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Biomedical subjects

R G Lee

Publications and source records attributed to R G Lee.

At least 55 records · Page 3Linked to original sources
PubMed1996

Pathology of human intestinal transplantation.

BACKGROUND & AIMS: Intestinal transplantation is a developing therapeutic option for patients with irreversible intestinal failure or short bowel syndrome. The aim of this study was to delineate the histopathology of human intestinal allografts and to define the features of intestinal rejection. METHODS: The histological features of 3015 endoscopic biopsy specimens and 23 allograft specimens from 62 intestinal recipients were analyzed retrospectively and correlated with clinical findings. RESULTS: Acute allograft rejection was characterized by a varying combination of crypt injury, mucosal infiltration primarily by mononuclear cells (including blastic lymphocytes), and increased crypt cell apoptosis (more than 2 per 10 crypts). It represented a patchy, often ileal-centered process that could progress to mucosal ulceration; later episodes (more than 100 days posttransplant) tended to show lesser cellular infiltration and greater apoptosis than earlier episodes. Correlation with clinical rejection was good (false-positive rate of 9%; false-negative rate of 26%). Two resected specimens showed obliterative arteriopathy indicative of chronic rejection. In other specimens, preservation injury, cytomegalovirus infection, post-transplant lymphoproliferative disorder, and nonspecific features of active or past mucosal injury could be recognized. CONCLUSIONS: Mucosal biopsy specimens are a useful means of monitoring intestinal allografts. Based on features validated by clinical correlation, acute rejection can be identified reliably and can be differentiated from the other pathological processes affecting the intestinal allograft.

Acute Disease↗
PubMed1996

Liver allograft pathology in liver/small bowel or multivisceral recipients.

Combined liver/small bowel (LSB) and multivisceral (MV) transplantation represents an alternative treatment for patients with short-gut syndrome complicated by end-stage liver disease. However, the question of whether the addition of an intestinal allograft alters the pathologic features of the transplanted liver remains unanswered. We, therefore, evaluated the histologic features of 51 liver biopsy specimens from 13 LSB or MV recipients and compared them with a matched control group of specimens from recipients of isolated liver allografts. In general, the histologic alterations were comparable in the LSB/MV and control groups. The primary difference was that portal and sinusoidal neutrophilia accompanied acute cellular rejection in 10 (63%) of 16 LSB/MV specimens but none of the control specimens. Concurrent culture results were positive in 5 of the 10 cases: bacterial overgrowth of the intestinal allograft was found in 3 cases, and bacteremia in 2 other cases, 1 of which had also a positive liver culture. In contrast, these cultures (n = 7) were negative in the six LSB/MV cases of neutrophil-free acute cellular rejection. Neutrophilia was also present in 26 additional LSB/MV specimens, including instances of preservation injury, sepsis, impaired bile flow due to ampullary dysfunction, and one case without an underlying diagnosis, but its frequency did not significantly differ from that of corresponding control cases. An additional finding was the occurrence of a "fibrosing cholestatic" pattern of acquired hepatitis C in 10 specimens from 2 LSB/MV recipients. Acute cellular reaction-associated neutrophilia in LSB/MV recipients may reflect portal bacteremia resulting from bacterial overgrowth and translocation from the intestinal graft or represent simply a nonspecific hepatic response to intestinal inflammatory processes.

Adult↗
PubMed1995

Mucosal perfusion and reactivity of the rat small intestinal allograft.

During acute rejection (AR), the endothelial targeting seen in the mucosal vessels of the intestinal allograft (IA) could impair the blood supply and response to luminal stimuli. To study the effect of AR in the perfusion and reactivity of the IA mucosa, we measured the mucosal blood flow in the ileum (IL) of 2 groups of control rats (Lewis and ACI) and in the native and grafted IL of syngeneic (ACI to ACI) and allogeneic (donor ACI to recipient Lewis) rats. Using reflectance spectrophotometry and laser-Doppler flowmetry, parameters of mucosal oxygen saturation (ISO2), hemoglobin content (IHB), and blood flow (FLOW) were obtained at baseline and after saline and 50% dextrose (D50) stimulation. When compared to controls, the isograft IL had similar perfusion (ISO2, IHB, and FLOW). The allograft IL showed ischemia (similar ISO2, and lower ISO2 and FLOW). In the allografts, the ISO2 and FLOW were lower than in the isografts. In response to D50, the native IL of all groups showed an increased IHB and FLOW (hyperemia); the isografts showed an increase only in IHB (partial response); the allografts did not show any response at all. In summary, the mucosal perfusion in the rejecting allografts, but not in the isografts, showed ischemia. The response to D50 seen in the native ilea was only partial in the isografts and absent in the allografts. Because these changes occurred before the onset of mucosal ulcerations, we postulate that they could be used as early indicators of AR.

Animals↗
PubMed1995

Mechanisms underlying functional recovery following stroke.

This article reviews recent evidence from animal experiments indicating that there is considerable potential for reorganization of representations and functions in in sensory and motor cortex following localized lesions or various manipulations of peripheral target structures. Three major mechanisms for this plastic reorganization are considered: unmasking of existing but functionally inactive pathways, sprouting of fibers from surviving neurons and formation of new synapses, and redundancy of CNS circuitry allowing alternative pathways to take over functions. Studies using positron emission tomography or transcranial magnetic stimulation suggest that similar forms of neuroplasticity may occur in the human brain and could contribute to functional recovery following stroke. The potential therapeutic implications are discussed.

Animals↗
PubMed1995

Preparatory postural adjustments in parkinsonian patients with postural instability.

