Quantitative thallium-201 scintigraphy after dipyridamole infusion combined with low level exercise in healthy volunteers

To establish test specific normal limits for quantitative analysis of uptake and washout of ²⁰¹Tl after dipyridamole infusion combined with low level exercise, 20 healthy volunteers were studied with low likelihood of coronary artery disease (CAD) assessed by a stepwise probability analysis based on age, sex, symptoms, resting electrocardiogram, and exercise electrocardiography. Likelihood of CAD in these volunteers was calculated as 1%. After dipyridamole infusion combined with low level exercise, one volunteer complained of headache; no other side effects were observed. There were no chest pain complaints. Maximal hemodynamic changes were achieved during the 6th and 7th min of the test. No ST segment depression was recorded. Visual analysis of the ²⁰¹Tl scintigrams was normal in all volunteers. Mean regional washout at 4 h was 44.37%±2.11%. The regional washout in the 70° LAO view (46.65%±1.10%) was significantly higher than in the anterior and 30° LAO views (43.44%±1.50% and 43.02%±1.45%, respectively). Profiles of uptake and washout of ²⁰¹Tl were different after dipyridamole infusion combined with low level exercise as compared to maximal exercise. Thus, in quantitative analysis of ²⁰¹Tl scintigraphy after dipyridamole infusion in conjunction with low level exercise as applied in the present study, it is mandatory to use normal limits of uptake and washout of ²⁰¹Tl derived from healthy volunteers who underwent the same combined protocol.     

Anaesthetic experience with paediatric interventional cardiology

Anaesthetic and sedation techniques, complications and outcomes were reviewed in 176 children undergoing 184 interventional cardiologic procedures. Techniques included sedation only, and ketamine, inhalational or narcotic anaesthesia. Ketamine infusion was the technique most frequently used. Ketamine was associated with a higher incidence of respiratory complications (P < 0.05) than the other techniques. The higher incidence of hypercarbia (15.6 per cent), which did not affect outcome, may be attributable to the use of supplemental sedatives. The incidence of upper airway obstruction (7.8 per cent) was similar to that of previous studies. Vascular compromise resulted from the procedure in 33 patients, necessitating surgical correction in 16. Cardiac perforation occurred in four cases, causing one death. Pulmonary valve stenosis was most amenable to balloon dilatation and aortic valve stenosis least amenable. Ketamine was the anaesthetic agent preferred by cardiologists for use in the catheterisation suite when general anaesthesia was required. Vigilant monitoring by anaesthetic staff is necessary during the procedure, and avoidance of concomitant narcotics is recommended if a ketamine technique with spontaneous ventilation is used. Les techniques anesthésiques et de sédation ainsi que les complications et les issues ont été revues chez 176 enfants subissant 184 procedures cardiaques. Les techniques ont inctu soil la sédation seulement, soit l’anesthésie à la kétamine, aux agents d’inhalation ou aux narcotiques. La perfusion de kétamine était la technique la plus fréquemment utilisée. La ketamine était associée à une plus grande incidence de complication respiratoire (P < 0.05) comparativement aux autres techniques. La plus grande incidence d’hypercarbie (15.6 pour cent), n’ayant pas affecté l’issue, pourrait être attribuée à l’utilisation additionnelle de sédatifs. L’incidence d’obstruction des voies aériennes supérieures (7.8 pour cent) était similaire aux études préalables. Un problème vasculaire suite à la procédure fut observé chez 33 patients dont 16 ont requis une correction chirurgicale. Une perforation cardiaque est survenue dans quatre cas provoquant le décès d’un seul patient. La sténose de la valve pulmonaire était la procédure la plus susceptible d’être dilatée et la sténose de la valve aortique la moins susceptible. La kétamine était l’agent anesthésique préféré par les cardiologistes lors des cathétérisations quand une anesthésie générate était requise. Une surveillance vigilante par une équipe anesthésique fut nécessaire durant la procedure. Il faut aussi éviter l’administration de narcotiques si la kétamine est administrée en respiration spontanée.

