Biomedical subjects

M Mittlböck

Publications and source records attributed to M Mittlböck.

At least 19 recordsLinked to original sources

PubMed2001

Evaluation of perianal sepsis: comparison of anal endosonography and magnetic resonance imaging.

The purpose of this study was to compare prospectively the diagnostic yield of anal endosonography (AES) and magnetic resonance imaging (MRI) in the assessment of perianal fistulae and abscesses. There were 39 patients (14 men, 25 women; mean age, 40 years) who underwent AES, performed with a 10-MHz rotating endoanal probe and MRI at 1.0 T (axial and coronal T2-weighted turbo spin-echo (TSE) and turbo-STIR sequences). Fistulae were classified as subcutaneous, intersphincteric, transsphincteric, high (i.e., high extrasphincteric or suprasphincteric), rectovaginal, and horseshoe and were compared with the surgical findings in all patients. Overall, 58 fistulae (subcutaneous, N = 7; intersphincteric, N = 9; transsphincteric, N = 16; high, N = 17; rectovaginal, N = 5; and horseshoe, N = 4) were detected at surgery. MRI showed a sensitivity of 84% and AES of 60% (P <.05). False-positive diagnoses were made in 6 patients (15%) with MRI and in 15 patients (26%) with AES, for a specificity of 68% and 21%, respectively (P <.05). Our findings show that MRI is superior to AES in the assessment of fistula-in-ano before major surgery. AES should be used only for orientation before minor procedures, such as incision or drainage of subcutaneous fistulae.

Adult↗

PubMed2001

A note on R2 measures for Poisson and logistic regression models when both models are applicable.

The aim of many epidemiological studies is the regression of a dichotomous outcome (e.g., death or affection by a certain disease) on prognostic covariables. Thereby the Poisson regression model is often used alternatively to the logistic regression model. Modelling the number of events and individual outcomes, respectively, both models lead to nearly the same results concerning the parameter estimates and their significances. However, when calculating the proportion of explained variation, quantified by an R2 measure, a large difference between both models usually occurs. We illustrate this difference by an example and explain it with theoretical arguments. We conclude, the R2 measure of the Poisson regression quantifies the predictability of event rates, but it is not adequate to quantify the predictability of the outcome of individual observations.

Adult↗

PubMed2000

Endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal angioplasty : results of a prospective randomized study.

BACKGROUND: Inasmuch as endovascular brachytherapy (BT) has gained recent interest because of its inhibitory effect on mechanisms leading to restenosis after percutaneous transluminal angioplasty (PTA), we performed this randomized study to determine its efficacy for prophylaxis of restenosis after femoropopliteal PTA. METHODS AND RESULTS: One hundred thirteen patients (63 men, 50 women; mean age 71 years) with de novo or recurrent femoropopliteal lesions were included in this randomized trial comparing the restenosis rate after PTA plus BT (57 patients, PTA+BT group) versus PTA (56 patients, PTA group) without stent implantation. The mean treated length was 16.7 cm (PTA+BT group) versus 14.8 cm (PTA group). In patients randomized to PTA plus BT, a dose of 12 Gy was applied by an (192)Ir source 3 mm from the source axis. Follow-up examinations included measurement of the ankle-brachial index, color-flow duplex sonography, and angiography. The primary end point of the study was patency after 6 months. The overall recurrence rate after 6 months was 15 (28.3%) of 53 in the PTA+BT group versus 29 (53.7%) of 54 in the PTA group (chi(2) test, P<0.05). The cumulative patency rates at 12 months of follow-up were 63.6% in the PTA+BT group and 35.3% in the PTA group (log-rank test, P<0.005). CONCLUSIONS: This is the first randomized study to demonstrate the efficacy of endovascular BT for prophylaxis of restenosis after femoropopliteal PTA. The value of this approach should now be improved by modification of the BT procedure and by combination with stent implantation.

Aged↗

PubMed2000

Intraarterial (192)Ir high-dose-rate brachytherapy for prophylaxis of restenosis after femoropopliteal percutaneous transluminal angioplasty: the prospective randomized Vienna-2-trial radiotherapy parameters and risk factors analysis.

