Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 23
Filter
1.
Intern Med ; 58(9): 1251-1256, 2019 May 01.
Article in English | MEDLINE | ID: mdl-30626805

ABSTRACT

Objective Tracheoarterial fistula (TAF) is a rare but devastating complication of tracheostomy caused by pressure necrosis from the elbow, tip, or over-inflated cuff of the tracheostomy tube. The incidence of TAF is reportedly higher in patients with neurological disorders than in those without such disorders. To evaluate the incidence of and factors contributing to the misalignment of tracheostomy tubes in bedridden patients with chronic neurological disorders. Methods We retrospectively assessed three-dimensionally reconstructed serial computed tomography (CT) images to see if the tip of the tube made contact with the tracheal wall and if the main arteries were running adjacent to the tube's elbow, tip or cuff. Results The tip of the tube was in contact with the tracheal wall in 14 of the 30 patients assessed. Among them, the tip was adjacent to the innominate artery in eight, the aortic arch in three and an aberrant right subclavian artery in one. In one patient with the tube tip adjacent to the aortic arch and the other four patients, the cuff of the tube was adjacent to the innominate artery across the tracheal wall. Patients with the tube tip in contact with the anterior tracheal wall had a significantly greater cervical lordosis angle than those without contact (p<0.05). Conclusion More than half of tracheostomized patients with chronic neurological disorders had a latent risk of TAF. The variability in the location of the innominate artery, anomalies of the aortic arch, and skeletal deformities may therefore be contributing factors.


Subject(s)
Nervous System Diseases/complications , Respiratory Tract Fistula/prevention & control , Tracheal Diseases/prevention & control , Tracheostomy/instrumentation , Vascular Fistula/prevention & control , Adult , Aged , Brachiocephalic Trunk/diagnostic imaging , Cardiovascular Abnormalities/diagnostic imaging , Chronic Disease , Female , Humans , Imaging, Three-Dimensional/methods , Male , Middle Aged , Respiratory Tract Fistula/etiology , Retrospective Studies , Subclavian Artery/abnormalities , Subclavian Artery/diagnostic imaging , Tomography, X-Ray Computed , Trachea/diagnostic imaging , Tracheal Diseases/etiology , Tracheostomy/adverse effects , Tracheostomy/methods , Vascular Fistula/etiology
3.
Intern Med ; 55(14): 1919-22, 2016.
Article in English | MEDLINE | ID: mdl-27432104

ABSTRACT

We occasionally observe long-term remission of cervical dystonia after several botulinum toxin treatments. However, botulinum toxin transiently acts on neuromuscular junctions. We herein report that a cervical dystonia patient with spinocerebellar ataxia type 1 could have long-term remission as a result of the depression of hypermetabolism in the bilateral putamen and primary sensorimotor cortex after botulinum toxin therapy. We suggest that botulinum toxin impacts the central nervous system, causing prolonged improvement through the normalization of basal ganglia circuits in addition to its effects at neuromuscular junctions.


Subject(s)
Botulinum Toxins, Type A/adverse effects , Brain/metabolism , Neuromuscular Agents/adverse effects , Spinocerebellar Ataxias/chemically induced , Torticollis/chemically induced , Adult , Dystonia , Humans , Male
4.
Neurobiol Dis ; 71: 1-13, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25107340

ABSTRACT

Mutations in vacuolar protein sorting 35 (VPS35) have been linked to familial Parkinson's disease (PD). VPS35, a component of the retromer, mediates the retrograde transport of cargo from the endosome to the trans-Golgi network. Here we showed that retromer depletion increases the lysosomal turnover of the mannose 6-phosphate receptor, thereby affecting the trafficking of cathepsin D (CTSD), a lysosome protease involved in α-synuclein (αSYN) degradation. VPS35 knockdown perturbed the maturation step of CTSD in parallel with the accumulation of αSYN in the lysosomes. Furthermore, we found that the knockdown of Drosophila VPS35 not only induced the accumulation of the detergent-insoluble αSYN species in the brain but also exacerbated both locomotor impairments and mild compound eye disorganization and interommatidial bristle loss in flies expressing human αSYN. These findings indicate that the retromer may play a crucial role in αSYN degradation by modulating the maturation of CTSD and might thereby contribute to the pathogenesis of the disease.


