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PubMed2001

Significant augmentation of pro-apoptotic gene therapy by pharmacologic bcl-xl down-regulation in mesothelioma.

The ratio of pro-apoptotic (PAP) and anti-apoptotic (AAP) bcl-2 proteins is important in apoptosis regulation. We sought to determine if inhibition of the AAP bcl-xl by sodium butyrate (SB) would augment apoptotic cellular death in mesothelioma when combined with adenoviral pro-apoptotic gene therapy (PAGT) by simultaneously increasing PAP and decreasing AAP in these cells. Human mesothelioma cell lines were exposed to AdBax, AdBak, Adp53, and SB alone as well as all vectors combined with SB at varying doses and time points. Cell death was assessed, and apoptosis evaluated by morphology and FACS. Isobologram analysis evaluated additive or synergistic effect. Cellular death and apoptosis were augmented by PAGT/SB combinations compared to monotherapy. Following AdBax/SB and AdBak/SB, a decrease of the AAP bcl-xl was noted in combination with increases in PAP bax and bak. By isobologram analysis, additive or synergistic cell killing was noted with both combinations. SB treatment did not significantly augment cell killing or apoptosis in combination with Adp53. PAGT/SB was more effective than monotherapy in induction of apoptotic cell death. Synergy may be due to the ability of SB to decrease bcl-xl with marked increases in PAP engendered by PAGT. Combination therapy with agents that down-regulate AAP in addition to PAGT may prove useful clinically.

Adenoviridae↗
PubMed2002

Comparison of clinical optic disc assessment with tests of early visual field loss.

PURPOSE: Clinical optic disc assessment may identify glaucomatous optic neuropathy prior to a patient developing visual field abnormalities on achromatic automated peri-metry (AAP). Tests targeting axons that are selectively damaged or whose redundancy is low, such as short wavelength automated perimetry (SWAP) and frequency doubling perimetry (FDP), may detect visual field loss before it is seen on AAP. This study investigated whether patients in whom characteristic glaucomatous optic disc damage was present without AAP abnormalities had visual field abnormalities with SWAP and FDP. METHODS: A sample of patients (n = 50) with ocular hypertension (normal AAP) were selected, who had SWAP, FDP and stereofundus photography performed. The photographs were then analysed by two glaucoma subspecialists who were masked to the assessments of the other and to the patients' SWAP and FDP results. A categorization of the optic discs was made as either normal or abnormal and this was compared with their SWAP and FDP findings. RESULTS: On comparing SWAP and FDP with clinical optic disc assessment as the 'gold standard', the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 33%, 92%, 57% and 81%, respectively, for SWAP and 25%, 89%, 49% and 79%, respectively, for FDP. CONCLUSION: In glaucoma suspects, the study suggests that SWAP and FDP identify subjects with early glaucomatous optic neuropathy missed by AAP.

False Positive Reactions↗
PubMed2001

Modulation of high-affinity IgE receptor expression in blood monocytes: opposite effect of IL-4 and glucocorticoids.

BACKGROUND: The expression of high-affinity IgE receptor (Fc epsilon RI) is increased in blood monocytes (BMs) from allergic patients compared with those of nonatopic subjects (NASs). OBJECTIVE: We investigated the in vitro effect of cytokines involved in allergic diseases on the modulation of Fc epsilon RI expression in BMs from allergic asthmatic patients (AAPs) and NASs. The influence of in vitro and in vivo treatments with glucocorticoids (GCs) was also assessed. METHODS: Fc epsilon RI alpha-chain expression on BMs evaluated by flow cytometry analysis was studied ex vivo in AAPs treated or not with GCs and in NASs. IgE receptor expression was also evaluated in vitro with or without stimulation by IL-4, IL-13, GM-CSF, and/or GCs. Messenger (m)RNA expression was also analyzed with RT-PCR. RESULTS: The expression of the Fc epsilon RI alpha chain was significantly increased in BMs from untreated patients, with AAPs compared with NASs (P <.05). In steroid-treated AAPs Fc epsilon RI alpha-chain expression returned to the level found in BMs from NASs. In vitro addition of IL-4 induced a dose-dependent increase in Fc epsilon RI alpha-chain expression on BMs from NASs, and this effect was significantly enhanced with BMs from AAPs. Fc epsilon RI alpha-chain mRNA was significantly upregulated by IL-4, whereas the beta chain was always undetectable. The gamma chain was not modulated by IL-4. Similar findings were obtained with IL-13. In contrast with CD23 expression, GM-CSF alone or in coincubation with IL-4 had no effect on Fc epsilon RI alpha-chain expression in BMs. Lastly, GCs significantly inhibited in vitro the IL-4-induced Fc epsilon RI alpha-chain expression (P <.05). CONCLUSION: Two different pathways by which Fc epsilon RI alpha-chain expression was modulated in BMs were identified: (1) the enhancing effect of IL-4 and IL-13 and (2) the inhibitory effect of GCs. Modulation of Fc epsilon RI alpha-chain expression on BMs may affect their capacity to regulate allergic inflammation.