PURPOSE: The aim of the Vienna-2-trial was to compare the restenosis rate of femoropopliteal arteries after percutaneous transluminal angioplasty (PTA) with or without intraarterial high-dose-rate (HDR) brachytherapy (BT) using an (192)Ir source. MATERIALS AND METHODS: A prospective, randomized trial was conducted from 11/96 to 8/98. A total of 113 patients (63 men, 50 women), with a mean age of 71 years (range, 43-89 years) were included. Inclusion criteria were (1) claudication or critical limb ischemia, (2) de-novo stenosis of 5 cm or more, (3) restenosis after former PTA of any length, and (4) no stent implantation. Patients were randomized after successful PTA for BT vs. no further treatment. A well-balanced patient distribution was achieved for the criteria used for stratification, as there were "de-novo stenosis vs. restenosis after former PTA," "stenosis vs. occlusion," "claudication vs. critical limb ischemia" and above these for "diabetes vs. nondiabetes." PTA length was not well balanced between the treatment arms: a PTA length of 4-10 cm was seen in 19 patients in the PTA alone group and in 11 patients in the PTA+BT group, whereas a PTA length of greater than 10 cm was seen in 35 patients and 42 patients, respectively. A dose of 12 Gy was prescribed in 3-mm distance from the source axis. According to AAPM recommendations, the dose was 6.8 Gy in 5-mm distance (vessel radius + 2 mm). Primary endpoint of the study was femoropopliteal patency after 6 months. RESULTS: PTA and additional BT were feasible and well tolerated by all 57 pts in this treatment arm. No acute, subacute, and late adverse side effects related to BT were seen after a mean follow up of 12 months (6-24 months) in 107 patients (PTA n = 54; PTA+ BT n = 53). Crude restenosis rate at 6 months was in the PTA arm 54% vs. 28% in the PTA + BT arm (chi(2) test; p < 0.013). Actuarial estimate of the patency rate was at 6 months 45% vs. 72% (p < 0.004). Comparison of restenosis rates for the different subgroups with risk factors (restenosis after former PTA, occlusion and PTA length >10 cm) showed significant decrease of the restenosis rate, if BT was added. Significant reduction was not achieved in diabetes patients. CONCLUSION: BT after femoropopliteal PTA is feasible and a safe therapeutic option. No BT related morbidity was observed. A significant reduction of the restenosis rate was obtained in the PTA+BT arm. Subgroup analysis showed significant decrease of restenosis rate in the subgroups with restenosis after former PTA, occlusion and PTA length of greater than 10 cm. With dose escalation and reduction of dose variation by a centering device a further significant decrease of restenosis rate can be expected.

Adult↗

PubMed2000

Increased apoptosis of hepatocytes in vascular occlusion after orthotopic liver transplantation.

Early vascular occlusion is liable to cause graft failure, and differential diagnosis between this condition and primary nonfunction (PNF) caused by preservation injury may be difficult. Apoptosis has been detected in immunomediated cytotoxicity and is known to be triggered by mild ischemia. In a retrospective analysis we investigated the role of apoptosis in vascular occlusion, PNF, and acute allograft rejection to improve the differential diagnosis of early graft failure. The liver graft histology of 75 patients (46 male, 29 female) a median 47 (1-64) years of age was screened semiquantitatively for the rate of apoptosis on the hematoxylin-eosin stain (HE) and by the in situ end nick labeling technique (TUNEL). This cohort included all patients who developed PNF (n = 9) or vascular occlusion (n = 11) after orthotopic liver transplantation (OLT) in the years 1992 to 1996. Within this period of time we performed 205 OLTs on 189 patients. We further included 22 patients with early acute rejection and 11 controls. The highest rates of apoptotic hepatocytes were seen in vascular occlusion (P < 0.001). Grafts with PNF were explanted 1-3 days after OLT and showed hepatocytes that were 100% necrotic. Cases of acute early rejection showed a significantly higher apoptotic cell count than did normal controls (P < 0.003), increasing in direct proportion to the severity of rejection. Screening biopsies for the rate of apoptosis can improve the efficacy and accuracy of differential diagnosis of early graft failure.

Adolescent↗

PubMed2000

Radical surgical therapy of abdominal cystic hydatid disease: factors of recurrence.

