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A Michelson

Publications and source records attributed to A Michelson.

11 recordsLinked to original sources
PubMed1999

Nitric oxide inhibits thrombin receptor-activating peptide-induced phosphoinositide 3-kinase activity in human platelets.

Although nitric oxide (NO) has potent antiplatelet actions, the signaling pathways affected by NO in the platelet are poorly understood. Since NO can induce platelet disaggregation and phosphoinositide 3-kinase (PI3-kinase) activation renders aggregation irreversible, we tested the hypothesis that NO exerts its antiplatelet effects at least in part by inhibiting PI3-kinase. The results demonstrate that the NO donor S-nitrosoglutathione (S-NO-glutathione) inhibits the stimulation of PI3-kinase associated with tyrosine-phosphorylated proteins and of p85/PI3-kinase associated with the SRC family kinase member LYN following the exposure of platelets to thrombin receptor-activating peptide. The activation of LYN-associated PI3-kinase was unrelated to changes in the amount of PI3-kinase physically associated with LYN signaling complexes but did require the activation of LYN and other tyrosine kinases. The cyclic GMP-dependent kinase activator 8-bromo-cyclic GMP had similar effects on PI3-kinase activity, consistent with a model in which the cyclic nucleotide mediates the effects of NO. Additional studies showed that wortmannin and S-NO-glutathione have additive inhibitory effects on thrombin receptor-activating peptide-induced platelet aggregation and the surface expression of platelet activation markers. These data provide evidence of a distinct and novel mechanism for the inhibitory effects of NO on platelet function.

Androstadienes↗
PubMed1999

Plasma glutathione peroxidase deficiency and platelet insensitivity to nitric oxide in children with familial stroke.

In a previous report by Freedman et al (J Clin Invest. 1996;97:979-987), plasma from 2 brothers with stroke or transient ischemic attack inactivated the antiplatelet effects of nitric oxide (NO), and this effect was found to be a consequence of a deficiency of plasma glutathione peroxidase (GSH-Px). In this study, we attempted to define the generalizability of this deficiency by studying NO-mediated antiplatelet effects in 7 families with familial childhood stroke. Seven families with familial childhood stroke that consecutively presented to a large referral center were included in the study. We monitored ADP-induced aggregation of normal gel-filtered platelets (GFP) in platelet-poor plasma (PPP) from normal individuals and from patients in the presence or absence of an NO donor (S-nitroso-glutathione). Surface P-selectin expression of normal GFP in patients' PPP was analyzed by flow cytometry after incubation with a P-selectin-specific monoclonal antibody in the presence or absence of the NO donor. We also measured GSH-Px activity in plasmas from family members and normal controls using standard methods. In 6 of 7 families, NO failed to inhibit platelet P-selectin expression and platelet aggregation in PPP from the affected family members and some of their relatives. Of 4 families studied, 3 probands and their corresponding affected parent had 50% decrease in plasma GSH-Px activity. In some patients with childhood stroke, impaired metabolism of reactive oxygen species as a result of reduced GSH-Px activity results in NO insufficiency that affects normal platelet inhibitory mechanisms and predisposes to arterial thrombosis.

Adolescent↗
PubMed1995

[Vestibular lesion in sudden deafness: a prognostic criterium for therapeutic success].

The influence of vestibular dysfunction on severity of initial hearing loss and success of therapy was evaluated in a retrospective study with 142 patients suffering from idiopathic sudden hearing loss. In 48% of these patients combined cochleovestibular disorders were found. In this group mean hearing loss was significantly higher (45 dB versus 32 dB) and hearing recovery after therapy (25% versus 38%) less pronounced. 83% of patients with high grades of vestibular disorders (Vestibular Index: > or = 9) showed a decrease of hearing function between 50 dB and 130 dB compared to 32% in the group with signs of low vestibular dysfunction. Additional vestibular lesion in patients with sudden deafness can be used as a criteria for prognosis. High grade vestibular lesion reduce the probability of complete hearing recovery.

