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Biomedical subjects

Y Levy

Publications and source records attributed to Y Levy.

340 records · Page 19Linked to original sources
PubMedDate not supplied

Serum lipoproteins in home total parenteral nutrition patients.

Patients maintained in our home total parenteral nutrition (HTPN) program receive very small amounts of cholesterol in their solutions. Because of the severe intestinal insufficiency which is characteristic of this group, they do not absorb significant amounts of cholesterol or bile salts from their intestines. We investigated the serum lipoproteins in nine patients maintained on HTPN for 36 +/- 4 (mean +/- SEM) months. Fat emulsions were given twice a week as a source of essential fatty acids. Mean serum cholesterol 110 +/- 6.5 mg/dl, LDL-cholesterol 75 +/- 6 mg/dl, and HDL-cholesterol 29 +/- 1 mg/dl, were at or below the 5th percentile compared with age- and sex-matched Lipid Research Clinic controls. HDL-cholesterol to serum cholesterol ratio was in the normal range (0.25 +/- 0.30). The mean serum cholesterol did not rise, but the mean serum triglyceride rose significantly from 72 +/- 4 to 104 +/- 16 mg/dl (p less than 0.05) immediately after completion of TPN infusions with fat emulsions. There was a negative correlation between the length of HTPN therapy and the total serum cholesterol (r = 0.43, p less than 0.05). Thus, HTPN patients have markedly depressed concentrations of total serum cholesterol, LDL-cholesterol, and HDL-cholesterol, but the ratio of HDL cholesterol to total serum cholesterol is in the normal range.

Adult↗
PubMedDate not supplied

Phosphate depletion syndrome: case report with bone and muscle histology findings and review of the literature.

A 44-yr-old woman with a 16-yr history of heavy antacid ingestion was evaluated for severe weight loss, weakness, bone pain, and multiple fractures. Laboratory investigation revealed severe hypophosphatemia with undetectable phosphate in the urine. Serum parathyroid hormone (PTH), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D levels were normal. Transiliac bone biopsy revealed evidence of mineralization defect compatible with hypophosphatemic osteomalacia. Bone densitometry documented decreased bone density with a low mineral content. Management included withdrawal of antacids and provision of phosphate-supplemented enteral nutrition, which resulted in prompt weight gain and resolution of the clinical and biochemical abnormalities. The pathogenesis, diagnosis and histological features of hypophosphatemic osteomalacia are discussed.

Adult↗
PubMedDate not supplied

Valvular deposition of antiphospholipid antibodies in the antiphospholipid syndrome: a clue to the origin of the disease.

In this report we present an unusual case of a 45-year-old female patient with systemic lupus erythematosus (SLE) who was hospitalized for mitral valve replacement. In her childhood she presented with mitral stenosis and chorea on which grounds a preliminary diagnosis of rheumatic fever was established. After a quiescent period lasting two decades her disease erupted with mitral stenosis, thromboembolic phenomena, and nephritis. Due to severe malfunctioning of her mitral valve, the patient eventually underwent mitral valve replacement. The antibodies involved in the pathogenesis of our patient's valvular disease were studied by immunohistochemical analysis, applying rabbit polyclonal anti-human IgG and IgM anti-human C3c and anti-idiotypes to a mouse monoclonal naturally occurring polyspecific human monoclonal anti-cardiolipin antibody termed S2.9, and to the 16/6 Id which defines a common Id on anti-DNA antibodies in patients with SLE. Immunoperoxidase staining using an anti-idiotype mAb to anti-cardiolipin antibodies demonstrated the deposition of these anti-bodies in the subendothelial layer of the valve. We believe that anti-phospholipid syndrome (APS) with SLE was the initial and primary disease in this patient. These findings clearly indicate that APS must be considered in the differential diagnosis of rheumatic fever, particularly in young female patients who present with mitral stenosis and chorea.

Adolescent↗
PubMedDate not supplied

Use of intravenous immunoglobulin in livedo vasculitis.