A series of 74 consecutive patients (48 women, 26 men) were operated for abdominal hydatid disease between June 1949 and December 1995. The patients ranged in age from 15 to 81 years (median 49 years). In 69 cases only the liver was affected; two patients had concomitant extrahepatic disease (one spleen, one spleen and lung), and 3 had cysts in the spleen only. Cysts were multiple in 11 patients and calcified in 24. Conservative surgical procedures were used for 22 cysts in 20 patients [open partial (n = 3), open total (n = 6), closed total cystectomy (n = 9), marsupialization (n = 2), drainage (n = 2)] and radical surgical procedures for 72 cysts in 54 patients [pericystectomy (n = 41), wedge liver resection or hemihepatectomy (n = 25), splenectomy (n = 5), radical resection of a lung cyst (n = 1)]. Altogether 37 patients (50%) were given perioperative antihelmintic chemotherapy with mebendazole (18 patients) or albendazole (19 patients). Operative mortality rates were 5.0% after conservative surgery and 1.8% after radical surgery. Morbidity rates were 25.0% following conservative surgery and 24.1% following radical surgery. Antihelmintic therapy was well tolerated by all but five patients. All side effects were entirely reversible. Among the 74 patients, 60 (81.0%) were available for long-term follow-up (median 7.2 years; range 2.0-47.0 years). Recurrence of disease was seen in 9 of 60 patients at an interval of 3 months to 20 years from the first operation. The rate of recurrence was significantly lower after radical surgical procedures (p = 0.03) and after closed removal of the cyst (p = 0.04).

Adolescent↗

PubMed2000

Functional and morphometric evaluation of end-to-side neurorrhaphy for muscle reinnervation.

This study was undertaken to quantify the effect of motor collateral sprouting in an end-to-side repair model allowing end organ contact. Besides documentation of the functional outcome of muscle reinnervation by end-to-side neurorrhaphy, this experimental work was performed to determine possible downgrading effects to the donor nerve at end organ level. In 24 female New Zealand White rabbits, the motor nerve branch to the rectus femoris muscle of the right hindlimb was dissected, cut, and sutured end-to-side to the motor branch to the vastus medialis muscle after creating an epineural window. The 24 rabbits were divided into two groups of 12 each, with the second group receiving additional crush injury of the vastus branch. After a period of 8 months, maximum tetanic tension in the reinnervated rectus femoris and the vastus medialis muscles was determined. The contralateral healthy side served as control. The reinnervated rectus femoris muscle showed an average maximum tetanic force of 24.9 N (control 26.2 N, p = 0.7827), and the donor- vastus medialis muscle 11.0 N (control 7.3 N, p = 0.0223). There were no statistically significant differences between the two experimental groups (p = 0.9914). The average number of regenerated myelinated nerve fibers in the rectus femoris motor branch was 1,185 +/- 342 (control, 806 +/- 166), and the mean diameter was 4.6 +/- 0.6 microm (control, 9.4 +/- 1.0 microm). In the motor branch to the vastus medialis muscle, the mean fiber number proximal to the coaptation site was 1227 (+/-441), and decreased distal to the coaptation site to 795 (+/-270). The average difference of axon counts in the donor nerve proximal to distal regarding the repair site was 483.7 +/- 264.2. In the contralateral motor branch to the vastus medialis muscle, 540 (+/- 175) myelinated nerve fibers were counted. In nearly all cross-section specimens of the motor branch to the vastus medialis muscle, altered nerve fibers could be identified in one fascicle distal and proximal to the repair site. The results show a relevant functional reinnervation by end-to-side neurorrhaphy without functional impairment of the donor muscle. It seems to be evident that most axons in the attached segment were derived from collateral sprouts. Nonetheless, the present study confirms that end-to-side neurorrhaphy is a reliable method of reconstruction for damaged nerves, which should be applied clinically in a more extended manner.

Anastomosis, Surgical↗

PubMed2000

TP53 mutation and p53 overexpression for prediction of response to neoadjuvant treatment in breast cancer patients.

