Multiple slow-growing nodules on the cheek.
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Adenoma, Pleomorphic↗
Biomedical subjects
Y Levy
Publications and source records attributed to Y Levy.
Catastrophic antiphospholipid syndrome: remission following leg amputation in 2 cases.
OBJECTIVE: The antiphospholipid syndrome is characterized by venous and arterial thrombotic events that are often recurrent, thrombocytopenia, recurrent fetal loss, and elevated titers of antiphospholipid antibodies. A subtype of patients with a particularly overwhelming clinical picture has been termed catastrophic antiphospholipid syndrome (CAPS). In this report, we present 2 patients who exhibited a similar multisystem disorder associated with gangrenous changes in the lower extremities. METHODS: Two patients with CAPS are presented, highlighting the impact of this disorder on the patients and the response to various therapeutic modalities. RESULTS: Both patients had pulmonary, cardiac, cutaneous, and neurologic findings consistent with CAPS. In addition, they had large purulent leg ulcers associated with livedo reticularis. Amputation of the legs in each case induced remission of the systemic illness. CONCLUSIONS: We believe that infection plays a significant role in the pathogenesis and amplification of the antiphospholipid syndrome. In certain patients, this association probably is mediated via immune mechanisms, which also enhance the genesis of atherosclerosis. After the foci of infection (suppurative leg ulcers) were removed, the underlying illness improved. These case studies provide an opportunity to study the interrelationship between several confounding factors that converge and lead to the development of this autoimmune condition.
Amputation, Surgical↗
Anti-endothelial cell antibodies from patients with thrombotic thrombocytopenic purpura specifically activate small vessel endothelial cells.
Thrombotic thrombocytopenic purpura (TTP) is an uncommon disease of an unknown etiology, characterized by consumptive thrombocytopenia, microangiopathic hemolytic anemia, fever and acute thrombotic complications, especially within the cerebral circulation. Although anti-endothelial cell antibodies (AECA) have occasionally been shown to be present in TTP, their role in the pathogenesis of the disease has never been ascertained. In the current study we demonstrated the pathogenic activity of affinity-purified anti-endothelial cell F(ab)2 antibodies (AECA/TTP) from four consecutive patients with active TTP. These AECA/TTP bound to and activated only microvascular endothelial cells (EC) and not large vessel EC. The specificity of AECA/TTP binding to microvascular EC was confirmed by competition assay employing membranes derived from small and large vessels EC. Activation included enhanced IL-6 and von Willebrand factor release from the EC followed by increased expression of adhesion molecules P-selectin, E-selectin and vascular cell adhesion molecule-1 on the EC, as evaluated by ELISA. Increased expression of adhesion molecules was followed by an increase in monocyte adhesion to EC. The level of soluble thrombomodulin (TM) also increased in the culture medium of activated microvascular EC upon exposure to AECA/TTP antibodies and was directly correlated to a decrease in cell-associated TM. Our data suggest that AECA/TTP directed against microvascular EC could play a pathogenic role in the development of endothelial injury in TTP that leads to thrombosis.
Antibody Specificity↗
Quality assessment of oral anticoagulant treatment in the Beer-Sheba district.
OBJECTIVE: To evaluate the adequacy of oral anticoagulation therapy in patients with either prosthetic heart valves or atrial fibrillation. DESIGN: Adequacy of anticoagulation therapy of patients treated with warfarin was determined before and after implementation of an improvement programme. SETTING: The central haematology laboratory of the Soroka Medical Center, Beer-Sheba Israel. STUDY PARTICIPANTS: One hundred and ten patients treated with chronic anticoagulation therapy were evaluated by measuring the international normalized ratio of the prothrombin time before and after implementation of an improvement plan aimed at improving anticoagulation control. INTERVENTION: A programme that included physician and patient education and procedural changes covering all aspects of anticoagulation therapy was implemented. MAIN OUTCOME MEASURE: The percent of international normalized ratio tests below, within and above the therapeutic range was determined. RESULTS: Prior to implementation of an improvement plan, only 32% of the measured international normalized ratio values were within the therapeutic range. 16% were above and 52% were below therapeutic range. Improvement intervention led to an increase in the proportion of international normalized ratio tests that fell within the therapeutic range from 32% to 43.2%. CONCLUSIONS: Improvement in the control of anticoagulation therapy of patients receiving long-term warfarin treatment is possible. A combined effort involving the community, physician and patient is required.
Administration, Oral↗
Longitudinal surveillance of antibiotic use in the hospital.
