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991.
Palmer Q. Bessey M.D. Zhu-ming Jiang M.D. Daniel J. Johnson M.D. Robert J. Smith M.D. Douglas W. Wilmore M.D. 《World journal of surgery》1989,13(4):465-470
To investigate the role of hormones as mediators of net skeletal muscle proteolysis following injury, healthy normal male volunteers received a continuous 76-hour infusion of the 3 stress hormones: hydrocortisone, glucagon, and epinephrine. As a control, each subject received a saline infusion during another 4-day period. Ten paired studies were conducted. Diets were constant and matched on both occasions. Triple hormone infusion achieved hormone concentrations similar to those seen following mild-moderate injury. After 72 hours of infusion, skeletal muscle intracellular glutamine concentrations were lower in the hormone studies than in the control group (N=4). Free amino acid concentrations in arterial whole blood and forearm amino acid efflux were little affected by hormonal infusion. Thus, alteration of the hormonal environment by the triple hormone infusion was not a sufficient stimulus to induce all of the changes in skeletal muscle proteolysis observed in critical illness. Since studies utilizing neurohormonal blockade have shown diminished net muscle proteolysis, the stress hormones appear to be necessary but not sufficient for the protein catabolic response to injury.
Supported by the National Institutes of Health Trauma Center Grant P50-GM 29327-03 and Clinical Research Center Grant no. 290-9299. 相似文献
Resumen Con el propósito de investigar el papel de las hormonas como agentes mediadores de la proteolisis muscular neta que se presenta en el trauma y en otros estados críticos, se administró una infusión de las 3 hormonas del estrés, hidrocortisona, glucagón, y epinefrina, a voluntarios sanos por períodos continuos de 76 horas. Como control, cada individuo recibió una infusión de solución salina durante otro período de 4 días. Se condujeron 10 estudios apareados, con dietas constantes y similares en ambas ocasiones. La infusión triple de hormonas produjo concentraciones sanguíneas hormonales similares a las observadas en pacientes con trauma leve-moderado. A las 72 horas de la infusión las concentraciones intracelulares de glutamina en el mÚsculo esquelético aparecieron menores que en los estudios de control (N=4). Las concentraciones de aminoácidos libres en la sangre arterial y el flujo de salida de aminoácidos en el antebrazo resultaron mínimamente afectados por la infusión hormonal. Por lo tanto, la alteración del medio hormonal producida por infusión triple de hormonas no representa un estímulo suficiente para inducir la totalidad de las alteraciones en la proteolisis del mÚsculo esquelético que se observa en la enfermedad crítica. Puesto que los estudios con bloqueo neurohumoral han demostrado una disminución en la proteolisis muscular neta, las hormonas del estrés parecen ser necesarias, pero no suficientes de por sí, para la respuesta catabólica a la injuria biológica.
Résumé Pour étudier le rôle des hormones dans la protéolyse posttraumatique de muscle squelettique, des volontaires de sexe mâle en bonne santé ont été perfusés pendant 76 heures avec les 3 hormones de stress: hydrocortisone, glucagon, et adrénaline. En contrôle, chaque patient a reÇu une perfusion de sérum physiologique pendant quatre jours. Dix études appariées ont été faites. Pendant les deux études, l'alimentation était la mÊme et constante. La perfusion des 3 hormones a provoqué une concentration semblable à celle qu'on observe après un traumatisme moyen. Après 72 heures, le taux de glutamine dans les muscles squelettiques était plus bas dans l'étude hormonale que dans l'étude contrôle (N=4). La concentration en acides aminés libres dans le sang artériel et notamment l'arrivée de sang dans l'avant-bras n'étaient que peu influencées par la perfusion hormonale. Ainsi, la perfusion avec augmentation de la concentration des 3 hormones de stress ne suffisait pas pour provoquer la protéolyse musculaire squelettique que l'on observe lors des maladies graves. Puisque d'autres études ont montré que le blocage neurohormonal diminue nettement la protéolyse musculaire, les hormones de stress semblent donc nécessaires mais non suffisantes dans la réponse catabolique protéinique au traumatisme.