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Presented in part at the Canadian Anaesthetists’ Society annual meeting in Halifax, June 1988.     

The effects of atrazine on microcosms developed from four natural plankton communities

Comparisons were made among Leffler microcosms developed from four different natural communities and exposed to 0, 20, 100, 200, 500, 1,000, and 5,000 g/L atrazine, a commonly used herbicide. Atrazine reduced net primary productivity, pH, and net productivity/respiration ratios in all four microcosm communities. In three of the four communities, the lowest observed (P < 0.05) effect concentration (LOEL) was 100 g/L. In the fourth community the LOEL was 200 g/L atrazine.The sensitivity and accuracy of bioassays with four different microcosm communities were evaluated by comparing results with values reported for acute and chronic single species bioassays, other types of microcosms, and experimental ponds exposed to similar concentrations of atrazine. The ranges of sensitivity noted in these experiments were less than the range reported for single species bioassays using common test organisms and similar to those reported for other microcosms. The similarity between Leffler microcosm results and the responses reported for the experimental ponds suggests that the Leffler microcosms accurately reflected concentrations causing ecosystem level changes in the experimental ponds.     

Relating cell and tissue mechanics: Implications and applications

The Differential Adhesion Hypothesis (DAH) posits that differences in adhesion provide the driving force for morphogenetic processes. A manifestation of differential adhesion is tissue liquidity and a measure for it is tissue surface tension. In terms of this property, DAH correctly predicts global developmental tissue patterns. However, it provides little information on how these patterns arise from the movement and shape changes of cells. We provide strong qualitative and quantitative support for tissue liquidity both in true developmental context and in vitro assays. We follow the movement and characteristic shape changes of individual cells in the course of specific tissue rearrangements leading to liquid-like configurations. Finally, we relate the measurable tissue-liquid properties to molecular entities, whose direct determination under realistic three-dimensional culture conditions is not possible. Our findings confirm the usefulness of tissue liquidity and provide the scientific underpinning for a novel tissue engineering technology. Developmental Dynamics 237:2438-2449, 2008. (c) 2008 Wiley-Liss, Inc.     

Association of human leucocyte low responsiveness to inducers of interferon alpha with HLA-DR 2

The influence of antigens of the major histocompatibility complex (MHC) on the production of interferon (IFN) alpha or IFN gamma by human peripheral blood leucocytes (PBL) in vitro has been studied. Synthesis of IFN gamma by PBL stimulated with purified phytohaemagglutinin (PHA-P) or protein A of Staphylococcus aureus (SpA) appeared not to be controlled by MHC antigens. The production of IFN alpha, however, was influenced by the HLA type of the donor. Low responsiveness of PBL to inducers of IFN alpha (influenza virus, Molt 4 cells) was associated with HLA-DR 2. Implications of these observations for studies of IFN production and natural killer (NK) cell activity are discussed.     

Characterization of DR blank alleles by restriction fragment length polymorphism (RFLP)

Using a combination of conventional DR serology and RFLP analysis of DR beta and DQ beta, we have been able to identify two different types of DR antigens which belong so far to the DR blank group. The antigen DR-LOT is found on a haplotype A29, Bw60, Cw3, DRblank, DRw52, DQw1. The DR beta-EcoRI RFLP pattern of this haplotype is different from the patterns observed for DR1, DR2, DR3, DR4, DR5, DRw6, DR7, DRw8, DRw9, DRw10, and appears to be composed of a combination of DR2 and DRw6. The DQ beta-EcoRI pattern shows that this haplotype carries the DQw1 split DQR2.6. The second DR blank antigen which we found in a total of five individuals (three unrelated persons and two parents) on B35 positive haplotypes is characterized by a DR beta-EcoRI RFLP pattern indistinguishable from DR1 and by negative reaction with anti-DR1 sera. This antigen appears to be identical to what has been described by Cambon-Thomsen et al. (1986) and Bidwell et al. (1985) as HLA-DR-BON and DR"BR" respectively. We have demonstrated that this antigen is in strong linkage disequilibrium with the DQw1 split DQR1.     