We describe a 36-year-old woman with livedo vasculitis (atrophie blanche) lasting for 15 years. After the failure of numerous therapeutic modalities the patient was treated with intravenous immunoglobulin. Significant resolution of the cutaneous lesions was seen with a concomitant alleviation of pain. To the best of our knowledge this is the first patient with livedo vasculitis described in the medical literature ever to be treated with IVIG and to achieve a successful outcome.

Adult↗
PubMedDate not supplied

Anti-cardiolipin antibody from a patient with antiphospholipid syndrome (APS) recognizes only an epitope expressed by cardiolipin/beta 2-glycoprotein-I (beta 2GPI) complex and induces APS.

OBJECTIVE: As the antiphospholipid syndrome (APS) is characterized by antibodies which bind negatively charged phospholipids either directly or mainly through different target epitopes located on the beta-2-glycoprotein-I (beta 2GPI) molecule, the aim of this study is to describe an additional target epitope for anti-cardiolipin binding. METHODS: The binding characteristics of affinity purified anti-cardiolipin antibodies from a patient with monoclonal gammopathy associated with clinically overt APS were studied; inhibition studies were also carried out. These antibodies were used for the active induction of experimental APS. RESULTS: The affinity purified anti-cardiolipin antibodies were found to bind a target epitope created by the complex of cardiolipin/beta 2GPI, while not reacting with a complex composed by another phospholipid (phosphatidylserine/beta 2GPI), as confirmed by direct binding and competition assays. Immunization of naive mice with this unique affinity purified anti-cardiolipin antibody resulted in the induction of experimental APS (thrombocytopenia, prolonged coagulation timed and fetal resorptions). The anti-cardiolipin/beta 2GPI injected mice developed high titers of mouse anti-cardiolipin/beta 2GPI antibodies with the same binding characteristics as the human antibody which was used for disease induction. CONCLUSION: APS is a unique syndrome that is characterized by a diversity of pathogenic anti-phospholipid antibodies which may explain the diversity of clinical manifestations reported in patients.

Aged↗
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Isotretinoin-induced adult onset Still's disease.

We describe a 21-year old man who was diagnosed as having adult onset Still's disease (AOSD) in association with isotretinoin treatment for acne conglobata. The patient was febrile, with a macular salmon pink rash, arthritis, hepatosplenomegaly, and axial lymphadenopathy. Laboratory results showed leukocytosis, mild liver dysfunction and negative rheumatoid factor and antinuclear antibodies. Isotretinoin, an orally active derivative of vitamin A, has been associated with various rheumatologic conditions such as arthralgia, myalgia, vasculitis and arthritis. The etiology of rheumatic disorders associated with retinoids is still obscure; however, it is presumed that immunomodulation by several mechanisms (such as an alteration of the cytokine balance) is probably ascribable to this interesting association.

Adult↗
PubMedDate not supplied

Induction of anti-RA33 hnRNP autoantibodies and transient spread to U1-A snRNP complex of spliceosome by idiotypic manipulation with anti-RA33 antibody preparation in mice.

