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PubMed1993

Influence of digoxin immune Fab therapy and renal dysfunction on the disposition of total and free digoxin.

OBJECTIVE: To characterize the disposition of total and free serum digoxin following the administration of digoxin Fab antibody in patients with varying degrees of renal function. DESIGN: Observational study of pharmacokinetics and pharmacodynamics. SETTING: Critical care and telemetry units of two university-affiliated teaching institutions, Hartford Hospital and Henry Ford Hospital. PATIENTS: Fourteen digoxin-intoxicated patients (baseline total digoxin > 3.2 nmol/mL) with mean (+/- SD) serum creatinine of 380.1 +/- 212.2 mumol/L who received digoxin Fab antibody therapy. MEASUREMENTS: Serum was drawn every 12 to 24 hours for 80 to 327 hours after Fab administration. Total and free digoxin were assayed in serum by fluorescence polarization immunoassay or modified immunofluorometric assay. RESULTS: Before Fab was administered, total digoxin ranged from 3.5 to 10.5 nmol/mL. After treatment with Fab, total digoxin increased rapidly to a mean (+/- SD) maximum of 51.8 +/- 22.7 nmol/mL and decreased to 7.2 +/- 4.7 nmol/mL at the last measurement. Total digoxin was eliminated in a two-phase fashion. The half-life of the initial phase of total digoxin decline was 11.6 +/- 4.1 hours, and the half-life of the second or terminal elimination phase was 118 +/- 57 hours. Free digoxin levels decreased rapidly following Fab therapy, to a mean nadir of 0.6 +/- 1.1 nmol/mL, but rebounded to a mean maximum free digoxin concentration of 1.7 +/- 1.3 nmol/mL in 77 +/- 46 hours. The time to maximum free digoxin rebound occurred later in patients with end-stage renal disease (n = 4) compared with other patients (127 +/- 40 hours compared with 55 +/- 28 hours). CONCLUSION: Elimination of digoxin following Fab therapy is prolonged in digoxin-toxic patients with renal dysfunction. In addition, rebound of free digoxin is delayed in anephric patients. Monitoring free digoxin following the administration of Fab may be of value in selected patients to guide additional Fab dosing, confirm possible rebound toxicity, or guide the reinitiation of digoxin therapy.

Adult↗
PubMed2000

[Biochemical characteristics of liver involvement in patients with antiphospholipid syndrome].

The incidence of hepatitis B and C virus and cytomegalovirus infection is high in patients with the antiphospholipid syndrome (APS). The specific features of virus infection in APS patients are determined by the activity of APS. During clinically manifest stage, the activities of aminotransferases, lactate dehydrogenase (LDH), and alkaline phosphatase increase, while during remission only aspartate aminotransferase and LDH levels remain high, for this latter enzyme high activities of isoenzymes LDH5 and LDH4 being recorded. These data indicate that the pathological process in APS involves not only the liver, but the sinusoidal endothelium as well. This seems to account for some other clinical and laboratory manifestations of APS, such as increased level of circulating immune complexes, dysfunction of physiological anticoagulants, etc.

Antiphospholipid Syndrome↗
PubMed2001

[Inflammatory myopathies].

Primary myositis (or inflammatory myopathies) comprises three main groups of diseases, based on clinical and immunohistochemical characteristics: polymyositis (PM), dermatomyositis (DM) and inclusion body myositis. Their clinical presentation and course are disparate, but a common characteristic is immune dysfunction-related inflammation of the striated muscles. Their etiologies are still not fully elucidated but associate environmental and, to a lesser degree, genetic factors. Nevertheless, considerable progress has recently been made in the understanding and management of these diseases.

Anti-Inflammatory Agents↗
PubMed2001

Neural networks in the assessment of HIV immunopathology.

