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Biomedical subjects

A Etzioni

Publications and source records attributed to A Etzioni.

At least 55 records · Page 3Linked to original sources
PubMed1998

High incidence of hypoglycemic episodes with neurologic manifestations in children with insulin dependent diabetes mellitus.

UNLABELLED: Hypoglycemia is a serious frequent complication of insulin therapy in type 1 diabetes. PATIENTS AND METHODS: We surveyed 139 IDDM patients. RESULTS: Forty-four patients (32%) reported at least one severe hypoglycemic episode. All patients with severe hypoglycemia experienced neurological manifestations. Symptoms included confusion and abnormal behavior, convulsions, coma, transient hemiparesis and one case of permanent hemiparesis. Most episodes occurred at night or during morning hours. 44% of episodes were related to delayed meal or snack, 11% to excess insulin administration and 13% to extra physical activity. HbA1c was significantly lower in patients with severe hypoglycemia compared with diabetic controls (7.33 +/- 1.09% and 9.45 +/- 4.32%, respectively).

Adolescent↗
PubMed1997

Cholangiopathy and tumors of the pancreas, liver, and biliary tree in boys with X-linked immunodeficiency with hyper-IgM.

We report an association between X-linked immunodeficiency with hyper-IgM (XHIM) and carcinomas affecting the liver, pancreas, biliary tree, and associated neuroectodermal endocrine cells. The tumors were fatal in eight of nine cases and in most instances were preceded by chronic cholangiopathy and/or cirrhosis. An additional group of subjects with XHIM had chronic inflammation of the liver or bile ducts but no malignancy. Many patients with XHIM were infected with cryptosporidia. CD40 is normally expressed on regenerating or inflammed bile duct epithelium. A CD40+ hepatocellular carcinoma cell line, HepG2, susceptible to cryptosporidia and CMV infection became resistant when cell surface CD40 was cross-linked by a CD40 ligand fusion protein. Apoptosis was triggered in HepG2 cells if protein synthesis was blocked by cycloheximide or if the cells were infected by cryptosporidia. Ligation of CD40 on biliary epithelium may contribute to defense against infection by intracellular pathogens. We propose that the CD40 ligand mutations that cause XHIM deprive the biliary epithelium of one line of defense against intracellular pathogens and that malignant transformation in the biliary tree follows chronic infection or inflammation. The resulting tumors may then progress without check by an effective immune response. Patients with XHIM who have abnormal liver function tests should be considered at increased risk for cholangiopathy or malignancy.

Adolescent↗
PubMed1997

Clinical spectrum of X-linked hyper-IgM syndrome.

We report the clinical and immunologic features and outcome in 56 patients with X-linked hyper-IgM syndrome, a disorder caused by mutations in the CD40 ligand gene. Upper and lower respiratory tract infections (the latter frequently caused by Pneumocystis carinii), chronic diarrhea, and liver involvement (both often associated with Cryptosporidium infection) were common. Many patients had chronic neutropenia associated with oral and rectal ulcers. The marked prevalence of infections caused by intracellular pathogens suggests some degree of impairment of cell-mediated immunity. Although lymphocyte counts and in vitro proliferation to mitogens were normal, a defective in vitro proliferative response to antigens was observed in some patients, and additional defects of cell-mediated immunity may be presumed on the basis of current knowledge of CD40-ligand function. All patients received regular infusions of immunoglobulins. Four patients underwent liver transplantation because of sclerosing cholangitis, which relapsed in there. Three patients underwent bone marrow transplantation. Thirteen patients (23%) died of infection and/or liver disease. X-linked hyper-IgM syndrome, once considered a clinical variant of hypogammaglobulinemia, is a severe immunodeficiency with significant cellular involvement and a high mortality rate.

Bone Marrow Transplantation↗
PubMed1997

Clostridium septicum infection in children with cyclic neutropenia.

Atraumatic Clostridium septicum infection is rare in infancy and childhood and is associated with a high mortality rate. Although in adults it has been reported to occur mainly in patients with gastrointestinal malignancy, pediatric cases were always associated with neutropenia. About 70% of the cases were described in children with neutropenia caused by chemotherapy and 30% were found in children with cyclic neutropenia. No case was described in children with other forms of congenital severe neutropenia. We describe three children with cyclic neutropenia and severe Clostridium septicum infection, discuss the various possibilities of causation, and the need for prompt and aggressive treatment of this serious condition.

Abdominal Muscles↗
PubMed1997

Human parvovirus B19 infection associated with idiopathic thrombocytopenic purpura in a child following liver transplantation.

BACKGROUND/AIMS: Idiopathic (autoimmune) thrombocytopenic purpura has been previously reported as a rare complication in children following parvovirus B19 infection. In the immunocompromised host who is unable to produce neutralizing antibody, an infection with parvovirus B19 can persist and cause chronic bone marrow failure. METHODS: We describe a child who had undergone liver transplantation and who had idiopathic thrombocytopenic purpura, whose history and laboratory findings suggested parvovirus B19 infection. The infection disappeared without persistent viremia, and the thrombocytopenia responded completely to the administration of gamma globulin while the patient was undergoing chronic immunosuppression therapy. RESULTS/CONCLUSION: Transplant physicians need to be aware of this complication, and parvovirus B19 infection should be included in the differential diagnosis of liver recipients presenting with severe thrombocytopenia.