OBJECTIVE: Anti-RA33 antibodies occur in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD) and target the A2/B1 protein of the heterogeneous nuclear ribonucleoprotein (hnRNP) complex 4 which forms part of the spliceosome. The aim of the present study was to evaluate the immune response and pathological features induced in mice immunized with anti-RA33 antibodies or patient-derived recombinant single-chain variable fragments (scFv) of anti-RA33 antibodies. METHODS: In the first set of the experiment, two strains of mice (C57BL/6J and BALB/c) were immunized with IgG preparations obtained from two patients with RA and one normal donor. One of the patients had high titer anti-RA33 antibodies; the other one showed weak borderline reactivity. In the second set of the experiment three groups of C57BL/6J mice were immunized, respectively, with affinity-purified (AP) anti-RA33 antibodies, scFv of anti-RA33 antibodies and normal human IgG. The immunological response induced in immunized mice was studied by immunoblotting and line immunoassay (LIA). The presence of arthritis, serositis or myositis was assessed six-months following initial immunization. RESULTS: While anti-RA33 antibodies developed in only two of the mice immunized with different human IgG fractions, anti-RA33 antibodies were clearly detected in 7 sera of 13 mice immunized with AP anti-RA33 antibodies three months after the boost immunization and, moreover, also in 2 sera of 13 mice immunized with scFv of anti-RA33 antibodies. In contrast, mice immunized with normal human IgG did not develop anti-RA33 antibodies. Interestingly, transient autoantibody production against another nuclear autoantigen, U1 snRNP, was observed in 3 C57BL/6J mice immunized with scFv and in 1 mouse immunized with AP autoantibodies. However, these immunological responses were not associated with pathological findings. CONCLUSIONS: Active immunization of naive mice with AP anti-RA33 antibodies and scFv of anti-RA33 antibodies resulted on the one hand in the production of murine anti-RA33 antibodies and led, on the other hand, to transient "autoantibody spread" to snRNP component of the spliceosome and other nuclear autoantigens. This "autoantibody spread" probably reflected disregulation of the idiotypic anti-idiotypic cascade.

Animals↗
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Transverse myelitis associated with chronic hepatitis C.

An infectious etiology is one of the postulated mechanisms for autoimmune diseases. An emergence of autoimmune phenomena associated with hepatitis C virus (HCV) infection has been reported. Transverse myelitis is an inflammatory disease of the spinal vasculature attributed to viral infections and to autoimmune diseases including systemic lupus erythematosus and the antiphospholipid syndrome. A 34-year-old male was admitted for the rapid onset of numbness of the lower extremities and urinary retention. His past history included hepatitis C infection. The neurological examination and MRI of the thoracic spine confirmed the diagnosis of transverse myelitis. Abnormal laboratory results were hyperglobulinemia, abnormal liver function tests, and positive ANF, anti-dsDNA antibodies, and p and c-ANCA. The patient was treated with high dose prednisone, then tapered to a low dose, but regained only partial neurological function after 15 months of prednisone therapy. Persistent neurological deficits and elevated ANF and ANCA were present at a follow-up of 30 months. We describe the first reported case of a patient with chronic HCV who developed transverse myelitis.

Adult↗
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Health effects from exposure to organophosphate pesticides in workers and residents in Israel.

Major findings from our work on exposures and effects from organophosphate-containing pesticides in selected occupational and community patients and groups in Israel are reviewed as a basis for recommending control measures. The worker groups were pilots, ground-crews, and field workers; exposed nonworkers were adults and children living in kibbutzim with drift exposures, and household residents in houses treated by pest exterminators. In all groups, evidence of exposure-illness associations was found even though persons with acute poisoning were not seen. Complaints (headache, dizziness, fatigue, nausea, breathing problems, abdominal cramps, and tingling in extremities) were associated with within-normal depressions in cholinesterase activity. Whole blood and plasma cholinesterase activity were slightly more sensitive indicators of mixed exposure than red blood cell cholinesterase activity. High alkyl phosphate levels and symptoms were seen in individuals with within-normal limit depressions in cholinesterase activity. Complaints of weakness and tingling in hands and feet, together with low-grade changes in nerve conduction, suggest the possible influence of agents with a neurotoxic esterase-type activity independent of cholinesterase activity. Transient in-season neuropsychological changes in tests of mood status and performance were associated with exposure. Recommendations for exposure reduction include: accelerating the already declining use of pesticides in general, and organophosphates in particular; promoting the shift from more to less toxic organophosphates and other pesticides; and introducing rigid performance specifications for closed systems in loading and mixing at end-user sites. Dermal protection remains a problem. Cholinesterase activity levels and symptom interviews are useful for monitoring workers at risk, but alkyl phosphate levels are the definitive measure of exposure, surveys, investigations and surveillance.