Surrogate markers are by definition quantifiable laboratory variables that have clinical and biological relevance to disease outcomes. Virologic and immunologic surrogate markers have proven useful in following HIV-associated viral burden, immune dysregulation, dysfunction and deficiency. Monitoring of sequential changes in these markers and their interrelationships may provide significant information about viral-host-drug dynamics. The complexity and fluidity of these changes necessitates that an efficient means be developed for their monitoring. We therefore generated a neural network-based model for assessing host dynamics over time and compared its performance with that of a multiple regression model. Both modeling approaches were applied to the actual, non-filtered, clinical observations on 58 HIV-infected individuals treated consistently with Highly Active Anti-Retroviral Therapy (HAART), for a period of over-52 weeks resulting in an average of 16 observations per patient throughout this time span. Results demonstrated that the neural network was at least as accurate as a multi-regression model. Since our dataset was modest in size we also believe that neural networks warrant further consideration for modeling the complexity of HIV-host dynamics on larger datasets.

Antiretroviral Therapy, Highly Active↗
PubMed1991

Imipenem/cilastatin as empirical treatment of severe infections in compromised patients.

Imipenem/cilastatin was administered as empirical treatment to 22 patients with severe infections, at dosages of 2 or 4 g/day, either alone or in combination with an aminoglycoside. The majority of patients had underlying diseases causing various degrees of immune system dysfunction. The overall cure rate was 77.2%, without significant differences according to the type of pathogen or dosage schedule; however one of the two observed failures was due to a resistant Pseudomonas aeruginosa. Strains recovered from improved patients were all sensitive to the drug. Only mild adverse effects were evidenced, without any alteration of laboratory parameters. Imipenem/cilastatin may be useful as monotherapy in empirical treatment of severe infections in compromised patients.

Adult↗
PubMed2002

A case of severe C4d-positive kidney allograft dysfunction in the absence of histomorphologic features of rejection.

Acute antibody-mediated (humoral) renal allograft rejection has emerged as a clinicopathological entity that carries a poor prognosis. Its diagnosis is based on typical pathohistologic features, serologic detection of donor-specific alloantibodies and the immunohistochemical finding of endothelial deposits of the complement split product C4d. We herein report a case of severe antibody-mediated graft injury after spousal-donor kidney transplantation. Despite an increased risk for humoral presensitization in the female recipient (three previous pregnancies), donor-specific alloantibodies were not detectable before transplantation. After initial graft function, severe graft dysfunction occurred one week after transplantation. A renal biopsy revealed no histomorphologic features of rejection. However, immunohistochemical detection of diffuse C4d deposits along peritubular capillaries suggested acute humoral rejection. The diagnosis of antibody-mediated rejection was confirmed by the detection of de-novo production of anti-donor alloantibodies. Graft dysfunction was resistant to high dose steroids or antilymphocyte antibody therapy. However, a recovery of graft function could be achieved by antibody elimination using immunoadsorption therapy. This case reinforces the high diagnostic value of C4d staining. In severe graft dysfunction humoral immune mechanisms should be considered, even when histopathologic features of humoral rejection are completely absent.

Adult↗
PubMed2000

Immunoactive Properties of Cerebrolysin.

In children (aged 3-8 years old) with minimal cerebral dysfunction the immune status was studied before and after cerebrolysin administration in the dosage of 1 ml per 10 kg of child's weight, intramuscularly, within one month. The cerebrolysin administration resulted in an increase in the level of CD19(+) cells with a simultaneous normalization of serum IgG and IgA levels. The count of CD4(+) lymphocytes has risen. Normalization of a relative count of CD16(+) cells (NK) was noted after cerebrolysin therapy. Expression of activation markers (CD25 and HLA DR) in total population of lymphocytes parallelly changed, achieving the parameters of the control group without any changes in expression of CD95 molecule. Under the cerebrolysin influence the activation mainly of T helpers could be observed in vitro.

Journal Article↗
PubMed2003

Modern methods of treatment of autoimmune myocarditis.

An updated version of the autoimmunity theory and the recent achievements in the investigation of the pathogenesis of autoimmune disorders have created new opportunities for the development and clinical application of a new generation of methods of treatment of the immune system dysfunctions. The present review is focused on questions related to modern and future developments in the treatment of autoimmune myocarditis. We discuss well-known drugs like corticosteroids and azathioprine, and some new and up-to-date methods of treatment of the autoimmune inflammation. Some of these methods are at the experimental stage of development and hopefully will be used to treat patients in the near future.

Autoimmune Diseases↗
PubMed2003

[Subacute myelitis revealed by human immunodeficiency virus infection].

