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Archosaurian respiration and the pelvic girdle aspiration breathing of crocodyliforms.

Birds and crocodylians, the only living archosaurs, are generally believed to employ pelvic girdle movements as a component of their respiratory mechanism. This in turn provides a phylogenetic basis for inferring that extinct archosaurs, including dinosaurs, also used pelvic girdle breathing. I examined lung ventilation through cineradiography (high-speed X-ray filming) and observed that alligators indeed rotate the pubis to increase tidal volume, but did not observe pelvic girdle movement contributing to lung ventilation in guinea fowl, emus or tinamous, despite extensive soft-tissue motion. Re-examination of fossil archosaurs reveals that pubic rotation evolved in basal crocodyliforms and that pelvic girdle breathing is not a general archosaurian mechanism. The appearance of pelvic aspiration in crocodyliforms is a striking example of the ability of amniotes to increase gas exchange or circumvent constraints on respiration through the evolution of novel accessory breathing mechanisms.

Adaptation, Physiological↗

Osteopenia in pregnancy during long-term heparin treatment: a radiological study post partum.

Osteopenia, sometimes with compression fractures of the spine, is a side-effect of long-term heparin treatment. The frequency is unknown. In this study, 70 women were given subcutaneous heparin as therapy for, or prophylaxis against, thromboembolism during pregnancy. All, except two, were examined by X-ray of the spine and hip first week post partum. The duration of treatment and the dosage of heparin varied. There were 12 (17%) with obvious osteopenia, including two women with multiple fractures of the spine (3%). Re-examination 6-12 months post partum showed that the changes were reversible in most cases. Another 18 women were examined about three years after heparin treatment during pregnancy. No obvious osteopenia was found among them or in a control group of 30 women examined in the first week post partum. The degree of osteopenia was not correlated with either the heparin dose or the duration of treatment. Women treated with heparin in consecutive pregnancies do not seem to have an increased risk of osteopenia.

Adult↗

[Further studies on serum calcium and inorganic phosphorus in postmenopause (author's transl)].

The author previously reported that the serum calcium (Ca) and inorganic phosphorus (P) levels were gradually decreased with advance in age in regularly menstruating women, but that they were rapidly increased soon after the menopause. In this experiment the changes of the serum Ca and P levels in postmenopausal women were studied more precisely in 410 peri- or post-menopausal subjects and 534 controls with regular menses. They were classified into 12 groups according to age or period since last menses. The clavicular cortical thickness was also measured as an index of bone resorption. Blood samples were taken between 9-11 A.M. after an overnight fast and the separated sera were applied to a Technicon Autoanalyzer SMA 12/60 and analyzed. The mean levels of Ca and P in serum were both increased following the menopause and reached a plateau in Groups F-3 (12-24 months since last menses) and G (2-5 years since last menses). In Group G (5-10 years since last menses) both the levels were slightly declined. Then a dissociation was observed in Groups I-1 and I-2. This was a successive decrease of Ca and a re-increase of P. This dissociation might be explained partly by the physiologic fall of parathyroid function. Furthermore the clavicular cortical thickness was measured with a micrometer in the middle of the clavicle on the chest X-ray film of the same subjects and the clavicular score was computed as Cortical width X 100/Whole width. The score was gradually but steadily reduced with the lapse of time after the menopause and in Group I-2 it was lowered to approximately 45% of that in the premenopausal groups. From these results it is certain that the decline of estrogen secretion led to the elevation of the serum Ca and P levels and subsequently to the reduction in the clavicular score.

Adult↗

Contrast media radiography in patients with retrosternal irrigation drainage for severe sternal wound infection.

