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1.
PURPOSE: To evaluate the effect of topical aqueous humor suppressants on the absorption of intravitreal perfluorocarbon gases. METHODS: Sulfur hexafluoride or perfluoropropane was injected intravitreally in five rabbits. Time to gas disappearance was measured in eyes treated with topical aqueous humor suppressants and in those not treated. RESULTS: The mean time (+/- SD) to disappearance of 0.4 cc of sulfur hexafluoride was 5.6 +/- 0.9 days, which was prolonged by 43% to 8.0 +/- 0.7 days with topical aqueous humor suppressants (P = .009). The mean time (+/- SD) to disappearance of 0.2 cc of perfluoropropane was 18.4 +/- 1.9 days, which was prolonged by 55% to 28.6 +/- 2.7 days with topical aqueous humor suppressants (P = .009). CONCLUSION: Aqueous suppressants prolong sulfur hexafluoride and perfluoropropane intravitreal gas bubble duration in rabbits.  相似文献   

2.
Spontaneously diabetic nonobese diabetic (NOD/Lt) mice were treated with anti-T-cell monoclonal antibodies (mAbs) at the time of grafting with vascularized segmental pancreas isografts. Recipients were either untreated or given anti-CD4 and/or anti-CD8 mAbs (0.5 mg/20-g mouse on each of 4 consecutive days), which reduced target cell levels to <5% of normal. Graft function was monitored by measuring blood glucose (BG) levels. Transplants were removed for histological examination when BG returned to >20 mmol/l for two consecutive readings. Isografts from 3- to 4-week-old prediabetic mice placed in untreated diabetic NOD mice ceased functioning in 9-13 days with a mean survival time (MST) +/- SD of 10 +/- 2. Treatment with anti-CD4 prolonged survival significantly (MST = 61 +/- 35 days, P < 0.05 compared with untreated control mice). Anti-CD8 treatment was less effective, but it still significantly improved graft survival (MST = 24 +/- 9 days, P < 0.05 compared with untreated control mice). Anti-CD8 plus anti-CD4 treatment was highly effective in inhibiting autoimmune destruction of the grafts (MST = 97 +/- 8 days). This clearly demonstrates that transient inactivation of most T-cells with anti-CD4 plus anti-CD8 mAbs effectively controls autoimmune disease in the isograft, despite recovery of CD4 and CD8 T-cells to normal levels. Although insulitis developed in the long-term grafts, insulitis scores did not increase between 33 and 100 days, and none of the mice progressed to IDDM in 100 days. Histology showed a predominantly peri-islet T-cell and macrophage infiltrate with ductal expression of the cytokines interleukin (IL)-4, IL-2, and interferon-gamma. There was little infiltrate or expression of cytokines within the islets. Thus, mAb treatment at the time of grafting allowed isograft survival and prevented progression from insulitis to beta-cell destruction.  相似文献   

3.
Seventy male Fischer 344 (F-344) rats were treated with s.c. injection of (-)deprenyl (0.5 mg/kg, n = 35) or physiological saline (n = 35) 3 times a week from the age of 18 months until the time of their natural death. The fifty percent survival time was 28 months in control animals and 30 months in the deprenyl treated group. The mean survival time after the start of treatment (18 months) and after 24 months were 378.3 +/- 97.4 days (mean +/- SD) and 196.3 +/- 97.4 days, respectively, in deprenyl treated rats and 328.7 +/- 108.8 days and 146.7 +/- 108.7 days in control rats. The increases in average life expectancies caused by deprenyl treatment (15% from 18 months and 34% from 24 months) were both statistically significant (P < 0.05, two-tailed t-test). The average body weights were comparable for both groups but the variation of body weight was greater in control groups, thus excluding the possibility that the life prolonging effect of deprenyl results from reduced dietary intake. The results confirm those of two previous studies (1,2) which reported a significant life prolonging effect of deprenyl in aged rats and lend added support to the results of a study on male F-344 rats where the effect was only marginally significant (16% increase after 24 months, P = 0.048 by one-tailed t test) (2).  相似文献   