Asthma↗
PubMed1977

Probing of beta-adrenergic receptors by novel fluorescent beta-adrenergic blockers.

The synthesis of two high-affinity fluorescent beta-adrenergic blockers is described: dl-N(1)-[2-hydroxy-3-(1-naphthyloxy)propyl]-N(2)-(9-acridyl)-1,2-propanediamine (9-aminoacridylpropanolol, 9-AAP) and dl-N-[2-hydroxy-3-(1-naphthyloxy)propyl]-N'-dansylethylenediamine (dansyl analogue of propranolol, DAPN). Both 9-AAP and DAPN inhibit competitively the l-epinephrine-dependent adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] in turkey erythrocyte membranes without affecting the fluoride-stimulated adenylate cyclase activity. Similarly, 9-AAP and DAPN inhibit in a competitive manner the binding of [(125)I]-iodohydroxybenzylpindolol to these beta-adrenergic receptors. The two fluorescent beta-adrenergic blockers 9-AAP and DAPN probe specifically beta-adrenergic receptors in the central nervous system as well as in other organs when injected into rats. The fluorescence pattern can be monitored by fluorescence microscopy performed on cryostat slices of these organs. The appearance of the characteristic fluorescence pattern can be blocked in a stereospecific fashion by a prior injection of l-propranolol and not by a prior injection of d-propranolol. These compounds therefore offer a powerful means to map beta-adrenergic receptors in vivo. The stereospecific displacement of 9-AAP from the beta-adrenergic receptors of turkey erythrocyte membranes by l-propranolol and by l-epinephrine can be detected in vitro using front-face fluorescence. The potential use of these compounds to probe beta-receptors in vitro and in vivo is discussed.

Adenylyl Cyclase Inhibitors↗
PubMed1982

Cell-specific differences in O6-alkylguanine DNA repair activity during continuous exposure to carcinogen.

The activity of the alkyl acceptor protein (AAP) responsible for repair of DNA containing the promutagenic lesion O6-alkylguanine was determined in hepatocytes and nonparenchymal cells (NPC) obtained from livers of control rats and rats exposed to hepatocarcinogens that primarily induce vascular or hepatocellular neoplasms. Basal levels of AAP activity were found to be 4-5 times higher in hepatocytes than in NPC. Exposure to 1,2-dimethylhydrazine or diethylnitrosamine produced a 2- to 3-fold enhancement of this activity in hepatocytes after exposure for as little as 3 days. The enhanced hepatocyte activity persisted throughout a 28-day exposure to 1,2-dimethylhydrazine. In contrast, AAP activity in NPC was decreased during the first week of exposure to 1,2-dimethylhydrazine and subsequently returned to control levels. No enhancement of AAP was apparent in the NPC. These and related data suggest that enhancement of this activity in rat hepatocytes is a response to cell proliferation. In contrast, the data clearly demonstrate that neither increased cell replication nor the presence of O6-alkylguanine was capable of enhancing AAP activity in NPC. Cellular differences in the repair of O6-alkylguanine appear to be a critical mechanism responsible for cell specificity in chemical carcinogenesis by alkylating agents.

