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Biomedical subjects

P Wolf

Publications and source records attributed to P Wolf.

At least 109 records · Page 6Linked to original sources
PubMed1999

Update on sequential isologous rat organ transplantation: pancreaticoduodenal and kidney transplantations.

This periodic report includes intermittent results of consecutive pancreaticoduodenal (Pd) and kidney (Kt) transplants in inbred rats and results on double kidney transplants that did not follow sequential transplant protocol. Eight 24-month-old Lewis pancreas, kidney, and aorta served histological controls showing normal histological architecture with no atherosclerosis developed in the aorta. Thirty-four month old pancreas and thirty-two month old kidneys, which resided in young hosts for at least three occasions, appeared as youthful Pd and Kt grafts. They show normal histological appearance for more than the expected life span of a Lewis rat. The fact that not only pancreases but also kidneys outlived their host leads to the study of other different organs' viability as aged valuable grafts. Nevertheless, the threats by the development of atherosclerosis in graft-associated aortas resulted in slow progression of the follow-ups.

Animals↗
PubMed1999

[Surgical strategy in the treatment of synchronous hepatic metastases of colorectal cancers. Analysis of a series of 59 operated on patients].

AIM OF THE STUDY: The surgical strategy for the treatment of resectable synchronous hepatic metastases of colorectal cancer remains controversial. The retrospective analysis of our series of resectable synchronous hepatic metastases is focused on the percentage of simultaneous resections, the circumstances, the indications, and the results of the one-step procedure compared to the two-step strategy. METHODS: From January 1st 1982 to December 31st 1996, 146 patients were operated on for resection of hepatic metastases of colorectal cancer. Fifty-nine (40%) presented with synchronous metastases, 28 (47.5%) of whom underwent simultaneous resection of the primary tumor and of the hepatic metastases (simultaneous resection group: SR). For the other 31 patients (52.5%), the hepatic resection was delayed for a mean interval of 6 +/- 4 months (delayed resection group: DR). RESULTS: The mean age in the two groups was not significantly different (56 years vs. 60 years). The need for blood transfusion and the volume required were not significantly different between the two groups. The duration of each surgical operation was comparable between the two groups (320 +/- 76 min vs. 308 +/- 88 min). Postoperative complications were observed in 18% of patients in the SR group and in 16% of patients in the DR group (no significant difference). There was no postoperative mortality in either group. Survival was 86, 63 and 43% at 1, 2, 3 years respectively in the SR group, and 81, 51 and 36% in the DR group, with no significant difference between the groups. CONCLUSION: Simultaneous resection of the primary tumor and the hepatic metastases does not increase neither mortality nor morbidity in our series. The best candidate for a one-step procedure is a patient with a right colonic tumor, in a good status, with liver synchronous metastases resectable by mean of a minor hepatectomy.

Actuarial Analysis↗
PubMed1999

Characterization of a pig-to-goat orthotopic lung xenotransplantation model to study beyond hyperacute rejection.

BACKGROUND: A pig-to-goat orthotopic lung xenograft model was developed to test whether depletion of goat xenoreactive antibodies against pig red blood cells would prolong pig lung xenograft survival. METHODS: Adult goats with anti-pig xenoreactive antibodies underwent left pneumonectomy followed by orthotopic transplantation of pig left lung (group 1) or immunodepletion of their xenoreactive antibodies by extracorporeal right pig lung perfusion before transplantation without (group 2) or with (group 3) complete clampage of the right pulmonary artery. In group 4, goat left lungs were orthotopically transplanted into pigs and served as negative controls (pig serum does not have anti-goat xenoreactive antibodies). Each study group included 5 animals. Immunosuppression in surviving recipients included cyclosporine and azathioprine. RESULTS: Group 1 recipients died 7 +/- 3 hours after xenograft reimplantation of severe pulmonary hypertension and dysfunction and vasogenic shock, with little evidence of histologic xenograft injury. Group 2 xenografts had a stable circulatory and respiratory function on reperfusion and survived 9 +/- 4 days. Group 3 animals also tolerated complete occlusion of the right pulmonary artery, and xenografts assured the total respiratory support for 4 +/- 1 days. After immunodepletion, goat serum showed no detectable titers of xenoreactive antibodies, which began to reappear by postoperative day 2, where xenografts showed histologic stigmata of acute (humoral and cellular-mediated) rejection that evolved to a complete xenograft necrose at death. Group 4 xenografts showed scattered features of acute rejection 5 +/- 1 days after the operation. CONCLUSIONS: Pig left lung xenografts can provide prolonged and complete respiratory support after depletion of goat xenoreactive antibodies, but they ultimately necrose once recipient xenoreactive antibodies return to pretransplantation values.

Animals↗
PubMed1999

Effects of corticosteroids on HCV infection.

