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Biomedical subjects

Stefan G Tullius

Publications and source records attributed to Stefan G Tullius.

23 records · Page 2Linked to original sources

Accumulation of crystal deposits in abdominal organs following perfusion with defrosted University of Wisconsin solutions.

Previous studies reported on both visible and invisible particles in University of Wisconsin (UW) solutions. Those particles originated from components of the bags. In recent clinical observations we noticed macroscopically visible, indissoluble particles in UW bags reaching subzero temperatures during transportation of organs and preservation solutions. In an experimental model we examined whether those particles could be detected following perfusion of abdominal organs with established perfusion solutions. UW-, HTK- or physiological saline solutions reached -3 +/- 0.5 degrees C under conditions frequently applied during transportation. UW solutions demonstrated the accumulation of visible, indissoluble crystals and were subsequently used for the perfusion of abdominal organs in LEW rats. After perfusion with UW solutions stored at freezing temperatures, crystals were detected in all abdominal organs localized in and around vessels, bile ducts, glomeruli and in the interstitium of harvested livers, kidneys and pancreas. By spectroscopy, we were able to characterize crystals as adenosine. A 40-microm pore-size filter eliminated crystals from UW solutions. Crystals were absent in organs perfused with HTK- or saline solutions kept at subzero conditions. UW solutions can reach subzero temperatures under commonly used transportation conditions. Under these conditions, visible crystals accumulate and can be detected in abdominal organs of an experimental system.

Adenosine↗

CMV hepatitis after liver transplantation: incidence, clinical course, and long-term follow-up.

Cytomegalovirus (CMV) hepatitis is described as the most frequent manifestation of CMV tissue invasive disease after liver transplantation. Its correlation with HLA-matching, hepatic artery thrombosis, and chronic rejection is still controversial. Risk factors, incidence, clinical course, and complications of CMV hepatitis were retrospectively analyzed in a 12-year series of 1,146 consecutive liver transplantations in 1,054 patients. All patients received only low-dose acyclovir but no gancyclovir prophylaxis. CMV infection was diagnosed by viral culture, pp65 antigenemia, or by polymerase chain reaction (PCR). CMV hepatitis was proven by liver biopsy. Treatment of CMV disease consisted of intravenous ganciclovir for a minimum of 14 days. Long-term follow-up of patients included monthly routine laboratory values and routine liver biopsies 1, 3 and 5 years after transplantation. CMV hepatitis was a rare event after liver transplantation, with a total incidence of 2.1% (24 cases). It was significantly more frequent in CMV seronegative (5.2%) than in seropositive recipients (0.7%). The leading indication in patients with CMV hepatitis was HCV cirrhosis (n = 8). The maximum number of pp65 positive white blood cells was 82 +/- 23 per 10,000 cells. Most courses manifested as isolated hepatitis; only 2 patients had disseminated disease. Nine of 24 patients had received OKT3 monoclonal antibodies because of steroid-resistant rejection before CMV hepatitis. In seronegative patients with CMV hepatitis, 71% revealed 1 or 2 HLA DR matches, in contrast to 32% in patients without CMV hepatitis. One-, 3-, and 5-year graft survival was 78%, 65%, and 59% in patients with CMV hepatitis compared with 88%, 81%, and 79% in patients without. Chronic rejection was observed in one patient, but already before onset of CMV hepatitis. Beneath D+R-constellation and OKT3 treatment as risk factors, HLA DR-matched grafts and HCV seem to favor manifestation of CMV hepatitis after liver transplantation. Long-term complications of CMV hepatitis were not observed, and especially no correlation with chronic rejection was found.

Acute Disease↗

The marginal kidney donor.

In parallel with increased clinical demand, less than optimal or so-called marginal kidney grafts are being used for transplantation. In addition to donor age, it appears that several factors may impact negatively on the quality of the graft. Most importantly, a more precise definition of the term 'marginal graft' is needed. The present review analyzes potential risk factors, suggests scoring systems for a more precise definition, and discusses potential treatment options to improve the quality of marginal grafts.

Humans↗

Pituitary function test and endocrine status in patient with cirrhosis of the liver before and after hepatic transplantation.

OBJECTIVE: Hormonal alterations caused by chronic liver disease are well described. In contrast, the reversibility of peripheral hormonal changes after orthotopic liver transplantation (OLT) has only partially been analyzed since the establishment of OLT as treatment of chronic hepatic failure. In addition it is not finally verified if chronic liver failure and especially hepatic encephalopathy also affect pituitary function. We therefore performed extensive endocrine studies including a global pituitary stimulation test before and after liver transplantation. METHODS: 22 patients with chronic alcoholic and non alcoholic liver failure were included in this prospective study. Basal hormone values (ACTH, cortisol, FSH, GH, IGF-I, LH, oestradiol, PRL, thyroid hormones and testosterone) were measured before and up to 5 years after OLT. Furthermore all patients underwent pituitary function tests with application of GRF, TRH, GnRH, and CRF before, 3 weeks and 3 months after OLT. RESULTS: Estradiol, LH and FSH increased significantly in postmenopausal and only slightly in premenopausal female patients after OLT. Total testosterone revealed no marked changes and was normal before and up to five years after OLT in male patients. After stimulation with GnRH the LH response in females and the FSH response in males was significantly higher three months after OLT than pretransplant. LH response in males and FSH response in females was only slightly higher after OLT. Peripheral IGF-I was low and growth hormone was elevated in all patients prior OLT. Growth hormone declined significantly three months afterwards. The response to GRF was highest prior OLT and decreased afterwards. Prolactin values were normal prior and post OLT. After stimulation with TRH prolactin values in male patients were significantly higher before OLT than afterwards. CONCLUSION: In the observed relatively small number of patients gross pituitary function in chronic liver failure remained intact, whereas slight alterations in several axis were found. These pituitary alterations are presumably only partially caused by feedback mechanisms. Both a normalisation of peripheral endocrine parameters and pituitary function were achieved by OLT despite significant alterations pretransplant.

Adrenocorticotropic Hormone↗

Influence of donor brain death on chronic rejection of renal transplants in rats.

The clinical observation that the results of kidney grafts from living donors (LD), regardless of relationship with the host, are consistently superior to those of cadavers suggests an effect of brain death (BD) on organ quality and function. This condition triggers a series of nonspecific inflammatory events that increase the intensity of the acute immunologic host responses after transplantation (Tx). Herein are examined the influences of this central injury on late changes in renal transplants in rats. A standardized model of BD was used. Groups included both allografts and isografts from normotensive brain dead donors and anesthetized LD. Renal function was determined every 4 wk after Tx, at which time representative grafts were examined by morphology and by reverse transcriptase-PCR. Long-term survival of brain-dead donor transplants was significantly less than LD grafts. Proteinuria was significantly elevated in recipients of grafts from BD donors versus LD controls as early as 6 wk postoperatively and increased progressively through the 52-wk follow up. These kidneys also showed consistently more intense and progressive deterioration in renal morphology. Changes in isografts from brain-dead donors were less marked and developed at a slower tempo than in allografts but were always greater than those in controls. The transcription of cytokines was significantly increased in all brain-dead donor grafts. Donor BD accelerates the progression of long-term changes associated with kidney Tx and is an important risk factor for chronic rejection. These results explain in part the clinically noted difference in long-term function between organs from cadaver and living sources.

Animals↗