1,2-Dimethylhydrazine↗
PubMed2002

Insulin receptor substrate and p55 orthologous adaptor proteins function in the Caenorhabditis elegans daf-2/insulin-like signaling pathway.

An insulin-like signaling pathway regulates development and lifespan in Caenorhabditis elegans. Genetic screens that identified many components of the C. elegans insulin pathway did not identify homologs of insulin receptor substrates or the phosphoinositide 3-kinase (PI3K) adaptor/regulatory subunit, which are both required for signaling by mammalian insulin/insulin-like growth factor I pathways. The C. elegans genome contains one homolog of each protein. The C. elegans versions of insulin receptor substrate (IST-1) and PI3K p50/p55 (AAP-1) share moderate sequence similarity with their vertebrate and Drosophila counterparts. Genetic experiments show that ist-1 and aap-1 potentiate C. elegans insulin-like signaling, although they are not required for signaling in the pathway under most conditions. Worms lacking AAP-1 activity because of the mutation aap-1(m889) constitutively arrest development at the dauer larval stage when raised at high temperatures. aap-1 mutants also live longer than wild-type animals, a phenotype observed in other C. elegans mutants with defects in DAF-2 signaling. Interestingly, IST-1 appears to be required for signaling through a pathway that may act in parallel to AGE-1/PI3K.

Amino Acid Sequence↗
PubMed1993

Cholesterol screening in children: should obesity be a risk factor?

To determine whether obesity should be added to the current American Academy of Pediatrics (AAP) criteria for cholesterol screening in childhood, the charts of 99 children referred for evaluation of either hypercholesterolemia (n = 53) or obesity (n = 45) were reviewed. Compared with obese children, nonobese hypercholesterolemic subjects were younger (8.4 vs 11.4 years) and had lower mean body mass index and % ideal body weight. Frequency of elevated (> 90th percentile for age) total and low-density lipoprotein cholesterols were similar in both groups. Fifty-three of 65 children who met the current AAP criteria were hypercholesterolemic, however, 23/76 hypercholesterolemic children failed to satisfy these screening criteria. Thirty-six of 45 obese children had cholesterol levels > 90th percentile, suggesting increased risk for hypercholesterolemia in this group. If obesity was added to the AAP criteria, 66/80 hypercholesterolemic subjects would have been identified. These modified criteria, vs AAP standards, significantly improved both their sensitivity (70 vs 87%, p < 0.02) and negative predictive value (45 vs 30%, p < 0.02). Pending further studies in larger pediatric populations, these data indicate that obesity should be considered a risk factor for hypercholesterolemia in childhood, and we recommend modifying the AAP screening criteria to include obese children.

Body Mass Index↗
PubMed2005

A randomized comparison of artesunate-atovaquone-proguanil versus quinine in treatment for uncomplicated falciparum malaria during pregnancy.

BACKGROUND: There is no safe, practical, and effective treatment for pregnant women infected with multidrug-resistant Plasmodium falciparum. METHODS: We recruited pregnant Karen women in the second or third trimesters of pregnancy who had uncomplicated falciparum malaria for a randomized, open-label trial with a restricted sequential trial design of 7 days of supervised quinine (SQ7) versus 3 days of artesunate-atovaquone-proguanil (AAP). RESULTS: Eight-one pregnant women entered the study between December 2001 and July 2003; 42 were treated with SQ7 and 39 were treated with AAP. Fever, parasite clearance, and duration of anemia were significantly better with AAP; the treatment failure rate was 7 times lower (5% [2/39] vs. 37% [15/41]; relative risk, 7.1 [95% confidence interval, 1.7-29.2]; P = .001). There were no significant differences in birth weight, duration of gestation, or congenital abnormality rates in newborns or in growth and developmental parameters of infants monitored for 1 year. CONCLUSION: AAP is a well-tolerated, effective, practical, but expensive treatment for multidrug-resistant falciparum malaria during the second or third trimesters of pregnancy. Despite the small number of subjects, our results add to the growing body of evidence that AAP is safe for the mother and the fetus.