A 35 year-old heterosexual man had a six months history of cervical myelitis with progressive paraplegia, leg weakness and paresthesia of the four extremities. Spinal cord MRI showed a high T2 signal intramedullary lesion wide from the bulbo-medullary junction to D4. Post gadolinium T1 sequence revealed an enhancement in front of C3-C4 vertebrae. VIH serology was positive. Corticosteroid treatment achieved a marked improvement. In addition to vacuolar myelopathy, well-known at the advanced stages of the HIV infection (AIDS), myelitis and clinical pictures simulating multiple sclerosis were described during early stages of the infection. These inflammatory lesions of the central nervous system and sometimes of the peripheral nervous system seems to be related to the immune response dysfunction induced by the VIH.

Adult↗
PubMed2004

Clonal stability of initial leukemia in a child with central nervous system relapse 7.4 years after bone marrow relapse of common acute lymphoblastic leukemic.

Second central nervous system (CNS) relapses represent about 7.3% of subsequent recurrences of childhood acute lymphoblastic leukemia (ALL). In most children these subsequent CNS relapses occur during the first 18 months after diagnosis of the first relapse (mean 1.42 +/- 0.73 years). We present a patient who suffered a second ALL relapse in the CNS more than seven years after diagnosis of his first relapse. The leukemic clone was completely stable over more than ten years as shown by minimal residual disease techniques. Possible reasons for the recurrence of the leukemic clone after this very long period of dormancy (e.g. role of the disease site, immune system dysfunction) are discussed.

Adolescent↗
PubMed2004

Stimulation of ileal epithelium growth and regeneration by dietary nucleotide extracts.

The gastrointestinal tract epithelium plays an important role not only in digestion and absorption of nutrients, but also in antigen and pathogen signal translocation toward the gut associated lymphoid tissue. Malnutrition in various degrees is recognized as the most common cause of the immune system dysfunction. Research done in the past several years has revealed that dietary nucleotides (dNT) represent an essential compound of nutrition because of their importance in metabolic pathways, energetic processes and nucleic acid synthesis during tissue renewal. Much evidence accumulated suggests that dNT are essential for the growth and maturation of the gut epithelia. In previous experiments we have documented immunoregulative properties of dNT-containing extracts. In this study Balb/c female mice were fed (1) standard diet, (2) dNT-supplemented diet, and (3) dNT-supplemented water for 4 weeks. The supplement in dose of 100 mg/kg/l comprised original extract (Imuregen, Uniregen Ltd., Náchod, Czech Republic). Samples of terminal ileum in each dietary group were removed for histological examination. The length of villi was evaluated by computer morphometry. The highest growth of intestinal villi was observed in group administered dNT-supplemented water. We have found no pathological changes of intestinal epithelium in any experimental group.

Animals↗
PubMed1992

Coronary vasculitis.

Although patients with immune system dysfunction leading to MI may be a small subpopulation, they present an interesting challenge. Early recognition of their condition and prompt anti-inflammatory therapy, along with modification of cardiac rehabilitation and teaching protocols, will promote favorable long-term outcomes.

Coronary Disease↗
PubMed2005

Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura.

BACKGROUND AND OBJECTIVES: Adult idiopathic thrombocytopenic purpura (ITP) is a chronic acquired organ-specific autoimmune hemorrhagic disease characterized by the production of antibodies against antigens on the membranes of platelet, resulting in enhanced Fc-mediated destruction of the platelets by macrophages in the reticuloendothelial system. Dysfunctional cellular immunity is considered important in the pathophysiology of ITP. The aim of this study was to explore the profile of type1 and type2 T cells in chronic ITP patients. DESIGN AND METHODS: The balance of Th1/Th2 and Tc1/Tc2 was studied by simultaneous analysis of intracellular cytokines of peripheral blood mononuclear cells and splenocytes in short-term cultures activated with PMA/ionomycin as well as mRNA expression of T-bet and GATA-3 in peripheral blood mononuclear cells and splenocytes using real-time polymerase chain reaction. RESULTS: Patients with active disease but not patients in remission had significant higher Th1/Th2 (p<0.01) and Tc1/Tc2 (p<0.01) ratios in peripheral blood (PB) and significant higher Th1/Th2 ratio in splenocytes (p<0.01) than those in the control group. The Tc1/Tc2 ratio in splenocytes in ITP patients was higher than that in control, but did not reach significant difference (p=0.082). GATA-3 mRNA expression in ITP patients was significantly lower both in PB (p<0.01) and in splenocytes (p<0.01) than in corresponding samples from controls while there was no difference in T-bet expression. INTERPRETATION AND CONCLUSIONS: Our data indicate that ITP is a T1 cell (Th1 and Tc1) predominant disease although the precise mechanisms await further functional assay. The T-bet/GATA-3 ratio may provide a surrogate marker of T1/T2 cytokine balance. Shifting the cytokine patterns from T1 to T2 might be a potential immunotherapy for ITP.

