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Biomedical subjects

J Fung

Publications and source records attributed to J Fung.

At least 127 records · Page 7Linked to original sources
PubMed1995

Abdominal multivisceral transplantation.

Under FK506-based immunosuppression, 13 abdominal multivisceral transplantations were performed in 6 children and 7 adults. Of the 13 recipients, 7 (53.8%) are alive and well with functioning grafts after 9 to 31 months. Six recipients died: three from PTLD, one from rejection, one from sepsis, and one from respiratory failure. In addition to rejection, postoperative complications occurring in more than isolated cases included PTLD (n = 6), abdominal abscess formation (n = 5), pancreatitis (n = 3), and ampullary dysfunction (n = 2). In addition, infection by enteric microorganisms was common during the early postoperative period. Currently, all 7 survivors are on an oral diet and have normal liver function. Two recipients (one insulin-dependent) require antidiabetes treatment, in one case following distal pancreatectomy and in the other after two episodes of pancreatic rejection. Thus, abdominal multivisceral transplantation is a difficult but feasible operation that demands complex and prolonged posttransplantation management. It is not yet ready for application and awaits a better strategy of immune modulation.

Abdomen↗
PubMed1995

Persistence of extrahepatic hepatitis B virus DNA in the absence of detectable hepatic replication in patients with baboon liver transplants.

The presence of hepatitis B virus (HBV) DNA in extrahepatic tissues has been well documented. Whether HBV DNA can persist in extrahepatic tissues for long periods of time in the absence of replication in the liver has not been determined previously. Recently, two patients with end-stage liver disease secondary to chronic active HBV were treated with baboon liver xenotransplants as these animals are felt to be resistant to HBV infection. Multiple tissues from these two patients were examined for HBV DNA using polymerase chain reaction (PCR). HBV DNA was not detectable in four of five samples of the liver xenografts. A positive signal was observed in a single assay for one sample, but this sample was not positive in subsequent assays. HBV DNA was detected in peripheral blood lymphocytes, spleen, kidney, bone marrow, pancreas, lymph node, heart and small intestine. The level of HBV DNA in these tissues was too low for the detection of HBV DNA replicative intermediates by Southern hybridization; thus, it could not be determined whether the HBV DNA in these tissues represented actively replicating HBV in extrahepatic sites, integrated HBV sequences, HBV in infiltrating lymphocytes, or deposition of HBV immune complexes originating from the plasma. However, it is clear from this study that HBV DNA persisted in multiple tissues for 70 days after replication in the liver had ceased or at least was below the level of detection by PCR.

Adult↗
PubMed1995

Role of nuclear medicine in liver transplantation.

Orthotopic liver transplantation is now a very well-established technique for treating patients with end-stage liver disease. Since 1967, more than 26,000 liver transplants have been performed, including 15,000 in the United States. The overall 1-year survival rate is approximately 80% and 5-year survival is 70%. Nuclear imaging plays an important role in the management of liver transplant recipients before and after liver transplantation. The evaluation of candidates potentially includes liver-spleen scan for liver volume, multiple gated acquisition scan, adenosine or stress thallium study, bone scan, and quantitative ventilation perfusion scan for hepatopulmonary syndrome. In the post-transplant phase, the deconvolution analysis (which corrects for the problem of recirculation) is a promising tool for diagnosing rejection, although its role in the transplant population has to be established. A variety of nuclear medicine techniques are helpful in the postoperative diagnosis of biliary complications. By performing a semiquantitative analysis to discriminate hepatocyte dysfunction from biliary disease and measuring hepatocyte extraction fraction by deconvolution analysis and excretion, (T1/2 values measured by the nonlinear list squares technique) have been very promising.

Biliary Tract↗
PubMed1995

Tacrolimus analysis: a comparison of different methods and matrices.