Severe wound infection after open-heart surgery is a potentially life-threatening complication, which is mostly treated by re-operation with debridement, and insertion of closed irrigation drainage. Until now there is no consensus about the appropriate duration of irrigation therapy. Since the retrosternal irrigation cavity is likely to become continually smaller as the infection heals, this study was intended to answer the question, as to whether this process can be made visible by the use of contrast media radiography, and whether this information could be used to determine when an irrigation therapy can safely be discontinued. In 1997, 34 patients suffered from sternal wound healing disturbances which required re-operation at our institution (incidence = 0.97%). During the re-operation, a closed retrosternal irrigation drainage was inserted. Of the 34 patients contrast media radiography examinations were carried out on the first, 4th and 12th postoperative day (POD), which consisted of an antero-posterior x-ray of the chest after contrast media injection through each inlet tube. At POD 4 and 12 in the majority of cases, the retrosternal irrigation cavity became smaller when compared with the previous x-ray examination. Only in three of the non-survivors there was a huge irrigation cavity visible at the 12th POD, which sometimes even included the pleural cavity. We conclude that in patients with mediastinitis treated by insertion of a closed irrigation drainage, the retrosternally irrigated cavity seems to become smaller over the therapeutic course of treatment. This process can be visualized by contrast media radiography. Results from this examination should be included in decision making about the best time for discontinuation of the irrigation therapy.

Anti-Infective Agents, Local↗

Biochemistry of ginseng root tissues affected by rusty root symptoms.

Ginseng rusty root, a disorder of unknown cause (s), in which reddish-brown to orange-brown areas develop on the surface of field-grown roots, was studied at the cellular and biochemical levels. Using light microscopy, the affected areas were shown to comprise of the epidermis and underlying 6-8 cell layers of the cortical tissues. Rusty root areas ranged from small clusters of 3-4 cells to larger expanding areas of >80 cells. These cells appeared golden-brown and stained a bluish-green with Toluidine Blue indicating the presence of phenolic compounds. Energy-dispersive X-ray spectroscopy and atomic emission spectrometry of affected epidermal cells revealed a significant accumulation of Fe, Al, Si, Mg and other cations when compared to adjoining healthy cells. The concentrations of the six most common ginsenosides found in ginseng roots (Rg(1), Re, Rb(1), Rc, Rb(2), and Rd) were reduced by 40-50% in rusty root-affected epidermal and cortical tissues when compared to adjacent healthy tissues. Total phenolic compounds were increased by up to threefold in affected tissues and HPLC analysis revealed significantly higher levels of quercetin, cinnamic acid, vanillic acid, p-coumaric acid, benzoic acid, chlorogenic acid and catechin. In vitro phenolic-metal binding assays confirmed that phenolic compounds were able to sequester positively-charged metal ions, in particular Fe, to form a phenolic-metal ion complex. In ginseng callus cultures, accumulation of phenolic compounds was increased threefold within 12 h of treatment with chitosan (1%), and to a lesser extent by wounding. Specific defense enzymes, namely phenylalanine ammonia-lyase (PAL, E.C. 4. 3. 1. 5.), polyphenoloxidase (PPO, E.C. 1. 10. 3. 1.) and peroxidase (POD, E.C. 1. 11. 1. 7.), were also significantly enhanced in treated callus tissues and in rusty root tissues. On field-grown ginseng roots, application of chitosan induced symptoms similar to rusty root, whereas wounding and ethylene treatments did not. Based on these results, rusty root symptoms on ginseng are proposed to result from an induction of host defense responses, especially phenolic production, in epidermal and underlying cortical cells. This induction is likely due to attempted invasion by as-yet uncharacterized chitin-containing soil fungi, which were observed in many of the affected cells. Subsequent oxidation of phenolic compounds and sequestration of metal ions, in particular Fe, appear to be largely responsible for the symptoms observed.

Cations↗

The benefit of functional-anatomical imaging with [18F]fluorodeoxyglucose utilizing a dual-head coincidence gamma camera with an integrated X-ray transmission system in non-small cell lung cancer.

