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Biomedical subjects

D G Stein

Publications and source records attributed to D G Stein.

At least 55 records · Page 3Linked to original sources
PubMed1992

GM1 ganglioside effects on astroglial response in the rat nucleus basalis magnocellularis and its cortical projection areas after electrolytic or ibotenic lesions.

We examined the effects of chronic GM1 ganglioside injections on the astroglial response to bilateral electrolytic or ibotenic acid lesions in the nucleus basalis magnocellularis (NBM) within the NBM and in three cortical projection areas of NBM neurons. Glial fibrillary acidic protein (GFAP) immunohistochemistry was used to visualize the reactive astrocytes. Twenty-six days after injury, extensive astrogliosis was observed within the NBM after both types of lesions. An increased number of GFAP-positive cells were found in the cortex of saline-treated rats following electrolytic but not ibotenic lesions. We suggest that the loss of fibers of passage within the lesion area may account for the difference in cortical gliosis following the two types of damage. Although 17 days of GM1 injections did not affect astrocyte morphology within the NBM, ganglioside treatment reduced the number of GFAP-positive cells after electrolytic but not after ibotenic lesions. Within the cortex, a decrease in GFAP immunoreactivity, size, and number of astrocytes was only observed after electrolytic lesion. These data indicate that a decrease in the astroglial response to injury is the result of an interaction between the type of injury (electrolytic lesion) and chronic GM1 treatment.

Analysis of Variance↗
PubMed1992

Leukocyte-depleted reperfusion of transplanted human hearts prevents ultrastructural evidence of reperfusion injury.

The present study examines whether leukocyte depletion can prevent postreperfusion ultrastructural injury in transplanted human hearts. Thirty-two patients undergoing orthotopic cardiac transplantation were randomized to receive either enriched, warm, whole blood (Group I; n = 16) or enriched, warm, leukocyte-depleted blood (Group II; n = 16) reperfusion. Donor hearts were arrested with 1 liter of 4 degrees C crystalloid cardioplegia and topically cooled. RV endomyocardial biopsies taken at end-ischemia and following reperfusion were assessed in a blinded fashion and graded according to injury (1 = minimal to 4 = severe). The mean ischemic time (Group I = 142 min, Group II = 153 min) was similar in the two groups. End-ischemic biopsies showed mild-moderate interstitial edema and mild capillary endothelial swelling in both groups with similar injury scores (Group 1 = 1.3 +/- 0.09 (means +/- SEM), Group 2 = 1.25 +/- 0.08). Postreperfusion biopsies in Group I showed nuclear chromatin clumping, moderate mitochondrial swelling, marked capillary endothelial swelling, and marked interstitial edema with a grade of 2.6 +/- 0.14 (P less than 0.001, paired t test). In contrast, postreperfusion biopsies in Group II showed minimal changes with a grade of 1.33 +/- 0.09, P less than 0.0001 in comparison to Group I Leukocyte-depleted reperfusion of human transplanted hearts prevents ultrastructural injury. This may allow safe extension of the ischemic period and result in improved graft function.

Biopsy↗
PubMed1992

Effects of BIM-22015, an analog of ACTH4-10, on functional recovery after frontal cortex injury.

Male rats, 90-100 days old, with frontal cortex lesions were given either subcutaneous sterile water (SW) as a vehicle control or 1, 10, or 100 micrograms of BIM-22015 every other day for 20 days. Brain-injured subjects tested in the Morris water maze with either 10 micrograms BIM-22015 or SW took significantly more trials than sham-operated rats to locate a submerged platform eight consecutive times within 60 s. The animals given 1 or 100 micrograms BIM-22015 took significantly fewer trials to reach criterion than brain-injured animals in the other drug treatment groups. On a percentage of savings, measured 8 days after reaching criterion, the brain-injured subjects given 1, 10, or 100 micrograms BIM-22015 did not differ from sham-operated rats. In contrast, the brain-injured animals given SW took longer to find the submerged platform than they did during the initial training. To assess long-term effects of the ACTH analog treatment, rats were trained on a delayed spatial alternation task 30 days after receiving the last injection. On this task, brain-injured rats treated with the 10-micrograms dose performed significantly better than those given sterile water. Acetylcholinesterase (AChE)-labeled neurons counted in the nucleus basalis magnocellularis indicated that rats with frontal cortex damage given the 10-micrograms treatment did not differ from the sham controls and had significantly more AChE-positive neurons than injured counterparts treated with SW or 100 micrograms.

