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Biomedical subjects

D Fries

Publications and source records attributed to D Fries.

At least 37 records · Page 2Linked to original sources

Color and pulsed Doppler ultrasound findings in normally functioning transjugular intrahepatic portosystemic shunts.

OBJECTIVE: To evaluate blood flow changes inside normally functioning transjugular intrahepatic portosystemic shunts (TIPS), using color Doppler ultrasound (CDUS) and pulsed Doppler ultrasound (PDUS). METHODS: A total of 72 patients (mean age 54, range 36-78 years) underwent TIPS placement, portal angiography, CDUS and PDUS examinations. Measurements inside the stent were taken at the portal side, at the central part and at the venous end of the TIPS. RESULTS: In well functioning TIPS the mean peak velocity (PV) on the portal side was 37 m/s (range 22-65 cm/s), in the area of the incoming intrahepatic portal branch the mean PV was 59 cm/s (range 40-95 cm/s) and at the side of the incoming hepatic vein the mean PV was 135 cm/s (range 88-220 cm/s). In the punctured hepatic and portal veins the mean PV was 25 cm/s (range 15-30 cm/s) and 18 cm/s (10-22 cm/s), respectively. The flow increase from the portal to the mid part (P less than or = 0.001) and to the venous side was statistically significant (P less than or = 0.001). CONCLUSION: A velocity gradient between the portal and the venous side of a TIPS is a normal finding caused by branches of the portal and hepatic vein joining the TIPS from the side and it is characteristic of a normally functioning TIPS.

Adult↗

Low platelet count and elevated serum thrombopoietin after severe trauma.

Platelet count is regularly low in patients after multiple trauma, mainly due to blood loss and dilution. Thrombopoietin (TPO) is the main regulator of the circulating platelet mass. Under several clinical conditions an inverse correlation between TPO and the circulating platelet mass was reported. Since platelets bind and internalize TPO, a platelet-dependent regulation of TPO was suggested. Thus, acute blood loss should be accompanied by elevated TPO. We measured serum TPO, platelets, interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in 17 multiple traumatized victims. Blood was collected within 12 h after trauma as well as in the morning of days 2, 4, 6 and 9 after admission at the intensive care unit. Platelet count was low at admission and remained low until day 4. Thereafter platelets increased until day 9. TPO nearly doubled within the first 2 d, reaching its maximum on day 6. IL-6 was initially very high and steadily decreased until day 9. VEGF increased 3-fold during the 9 d. Statistically significant correlations of TPO were found with platelets and IL-6, but not with VEGF. In multiple traumatized patients low platelet count is followed by a rapid increase in serum TPO. This fits into the concept of a feedback regulation between circulating TPO and platelet mass.

Adult↗

[Results of doppler sonography in normally functioning transjugular portosystemic shunts].

PURPOSE: The objective of this study was to evaluate blood flow changes inside normally functioning transjugular intrahepatic portosystemic shunts (TIPS), using Colour Doppler ultrasound (CDUS) and pulsed Doppler ultrasound (PDUS). MATERIAL AND METHODS: In a prospective study 72 patients (mean age 54, range 36-78 years) underwent TIPS placement, portal angiography, CDUS and PDUS examinations. Along the TIPS Doppler measurements were taken at the portal in the central part and at the venous end of the TIPS. RESULTS: In well functioning TIPS the mean peak velocity (PV) on the portal side was 39 cm/s (range 22-72 cm/s), in the area of the incoming right portal end, branch 62 cm/s (range 40-109 cm/s) and at the site of the incoming hepatic vein 139 cm/s (range 88-220 cm/s). In the punctured portal and hepatic vein the mean PV was 25 cm/s (range 15-30 cm/s) and 18 cm/s (15-22 cm/s) respectively. CONCLUSION: A velocity gradient between the portal and the venous side of the TIPS is a normal finding, caused by the branches of the portal and hepatic vein, joining the TIPS from the side and is characteristic of a normally functioning TIPS.

Adult↗

[Implementing limited therapy methods in intensive care units: discontinuing therapy, reducing therapy and withholding therapy in intensive care units of the Innsbruck University Clinics].