Adolescent↗
PubMed2005

Polarization and apoptosis of T cell subsets in idiopathic thrombocytopenic purpura.

It is well-known that idiopathic thrombocytopenic purpura (ITP) is an acquired organ-specific autoimmune hemorrhagic disease and dysfunctional cellular immunity is considered important in the pathophysiology of ITP. However, polarization patterns and apoptosis profiles of T lymphocytes remain unclear. In this study, we investigated the polarization of T cell subsets, the expressions of apoptotic proteins Fas/FasL on the subsets and the level of anti-apoptotic gene bcl-2 and bax mRNA. It was demonstrated that the ratios of Th1/Th2 and Tc1/Tc2 in ITP children were increased obviously and that the average percentages were increased clearly for Th1 and Th2, but not for Tc1 and Tc2. In ITP children, the enhancing expressions were detected for FasL on Th1 and Tc1 and for Fas on Th2 and Tc2. With increasing level of bcl-2 mRNA and decreasing expression of bax mRNA in ITP children, the ratio of bcl-2/bax mRNA was improved obviously, which was positive correlated with the ratio of Th1/Th2. Taken together, our findings indicate that ITP is a Th1 predominant disease. This polarization pattern of T cell subsets might be related to the high ratio of bcl-2/bax mRNA and the abnormal expressions of Fas and FasL on T cell subsets.

Apoptosis↗
PubMed2005

B-cell depletion for rheumatic diseases: where are we?

Immune system dysfunction is common to rheumatic disorders, with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) being classic examples. Altered development and function of B cells may play a prominent role. B-cell abnormalities also occur in other rheumatic diseases, eg, Sjogren's syndrome, Behcet's disease, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and dermatomyositis. Hence, B-cell depletion has been investigated as a therapeutic option. Clinical trials in RA and SLE have shown that rituximab, an anti-CD20 monoclonal antibody, can profoundly reduce disease activity and is generally well tolerated. Reports of rituximab treatment for ANCA-associated vasculitis and dermatomyositis are also promising. These encouraging results validate the strategy of B-cell depletion in various rheumatic diseases. B-cell depletion with rituximab is under study in larger clinical trials for the purposes of regulatory approval to define more closely its place in RA and SLE treatment paradigms, and smaller clinical trials are ongoing or planned in associated inflammatory diseases.

B-Lymphocytes↗
PubMedDate not supplied

[Systemic inflammatory response in pediatric cardiac surgery].

Systemic Inflammatory Response (SIR) constitutes generalized, non-specific response to tissue injury of whatever etiology, and is a rapid, highly amplified, controlled humeral and cellular response. Cardiopulmonary Bypass (CPB) is necessary in many cardiac surgery as in adults as children. Also we know the undesirable effects of SIR. The pediatric surgical team to treat of management very well if exist the threat of undesirable outcome after CPB. There are several key components of the inflammatory response to cardiac surgery involve the complement, immune and endothelial systems. Cytokines may exert either proinflammatory or antiinflammatory effects. Cytokines are essential for immunologic and physiologic homeostasis, are normally subject to thight homeostatic control, and are produced in response to a variety of physiologic and pathologic stimuli. An uncontrolled inflammatory response appears to play a significant role in the morbidity or mortality observed in patients undergoing CPB. The inflammatory response contributes to the pathogenesis of acute pulmonary, cardiovascular, neurologic, splanchnic, hematologic, and immune system dysfunction following cardiac surgery. The development of strategies to control the inflammatory response following cardiac surgery is currently the focus of considerable research efforts. Diverse techniques, including maintenance of hemodynamic stability, minimization of exposure to CPB circuitry, and pharmacologic and immunomodulatory agents have been studied. Also hemofiltration, leukodepletion, the use of serine protease inhibitors and corticosteroids. Molecular biology is revolutionizing medicine and the ability to assess the impact of genetic variability on disease characterization and perioperative outcome. Recent evidence suggests that the degree and severity of surgical-induced inflammation may be significantly influenced by genotype.