BACKGROUND: Postural instability is a common problem in patients with Parkinson's disease. This paper reports results of a study undertaken to investigate some of the possible mechanisms responsible for this instability. METHODS: Preparatory postural adjustments associated with a lateral leg raising task were studied in five parkinsonian patients and four age-matched controls. Recordings included ground reaction forces, kinematics, and surface EMG activity from multiple leg muscles. RESULTS: In normal subjects there was a well-defined sequence of events preceding the onset of leg elevation, beginning with a transfer of centre of foot pressure (CP), initially toward the moving leg and then back to the support side, followed by displacement of the trunk toward the support side. In the more severely affected parkinsonian patients, the amplitude of the initial displacement of CP was markedly reduced. The interval between the earliest force changes and the onset of leg elevation was prolonged and the relative timing of the kenematic adjustments during this interval was disrupted. In addition the alternating burst and periods of inhibition observed in the EMG recordings from the normal subjects were replaced by continuous tonic EMG activity. CONCLUSIONS: These observations suggest that abnormalities in programming preparatory postural adjustments may contribute to postural instability in some patients with advanced Parkinson's disease.

Aged↗
PubMed1995

Outcome analysis of 71 clinical intestinal transplantations.

OBJECTIVE: The aim of the study was to determine risk factors associated with graft failure and mortality after transplantation of the intestine alone or as part of an organ complex. SUMMARY BACKGROUND DATA: Even with modern immunosuppressive therapies, clinical intestinal transplantation remains a difficult and unreliable procedure. Causes for this and solutions are needed. METHODS: Between May 1990 and February 1995, 71 intestinal transplantations were performed in 66 patients using tacrolimus and low-dose steroids. The first 63 patients, all but one treated 1 to 5 years ago, received either isolated grafts (n = 22), liver and intestinal grafts (n = 30), or multivisceral grafts (n = 11). Three more recipients of allografts who recently underwent surgery and one undergoing retransplantation were given unaltered donor bone marrow cells perioperatively as a biologic adjuvant. RESULTS: Of the first 63 recipients, 32 are alive: 28 have functioning primary grafts and 4 have resumed total parenteral nutrition after graft enterectomy. Thirty-five primary grafts were lost to technical and management errors (n = 10), rejection (n = 6), and infection (n = 19). Regression analysis revealed that duration of surgery, positive donor cytomegalovirus (CMV) serology, inclusion of graft colon, OKT3 use, steroid recycle, and high tacrolimus blood levels contributed to graft loss. All four intestine and bone marrow recipients are alive for 2-3 months without evidence of graft-versus-host disease. CONCLUSION: To improve outcome after intestinal transplantation with previous management protocols, it will be necessary to avoid predictably difficult patients, CMV seropositive donors, and inclusion of the graft colon. Bone marrow transplantation may further improve outcome by ameliorating the biologic barriers of rejection and infection and allowing less restrictive selection criteria.

Adult↗
PubMed1994

Adaptive modification of oculomotor pursuit influences manual tracking responses.

We have addressed the question of whether adaptively modifying the oculomotor response to a visual pursuit stimulus has an influence on a related manual tracking response. Subjects used their unseen right hand to track targets moving at constant velocities while visually fixating a stationary LED. Manual tracking performance was compared before and after a 20 min period during which smooth pursuit eye movements alone were adaptively enhanced by adding 50% of the instantaneous eye position signal to target position. Compared with the preadaptation trials, hand gain was markedly increased during the postadaptation period. These results imply that the adaptation occurred at a level common to both motor systems, probably in CNS structures concerned with visual motion processing.

Adaptation, Physiological↗
PubMed1994

The contribution of retinal and extraretinal signals to manual tracking movements.

We have assessed the contribution made by retinal and extraretinal signals when subjects used their hand to track targets moving at constant velocities. Comparisons were made between responses produced under the following conditions: (1) with full vision of the hand and unrestricted movement of the eyes, (2) without vision of the hand or (3) while visually fixating a stationary LED. Target velocity was varied in a pseudo-random order across trials. In each condition response latency decreased as target velocity was increased. There was a approximately 24 ms increase in latency when vision of the hand was removed or eye movements were restricted. Under normal conditions, subjects were able to accurately catch up to and match target velocity with their hand. When vision of the hand was removed, subjects lagged behind the target but were able to match target velocity. This deficit was eliminated when vision of the hand was made available for the beginning of the response. When subjects were required to visually fixate they could catch up to the target with their hand, but subsequently produced a steady state hand velocity that was greater than target velocity. When the LED was positioned such that the target started in the peripheral visual field, the overestimation of target velocity was evident from the beginning of the response: subjects produced initial accelerations with their hand that were significantly greater than in normal conditions. Finally, normal responses were produced when subjects were required to visually pursue a second target that moved at the same speed and in the same direction as the main target.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Quantitative analysis of human movement synergies: constructive pattern analysis for gait.

To record three-dimensional coordinates of the joints from normal human subjects during locomotion, we used a digital motion analysis system (ELITE). Recordings were obtained under several different conditions, which included normal walking and stepping over obstacles. Principal component analysis was used to analyze coordinate data after conversion of the data to segmental angles. This technique gave a stable summary of the redundancy in gait kinematic data in the form of reduced variables (principal components). By modeling the shapes of the phase plots of reduced variables (distortion analysis) and using a limited number of model parameters, good resolution was obtained between subtly different conditions. Hence, it was possible to accurately resolve small distributed changes in gait patterns within subjects. These methods seem particularly suited to longitudinal studies in which relevant movement features are not known a priori. Assumptions and neurophysiological applications are discussed.

Journal Article↗