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1.
STEPHEN K. DORDUNOO JAMES L. FORD MICHAEL H. RUBINSTEIN 《The Journal of pharmacy and pharmacology》1997,49(4):390-396
The effect of storage on the physical stability of solid dispersions of triamterene or temazepam in polyethylene glycols was studied using differential scanning calorimetry (DSC), particle-size analysis and dissolution methods. The enthalpies of fusion of the carriers, without included drug and previously fused and crystallized, increased on storage. Analysis of similarly treated solid dispersions, containing either 10% temazepam or 10% triamterene, showed that each drug influenced the morphology of the polyethylene glycol (PEG). The enthalpies and melting points of the solidus components of the dispersions' carriers were initially reduced after preparation, but on storage these increased. The particle sizes of the drugs dispersed in the PEGs increased on storage. The changes in dissolution after storage of triamterene or temazepam dispersions were smaller for dispersions in PEG 1500 than for dispersions in PEGs of higher molecular weight (PEG 2000, PEG 4000 or PEG 6000) in which the reduction in dissolution was particularly marked during the first month of storage. The rank order of changes in dissolution were PEG 1500 ? PEG 2000 < PEG 4000 ~ PEG 6000. 相似文献
2.
WARHEIT DAVID B.; KELLY DAVID P.; CARAKOSTAS MICHAEL C.; SINGER ALLEN W. 《Toxicological sciences》1989,12(2):333-345
A 90-Day Inhalation Toxiaty Study with Benomyl in Rats. WARHEIT,D. B., KELLY, D. P., CARAKOSTAS, M. C., AND SINGER, A. W. (1989).Fundam Appl Toxicol./ 12, 333-345. Benomyl [methyl 1-(butylcarbamoyl)-2-benzimidazolecarbamate,CAS Registry No. 17804-35-2] is a fungicide and the possibilityfor inhalation exposure exists for field workers. To assessthe toxicity of benomyl, groups of 20 male and 20 female CDrats were exposed nose-only 6 hr a day, 5 days a week, to concentrationsof 0, 10, 50 or 200 mg/m3 of a benomyl atmosphere. At the midpoint(approximately 45 days on test) and at the end of the exposureperiod, blood and urine samples for clinical evaluation werecollected from 10 rats/group/sex, and these animals were sacrificedfor pathological examination. Similar evaluations were performadon all remaining rats at the end of the 90-day test period.After approximately 45 days on test, compoundrelated degenerationof the olfactory epithelium was observed in all males and in8 of 10 female rats exposed to 200 mg/m3 benomyl. Two male ratsexposed to 50 mg/m3 had similar, although less severe, areasof olfactory epithelial degeneration. After approximately 90days of exposure, the remaining 10 rats/group/sex were sacrificedand examined. Of these rats, all of the males and females exposedto 200 mg/m3 had olfactory degeneration, along with 3 malesexposed to 50 mg/m3 of benomyl. No other observed lesions wereinterpreted to have been caused by the benomyl exposure. Inaddition, male rats exposed to 200 mg/m3 benomyl had depressedmean body weights compared to controls and this finding correlatedwith a reduction in food consumption. Based on pathologicalobservations, 10 mg/m3 represents the no-observable-effect level(NOEL) for the male rats, and 50 mg/m3 is the NOEL for the femalerats. 相似文献
3.
Pleomorphic Ventricular Tachycardia: Demonstration of Conduction Reversal Within the Reentry Circuit
KARL-HEINZ KUCK MICHAEL SCHLÜTER KLAUS-PETER KUNZE MANFRED GEIGER 《Pacing and clinical electrophysiology : PACE》1989,12(7):1055-1064
A case is presented of a patient with incessant venfricular tacbycardia of left bundle branch block morphology. Endocardial mapping revealed the site of earliest activation during tachycardia to be the proximal right ventricular septum. Pacing at this site elicited the clinical tachycardia, whereas pacing at the proximal left ventricular septum induced a right bundle branch block morphology identical to that of a previously recorded spontaneous ventricuiar tachycardia. Electrophysiological evidence is given that both types of tachycardia originate from a single reentry circuit located in the proximal ventricular septum in which the reentrant wavefront may travel either orthodromically (during spontaneous tachycardia and right ventricular pacing) or antidromically (during left ventricular pacing). 相似文献
4.