AIM: To evaluate functional-anatomical imaging with 2-[F]fluoro-2-deoxy-D-glucose (F-FDG) utilizing a dual-head coincidence gamma camera with an integrated X-ray transmission system for attenuation correction, anatomical mapping, and image fusion compared to conventional diagnostics by computed tomography (CT) in non-small cell lung cancer (NSCLC). METHODS: Thirty-five patients with NSCLC underwent FDG imaging of the thoracic area using a dual-head coincidence gamma camera (DHC) with an integrated X-ray transmission system. State-of-the-art CT scans had been performed before. Whole-body dedicated FDG positron emission tomography (PET) was performed immediately prior to DHC. Staging by CT and DHC, and DHC with integrated image fusion (FDHC) were re-evaluated with regard to detectable lesions, correct anatomical diagnoses, and clinical impact. Results of DHC and PET were compared for analysis of limitations of DHC. RESULTS: One hundred and thirteen tumour lesions were identified by CT. DHC detected 128 lesions overall: 102 true positive CT lesions were confirmed, 25 additional lesions were detected which affected staging in eight patients, and one false positive lung lesion did not show up in DHC. Nine CT lesions were missed by DHC (lymph node and lung). PET detected 150 areas of focally enhanced uptake, delivering two false positive results (nuchal muscles, pneumonia). Final evaluation confirmed 148 malignant lesions. Compared to CT, the results of DHC changed staging or treatment in 8/35 patients (23%). Lesion detection by DHC was limited by tumour size and intensity of FDG uptake. Image fusion provided relevant clinical information in 9/35 patients (26%). CONCLUSION: Functional imaging in NSCLC with this dual-head gamma camera is superior to morphological imaging by CT, although inferior to dedicated PET imaging. Combined functional-anatomical imaging has the potential to improve staging and localization procedures before surgery or radiotherapy.

Adult↗

Solvent change co-precipitation with hydroxypropyl methylcellulose phthalate to improve dissolution characteristics of a poorly water-soluble drug.

Research compound GWX belongs to biopharmaceutical classification system type II, and hence shows dissolution-rate-limited absorption. To improve its dissolution performance, GWX was formulated as a co-precipitate with hydroxypropyl methylcellulose phthalate (HPMCP). Co-precipitates with various drug-HPMCP ratios were prepared and characterised using modulated differential scanning calorimetry (MDSC), X-ray powder diffraction, HPLC and dissolution testing. Co-precipitates with 1:9 and 2:8 drug-HPMCP ratios showed the highest extent of dissolution after both 5 and 90 min, followed by 3:7, 4:6, and 5:5 drug-HPMCP co-precipitates, in respective order. Co-precipitates with drug-HPMCP ratios of 6:4 and greater showed no significant improvement in dissolution over crystalline drug alone. The amounts of crystalline and amorphous drug in co-precipitates, as determined by MDSC, and HPLC quantification of the total amount of drug in co-precipitates were used to determine the amount of drug incorporated into solid solution. It was found that dissolution rate and extent was correlated to the amount of drug incorporated into amorphous solid solution for the 1:9 to 5:5 drug-HPMCP ratio co-precipitates. Amorphous drug alone and physical mixtures of drug and HPMCP showed very little and no significant improvement in dissolution rate or extent, respectively, above crystalline drug alone. Amorphous drug alone re-crystallized to a large extent within 1 min of contact with the dissolution medium, whereas 4:6 drug-HPMCP co-precipitate showed a lower degree of re-crystallization and 2:8 drug-HPMCP co-precipitate showed very little re-crystallization. It was concluded that the likely mechanisms of improved dissolution of low drug-HPMCP ratio co-precipitates were improved wetting or increased surface area for mass transfer, thermodynamically enhanced dissolution of a higher energy amorphous form and inhibition of re-crystallization, when drug was incorporated into solid solution.

Biological Availability↗

Properties of frozen sections relevant to quantitative microanalysis.

Difficulties in the quantitative X-ray microanalysis of frozen sections may conceivably arise from ice-crystal damage and from electron-beam damage. X-ray peak-to-continuum ratios are commonly taken as a quantitative index of elemental concentrations. But recent reports suggest that in dehydrated frozen sections such ratios vary greatly with the scale of ice-crystal formation existing prior to sublimation. The experiments in these reports are re-interpreted here; it is argued that peak intensities may be affected by ice-crystal scale but that ratios of peak to continuum should not be affected after corrections for exogenous continuum. The accuracy of the peak-to-continuum method is affected by beam-induced loss of mass from microvolumes during analysis. Mass loss can be reduced or slowed by a cold-stage. For example, the radiation sensitivity for loss of chlorine from PVC is reduced by a factor of 1000 or more with reduction of temperature from 300 to 100 K. For sections of soft tissue the effectiveness of cooling is not nearly so striking but at 100 K, analyses of 1 micron frozen-hydrated sections by the continuum method, with spatial resolution of the order of 1 micron, can be completed before substantial mass loss occurs. However, analysis of frozen-hydrated sections by the continuum method at much higher resolution, say 100 nm resolution in 100 nm sections, is precluded by mass loss. Measurements of local mass can be achieved with much lower dose by observation and calibration of the electron transmission or backscattering. But even with these methods, several problems remain in achieving quantitative X-ray analysis at very high resolution.

