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

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by mutations in the gene for Bruton tyrosine kinase (BTK) that result in the deficient development of B lymphocytes and hypogammaglobulinemia. Because the disorder is uncommon, no single institution has had sufficient numbers of patients to develop a comprehensive clinical picture of the disorder. Accordingly, a national registry of United States residents with XLA was established in 1999 to provide an updated clinical view of the disorder in a large cohort of patients. A total of 201 patients were registered by 66 physicians. The estimated birth rate for the 10-year period of 1988-1997 was 1/379,000. Infection was the most common initial clinical presentation (85%), followed by a positive family history (41%) and neutropenia (11%). Although the average age of diagnosis was younger in patients with a positive family history (mean, 2.59 yr) than in patients with a negative family history (mean, 5.37 yr) (p < 0.001), only 34.5% of patients with a positive family history at the time of their birth were diagnosed before clinical symptoms developed-that is, based on family history alone. Seventy percent of patients had at least 1 episode of otitis, 62% at least 1 episode of pneumonia, 60% at least 1 episode of sinusitis, 23% at least 1 episode of chronic/recurrent diarrhea, 21% at least 1 episode of conjunctivitis, 18% at least 1 episode of pyoderma and/or cellulitis, 11% at least 1 episode of meningitis/encephalitis, 10% at least 1 episode of sepsis, 8% at least 1 episode of septic arthritis, 6% at least 1 episode of hepatitis, and 3% at least 1 episode of osteomyelitis. Fourteen of 201 (6.9%) patients were dead at the time they were entered in the Registry. However, in a prospective 4 /4-year follow-up of living patients, only 3/80 (3.75%) patients died. Causes of death included disseminated enterovirus infection (n = 6), pulmonary insufficiency (n = 5), adenovirus infection (n = 1), sepsis (n = 1), acquired immunodeficiency disease syndrome (AIDS) (n = 1), myocarditis (n = 1), hepatitis (n = 2), and stem cell transplantation (n = 1).
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PMID:X-linked agammaglobulinemia: report on a United States registry of 201 patients. 1686 44

Experiments to evaluate the effect of the level and duration of endotoxaemia on the meningeal inflammatory response were performed in order to determine if systemic inflammation alters meningitis. Rabbits received either saline or Escherichia coli O111:B4 lipopolysacharide (LPS) intravenously at various doses (1, 3 or 10 microg) and times (-8, -2 or 0 h) before an intracisternal injection of 20 ng LPS. An intracisternal LPS injection together with saline intravenously produced a peak cerebrospinal fluid (CSF) tumour necrosis factor (TNF) level (95 +/- 26 ng/ml) at 2 h and peak leucocyte level (5413 +/- 764 cells/microl) at 4 h post-injection. Blood leucocytes were slightly elevated (12 000 +/- 500/microl at 0 h; 16 900 +/- 280/microl at 8 h) but plasma TNF was always undetectable (< 0.05 ng/ml). Conversely, intravenous injection of 3 or 10 microg LPS 2 h prior to intracisternal LPS injection impaired pleocytosis (peak < 220 cells/microl) and delayed ( approximately 4 h) and reduced peak CSF TNF levels (3 microg LPS 5.0 +/- 1.2 ng/ml; 10 microg LPS 6.9 +/- 1.9; P < 0.05). Intravenous administration of 1 microg LPS was less inhibitory to CSF inflammation, but delayed onset (peak 1100 +/- 60 leucocytes/microl CSF at 8 h; 6.3 +/- 0.3 ng TNF/ml CSF at 4 h; both P < 0.05). Neutropenia nadirs were dependent on LPS dose (1 microg, 4500 +/- 1700; 3 microg, 1900 +/- 60; 10 microg, 1100 +/- 100 all at 4 h post-intravenous dose). Peak plasma TNF levels were not dose-dependent (> 8 ng/ml), but plasma TNF was always detectable (> 0.2 ng/ml at 10 h post-intravenous dose). Intravenous LPS administration at 0 h also blocked pleocytosis, but the inhibitory effect was lost when administration at -8 h. In conclusion, the degree and duration of endotoxaemia affect the meningeal inflammatory response to LPS in experimental meningitis.
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PMID:Systemic inflammation alters the inflammatory response in experimental lipopolysaccharide-induced meningitis. 1717 70

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.
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PMID:Neutropenia in patients with primary antibody deficiency disorders. 1730 96