Adolescent↗
PubMed1999

Shr3p mediates specific COPII coatomer-cargo interactions required for the packaging of amino acid permeases into ER-derived transport vesicles.

The SHR3 gene of Saccharomyces cerevisiae encodes an integral membrane component of the endoplasmic reticulum (ER) with four membrane-spanning segments and a hydrophilic, cytoplasmically oriented carboxyl-terminal domain. Mutations in SHR3 specifically impede the transport of all 18 members of the amino acid permease (aap) gene family away from the ER. Shr3p does not itself exit the ER. Aaps fully integrate into the ER membrane and fold properly independently of Shr3p. Shr3p physically associates with the general aap Gap1p but not Sec61p, Gal2p, or Pma1p in a complex that can be purified from N-dodecylmaltoside-solubilized membranes. Pulse-chase experiments indicate that the Shr3p-Gap1p association is transient, a reflection of the exit of Gap1p from the ER. The ER-derived vesicle COPII coatomer components Sec13p, Sec23p, Sec24p, and Sec31p but not Sar1p bind Shr3p via interactions with its carboxyl-terminal domain. The mutant shr3-23p, a nonfunctional membrane-associated protein, is unable to associate with aaps but retains the capacity to bind COPII components. The overexpression of either Shr3p or shr3-23p partially suppresses the temperature-sensitive sec12-1 allele. These results are consistent with a model in which Shr3p acts as a packaging chaperone that initiates ER-derived transport vesicle formation in the proximity of aaps by facilitating the membrane association and assembly of COPII coatomer components.

Amino Acid Transport Systems↗
PubMed1991

L-ascorbyl-2-monophosphate has equal antiscorbutic activity as L-ascorbic acid but L-ascorbyl-2-sulfate is inferior to L-ascorbic acid for channel catfish.

Channel catfish (Ictalurus punctatus) fingerlings (13 g average initial weight) were fed semipurified diets supplemented with 0, 0.06, 0.12, 0.24 and 0.72 mmol/kg (0, 11, 22, 44 or 132 mg/kg) of ascorbic acid molar equivalent supplied by either L-ascorbic acid, L-ascorbyl-2-monophosphate (Mg salt) (AAP), or L-ascorbyl-2-sulfate (K salt) (AAS). After 14 wk, weight gains were equal for all fish fed diets containing L-ascorbic acid or AAP; however, growth rates were less for fish fed AAS at all dietary levels and for fish fed the ascorbic acid-free diet (control). There were no gross signs of vitamin C deficiency in any of the fish fed L-ascorbic acid or AAP, whereas spinal deformities were found in the controls and in fish fed all but the highest concentration of AAS. The percentage of spinal deformities decreased as dietary levels of AAS increased. Reduced bone collagen content and histopathology in liver and gill tissues also indicated ascorbic acid deficiency in the controls and in fish fed all but the highest concentration of AAS. Limited histopathology was found in fish fed the lowest level of L-ascorbic acid but not in those fed the lowest level of AAP. Regression analysis of weight gain data showed that the vitamin activity of ascorbic acid from AAS was only 5.2% of that from L-ascorbic acid for growth. This study indicates that AAP has equimolar activity to L-ascorbic acid as a vitamin C source for channel catfish and that AAS has vitamin activity for this species but at a much lower level than the other compounds.

Administration, Oral↗
PubMed2006

Nuclear translocation of endonuclease G and apoptosis-inducing factor during acetaminophen-induced liver cell injury.