Cardiac Surgical Procedures↗
PubMed2006

Role of azathioprine in preventing recurrences in a patient of recurrent erythema nodosum leprosum.

The pathogenesis of erythema nodosum leprosum (ENL) involves both immune complex deposition and dysfunction of cell mediated immunity. Tumour necrosis factor-alpha (TNF-alpha) plays an important role in its pathogenesis. Thalidomide and corticosteroids are the mainstay of treatment for ENL. However, there are often severe limitations to their use. We report a case of recurrent ENL treated successfully with azathioprine. A 15-year-old unmarried girl with lepromatous leprosy had recurrent ENL for 2 years. She was treated with WHO-MB MDT and prednisolone in doses of 40-90 mg a day for 2-12 weeks. Her condition was inadequately controlled. The patient was therefore treated with thalidomide 300 mg and prednisolone 40 mg. The symptoms subsided after 5 days and ENL lesions healed in 2 weeks. Prednisolone was reduced by 10 mg per week and stopped, while thalidomide was reduced to 100 twice daily after 4 weeks. Azathioprine 100 mg (2 mg/kg per day) daily orally was added to prevent recurrences. Thalidomide was further reduced and stopped after another 4 weeks while she continued with azathioprine in the same doses for 8 months. There was no recurrence of ENL lesions and no side effects of the therapy. MB-MDT was stopped 1 year ago, and she is on follow-up without any relapse. Azathioprine, therefore, appears to be an effective and safe drug to prevent recurrences of ENL.

Administration, Oral↗
PubMed1991

Occurrence of serum antisperm antibodies in patients with cystic fibrosis.

OBJECTIVE: To determine if acquired obstruction of the vas deferens in men with cystic fibrosis (CF) induced the development of antisperm antibodies with genital tract obstruction similar to other men. DESIGN: Serum antisperm antibodies were assayed by an indirect immunobead test and an indirect immunofluorescence assay. Both homologous (human sperm/human zona) and heterologous (human sperm/zona-free hamster ova) sperm/egg interactions were evaluated in the presence of serum antisperm antibodies from patients with CF. SETTING: Cystic Fibrosis Clinic at the University of Oklahoma Health Sciences Center, a tertiary care referral center. PATIENTS: Fifteen CF patients (10 male and 5 female), 3 non-CF antisperm antibody-positive infertile patients (2 male and 1 female), 20 fertile controls (7 males and 13 females), and 9 fertile sperm donors were used. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Serum antisperm antibody levels in patients with CF. In those patients with antisperm antibodies, determine effect of these sperm antibodies on sperm/egg interactions and complement-mediated events. RESULTS: Sera from 3 (30%) of 10 men with CF demonstrated immunoglobulin (Ig)G, IgA, and/or IgM antisperm antibodies, whereas sera from all 5 CF women and the 20 control sera were negative for antisperm antibodies. The maximal titers for IgG, IgA, and IgM antisperm antibody were 1:8, 192, 1:256, and 1:64, respectively. The immunobead binding, which was restricted to the sperm head and tail-tip or the midpiece and tail-tip, correlated with the indirect immunofluorescence pattern. Antisperm antibody-positive sera from men with CF impaired both the binding and penetration of human zonae and the penetration of hamster ova by human sperm. CONCLUSIONS: Similar to other men with congenital or acquired obstruction of their genital tract, antisperm antibodies may occur in some men with CF. Antisperm antibodies may contribute to immune sperm dysfunction in some men with CF by activated complement-mediated events and interfering with sperm/egg interactions.

Adolescent↗