Supported by the National Institutes of Health Trauma Center Grant P50-GM 29327-03 and Clinical Research Center Grant no. 290-9299. 相似文献
992.
David J. Murray Robert B. Forbes Judith B. Dillman Larry T. Mahoney David L. Dull 《Journal canadien d'anesthésie》1989,36(3):295-300
In this study, two-dimensional and pulsed Doppler echocardiography were used to measure cardiovascular changes before and
after IV atropine in 31 infants and small children during halothane (n = 15) or isoflurane (n = 16) anaesthesia. Prior to
induction of anaesthesia heart rate (HR), mean blood pressure (MBP), and two0dimensional echocardiographic dimensions of the
left ventricle and pulmonary artery bloodflow velocity were measured by pulsed Doppler echocardiography. Cardiovascular measurements
were repeated while anaesthesia was maintained at 1.5 MAC halothane (n = 15) or isoflurane (n = 16). Atropine 0.02 mg·kg−1 IV was then administered and two minutes later, a third set of cardiovascular data was obtained. Heart rate decreased during
halothane anaesthesia but did not change significantly during isoflurane anaesthesia. Mean blood pressure, cardiac output
(CO) and stroke volume (SV) decreased similarly during 1.5 MAC halothane or isoflurane anaesthesia. Ejection fraction (EF)
decreased and left ventricular end-diastolic volume (LVEDV) increased significantly in bothgroups, but decreases in EF (32
± 5 percentvs18 ± 5 per cent) and increases in LVEDV (18 ± 7 per cent vs7 ± 5 per cent) were significantly greater during
halothane than during isoflurane anaesthesia. Following atropine, HR increased more in the patients maintained with halothane
(31 ± 6 per cent), than during isoflurane anaesthesia (18 ± 5 per cent). Atropine increased CO in both groups of patients,
but SV and EF remained unchanged. When compared with awake values, HR increased similarly and significantly (18 ± 4 per cent)
following atropine in both groups, and CO returned to control levels. Halothane decreased EF and increased LVEDV more than
isoflurane at 1.5 MAC end— expired anaesthetic levels. Atropine did not diminish the myocardial depression produced by halothane
or isoflurane. The increase in CO following atropine during halothane and isoflurane anaesthesia in infants and small children
is the result of increases in HR alone.
Nous avons utilisé un appareil à échocardiographie bi-dimensionnelle couplé à un Doppler pulsé chez des bébés et de jeunes
enfants pour évaluer l’impact hémodynamique de l’halothane (n = 15) et de l’isoflurane (n = 16) et la modification possible
de ces effets par l’atropine. Nous avons mesure la frequence cardiaque (FC), la pression artérielle moyenne (PAM), la dimension
de la cavité ventriculaire gauche (par écho bi-dimensionnelle) et la vélocité du flot sanguin pulmonaire (par Doppler) et
ce, en trois occasions soit avant l’induction, après l’instauration de 1.5 MAC d’halothane ou d’isoflurane et finalement,
deux minutes après l’injection IV de 0.02 mg·kg−1 d’atropine. On ne nota une baisse de la frequence cardiaque qu’avec l’halothane tandis que la PAM, le débit cardiaque (DC)
et le volume d’éjection (VE) diminuaient autant avec l’un ou l’autre anesthésique. La diminution de la fraction d’éjection
(FE) et l’augmentation du volume télédiastolique du ventricule gauche (VTDVG) significatives pour les deux groupes, étaienl
plus marqué avec l’halothane qu’avec l’isoflurane: FE 32 ± 5 pour cent vs18 ±5 pour cent; VTDVG 18 ± 7 pour cent vs 7 ± 5
pour cent. Avec l’atropine, la FC monta plus dans le groupe halothane (31 ± 6 pour cent) que dans le groupe isoflurane (18
± 5 pour cent), le DC augmentant dans les deux groupes, alors que le VE et la FE demeuraient inchangés. Comparée aux mesures
pré-induction, l’atropine amenait une hausse significative de la FC, semblable dans les deux groupes (18 ± 4 pour cent) et
restaurait le DC. Donc, chez les bebes et les jeunes enfants, a 1.5 MAC, l’halothane diminue la FE et augmente le VTDVG plus
que ne le fait l’isoflurane. L’atropine ne modifie pas la depression myocardique et elle ne restaure le DC que par une hausse
de la FC.