The risk factors for clinical recurrent hepatitis C in liver transplant recipients are not clearly defined. It has been suggested that the corticosteroids included in the treatments of patients undergoing allograft rejection might induce acute hepatitis by increasing HCV replication. In this study we investigated the effects of corticosteroid boluses on HCV viremia in liver allograft recipients treated for acute rejection. Since we had previously developed a model of HCV replication in peripheral blood mononuclear cells (PBMC) in vitro, we also studied the effects of corticosteroids on HCV replication in vitro. A transient peak of HCV viremia was observed in patients treated with corticosteroid boluses for an acute allograft rejection. In the cell cultures, corticosteroids induced an increase of the total amount of viral RNA detectable. Our results demonstrate that corticosteroids induce an increase of hepatitis C virus replication in vivo and in vitro.

Adrenal Cortex Hormones↗
PubMed1999

Benign epileptic discharges in patients with lesional partial epilepsies.

Case reports of four patients with therapy-resistant lesional partial epilepsies and additional foci of benign epileptic discharges of childhood, in addition to the usual electroencephalogram (EEG) changes, are presented. A family history of epileptic or febrile seizures in childhood was reported in all four patients. A distant relative of one patient, not manifesting seizures, demonstrated rolandic spikes on EEG. An abnormal pregnancy (polyhydramnion, premature pains, induced labor because of an abnormal CTG , placenta insufficiency) was reported in one patient, risk factors during birth (birth 14 days after term, placenta insufficiency) were reported in one, and bacterial meningitis at 4 weeks of age was reported in one. All patients manifested a retarded, partly severe, unfavorable infantile psychomotor development. An early seizure onset was observed in all patients (in three patients during the first year of life and in one patient during the second year). A hemifacial seizure symptomatology was seen, in addition to other symptoms, in two patients, possibly indicating the seizure pattern indicative of benign partial seizures; seizures occurred exclusively in sleep in one patient. The benign focus was never located in the lesional area. It was recorded over the same hemisphere in two patients and over the other hemisphere in the other two.

Cerebral Cortex↗
PubMed1999

Screening for basiliximab exposure-response relationships in renal allotransplantation.

The immunosuppressant basiliximab--a chimeric monoclonal antibody specific to the interleukin-2 receptor on activated T-lymphocytes--significantly reduces the incidence of acute cellular rejection following renal transplantation. Screening for exposure-response relationships was performed within a randomized, blinded, placebo-controlled efficacy trial in which patients received 40 mg basiliximab (20 mg on days 0 and 4) by intravenous infusion in addition to cyclosporine and corticosteroids. In a subset of patients, serum samples were collected pre-transplant and once in weeks 2, 3 and 4 for determination of basiliximab concentrations. A population pharmacostatistical model was used to derive individual empirical Bayes estimates of each patient's pharmacokinetic parameters. Biopsy-confirmed acute rejection episodes were recorded to month 6 post-transplant. Forty basiliximab-treated patients were evaluated, 30 men and 10 women, aged 48 +/- 12 yr (range, 24-73) and weighing 72.4 +/- 12.9 kg (range, 52.5-107.5). The basiliximab distribution volume was 7.5 +/- 1.7 L, the half-life 7.5 +/- 2.5 d and the clearance 33 +/- 12 mL/h. There was no clinically relevant influence of weight, age, or gender on basiliximab disposition. Receptor-saturating serum basiliximab concentrations (> 0.2 microgram/mL) were maintained for 41 +/- 23 d. Twenty-five patients remained rejection-free over the 6-month observation period, while a total of 26 biopsy-confirmed acute rejection episodes occurred in the remaining 14 patients. Of these episodes, 12 occurred during receptor blockade. No apparent relationship to basiliximab concentration on the day of onset was observed range, 0.1-9.0 microgram/mL) nor did the time of suppression offset represent a period of increased risk for rejection episodes. Fourteen rejection episodes occurred after basiliximab had cleared from the serum. The durations of receptor suppression preceding these events did not differ compared with those in patients who remained rejection-free: 32 +/- 11 versus 45 +/- 26 d, respectively (p = 0.1269). Given the durations of receptor saturation achieved with the chosen basiliximab regimen, this screen for exposure-response relationships did not identify the duration of receptor saturation in peripheral blood as a predictive factor for acute rejection episodes. Further exploration for exposure-effect relationships in a larger population is warranted.

Adult↗
PubMed1999

Possibilities of non-pharmacological conservative treatment of epilepsy.