Adolescent↗
PubMed1993

[Preventive antibiotic administration in rhinoplasty. Tissue level and pharmacokinetics with reference to rhinoplasty techniques].

Prophylactic antibiotics (cefuroxime 1500 mg) were administered during induction of anesthesia to 34 patients undergoing nasal surgery. The infusion ended at the time of mucosa incision (mean infusion time: 22 min). A hemitransfixion incision was followed by elevation of the mucoperichondrium on both sides of the septum. The blood supply of the cartilage was thus diminished essentially. In the septal cartilage, the concentration of cefuroxime 68 min after the administrations of antibiotic was 28.1 micrograms/g; this concentration was 19.8 micrograms/g in the septal bone at 74 min. The mean peak plasma concentration was 158 micrograms/ml and the end half-life elimination time 77 min. High antibiotic concentrations in the cartilage resulted from passive diffusion through the septal mucosa and occurred at a mean time of 22 min. The time between the start of infusion at the induction of anesthesia and interruption of the septal blood supply by separating of the septum from overlying soft tissues was sufficient for developing high antibiotic concentrations. During nasal surgery the routine approach to the septum had no influence on the efficacy of antimicrobial prophylaxis.

Adult↗
PubMed1992

Paranasal sinusitis associated with nasotracheal and orotracheal long-term intubation.

The impact of nasotracheal and orotracheal long-term intubation on the development of sinusitis paranasalis was investigated in a prospective study. Daily A-scan ultrasound examinations of the maxillary sinuses were performed on 44 intensive care unit patients (20 nasally, 24 orally intubated) who required prolonged intubation (greater than 24 hours). At the end of the investigation period 19 (95%) of 20 nasotracheally and 15 (63%) of 24 orotracheally intubated patients showed pathologic antral sinus findings. In nasally intubated patients the incidence of bilateral sinusitis was significantly higher and its onset sooner. Pathologic organisms were found in the sinus aspirates in seven of 13 nasotracheally intubated patients, but only in two of nine patients with an oral tube. Thus, the nasotracheal tube can be seen as an adding factor in the development of sinusitis paranasalis.

Adult↗
PubMed1991

[Sinusitis in long-term intubated, intensive care patients: nasal versus oral intubation].

UNLABELLED: Discussion of paranasal sinusitis as a nosocomial infection in the mechanically ventilated intensive care (ICU) patient has recently been intensified. Some authors have emphasized nasotracheal intubation as a possible pathogenetic pathway. The aim of this study was to investigate the impact of nasotracheal or orotracheal intubation on the development of sinusitis in ICU patients. METHODS: In a prospective study, we followed 44 patients who required mechanical ventilation (greater than 24 h) in the ICU because of prolonged recovery from abdominal, thoracic, or posttraumatic surgery. Twenty patients were intubated nasotracheally and 24 orotracheally. Assignment to the groups was random. All were provided with a nasogastric tube and initially treated with systemic antibiotics. They received local antimicrobial prophylaxis of the nose, oropharynx, and stomach. Daily a-scan examinations of the maxillary sinuses were performed from the day of admission to the ICU until extubation, tracheotomy, death, or transfer. The average observation period was 6.9 days in the oral group and 7.1 days in the nasal group. In the case of a pathologic finding, aspiration of the antral sinus was carried out. In this study sinusitis indicated a sonographic finding; it did not necessarily imply a bacterial infection. RESULTS: At the beginning of the observation period, 6 patients in the oral group and 4 in the nasal group already had a pathologic maxillary sinus finding. At the end, in 15 of 24 in the oral group and 19 of 20 in the nasal group unilateral or bilateral sinusitis could be demonstrated. Development of bilateral sinusitis (13/20 in the nasotracheal group, 8/24 in the orotracheal group) was mainly observed after the appearance of unilateral sinusitis. The site corresponded to the site of the nasal tube in 65%. Unilateral paranasal infection was observed in nasotracheally and orotracheally intubated patients after an average of 2.8 and 2.6 days, respectively, whereas bilateral sinusitis had an average time delay of 4.5 and 5.7 days. Aspiration of the maxillary sinus was performed in 22 of 34 cases with sinusitis. Pathogenic organisms could be demonstrated in 7 of 13 nasotracheally intubated patients but only 2 of 9 with orotracheal tubes. CONCLUSION: We found that patients intubated orotracheally developed significantly less sinusitis than those intubated nasotracheally. Edema, local infection of the nasal mucosa, or mechanical obstruction of sinus drainage pathways by the tube are possible explanations. The fact that 63% of orally intubated patients had a pathologic maxillary sinus finding as well suggests that in addition to other reasons, an increased central venous pressure, positive pressure ventilation, and the supine position must be regarded as predisposing factors that increase the incidence of sinusitis. We conclude that the conditions of critically ill patients predispose to the development of sinusitis. Nasotracheal intubation is to be regarded as an additional risk, and therefore oral intubation should be preferred.