Subject(s)
Drosophila Proteins/genetics , Lysosomes/metabolism , Mutation/genetics , Parkinson Disease/genetics , Parkinson Disease/metabolism , Vesicular Transport Proteins/genetics , alpha-Synuclein/metabolism , Animals , Animals, Genetically Modified , Brain/metabolism , Brain/pathology , Cathepsin D/metabolism , Disease Models, Animal , Drosophila , Eye/metabolism , Eye/pathology , Gene Expression Regulation/genetics , HEK293 Cells , Humans , Immunoprecipitation , Locomotion/genetics , Parkinson Disease/pathology , Protein Transport/genetics , RNA Interference/physiology , Subcellular Fractions/metabolism , Subcellular Fractions/ultrastructure
5.
Case Rep Neurol ; 6(1): 92-5, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24761145

ABSTRACT

Freezing of gait (FOG) is one of the factors that reduce the quality of life in patients with Parkinson's disease (PD). Imagining bicycling before gait start provided improvement in FOG in 2 PD patients. Imagining and mimicking bicycling after the initiation of gait allowed the rhythmic gait to continue without interruption. We suggest that imagining and mimicking bicycling, which are nonexternal cues, could serve as a helpful therapeutic approach for the intractable freezing and interruption of gait of PD patients.

6.
J Parkinsons Dis ; 4(2): 181-7, 2014.
Article in English | MEDLINE | ID: mdl-24625830

ABSTRACT

Dementia is one of the most debilitating symptoms of Parkinson's disease (PD), but the development of dementia is still difficult to predict at early stages of the disease. We recently found that hyposmia, one of the most typical non-motor features of PD, was a predictive feature of Parkinson's disease with dementia (PDD). In that work, multivariate logistic analysis identified severe hyposmia and visuoperceptual impairment as independent risk factors for subsequent dementia within 3 years. The patients with severe hyposmia had an 18.7-fold increase in their risk of dementia for each 1 SD (2.8) decrease in scores on the odor stick identification test for Japanese (OSIT-J). We also found an association between severe hyposmia and a specific pattern of cerebral metabolic decline, which was identical to findings observed in PDD. Furthermore, volumetric magnetic resonance imaging analyses demonstrated close relationships between olfactory dysfunction and atrophy of focal brain structures, including the amygdala and other limbic structures. Our findings suggest that brain regions related to olfactory function are closely associated with cognitive decline and that severe hyposmia is a prominent clinical feature that predicts the subsequent development of PDD. We have now started a randomized, double-blind study using donepezil for the PD group with severe hyposmia. We hope that this clinical trial will allow us to establish a therapeutic intervention that can improve the prognosis of advanced PD.


Subject(s)
Dementia/diagnosis , Dementia/etiology , Olfaction Disorders/etiology , Parkinson Disease/complications , Aged , Brain/metabolism , Dementia/metabolism , Female , Humans , Male , Middle Aged , Olfaction Disorders/metabolism , Parkinson Disease/metabolism , Randomized Controlled Trials as Topic , Risk Factors
7.
BMJ Open ; 3(3)2013 Mar 01.
Article in English | MEDLINE | ID: mdl-23457325

ABSTRACT

OBJECTIVE: Dysphagia is one of the cardinal symptoms of Parkinson's disease (PD). It is closely related to the quality of life and longevity of PD patients. The aim of the study is to clarify the pathophysiological mechanisms responsible for dysphagia in PD. DESIGN: A cross-sectional and longitudinal comparative study. SETTING: Tohoku University Hospital. PARTICIPANTS: Eight patients with dysphagia, 15 patients without dysphagia and 10 normal control subjects. MAIN OUTCOME MEASURES: The time needed for swallowing initiation and changes in brain glucose metabolism at baseline and after a 3-year follow-up period. RESULTS: The time needed for swallowing initiation was significantly longer in the patients with dysphagia compared with the patients without dysphagia at baseline and after the 3-year follow-up period (p<0.05). The patients with dysphagia exhibited hypometabolism in the supplementary motor area (SMA) and the anterior cingulate cortex (ACC) compared with the 10 normal control subjects at baseline (uncorrected p<0.001). After the 3-year follow-up period, the number of brain areas showing hypometabolism increased, involving not only the SMA and the ACC but also the bilateral medial frontal lobes, middle cingulate cortex, thalamus and right superior, middle, inferior and orbital frontal gyri (uncorrected p<0.001). In contrast, the patients without dysphagia showed virtually no regional hypometabolism at baseline (uncorrected p<0.001) and only a small degree of hypometabolism in the SMA and ACC after the 3-year follow-up period (uncorrected p<0.001). CONCLUSIONS: These results suggest that dysphagia in PD patients is mainly related to a difficulty in swallowing initiation that is based on a combination of poor movement planning due to SMA dysfunction and impaired cognitive processing due to ACC dysfunction.