Mitochondrial dysfunction and internucleosomal DNA fragmentation are well-recognized features of acetaminophen (AAP)-induced hepatocyte cell death. However, the endonucleases responsible for this effect have not been identified. Apoptosis-inducing factor (AIF) and endonuclease G are nucleases located in the intermembrane space of mitochondria. AIF is thought to trigger chromatin condensation and induce cleavage of DNA into high molecular weight fragments (50-300 kb), and endonuclease G can produce oligonucleosomal DNA fragments. Therefore, the objective of this investigation was to test the hypothesis that endonuclease G and AIF could be involved in AAP-induced nuclear DNA fragmentation. Using immunofluorescence microscopy, it was shown that in primary cultured mouse hepatocytes, endonuclease G and AIF translocated to the nucleus between 3 and 6 h after exposure to 5 mM AAP. In contrast, other mitochondrial intermembrane proteins such as cytochrome c or the second mitochondria-derived activator of caspases (Smac) did not accumulate in the nucleus. The translocation of AIF and endonuclease G correlated with mitochondrial dysfunction as indicated by the progressive loss of the mitochondrial membrane potential (measured with the JC-1 assay) and the appearance of nuclear DNA fragments in the cytosol (determined by an anti-histone ELISA). Pretreatment with 20mM N-acetylcysteine prevented mitochondrial dysfunction, the nuclear translocation of endonuclease G and AIF, and the nuclear DNA fragmentation. The data support the conclusion that endonuclease G and AIF translocate to the nucleus in response to AAP-induced mitochondrial dysfunction and may be responsible, at least in part, for the initial DNA fragmentation during AAP hepatotoxicity.

Acetaminophen↗
PubMed2005

Interactions of alcohol dehydrogenase to p-hydroxyacetophenone-sepharose and p-acetamidophenol-sepharose.

BACKGROUND: p-Hydroxyacetophenone (HAP)-sepharose is known to be an effective ligand for isolation of aldehyde dehydrogenase and chloramphenicol acetyltransferase. In this study, we investigated ligand specificities to alcohol dehydrogenase (ADH) using p-HAP-sepharose and p-acetamidophenol (AAP)-sepharose. METHODS: p-HAP and p-AAP were coupled to epoxy-activated sepharose and used as ligands for affinity chromatography to detect binding proteins. Fractions of affinity chromatography were collected and separated by SDS-PAGE. Commassie brilliant blue staining was carried out for detecting proteins. For determining protein sequences, polypeptide was separated by HPLC after cleavage of Lys-specific protease digestion. RESULTS: p-HAP ligands have the ability to bind to seven proteins, including class I ADH extracted from a rat cytosolic fraction as well as HLADH (horse liver ADH). p-HAP, p-AAP and benzaldehyde (10 mM each) could elute HLADH from the complex of HLADH-pHAP-sepharose column. On the other hand, p-AAP-sepharose has no ability to bind to HLADH, although three proteins from a rat liver cytosolic fraction were found to be able to bind to p-AAP-sepharose. CONCLUSIONS: p-HAP binds to ADH in a structure-specific manner and this binding is nonspecific to species of origin of ADH.

Acetaminophen↗
PubMed2006

The effect of an interventional program on adherence to the american academy of pediatrics guidelines for palivizumab prophylaxis.

OBJECTIVE: To determine the effect of an interventional program designed to improve adherence to American Academy of Pediatrics (AAP) guidelines for palivizumab prophylaxis. METHODS: The study was carried out at the Children's Hospital, University of California, Irvine Medical Center and its affiliated clinics. An interventional program focusing on education of health care workers on AAP guidelines, updating health care providers about respiratory syncytial virus (RSV) activity, as well as designating a single clinic with effective screening of referrals for administration of palivizumab, was implemented during the summer of 2004. The medical records of infants who had received at least 1 dose of palivizumab or were eligible to receive palivizumab during the 2003-2004 and the 2004-2005 RSV seasons at the University of California, Irvine Medical Center were reviewed. The proportion of patients who received injections according to AAP guidelines was compared. RESULTS: After the intervention, the proportion of patients who received palivizumab injections according to AAP recommendations increased from 39% to 61% (P < 0.0001). The program decreased the proportion of unnecessary injections significantly (140/525, or 27%, in 2003-2004 to 33/323, or 10%, in 2004-2005; P < 0.0001) but did not change the proportion of missing injections. The program resulted in a significant drop (14% to 2%; P < 0.0001) in proportion of palivizumab injections that were given too late, when RSV activity had subsided. RSV hospitalization rates did not change as a result of the intervention. CONCLUSIONS: Our interventional program improved adherence to AAP guidelines mainly by decreasing the unnecessary palivizumab injections.