Supported by PHS Grant No. 8507300 from the College of Medicine, University of Iowa Hospital, Iowa City, IA. 相似文献
Supported by PHS Grant No. 8507300 from the College of Medicine, University of Iowa Hospital, Iowa City, IA. 相似文献
993.
Patients' perceptions of their clinical interactions: development of the multidimensional desire for control scales 总被引:2,自引:0,他引:2
Anderson Lynda A.; DeVellis Robert F.; Boyles Barbara; Feussner John R. 《Health education research》1989,4(3):383-397
Interventions oriented toward enhancing patient-provider communicationwill benefit from having a satisfactory measure of patientsdesires for control in clinical interactions. Findings fromtwo studies are reported describing the development and validationof the Multidimensional Desire for Control (MDC) Scales. A totalof 160 patients with non-insulin-dependent diabetes (NIDDM)participated in the first study, which was designed to developand validate a measure of patients desires for control.Factor analysis yielded three subscales reflecting patientsdesires for: (i) personal, (ii) clinician, and (ii) shared controlin the interaction. Alphas for the three subscales were high( 0.750.86). Correlations with other measures of controlwere suggestive of good construct validity. The second investigationinvolves a replication study verifying the factorial compositionand validity of the scales. An independent sample of 109 patientswith NIDDM participated in this study. Findings support thereliability of the subscales (0.750.81). Furthermore,patients desires for control were significantly associatedwith patient satisfaction, with desire for personal controlnegatively related to patient satisfaction (r = 0.30,0.41, affective and behavioural dimensions, respectively)and desire for clinician control positively related to satisfaction(r = 0.44, 0.28, 0.31, affective, behavioral, and cognitivedimensions, respectively). 相似文献
994.
Eileen Mary Grealish Robert P. Hawkins Pamela Meadowcroft Pamela Weaver Sharon S. Frost Percilla Lynch 《Child & youth care forum》1989,18(1):49-61
Many youth, their parents, and social services regard the unification of the family as the most desirable outcome for youth in out-of-home placements. This goal is often difficult to achieve because the families of these troubled/troubling youths are often severely dysfunctional, with multiple problems. A group process model for serving natural parents of youth in placement is described which, in conjunction with one-on-one interactions with professionals, appears to have a positive impact on these families and on youths' return home. Group components that seem particularly important are described, including attendance by invitation only, public commitment to attend and participate, reminder prompts, transportation support, babysitting support, refreshments, opportunity to visit with their child, defined staff roles, an empowering approach, and starting where the parent is. The group process maintained a relatively high level of both attendance and participation by the targeted parents. Participants tended to achieve most goals that they set in the group. Our experience indicates that interventions with natural parents of troubled youth can enable even a very dysfunctional family to improve enough to receive youth back into their home.The authors are grateful for the assistance of Sharon Estill, Jim Bernardo, Anita Mentzer, Dave Walker, and Suni Dague-Lyman for assistance in collecting the data reported here. Debbie Buchanan and others have been a great assistance in transporting families. 相似文献
995.
996.