Acetylcholinesterase↗
PubMed1992

Perfluorochemical reperfusion limits myocardial reperfusion injury after prolonged hypothermic global ischemia.

The ability of an oxygenated perfluorochemical (Fluosol) to limit myocardial reperfusion injury following global hypothermic ischemic insult was investigated. Neonatal piglet hearts were arrested with cold crystalloid cardioplegia and stored for 12 hours in 2 degrees C saline. Reperfusion was carried out using an isolated, blood-perfused, working heart preparation. Hearts were initially reperfused (10 minutes) with either whole blood (WB, n = 6), unmodified perfluorochemical (PFC, n = 8), or aspartate/glutamate-enriched perfluorochemical cardioplegia (PFC+, n = 6), prior to institution of whole blood perfusion, functional evaluation and left ventricular biopsy. A control group (C, n = 7) was evaluated without an intervening period of ischemia. At a left ventricular diastolic pressure of 9 mm Hg WB hearts developed a left-ventricular stroke work index (SWI) of 3.8 +/- 2.3 x 10(3) erg/g (mean +/- standard error of the mean). Under similar conditions, PFC-reperfused hearts achieved a SWI of 14.6 +/- 1.3 x 10(3), significantly greater than that of WB (p less than 0.001). SWI for PFC+ hearts was 19.8 +/- 1.6 x 10(3), significantly increased over that of PFC (p less than 0.01), and not different from values obtained for C (19.2 +/- 0.8 x 10(3)). In addition, PFC-reperfused hearts demonstrated superior maintenance (p less than 0.05) of ATP (2.08 +/- 0.16 umole/g), compared to WB (1.50 +/- 0.19), while preservation of ATP in PFC+ hearts (2.99 +/- 0.12), was significantly increased over that of PFC (p less than 0.001), and not significantly different from that for C (2.68 +/- 0.17).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Total cavopulmonary anastomosis versus conventional modified Fontan procedure.

The total cavopulmonary anastomosis, lateral tunnel Fontan, has been advocated as a preferred method for Fontan type repair. From 1987 to July 1990, 39 patients underwent total cavopulmonary anastomoses (group 1) and 39 patients underwent modified Fontan procedures (group 2); patients receiving adjustable atrial septal defects were excluded. Diagnoses in group 1 included tricuspid atresia in 5 patients, single ventricle in 32, and pulmonary atresia and intact ventricular septum in 2. Diagnoses in group 2 included tricuspid atresia in 20, single ventricle in 17, hypoplastic left heart syndrome in 1, and pulmonary atresia and intact ventricular septum in 1. There were no significant differences in age, weight, cross-clamp time, duration of inotropic support, postoperative effusions, or hospital stay between the two groups. Early mortality in group 1 was 7.7% (3/39) and in group 2, 2.6% (1/39). There was no difference in the incidence of early dysrhythmias or early pacemaker placement. Late mortality was 2.8% in group 1 and 8% in group 2 with a mean follow-up of 18 and 25 months, respectively. Follow-up in group 1 revealed 33 patients in normal sinus rhythm and 1 patient with episodes of supraventricular tachycardia; no additional patients have required pacemakers. Follow-up in group 2 revealed 27 patients in normal sinus rhythm and supraventricular tachycardia in 4 patients; 5 additional patients have required pacemaker placement. There is no apparent difference in early outcome between the total cavopulmonary anastomosis and the conventional modified Fontan. However, there appears to be an increased incidence of late dysrhythmias and the need for pacemaker placement in the conventional modified Fontan group compared with the lateral tunnel group.

Adolescent↗
PubMed1991

Intracerebral administration of alpha-tocopherol-containing liposomes facilitates behavioral recovery in rats with bilateral lesions of the frontal cortex.

Adult rats with bilateral frontal cortex lesions received intracerebral infusion of phosphatidylcholine liposomes, or D-alpha-tocopherol-enriched liposomes, delivered continuously for 7 days to the damaged cortex by subcutaneous osmotic pumps. All subjects were first tested on a delayed spatial alternation task and then, 90 days later, on a spatial navigation task in the Morris water maze. Both tests showed that brain-injured rats with alpha-tocopherol treatment were less impaired than counterparts treated with plain liposomes. Alpha-tocopherol also reduced some of the injury-induced, secondary reactive changes that typically follow damage to the frontal cortex.