Antibodies, Monoclonal↗
PubMed2005

Response rates and response bias for 50 surveys of pediatricians.

RESEARCH OBJECTIVE: To track response rates across time for surveys of pediatricians, to explore whether response bias is present for these surveys, and to examine whether response bias increases with lower response rates. DATA SOURCE/STUDY SETTING: A total of 63,473 cases were gathered from 50 different surveys of pediatricians conducted by the American Academy of Pediatrics (AAP) since 1994. Thirty-one surveys targeted active U.S. members of the AAP, six targeted pediatric residents, and the remaining 13 targeted AAP-member and nonmember pediatric subspecialists. Information for the full target samples, including nonrespondents, was collected using administrative databases of the AAP and the American Board of Pediatrics. STUDY DESIGN: To assess bias for each survey, age, gender, location, and AAP membership type were compared for respondents and the full target sample. Correlational analyses were conducted to examine whether surveys with lower response rates had increasing levels of response bias. PRINCIPAL FINDINGS: Response rates to the 50 surveys examined declined significantly across survey years (1994-2002). Response rates ranged from 52 to 81 percent with an average of 68 percent. Comparisons between respondents and the full target samples showed the respondent group to be younger, to have more females, and to have less specialty-fellow members. Response bias was not apparent for pediatricians' geographical location. The average response bias, however, was fairly small for all factors: age (0.45 years younger), gender (1.4 percentage points more females), and membership type (1.1 percentage points fewer specialty-fellow members). Gender response bias was found to be inversely associated with survey response rates (r=-0.38). Even for the surveys with the lowest response rates, amount of response bias never exceeded 5 percentage points for gender, 3 years for age, or 3 percent for membership type. CONCLUSIONS: While response biases favoring women, young physicians, and nonspecialty-fellow members were found across the 52-81 percent response rates examined in this study, the amount of bias was minimal for these factors that could be tested. At least for surveys of pediatricians, more attention should be devoted by investigators to assessments of response bias rather than relying on response rates as a proxy of response bias.

Adult↗
PubMed1997

The general amino acid permease of Rhizobium leguminosarum strain 3841 is negatively regulated by the Ntr system.

Cosmid-borne and chromosomal lacZ fusions to aapJ. aapQ and aapM were used to examine the nitrogen regulation of the general amino acid permease (Aap) of Rhizobium leguminosarum strain 3841. Transcription of the first gene of the operon (aapJ), which encodes the periplasmic binding protein, was 2-4-fold higher than aapQ and aapM, which encode the integral membrane proteins, under various growth conditions. This may be due to the presence of a putative stem loop in the intergenic region between aapJ and aapQ. All aap fusions were derepressed 3-5-fold after growth on glutamate as a nitrogen source, which effectively causes nitrogen limitation. An ntrC mutant was derepressed for transcription of the aap operon and had high rates of amino acid transport when grown on ammonia as the nitrogen source. Thus NtrC negatively regulates the aap operon, contrary to its usual role in positive gene activation. These results confirm that the aap-operon is subject to complex regulation involving both transcriptional and post-transcriptional factors.

Amino Acid Transport Systems↗
PubMed2004

Novel haloperoxidase from the agaric basidiomycete Agrocybe aegerita oxidizes aryl alcohols and aldehydes.