Adolescent↗
PubMedDate not supplied

Outcome of patients with scleroderma admitted to intensive care unit. A report of nine cases.

OBJECTIVE: Patients with systemic rheumatic disease constitute a small percentage of admissions to the medical intensive care units (ICUs). Systemic sclerosis (SSc) is one of the rheumatic diseases that together with secondary complications may lead to a critical illness requiring hospitalization in the ICU. We present the features, clinical course and outcome of critically ill patients with scleroderma that were admitted to the ICU. METHODS: The medical records of nine patients with diagnosis of scleroderma (8 female, 1 male), admitted to the intensive care unit of Sheba Medical Center during the 11-year interval between 1991 and 2002, were reviewed. RESULTS: The mean age of the patients at the time of admission to the ICU was 48 +/- 13 [SD] years. The mean duration of SSc from diagnosis to the ICU admission was 8 +/- 8 years. Six patients had diffuse SSc, two patients had limited SSc and one patient had juvenile diffuse morphea. The main reasons for admission to the ICU were: infection/ septic syndrome (n = 4), scleroderma renal crisis (SRC) with pulmonary congestion (n = 2), acute renal failure associated with diffuse alveolar hemorrhage namely scleroderma- pulmonary - renal syndrome (SPRS) (n = 1), iatrogenic pericardial tamponade (n = 1), mesenteric ischemia (n = 1). The patients had high severity illness score (mean APACHE II 25 +/- 3). Eight out of nine patients (89%) that were admitted to the ICU died during the hospitalization, six (66.6%) of them died in the ICU. Septic complications as the main cause of death were determined in five patients (62.5%), while four of them had pneumonia and acute respiratory failure along with underlying severe pulmonary fibrosis. Lungs and kidneys were the most common severely affected organs by SSc in our patients. CONCLUSION: The outcome of scleroderma patients admitted to the ICU was extremely poor. Infectious complication was the most common cause of death in our patients. Although infections are treatable, the high mortality rate for this group of patients was dependent on the severity of the underlying visceral organ involvement, particularly severe pulmonary fibrosis. The severity of this involvement is a poor outcome predictor. An early diagnosis and an appropriate treatment of such complications may help to reduce the mortality in scleroderma patients.

Adult↗
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Cerebrospinal fluid findings in infants with nonpolio enteroviral meningitis.

We studied 25 infants aged less than 9 months who were diagnosed as having nonpolio enteroviral meningitis (EM) confirmed by virus isolation from cerebrospinal fluid (CSF). CSF protein, glucose and cellular content in these infants was compared with that of 125 age-matched febrile infants without cerebromeningeal illness. In order to control for changes occurring in the CSF during the first 2 months of life, the studied infants and the control subjects were stratified into 2-week age-groups and were compared. All but three of the infants with EM had increased CSF leukocyte count, and 10 infants showed domination of the polymorphonuclear leukocytes in the CSF. Only two had increased CSF protein levels, and low CSF/blood glucose ratios were found in all but two cases. None of the infants with EM had increased values of CSF protein concomitant with decreased CSF/blood glucose ratio. CSF in EM is characterized by increased white blood cell count in contrast with normal or near-normal CSF protein and glucose levels. In some infants, enterovirus isolation may be the only evidence of EM.

Age Factors↗
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IgA in Sjögren's syndrome.

Patients with Sjögren's syndrome (SS) display two sets of immunological abnormalities. B cells are oligoclonally activated, resulting in hypergammaglobulinaemia, elevated levels of circulating immune complexes (CIC) and non-organ specific autoantibodies. The cellular arm of the immune response is also involved, as shown by the predominance of activated T cells within the exocrine gland infiltrate. IgA could well bridge the gap between activated B cells and defective T cells and by doing so, play a pivotal role in the pathogenesis of SS. This interpretation is supported by the high proportion of IgA in immunoglobulin(Igl) production at the mucosal level. Additionally, IgA is the Igl class most dependent on T cell help. A number of studies over the past 15 years have reported high levels of serum and secretory IgA, IgA-rheumatoid factor and IgA-containing CIC. A correlation between disease activity and the latter abnormalities has recently been shown. There is, however, a need for longitudinal assessment of total IgA and IgA autoantibodies in order to further evaluate their role in the pathogenesis of the disease.