4.
PURPOSE: Measuring the concentration of oxygen in the aqueous humor without penetrating the eye would provide a new dimension in understanding aqueous humor and corneal dynamics. In this study a preinvasive method was developed for determining the cameral oxygen concentration in anesthetized rabbits by measuring the excited-state lifetime of a phosphorescent dye. METHODS: A scanning ocular fluorometer was designed to excite phosphorescence with a brief flash of light and to measure the decay of luminescence for as long as 1000 microsec after excitation. The measurement window was scanned through the depth of the anterior chamber or fixed at the mid-anterior chamber. A depot of the phosphorescent dye Pd-uroporphyrin was injected into the vitreous of eight pigmented rabbits, and within a few days the dye was measurable in the anterior chamber. The excited-state lifetime of this dye is inversely correlated to oxygen concentration and was calibrated by measuring the lifetime of dye in cuvettes equilibrated with oxygen-nitrogen mixtures. Oxygen tensions were determined from lifetimes measured in the open eye, under a polymethylmethacrylate (PMMA) contact lens, under two oxygen-permeable contact lenses, and immediately after lid closure. RESULTS: Oxygen tension in the mid-anterior chamber before placing a PMMA contact lens was 23 +/- 3 mm Hg (mean +/- SD; n = 6). After 20 minutes of PMMA lens wear, oxygen tension decreased to 4 +/- 2 mm Hg. When the focal diamond was scanned through the anterior chamber, oxygen tension was 24 +/- 5 mm Hg near the corneal endothelium and decreased to 17 +/- 8 mm Hg near the crystalline lens. Under the PMMA contact lens this gradient reversed: Oxygen tensions near the endothelium and lens were 3 +/- 2 mm Hg and 6 +/- 2 mm Hg, respectively. Lid closure for 10 minutes or longer decreased the mid-anterior chamber oxygen tension from 21 +/- 2 mm Hg (n = 19 measurements from seven animals) to 10 +/- 3 mm Hg (n = 15 measurements from five animals). CONCLUSIONS: Measuring excited-state lifetime of phosphorescent dyes in the anterior chamber provides a useful method for determining oxygen concentration in vivo, without penetrating the eye. Cameral oxygen tension under PMMA contact lenses are significantly lower than in the uncovered eye. The profile of oxygen tension through the anterior chamber suggests that oxygen is supplied transcorneally to the aqueous humor.  相似文献   

5.
The number of silver stained nucleolar organiser regions (Ag-NORs) was enumerated in the biopsy specimens of 73 patients with human pancreatic adenocarcinoma. The number of Ag-NORs was related to histological features, S-phase fraction (SPF), DNA ploidy, morphometric nuclear features, clinical stage and survival. Grade I tumours had on average fewer Ag-NORs (mean +/- SD, 5.2 +/- 2.0) than grade II (mean +/- SD, 5.9 +/- 1.6) or grade III (mean +/- SD, 6.6 +/- 2.6) tumours. Patients with low SPF (0-7%) values had lower mean Ag-NORs counts (5.7 +/- 1.0) than patients with a high SPF (7%) (6.6 +/- 2.0) (p = 0.05) and the number of Ag-NORs was related almost significantly to mitotic index (p = 0.09). The Ag-NORs were not related significantly to DNA ploidy or to clinical stage. In survival analysis the number of Ag-NORs predicted prognosis significantly (p = 0.03). From the results we conclude that Ag-NORs are related to several malignant features in human pancreatic adenocarcinoma and that the number of Ag-NORs predicts survival.  相似文献   

6.
PURPOSE: The purpose of this study was to devise and evaluate a laboratory test of cycling performance that simulates the variable power demands of competitive road racing. The test is a 100-km time trial interspersed with four 1-km and four 4-km sprints. METHODS: On three occasions separated by 5-7 d, eight endurance-trained cyclists (peak oxygen uptake 5.0 +/- 0.7 L.min-1, peak power output 411 +/- 43 W, mean +/- SD) performed the test on their own bikes mounted on an air-braked Kingcycle ergometer. Subjects were free to regulate their power output but were asked to complete each sprint and the full distance as quickly as possible. The only feedback given to the cyclists during each test was elapsed distance. RESULTS: In the first test, time for the 100 km and mean times for the 1-km and 4-km sprints were 151:42 +/- 10:36, 1:16 +/- 0:06, and 5:31 +/- 0:16 min:s, respectively; these times improved by 1.6-2.2% in the second test, but there was little further improvement in the third test (0.7 to -0.5%). The between-test correlation for 100-km time was 0.93 (95% CI 0.79 to 0.98), and the within-cyclist coefficient of variation was 1.7% (95% CI 1.1 to 2.5%). Mean sprint performance showed similar good reliability (within-subject variation and correlations for the 1-km and 4-km sprint times of 1.9%, 2.0%, 0.93, and 0.81, respectively). CONCLUSIONS: The high reliability of this laboratory test will make the test useful for research on performance of competitive road cyclists.  相似文献   