Rami Saydjari James R. Upp Jr. Robert W. Alexander Sam C. Barranco Courtney M. Townsend Jr. James C. Thompson 《Investigational new drugs》1989,7(2-3):131-138
Summary The glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), has been shown to inhibit the growth of certain cancers. -Difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase (ODC), the ratelimiting enzyme in polyamine biosynthesis. DFMO has been shown to inhibit cancer growth in a number of models. The present study was designed to investigate the effects of 2-DG alone and combined with DFMO on MC-26 mouse colon adenocarcinoma tumors growing in vivo. Twenty-eight male Balb/c mice were inoculated with 250,000 MC-26 cells, and then randomized into four groups of 7 each: group I served as control; group II received DFMO (3% in drinking water); group III received 2-DG (500 mg/kg/d IP); group IV received a combination of 2-DG and DFMO. Treatment began 5 days after tumor cell inoculation. MC-26 tumor area was reduced 73% by DFMO compared to a 24% reduction caused by 2-DG. The tumor weight was reduced 80% by DFMO and 52% by 2-DG. The tumor contents of DNA, RNA, and protein were significantly reduced by DFMO but not 2-DG. The tumor concentration of the polyamines putrescine and spermidine were reduced by DFMO alone or combined with 2-DG while spermine levels remained unchanged. 2-DG alone did not alter polyamine levels. These results indicate that both 2-DG and DFMO, when added as single agents, inhibit tumor growth. However, the addition of 2-DG to the DFMO regimen inhibited the antitumor effects of DFMO. Survival studies performed on MC-26 cells in vitro corroborated the antagonisms between DFMO and 2-DG that were shown in vivo.Dr. Upp was awarded a fellowship grant from the American Cancer Society Texas Division. 相似文献
997.
J J Robert M Orosco C Rouch C Jacquot Y Cohen 《Pharmacology, biochemistry, and behavior》1989,34(3):577-583
The relationship between the effects of opiates on food intake and on central monoamines in various brain areas was investigated in normophagic and obese "cafeteria" rats. Three agonists, beta-endorphin, dynorphin, and D-Ser2-Leu-Enk-Thr6 (DSLET) and an antagonist, naltrexone, were used. The three agonists enhanced feeling in normophagic rats but had different dopaminergic effects. Serotonergic metabolism increased concomitantly with the enhancement of feeding by the agonists, whereas it decreased following treatment with the antagonist naltrexone. In the cafeteria rats, although the feeding effects of dynorphin and DSLET occurred earlier, there was a complete lack of monoaminergic effects. beta-Endorphin was completely devoid of effects in this model. There would, thus, appear to be a positive correlation between the behavioural effects of these opiates and serotonergic metabolism in normophagic rats, while stimulated feeding situations ("cafeteria" rats) the disruption of a monoaminergic modulation does not prohibit a direct effect on feeding. 相似文献
998.
Chien Yie W. Chien Te-yen Bagdon Robert E. Huang Yih C. Bierman Robert H. 《Pharmaceutical research》1989,6(12):1000-1010
Several transdermal contraceptive device (TCD) formulations were developed to provide a dual-controlled transdermal delivery of levonorgestrel (LN), a potent progestin, and 17-estradiol (E2), a natural estrogen. Using a sensitive HPLC method, the in vitro release and skin permeation profiles of LN and E2 from various TCD formulations were simultaneously characterized in the hydrodynamically well-calibrated Valia–Chien skin permeation cells and both were found to follow zero-order kinetics. The rates of drug release and skin permeation were observed to vary significantly depending upon some formulation parameters. Six-month stability studies were performed on seven formulations at room and elevated temperatures (37 and 45°C), and two (Formulations 4 and 5) were found to be acceptable, based on drug recovery, release rate, and skin permeation rate data. Judging from the 6-month accelerated stability studies, it is projected these two formulations will have shelf-life of at least 2 years. As a result of development of an efficient manufacturing process, Formulation 4 was selected for further evaluation. One-week primary skin irritation evaluation in 6 rabbits indicated that Formulation 4 is nonirritating, and it was thus selected for Phase I clinical bioavailability/dose proportionality studies in 12 healthy female volunteers of child-bearing age. Results of pharmacokinetic and pharmacodynamic analyses demonstrated that it is capable of achieving and maintaining a steady-state serum level of LN throughout the 3-week treatment period by weekly applications of one or two TCD patches (10 or 20 cm2). A dose proportionality was obtained in the serum drug levels, daily dose delivered, and contraception efficacy. An excellent correlation was obtained for the rates of transdermal delivery determined by the in vitro studies using human cadaver skin, the in vivo studies in rabbits, and the clinical studies in living subjects. 相似文献
999.