Child↗
PubMed1997

Cyclosporin A in hyperimmunoglobulin E syndrome.

BACKGROUND: The hyperimmunoglobulinemia E syndrome is a serious disorder of an unknown etiology without effective treatment. Cyclosporin A has immunosuppressive properties. Its effect in a patient with hyperimmunoglobulinemia E syndrome was evaluated. METHODS: We report a 3-year-old boy with severe hyperimmunoglobulinemia E syndrome in whom various therapeutic modalities were ineffective. He was started on cyclosporin A 3 mg/kg/d for 6 months. We examined several humoral and cellular immune functions during the treatment period and monitored his clinical condition. RESULTS: Marked improvement in his clinical condition was observed during therapy with cyclosporin A. There was a significant decrease in serum IgE and significant increase in neutrophil chemotactic function. No change in CD40 ligand expression was observed. Cyclosporin A blood level did not exceed 150 ng/mL during the study. CONCLUSIONS: A small dose of cyclosporin A (3 to 5 mg/kg/d) is beneficial in patients with hyperimmunoglobulinemia E syndrome. It should be considered in severe cases where other therapeutic modalities have failed.

Antibody Formation↗
PubMed1997

Antigen-specific immune responsiveness and lymphocyte recruitment in leukocyte adhesion deficiency type II.

The leukocyte adhesion deficiency syndrome type II (LAD-II) is caused by a general defect in fucose metabolism, which leads to the absence of fucosylated sugar determinants such as the selectin ligand SLe(x). In view of the important role of selectins in lymphocyte migration and homing, we have explored the in vivo immune responsiveness and lymphocyte recruitment to the skin, in response to the neo-antigen keyhole limpet hemocyanin (KLH) in a LAD-II patient. We observed a normal priming of KLH-specific T cells as well as a strong in vivo anti-KLH antibody response, both indicative of a normal T-B cell function and collaboration. Skin biopsies from the patient's skin taken prior to antigenic challenge showed the presence of normal numbers and subsets of T cells. Upon KLH injection, a large number of T cells were found to be recruited to the site of challenge, which was paralleled by up-regulation of the endothelial adhesion molecules ICAM-1 (CD54), VCAM-1 (CD106) and E-selectin (CD62E). The recruited T cell showed a normal subset distribution but lacked cutaneous lymphocyte antigen (CLA), the cutaneous homing receptor. However, the clinical symptoms of delayed-type hypersensitivity in the patient (redness and swelling) were severely depressed compared to that in the controls. In conclusion, the LAD-II patient showed a normal T cell priming and T cell-dependent antibody response, a normal baseline skin homing, and a significant T cell recruitment to the site of KLH challenge, indicating that fucosylated sugar determinants such as SLe(x) and CLA are not strictly required for adequate immune responsiveness and (skin) homing.

Antibody Formation↗
PubMed1997

Leukocyte adhesion defects.

Studies of genetic deficiency syndromes have provided important insights into the molecular basis and biology of leukocyte emigration. Both animal and human deficiency syndromes have been described.

Animals↗
PubMed1997

Repeated BCG vaccination is more effective than a single dose in preventing diabetes in non-obese diabetic (NOD) mice.

Stimulation of the non-obese diabetic (NOD) mouse immune-system with a single bacillus Calmette-Guerin (BCG) vaccination can inhibit the development of diabetes. The optimal dose, and the time and number of vaccinations is still to be clarified. In this study we evaluated the protective effect of repeated BCG vaccinations on preventing diabetes in NOD mice. 17/32 (53%) of the control group, 8/31 (26%) of the single vaccine-treated (at age 35 days) mice, and 7/23 (30%) of the single vaccine-treated (at age 90 days) mice developed diabetes, and none of the repeated BCG vaccination (at age 35 & 90 days, n = 14) animals developed the disease, up to 250 days of age (p < 0.05, compared with controls and each of the single-vaccination groups). While the severity of insulitis was lower in repeatedly BCG-treated mice at age 120 days as compared with controls and single BCG-vaccination groups, we could not detect significant differences in the Intracellular adhesion molecule-1 (ICAM-1) expression between the various groups. There were no differences in weight gain and blood hematocrit between the different groups. Our report demonstrates that repeated BCG vaccination is safe and more effective than a single dose in preventing type I diabetes in NOD mice. This data should be considered in planning new human trials with BCG.

Animals↗
PubMed1996

Familial relapsing thrombotic micro-angiopathy in two siblings.