7.
The purpose of this study was to evaluate the efficacy of local immunosuppression with intraportal administration of cyclosporine (CsA) in liver transplantation. Mongrel dogs weighing 12-18kg were used. Orthotopic liver transplantation was performed, and animals were divided to the following groups. Group I (n = 7): no treatment, group II (n = 7): CsA 5mg/kg/day intermittent iv, group III (n = 5): CsA 3mg/kg/day continuous iv and group IV (n = 8): CsA 3mg/kg/day continuous portal infusion. Immunosuppressive treatments were carried out for two weeks postransplant. Median survival time (MST) of group IV was significantly prolonged (MST = 18 days, range 10-85 days; p < 0.025) compared with group I (7 days, range 6-13), group II (10 days, range 7-16) and group III (7 days, range 6-10). Data of blood chemical analyses showed that hepatic dysfunction was significantly diminished in group IV compared with other groups (p < 0.05). Blood concentration of CsA on the 5th day (mean +/- SEM) was significantly lower in group IV (238 +/- 22ng/ml) than in group III (438 +/- 113ng/ml). Histologic findings showed that rejection reaction was effectively suppressed in group IV, although SG2M% (mean +/- SEM) of peripheral mononuclear cells of group IV (10.6 +/- 3.3%) was equal to that of group III (11.3 +/- 1.7%). In conclusion, local immunosuppression could achieve prominent effect in preventing hepatic graft rejection with limited systemic immunosuppression.  相似文献   

8.
OBJECTIVES: To test the practicablity of a new spectrophotometric method using pulse oximetric techniques in combination with special filters for the noninvasive determination of cerebral arterial and venous oxygen saturation and oxygen extraction in neonatal intensive care unit patients. The spectrophotometer used three different wavelengths at a sampling rate of 100 Hz. DESIGN: Clinical evaluation of a new method and comparison with previously published data. SETTING: Design and construction of the special spectrophotometer at the Biomedical Engineering Laboratory of the Swiss Federal Institute of Technology. Measurements in the neonatal intensive care unit of the University Hospital, Zurich, Switzerland. PATIENTS: Convenience sample of 15 clinically stable newborn infants, who were mechanically ventilated and receiving supplemental oxygen. Median gestational age was 29 5/7 wks (range 26 3/ 7 to 36 0/7), median birth weight was 1555 g (720 to 2500), median postnatal age was 4 days (1 to 10). INTERVENTIONS: The emitter and receiver were placed on the forehead near the sagittal sinus, between 2 and 2.8 cm apart, and the pulsating light attenuations (arterial and venous pulse waves) were recorded. MEASUREMENTS AND MAIN RESULTS: Arterial and venous pulse waves were satisfactory in 10 of 15 infants. Mean cerebral arterial oxygen saturation was 89.9 +/- 5.4% (SD), mean cerebral venous oxygen saturation was 73.0 +/- 8.9%, and mean cerebral oxygen extraction was 16.9 +/- 11.7%. A linear regression analysis demonstrated a significant correlation between mean PCO2 and venous oxygen saturation (slope 1.0%/torr, p < .05) and between mean PCO2 and cerebral oxygen extraction (slope -1.3%/torr, p < .05). CONCLUSION: This new method has the potential for monitoring continuously, noninvasively, and simultaneously cerebral arterial and venous oxygen saturation and oxygen extraction in mechanically ventilated preterm infants.  相似文献   