8.
Mol Neurodegener ; 7: 38, 2012 Aug 14.
Article in English | MEDLINE | ID: mdl-22892036

ABSTRACT

BACKGROUND: The intracellular deposition of misfolded proteins is a common neuropathological hallmark of most neurodegenerative disorders. Increasing evidence suggests that these pathogenic proteins may spread to neighboring cells and induce the propagation of neurodegeneration. RESULTS: In this study, we have demonstrated that α-synuclein (αSYN), a major constituent of intracellular inclusions in synucleinopathies, was taken up by neuronal and oligodendroglial cells in both a time- and concentration-dependent manner. Once incorporated, the extracellular αSYN was immediately assembled into high-molecular-weight oligomers and subsequently formed cytoplasmic inclusion bodies. Furthermore, αSYN uptake by neurons and cells of the oligodendroglial lineage was markedly decreased by the genetic suppression and pharmacological inhibition of the dynamin GTPases, suggesting the involvement of the endocytic pathway in this process. CONCLUSIONS: Our findings shed light on the mode of αSYN uptake by neuronal and oligodendroglial cells and identify therapeutic strategies aimed at reducing the propagation of protein misfolding.


Subject(s)
Dynamins/antagonists & inhibitors , Neurodegenerative Diseases/metabolism , Neurons/metabolism , Oligodendroglia/metabolism , alpha-Synuclein/metabolism , Animals , Blotting, Western , Cell Line , Coculture Techniques , Endocytosis , Enzyme Inhibitors , Fluorescent Antibody Technique , Humans , Inclusion Bodies/metabolism , Inclusion Bodies/pathology , Mice , Microscopy, Confocal , Neurodegenerative Diseases/pathology , Neurons/pathology , Oligodendroglia/pathology
9.
Brain ; 135(Pt 1): 161-9, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22287381

ABSTRACT

Dementia is one of the most debilitating symptoms of Parkinson's disease. A recent longitudinal study suggests that up to 80% of patients with Parkinson's disease will eventually develop dementia. Despite its clinical importance, the development of dementia is still difficult to predict at early stages. We previously identified olfactory dysfunction as one of the most important indicators of cortical hypometabolism in Parkinson's disease. In this study, we investigated the possible associations between olfactory dysfunction and the risk of developing dementia within a 3-year observation period. Forty-four patients with Parkinson's disease without dementia underwent the odour stick identification test for Japanese, memory and visuoperceptual assessments, (18)F-fluorodeoxyglucose positron emission tomography scans and magnetic resonance imaging scans at baseline and 3 years later. A subgroup of patients with Parkinson's disease who exhibited severe hyposmia at baseline showed more pronounced cognitive decline at the follow-up survey. By the end of the study, 10 of 44 patients with Parkinson's disease had developed dementia, all of whom had severe hyposmia at baseline. The multivariate logistic analysis identified severe hyposmia and visuoperceptual impairment as independent risk factors for subsequent dementia within 3 years. The patients with severe hyposmia had an 18.7-fold increase in their risk of dementia for each 1 SD (2.8) decrease in the score of odour stick identification test for Japanese. We also found an association between severe hyposmia and a characteristic distribution of cerebral metabolic decline, which was identical to that of dementia associated with Parkinson's disease. Furthermore, volumetric magnetic resonance imaging analyses demonstrated close relationships between olfactory dysfunction and the atrophy of focal brain structures, including the amygdala and other limbic structures. Together, our findings suggest that brain regions related to olfactory function are closely associated with cognitive decline and that severe hyposmia is a prominent clinical feature that predicts the subsequent development of Parkinson's disease dementia.