INTRODUCTION: The intensive care physician is frequently confronted with the decision to withhold or withdraw therapy in patients with a poor prognosis. Apart from the legal implications, the practical management of withholding or withdrawing intensive care treatment continues to be indistinct. The subject has not been investigated in Austria or Germany. The aim of the study was to examine the different points of view of intensive care physicians and the various procedures to limit therapy in patients with a poor prognosis. METHODS: We interviewed physicians working at different intensive care departments of the University Hospital of Innsbruck from March to April 1998. RESULTS: Withholding treatment was given preference over withdrawing treatment. In regard of withdrawing treatment, 64% of the interviewed physicians felt more uncertain. In the decision making process the potential reversibility of disease was estimated to be more important than the wish of the patient. Hemofiltration and antibiotics were mentioned as the first measures the physicians would withdraw. The last measure that would be withheld was ventilatory support. Sixty-three per cent of the physicians felt that sedation and analgesia should be continued. In regard of withholding or withdrawing treatment 83% voted for an obligatory DNR order. CONCLUSION: Before withholding or withdrawing intensive care therapy, a medical specialist must determine and document the futile prognosis of the patient. If the patient's wish is unknown, all further decisions should be made in agreement with all participants. The goal of the therapy is to provide the patient maximum comfort under minimal intensive care treatment.

Attitude of Health Personnel↗

Effect of N8-acetylspermidine deacetylase inhibition on the growth of L1210 cells.

A selective inhibitor of N8-acetylspermidine deacetylase has been employed to study the role of N8-acetylspermidine deacetylation in the regulation of L1210 cell growth. This inhibitor, 7-[N-(3-aminopropyl) amino] heptan-2-one (APAH), was found to stimulate the growth of L1210 cells at concentrations between 10 microM and 0.5 mM. Maximum stimulation was seen at 100 microM, resulting in significantly increased rates of cell division and maximum cell density. N8-Acetylspermidine levels in L1210 cells were shown to increase significantly after the APAH treatment as would be expected for deacetylase inhibition. The effects of deacetylase inhibition were mimicked by addition of N8-acetylspermidine to the culture medium at concentrations greater than 1 mM as indicated by a subsequent increase in rate of cell growth and maximum cell density. The magnitudes of the increases in growth observed were not large, but this might be expected in cells that are already in a rapid growth phase. Other exogenously added polyamines including N1-acetylspermidine, spermidine, putrescine, and spermine did not stimulate cell growth. These data suggest that stimulation of cell growth occurs as a consequence of N8-acetylspermidine accumulation and N8-acetylspermidine deacetylase inhibition.

Amidohydrolases↗

[On the topic of do not resuscitate (DNR) orders on intensive care units: an evaluation of the present status on intensive care units of the Innsbruck University clinics].

INTRODUCTION: Intensive care physicians are frequently called upon to decide whether intensive care treatment is justified. Critically ill patients with a poor prognosis receive "Do Not Resuscitate (DNR) Orders", which entitles the physician in charge to withhold cardiopulmonary resuscitation in case of cardiac arrest. Guidelines concerning the implementation of DNR orders do not exist for Austrian intensive care units. The aim of this study was to evaluate the different practices of issuing a DNR order in the departments of intensive care medicine at the University Hospital of Innsbruck. METHODS: Forty-nine physicians working in intensive care units were interviewed about the different procedures in the management of a DNR order. Furthermore, the various answers of senior physicians and assistant physicians were evaluated. RESULTS: Thirty-nine per cent of the interviewed physicians reported that DNR orders were always issued in writing. According to the answers of 63% of intensive care physicians, the decision to issue a DNR order is usually made by senior physicians. Twenty-nine per cent mentioned that nurses are never included in the decision making process and 6%, that the family is not included in the decision making process. According to 29%, the family is regularly informed about a written DNR order. Twenty per cent of the interviewed physicians reported that the quality of the administration of a written DNR order is very good, 6% that the quality is poor. CONCLUSION: We believe that the unsatisfactory situation in regard of DNR orders is not due to inactivity on the part of physicians, but is more likely a result of the inconclusive and, in part, contradictory legal situation. The physician is compelled to take a major decision within a poorly defined legal situation.

Adult↗

[Doppler ultrasound determination of average blood flow velocity and flow volume in transjugular intrahepatic portosystemic shunt (TIPS)].

AIM: To determine if duplex sonographic measured Time Average Motion (TAM) is an effective parameter for screening examination in routine follow-up after TIPS implantation. PATIENTS AND METHODS: 35 patients underwent duplex sonographic examination by a 3.5 MHz transducer with a follow-up for 12.4 months. RESULTS: A reduction of TAM about 60% from baseline proved with a sensitivity of 90% and a specificity of 93.7% the presence of a hemodynamic relevant stenosis, which was confirmed with angiography. We failed to establish a threshold which pointed out with acceptable accuracy the presence of shunt dysfunction. CONCLUSION: TAM is a good parameter in colour-duplex sonography which permits an objective view of TIPS-function. Angiography should be performed only in patients with suspect duplex-results or clinical worsening. A secondary sign of shunt dysfunction is increasing ascites.