We evaluated antimicrobial use in our hospital by department, including indications for use, source of infections, use of the microbiology laboratory, and appropriateness of prescribing, in a prospective, comparative, non-interventional study of all patients receiving antimicrobial agents. We excluded departments where antimicrobial use was negligible. The other 19 departments were followed for 3 (n=4) or 4 (n=15) months, including 2 consecutive months in the spring-summer and either 1 or 2 in the autumn-winter. Antimicrobial therapy was followed from initiation, through possible adaptations, and possible change from intravenous to oral therapy, until discontinuation of treatment. Overall, 6376 antibiotics were given to 2306 patients. Of the surveyed hospitalized patients, 62%+/-22% received antibiotics, with a range of 4-100% per department. Antibiotics were prescribed for infections acquired in the community (3037 instances, 47%), in the hospital (2182, 34%), in a nursing home (575, 9%), and for prophylaxis continued post-operatively (582, 9%). The most common indications for antimicrobial use were: respiratory tract infection (1729, 27%), urinary tract infection (955, 15%), sepsis (701, 11%), intra-abdominal infections (663, 10%), prophylaxis 582 (9%), soft-tissue infection (572, 9%), and surgical site infection (319, 5%). Univariate indicators for appropriateness of treatment were: age, department, site of infection, source of infection, antimicrobial drug and serum creatinine (all p<0.001). Forty-nine antimicrobials were prescribed in 279 combinations, 58% as single agent and 42% as drug combinations. Half of all antimicrobial use consisted of four agents: cefuroxime (19.1%), metronidazole (11.3%), gentamicin (10.6%) and ampicillin (10.2%), which together accounted for 20% of expenditure on antibiotics. Although use of as many as 53% of antimicrobials (26/49) surveyed was restricted, use in this category accounted for only 29% of all antimicrobial courses. Of 6376 antibiotic courses, 4101 (64%) were given intravenously and 2275 (36%) orally. Appropriateness of use of restricted drugs was lower (70%) than of unrestricted ones (84%, p<0.001). Of 24571 defined daily doses (DDD) given orally, 4587 (19%) were restricted, compared to 7264 (34%) of 21602 DDDs given intravenously (p<0.001). Antibiotic treatment in our hospital appears to be substantial and increasing, justifying efforts to improve appropriateness of therapy and improve clinical and financial results.
Administration, Oral↗
Coronary artery disease but not coronary calcification is associated with elevated levels of cardiolipin, beta-2-glycoprotein-I, and oxidized LDL antibodies.
BACKGROUND: Autoimmune factors have been shown to play a role in atherosclerosis. The aim of this study is to correlate 5 autoantibodies (anticardiolipin, anti-CL, beta2-glycoprotein-I, beta2GPI, phosphatidylcholine, oxidized low-density lipoprotein, oxLDL, endothelial cell) with the presence of coronary heart disease, angiographic findings, and with coronary artery calcification. METHODS: The levels of the 5 autoantibodies and a control antifibroblast line of 126 coronary heart disease patients and 20 healthy controls were measured. Fifty-one patients underwent coronary angiography, and 98 patients had coronary artery calcium determination using spiral computerized tomography (dual mode). RESULTS: Levels of 3 autoantibodies (anti-CL, beta2GPI, oxLDL) were significantly elevated in coronary heart disease patients compared with controls (p < 0.001, p = 0.001, p < 0.001, respectively). Within the subgroup of patients with significant coronary artery stenosis, anti-CL antibodies were also elevated (p = 0.008). No correlation was found between anti-CL, and anti-beta2GPI autoantibody levels and coronary calcium scores as measured by spiral computerized tomography. However, anti-oxLDL antibodies were raised in patients with no calcification detected by spiral computerized tomography, compared with the patients with any coronary calcification (p = 0.046). CONCLUSION: Anti-CL, beta2GPI and oxLDL antibodies are elevated in coronary heart disease patients regardless of coronary calcification.
Aged↗
Adverse effects of intravenous immunoglobulin therapy in 56 patients with autoimmune diseases.
OBJECTIVE: To test the adverse effects and viral safety of intravenous immunoglobulin (IVIg) use in autoimmune diseases. METHODS: Fifty-six patients with various autoimmune diseases who were treated with one to six IVIg courses were evaluated for the presence of adverse effects following IVIg therapy and were screened before and after the treatment for the presence of serum human immunodeficiency virus antibodies, hepatitis C virus antibodies, and hepatitis B surface antigen. RESULTS: Among the 56 patients, 20 (36%) had at least one adverse effect following at least one of the treatment courses. These included headache, low-grade fever, chills, anemia, low-back pain, transient hypotension, nausea, intensified perspiration, and superficial and deep vein thromboses. Whereas the presence of adverse effect to IVIg was unrelated to either the clinical response to the treatment or to the nature of the autoimmune disease, the occurrence of an adverse effect in the first treatment course was significantly associated with a greater chance for an adverse effect in the subsequent courses. No transmission of any of the three viral agents examined could be detected. CONCLUSIONS: Although IVIg use in autoimmune diseases is associated with adverse effects in about one third of the patients, these effects are usually mild and transient. Patients who develop adverse effects during the first treatment course may be at increased risk of adverse effects during the subsequent IVIg courses.
