Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

X-linked hyperimmunoglobulin M (X-HIM) is a rare inherited immune deficiency disease that was first described in 1961. Affected patients suffer recurrent pyogenic and opportunistic infections, neutropenia, and an increased susceptibility to cancer. In 1993, five groups independently showed that this disease results from defects in the CD40 ligand gene. CD40 ligand is a 39-kDa protein expressed on the surface of activated CD4+ T cells that delivers contact-dependent signals to CD40-expressing cells: B cells, monocytes, dendritic cells, epithelial cells, endothelial cells, and fibroblasts. The loss of interaction between CD40 and its ligand results in an impairment of T-cell function, of B-cell differentiation, and of monocyte function. Identification of the genetic defect in X-HIM has provided a definitive diagnosis of the disease, a better description of the clinical manifestations, and the capacity for genetic screening. Studies of the role of CD40 and its ligand in the immune response from many laboratories around the world have provided a better understanding of the pathogenesis of the disease. Further research may lead to novel and definitive therapeutic options for patients with X-HIM.
 ...
PMID:The X-linked hyperimmunoglobulin M syndrome. 980 Dec 61

Invasive pulmonary aspergillosis is an opportunistic infection occurring in a background of severe immune depression. The majority of cases occur in patients who have malignant hematologic disease, particularly during chemotherapy induction or consolidations phases for acute non-lymphocytic leukemia. The principal risk factors are profound (PN < 500 per mm3) and prolonged (very high risk beyond 20 days) neutropenia, perturbed phagocyte function and cellular immune deficiency (AIDS, immunosuppressive treatment in organ and bone marrow recipients). Clinically, invasive pulmonary aspergillosis presents as acute non-specific pneumonia with cough, chest pain and fever. The severe infection rapidly becomes life-threatening. The development of massive hemoptysis is a major risk. We report four cases of invasive pulmonary aspergillosis in patients who had hemoptysis. All four patients developed non-specific pneumonia resistant to broad-spectrum antibiotics during post-chemotherapy aplasia. Computed tomography of the thorax and bronchoscopy with bronchoalveolar lavage was performed due to the occurrence of hemoptysis. In the first two cases, the patients were recovering from aplasia. The thoracic CT scan showed evidence of a cavitating mass with peripheral vessels. Bronchoscopy findings suggested mucosal lesions. The patients were managed surgically. Pathology confirmed the diagnosis of invasive pulmonary aspergillosis with the presence of ischemic necrosis of the pulmonary parenchyma harboring numerous aspergillus filaments. Outcome was favorable and chemotherapy was re-initiated in one case. These two patient died from their hematological disease a few months later. The other two patients remained in aplasia. A CT of the thorax showed multifocal infiltration with vascular contact. Bronchoscopy was again suggestive. One patient developed massive hemoptysis with respiratory distress. Embolization was performed but the patient died two days after onset of hemoptysis. In the last case, embolization was successful and outcome was favorable enabling a bone marrow allograft; the patient died a few months later from the hematological disease. The potential gravity of hemoptysis in the course of invasive pulmonary aspergillosis should lead to early treatment with emergency CT scan and, if possible, bronchoscopy with bronchoalveolar lavage to establish the therapeutic strategy based on surgical excision or embolization of the pulmonary or bronchial arteries.
 ...
PMID:[Management of hemoptysis in invasive pulmonary aspergillosis]. 992 34

Professional phagocytes (polymorphonuclear neutrophils and monocytes/macrophages) are a main component of the immune system. These cells are involved in both host defenses and various pathological settings characterized by excessive inflammation. Accordingly, they are key targets for immunomodulatory drugs, among which antibacterial agents are promising candidates. The basic and historical concepts of immunomodulation will first be briefly reviewed. Phagocyte complexity will then be unravelled (at least in terms of what we know about the origin, subsets, ambivalent roles, functional capacities, and transductional pathways of this cell and how to explore them). The core subject of this review will be the many possible interactions between antibacterial agents and phagocytes, classified according to demonstrated or potential clinical relevance (e.g., neutropenia, intracellular accumulation, and modulation of bacterial virulence). A detailed review of direct in vitro effects will be provided for the various antibacterial drug families, followed by a discussion of the clinical relevance of these effects in two particular settings: immune deficiency and inflammatory diseases. The prophylactic and therapeutic use of immunomodulatory antibiotics will be considered before conclusions are drawn about the emerging (optimistic) vision of future therapeutic prospects to deal with largely unknown new diseases and new pathogens by using new agents, new techniques, and a better understanding of the phagocyte in particular and the immune system in general.
 ...
PMID:Interference of antibacterial agents with phagocyte functions: immunomodulation or "immuno-fairy tales"? 1102 61

