Recent progress in diagnosis and treatment of osteogenesis imperfecta

Osteogenesis imperfecta (OI) is an inheritable disorder characterized by bone fragility with various symptoms of connective tissue disorders. OI is commonly classified by Sillence's classification into four types according to the clinical features. The cardinal symptom is pathologic fracture, which is often recognized before birth, is frequent during infancy and childhood, then decreases at puberty. Bone mineral density is markedly decreased in OI, especially of the lumbar spine. Bone deformities are frequently observed in the long bones of the extremities, and spinal deformities and compression fractures are also common. Growth retardation is extremely severe, especially in type III. Calcitonin has been the most common therapy for OI. Recently, bisphosphonates have been found to be potent drugs that increase bone mass in OI patients. To prevent further fracture or bone deformity, appropriate orthopedic managements, including intramedullary rodding, are critically important. Growth hormone is effective in stimulating bone growth during childhood. The pathogenesis of OI is quantitative or qualitative abnormalities of type I collagen. The clinical features of each type usually correspond to the type of mutation. Several possibilities for gene therapy have been proposed.     

Acute tubulointerstitial nephritis associated with piperacillin therapy in a boy with glomerulonephritis

An 11-year-old boy with glomerulonephritis developed acute renal failure 4 days after beginning piperacillin (PIPC) treatment. Renal biopsy revealed acute tubulointerstitial nephritis (ATIN) with marked eosinophils. A lymphocyte stimulation test (LST) for PIPC demonstrated an extremely high LST index of 626%. The serum levels of immunoglobulin E and eosinophil cationic protein also showed a significant increase at 9021 IU/mL and greater than 150 μg/L, respectively. These observations suggest that a hypersensitivity reaction might play a role in the pathogenesis of ATIN. This is the first report to describe PIPC-induced ATIN in a child.     

EFFECT OF PORCINE CALCITONIN THERAPY ON VITAMIN D METABOLISM AND CLINICAL RESPONSE IN A PATIENT WITH OSTEOGENESIS IMPERFECTA

ABSTRACT. A 1 11/12-year-old girl with osteogenesis imperfecta was treated with porcine calcitonin. Eight bone fractures occurred in the previous 20 months before therapy, but none occurred during eight months of therapy. There was also a significant improvement in linear growth and radiographic bone density. This is the first study of the effect of calcitonin on vitamin D metabolism in a human. The high plasma levels of 1,25 dihydroxy-vitamin D (1,25-(OH)₂-D) and 24,25 dihydroxy-vitamin D (24,25-(OH)₂-D) before calcitonin therapy decreased after therapy. Plasma 25 hydroxy-vitamin D (25-OH-D) concentration, which normal in level before calcitonin therapy, was normal or slightly decreased during administration. It is concluded that calcitonin probably influences vitamin D metabolism in a patient with osteogenesis imperfecta.     

Colchicine in the treatment of the cutaneous manifestations of Behçet's disease

Five patients with Behçet's disease were satisfactorily treated with colchicine. Oral aphthosis, erythema nodosum-like lesions and genital erosions improved greatly within a month as did laboratory findings. We believe colchicine to be the first choice in the management of the cutaneous and ocular lesions of Behçet's disease.     

Cerulein-induced Pancreatic Polypeptide Secretion

Intramuscular administration of cerulein caused an abrupt rise in plasma pancreatic polypeptide (PP) in normal subjects. Pretreatment by atropine tended to lower the basal plasma PP level and significantly blunted the cerulein-induced PP secretion. It appears, therefore, that PP secretion induced by cerulein is under vagal control. In addition, in normal subjects, a gallbladder series first revealed a well-filled gallbladder of normal size and shape, which then contracted most strongly after a cerulein injection at a time corresponding exactly with the peak plasma PP levels produced by the cerulein. Since exogenous PP is known to cause a relaxation of the gallbladder, it is possible that endogenous PP plays an important role in gallbladder motility.     