Adult↗
PubMed1990

[The effect of endonasal paranasal sinus surgery on lung function of patients with bronchial asthma].

Lung function tests of 13 patients suffering from manifest asthma and of 4 patients showing only bronchial hyperreactivity were performed before and on an average of 12 months after endonasal surgery of the paranasal sinuses. In the four subjects, bronchial hyperreactivity was no longer detectable postoperatively by provocation with carbachol. Five asthmatics could stop medication of 1 to 3 of their drugs, five others were able to reduce the dosage of one of their drugs to 50% or more. Lung function and medication was unchanged in two asthmatic patients, one patient had to add a drug to his medication while showing an unchanged lung function. In patients with asthma and chronic paranasal sinusitis, endoscopic endonasal sinus surgery (together with flanking measures, e.g. septal correction) is able to improve antiasthmatic therapy in a high percentage.

Adult↗
PubMed1986

[Perioperative antibiotic prevention with cefoxitin in cesarean section. Management and uses].

Antibiotic prophylaxis and febrile morbidity following non-elective Caesarean section were studied retrospectively. Febrile morbidity was found to be 5.4% in the treated group as compared to 20% in the untreated group. Percentage of endomyometritis was 2.2% in the treated group and 16% in the untreated group. Our results prove the efficacy of antibiotic prophylaxis in patients undergoing Caesarean section. Antibiotic application in 79% of all these patients led to a significant reduction in puerperal febrile morbidity and endomyometritis. Experience shows that positive results gained by the study do not have a positive feedback on the ward if there is lack of communication or reconfirmation.

Cefoxitin↗
PubMed1980

Cloning and direct examination of a structurally abnormal human beta 0-thalassemia globin gene.

Restriction endonuclease mapping permitted identification of a form of beta 0-thalassemia in which a partial deletion of the beta-globin structural gene occurred [Orkin, S. H., Old, J. M., Weatherall, D. J. & Nathan, D. G. (1979) Proc. Natil. Acad. Sci. USA 76, 2400-2404]. To analyze its structure more directly, this abnormal human gene has now been cloned in bacteriophage lambda gtWES. Restriction mapping of the cloned gene and of a normal beta-globin gene contained in the phage H beta G1 confirmed previous findings regarding the presence of a deletion toward the 3' end of the gene but could not establish its position more accurately. Electron microscopy of the hybrid of the beta-thalassemia gene with globin RNA (R-loop analysis) provided unequivocal evidence for a deletion with the beta-globin structural gene. Hybridization of restriction fragments of the mutant gene with homologous fragments of H beta G1 (heteroduplex analysis) revealed a continuous, internal deletion of about 0.6 kilobase of DNA in the mutant gene and permitted its localization within the beta-globin gene region. This deletion removed the terminal third of the large intervening sequence within the beta-globin gene, the entire 3' coding block (extending from codon 105 to the end of the gene), and approximately 150 base pairs of DNA past the end of the normal globin gene.

Bacteriophage lambda↗