The value of p53 to predict the cytotoxic effect of two commonly used chemotherapy regimens was assessed in patients with advanced breast cancer. Response to a DNA-damaging combination therapy [fluorouracil, epirubicin, cyclophosphamide (FEC] considered to induce p53-dependent apoptosis was compared with a microtubule stabilizing therapy (paclitaxel) expected to be independent of p53 function. The p53 status of the patients' breast tumors was assessed using both immunohistochemistry (IHC) and direct sequencing of the entire p53 gene. p53 findings were correlated with treatment response, and linkage between p53 function and cellular response was assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. In a series of 67 breast tumors, 19% had TP53 gene mutations, 40% had a positive p53 IHC, and 12% had both. In the FEC group, treatment failure was related to both the presence of TP53 gene mutations (P = 0.0029) and a positive IHC (P < 0.0001). Apoptosis was almost exclusively found in tumors having normal p53 in both parameters (P < 0.0001). In the paclitaxel group, treatment response was neither related to apoptosis nor to normal p53. Combination of sequencing and IHC results revealed a significant association between abnormal p53 and response to paclitaxel (P = 0.011). We found TP53 mutations, as well as p53 protein overexpression, to be associated with response to chemotherapy. Whereas clinical response to FEC was found to be dependent on normal p53, the cytotoxicity of paclitaxel was related to defective p53. The efficiency of paclitaxel during mitosis might be supported by lack of G1 arrest due to p53 deficiency. Therefore, patients with p53-deficient tumors may benefit from paclitaxel.

Antineoplastic Agents, Phytogenic↗

PubMed1999

The TP53 genotype but not immunohistochemical result is predictive of response to cisplatin-based neoadjuvant therapy in stage III non-small cell lung cancer.

BACKGROUND: The cytotoxic effects of cisplatin and anthracyclins have been attributed to apoptosis induction, which has been recognized as a major function of the TP53 gene. The TP53 gene appears to be mutated in about 50% of cases of non-small cell lung cancer. A possible dependence of chemotherapy response on TP53 genotype was evaluated retrospectively in a group of patients with advanced non-small cell lung cancer and induction treatment. METHODS: Patients with complete or partial remission were compared with those with stable or progressive disease with respect to TP53 genotype and overall survival. Mutations in the TP53 gene were detected by complete direct sequencing (exons 2-11). RESULTS: A normal TP53 genotype proved to be significantly associated with major response to chemotherapy (P <.001). Overall, no association was found between p53 protein expression and TP53 genotype. A normal TP53 genotype was found to be highly sensitive in predicting response to treatment, whereas a mutant genotype was revealed to be specific in predicting lack of response. The difference in overall length of survival was significant between patients exhibiting a normal TP53 genotype (corresponding to those whose disease responded to chemotherapy) and patients showing mutant TP53 genotype (corresponding to those who had disease resistant to chemotherapy, P =.027). CONCLUSIONS: In a small cohort of patients with advanced non-small cell lung cancer we found a direct link between normal TP53 genotype and response to cisplatin-based induction treatment and also between mutant genotype and resistance to treatment, whereas p53 immunohistochemical result was predictive of neither.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

Computing measures of explained variation for logistic regression models.

The proportion of explained variation (R2) is frequently used in the general linear model but in logistic regression no standard definition of R2 exists. We present a SAS macro which calculates two R2-measures based on Pearson and on deviance residuals for logistic regression. Also, adjusted versions for both measures are given, which should prevent the inflation of R2 in small samples.

Computer Simulation↗

PubMed1999

Progression of burn wound depth by systemical application of a vasoconstrictor: an experimental study with a new rabbit model.

The final depth of a necrosis resulting from burn trauma is determined within 3 days. The zone of stasis has the potential for complete regeneration or there may be ischemic influences that lead to necrosis. In our model, we examined the dermal influence of vasoconstrictors with reference to the development of burn necrosis. On the backs of New Zealand white rabbits (4.0-4.5 kg) standardized lesions were made with a heated aluminum stamp at 80 degrees C, 14 s in duration. The lesions were intradermal, whereby the border zone of the coagulated tissue was found in the middle two quarters of the dermis in 100% of untreated animals after 72 h. For dermal vasoconstriction epinephrine in a dose of 0.5 microg/kg/min was used. There were two groups of seven animals each. One group received epinephrine and the dosage was dependent on the clinical state of the animal. Several cycles were administered within a 3-day period. The reduction of skin perfusion was documented by Laser-Doppler-flowmetry. After 3 days, the skin with the lesions was excised and using a hematoxylin dye, a histological examination followed. The parameter used to determine the efficacy was the thickness of the uncoagulated part of the excised dermis. Over a period of 48 h, an average of 2.3 epinephrine cycles of average of 88 min per animal in duration resulted in an average reduction of skin diffusion of 41%. The uncoagulated part of the dermis in the epinephrine group was 28.6% average; in the control group, this was 43.5%. The statistical analysis revealed significant differences with a p-value of 0.0312 (significant, when value is less than 0.05). The test results indicate that temporary reduction of skin perfusion through external administration of vasocontrictors may lead to progression of burn necrosis in our animal model. Clinically, this result indicates that for patients with burn injuries and systemic inflammatory response syndrome who have insufficient volume therapy, the administration of vasocontrictors may produce similar results in the injured area.