9.
Sensitivity to ischemia and reperfusion injury is a main problem afflicting tissues exposed to a prolonged period of oxygen deprivation. The generation of oxygen free radicals, in particular, is considered a major cause of postischemic reperfusion injury. However, studies on the mechanisms of production of free radicals are limited by the difficulty to measure in real time their formation and to discriminate between the different oxyradical species. The aim of this study was to determine whether the formation of oxygen free radicals occurs in murine osteoblastlike cells (MC3T3-E1) exposed to anoxia and reoxygenation and to explore its relation to the reoxygenation injury. Cells were cast in agarose and perfused with oxygenated Krebs-Henseleit bicarbonate buffer. Anoxia was obtained by shifting the gas phase of the media to 95% N2-5% CO2. Oxygen free radicals were detected by enhanced chemiluminescence: anion superoxide or hydrogen peroxide was measured by adding lucigenin or luminol plus horseradish peroxidase to the media, respectively. Cell injury was assessed by the rate of lactate dehydrogenase release. During the control period, lucigenin and luminol plus horseradish chemiluminescences were 15 +/- 1 nA per chamber and 20 +/- 2 nA per chamber, respectively. and lactate dehydrogenase release was 10 +/- 1 mU per minute. During anoxia, both chemiluminescences dropped to background levels, although lactate dehydrogenase release increased progressively to 38 +/- 7 mU per minute. During reoxygenation, O2 formation increased sharply to 45 +/- 6 nA and decreased to control levels; H2O2 production increased slowly, reaching 42 +/- 7 nA at the end of the reoxygenation period; lactate dehydrogenase declined progressively to control values. These results show that osteoblastlike cells produce measurable amounts of superoxide and hydrogen peroxide radicals during reoxygenation. Because lactate dehydrogenase release did not appear to relate to chemiluminescence, oxyradical flux may serve as a signal for other events that eventually lead to cell injury.  相似文献   

10.
The effect of local cyclosporine therapy upon corneal transplant survival was investigated. A high risk rabbit model with vascularized corneas was used to assess the efficacy of subconjunctivally implanted degradable devices for cyclosporine therapy. Animals were divided into four groups, receiving either no therapy, a placebo PLGA device, or drug containing devices implanted either at the time of transplantation or two weeks previous. The mean survival times of animals in the control and placebo groups were statistically equivalent (21 +/- 4 days vs 18 +/- 4 days). Devices containing CsA improved the survival time of grafts. Predosing the animals with CsA improved the survival time to 28 +/- 7 days, and CsA devices implanted at the time of transplantation increased the survival time to 35 +/- 7 days. The improvement in survival times was consistent with the in vitro drug release profiles. No systemic CsA was detected, suggesting that the effect may have been local. Histological assessment indicated that devices were well tolerated.  相似文献   

11.
PURPOSE: To assess the accuracy of intraarterial measurement of transstenotic pressure gradients for the detection of hemodynamically suboptimal iliac angioplasty. METHODS: In 14 patients, referred for diagnostic angiography, mean pressure gradients in the aorta and iliac artery were obtained twice, using a double-sensor pressure catheter. Additional iliac measurements were performed during pharmacologically induced flow augmentation. Repeatability was assessed by calculation of the mean difference plus standard deviation (MD +/- SD) and repeatability coefficient (2 x SD). These results were extrapolated to 137 iliac angioplasty procedures with secondary stenting where there was a residual pressure gradient > 10 mmHg. RESULTS: MD +/- SD for repeated measurements at rest and during flow augmentation were 0 +/- 2 mmHg and 1 +/- 3 mmHg, respectively. Repeatability coefficients were 3 and 6 mmHg. Mean pressure gradients after hemodynamically insufficient angioplasty were 8 +/- 7 mmHg at rest and 17 +/- 5 mmHg following vasodilatation. Inaccurate pressure recordings may have led to inappropriate stent placement in less than 2.5%, and inappropriate denial of stent placement in less than 5% of the lesions. CONCLUSION: Variability of intraarterial pressure measurements has little consequence in the detection of hemodynamically significant stenosis after angioplasty.  相似文献   