Subject(s)
Brain/diagnostic imaging , Dementia/complications , Dementia/diagnostic imaging , Olfaction Disorders/complications , Parkinson Disease/complications , Aged , Brain/physiopathology , Cross-Sectional Studies , Dementia/physiopathology , Female , Humans , Longitudinal Studies , Male , Middle Aged , Neuropsychological Tests , Odorants , Olfaction Disorders/diagnostic imaging , Olfaction Disorders/physiopathology , Parkinson Disease/diagnostic imaging , Parkinson Disease/physiopathology , Radionuclide Imaging
10.
Parkinsonism Relat Disord ; 17(9): 698-700, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21840242

ABSTRACT

We aimed to study whether either [(123)l] myocardial meta-iodobenzylguanidine (MIBG) myocardial scintigraphy or the odor stick identification test for Japanese (OSIT-J) is effective in differentiating Parkinson's disease (PD) from multiple system atrophy (MSA). We compared the MIBG accumulation and olfactory score between 42 PD and 42 MSA (19 MSA-P and 23 MSA-C) patients in the early stages. [(123)l] MIBG myocardial scintigraphy showed higher sensitivity and the olfactory test higher specificity in differentiating PD from MSA. There were significant differences between PD and MSA-C (p = 0.0019) instead of MSA-P (p > 0.05) in the MIBG accumulation, while there were significant differences between PD and MSA-P (p = 0.0003) or MSA-C (p = 0.0003) in the OSIT-J score. Our data suggest that the olfactory test can be useful as a clinical tool with its higher specificity in differentiating PD from MSA in the early stages and, moreover, support the discrimination of PD from MSA-P.


Subject(s)
3-Iodobenzylguanidine , Multiple System Atrophy/diagnosis , Parkinson Disease/diagnosis , Radiopharmaceuticals , Aged , Diagnosis, Differential , Female , Humans , Iodine Radioisotopes , Male , Middle Aged , Multiple System Atrophy/complications , Myocardial Perfusion Imaging , Olfaction Disorders/diagnosis , Olfaction Disorders/etiology , Parkinson Disease/complications , Sensitivity and Specificity
11.
Am J Infect Control ; 39(4): 309-13, 2011 May.
Article in English | MEDLINE | ID: mdl-20965611

ABSTRACT

BACKGROUND: Catheter hub contamination has been recognized as a source of catheter-related bloodstream infections. We have investigated the efficacy of a protection cap for a needleless injection device in preventing intraluminal catheter contamination, compared with a conventional 3-way stopcock. METHODS: Adult patients requiring an intravascular catheter placement for at least 48 hours in an intensive care unit were randomly assigned to receive either the needleless injection device with protection cap (test group, n = 31, number of devices = 151) or with a conventional 3-way stopcock (comparator group, n = 33, number of devices = 179). To evaluate intraluminal contamination, we examined the bacteria isolated in the inline bacterial filters, which were attached downstream of the injection ports. RESULTS: The incidence of bacterial contamination was significantly different between the groups (test group 2/151 (1.3%) vs comparator group 11/179 (6.2%), P = .04). There was no correlation between the microbial contamination rate and the in situ time of catheter or numbers of injections. CONCLUSION: The protection cap for needleless injection devices decreased microbial transfer from the injection port to the intraluminal fluid pathway and lowered the risk of catheter-related bloodstream infections.


Subject(s)
Bacteremia/prevention & control , Bacteria/isolation & purification , Catheter-Related Infections/prevention & control , Catheterization/methods , Catheters/microbiology , Cross Infection/prevention & control , Equipment and Supplies/microbiology , Adolescent , Adult , Aged , Aged, 80 and over , Bacteremia/epidemiology , Catheter-Related Infections/epidemiology , Cross Infection/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Prospective Studies , Young Adult
12.
PLoS One ; 6(12): e29460, 2011.
Article in English | MEDLINE | ID: mdl-22216284