Administration, Topical↗

PubMed1999

Prognostic significance of mutations in the p53 gene, particularly in the zinc-binding domains, in lymph node- and steroid receptor positive breast cancer patients. Austrian Breast Cancer Study Group.

The aim of our study was to evaluate if p53 mutations, especially those in the L2/L3 domains of the p53 gene, add prognostic information for node-positive and steroid receptor positive breast cancer patients. Two hundred and five tumour samples from a randomised clinical trial of 596 lymph node- and steroid receptor positive breast cancer patients were included. All patients had been randomly allocated to receive 20 mg of adjuvant tamoxifen (TAM) daily for 2 years or TAM plus one cycle of low-dose, short-term chemotherapy. For detection of p53 mutations we used in vitro amplification by polymerase chain reaction and consecutively performed temperature gradient gel electrophoresis (PCR-TGGE) and direct sequencing. We found p53 mutations in 42/205 (20%) cases: 16/42 (38%) p53 mutations occurred within the L2/L3 domains of the p53 gene, and 26/42 (62%) outside the L2/L3 domains. p53 mutation served as a statistically significant parameter in predicting disease-free survival in univariate (P = 0.02) and multivariate (P = 0.009) analysis. For overall survival, no significant differences were observed. Patients with tumours that had p53 mutations within the L2/L3 domains of the gene showed no significant difference to those with mutations outside the L2/L3 domains for disease-free survival. For overall survival, mutations in the L2/L3 domains showed a marginally significant difference (P = 0.05) in multivariate analysis, but not in univariate analysis (P = 0.13). We conclude that mutation in the L2/L3 domains of the p53 gene is not an independent prognostic indicator of disease outcome for patients suffering from breast cancer with lymph node metastases and positive steroid receptors.

Adult↗

PubMed1999

Noninvasive monitoring of peak filling rate with acoustic quantification echocardiography accurately detects acute cardiac allograft rejection.

BACKGROUND: Acute cardiac allograft rejection is associated with early diastolic dysfunction. The development of chronic rejection is dependent on the frequency and severity of acute rejection episodes. Therefore, early diagnosis and therapy influence long-term survival significantly. For the first time, acoustic quantification, a new echocardiographic technology for on-line measurement of cardiac volumes and their changes, facilitates quantitative assessment of systolic and diastolic function noninvasively. METHODS: Since May 1996, all consecutive patients after cardiac transplantation (n = 94) underwent 475 endomyocardial biopsies and the same number of echocardiographic studies within 6 hours after biopsy before the histological results were available. RESULTS: Nineteen patients showed 23 episodes of acute rejection (ISHLT > or = 2). There was a significant decrease in left ventricular peak filling rate [PFR: end-diastolic volume (EDV)/ second) as a parameter of diastolic function during rejection (2.9 +/- 0.4, n = 23) as compared to PFR measured under nonrejection status (4.5 +/- 0.8; n = 452; p < 0.0001). Most importantly we found that in these 19 patients showing rejection, the PFR was normal in the last examination before rejection, but was significantly reduced during rejection (2.9 +/- 0.4 vs 4.5 +/- 0.7; n = 23, p < 0.0001). After successful rejection therapy, PFR again normalized in all patients, with the exception of 1 patient with steroid-refractory humoral rejection. We calculated sensitivity and specificity for several cutpoints for the event "first rejection" in 15 patients and plotted them in a receiver operating characteristic curve, showing that a PFR > or = 4.0 EDV/second is never associated with treatable rejection. A decrease of PFR of more than 18% from its prevalue of the last biopsy with no rejection increases the accuracy for the diagnosis of rejection significantly. CONCLUSIONS: We conclude that diastolic dysfunction during acute cardiac allograft rejection can be accurately detected by noninvasive measurement of peak filling rate with acoustic quantification echocardiography. Monitoring of this parameter provides reliable discrimination between treatable and nontreatable rejection.