Adult↗

Gastrointestinal complications in renal transplantation.

One wonders whether the use of cyclosporin, histamine receptor antagonists, low doses of steroids, and early diagnosis and treatment actually modify the incidence, morbidity, and mortality of gastrointestinal (GI) and pancreatic complications in renal transplantation. To find out, we reviewed 614 kidney transplant recipients between January 1984 and December 1988. One hundred patients (16.2%) were found to have GI and/or pancreatic complications in the following distribution: 9.6% gastroduodenal, 1.3% pancreatic, 4% colonic, and 0.4% small bowel. None of the patients presenting a gastroduodenal ulcer had perforation or bleeding. Fifty-five percent of the patients with this complication had a past history of eso-gastroduodenal disease, compared to 19.6% in recipients without gastroduodenal complications. Some 4.4% of the patients had a small bowel or a colonic complication and four died of peritonitis due to bowel perforation. Mortality was 35% in those having intestinal resection and/or perforation with peritonitis. Sixteen percent of patients with colonic complications had a known history of diverticula, compared to 3% for those without colonic complications. The incidence of GI and/or pancreatic complications in renal transplant recipients remains high and has caused 1.1% of the deaths in our series. Mortality is essentially due to upper GI bleeding, peritonitis following perforation, and infectious colitis. Better detection of gastroduodenal and colonic disease before transplantation seems to be mandatory. Prevention with histamine H2 receptor antagonists and early surgical treatment of complicated colonic diverticula help to reduce the morbidity and mortality in kidney graft recipients.

Adult↗

Prophylactic use of the IL-2 receptor-specific monoclonal antibody LO-Tact-1 with cyclosporin A and steroids in renal transplantation.

LO-Tact-1 is a rat anti-human monoclonal antibody which is directed to the 55-kDa alpha-chain of the interleukin 2 (IL2) receptor. We conducted a pilot trial in 15 first-time cadaveric renal transplant patients undergoing for immunosuppression a 14-day course of LO-Tact-1 (10 mg i.v. daily) together with cyclosporine, low dose steroids (0.5 mg/kg) and azathioprine. Results showed a good immunosuppressive effect, as measured by the similar incidence of acute rejection episodes (0.6 per patient) when compared with 20 patients treated during the same period with our standard quadruple prophylactic combination with higher initial doses of steroids (2 mg/kg) and antilymphocyte globulin (ALG) instead of LO-Tact-1 (0.4 per patient). At 2 years post-transplant, graft survival was 93%, and only 1 patient lost his kidney by rejection. No local or general adverse effect of antibody administration was encountered, and haematological changes remained of minor importance. Local bacterial infection was observed in 3 patients, but viral diseases (including cytomegalovirus, CMV) remained exceptional. In contrast, severe clinical CMV infections occurred in 3 patients (15%) treated by ALG. Nine of 15 patients developed rat-specific antibodies, but only 4 before the completion of LO-Tact-1 treatment, without any correlation with the further development of acute rejection. Patients who suffered rejection had lower LO-Tact-1 levels and higher soluble IL2 receptor levels during the period of infusion, suggesting the crucial importance of pharmacokinetic monitoring to adjust individual doses.

Adrenal Cortex Hormones↗

Immunoadsorption of anti-HLA antibodies for highly sensitized patients awaiting renal transplantation.

Fifteen end-stage renal disease patients with high titres of panel reactive (PRA) antibodies were treated with immunoadsorption (IA) on sepharose-bound protein A columns in order to remove anti-HLA antibodies and facilitate transplantation. Infectious complications were not observed after IA and transplantation, and the procedure was well tolerated. In spite of the use of adjunctive immunosuppressive treatment with cyclophosphamide and prednisolone, this method produced only variable effects in lowering panel reaction antibodies, and was hampered by high de novo resynthesis of anti-HLA antibodies. Patients whose pre-IA antibody titre was greater than or equal to 1:64 clearly did not benefit from the procedure, but other immunological criteria were not predictive of efficacy. Twelve patients were transplanted on the basis of a negative cross-match with current serum, historical sera being retrospectively tested. Surprisingly, seven patients received a well-matched graft with both pre- and post-IA negative cross-matching. Graft survival was 86% in this group. Conversely, in the group of five transplants which were performed in recipients having a positive historical cross-match with the donor, graft survival was only 40%. One patient died with a functional graft, and two grafts failed due to hyperacute humoral rejection. Humoral rejection in a third patient was successfully treated by a second IA course and administration of polyclonal IgG. We conclude that IA is a safe procedure for managing hyperimmunized transplant candidates. However, its efficacy remains variable, and a better definition of patients who should benefit from IA needs to be found.