ABSTRACT

Many neurodegenerative diseases share a common pathological feature: the deposition of amyloid-like fibrils composed of misfolded proteins. Emerging evidence suggests that these proteins may spread from cell-to-cell and encourage the propagation of neurodegeneration in a prion-like manner. Here, we demonstrated that α-synuclein (αSYN), a principal culprit for Lewy pathology in Parkinson's disease (PD), was present in endosomal compartments and detectably secreted into the extracellular milieu. Unlike prion protein, extracellular αSYN was mainly recovered in the supernatant fraction rather than in exosome-containing pellets from the neuronal culture medium and cerebrospinal fluid. Surprisingly, impaired biogenesis of multivesicular body (MVB), an organelle from which exosomes are derived, by dominant-negative mutant vacuolar protein sorting 4 (VPS4) not only interfered with lysosomal targeting of αSYN but facilitated αSYN secretion. The hypersecretion of αSYN in VPS4-defective cells was efficiently restored by the functional disruption of recycling endosome regulator Rab11a. Furthermore, both brainstem and cortical Lewy bodies in PD were found to be immunoreactive for VPS4. Thus, VPS4, a master regulator of MVB sorting, may serve as a determinant of lysosomal targeting or extracellular secretion of αSYN and thereby contribute to the intercellular propagation of Lewy pathology in PD.


Subject(s)
Endosomal Sorting Complexes Required for Transport/physiology , Lysosomes/metabolism , Vacuolar Proton-Translocating ATPases/physiology , alpha-Synuclein/metabolism , ATPases Associated with Diverse Cellular Activities , Cell Compartmentation , Culture Media , Endosomes/metabolism , Humans
13.
Neurochem Int ; 57(8): 857-66, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20849899

ABSTRACT

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder presenting variable combinations of parkinsonism, cerebellar ataxia, corticospinal and autonomic dysfunction. Alpha-synuclein (α-SYN)-immunopositive glial cytoplasmic inclusions (GCIs) represent the neuropathological hallmark of MSA, and tubulin polymerization promoting protein (TPPP)/p25 in oligodendroglia has been known as a potent stimulator of α-SYN aggregation. To gain insight into the molecular pathomechanisms of GCI formation and subsequent oligodendroglial degeneration, we ectopically expressed α-SYN and TPPP in HEK293T and oligodendroglial KG1C cell lines. Here we showed that TPPP specifically accelerated α-SYN oligomer formation and co-immunoprecipitation analysis revealed the specific interaction of TPPP and α-SYN. Moreover, phosphorylation of α-SYN at Ser-129 facilitated the TPPP-mediated α-SYN oligomerization. TPPP facilitated α-SYN-positive cytoplasmic perinuclear inclusions mimicking GCI in both cell lines; however, apoptotic cell death was only observed in KG1C cells. This apoptotic cell death was partly rescued by sirtuin 2 (SIRT2) inhibition. Together, our results provide further insight into the molecular pathogenesis of MSA and potential therapeutic approaches.


Subject(s)
Multiple System Atrophy/metabolism , Multiple System Atrophy/pathology , Nerve Tissue Proteins/physiology , Oligodendroglia/metabolism , Oligodendroglia/pathology , Sirtuin 2/antagonists & inhibitors , Sirtuin 2/physiology , alpha-Synuclein/physiology , Apoptosis/physiology , Gene Expression Regulation, Enzymologic/physiology , Glycogen Synthase Kinase 3/antagonists & inhibitors , HEK293 Cells , Humans , Multiple System Atrophy/enzymology , Nerve Tissue Proteins/biosynthesis , Nerve Tissue Proteins/genetics , Oligodendroglia/enzymology , Phosphorylation/physiology , Serine/chemistry , Serine/metabolism
15.
J Infect Chemother ; 13(4): 235-54, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17721687