Electron Probe Microanalysis↗

A new algorithm for deriving pulsatile blood flow waveforms tested using stimulated dynamic angiographic data.

In vascular pathology the assessment of disease severity and monitoring of treatment requires quantitative and reproducible measurements of arterial blood flow. We have developed a new technique for processing sequences of dynamic digital X-ray angiographic images. We have tested it using computer simulated angiographic data which includes the effect of pulsatile blood flow and X-ray quantum noise. A parametric image was formed in which the image grey-level represents dye concentration as a function of time and distance along a vessel segment. Adjacent concentration--distance profiles in the parametric image were re-registered along the vessel axis until a match occurred. A match was defined as the point where the sum of squares of the differences in the two profiles was a minimum. The distance translated per frame interval is equal to the bolus velocity. We have tested several contrast medium injection methods including constant flow and a range of discrete pulses per second. The technique proved to be robust and independent of injection technique. Average blood flow was measured for simulated pulsatile waveforms with mean flows of up to 650 ml/min (peak velocities up to 186 cm/s) in a range of diameters from 2 mm to 6 mm. The standard deviation of the error in the mean flow estimates over the whole range of velocities and vessel sizes was +/- 1.4 cm/s.

Algorithms↗

Usefulness of performing colonoscopy one year after endoscopic polypectomy.

This retrospective study defines a population with neoplastic colonic polyps who have had colonoscopic polypectomy and, in follow-up within one year, a repeat colonoscopic evaluation. The population was broken down into two groups, one group that had polyps at the second examination and one group that did not. This study determined which factor(s) were significant among this population in distinguishing whether new polyps would be found at one year follow-up. The authors found that among the many variables studied, only polyp multiplicity was significant in predicting polyp recurrence. More than one polyp found at index colonoscopy led to a significant chance of having a new polyp after only one year. Also, it was demonstrated that these "new" polyps were unlikely to have been "missed" polyps from the initial colonoscopy. Because of the shifting location, smaller size, and fewer instances of histologic atypia in these polyps compared with those at index examination, the authors believe that polyps found after one year may be assumed to have arisen de novo. Finally, the authors show that a significant number of polyps occur beyond the reach of the flexible sigmoidoscope (approximately 60 cm). The authors recommend that patients who have polyps undergo a colonoscopic examination. When patients are re-evaluated after having colonoscopic neoplastic polypectomy, they should undergo repeat colonoscopy.

Adenoma↗

Molecular aspects of rapid, reversible, Ca2+-dependent de-phosphorylation of pp63/parafusin during stimulated exo-endocytosis in Paramecium cells.

Ca2+ signalling governs stimulated exocytosis and exocytosis-coupled endocytosis also in Paramecium cells. Upon stimulation, the < or =10(3) dense-core exocytotic organelles (trichocysts) can be synchronously (80 ms) released, followed by endocytotic membrane resealing (350 ms) and retrieval. Paramecium is the most synchronous dense-core exocytotic system known, allowing to dissect rapidly reversible Ca2+-dependent phenomena. This holds for the reversible de-/re-phosphorylation cycle of a 63 kD phosphoprotein, pp63/parafusin (pf), which we have cloned, immuno-localised, and characterised as phosphoglucomutase, the enzyme funneling glucose into the glycolytic pathway. It was isolated ex vivo, followed by MALDI analysis, while X-ray structure analysis was performed after heterologous expression. We found multiple phosphorylation of superficial Ser/Thr residues. Although present also in exo(-) mutants, pp63/pf is selectively de-phosphorylated only in exo(+) strains during synchronous exocytosis (80 ms) and re-phosphorylated within approximately 20 s, i.e., the time required to re-establish [Ca2+] homeostasis. We have isolated relevant protein phosphatases and kinases and probed their activity on pp63/pf in vitro. We consider Ca2+/calmodulin-activated PP2B (calcineurin, whose subunits have been cloned) relevant for de-phosphorylation. Re-phosphorylation can be achieved by two protein kinases that also have been cloned. One is activated by cGMP (PKG) which in turn is formed by Ca2+-activated guanylate cyclase. Another kinase, casein kinase 2, is inhibited by Ca2+ and, hence, activated with some delay in parallel to decreasing [Ca2+] after exocytosis. In total, several Ca2+-sensitive cycles cooperate whose protein components have been localised to the cell cortex. Regulation of the phosphorylation degree of pp63/pf may affect structure binding on a microscale and/or its enzymatic activity. All this may serve fueling substrate into glycolysis with increased ATP re-formation (compromised in exo(-) mutants) and NADH formation, with effects on Ca2+ signalling including mobilisation from cortical stores (alveolar sacs) and overall effects on ATP and Ca2+ dynamics during synchronous exo- and endocytosis.