Adsorption↗

[Liddle syndrome (or pseudo-hyperaldosteronism). Long-term development and erythrocyte potassium flow study in 4 cases].

BACKGROUND: Liddle's syndrome (or pseudoprimary aldosteronism) is a rare hereditary disease; only 18 cases have been reported since 1963. Its cause remains unclear, but one of its features is increased cell membrane permeability to ions. PATIENTS AND METHODS: A diagnosis of Liddle's syndrome was made in 4 new cases, all female, two of them sisters (cases n0 3 and 4), at the ages of 2, 12, 5 and 4 years. The first manifestations were dehydratation with hypokalemia at 6 months (case n0 1), hypertension at 2 years (case n0 2), polydipsia with poor weight and height gain at 5 and 4 years of age (cases n0 3 and 4). At diagnosis, all the patients had severe hypertension, metabolic alkalosis, hypokalemia and hyperkaliuria, low plasma renin activity and serum aldosterone levels. Administration of antihypertensive agents was without effect, but the hypertension was reduced when triamterene and low-sodium diet were used. Hypercalciuria was observed in 2 cases and nephrocalcinosis in 2 (case n0 1 had both hypercalciuria and nephrocalcinosis). The 2 oldest patients (n0 3 and 4) developed progressive kidney failure, possibly due to reno-vascular disease secondary to hypertension. Patient n0 3 underwent kidney transplantation 18 years after the first symptoms of the disease. This resulted in the complete disappearance of her hypokalemia and hypertension. The red blood cell membrane permeability to K+ and Cl- was studied in all 4 cases before triamterene treatment. The passive permeability to K+ and (K+/Cl-) cotransport were both elevated. A second study, 3 years (cases n0 2 and 3) and 8 years (cases n0 1 and 4) later, of patients treated with triamterene showed low values for passive K+ permeability and (K+/Cl-)-cotransport. CONCLUSIONS: The 4 new cases of Liddle's syndrome had the classic features of the disease, except for hypercalciuria and nephrocalcinosis in 2 of them. The cell membrane permeability data are difficult to interpret. Hypokalemia and hypertension were immediately corrected after kidney transplantation in one case and remained so for 4 years, suggesting that this disease is tubular in origin.

Aldosterone↗

How to deal with the hyperimmunized potential recipients.

End-stage renal disease (ESRD) patients with high levels of anti-HLA panel reactive antibodies (PRA) represent an increasing group in which sensitization, induced by pregnancies, previous transplants, and blood transfusions, considerably delay the opportunity to receive a graft. Currently, more than 50% of the 4700 patients awaiting transplantation in France are sensitized, of which 33% are defined as hyperimmunized (PRA greater than = 80%), and only 9.5% of the total number of transplants have been done in highly sensitized recipients. The magnitude of this problem, similar in Europe and North America, explains why more active strategies for managing hyperimmunized patients have been introduced during the past decade. Clearly, the simplest is finding of a well-matched organ that does not carry the HLA antigens against which the recipient has generated antibody, but that is limited by the number of shared grafts. The second is the development of a new cross-matching technique prior to transplantation. Attempts at immunoregulation of secreting B cell clones have been carried out using either hypertransfusions or injection of polyclonal Ig. Finally, removal and prevention of the resynthesis of HLA antibodies is a most attractive approach using immunoadsorption (IA) system with sepharose-bound protein-A columns. In our unit, fifteen ESRD patients with high levels of PRA were treated with IA. Infectious complications were not observed after IA and transplantation, and the procedure was well tolerated. In spite of the use of adjunctive immunosuppressive treatment with cyclophosphamide and prednisolone, this method produced only variable effects in lowering PRA levels, and was hampered by high de novo resynthesis of anti-HLA antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗

[Treatment of cytomegalovirus infections with ganciclovir in kidney transplant recipients. Clinical and pharmacokinetic study].