ABSTRACT

Changes in nasopharyngeal bacterial flora in adults with acute upper respiratory tract infection on administration of antimicrobial agents were investigated, and how these changes contrasted with those in children. Many patients with acute sinusitis due to allergies, and patients with malignancy and diabetes mellitus were included in the investigation. The detection rates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, the major bacteria of acute otitis media (AOM), were 22%, 10%, and 7% respectively, which were significantly lower than those for children. Gram stain examination of nasopharyngeal swab samples showed a significant relation between leukocyte infiltration and the detection amount of S. pneumoniae (P = 0.0086). A significant relation (P = 0.0134) was also observed when H. influenzae was simultaneously detected. No significant change in the three major AOM bacteria present in nasopharyngeal bacterial flora after administration of antimicrobial agents was observed. However, all S. pneumoniae and H. influenzae detected after antimicrobial agent administration had the beta-lactam-resistance gene. It was observed that a significant improvement in leukocyte infiltration occurred 6 to 10 days after antimicrobial agent administration. In contrast, a significant improvement in children was observed at 2 to 5 days. In the adult subjects, this improvement was probably due to spontaneous remission rather than the effect of the antimicrobial agents. Although investigation of the long-term administration of antimicrobial agents was also conducted, its benefits for the patients were not elucidated.


Subject(s)
Drug Resistance, Multiple, Bacterial/genetics , Nasopharynx/microbiology , Otitis Media/microbiology , Respiratory Tract Infections/microbiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Child , Female , Haemophilus influenzae/drug effects , Haemophilus influenzae/genetics , Humans , Japan , Male , Middle Aged , Moraxella catarrhalis/drug effects , Moraxella catarrhalis/genetics , Otitis Media/drug therapy , Respiratory Tract Infections/drug therapy , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/genetics , Treatment Outcome
16.
J Infect Chemother ; 12(5): 287-304, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17109094

ABSTRACT

In our first report, we investigated nasopharyngeal bacterial flora related to penicillin-resistant Streptococcus pneumoniae (PRSP) and beta-lactamase-negative ampicillin-resistant Haemophilus influenzae (BLNAR) and their relation to acute upper respiratory tract infection (AURTI). This report analyzes the results of a study of nasopharyngeal bacterial flora before the administration of antimicrobial agents in 172 AURTI patients aged 6 years or younger. In addition to Gram staining, microscopic observation, and culturing, a polymerase chain reaction (PCR) method was used to identify PRSP (gPRSP) and BLNAR (gBLNAR) drug-resistant genes. Of the patients analyzed, 90% had acute otitis media (AOM) and were aged 2 years or younger. The antimicrobial agents administered were amoxicillin (34%), clavulanic acid/amoxicillin (11%), cefditren pivoxil (CDTR-PI) (43%), and others (12%). This was particularly true for patients administered CDTR-PI, among whom there were many who had already suffered one or more episodes of AOM by the age of 1 year or younger, and many in which gPRSP were detected (P < 0.01). There was a significant relation between the degree of nasopharyngeal inflammation indicated by leukocyte infiltration images and the amount of S. pneumoniae and H. influenzae detected, which are the main pathogenic bacteria causing AOM (P < 0.01). In addition to leukocyte infiltration images, there were cases in which shedding of ciliated cells was observed and/or giant monocytic cells. Both nasopharyngeal leukocyte infiltration images and/or shed cell findings observed in infant AURTI cases are important indices for the prompt detection of gPRSP and/or gBLNAR and appropriate doses of antimicrobial agents.


Subject(s)
Anti-Infective Agents/therapeutic use , Haemophilus influenzae/isolation & purification , Nasopharynx/microbiology , Streptococcus pneumoniae/isolation & purification , Age Factors , Ampicillin Resistance , Child , Child, Preschool , Female , Haemophilus Infections/drug therapy , Haemophilus Infections/microbiology , Haemophilus influenzae/enzymology , Haemophilus influenzae/genetics , Humans , Infant , Male , Nasopharynx/drug effects , Otitis Media/drug therapy , Otitis Media/microbiology , Pneumococcal Infections/drug therapy , Pneumococcal Infections/microbiology , Polymerase Chain Reaction/methods , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/microbiology , Streptococcus pneumoniae/genetics , beta-Lactamases/metabolism
17.
J Infect Chemother ; 12(5): 305-30, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17109095