12.
OBJECTIVE: To investigate the effects of adjunctive therapy with parenteral N-acetyl-L-cysteine in patients with newly diagnosed septic shock. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Multidisciplinary intensive care unit at a university teaching hospital. PATIENTS: Twenty patients (N-acetyl-L-cysteine group [n = 10], placebo group [n = 10]), 15 male and five female, of mean age 64 +/- 15 (SD) yrs and Acute Physiology and Chronic health Evaluation (APACHE) II score 33 +/- 6, with septic shock within 24 hrs of diagnosis. INTERVENTIONS: After a 2-hr stabilization period (time-zero minus 2 hrs to time-zero), patients received either N-acetyl-L-cysteine in 5% dextrose (150 mg/kg in 100 mL over 15 mins, followed by 50 mg/kg in 250 mL over 4 hrs, and then 100 mg/kg/24 hrs in 500 mL for 44 hrs; N-acetyl-L-cysteine group) or the equivalent volume of 5% dextrose (placebo group). MEASUREMENTS AND MAIN RESULTS: Hemodynamic and oxygen transport indices were measured at time-zero minus 2 hrs and time-zero, and at multiple time points thereafter until completion of the trial infusion (time-zero plus 48 hrs). A daily Organ Failure Score was recorded for 14 days. Treatment group demographics and hemodynamic variables did not differ significantly between the two groups at time-zero. Mean (SD), pooled mean arterial pressure (MAP), and cardiac index were 75 +/- 15 mm Hg and 3.9 +/- 1.2 L/min/m2, respectively. Over the next 48 hrs, in the N-acetyl-L-cysteine group, there was a progressive decrease, relative to both time-zero and the placebo group, in MAP, cardiac index, and left ventricular stroke work index (p < .01, repeated-measures analysis of variance). Percentage reductions in these values relative to the placebo group at 48 hrs were 23%, 18%, and 43%, respectively Oxygen transport indices, arterial blood gas analyses, Pao2/Fio2 ratio, and shunt did not differ over time between the groups. There was no difference in either daily Organ Failure Score over time (p > .01, repeated-measures analysis of variance) or hospital mortality rate (90% N-acetyl-L-cysteine group, 50% placebo group) (p > .1, logistic regression) between the two groups. CONCLUSION: Adjunctive therapy with N-acetyl-L-cysteine in newly diagnosed septic shock was associated with a depression in cardiovascular performance, as indicated by progressive reductions in cardiac index, left ventricular stroke work index, and MAP.  相似文献   

13.
BACKGROUND: We wished to determine whether transcutaneous oximetry or laser Doppler flowmetry (LDF) could identify patients at risk for wound failure after conservative, limb-sparing surgery for extremity sarcomas. METHODS: Studies were performed on postoperative days (PODs) 1, 4/5, 7, and 9. Measurements of transcutaneous oxygen pressure (tcPO2) were taken at breathing room air (BL) and 100% oxygen (rate tcPO2). LDF measurements were taken at multiple sites along the wound, and a perfusion index was calculated. RESULTS: Twenty-four patients were studied. Four (17%) had nonhealing wounds. There was no difference in tcPO2 (BL) values between healed and nonhealing wounds. Measurement of rate tcPO2 on POD 1 was significantly lower in the nonhealing wounds than in those with normal healing (28.5 +/- 12.1 mm Hg vs 14.3 +/- 16.2 mm Hg, mean +/- SD, p = 0.03). Rate tcPO2 values increased significantly in healing wounds from POD 1 to PODs 7 and 9 (p = 0.006, p = 0.009). This increase was absent in nonhealing wounds. A clear separation was noted in rate tcPO2 values between groups, with a minimum rate tcPO2 value recorded in a healed wound of 9 mm Hg/min, compared with the maximum value in a nonhealing wound of 7 mm Hg/min. The LDF perfusion index failed to predict wound healing at any of the measured time points. CONCLUSIONS: This study showed that measurement of tcPO2 during oxygen inhalation can accurately predict wound healing in patients after excision of an extremity sarcoma.  相似文献   