UNLABELLED: Two siblings, a 12-year-old girl and a 7-year-old boy, had recurrent episodes of haemolytic-uraemic syndrome/thrombotic thrombocytopenic purpura, manifested mainly by thrombocytopenia and micro-angiopathic haemolytic anaemia. During 11 years of follow up the girl responded only to steroids, whereas many other therapeutic modalities were ineffective. Following treatment with low dose danazol relapses became fewer and of diminished severity and completely subsided after 6 months. The boy started his illness with signs of haemolytic uraemic syndrome and later developed neurological manifestations. During a 6 year follow up he responded only to plasma exchange. Although chronic thrombocytopenia persisted during the past 3 years, the boy's clinical condition improved. CONCLUSION: A family with two children with recurrent episodes of thrombotic thrombocytopenic purpura is described. In one child danazol could have had a beneficial effect.

Anemia, Hemolytic↗
PubMed1996

Activation of NADPH oxidase required for macrophage-mediated oxidation of low-density lipoprotein.

Low-density lipoprotein (LDL) oxidation by arterial wall cells, a key event during early atherogenesis, was suggested to involve the activation of 15-lipoxygenase and/or nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We sought to analyze the role of these oxygenases in macrophage-mediated oxidation of LDL under oxidative stress. Upon incubation of LDL with the J-774 A.1 macrophage-like cell line or with human monocyte-derived macrophages (HMDM) in the presence of 1 micromol/L CuSO4, the release of superoxide anions to the medium was demonstrated. Under these conditions, the cytosolic protein components of the NADPH oxidase complex, P-47 and P-67, translocated to the plasma membrane, indicating LDL-mediated activation of the NADPH oxidase complex. Under the above-mentioned experimental conditions, the macrophage 15-lipoxygenase was also activated, as determined by the release of 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) and 13-hydroxyoctadecadienoic acid (13-HODE) to the medium. Inhibition of the macrophage NADPH oxidase with apocynin or dismutation of superoxide anions, the product of NADPH oxidase activation, with superoxide dismutase (SOD) significantly inhibited macrophage-mediated oxidation of LDL (by 61% to 89%) under these conditions. Phorbol myristate acetate (PMA), which causes NADPH oxidase activation in J-774 A.1 macrophages, had no significant effect on 15-lipoxygenase activity, but still resulted in cell-mediated oxidation of LDL. Finally, HMDM from two patients with chronic granulomatous disease (CGD) that were shown to lack active NADPH oxidase, but to possess almost normal 15-lipoxygenase activity failed to oxidize LDL. We thus conclude that LDL-induced NADPH oxidase activation (under oxidative stress) is required for macrophage-mediated oxidation of LDL, whereas activation of 15-lipoxygenase may not be sufficient for LDL oxidation under these conditions.

Adolescent↗
PubMed1996

Major histocompatibility complex class II deficiency: a clinical review.

Major histocompatibility complex Class II deficiency or bare lymphocyte syndrome is a rare combined immunodeficiency that accounts for 5% of all cases of severe combined immunodeficiency. The syndrome is characterized by a lack of human leucocyte antigen Class II gene expression, absence of cellular and humoral T-cell immune response to foreign antigens, and impaired antibody productions, resulting in extreme susceptibility to viral, bacterial and fungal infections. In some patients, there is a reduced cell surface expression of human leucocyte antigen Class I molecules also. Major histocompatibility complex Class II deficiency is an autosomal recessive disease, most frequent in the Mediterranean area. The disease is caused by impaired gene regulation involving trans-acting proteins. Somatic cell genetics using cell fusion experiments identified four complementation groups, all resulting in the same clinical manifestation. Two regulatory genes have been identified so far: Class II trans activator and regulatory factor X5. Supportive treatment includes intravenous gammaglobulin and prophylaxis against Pneumocystis carinii. The only curative treatment is bone-marrow transplantation.

Female↗
PubMed1996

Adhesion molecules--their role in health and disease.

Adhesion molecules play a major role in the recruitment of neutrophils to the site of inflammation. Neutrophils' localization is dynamic and involves multiple steps. In each step a different family of adhesion molecules takes part. The rolling phase is mediated by the selectin family, the E-, L-, and P- selectins, and their ligand, sialyl Lewis X. The next step, the activation and firm adhesion of the neutrophils to the endothelium, is regulated by the integrin family and their ligand, the Ig superfamily. The final step of transendothelial migration is again mediated by these two families of adhesion molecules. Although many in vitro studies were able to show the role of these molecules, their real importance was demonstrated in rare disease states where one of the adhesion molecule was absent. Two adhesion molecule deficiencies were described, both characterized by recurrent infections, defect in wound healing, and marked leukocytosis. Leukocyte adhesion deficiency (LAD) I is caused by a defect in the beta subunit of the integrin molecule, whereas in LAD II, the ligand for the selectin, the sialyl Lewis X is markedly decreased. Further insight was also gained with the generation of strains of mice deficient in one or another adhesion molecules (knock-out mice) Exploiting current knowledge on adhesion molecules and their role in health and disease, several trials have been designed to assess the effect of blocking their activity in conditions associated with increased expression of various adhesion molecules.

Animals↗