Animals↗
PubMed1991

Fetal brain tissue grafting as therapy for brain dysfunctions: Unanswered questions, unknown factors, and practical concerns.

Grafting of embryonic neural tissue into the brains of adult patients is being given serious consideration as therapy for a variety of degenerative and traumatic disorders. It has been argued that neural transplantation can promote functional recovery by replacement of damaged nerve cells, the reestablishment of specific nerve pathways lost as a result of injury, the release of specific neurotransmitters, or the production of factors that promote neuronal growth. This review evaluates the use of transplants to promote recovery from brain injury and highlights the kinds of questions and problems that clinicians need to consider before recommending this form of therapy to patients.

Brain Injuries↗
PubMed1991

Complete functional recovery after 24-hour heart preservation with University of Wisconsin solution and modified reperfusion.

Successful long-term myocardial preservation is dependent on optimizing conditions during arrest, storage, and reperfusion. Neonatal piglet hearts were arrested and stored in University of Wisconsin solution (UW) at 4 degrees C for 24 hours and reperfused on a blood-perfused, adult animal-supported isolated circuit. Results were compared with nonischemic continuously perfused control hearts (group 1, n = 5). The initial 10 minutes of reperfusion in groups 2-4 was modified by aspartate/glutamate-enriched leukocyte-depleted blood cardioplegia (group 2, n = 7), leukocyte depletion alone (group 3, n = 9), and aspartate/glutamate-enriched blood cardioplegia alone (group 4, n = 6). After 10 minutes, perfusion was continued with unmodified whole blood. In group 5 (n = 9), unmodified whole blood was used for initial reperfusion as well as subsequent perfusion. The stroke work index was determined 60 minutes after reperfusion. Biopsies for high-energy phosphates, myocardial water content, and electron microscopy were obtained after functional assessment. The stroke work index at left ventricular end-diastolic pressure of 9 mm Hg did not differ between groups 1 and 2 (19.0 +/- 1.4 x 10(3) and 19.0 +/- 1.5 x 10(3) [mean +/- SEM] erg/g, respectively). These were both different from group 5 (13.3 +/- 0.8 x 10(3) erg/g, p less than 0.05). Group 3 showed improved function (15.7 +/- 0.7 x 10(3) erg/g), but this did not reach statistical significance when compared with group 5. No difference was found between groups 4 and 5. Myocardial water content, high-energy phosphate levels, and ultrastructure were similar in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1991

Results of total cavopulmonary connection in the treatment of patients with a functional single ventricle.

Total cavopulmonary connection was proposed as a modification of the Fontan procedure that might have greater benefits than previous methods. To assess this procedure we reviewed case histories of 38 patients (aged 17 months to 30 years) who underwent Fontan procedures with cavopulmonary anastomoses between January 1987 and December 1989. The group included 32 patients with univentricular heart, 2 with pulmonary atresia and intact ventricular septum, 3 with tricuspid atresia, and 1 with hypoplastic left heart syndrome. One or more previous palliative procedures were performed in 34 patients, including 19 systemic-pulmonary shunts, 16 pulmonary artery bandings, 7 atrial septectomies/septostomies, 7 Glenn shunts, and 1 patent ductus arteriosus ligation. Preoperative hemodynamics showed a pulmonary artery pressure of 12 mm Hg (range 6 to 22 mm Hg), pulmonary-systemic flow ratio of 1.6 (range 0.37 to 3.0), left ventricular end-diastolic pressure 9 mm Hg (range 3 to 15 mm Hg), and systemic arterial oxygen saturation of 82% (range 67% to 94%). Concomitant with cavopulmonary connection, 13 patients underwent additional procedures, including 9 atrioventricular valve annuloplasties, 4 Damus-Stansel-Kaye procedures, and 2 resections of subaortic membranes. Modifying the Fontan procedure in this fashion was particularly useful in the management of 2 patients with pulmonary atresia and intact ventricular septum who had right ventricular-dependent coronary blood flow. Cavopulmonary anastomosis and atrial septectomy were performed in both patients, with resultant inflow of oxygenated blood to the right ventricle and coronary arteries. Excellent postoperative results were noted in each. Postextubation hemodynamics for the entire group included a mean right atrial pressure of 13 mm Hg (range 11 to 17 mm Hg), a mean left atrial pressure of 6 mm Hg (range 3 to 12 mm Hg), and a room air oxygen saturation of 96% (range 92% to 98%). Seven patients had pleural effusions, 3 required postoperative pacemaker placement, and 2 required reoperation for tamponade. A venous assist device was required in one patient on the second postoperative day, but the patient was weaned successfully within 24 hours. One early death (2.6%) occurred in a patient who had intractable ventricular fibrillation 2 days after operation. There was one late cardiac death (2.7%) caused by ventricular failure and one late noncardiac death. These results demonstrate that total cavopulmonary connection provides excellent early definitive treatment, with low morbidity and mortality, for a variety of complex congenital heart lesions.