The main risk factors of infectious complications in cancer patients result from immune deficiency more or less related to cancer. Prognosis is related to the type and grade of the underlying disease. Prospective studies should be conducted to update data on the frequency of infections, morbidity and mortality (expert agreement). Prospective studies are needed to follow the epidemiology in cancer patients, particularly in neutropenic patients (expert agreement). Prospective studies should be conducted to determine prognosis factors allowing precise recognition of "low-risk" neutropenic patients with fever who could benefit from home care (expert agreement). When infection is suspected, the first criterion determining the therapeutic attitude concern signs of gravity requiring emergency care (septic shock). Beyond this situation, the first criterion determining the therapeutic attitude is the severity of the neutropenia. Microbial diagnosis is essential for initiating and later adapting anti-infectious treatment as well as for assessing efficacy.
 ...
PMID:[Infection and cancer: general information and specific questions]. 1107 68

Cellular immunity to viral and fungal antigens is often suppressed after stem cell transplantation. Viral infections, in particular infections with cytomegalovirus and Epstein-Barr virus, are often reactivated after allogeneic stem cell transplantation. Pathogenetic factors are immune deficiency and T-cell stimulation in the course of graft-versus-host reactions. Fungal infections are opportunistic infections derived with ubiquitous microorganisms. Immune deficiency, neutropenia, steroid treatment, and antibiotic treatment contribute to the pathogenesis. The study of viral and fungal immunity after allogeneic stem cell transplantation gives insight into the reconstitution of the immune system and tolerance.
 ...
PMID:Cellular immunity to viral and fungal antigens after stem cell transplantation. 1239 69

Recent epidemiological surveys have demonstrated an important increase in nosocomial infections among which Candida sp. plays an increasingly prominent role. Candida is now involved in about 10% of all septicemia and leads to a very high mortality rate in immunodepressed patients. Clinical studies show that any modification of the host immune status can facilitate the proliferation of endogenous Candida which, according to the importance of the immune deficiency, can provoke diseases ranging from benign localized mucocutaneous candidosis to sometimes lethal systemic invasions. The pathogenic behavior of Candida cells is mainly due to a very high phenotypic biodiversity. Following even very slight environmental modifications, it may change its behavior through the appearance of new or amplified properties such as tube formation, adherence, protease secretion, etc. Together with the impairment of host defenses, these new invasive properties lead to the so-called opportunistic pathogenicity of Candida cells. From a host point of view, after the integrity of surface teguments, the mucosal protection is ensured by the Th1 "cellular" immune response which, through pro-inflammatory cytokine production, boosts the efficacy of the phagocytes (Polymorphonuclear cells and macrophages). Neutrophils are of particular importance as deep seated Candida proliferation is mostly associated with neutropenia. Whatever the pathogenic process, it is mostly due to modifications provoked by increasing medical awareness which makes patients more susceptible to illness. A better knowledge of the precise mechanisms involved and would lead to improved strategies for prevention.
 ...
PMID:Risk factors and physiopathology of candidiasis. 1548 18

Patients suffering from acute leukemia are at high risk for invasive aspergillosis and a large review and a recent clinical trial have shown that they represent the largest group of patients developing the disease. New host groups such as patients with multiple myeloma or low-grade lymphoproliferative disorders have contributed to an increase in the incidence of invasive aspergillosis over recent years. There are substantial differences in the diagnostic strategy and therapeutic outcome of disease between patients with a hematological malignancy and other host groups such as allogeneic hematopoietic stem cell transplant patients. Galactomannan detection ELISA test is more specific in adult patients with hematological malignancies than in hematopoietic stem cell transplantation recipients. As a result of possible improvement of the underlying immune deficiency upon recovery from neutropenia, survival is higher in leukemic patients with invasive aspergillosis than in other host groups. However, there is currently no evidence of an effective antifungal prophylaxis strategy against aspergillosis in leukemic patients. As these patients account for a majority of the aspergillosis cases, clinical trials on prophylaxis should not only be focused on allogeneic stem transplant recipients but also be designed for the patient with leukemia.
 ...
PMID:Invasive aspergillosis in the hematologic and immunologic patient: new findings and key questions in leukemia. 1611 Aug 15