5.
The interactive role of mucosal T lymphocytes in intestinal growth, development and enteropathy 总被引:2,自引:0,他引:2
Abstract Over the past 15–20 years, research has progressively focused on the mucosal T cell as the central factor in the initiation of physiological or pathological changes, first in the growth and maturation of the early (postnatal) intestine, and second in adult-type enteropathies resulting from sensitivity to either food or pathogen-derived antigens. T cell-mediated events may be measured, for example, in terms of specific immunopathologic patterns of change and injury, such as type 1 (lymphocyte infiltration), type 2 (crypt hyperplasia) and type 3 (flat-destructive), which can be recognized and quantitated microscopically; by determination of lymphocyte reactivity through secretion of interleukin-2 receptors (IL-2R) into plasma or expression by mucosal lymphocytes; by quantitation of lymphocyte subsets emigrating into inflamed tissues by immunoperoxidase-labelled monoclonal antibodies; or by the determination of T cell receptor polymorphisms. Alterations in intestinal growth, structure and function at weaning are likely to be T cell-mediated as they are analogous to the same type 1/2 lesions that reflect modulation of adult mucosal architecture in food and parasite-induced hypersensitivity reactions. Enteropathies associated with HIV infection and T cell deficiency display a milder degree of villous flattening and impaired crypt hyperplasia than that typical of gluten-sensitivity, suggesting a reversion to lesser degrees of mucosal pathology (type 1/2). Clearly more information will accrue; meanwhile the remarks in this brief survey should provide a firm basis whereby clinician and scientist can meet, and together recognize and further dissect the modulatory effect of T lymphocytes on mucosal structure and function. 相似文献
6.
BRIAN J. STOCKMAN CAROL A. BANNOW ROBERT M. MICELI MICHAEL E. DEGRAAF H. DAVID FISCHER CLARK W. SMITH 《Chemical biology & drug design》1995,45(1):11-16
Epitope libraries provide a method to identify peptide ligands for antibodies, receptors or other binding proteins. As such, they provide a powerful tool to rapidly identify lead ligands in the drug discovery process. In an attempt to correlate structural information with the results from peptide screening, we have used NMR spectroscopy of peptide/antibody complexes to demonstrate that core residues identified through a two-stage selection process undergo a larger structural change upon binding antibody than do positions in the peptide amenable to a variety of side chains. The model system used was the M2 monoclonal antibody/Flag? octapeptide epitope system. We have analyzed two peptides: Ac-Asp-Tyr-Lys-Leu-Gly-Asp-Asp-Leu-NH2 (peptide l), which contains several non-core positions randomized, and Ac-Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Leu-NH2 (peptide 2), which closely corresponds to the original Flag? sequence. Enrichment of the peptides with 15N facilitated the investigation by permitting spectral editing of the peptide resonances in the presence of antibody. For peptide 1 the absolute shifts for the free vs. Fab-bound peptide were found to be largest for the amide groups of Asp-1 and Asp-6, in agreement with classification of these residues as critical by the phage display library selection process. For peptide 2 the largest absolute shifts were observed for Asp-1 and Asp-4, with the other aspartic acid residues also showing significant but smaller changes. © Munksgaard 1995. 相似文献
7.