Adolescent↗
PubMed1991

Cardiac preservation in patients undergoing transplantation. A clinical trial comparing University of Wisconsin solution and Stanford solution.

Recent laboratory investigations have shown significantly improved donor heart preservation and function when the University of Wisconsin solution (UW) is used for arrest and storage. These findings prompted us to compare UW to Stanford solution in a clinical trial. After giving informed consent, patients were blindly randomized to receive a heart arrested and stored in UW or a heart arrested in Stanford solution and stored in normal saline. Orthotopic transplants were performed in a routine manner. Fourteen patients with a mean age of 54 years were randomized to UW, and 15 patients with a mean age of 51 years were randomized to Stanford solution. Mean donor ages (UW 27 years, Stanford 24 years) and ischemic times (UW 150 minutes, Stanford 135 minutes) were similar. Several differences were observed intraoperatively. At end ischemia, mean adenosine triphosphate (UW 5.87 mmol/gm wet weight, Stanford 4.75 mmol/gm) and creatine phosphate (UW 9.26 mmol/gm, Stanford 4.75 mmol/gm) levels were higher in the UW hearts (p less than 0.05). Defibrillation requirements (UW 14% [2/14], Stanford 53% [8/15]) were significantly less in the UW group (p = 0.05). The number of patients requiring temporary intraoperative pacing also showed a significant difference with 7% (1/14) of UW patients versus 47% (7/15) of Stanford patients requiring pacing (p less than 0.05). Intraoperative requirement for inotropic support showed a trend in favor of the UW group. End-ischemic and postreperfusion histologic characteristics were similar between the two groups. No differences in hemodynamics or ejection fractions were noted postoperatively, but trends toward improved rhythm and decreased inotropic support were present in the UW group. Overall 6-month survival rates were similar (UW 86% [12/14], Stanford 93% [14/15]). No preservation-related deaths occurred. We conclude: (1) UW is a safe and effective preservation solution for human cardiac transplantation; (2) considering the improved end-ischemic adenosine triphosphate and creatine phosphate levels, decreased defibrillations, decreased intraoperative pacing, and trend toward decreased requirement for inotropic support in the UW group, UW appears to be superior to Stanford solution for donor heart preservation.

Adenosine Triphosphate↗
PubMed1990

Functional recovery following transplants of embryonic brain tissue in rats with lesions of visual, frontal and motor cortex: problems and prospects for future research.

In animals, fetal brain tissue grafts into damaged adult host brain reduce some of the functional deficits caused by brain lesions. Although neurons from transplants survive and develop reciprocal connections with host brain tissue, such connections are generally not enough to replace damaged fibers completely and support behavioral recovery observed. Moreover, grafts never exhibit a normal morphological appearance as compared to adult tissue, but some metabolic activity is occasionally detected within the transplant. Release and/or diffusion of trophic substances from the transplant, in addition to those from the damage host brain, may partially restore neuronal and behavioral functions especially after lesions of the visual cortex. In this case, it can be hypothesized that fetal transplants serve as "living mini-pumps". In addition, there is evidence that the combination of trophic substances (e.g. GM1 ganglioside) and fetal brain transplants may provide a better opportunity for recovery than either treatment given by itself.

Animals↗
PubMed1990

Effects of interleukin 2 on cardiac function in the isolated rat heart.