The carbapenems are beta-lactam antimicrobial agents with an exceptionally broad spectrum of activity. Older carbapenems, such as imipenem, were often susceptible to degradation by the enzyme dehydropeptidase-1 (DHP-1) located in renal tubules and required co-administration with a DHP-1 inhibitor such as cilastatin. Later additions to the class such as meropenem, ertapenem and doripenem demonstrated increased stability to DHP-1 and are administered without a DHP-1 inhibitor. Like all beta-lactam antimicrobial agents, carbapenems act by inhibiting bacterial cell wall synthesis by binding to and inactivating penicillin-binding proteins (PBPs). Carbapenems are stable to most beta-lactamases including AmpC beta-lactamases and extended-spectrum beta-lactamases. Resistance to carbapenems develops when bacteria acquire or develop structural changes within their PBPs, when they acquire metallo-beta-lactamases that are capable of rapidly degrading carbapenems, or when changes in membrane permeability arise as a result of loss of specific outer membrane porins. Carbapenems (imipenem, meropenem, doripenem) possess broad-spectrum in vitro activity, which includes activity against many Gram-positive, Gram-negative and anaerobic bacteria; carbapenems lack activity against Enterococcus faecium, methicillin-resistant Staphylococcus aureus and Stenotrophomonas maltophilia. Compared with imipenem, meropenem and doripenem, the spectrum of activity of ertapenem is more limited primarily because it lacks activity against Pseudomonas aeruginosa and Enterococcus spp. Imipenem, meropenem and doripenem have in vivo half lives of approximately 1 hour, while ertapenem has a half-life of approximately 4 hours making it suitable for once-daily administration. As with other beta-lactam antimicrobial agents, the most important pharmacodynamic parameter predicting in vivo efficacy is the time that the plasma drug concentration is maintained above the minimum inhibitory concentration (T>MIC). Imipenem/cilastatin and meropenem have been studied in comparative clinical trials establishing their efficacy in the treatment of a variety of infections including complicated intra-abdominal infections, skin and skin structure infections, community-acquired pneumonia, nosocomial pneumonia, complicated urinary tract infections, meningitis (meropenem only) and febrile neutropenia. The current role for imipenem/cilastatin and meropenem in therapy remains for use in moderate to severe nosocomial and polymicrobial infections. The unique antimicrobial spectrum and pharmacokinetic properties of ertapenem make it more suited to treatment of community-acquired infections and outpatient intravenous antimicrobial therapy than for the treatment of nosocomial infections. Doripenem is a promising new carbapenem with similar properties to those of meropenem, although it appears to have more potent in vitro activity against P. aeruginosa than meropenem. Clinical trials are required to establish the efficacy and safety of doripenem in moderate to severe infections, including nosocomial infections.
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PMID:Comparative review of the carbapenems. 1748 46

Multiple factors influence the outcome of fungal infection of the central nervous system (CNS). The host and the pathogen in concert with drug delivery across the blood-brain barrier and drug activity are key factors in outcome. Drug costs can be prohibitively expensive. Drug toxicity with standard antifungal agents such as amphotericin B (infusion rate toxicity) can be reduced using simple techniques such as slower infusion and appropriate saline loading. Continuous infusion can allow relatively large doses of amphotericin B (up to 2 mg/kg/day, remaining below 0.08 mg/kg/hour) to be given with toxicity profiles comparable to expensive lipid formulations of amphotericin B. Dedicated peripherally inserted central catheters can remain in situ for weeks to months and are safe and relatively inexpensive. Correction of metabolic pathology in the case of mucormycosis and resolution of neutropenia are essential to effective treatment of filamentous fungal infections such as Mucor, Aspergillus and Scedosporium. The pharmacology and pharmacokinetics of the current major antifungal agents used to treat fungal infections of the CNS are reviewed. Tables that provide information about achievable CNS drug levels, antifungal susceptibilities and the likelihood of intrinsic drug resistance of significant fungal pathogens have been included to help the clinician with therapy. Treatment recommendations for Cryptococcal and Candida meningitis and for rhinocerebral infection with Mucor and Aspergillus have been included.
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PMID:Fungal infections of the central nervous system: A review of fungal pathogens and treatment. 1792 54

We report a case of 15-year-old girl with T-cell acute lymphoblastic leukemia who had fever, neutropenia, and severe headache while receiving maintenance chemotherapy. Cerebrospinal fluid testing revealed a lymphocytic pleocytosis and no evidence of relapsed leukemia. Meningitis caused by lymphocytic choriomeningitis virus was identified serologically. The patient's course was complicated by hydrocephalus requiring ventriculoperitoneal shunt placement and by an intracranial hemorrhage. Lymphocytic choriomeningitis virus is a rare cause of aseptic meningitis that should be considered in the symptomatic immunocompromised patient with an appropriate exposure history.
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PMID:Meningitis caused by lymphocytic choriomeningitis virus in a patient with leukemia. 1901 81