Adolescent↗
High-dose intravenous immunoglobulins for lupus nephritis--a salvage immunomodulation.
Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease with a great diversity of clinical manifestations which is difficult to manage. IVIGs represent promising immunoregulatory agents with the ability to control SLE without subsequent predisposition to infectious complications. Despite the implied risk of developing renal failure due to IVIG, considerable beneficial effects on lupus nephritis are reported. In this review, the clinical and adverse effects, and mechanism of action, with special emphasis on modulation, of idiotypic network is discussed.
Humans↗
A syndrome of transient encephalopathy associated with adenovirus infection.
BACKGROUND AND OBJECTIVE: Adenovirus is a common pathogen in the pediatric population. Respiratory, gastrointestinal, or renal systems are often involved in adenovirus infections. Several neurologic syndromes have been attributed to adenovirus, such as adenovirus aseptic meningitis, myelitis, subacute focal encephalitis, and Reye-like syndrome. The purpose of this study was to describe the clinical features and encephalography findings in 7 infants treated in our center for a syndrome of transient encephalopathy associated with adenovirus infection. STUDY PARTICIPANTS: Three females and 4 males ages 7 to 34 months seen in our department between July 1983 and February 1984 and September 1998 and May 1999 presented with fever of at least 7 days' duration and a gradual decline in the state of alertness. Score on the Glasgow Coma Scale ranged from 9 to 12. Findings on lumbar puncture were normal. In all 7 patients, the encephalogram showed moderate to severe background slowing compatible with encephalopathy. All patients were catarrheal and had mild hepatomegaly with slight elevation of liver enzymes. Some had bronchopneumonia, diarrhea, and conjunctivitis either isolated or in combination. METHODS AND RESULTS: Adenovirus was isolated by immunfluorescence technique in all patients-from the sputum in 3 patients, nasopharynx in 5, conjunctiva in 4, and rectal swab in 5. In 5 patients, serotyping was performed by an antibody neutralization method. Adenovirus type 3 was ascertained from a nasal swab in 1 patient, sputum specimens in 3, throat swab in 3, and rectal cultures in 5. The clinical course was characterized by a progressive recovery of alertness. After several days, there was a complete reversal of neurologic findings. CONCLUSION: We suggest that this syndrome of transient encephalopathy is a distinct entity and should be considered as another of the several neurologic syndromes known to be associated with adenovirus infection.
Adenoviridae↗
[Intravenous immunoglobulins treatment of patients with Graves' ophthalmopathy].
Graves' ophthalmopathy is an autoimmune disease manifested as exophthalmus, lid lag and diplopia. As in the accompanying autoimmune thyroid disease, there is an autoimmune homonal and cellular attack on the orbita, mainly the retro-orbital tissues. Steroids are the cornerstone of therapy. We reviewed the evidence for a similar therapeutic effect of i.v., immunoglobulins (IVIGs) and their better side affect profile as compared to steroids. We also described an impressive therapeutic success with IVIG given to a patient with resistant ophthalmopathy. The clinical picture of Graves' ophthalmopathy is attributed to a pathologic hyper--activation of orbital fibroblasts, deposition of collagen and glycosaminoglycans in the extra-cellular matrix and eventually fibrosis. These are mediated by leucoregulin, IL-1, IFN-gamma, and TGF-beta--all secreted by lymphocytes and mast cells in the retorbital space. Another mode of cell activation is by binding of autoantibodies (presumably thyroid stimulating Ab's) to an antigenic determinant on the surface of fibroblasts. I.v. immunoglobulins, known today to be active in a variety of autoimmune processes, exert their effect on autoantibodies, complement, phagocytic cells etc. IVIGs also inhibit orbital lymphocytes and fibroblasts through inhibition of IL-1 or/and TGF-beta.
Aged↗
[Eosinophilic ascites as a presenting symptom of the hypereosinophilic syndrome].
We report a case of a 22 year old man with a history of bronchial asthma, suffering from diarrhea, eosinophilic ascites and prominent blood and bone marrow eosinophilia. The patient responded to corticosteroid treatment. Later, hydroxyurea was added to this treatment because of recurrence of eosinophilia, ascites and hepatosplenomegaly. Eosinophilic ascites is rarely the outstanding symptom of the hypereosinophilic syndrome. Following the exclusion of other reasons for eosinophilia, concomitant unexplained hepatosplenomegaly suggested the diagnosis of a hyperereosinophilic syndrome.
Adult↗
Homocysteine and cardiovascular risk in patients with diabetes mellitus.