Antigen-Antibody Complex↗
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The novel analog 1,24(S)-dihydroxyvitamin D2 is as equipotent as 1,25-dihydroxyvitamin D3 in growth regulation of cancer cell lines.

The physiologically active metabolite of the vitamin D seco-steroid hormone, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is a major regulator of mineral homeostasis. Recent evidence also suggests its role in regulating proliferation and differentiation of cells, including cancer cells. Therapeutic application of 1,25(OH)2D3 to hyperproliferative disease, such as cancer, is thwarted by its hypercalcemic activity. To overcome this problem, analogs of 1,25(OH)2D3 have been produced which retain growth regulating properties and exhibit decreased hypercalcemic activity. In the present study, the efficacy of the vitamin D2 analog, 1,24(S)-dihydroxyvitamin D2 (1,24(S)-(OH)2D2) in the inhibition of cancer cell proliferation and in inducing differentiation of cancer cells was compared to that of 1,25(OH)2D3. By the [3H]-thymidine incorporation procedure, 1,24(S)-(OH)2D2 is as equipotent as 1,25(OH)2D3 in inhibiting the proliferation of five different cell lines, ROS 17/2.8, the rat osteosarcoma cell line, MCF-7, the human breast cancer cell line, HD-11, the chick bone marrow v myc transformed cell line, HT-29, the human colon cancer cell line and HL-60, the human leukemia cell line. The inhibitory action was dose and time-dependent. The NBT reduction method indicated that 1,24(S)-(OH)2D2 induces the differentiation of the human leukemia cell (HL-60) to the same extent as 1,25(OH)2D3. Notwithstanding the vast similarity between 1,24(S)-(OH)2D2 and 1,25(OH)2D3 with regard to the above activities, they differ in their effects on calcium regulation. In conclusion, the present results encourage the use of 1,24(S)-(OH)2D2 for the treatment of cancer disease in vivo.

Animals↗
PubMedDate not supplied

Association of 16/6 and SA1 anti-DNA idiotypes with anticardiolipin antibodies and clinical manifestations in a large cohort of SLE patients. European Concerted Action on the Immunogenetics of SLE.

OBJECTIVE: The SA1 and 16/6 idiotypes can be found in some patients with systemic lupus erythematosus (SLE) or anti-phospholipid syndrome (APS). The aim of this study was to ascertain the prevalence of these idiotypes in a large cohort of SLE patients, and to determine whether their presence is correlated with the anticardiolipin (aCL) and anti-dsDNA antibodies or with the clinical manifestations of SLE. METHODS: 492 SLE patients were evaluated for clinical manifestations of SLE and were assigned a disease severity score. ds-DNA autoantibodies, aCL autoantibodies of the IgM, IgG and IgA isotypes, and SA1 and 16/6 idiotypes were also determined in these patients. RESULTS: The prevalence of the SA1 and 16/6 idiotypes in the 492 SLE patients was found to be 11% and 5.1%, respectively, and these idiotypes were significantly more prevalent in the patients who had aCL antibodies of either the IgG, IgM or IgA isotypes. Moreover, while the 16/6 idiotype was not associated with the clinical manifestation of either SLE or APS, the SA1 idiotype was found significantly more frequently in patients who had vascular events Raynaud's phenomenon or hemolytic anemia (p = 0.016, 0.01, 0.01, respectively). CONCLUSION: SLE patients with the SA1 idiotype may run a higher risk of developing vascular events, Raynaud's phenomenon or hemolytic anemia. These clinical manifestations can be attributed to both SLE and secondary APS when aCL autoantibodies are also found. These results indicate that the possible pathogenicity of certain idiotypes in SLE cannot be excluded.

Adolescent↗