Adoptive immunotherapy with IL 2 is associated with severe cardiovascular toxicities including peripheral and pulmonary edema, hypotension decreased systemic vascular resistance, increased heart rate, and an increased cardiac index. The purpose of this investigation was to determine whether IL 2 alone or in combination with lymphokine-activated killer cells (LAK) cells depress cardiac function using the isolated, perfused, working rat heart preparation. Male Sprague-Dawley rats (250-350 g) were anesthetized and the hearts were removed and placed on the perfusion apparatus. Hearts were perfused with oxygenated Krebs-Henseleit buffer (KHB), or oxygenated KHB containing IL 2 alone, IL 2-Media (cell culture media supplemented with 1,500 U IL 2/ml), LYMPH (cell culture media from cultured mononuclear cells from healthy volunteers), or LAK (cell culture media from cultured lymphocytes harvested from patients receiving IL 2/LAK in the presence of 1,500 U/ml IL 2). The cells were removed before perfusion (n = 9). Cardiac output and coronary flow were measured at 20-min intervals with preload constant (afterload varied or afterload constant (preload varied). The results indicate a significant depression in cardiac function in hearts treated with LAK. This depression was evident at 20 min and was more pronounced at 60 min. Washout of the KHB plus LAK reversed this depression. Thus, IL 2-stimulated/cultured human mononuclear cells produce a soluble factor that produces a reversible severe depression of cardiac function.

Animals↗
PubMed1990

Some functional consequences of chronic GM1 ganglioside administration in brain damaged rats.

Systemic injections of GM1 gangliosides can enhance behavioral recovery from brain damage as measured by a number of cognitive tasks. The functional recovery is not due to GM1-induced alterations in activity, emotional arousal, or heightened sensitivity to mild, noxious stimulation. In addition, the recovery endures long after all treatments are terminated. Although the specific actions by which GM1 treatments facilitate recovery are unknown, evidence does suggest that both anomalous sprouting and protection of neurons from secondary consequences of injury may be involved in the repair process.

Animals↗
PubMed1989

Ginkgo biloba extract facilitates recovery from penetrating brain injury in adult male rats.

Adult, male Sprague-Dawley rats received 100 mg/kg Ginkgo biloba extract (GBE) intraperitoneally for 30 days. GBE reduced overall activity and decreased sensitivity to light in the open field maze. The rats were also less responsive to noxious stimuli after 13 days of treatment with GBE. After the last injection, all subjects were trained on a delayed-spatial alternation task. Subsequent to acquisition of the spatial task, the rats received either sham operations and saline or bilateral frontal cortex lesions treated with either saline or GBE. Thirty additional days of treatment began on the day of injury, and open field behavior, analgesia, and metabolic activity measurements were again measured. The rats with lesions treated with saline were more active than their GBE-treated counterparts and sham controls but there were no differences in response to illumination or noxious stimuli. Retention of the delayed-spatial alternation indicated that rats with lesions treated with GBE were less impaired than brain-injured subjects receiving saline treatment. Histological examination showed that GBE reduced the extent of brain swelling in response to the injury.

Animals↗
PubMed1988

Recovery from perseverative behavior after entorhinal cortex lesions in rats.

In a previous investigation we observed that entorhinal cortex lesions produce an impairment in spatial alternation characterized by repeated responses in one direction (i.e. 'perseveration'). Since this impairment disappears at the same time when the dentate gyrus is reinnervated by several of its remaining afferents, recovery from perseveration and sprouting may be related. To test this possibility, we examined the performance of two groups of rats with bilateral entorhinal lesions: one group began testing for retention of an alternation task on day 2 after the lesions; the other group began on day 12 (i.e. the time at which hippocampal sprouting occurs). Both groups exhibited significantly greater perseveration than their respective sham-operated groups over the first 6-12 days of testing. Thus, postoperative testing was required to facilitate the shift from perseverative to non-perseverative responding independent of the time at which sprouting in the dentate gyrus became established.

Animals↗
PubMed1988

Temporal factors influence recovery of function after embryonic brain tissue transplants in adult rats with frontal cortex lesions.

Adult rats with lesions of the medial frontal cortex received implants of frontal cortex taken from embryos on the 19th day of gestation and placed directly into the zone of injury at 7, 14, 30, or 60 days after initial surgery. Another group was given bilateral frontal lesions, followed 20 days later by a second small lesion to enhance the release of putative neurotrophic factors. They then received transplants 7 days after this second operation. All rats began postoperative training on a spatial alternation learning task within 4 days after the implants of fetal tissue. The brain-damaged rats with transplants at 7 or 14 days after surgery significantly improved postoperative acquisition of spatial alternation. Transplants made 30 or 60 days postoperatively had no effect; these groups were as impaired as those with lesions alone. The animals given a second, "priming" lesion after a 20-day delay, followed by implants of fetal brain tissue, performed as poorly as the group with frontal cortex lesions alone.

Animals↗