reactive oxygen species by cell-free systems (using xanthine/xanthine oxidase, with or without myeloperoxidase) and by colorectal biopsies from patients with ulcerative colitis using luminol-amplified chemiluminescence. RESULTS: 5-aminosalicylic acid and balsalazide were more potent antioxidants than 4-aminosalicylic acid or N-acetyl-5-aminosalicylic acid in cell-free systems. 5-aminosalicylic acid (20 mM) and balsalazide (20 mM) inhibited rectal biopsy chemiluminescence by 93% and 100%, respectively, compared with only 59% inhibition by 4-aminosalicylic acid (20 mM). Hydrocortisone, metronidazole and verapamil had no significant effect on chemiluminescence in any system. Ascorbate (20 mM) inhibited chemiluminescence by 100% in cell-free systems and by 60% in rectal biopsies. N-acetyl cysteine (10 mM), and both oxidized and reduced glutathione (10 mM), completely inhibited chemiluminescence in cell-free systems, but not with rectal biopsies. CONCLUSIONS: The antioxidant effects of compounds varies between cell-free systems and inflamed colorectal biopsies. The effect of drugs on the chemiluminescence produced by these two assay systems is useful for screening potentially new antioxidant treatments for inflammatory bowel disease. Ascorbate seems worth further study as a novel therapy. (+info)