Analysis of very long-chain fatty acids using electrospray ionization mass spectrometry

Elevated levels of very long-chain fatty acids (VLCFA) in plasma and tissues are the biochemical hallmark for patients with X-linked adrenoleukodystrophy (X-ALD). Current methods for the determination of VLCFA levels are laborious and time-consuming. We describe a rapid and easy method using electrospray ionization mass spectrometry (ESI-MS) with deuterated internal standards. VLCFA are hydrolyzed, extracted, and quantified in less than 4h. This includes 2h of hydrolysis and 4min of quantification. We validated the method by analyzing 60 plasma samples from controls and patients with X-ALD or Zellweger syndrome using both the ESI-MS protocol and an established method for VLCFA analysis using gas chromatography (GC). The C26:0 concentrations determined with ESI-MS in plasma and fibroblasts of X-ALD patients are in good agreement with those reported previously for GC and GC-MS. Besides saturated straight chain VLCFA, we also determined the concentrations of the mono-unsaturated VLCFA C24:1 and C26:1 and established that while C24:1 levels are not elevated, C26:1 levels are elevated in both plasma and fibroblasts from X-ALD patients.     

No association between the Pro197Leu polymorphism in the glutathione peroxidase (GPX1) gene and schizophrenia

OBJECTIVE: Oxidative stress such as free radical-mediated neuronal dysfunction may be involved in the pathophysiology of schizophrenia. The human glutathione peroxidase (GPX1) is a selenium-dependent enzyme, which plays an important role in the detoxification of free radicals. We therefore hypothesized that the GPX1 gene, which is located on chromosome 3p21.3, may be involved in the pathophysiology of schizophrenia. The aim of this study is to examine whether a potentially functional polymorphism, a proline (Pro) to leucine (Leu) substitution at codon 197 (Pro197Leu) of the human GPX1 gene, is associated with susceptibility to schizophrenia. METHODS: We genotyped the Pro197Leu polymorphism in a total of 113 nuclear families that had a proband with schizophrenia. Genetic association was tested using the transmission disequilibrium test (TDT), the sib transmission disequilibrium test (STDT), and the family-based association test (FBAT). RESULTS: The minor allele (Leu) frequency was calculated to be 0.282. We could not find significant transmission disequilibrium of the alleles for the Pro197Leu polymorphism in the GPX1 gene in association with the presence of schizophrenia in our family sample (TDT, chi2=0.03, degrees of freedom=1, P=0.86; combined TDT-STDT, Z'=-0.052, P=0.47; FBAT, Z=0.000, P=1.000). CONCLUSION: The results of this study suggest that the GPX1 polymorphism is unlikely to be associated with susceptibility to schizophrenia.     

Evaluation of hyperforin analogues for inhibition of 5-lipoxygenase

The acylphloroglucinol hyperforin, a constituent of the herb Hypericum perforatum (St. John's wort), was recently identified as potent and direct inhibitor of 5-lipoxygenase (5-LO), the key enzyme in the biosynthesis of proinflammatory leukotrienes. In this study, naturally occurring analogues of hyperforin, isolated from H. perforatum, as well as a series of synthetic derivatives obtained by chemical modification of hyperforin by acylation, alkylation or oxidation, were analysed for the inhibition of 5-LO. The efficacies of these compounds were evaluated in intact human polymorphonuclear leukocytes, but also the inhibitory effects on isolated recombinant human 5-LO were investigated. Our data show that some of the oxidised hyperforin derivatives possess even improved efficacy, whereas alkylation and acylation have detrimental effects.