14.
OBJECTIVE: To compare the short-term and long-term efficacy of using releasable sutures vs conventional interrupted sutures for scleral flap suturing in trabeculectomy. DESIGN: A prospective randomized study. SETTING: A university-affiliated referral eye hospital. PATIENTS: Thirty consecutive patients requiring trabeculectomy for uncontrolled primary glaucoma. INTERVENTION: Fifteen patients underwent trabeculectomy with permanent interrupted sutures; the same number underwent trabeculectomy with releasable sutures. MAIN OUTCOME MEASURES: Incidence of short-term shallowing of anterior chamber or hypotony and related complications, and long-term intraocular pressure control and bleb score. RESULTS: The mean percentage reduction in intraocular pressure on day 1 in the group with releasable sutures was 55.2%, while only a 0.8% reduction in anterior chamber depth was noted. This compared with figures of 59.3% and 10.1%, respectively, in the group without releasable sutures. Hypotony (intraocular pressure < or =6 mm Hg) was noted in 8 (53%) of cases without releasable sutures and 3 (20%) of cases with releasable sutures. Shallow anterior chamber (central anterior chamber depth, < or =1 mm) was noted in 5 (33%) of cases without releasable sutures and 1 (7%) of cases with releasable sutures. The mean +/- SD final bleb score was 5.4 +/- 0.3 in the group with releasable sutures compared with 4.2 +/- 0.6 in the group without releasable sutures (P<.001). The mean +/- SD final intraocular pressure at the end of 12 months was 16.9 +/- 1.2 mm Hg in the group without releasable sutures and 15.0 +/- 0.9 mm Hg in the group with releasable sutures (P<.001). Final intraocular pressure was controlled (intraocular pressure < or =21 mm Hg) in all patients in the group with releasable sutures, giving a success rate of 100%, and in 12 patients in the group without releasable sutures, giving a success rate of 80%. CONCLUSIONS: Use of releasable sutures is an effective way at no extra cost or instrumentation to maximize the long-term bleb score and lower intraocular pressure, and to minimize the short-term complications of trabeculectomy.  相似文献   

15.
Recent evidence suggests that approximately 90% of retinal ganglion cells (RGCs) die by the process of apoptosis within 14 days of optic nerve transection. RGCs begin to disappear from the retina between 5 and 7 days postaxotomy when the highest percentage of RGCs show characteristics typical of apoptosis. A single intraocular injection of glial cell-line derived neurotrophic factor (GDNF) given at the time of axotomy resulted in a delay in the initiation of RGC death and increased the densities of surviving RGCs at 7, 10 and 14 days postaxotomy. The mean RGC densities in GDNF treated retinas at 7 (2381 +/- 144), 10 (1561 +/- 117) and 14 (1123 +/- 116) days postaxotomy were significantly higher than that of controls (1835 +/- 82, 835 +/- 272 and 485 +/- 39, respectively). The loss of RGCs was paralleled by increases in TUNEL positive staining in control retinas and a lower percentage of TUNEL positive cells in GDNF treated retinas at 5, 7 and 10 days postaxotomy. These results suggest that GDNF is capable of promoting RGC survival following injury, possibly by interfering with an essential step in apoptosis.  相似文献   

16.
Visual evoked potentials (VEPs) of the pattern shift reversal type were determined in a representative group of 57 prisoners of war (POWs) released in 1992 from detention camps in former Yugoslavia. The parameters were correlated with the conditions in four camps (1-4). All subjects were male, with a mean age of 34.75 years (SD +/- 8.92), average length of imprisonment 192.7 days (SD +/- 77.6), mean loss of body mass during imprisonment 19.32% (SD +/- 9.54), and the average number of reported blows to the head and neck was 25.7 (SD +/- 20.3). VEPs were determined on average 290.5 days after the last craniocerebral trauma caused by blows to the head and neck (SD +/- 152.0) i.e., on average 218.5 days after release from the camp (SD +/- 164.3). Although all the 57 POWs reported being maltreated to a certain extent, 14 reported being subjected to particularly brutal forms of torture, 5 had been held in solitary confinement and 25 had lost consciousness at least once. Solitary confinement and loss of consciousness had the most significant effect on VEPs, and the altered VEP parameters correlated significantly with the craniocerebral trauma experienced, loss of body mass and the length of time since the last craniocerebral trauma until examination, and from release until examination. However, the length of imprisonment and treatment in the camps did not have a significant effect on VEP parameters. The study confirmed that under such conditions the age of the subject is a risk factor. The results of this study also confirmed that prisoners in one camp had been subjected to the worst maltreatment.  相似文献   