We determined the through blood and plasma concentrations of tacrolimus from the day of transplantation through 30 days posttransplantation in four liver and four kidney transplant patients by three different methods. The first method involved a solid phase extraction of the blood or plasma using Sep-Pak columns (SPs) followed by quantitation of tacrolimus using an enzyme-linked immunosorbent assay (ELISA); the second method involved a liquid-liquid extraction using methylene chloride (MC) followed by quantitation of tacrolimus using the ELISA, and the third method involved a high-performance liquid chromatography (HPLC) fractionation of the extract obtained from the solid-phase extraction and quantitation of tacrolimus in the fractions by ELISA. The trough plasma tacrolimus concentrations ranged from 0.1 to 5.2 ng/ml. While the trough plasma concentrations of tacrolimus were similar and independent of the method of analysis in kidney transplant patients and in liver transplant patients with normal biochemical profile, in patients with liver dysfunction, tacrolimus plasma concentrations were higher when measured by SP-ELISA and MC-ELISA methods as compared to the HPLC-ELISA method. In plasma samples obtained from liver transplant patients with liver dysfunction, the presence of some metabolites that cross-reacted with the antibody used in the ELISA could be documented in the HPLC fraction corresponding to the metabolites. This indicates that while tacrolimus metabolites that cross-react significantly with the antibody used in the ELISA do not accumulate in kidney transplant patients, they can appear in the plasma of patients, they can appear in the plasma of patients with liver dysfunction. The trough blood tacrolimus concentrations in patients were significantly higher than the corresponding plasma concentrations and ranged from 1.4 to 107 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1995

Determinants of postural orientation in quadrupedal stance.

The purpose of this study was to investigate the determinants of postural orientation by examining stance kinematics and kinetics at various interpaw distances. Four adult cats were trained to stand, unrestrained, on a force platform. Three-dimensional ground reaction forces and kinematics, as well as EMG activities, were recorded during stance at five different anteroposterior (AP) distances and two widths. Stance distance was varied by changing the distance between the four force plates mounted on the platform. All cats used a strategy of maintaining a constant horizontal orientation of the trunk and levering the limbs at the girdles while maintaining constant intralimb geometry to accommodate the changes in stance distance. The direction of the ground reaction forces covaried with the limb axes. As a result, the joint torques were conserved in the forelimb, and varied within small ranges in the hind. Increased tonic activity in the extensors of the back, the hip, and the ankle was observed at shorter distances while increased knee extensor activity was observed at longer distances. A cost function, defined as the sum of squared 3-D joint torques, was minimal for the hindlimb at a stance distance which corresponded to the preferred distance naturally assumed by each cat on the floor. Thus, in the maintenance of stance posture, trunk orientation and intralimb geometry is constrained, the goal of which is to minimize muscular effort or energy expenditure.

Animals↗
PubMed1995

The current status of hepatic transplantation at the University of Pittsburgh.

Tacrolimus is a more potent and satisfactory immunosuppressant than CyA for combination therapy with prednisone. In randomized trials comparing the 2 drugs, the ability of tacrolimus to rescue intractably rejecting grafts on the competing CyA arm allowed equalization of patient and graft survival on both arms when the intent-to-treat analytic methodology was applied. The ability of tacrolimus to systematically rescue the treatment failures of CyA suggested, as a matter of common sense, that it is the preferred baseline drug for hepatic transplantation. This conclusion was supported by analysis of secondary end points, including the ability to prevent rejection. Hepatic-intestinal, multivisceral and isolated intestinal transplantation became feasible on a practical basis only after the advent of tacrolimus. Nevertheless, better management strategies must be devised before intestinal transplantation, alone or with other abdominal viscera, will meet its potential. One such strategy is based on the discovery of the presence of previously unsuspected, low-level donor leukocyte chimerism in long-surviving allograft recipients. We believe that this chimerism is the essential explanation for the feasibility of organ transplantation and a link to the acquired neonatal tolerance demonstrated by Billingham, Brent and Medawar (32). The hematolymphopoietic chimerism in organ recipients explains why weaning to a drug-free state in selected long-term survivors is frequently feasible and particularly if the allograft is a liver. Weaning should never be attempted without a stepwise protocol and careful monitoring of graft function. Recognition of the natural chimerism that develops after whole organ transplantation has led to efforts to augment it with perioperative donor BM infusion. This procedure has been shown to be free of significant complications (including GVHD) in all kinds of whole organ recipients, including those given intestine. The prospects of clinical xenotransplantation must be evaluated in the same context of chimerism as that delineated for allotransplantation with the discovery of spontaneous chimerism. Before addressing chimerism-related questions in xenotransplantation, the additional barrier of the complement activation syndromes that cause hyperacute rejection will have to be surmounted. Although measures to effectively transplant xenografts have so far eluded us, the availability of the more potent drug, tacrolimus, and recognition of the seminal basis of allograft (or xenograft) acceptance via chimerism has inserted an element of reality into the largely wishful thinking that has been evident in discussions about the future of xenotransplantation.