Acute Disease↗

PubMed1999

Attenuation of catecholamine-induced immunosuppression in whole blood from patients with sepsis.

Studies performed on healthy volunteers have revealed that catecholamines down-regulate the lipopolysaccharide (LPS)-induced production of tumor necrosis factor (TNF)alpha, interleukin (IL)-6, and IL-1beta. We extended this observation and show that this effect is based on changes in the mRNA concentration of these cytokines. Catecholamines are increased in severe sepsis due to endogenous production and have to be administered exogenously when the disease has proceeded to the state of prolonged hypotension. We here investigated whether the immunomodulating effect of catecholamines could also be demonstrated in the blood of patients with prolonged severe sepsis and of those in prolonged septic shock. Blood was stimulated ex vivo with LPS in the presence and absence of epinephrine and the cytokine protein concentration was determined. In blood of healthy volunteers, epinephrine reduced the LPS-stimulated synthesis of TNFalpha by 62.5% (P< 0.0001), of IL-6 by 39% (P< 0.0001), and of IL-1beta by 40% (P= 0.015), and increased the LPS-stimulated IL-10 production by 77.8% (P < 0.0001). Correspondingly, in blood of patients with prolonged severe sepsis, TNFalpha was reduced by 67.2% (P < 0.0001) and IL-6 was reduced by 32.9% (P < 0.0001); IL-1beta and IL-10 were not modulated by catecholamines in these patients. In blood samples of patients in prolonged septic shock, epinephrine did not modulate cytokine levels of IL-6 and IL-10, and decreased TNFalpha only by 36.4% (P < 0.0001). Interestingly, epinephrine suppressed the IL-1beta production by 73% (P < 0.0001) in blood of patients in prolonged septic shock, which was twice as much as in blood samples of healthy volunteers. The altered response of septic blood to catecholamines might be due to an altered reactivity of leukocytes in the prolonged disease although an additional role of preexisting catecholamines cannot be completely excluded.

Adrenergic beta-1 Receptor Antagonists↗

PubMed1999

Randomized trial of low-dose chemotherapy added to tamoxifen in patients with receptor-positive and lymph node-positive breast cancer.

PURPOSE: To evaluate the outcome in patients with stage II hormone receptor-positive breast cancer treated or not treated with low-dose, short-term chemotherapy in addition to tamoxifen in terms of disease-free and overall survival. PATIENTS AND METHODS: A total of 613 patients were randomized to receive either low-dose chemotherapy (doxorubicin 20 mg/m(2) and vincristine 1 mg/m(2) on day 1; cyclophosphamide 300 mg/m(2); methotrexate 25 mg/m(2); and fluorouracil 600 mg/m(2) on days 29 and 36 intravenously) or no chemotherapy in addition to 20 mg of tamoxifen orally for 2 years. A third group without any treatment (postmenopausal patients only) was terminated after the accrual of 79 patients due to ethical reasons. RESULTS: After a median follow-up period of 7.5 years, the addition of chemotherapy did not improve the outcome in patients as compared with those treated with tamoxifen alone, neither with respect to disease-free nor overall survival. Multivariate analysis of prognostic factors for disease-free survival revealed menopausal status, in addition to nodal status, progesterone receptor, and histologic grade as significant. Both untreated postmenopausal and tamoxifen-treated premenopausal patients showed identical prognoses significantly inferior to the tamoxifen-treated postmenopausal cohort. Prognostic factors for overall survival in the multivariate analysis showed nodal and tumor stage, tumor grade, and hormone receptor level as significant. CONCLUSION: Low-dose chemotherapy in addition to tamoxifen does not improve the prognosis of stage II breast cancer patients with hormone-responsive tumors. Tamoxifen-treated postmenopausal patients show a significantly better prognosis than premenopausal patients, favoring the hypothesis of a more pronounced effect of tamoxifen in the older age groups.