Agrocybe aegerita, a bark mulch- and wood-colonizing basidiomycete, was found to produce a peroxidase (AaP) that oxidizes aryl alcohols, such as veratryl and benzyl alcohols, into the corresponding aldehydes and then into benzoic acids. The enzyme also catalyzed the oxidation of typical peroxidase substrates, such as 2,6-dimethoxyphenol (DMP) or 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS). A. aegerita peroxidase production depended on the concentration of organic nitrogen in the medium, and highest enzyme levels were detected in the presence of soybean meal. Two fractions of the enzyme, AaP I and AaP II, which had identical molecular masses (46 kDa) and isoelectric points of 4.6 to 5.4 and 4.9 to 5.6, respectively (corresponding to six different isoforms), were identified after several steps of purification, including anion- and cation-exchange chromatography. The optimum pH for the oxidation of aryl alcohols was found to be around 7, and the enzyme required relatively high concentrations of H(2)O(2) (2 mM) for optimum activity. The apparent K(m) values for ABTS, DMP, benzyl alcohol, veratryl alcohol, and H(2)O(2) were 37, 298, 1,001, 2,367 and 1,313 microM, respectively. The N-terminal amino acid sequences of the main AaP II spots blotted after two-dimensional gel electrophoresis were almost identical and exhibited almost no homology to the sequences of other peroxidases from basidiomycetes, but they shared the first three amino acids, as well as two additional amino acids, with the heme chloroperoxidase (CPO) from the ascomycete Caldariomyces fumago. This finding is consistent with the fact that AaP halogenates monochlorodimedone, the specific substrate of CPO. The existence of haloperoxidases in basidiomycetous fungi may be of general significance for the natural formation of chlorinated organic compounds in forest soils.

Agaricales↗
PubMed1988

Pleural pressure between diaphragm and rib cage during inspiratory muscle activity.

We measured the changes in pleural surface pressure (delta Ppl) in the area of apposition of the rib cage to the diaphragm (Aap) in anesthetized dogs during spontaneous breathing, inspiratory efforts after airway occlusion at functional residual capacity, and phrenic stimulation. Intact dogs were in supine or lateral posture; partially eviscerated dogs were in lateral posture. delta Ppl,ap often differed significantly from changes in abdominal pressure (delta Pab); sometimes they differed in sign (except during phrenic stimulation). Changes in transdiaphragmatic pressure in Aap (delta Pdi,ap) could be positive or negative and were less in eviscerated than in intact dogs. delta Pdi,ap could differ in sign among respiratory maneuvers and over different parts of Aap. Hence average delta Pdi,ap should be closer to zero than delta Pdi,ap at a given site. Since delta Ppl,ap = delta Prc,ap, where Prc,ap represents rib cage pressure in Aap, delta Pdi,ap = delta Pab - delta Prc,ap. Hence, considering that delta Pab and delta Prc depend on different factors, delta Pdi,ap may differ from zero. This pressure difference seems related to the interaction between two semisolid structures (contracted diaphragm and rib cage in Aap) constrained to the same shape and position.

Animals↗
PubMed2001

Atherosclerotic aortic arch plaques in cryptogenic stroke: a microembolic signal monitoring study.

BACKGROUND AND PURPOSE: To find out the prevalence of relevant atherosclerotic plaques in the aortic arch and their potential role as a source of embolism in cryptogenic stroke. METHODS: We performed a transoesophageal echocardiography (TEE) on 49 patients with cryptogenic stroke from a total series of 212 non-selected patients with acute ischaemic stroke studied prospectively by cranial computed tomography (CT), colour-duplex and transcranial Doppler (TCD) sonography with micro-embolic signal (MES) monitoring. Cryptogenic stroke was diagnosed in those patients without carotid or intracranial stenosis > 50%, nor lacunar or cardio-embolic strokes. We defined relevant plaques as those > or = 4 mm thick located in the ascending aorta or proximal arch. RESULTS: Twenty-three patients (46.9%) had atherosclerotic aortic plaques (AAP): 3 in the ascending aorta (in 1 > or = 4 mm), 11 in the proximal aortic arch (in 4 > or = 4 mm) and 9 in the descending aorta (in 5 > or = 4 mm). Hence, 5 patients (10.2%) had relevant plaques. Aortic plaques were significantly related to older age (p < 0.001) and male gender (p = 0.042). A carotid artery stenosis < 50% was found in 39% of patients with AAP and in 8% of those without AAP (p = 0.009). MES were detected in 3 patients with plaques > or = 4 mm thick, but not in those without AAP or with AAP < 4 mm thick (p = 0.006). CONCLUSION: Although few patients with cryptogenic stroke had relevant plaques in our non-selected population, our results support the hypothesis that relevant aortic plaques have embolic potential.

Aged↗