Invasive candidiasis (IC) includes candidemia, disseminated candidiasis with deep organ involvement, endocarditis and meningitis. IC has an attributable mortality of 40% to 50% and is increasingly reported in intensive care units (ICUs). Candida albicans and non-albicans strains are both responsible for infections in ICUs, where empirical and targeted treatments especially need to be initially appropriate. This review synthesizes the most recent guidelines for IC and candidemia from an ICU perspective. Essentially, patients who have been previously exposed to azoles have a higher probability of being infected by azole-resistant or non-albicans strains. Infection site, illness severity, neutropenia, hemodynamic status, organ failure and concomitant drug treatments are host-related factors that influence the choice of anti-fungal treatment. In general, echinocandins are currently favored for empiric treatment of candidemia, especially in critically ill patients or those with previous azole exposure. Pharmacokinetic properties and side effects suggest that polyenes should be avoided in patients with renal failure, and that echinocandins and azoles should be avoided in patients with severe hepatic dysfunction.
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PMID:Invasive candidiasis and candidemia: new guidelines. 1907

Today, mycotic infections in immunocompromised patients are mainly caused by Candida spp. and Aspergillus spp. The patients most sensitive to these infections are those with some kind of cell-mediated immunity quantitative or qualitative alteration (i.e., blood-related cancer, primary or secondary neutropenia, immunosuppressive disease or therapy, etc.). Candida infection in the immunosupressed patient comprises a wide range of serious diseases such as candidemia, chronic disseminated candididasis, endocarditis, meningitis and endophthalmitis. Therefore, infection by Candida spp. is considered secondary to the technological and medical advances which extend the life of patients with chronic diseases.
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PMID:[Fungal (Candida) infections in the immunocompromised pediatric patient]. 1953 73

Infections with rare pathogens are being recognized with increasing frequency in severely immunocompromised patients. As a result of these patients' underlying compromised defenses and susceptibility to atypical organisms, tissue biopsies from patients within this population may demonstrate nonclassical histopathological findings. Here, we describe an unusual granulomatous reaction to gram-positive cocci in the skin of a 52-year-old man undergoing salvage chemotherapy for acute myeloid leukemia. The patient presented with a papular eruption on the arms, trunk, and face and fever; concomitant blood cultures were positive for Rothia mucilaginosa and Streptococcus salivarius. Histologic evaluation revealed a granulomatous dermatitis associated with numerous small, round, predominantly intracellular bacteria. Classically, cutaneous infiltrates associated with coccoid bacterial infections are suppurative and not granulomatous. The intracellular organisms stained positive for Gram, periodic acid-Schiff, and Grocott methenamine silver stains, suggestive of R. mucilaginosa. Rothia mucilaginosa, a component of the oral flora, was first reported as a human pathogen in 1978. Although the majority of cases in the literature have described R. mucilaginosa bacteremia, other reported manifestations include meningitis, endocarditis, pneumonia, osteomyelitis, and peritonitis. To our knowledge, however, only 1 prior report has described a cutaneous manifestation of R. mucilaginosa septicemia, which occurred in a patient with neutropenia. This is the second reported case of an infectious granulomatous dermatitis associated with R. mucilaginosa bacteremia and raises awareness of this unusual histopathological presentation in the setting of a bacterial infection affecting the skin.
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PMID:Infectious granulomatous dermatitis associated with Rothia mucilaginosa bacteremia: A case report. 1994 Jul 46

West Nile Virus (WNV) is a neurotropic flavivirus that can cause debilitating diseases, such as encephalitis, meningitis, or flaccid paralysis. We report the safety, pharmacokinetics, and immunogenicity of a recombinant humanized monoclonal antibody (MGAWN1) targeting the E protein of WNV in a phase 1 study, the first to be performed on humans. A single intravenous infusion of saline or of MGAWN1 at escalating doses (0.3, 1, 3, 10, or 30 mg/kg of body weight) was administered to 40 healthy volunteers (30 receiving MGAWN1; 10 receiving placebo). Subjects were evaluated on days 0, 1, 3, 7, 14, 21, 28, 42, 56, 91, 120, and 180 by clinical assessments, clinical laboratory studies, electrocardiograms (ECGs), and pharmacokinetic and immunogenicity assays. All 40 subjects tolerated the infusion of the study drug, and 39 subjects completed the study. One serious adverse event of schizophrenia occurred in the 0.3-mg/kg cohort. One grade 3 neutropenia occurred in the 3-mg/kg cohort. Six MGAWN1-treated subjects experienced 11 drug-related adverse events, including diarrhea (1 subject), chest discomfort (1), oral herpes (1), rhinitis (1), neutropenia (2), leukopenia (1), dizziness (1), headache (2), and somnolence (1). In the 30-mg/kg cohort, MGAWN1 had a half-life of 26.7 days and a maximum concentration in serum (C(max)) of 953 microg/ml. This study suggests that single infusions of MGAWN1 up to 30 mg/kg appear to be safe and well tolerated in healthy subjects. The C(max) of 953 microg/ml exceeds the target level in serum estimated from hamster studies by 28-fold and should provide excess WNV neutralizing activity and penetration into the brain and cerebrospinal fluid (CSF). Further evaluation of MGAWN1 for the treatment of West Nile virus infections is warranted.
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PMID:Safety and pharmacokinetics of single intravenous dose of MGAWN1, a novel monoclonal antibody to West Nile virus. 2035 Sep 45


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