Adolescent↗
PubMed1994

Early death or retransplantation in adults after orthotopic liver transplantation. Can outcome be predicted?

Early, reliable outcome prediction after a liver transplant would help improve organ use by minimizing unnecessary retransplantations. At the same time, early intervention in those cases destined to fail may ameliorate the high morbidity and mortality associated with retransplantation. The purpose of this study was to analyze several parameters that have been identified in the past as being associated with patient and graft outcome, and to try to develop a model that would allow us to make predictions based on data available in the early postoperative period. A total of 148 patients were followed in a prospective, observational study. Graft failure was defined as patient death or retransplantation within 3 months of surgery. Preoperative variables studied included patient demographics, need for life support, presence of ascites, serum bilirubin, serum albumin, prothrombin time, serum creatinine, and the results of the cytotoxic crossmatch. During the first 5 postoperative days, standard measurements included serum transaminases, serum bilirubin, ketone body ratio, prothrombin time, factor V, and serum lactate. Oxygen consumption was measured shortly after surgery, once the patients had rewarmed to 36 degrees C. There were 131 successful transplants (88.5%) and 17 failures (11.5%). Most of the variables studied were found to be associated with outcome (by univariate analysis) at different points in the early postoperative period. However, receiver operating characteristic curve analysis showed that the predictive ability of even the best parameter was not adequate to make decisions on individual patients. Multivariate analysis, using stepwise logistic regression, yielded a model with an overall accuracy of 92.7%. Again, receiver operating characteristic curve analysis suggested that this model did not achieve the discriminating power needed for routine clinical use. We are still not able to accurately predict outcome in the early posttransplant period. We must be very careful when evaluating parameters, or scoring systems, that are said to accomplish this. It is especially important in this era of cost containment, with its renewed pressures to guide therapy based on our perceived understanding of a patient's future clinical course.

Bilirubin↗
PubMed1994

Small intestinal transplantation in humans with or without the colon.

Under FK506-based immunosuppression, 16 cadaveric small bowel transplantations were performed in 15 recipients with (n = 5) or without (n = 11) the large bowel. Twelve (80%) patients are alive after 1.5 to 19 months, 11 bearing their grafts, of which 4 include colon. The actuarial one-year patient and graft survivals are 87.5% and 65.9%, respectively. Five grafts were lost to acute (n = 4) or chronic (n = 1) rejection, and 3 of these patients subsequently died after 376, 440, and 776 days total survival. Six recipients developed severe CMV infection that was strongly associated with seronegative status preoperatively and receipt of grafts from CMV positive donors; 3 died, and the other 3 required prolonged hospitalization. Currently, 9 patients are free from TPN 1-18 months postoperatively, 2 require partial TPN, and one has returned to TPN after graft removal. The results show the feasibility of small bowel transplantation but emphasize the difficulty of managing these recipients not only early but long after their operation.

Adult↗
PubMed1994

Recurrent and de novo giant cell hepatitis after orthotopic liver transplantation.

This study examines the clinical and pathologic course of seven patients who developed giant cell hepatitis (GCH) after liver transplantation. Five of these patients also had GCH as their native liver disease and experienced a particularly aggressive course because of recurrent disease, beginning 1-21 months after transplantation. Two died and another two required hepatic retransplantation because of recurrent GCH; one of them had GCH recurrence in a second liver allograft. A remaining patient with recurrent GCH is alive 6 years after transplantation. Follow-up of the two patients who developed de novo GCH between 8 and 24 months after hepatic transplantation showed active micronodular cirrhosis in one and persistent giant cell transformation in the other at 4 years. All of the patients were serologically negative for hepatitis C virus, hepatitis B virus, and human immunodeficiency virus before transplantation. One patient became positive for hepatitis C virus after transplantation. Two patients had an associated autoimmune syndrome, which could have been accounted for by the GCH. None had a history of drug exposure. Interestingly, human papilloma virus (HPV) type 6 was detected by PCR analysis of liver tissues with GCH from one of three cases before and three of four cases after transplantation. This small series shows that GCH occurs in liver allografts, but it is uncommon. Documentation of recurrent disease in five of seven patients suggests that GCH in a subgroup of patients may be related to a transmissible agent, or that a particular recipient may injure livers in a way that elicits a giant cell reaction.