Vassilios I. Avramis William C. Powell Robert A. Mecum 《Cancer chemotherapy and pharmacology》1989,25(1):19-24
Summary 1--d-arabinosyl-5-azacytosine (ara-AC) is a relatively new antitumor agent under clinical investigation, which has the 2- arabinosyl configuration found in the tumoricidal drug ara-C and the nitrogen substitution in the 5-position of the pyrimidine ring found in 5-azacytidine (5-aza-C). The present study examined the cellular metabolism and the effect on DNA methylation of ara-AC in human CCRF/CEM cells sensitive and resistant to ara-C. The triphosphate anabolite of the drug, ara-ACTP, was the major anabolite in the CEM cellular extracts, peaking at 50.6±23 M 4 h after incubation with IC50 concentrations (0.25 M) of [3H]ara-AC. The mono- and diphosphate anabolites accumulated 10-fold lower cellular concentrations than ara-ACTP. The nucleoside triphosphate (NTP) pools and, especially, cellular ATP declined significantly by 9 h after the initiation of drug treatment and remained depleted for the 24-h treatment. The drug anabolite was gradually incorporated into both RNA and DNA, peaking in CEM/0 at 3.44 and 0.14 nmol/107 cells, respectively. The DNA methylation levels in these cells declined rapidly after treatment with ara-AC, attaining a nadir plateau at 29% of control methylation value. The deoxycytidine kinase (dCk) mutant CEM cell line [CEM/dCk(–)] neither activated ara-AC at appreciable levels nor induced DNA hypomethylation at low concentrations (0.25–1 M). However, the drug was activated at 0.2–1 M extracellular concentrations of ara-AC, probably by an as yet unknown nucleoside kinase at approximately 10% of the amount in CEM/0 cells. Ara-AC appears to mediate its cytotoxic action through the accumulation of its triphosphate anabolite, ara-ACTP, and the subsequent incorporation into nucleic acids. DNA methylation may also contribute to its cytotoxicity.Abbreviations 5-aza-C
5-azacytidine
- ara-AC
1--d-arabinofuranosyl-5-azacytosine
- ara-ACTP
1--d-arabinofuranosyl-5-azacytosine 5-triphosphate
- dCk
deoxycytidine kinase
- PCA
perchloric acid
- SAX
strong anion exchange
- PBS
phosphate-buffered saline
Supported by research grant CA 38905 from the National Institute of Health, NCI, and the T. J. Martell Foundation for Leukemia and Cancer Research, The Neil Bogart Memorial Laboratories 相似文献
1000.
Summary In the present investigation, administration of a single i.p. dose of the anticancer drug merbarone [5-(N-phenylcarboxamido)-2-thiobarbituric acid] produced an acute and reversible decrease in renal function in female but not male Fischer 344 rats. The renal lesion in female rats was biochemically characterized as a decrease inp-aminohippuric acid accumulation by renal slices along with polyuria, glucosuria, proteinuria, and enzymuria. These functional changes were accompanied by histopathologic changes of focal tubular necrosis that was confined to the deep cortex and outer stripe of the outer medulla. The changes in these parameters were dose-dependent and were observed at doses as low as 0.2×MELD10 (12 mg/kg). This low merbarone dose increased urinary glucose and protein excretion by 26- and 9-fold, respectively, in the initial 16-h urine collection in female rats. This increase was accompanied by a 2- to 15-fold increase in the excretion ofN-acetyl--d-glucosaminidase (NAG), -glutamyl transpeptidase (-GTP), and lactate dehydrogenase (LDH) activities. No significant changes in renal function were observed in male rats apart from mild enzymuria after a high dose of merbarone (36 mg/kg). The drug did not increase urea nitrogen levels in male or female rats, reflecting the focal nature of this tubular lesion. Merbarone produced small elevations in serum transaminase activities [i. e., glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT)] at doses that produced marked alterations in renal function in female rats, suggesting only mild hepatotoxicity. The present study establishes the kidney as a possible dose-limiting target organ for merbarone toxicity. 相似文献