Age Factors↗

PubMed1998

[Liver transplantation in acute liver failure].

Acute hepatic failure is characterized by jaundice and hepatic encephalopathy within eight weeks after the onset of disease. Although acute hepatic failure is a rare occurrence, its rapid progression and high mortality (50 to 90%, depending on the etiology of disease) necessitate immediate intervention. In the absence of causal therapy, orthotopic liver transplantation is currently the only definitive and effective means of treating acute hepatic failure in Europe, acute hepatic failure accounts for 11% of all liver transplantations. At the University department of transplantation surgery in Vienna a total of 27 patients with acute hepatic failure underwent 31 liver transplantations in the last 10 years (1.1.1987 to 31.12.1996). Twenty (74%) of the 27 patients survived the acute event and were discharged from hospital in good general condition after a median postoperative stay of 25 days (range 14-81 days). Seven patients (26%) died between the first and 34th postoperative day (median 26 days) in the intensive care unit, although all potential modern options of intensive care and surgery were used. The causes of death were irreversible cerebral edema (n = 3), multiple organ failure due to bacterial sepsis (n = 3) and uncontrollable haemolysis (n = 1). With a 3-year graft survival rate of 70% the 3-year patient survival rate was 74%. A retrospective analysis of our patients revealed that the postoperative graft function and the incidence of re-transplantation were significant prognostic factors (p < 0.05) for survival following orthotopic liver transplantation for acute hepatic failure. In the absence of further prognostically relevant preoperative indices and in consideration of the potentially fulminant progression of disease, we strongly recommend that any patient, in whom acute hepatic failure is suspected, is immediately transferred to a specialized center with experience both in the conservative treatment of acute hepatic failure and emergency liver transplantation.

Adolescent↗

PubMed1998

The interpretation of clinical trials of immediate versus delayed therapy.

Prospective, randomised clinical comparisons with a control group are the ideal way to evaluate the effectiveness of a new therapy. However if the new therapy is already available, then it may be unethical to refuse patients this treatment indefinitely. In some trials, patients randomised to the control group receive placebo until their condition deteriorates, and are then switched to the new therapy. Patients randomised to the experimental group receive the new treatment immediately. An analysis following the intention-to-treat principle will be a valid comparison of the two treatment policies actually used. However, such an analysis will underestimate the effect of immediate therapy relative to completely untreated controls, and in particular a negative conclusion should not be interpreted to mean that the therapy is ineffective. In this paper we introduce a parametric approach, which models the dependence between the survival time and the time of switching to the new treatment. This is used first to illustrate the lack of power of the intention-to-treat analysis for evaluating the therapy relative to a pure control. More speculatively, an alternative method of analysis based on our model is presented. We illustrate the issues with data from a prospective randomised study, in which one group of HIV-positive patients received zidovudine immediately after randomisation while control patients were switched to zidovudine only when their condition deteriorated.

Anti-HIV Agents↗

PubMed1998

Apoptotic hepatocytes in rejection and vascular occlusion in liver allograft specimens.

AIMS: Programmed cell death (apoptosis) has been described in different hepatobiliary diseases and in immune-mediated cytotoxicity. Apoptosis of hepatocytes and bile duct epithelial cells was detected in chronic liver allograft rejection. In severe acute rejection a DNA fragmentation in-situ assay showed positivity of apoptotic cells and centrilobular necrosis. Although apoptosis is triggered by ischaemia, the potential role of apoptosis in tissue damage caused by hepatic vascular occlusion after orthotopic liver transplantation has not yet been investigated. METHODS AND RESULTS: We examined biopsies for apoptotic cell death in 50 liver allografts: 29 with acute liver rejection, six without rejection, five time-zero biopsies, and 10 cases with hepatic artery thrombosis. In addition to a semiquantitative assessment of apoptotic bodies in haematoxylin and eosin stains, an in-situ end nick-labelling technique (TUNEL) was used to detect DNA fragmentation. In all cases with hepatic artery thrombosis the incidence of apoptosis was found significantly increased in comparison to acute rejection. CONCLUSIONS: As apoptosis is a mechanism in the early stages of tissue damage prior to necrosis, increased apoptosis in liver allograft biopsies might be regarded as a signal of early ischaemia indicating initial vascular occlusion.

Adolescent↗