ABSTRACT

This report focuses on changes in the nasopharyngeal bacterial flora before and after administration of antimicrobial agents in 172 cases of acute upper respiratory infection in patients aged 6 years or younger. The antimicrobial agents administered were amoxicillin (AMPC) (34%), clavulanic acid/amoxicillin compound (11%), cefditren pivoxil (CDTR-PI) (43%), and others (12%). Changes in nasopharyngeal bacterial flora were investigated with reexaminations conducted after 2-5 days (day 2-5 subgroup), 6-10 days (day 6-10 subgroup), and 11 days and thereafter. There was a significant reduction in the Streptococcus pneumoniae detected in the group administered AMPC (AMPC group) in the day 2-5 subgroup and the day 6-10 subgroup. There was also a significant decrease in H. influenzae in the group administered CDTR-PI (CDTR-PI group) in the day 2-5 subgroup. From this it was inferred that for the most part significant changes in infectious nasopharyngeal bacteria occurred in the day 2-5 subgroups. However, a significant improvement in the degree of inflammation, as indicated by leukocyte infiltration images for the AMPC group, was observed in the day 2-5 subgroup, and for the CDTR-PI group in the day 6-10 subgroup. On the other hand, in both the antimicrobial agent groups, S. pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were newly detected at reexamination. Furthermore, a difference in the incidence of these bacteria was observed between the 2 antimicrobial agent groups. It was suggested that such phenomena related to the survival of resistant strains or a recurrence otitis media.


Subject(s)
Anti-Infective Agents/therapeutic use , Haemophilus influenzae/isolation & purification , Moraxella catarrhalis/isolation & purification , Nasopharynx/microbiology , Respiratory Tract Infections/drug therapy , Streptococcus pneumoniae/isolation & purification , Child , Child, Preschool , Drug Resistance , Female , Haemophilus Infections/microbiology , Humans , Infant , Male , Moraxellaceae Infections/microbiology , Nasopharynx/drug effects , Otitis Media/drug therapy , Otitis Media/microbiology , Pneumococcal Infections/microbiology , Polymerase Chain Reaction/methods , Respiratory Tract Infections/microbiology
18.
J Infect Chemother ; 12(2): 83-96, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16648948

ABSTRACT

With the appearance of penicillin-resistant Streptococcus pneumoniae, there has been increasing debate concerning antimicrobial treatments for acute upper respiratory tract infection (AURTI) and acute otitis media in children. This study compares the nasopharyngeal bacterial flora in patients with AURTI (AURTI group; 710 subjects) and healthy subjects (HS group; 380 subjects). The comparisons were made between subjects aged 6 years or younger (0-6 subgroup: 330 subjects), between 7 and 74 years (7-74 subgroup: 668 subjects), and 75 years and older (92 subjects), because the subjects were subgrouped as described above dependent on the maturity of the protective immunity. In the HS group 7-74 subgroup, viridans group streptococci, Staphylococcus aureus, coagulase-negative staphylococci, and Corynebacterium sp. with a detection rate of 10% or more were classified as normal nasal flora (NNF), and Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were classified as drum cavity pathogens (DCP). In the 0-6 subgroup, although the detection rate for DCP bacteria in the AURTI group tended to be high, it did not reach a significant difference, whereas the detection rate for NNF bacteria was significantly lower. This trend was also observed to some degree in the other age subgroup. In the 0-6 subgroup, leukocyte infiltration observed with a microscope indicated the closest relationship between S. pneumoniae detection rate and detection quantity. These results suggest that in the 0-6 subgroup the tendency for patients with AURTI to have NNF bacteria as well as DCP bacteria should be taken into consideration.


Subject(s)
Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/isolation & purification , Otitis Media/microbiology , Respiratory Tract Infections/microbiology , Acute Disease , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Child , Child, Preschool , Drug Resistance, Bacterial , Humans , Infant , Middle Aged , Nasopharynx/microbiology , Neutrophils/immunology , Otitis Media/immunology , Respiratory Tract Infections/immunology
19.
J Infect Chemother ; 8(1): 50-8, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11957120