Ganciclovir (DHPG) was used in 32 renal transplant recipients with proven cytomegalovirus (CMV) disease. Mean time of CMV occurrence from grafting was 49 days. CMV disease was recognized on the combination of both clinical signs and histological or virological findings. DHPG treatment, adapted to renal function was given for 14 days and a pharmacokinetic study was performed at days 1, 7 and 14. Twenty nine patients, 10 of whom has severe to moderate disease, were improved by treatment. Three patients died, 2 of them with severe pulmonary and hepatic diseases. Few adverse effects were observed (leucopenia: n = 7, thrombopenia: n = 2, abdominal pain: n = 1). CMV was no longer found in virological samples in 80 percent of the patients. Maximal plasma concentration of DHPG (9.3 +/- 0.3 micrograms/ml, m +/- SEM) was reached at the end of the one hour infusion and decreased according to a biexponential model. The half life of elimination was 3.35 +/- 0.32 hours, the metabolic clearance 128 +/- 7 ml/min and the distribution volume about 50 percent body weight (0.48 +/- 0.02 l/kg). The clearance of DHPG was greater than creatinine clearance, and was linearly correlated with it, suggesting that renal elimination was important, both by glomerular filtration and tubular secretion. These results indicate that DHPG is effective and well tolerated for the treatment of CMV disease in renal transplant recipients. Renal elimination of the drug requires dosage adjustment to renal function.

Adult↗

[Acute clinical syndrome associated with OKT3 administration. Prevention by single injection of an anti-human TNF monoclonal antibody].

This study analyzed the capacity of an anti-human tumour necrosis factor (TNF) monoclonal antibody, CB006 (murine IgG1, Celltech), to prevent the OKT3-induced acute clinical syndrome. Fourteen renal allograft recipients undergoing prophylactic OKT3 therapy were included. CB006 was administered as a single i.v. injection, 0.4 mg/kg (Group I, 7 patients) and 2 mg/kg (Group II, 7 patients), one hour prior to the first OKT3 administration. Nineteen consecutive patients that were part of a randomized multicenter trial constituted the historical control group. In all patients CB006 was perfectly well tolerated and significantly decreased the frequency of the common OKT3-associated acute symptoms. None of the CB006 pretreated patients showed severe life threatening symptoms (hypotension, respiratory distress or neurotoxicity), observed in 10 per cent of historical controls. At variance with controls, in CB006 treated patients gastrointestinal symptoms (vomiting, diarrhea) and pyrexia (body temperature greater than or equal to 39 degrees C) appeared in low frequency, were mild and short lasting, never promoting major prostration of the patients due to electrolytes and fluid loss. Importantly, the presence in some patients of these mild symptoms, correlated with detectable bioactive TNF in the circulation thus reflecting incomplete blockade by CB006 of OKT3-induced TNF. CB006 pharmacokinetics data further stressed the need for adequate dosage adaptation. CB006 did not affect the biological or clinical effectiveness of OKT3. None of the patients showed evidence of anti-CB006 xeno-sensitization.

Antibodies, Monoclonal↗

[Treatment with Lo-Tact-1, a monoclonal antibody to the interleukin-2 receptor, in kidney transplantation].

From May to August 1989 15 cadaver-donor renal transplant recipients were treated for 14 days with LO-Tact-1 (10 mg i.v. per day) in combination with cyclosporin (8 mg/kg/day from day-1), low-dose steroids (1/2 mg/kg/day from day 1, then reduced to 0.25 mg/kg at day 26 and 10 mg/day at day 45), and azathioprine (1 mg/kg/day) started at day 45. LO-Tact-1 is a rat monoclonal antibody which is directed to the interleukin-2 receptor. The control group consisted of 20 patients receiving cyclosporin, high-dose steroids (2 mg/day at day 1) and a 14-day course of polyclonal horse antilymphocyte globulins (ALG). Seven patients experienced 9 rejections during the first 3 months post-transplant between day 10 and day 67 (mean 0.6 per patient), comparable to the incidence of rejections in the control group: 8 rejections in 7 patients (mean 0.4 per patient). All rejections were reversed by steroid boluses and ATG. To date, all study patients have functioning grafts, and at 1-year post-transplant, the mean blood creatinine level is 161.2 mumol/l. In the control group, one patient died of CMV infection, and 2 other grafts failed due to rejection. No adverse effect of antibody administration was observed, and hematological changes remained of minor importance. Viral infections were not observed, except one case of herpes simplex. Comparatively, clinical CMV infections occurred in 3 patients receiving ALG (15 percent). Our data suggest that a combination anti-IL-2 monoclonal antibody, cyclosporin and low-dose steroids can safely be administered to allograft recipients, avoid severe viral infections, and, in our early experience, is as potent as the powerful combination ALG, cyclosporin and high-doses steroids in preventing allograft rejection.

Adult↗