Adult↗
PubMed1994

Stance control in the chronic spinal cat.

1. A longitudinal study of the control of quiet and perturbed stance was conducted before and for 1 yr after complete spinal transection (T12) in a cat trained to stand on a moveable force platform. 2. With daily training, the spinal cat recovered full weight support and some intermittent control of lateral stability within 1 mo. Within the second month postspinalization, the spinal cat achieved the ability to maintain independent, unassisted stance (no external support or stimulation) for up to 45 s during quiet stance, as well as for 62-97% of the trials of horizontal translations of the support surface. 3. Control of lateral stability in the spinal cat was severely compromised, however, as eventually the spinal cat always lost its balance. Head movements and the tendency for the hindlimbs to initiate stepping movements were more destabilizing than platform translations. 4. Our preliminary results indicate that the recovery of partial lateral stability of the hindquarters in the spinal cat is the product of passive muscle properties and segmental reflexes, which, in isolation can provide only limited balance control in the chronic spinal cat.

Animals↗
PubMed1994

Effects of conditioning cutaneomuscular stimulation on the soleus H-reflex in normal and spastic paretic subjects during walking and standing.

1. The modulation of the soleus H-reflex by a conditioning cutaneomuscular stimulation was investigated in 10 normal and 10 spastic paretic subjects who suffered from incomplete spinal cord lesions. The different motor tasks examined were standing, locomotion, and the maintenance of static limb postures to mimic critical gait events. The test soleus H-reflex was obtained by stimulating the tibial nerve in the popliteal fossa with a single 1-ms pulse at an intensity that produced a barely detectable M wave. The conditioning stimulus, consisting of an 11-ms train of three 1-ms pulses at 200 Hz, was delivered to the ipsilateral medial plantar arch, stimulating predominantly the medial plantar nerve, at an innocuous intensity of 2.5-3.0 X sensory threshold and at a conditioning-test delay of 45 ms. 2. During quiet standing, the H-reflex amplitude was inhibited only marginally by the conditioning cutaneomuscular stimulation, not reaching statistical significance in either the normal or spastic group of subjects. Although there was a trend of reflex inhibition in the normal subjects as the conditioning intensity was increased, a reversed trend of reflex facilitation was observed in the spastic patients. 3. During treadmill walking, the conditioned H-reflex was inhibited significantly during all phases in all the normal subjects and in one mildly impaired patient. In the moderately and severely impaired patients, cutaneomuscular stimulation selectively inhibited the soleus H-reflex in the early stance and swing phases, thereby producing a near normal phasic modulation pattern. Such modulatory effects were not present under static gait-mimicking conditions. 4. The task-specific and phase-dependent effects of cutaneomuscular stimulation on the soleus H-reflex in the spinal cord-injured patients revealed strong inhibitory influence on Ia afferents from cutaneomuscular inputs. It is plausible that inhibition occurs at both pre- and postsynaptic levels. 5. It is concluded that normal Ia modulatory mechanisms during locomotion are deficient in spastic spinal cord-injured patients and can partially and artificially be restored by cutaneomuscular stimulation applied to the sole of the foot. This can be used as a functional electrical stimulation (FES) regime in gait rehabilitation.

Adult↗
PubMed1994

Intestinal transplantation at the University of Pittsburgh.

Our experience with clinical intestinal transplantation under FK 506 immunosuppression showed that 50% of the recipients were able to be independent from TPN after transplantation, but 10% require partial TPN with functioning grafts, 10% needed total TPN after graft removal, and 30% of the recipients died postoperatively, mostly from sepsis due to severe graft rejection. For further improvement in patient survival and in the quality of life for patients after intestinal transplantation, it is mandatory to establish a new strategy for treatment and prevention of graft rejection and systemic infection.

Adult↗