17.
OBJECTIVE: To measure the effect of hypertension on neointima formation after balloon injury of rat aorta and its association with the local angiotensin converting enzyme (ACE) concentration. Balloon angioplasty of the thoracic aorta using a 2 French Fogarty catheter was performed in spontaneously hypertensive rats (SHR) and normotensive Sprague-Dawley (SD) rats. RESULTS: The injured aortic wall of SHR had already significantly higher ACE concentrations than did the uninjured aortic wall of normotensive SD rats (media: 729 +/- 37 dpm/mm2 in SHR versus 496 +/- 38 dpm/mm2 in SD rats, P < 0.01; intima: 83 +/- 5 dpm/mm2 versus 68 +/- 6 dpm/mm2 in SD rats, P < 0.01). Fourteen days after injury of the aorta the hypertensive rats had significantly higher neointima: media ratios than did the normotensive rats (0.83 +/- 0.09 versus 068 +/- 0.01, P < 0.01). This was associated with a significant increase in vascular media and neointima ACE concentrations in SHR (media 965 +/- 25 dpm/mm2, neointima 614 +/- 48 dpm/mm2) compared with those in normotensive SD rats after balloon angioplasty (media 669 +/- 23 dpm/mm2, neointima 287 +/- 33 dpm/mm2, P < 0.01). ACE inhibitor treatment with 10 mg/kg body weight lisinopril daily for 14 days by gavage reduced neointima proliferation in hypertensive and normotensive rats (neointima: media ratio: 0.35 +/- 0.02 for SHR, P < 0.01, versus untreated SHR with balloon injury; 0.28 +/- 0.01 for SD, P < 0.01, versus untreated SD rats with balloon injury). This was associated with significant vascular media ACE inhibition (SHR 149 +/- 9 dpm/mm2; SD rats 118 +/- 7 dpm/mm2; P < 0.01 versus untreated controls with balloon injury) and neointima ACE inhibition (SHR 73 +/- 4 dpm/mm2, SD rats 63 +/- 7 dpm/mm2, P < 0.01, versus untreated controls with balloon injury), but also lowered the blood pressure in SHR significantly (to 148 +/- 5 mmHg, P < 0.01, versus untreated SHR with balloon injury). When this drop in blood pressure was prevented by feeding the rats a high-salt diet (SHR with ACE inhibitor plus high salt-diet group blood pressure 193 +/- 3 mmHg, P = 0.57, versus untreated SHR) hypertension per se without the local ACE increase (ACE concentration in SHR with ACE inhibitor high-salt diet rats' media 167 +/- 10 dpm/mm2 and neointima 81 +/- 9 dpm/mm2) had only a mild effect on neointima formation after balloon angioplasty (neointima: media ratio 0.4 +/- 0.01 for SHR with ACE inhibitor plus high-salt diet versus 0.35 +/- 0.02 for SHR with ACE inhibitor plus normal-salt diet P < 0.05). Treatment with 10 mg/kg body weight angiotensin II subtype 1 receptor antagonist losartan potassium daily for 14 days by gavage was associated with a reduction in neointima formation similar to that observed with the ACE inhibitor both for SHR and for SD rats (neointima: media ratio 0.32 +/- 0.04 for SHR with losartan, 0.27 +/- 0.03 for SD rats with losartan; P < 0.01, versus untreated controls with balloon injury) suggesting that ACE inhibitor prevented neointima formation, at least in part by, reducing the local production of angiotensin II. CONCLUSION: Neointima formation after balloon angioplasty in SHR is increased compared with that in normotensive SD rats. This is due mainly to there being a higher degree of activation of the renin-angiotensin system in the aorta of the SHR before and after balloon injury compared with that in normotensive SD rats measured in terms of the increased vascular ACE concentrations. Blood pressure alone had only a moderate effect on neointima formation.  相似文献   