Vagal Enhancement as Evidence of Residual Ischemia After Inferior Myocardial Infarction

Background: Acute inferior myocardial infarction (MI) often induces transient sinus bradycardia through vagal enhancement, known as Bezold-Jarisch reflex, which is explained by preferential distribution of vagal nerve in the inferior wall. We examined vagal activity in relation to the occurrence of residual ischemia in patients with old inferior MI and assessed its diagnostic usefulness.
Methods: Exercise myocardial scintigraphy was performed in 15 patients with old inferior MI, 19 angina pectoris (AP) patients with inferior ischemia but no MI, and 32 control subjects who had no evidence of cardiac disease. We analyzed the connection of residual ischemia in old MI with ST-segment response to exercise and with vagal activity as determined by coefficient of component variance of high frequency (CCV_HF).
Results: Exercise-induced percentage change in CCV_HF was higher in patients with old MI and residual ischemia (18.8 ± 13.5%) and AP (5.5 ± 9.7%) than old MI but no residual ischemia (–24.1 ± 4.9%) or control (–22.8 ± 4.5%, P = 0.006). Percentage change in CCV_HF > –5% had a good diagnostic value for the detection of residual ischemia in patients with old inferior MI with sensitivity of 83%, specificity of 89%, accuracy of 87%, and positive likelihood ratio of 7.50, which was higher than that of ST-segment depression (67%, 50%, 56%, and 1.33).
Conclusions: Vagal enhancement was associated with residual ischemia in old inferior MI as well as inferior AP. Measurement of CCV_HF is useful in improving the diagnostic reliability of exercise electrocardiography in patients with old inferior MI.     

Effects of the anti-ICAM-1 monoclonal antibody on dextran sodium sulphate-induced colitis in rats

Increased expression of intercellular adhesion molecule-1 (ICAM-1) in the colon of inflammatory bowel disease (IBD) has been reported. We evaluated the effects of monoclonal antibodies to ICAM-1 on acute colitis induced by dextran sodium sulphate (DSS) in rats. Colitis was induced by feeding rats 3% DSS for 7 days. Anti-ICAM-1 antibody or vehicle alone was injected intraperitoneally in rats daily from day 0 to day 6. On day 7 the rats were killed and colitis was evaluated histologically. Prophylactic treatment with anti-ICAM-1 significantly attenuated colonic damage, neutrophil infiltration and the shortening of the colon in DSS colitis. Our findings demonstrate that ICAM-1 plays an important role in this model of inflammatory bowel disease. Although this study does not directly address the effect of anti-ICAM-1 therapy in IBD, our findings encourage experiments using therapies that target ICAM-1 in rats with already developed disease.     

Reversal of altered intestinal mucosal immunity in rats fed elemental diet by supplementation of oleic acid

We have previously demonstrated that elemental diet (ED) induces decreased lymphocyte transport in intestinal lymph and significant changes in T cell subsets and the number of IgA-containing cells in gut-associated lymphoid tissues of rats. In order to examine whether the low fat content contributes to the induction of immunological changes in gut-associated lymphoid tissues, the effects of additional fatty acid in the ED were investigated. Rats were divided into four groups: elemental diet alone, elemental diet supplemented with 5% oleic acid (OA), elemental diet with 10% OA and conventional diet as a control. These diets were given at the same daily calorie intake for 4 weeks. The flow rate of intestinal lymph showed no significant difference between the four groups. However, lymphocyte flux as well as the percentage of CD3⁺ and CD4⁺ cells were significantly greater in the control and the 10% OA groups than in the ED and 5% OA groups. Intestinal lymph showed decreased concentrations of IgG and IgA in the ED group, whereas the addition of 10% OA significantly attenuated the decrease in these levels. In mesenteric lymph nodes, the CD4⁺/CD8⁺ ratio was significantly decreased in the ED group, but 10% OA reversed this change. Immunohistochemical analysis of the ileal mucosa showed that in the ED group the population of CD4⁺ cells was decreased, while the number of CD8⁺ cells was increased. Supplementation of OA to ED produced similar stepwise attenuation of the changes in lymphocyte subpopulations in the lamina propria, while the 10% OA group reached levels that were not statistically different from controls. In the elemental diet, group, there was a significant decrease in immunoglobulin-containing cells of the IgA class in the lamina propria of the intestine. Similarly, the addition of OA induced dose-dependent recovery in the number of IgA-containing cells. These results suggest that a low dietary concentration of fat may be closely related to changes in lymphocyte transport in intestinal lymph and mucosal immunity of intestinal mucosa induced by the feeding of a long-term ED.