Animals↗

Microscopic fragmentation model for galactic cosmic ray studies.

We describe theoretical considerations for developing models of heavy ion fragmentation appropriate for galactic cosmic ray studies. Previous models have been based on parametric fits to limited experimental data or models that ignored some aspects of the reaction dynamics, including nuclear cluster effects. The abrasion-ablation description of the fragmentation process is re-formulated to describe the excitation spectrum of pre-fragment nuclei. The resulting spectrum is shown to be related to the many-body response of the nuclear ground-state and excited states, and an approach to simplify this function is discussed. An analytic solution to the nuclear de-excitation process is described which includes a realistic level spectrum of the GCR nuclei (A < 60). Comparisons are made to experiments for fragmentation of 24Mg, 32S, and 56Fe beams on several targets and results are discussed.

Cosmic Radiation↗

Unsymmetrical dirhenium complexes that contain [Re(2)](6+) and [Re(2)](5+) cores complexed by tridentate ligands with P(2)O and P(2)N donor sets.

The quadruply bonded dirhenium(III) complex (n-Bu(4)N)(2)Re(2)Cl(8) reacts with tridentate ligands that contain essentially planar P,O,P donor sets to afford the complexes Re(2)Cl(6)(eta(3)-L(1)) (3) (L(1) = bis[2-(diphenylphosphino)phenyl]ether) and (n-Bu(4)N)[Re(2)Cl(7)(eta(1)-L(2))] (4) (L(2) = 4,6-bis(diphenylphosphino)dibenzofuran). Spectroscopic and electrochemical data support the unsymmetrical structure Cl(4)ReReCl(2)(eta(3)-L(1)) in the case of 3, while 4 contains monodentate P-bound L(2) both complexes contain Re---Re bonds. The synthon cis-Re(2)(mu-O(2)CCH(3))(2)Cl(4)(H(2)O)(2) reacts with ligands L(1), L(2), 2,6-bis(diphenylphosphinomethyl)pyridine (L(3)), bis[2-(diphenylphosphino)ethyl]amine (L(4)), and N,N-bis[2-(diphenylphosphino)ethyl]trimethylacetamide (L(5)) to give the paramagnetic complexes Re(2)(mu-O(2)CCH(3))Cl(4)(eta(3)-L(n)) (5-9) with Re bonds. The lability of the mu-acetato ligands in 5-9 has been demonstrated by the reactions of compounds 5 (n = 1) and 7 (n = 3) with 4-Ph(2)PC(6)H(4)CO(2)H, 2-Ph(2)PC(6)H(4)CO(2)H, and quinoline-4-carboxylic acid to give complexes 10-12 (from 5) and 13-15 (from 7), respectively. These products contain uncoordinated donor atoms that can be used to produce mixed-metal assemblies. Compounds 5 and 7 also react with terephthalic acid (1,4-C(6)H(4)(CO(2)H) to give [Re(2)Cl(4)(eta(3)-L(1))](2)(mu-O(2)CC(6)H(4)CO(2)) (16) and [Re(2)Cl(4)(eta(3)-L(3))](2)(mu-O(2)CC(6)H(4)CO(2)) (17) in which electronic coupling between the paramagnetic sets of dirhenium units is very weak. Single-crystal X-ray structure determinations have been carried out on complexes 5-8, 11, 12, and 14-16.

Journal Article↗