ABSTRACT

We established breakpoints for differentiating ampicillin (ABPC)-susceptible strains from resistant strains among Haemophilus influenzae isolates according to susceptibility to various beta-lactam antibiotics, using a disc method. Susceptibility testing of isolates for 13 beta-lactam agents was followed by analysis of the resistance genes, using a polymerase chain reaction (PCR) to identify the TEM-1 beta-lactamase gene ( bla) and the ftsI gene encoding penicillin-binding protein (PBP) 3, which affects beta-lactam minimum inhibitory concentrations (MICs). A total of 228 H. influenzae isolates were classified into 114 beta-lactamase-negative, ABPC-susceptible (BLNAS) strains; 29 beta-lactamase-negative, ABPC-resistant (BLNAR) strains; 53 low-BLNAR strains with a low degree of ABPC resistance; 27 TEM-1-producing strains (BLPAR); and 5 strains with ftsI gene mutations in addition to TEM-1 production (BLPACR) according to the PCR results. To identify resistant strains by disc-method susceptibility testing, the zone of inhibition was measured for ABPC (10 microg/disc), cefaclor (30 microg/disc), cefpodoxime (10 microg/disc), and cefdinir (5 microg/disc) discs. Strains were identified as BLNAS without resistant genes when the diameter was > or =27 mm for the ABPC disc and > or =21 mm for the cefaclor disc. Other strains were identified as BLNAR when the diameter was < or =22 mm for the cefpodoxime disc and < or =17 mm for the cefdinir disc. Remaining strains were identified as low-BLNAR. These criteria differentiated resistance types with high accuracy. A discrepancy was noted between genetic results and disc-testing breakpoints for differentiating resistant from susceptible H. influenzae. A disc-testing breakpoint for cefditoren (5 microg/disc) was proposed, with the susceptibility statistically defined as a diameter of > or =24 mm, which corresponds to the breakpoint (1 microg/ml) of the microdilution method recommended by the Japanese Society of Chemotherapy.


Subject(s)
Haemophilus influenzae/drug effects , Microbial Sensitivity Tests/methods , beta-Lactamases/metabolism , Ampicillin Resistance , Anti-Bacterial Agents/pharmacology , Haemophilus influenzae/enzymology , Humans , beta-Lactams
20.
J Infect Chemother ; 3(4): 190-197, 1997.
Article in English | MEDLINE | ID: mdl-29681341

ABSTRACT

To identify penicillin (Pc) and other ß-lactam resistance in 310 clinical isolates of Streptococcus pneumoniae by polymerase chain reaction (PCR), 3 sets of primers were designed to amplify Pc-binding protein (PBP) genes previously detected in Pc-susceptible strains: 1) a 430-bp fragment of the pbp1a gene, 2) a 292-bp fragment of the pbp2x gene, and 3) a 77-bp fragment of the pbp2b gene. The amplified regions of each PBP gene were positioned in highly divergent sequences of Pc-resistant S. pneumoniae. In other words, isolates for which these DNA fragments were detected were regarded as possessing sequences almost the same as that of the susceptible R6 strain and those for which these DNA fragments were not detected were assumed to have mutations. A set of primers that amplify 273 bp of the autolysin (lytA) gene to identify S. pneumoniae was applied as well. Of 166 isolates for which the minimum inhibitory concentration (MIC) of Pc were ≤0.06µg/mL, 83 (50.0%) were confirmed to be true susceptible strains with no PBP gene mutation and most of the remaining strains were found to possess pbp2x mutation. In contrast, most of 109 isolates for which the MIC of Pc were ≥0.5 µg/mL were confirmed to possess mutations in all three PBP genes. Thirty-five strain for which the MIC of Pc ranged from 0.125 to 0.25µg/mL possessed various PBP gene mutations. The relationships between susceptibilities to 9 ß-lactams of S. pneumoniae and PBP gene mutation were analyzed by multiple regression analysis. Antibiotics were classified into 4 types according to the differences in PBP gene mutation affecting their MIC levels, 1) the MIC of Pc and ampicillin were affected by pbp1a and pbp2b mutations; 2) those of cefotaxime, cefpodoxime, and cefditoren were affected clearly by pbp2x mutation; 3) those of cefaclor and cefdinir were affected more strongly by pbp1a mutation than the pbp2x; and 4) the MIC of faropenem and imipenem were affected strongly by pbp2b mutation. These findings suggest that it may be possible to easily determine whether a S. pneumoniae isolate is susceptible or resistant to Pc, cefotaxime, and other ß-lactams by applying PCR using a combination of primers.

SELECTION OF CITATIONS
SEARCH DETAIL
...