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)

GBS (Group B Hemolytic Streptococci) cause pulmonary hypertension with associated neutropenia. We investigated whether there is a correlation between the neutropenia of sepsis and GBS-induced pulmonary vasoconstriction, through study of the effects of inhibiting pulmonary vasoconstriction on the neutropenia of GBS in newborn piglets. Fifteen piglets were infused with GBS. After one hour, animals were given either a thromboxane inhibitor (DAZ), a combined cyclooxygenase/lipoxygenase inhibitor, BW755C, or placebo. With GBS infusion, WBC and PMN counts dropped steadily, from similar baselines, to 2250 +/- 570, 3300 +/- 500 and 5400 +/- 1100 cells/mm3 respectively (p less than 0.05; DAZ and BW vs. placebo). PMN's dropped similarly to 710 +/- 320, 2390 + 1240 and 3130 +/- 1050 cells/mm3 respectively (p less than 0.05; DAZ vs. BW and placebo). The drop in WBC's predominantly resulted from proportional decreases in PMN's (DAZ: r = 0.98; BW: r = 0.88; placebo r = 0.93). Compared to GBS alone, DAZ reduced pulmonary vasoconstriction, but exacerbated the granulocytopenia. BW755C similarly reduced pulmonary hypertension: however, it ameliorated the exacerbation of GBS induced neutropenia described above. These data imply that there is no direct correlation between GBS induced granulocytopenia and pulmonary hypertension.
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PMID:Prostanoid inhibition and group B hemolytic streptococci (GBS) induced neutropenia in newborn piglets. 212 31

A rabbit model was used to characterize the effects of high (Group II, 100 mg/kg) and low (Group III, 10 mg/kg) dose ibuprofen in modulating the hemodynamic and hematologic manifestations of group B streptococcal shock. Short-term survival was significantly increased with ibuprofen pretreatment. Ibuprofen failed to prevent GBS-induced shock, although shock was favorably modified in a dose dependent manner. Likewise, GBS-induced increases in 6KPGF1a and TxB2 were not prevented but were modified in Group II at 120 min. However, neutropenia, thrombocytopenia, and acidosis were not prevented by pretreatment with ibuprofen and may have been exacerbated. Thus, ibuprofen modifies but does not prevent GBS-induced hemodynamic and hematologic manifestation.
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PMID:Ibuprofen in experimental group B streptococcal shock. 327 16

Preliminary evidence (n = 15) with semiquantitative (latex) determinations of C-reactive protein (CRP) suggested an unreliable CRP response in systemic Group B streptococcal infection. Recent experience with sequential, quantitative determinations of CRP in 10 infants surviving GBS infection documents that CRP can rise rapidly with systemic infection and fall rapidly with appropriate treatment. One infant with asymptomatic bacteremia had no increase in CRP, but in nine others with sepsis and/or meningitis the peak concentrations were from 4.2 to 31.9 mg/dl. Duration of elevated CRP ranged from 2 days in benign illness to 17 days in severe meningitis. Two infants with neurologic sequelae had concentrations greater than 20 mg/dl. Leukopenia, neutropenia and elevated immature neutrophil:total neutrophil ratio were frequently observed at the onset of infection. Leukocyte counts may be most helpful in making an early diagnosis, whereas CRP concentrations may document response, influence duration of antibiotic therapy and provide prognostic information.
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PMID:Response of C-reactive protein in neonatal Group B streptococcal infection. 388 78

Despite advances in the use of newer antimicrobials and aggressive supportive care, sepsis and its sequalae remain a major source of morbidity and mortality in the neonate. The VLBW neonate is especially at high risk. We and others have demonstrated that neonatal MNC are deficient in their production of G-CSF and GM-CSF, which, in part, may explain the neonates propensity to develop neutropenia during times of sepsis. G-CSF and GM-CSF have been shown to both enhance neonatal neutrophil superoxide production in vitro and to increase circulating neutrophil numbers through expansion of the NSP in the BM in neonatal rats and humans. G-CSF is protective (if given with or before antibiotics) during experimental GBS in the neonatal rat and appears to be well tolerated (both short term and 2 years after its use) in the human neonate. In a phase II randomized pilot multicenter study, GM-CSF prophylaxis in the VLBW neonate was well tolerated during 4 weeks of administration and was noted to have significantly reduced the incidence of nosocomial infections. Future efficacy and safety studies in more neonates need to be completed and assessed before the routine pharmacologic use of G-CSF or GM-CSF is recommended to prevent and treat neonatal sepsis.
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PMID:Rationale and potential use of cytokines in the prevention and treatment of neonatal sepsis. 977 42

Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous group of peripheral neuropathies. Different chromosomal loci have been linked with three autosomal dominant, 'intermediate' types of CMT: DI-CMTA, DI-CMTB and DI-CMTC. We refined the locus associated with DI-CMTB on chromosome 19p12-13.2 to 4.2 Mb in three unrelated families with CMT originating from Australia, Belgium and North America. After screening candidate genes, we identified unique mutations in dynamin 2 (DNM2) in all families. DNM2 belongs to the family of large GTPases and is part of the cellular fusion-fission apparatus. In transiently transfected cell lines, mutations of DNM2 substantially diminish binding of DNM2 to membranes by altering the conformation of the beta3/beta4 loop of the pleckstrin homology domain. Additionally, in the Australian and Belgian pedigrees, which carry two different mutations affecting the same amino acid, Lys558, CMT cosegregated with neutropenia, which has not previously been associated with CMT neuropathies.
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PMID:Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease. 1573 54

Mutations in dynamin 2 (DNM2) have been associated with autosomal dominant centronuclear myopathy, dominant intermediate Charcot-Marie-Tooth (CMT) type B and CMT2. Here, we report a novel DNM2 mutation in the Pleckstrin homology domain of DNM2 (p.K559del) in a patient with an axonal length-dependent sensorimotor polyneuropathy predominantly affecting the lower limbs. Neuropathy is associated with congenital cataracts, ophthalmoparesis, ptosis and neutropenia. There was no evidence of a skeletal myopathy on EMG or muscle biopsy. We suggest that this constellation of clinical features can help the diagnosis and selection of patients for direct DNM2 genetic analysis.
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PMID:A novel mutation in the dynamin 2 gene in a Charcot-Marie-Tooth type 2 patient: clinical and pathological findings. 1839 88

Dynamin 2 gene (DNM2) mutations result in an autosomal dominant centronuclear myopathy (CNM) and a Charcot-Marie-Tooth (CMT) neuropathy. DNM2-CMT but not DNM2-CNM patients were noted to have neutropenia. We here report a man with paravertebral muscles hypertrophy and mild neutropenia. His muscle biopsy was typical for CNM with additional "necklace" fibers. Sequencing of DNM2 revealed a known heterozygous c.1269C>T (p.Arg369Trp) mutation. Necklace fibers were considered as a pathological hallmark of late onset X-linked CNM due to mutations in MTM1 but have not been observed in DNM2-CNM. The findings broaden the features of DNM2-myopathy.
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PMID:Sporadic centronuclear myopathy with muscle pseudohypertrophy, neutropenia, and necklace fibers due to a DNM2 mutation. 2124 64

Mutations in the Dynamin 2 gene (DNM2) cause autosomal dominant centronuclear myopathy or autosomal dominant (AD) Charcot-Marie-Tooth (CMT) disease. Here the authors report one large Czech family with 15 members affected with an AD CMT phenotype of extraordinary variability. Genetic linkage analysis using SNP arrays revealed a locus of about 9.6 Mb on chromosome 19p13.1-13.2. In this critical interval, 373 genes were located. The only gene herein known to be associated with an intermediate type of CMT was Dynamin 2 (DNM2). Subsequent sequence analysis of the DNM2 gene in the index patient revealed a novel missense mutation p.Met580Thr. This missense mutation segregated with the neuropathy, indicating the causal character of this mutation. The phenotype of CMT in this family shows mild to moderate impairment with relatively preserved upper limbs and a very broad range of the onset of clinical symptoms from an early onset around the age of 12 to the late onset during the fifth decade. Electrophysiology showed an intermediate type of peripheral neuropathy. The motor median nerve conduction velocity varied from 36 m/s to normal values with signs of asymmetrical affection of peripheral nerves. No additional symptoms such as cranial nerve involvement, cataract, and signs of neutropenia or myopathy syndrome were observed in any member of the family yet. The progression was slow with no loss of ambulation. The authors suggest that the characterization of clinical variability in a single family may help to direct the genetic analysis directly to the rarely observed DNM2 mutations.
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PMID:Phenotypic variability in a large Czech family with a dynamin 2-associated Charcot-Marie-Tooth neuropathy. 2209 29

Charcot-Marie-Tooth (CMT) disease or hereditary motor and sensory neuropathy is a genetically and clinically heterogeneous group of disorders of the peripheral nervous system. Mutations in multiple genes are currently known. We report an original case of CMT associated with chronic neutropenia in a patient with a K562del mutation in the dynamin 2 (DNM2) gene in a patient presenting with alterated cognitive function. Associated manifestations may guide molecular study.
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PMID:[Non-fortuitous dynamin II mutation-related association: neutropenia and Charcot-Marie-Tooth disease]. 2238 72