Patients with dysmorphic disorders seem to have frequent respiratory infections that may be attributed to associated anatomic or neurological abnormalities, but immune defects may contribute to their susceptibility to infections. We screened subjects with dysmorphic conditions for major hematologic, B-cell and T-cell defects. We studied 84 subjects with dysmorphic disorders: 29 with chromosomal disorders, 27 with single gene disorders, and 28 with unclassified dysmorphic disorders. They were evaluated by physical examination; medical history suggestive of possible immune deficiency; complete blood count; serum immunoglobulin G (IgG), IgA, and IgM levels; and lymphocyte subsets. Low laboratory values (less than fifth percentile for age) were detected in 54.8%; was highest in the chromosomal disorder group (79.3%) followed by the single gene disorder group (55.6%) and was lowest in the unclassified dysmorphic disorder group (28.6%). The most common low values were in the CD19 and CD16/56 lymphocyte subpopulations followed by IgG and IgA levels. None of the subjects had neutropenia or thrombocytopenia. History of significant recurrent infections was noted in five subjects, all of whom had abnormal laboratory values. The highest frequency of abnormal laboratory values was in Down syndrome followed by Turner syndrome and chromosome deletions. We concluded that patients with dysmorphic disorders, particularly those with chromosomal disorders, have a high frequency of various B-cell and T-cell defects that may be contributing to their susceptibility to infection. Studies are needed to further delineate the immunologic defects in that population and to investigate a possible genetic basis at the molecular level.
 ...
PMID:Immune defects in subjects with dysmorphic disorders. 1645 May 72

Cyclic neutropenia is a rare immunodeficiency syndrome, characterized by regular periodic oscillations in the circulating neutrophil count from normal to neutropenic levels through 3 weeks period, and lasting for 3-6 days. In order to determine the clinical features of cyclic neutropenia, this study was performed. Seven patients with cyclic neutropenia (3 males and 4 females), who experienced neutropenic periods every 3 weeks (5 with severe and 2 with moderate neutropenia), were investigated in this study. They had been referred to Iranian Primary Immunodeficiency Registry during 23 years (1980-2003). The range of patients' ages was from 7 to 13 years (median 11 years). The median age at the onset of the disease was 12 months (1 month- 2 years) and the median age of diagnosis was 2 (1.5-5) years, with a median diagnosis delay of 1 year (2 months- 5 years). Neutropenia was associated with leukopenia (3 patients), anemia (3 patients), and thrombocytopenia (1 patient). Patients were asymptomatic in healthy phase, but during the episode of neutropenia suffered from aphthous ulcers, abscesses and overwhelming infections. The most commonly occurred manifestations were: otitis media (6 cases), oral ulcers (5 cases), abscesses (4 cases), pneumonia (3 cases), diarrhea (3 cases), oral candidiasis (3 cases), cutaneous infections (2 cases), and periodontitis (2 cases). One of these patients subsequently died because of recurrent infections. Unusual, persistent or severe infections should be the initiating factors to search for an immune deficiency syndrome such as cyclic neutropenia, because a delay in diagnosis may result in chronic infection, irretrievable end-organ damage or even death of the patient.
 ...
PMID:Clinical and laboratory findings in Iranian children with cyclic neutropenia. 1730 90

Neutropenia is characterized by decrease in the absolute number of circulating neutrophils and an increase susceptibility to infections. The current study was performed in order to explain the clinical and laboratory findings of patients with antibody deficiency disorders associated neutropenia. The patients' records of 19 neutropenic cases out of 207 patients with antibody deficiencies, who had been referred to Children's Medical Center and enrolled in Iranian primary immunodeficiency registry, were reviewed. Nineteen cases (14 male and 5 female), with a mean age of 10.7+/-5.7 years, were associated with neutropenia (9.2%). The disorders with associated neutropenia were Hyper IgM syndromes (3 of 8), Common variable immunodeficiency (13 of 109), and X-linked agammaglobulinemia (3 of 45). The median age for the onset of disease and diagnosis age were 15 months (1-134) and 3.8 years (6 months-13 years), respectively. The most common infections during the course of illness were pneumonia (13 cases), diarrhea (12 cases), oral candidiasis (9 cases), otitis media (6 cases), sinusitis (6 cases), cutaneous infections (5 cases), and abscess (5 cases). Other less frequent infections were: conjunctivitis, oral ulcers, meningitis, and osteomyelitis. Three neutropenic patients died because of recurrent infections. Neutropenia may occur in any of the primary immunodeficiency disorders. Persistent or severe infections always pose a supposition, which deserves further evaluation for detecting an underlying immune deficiency syndrome and neutropenia, since a delay in diagnosis may result in a serious organ damage or even death of the patient.
 ...
PMID:Neutropenia in patients with primary antibody deficiency disorders. 1730 96


<< Previous 1 2 3 4 5 Next >>