18.
Twenty patients with intestinal bacterial overgrowth and 20 control subjects were investigated for bile acid deconjugation, by measuring 14CO2 in the breath after cholyl-1-[14C]glycine administration. 14CO2 output/24h was 11.0 +/- 5.2% (mean +/- SD) in controls and 54.2 +/- 14.0% (mean +/- SD) in bacterial-overgrowth patients (P less than .001). 14CO2 excretion rate in 12h, when normalized to 100% of the dose at the 12th hour, gave an even finer discrimination between the two groups (no false responses). 14C in stool, analyzed in 20 malabsorption patients and 20 controls by two different techniques, was 6.6 +/- 4% and 31.38 +/- 21.7% (mean +/- SD), respectively. Results by the two different techniques described here correlated well (r = .99). Bile acid malabsorption was in reasonable agreement (r = .67) with percentage of "chenoid" (chenodeoxycholic acid plus ursodeoxycholic acid) in the stool by gas-liquid chromatography; a poorer correlation was observed when "chenoid" plus "choloid" (cholic acid plus its epimers) were plotted vs. -4C in stool (r = .57, n = 15).  相似文献   

19.
Autochthonous neurogenic tumors of the rat induced by transplacental application of ethylnitrosourea were used for the first time to study their suitability as tumor models for experimental chemotherapy. Of 189 transplacentally treated rats, 87% developed neurogenic tumors. After the initial clinical diagnosis of a neurogenic tumor, additional malignant tumors often occurred. The mean number of neurogenic tumors from 62 untreated control rats increased from 1.0 per rat at the time of randomization to 1.2 as revealed by autopsy and 1.5 tumors by histological examinations. Out of all neurogenic tumors, tumors of the brain were observed in 31%, tumors of cranial nerves in 36% (90% tumors of trigeminal nerve), tumors of spinal cord in 21%, and tumors of peripheral nerves in 10%. The median survival time until natural death of 62 control rats was 228 days. Rats with tumors of peripheral nerves lived shortest, followed by rats with tumors of cranial nerves, tumors of the spinal cord, and brain tumors. Brain tumors were mainly astrocytomas and oligodendrogliomas. The survival time of untreated rats from randomization to natural death was longest for those with brain tumors, followed by tumors of peripheral nerves, cranial nerves, and tumors of the spinal cord. There was great variation in survival time from a few days to more than 6 months. To study the responsiveness to chemotherapy, 62 rats received BCNU as a single intravenous dose of 9 and later 10 mg/kg. Sixty-two untreated control rats had a median survival time of 36 days (95% confidence interval 26-52 days), the treated rats 43.5 days (26-62 days). The difference was not statistically significant. BCNU produced a remission or a no change of neurologic symptoms in 60% (37 out of 62) in comparison to 39% (24 out of 62) in the control group (p less than 0.05). The advantages and disadvantages of the present models are discussed. Due to methodical problems and the marginal response to BCNU, autochthonous neurogenic tumors of the rat are not suitable as models for chemotherapeutic studies.  相似文献   

20.
Some patients with early-stage cirrhosis preserve hepatic function, whereas others have little hepatic reserve and rapidly deteriorate. The aim of this study was to use quantitative tests of liver function (QLFTs) to define the degree of functional hepatic impairment in patients with early-stage cirrhosis (Child-Pugh score 5-7) and to determine whether the tests predicted subsequent hepatic decompensation. We recruited 10 cirrhotic (Cr) patients and 10 healthy controls (NI), who were well matched for race, age, weight, and gender. Clearances of caffeine (CF) and antipyrine (AP) after oral administration were measured from timed samples of saliva. The clearance of cholate (CA) was measured from serum samples obtained after simultaneous oral ([2,2,4,4-2H]CA) and intravenous ([24-13C]CA) administration. CA shunt was calculated as (Cl i.v./Clo x 100%). CF elimination rate (Cr v NI, mean +/- SD: 0.03 +/- 0.02 v 0.075 +/- 0.018 h-1, P < .0005) and AP clearance (24 +/- 16 v 40 +/- 7 mL/minute, P < .02) were reduced in Cr patients. CA shunt was increased in Cr patients (43 +/- 18 v 18 +/- 7%, P < .002). Five Cr patients decompensated during follow-up and had the worst CA shunts (76%, 66%, 51%, 48%, and 45%). Three subsequently received successful orthotopic liver transplantation, 1 died of hepatoma, and 1 is on the waiting list for transplantation. In conclusion, QLFTs define the degree of functional impairment in early cirrhosis and may identify Cr patients at greatest risk of decompensation who may require transplantation for survival.  相似文献   

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