BACKGROUND AND AIM: Diabetes mellitus is the most common metabolic disorder in the Western world with coronary artery disease as its leading cause of mortality. Conventional coronary risk factors do not explain the high morbidity rate and there is strong evidence linking hyperhomocystinemia and premature atherosclerosis. Therefore, we reviewed the relationship between homocysteine and diabetes mellitus. DATA SYNTHESIS: The literature dealing with diabetes mellitus, B vitamins and metformin was reviewed. Some studies show higher than normal fasting and postmethionine load levels of plasma homocysteine in diabetes patients, particularly in those with nephropathy and microalbuminutia. Metformin use and low plasma B vitamins are other potential mechanisms resulting in hyperhomocysteinemia in these patients. CONCLUSIONS: Abnormal homocysteine concentration is prevalent in subsets of diabetic patients; its relationship with excess cardiovascular morbidity is not yet clear. Consequently, large prospective studies are essential in order to follow the effects of homocysteine and its normalization on accelerated artherosclerosis in diabetes.
Coronary Disease↗
Shrinkage of melanoma metastases following high dose intravenous immunoglobulin treatment.
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Adult↗
Myalgia, fever, abnormal muscle enzymes and blue urine in a farmworker from Thailand.
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Adult↗
Cytokine levels in various intravenous immunoglobulin (IVIg) preparations.
The mechanisms of action of intravenous immunoglobulin (IVIg) in autoimmune diseases include modulation of cytokine levels. We examined therefore whether direct infusion of abnormally high levels of 13 different cytokines or cytokine-inhibitors within 5 different IVIg preparations have any role in modulation of their levels. None of the measured cytokines in any of the IVIg preparations tested were above the normal levels, and regarding some no traces could be detected. Hence, modulation of cytokine levels following IVIg therapy involves other mechanisms such as interference with their secretion or cytokine-specific blocking antibodies, rather than direct infusion of cytokines.
Cytokines↗
Characterization and optimization of a real-time, parallel, label-free, polypyrrole-based DNA sensor by surface plasmon resonance imaging.
We describe in this paper a methodology to quantify multispot parallel DNA hybridizations and denaturations on gold surfaces by using, on one hand, a polypyrrole-based surface functionalization based on an electrospotting process and, on the other hand, surface plasmon resonance imaging allowing real-time measurements on several DNA spots at a time. Two characterization steps were performed in order to optimize the immobilization of oligonucleotide probes and, thus, to increase the signal-to-noise ratio of monitored hybridization signals: the first step consisted of characterizing the signal dependence upon the density of immobilized 15-mer probes, and, the second step, in analyzing the hybridization response versus spot thickness. We further demonstrated that a surface density of polypyrrole/DNA probes of approximately 130 fmol/ mm2 (590 pg/mm2) optimizes the hybridization signal that can be detected directly. Optimal thickness of the spot was found to be close to 11 nm. Specificity and regeneration steps on each spot have also been demonstrated successfully, showing this method to be very competitive and convenient in use.
Base Sequence↗
Impaired antibody affinity maturation process characterizes a subset of patients with common variable immunodeficiency.
Common variable immunodeficiency (CVID) is an heterogeneous syndrome characterized by decreased levels of serum Ig and recurrent bacterial infection. Here, we were interested to study whether a qualitative defect of the affinity Ab maturation process could be combined to the low level of serum Ig in a cohort of 38 CVID patients. For this, we designed a novel and rapid screening test for the detection of hypomutated V gene expressed by memory B cells. This test delineated a subset of 9/38 (23%) CVID patients with an abnormal pattern of Ig V gene mutation. The mean frequency of V gene mutation of this subset was significantly lower (1.74%) compared with other CVID patients (5.46%) and normal donors (6.5%) (p<0.0001). The mean age of this subgroup was significantly higher than other hypogammaglobulinemic patients with normal levels of V gene mutation (p<0.02), whereas no difference in the duration of symptoms was noted between the two groups. This suggests that hypomutation characterizes patients who began CVID late in life. Recently, it was shown that non-Ig sequences, such as the intronic BCL-6 gene, could be the target of the somatic hypermutation process in normal memory B cells. Our finding of a normal mutation frequency of the BCL-6 gene in two hypomutated CVID point to a defect of the Ig targeting of hypermutation machinery in these cases.
Adult↗
Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2).
The activation-induced cytidine deaminase (AID) gene, specifically expressed in germinal center B cells in mice, is a member of the cytidine deaminase family. We herein report mutations in the human counterpart of AID in patients with the autosomal recessive form of hyper-IgM syndrome (HIGM2). Three major abnormalities characterize AID deficiency: (1) the absence of immunoglobulin class switch recombination, (2) the lack of immunoglobulin somatic hypermutations, and (3) lymph node hyperplasia caused by the presence of giant germinal centers. The phenotype observed in HIGM2 patients (and in AID-/- mice) demonstrates the absolute requirement for AID in several crucial steps of B cell terminal differentiation necessary for efficient antibody responses.
APOBEC-1 Deaminase↗