BERNHARD FREY MICHAEL WUTTE RUDOLF BERGER CLEANTHIS IOANNIDES MARTIN HÜLSMANN BRIGITTE STANEK RICHARD PACKER 《Pacing and clinical electrophysiology : PACE》1995,18(1):152-158
To investigate the impact of staged therapy for advanced heart failure on therapeutic endpoints, 236 consecutive patients (coronary artery disease/dilated cardiomyopathy in 61/175 patients, left ventricular ejection fraction 14%± 5%, New York Heart Association Class IIl/IIIIV in 102/79/55 patients, respectively) with advanced heart failure were prospectively followed. One hundred thirtyseven patients enrolled from January 1989 to December 1991 were treated conventionally with digoxin, furosemide, and low dose angiotension converting enzyme (ACE) inhibition. Patients refractory to this therapy underwent urgent heart transplantation. Ninetynine patients enrolled from January 1992 to August 1993 underwent staged therapy: stage 1: maximal tolerated ACE inhibition; stage 2: therapy with PGE1 for preand afterload reduction to achieve hemodynamic stabilization; or stage 3: refractory patients bridged to heart transplantation with continuous outpatient dobutamine. Sudden death was defined as death within 1 hour of symptoms if heart failure symptoms remained stable over the previous 7 days. Conventionally treated patients were followed for 10 ± 9 months; patients who underwent staged therapy for 9 ±5 months. In the group of patients that underwent standard therapy, 39 of 137 (28%) patients died: 5 (13%) deaths occurred suddenly, and death due to progressive pump failure occurred in the remaining 34 (87%) patients. In the group of patients that underwent staged therapy, 25 of 99 (25%) patients died: 13 (52%) deaths occurred suddenly, and 12 (48%) deaths occurred due to progressive pump failure. Thus, patients who underwent staged therapy were at increased risk for sudden death (P = 0.01, relative risk 3.4, 95% confidence interval 1.2–9.7) but were at lower risk for death from pump failure (P = 0.009, relative risk 0.44, 95% confidence interval 0.22–0.84). In patients who underwent therapy with continuous outpatient PGE1 (n = 7) or dobutamine (n= 21), risk for sudden death (P = NS by log rank test) did not increase. In conclusion, staged therapy significantly reduced death from pump failure; however, patients who could be stabilized and considered too well for heart transplantation were at increased risk for sudden death. Thus, overall survival did not improve. Of note, outpatient dobutamine did not increase the risk for sudden death. 相似文献
8.
HEINER LANGENFELD AXEL KREIN MICHAEL KIRSTEIN LUDWIG BINNER† EUROPEAN PEA CLINICAL INVESTIGATION GROUP 《Pacing and clinical electrophysiology : PACE》1998,21(11):2187-2191
The peak endocardial acceleration (PEA, unit g) shows a near correlation with myocardial contractility during the isometric systolic contraction of the heart (dP/dtmax), with sympathetic activity and, thus, with physiological heart rate modulation. The (Biomechanical Endocardial Sorin Transducer (BEST) sensor is incorporated in the tip of a pacing lead and measures PEA directly near the myocardium. In an international study, the lead was implanted with the dual chamber pacemaker Living-1 (Sorin) in 105 patients. The behavior of the PEA signal was tested under conditions of physical and mental stress and during daily life activities by 24-hour recordings of PEA (PEA Holter) at 1 to 2 months and approximately 1 year after implantation. Implantation of the BEST lead was performed without complications in all patients. The sensor functioned properly in the short- and long-term in 98% of patients. Although PEA values differed from patient to patient, the values closely reflected the variations in sympathetic activity due to physical and mental stress in each patient. During exercise and during daily life activities a close correlation between PEA and heart rate was observed among patients with normal sinus rhythm. Peak endocardial acceleration allows a nearly physiological control of the pacing rate. 相似文献
9.
The debate about the future role of the general practitionerincludes discussion about the range of services which shouldbe on offer in addition to general medical services. Drawingon evidence from a nationally representative sample of 1419general practitioners this paper examines the reality of whatis currently being provided in general practice in the UK. Theanalyses produce figures that are compatible with the hypothesisthat there is a form of creeping specialization taking placewith general practitioners tending to provide one type of serviceat the exclusion of the others. Doctors appeared to clusterinto three distinct groupsopportunistic health educators,minor surgeons and those who provide services for women. Theimplications of these and other findings are discussed. 相似文献
10.
MICHAL J. KANTOCH ROXANE McKAY MICHAEL J. TYRRELL 《Pacing and clinical electrophysiology : PACE》1993,16(9):1887-1891
An 11-year-old girl who underwent Mustard's operation for complete transposition of the great arteries in infancy, developed Mobitz type II second-degree AV block 81/2 years later. A transvenous, active fixation left ventricular lead was inserted and connected to a rate responsive pacemaker. Two years later the lead dislodged due to the child's growth. A new active fixation electrode was positioned in the left ventricle below the pulmonary valve, leaving an electrode loop in the ventricle. Such an approach may prevent lead dislodgement due to growth after intraatrial repair for transposition of the great arteries, but regular radiological or echocardiographic follow-up of lead position is recommended in these patients. 相似文献