This study set out to assess the effect of non-pharmacological conservative (NPC) interventions as alternatives to antiepileptic pharmacotherapy. A prospective follow-up cohort study was conducted in an outpatient seizure clinic of a referral center for epilepsy. Twenty-five patients (nine males, 16 females) aged 16-45, with at least two well-described epileptic seizures, were included who had rejected antiepileptic pharmacotherapy. Twelve had idiopathic generalized epilepsy, 11 had symptomatic or cryptogenic localization-related epilepsy, and two had epilepsy with generalized and focal signs. Twenty-three of the patients were followed for more than 2 years. The patients were treated with arrest after focal seizure onset (2 cases), sensory protection against reflex seizures (3 cases), avoidance of non-specific seizure-precipitating factors ('life hygiene', 16 cases), and/or miscellaneous interventions (8 cases). The main outcome measures were complete seizure control (more than 2 years) or sufficient improvement to continue with NPC treatment alone. Eight of the 23 patients were completely seizure free for more than 4 years, and three were sufficiently improved to continue NPC treatment without drugs. Trends were observed for patients with idiopathic generalized epilepsies with less than seven convulsive seizures, and with only one seizure type to respond better to NPC treatment. The duration of epilepsy, and the finding of generalized epileptiform discharge in the EEG had no influence on the outcome. Rational NPC treatments which are aimed at specific factors in the precipitation and development of epileptic seizures can be useful therapeutic alternatives for patients with milder forms of epilepsy. Apart from photosensitive patients, those most likely to profit are patients with idiopathic generalized epilepsy, a maximum of six generalized tonic-clonic seizures which were precipitated by lack of sleep or excessive alcohol intake, and with no or rare concomitant absences. In such cases, NPC treatment may be as effective as pharmacotherapy and gives the patient a positive experience of regained self-control.

Adolescent↗
PubMed1999

Gabapentin add-on treatment: how many patients become seizure-free? An open-label multicenter study.

The aim of the study was to find out the percentage of patients with localization-related epilepsy achieving complete seizure control with gabapentin (GBP) add-on therapy. Patients under anti-epileptic drug monotherapy during 8 weeks baseline (BSL) with 6 or more seizures were treated with GBP for 26 weeks up to 2400 mg/day. Patients obtaining complete seizure control of all seizures or any partial seizure type during the last 8 weeks were calculated. Seizure frequency was compared between BSL and last 8 weeks. In all, 110 patients were enrolled (92 completed, 18 discontinued): mean age of the completers: 37.6 years (range 16-72), median seizure frequency per 28 days at BSL: 6.8 (2.5-24.5), mean duration of epilepsy: 17.6 years (0.2-51.4), mean duration with GBP for completers: 182.8 days (144-187). Complete seizure control of all seizures was achieved in 8.7% of patients (simple partial seizures: 13.3%, complex partial seizures 24.3%, secondarily generalized seizures: 61.5%): 38% of the patients became seizure-free in at least 1 seizure-type; 40% experienced adverse events. Assessment for quality of life (QoL) and trough plasma levels of GBP did not correlate with the good effect of GBP.

Acetates↗
PubMed1999

Photoprotection by topical DNA repair enzymes: molecular correlates of clinical studies.

A new approach to photoprotection is to repair DNA damage after UV exposure. This can be accomplished by delivery of a DNA repair enzyme with specificity to UV-induced cyclobutane pyrimidine dimers into skin by means of specially engineered liposomes. Treatment of DNA-repair-deficient xeroderma pigmentosum patients or skin cancer patients with T4N5 liposome lotion containing such DNA repair liposomes increases the removal of DNA damage in the first few hours after treatment. In these studies, a DNA repair effect was observed in some patients treated with heat-inactivated enzyme. Unexpectedly, it was discovered that the heat-inactivated T4 endonuclease V enzyme refolds and recovers enzymatic activity. These studies demonstrate that measurements of molecular changes induced by biological drugs are useful adjuvants to clinical studies.

Administration, Topical↗
PubMed1999

Protection against hyperacute xenograft rejection of transgenic rat hearts expressing human decay accelerating factor (DAF) transplanted into primates.

BACKGROUND: Production of transgenic pigs for multiple transgenes is part of a potential strategy to prevent immunological events involved in xenograft rejection. Use of a genetically engineerable rodent as a donor in primates could allow testing in vivo of the effects of different transgenes on controlling xenograft rejection. As a first step in the development of a donor containing multiple transgenes, transgenic rats for human decay-accelerating factor (DAF) were used as heart donors to test their resistance against complement (C)-mediated rejection by non-human primates. MATERIALS AND METHODS: Transgenic rats were generated by using a construct containing the human DAF cDNA under the transcriptional control of the endothelial cell (EC)-specific human ICAM-2 promoter. DAF expression was evaluated by immunohistology and by FACS analysis of purified ECs. Resistance of transgenic hearts against C-mediated damage was evaluated by ex vivo perfusion with human serum and by transplantation into cynomolgus monkeys. RESULTS: Immunohistological analysis of DAF expression in several organs from two transgenic lines showed uniform expression on the endothelium of all blood vessels. ECs purified from transgenic hearts showed 50% DAF expression compared to human ECs and >70% reduction of C-dependent cell lysis compared to control rat ECs. Hemizygous transgenic hearts perfused with human serum showed normal function for >60 min vs. 11. 2 +/- 1.7 min in controls. Hemi- or homozygous transgenic hearts transplanted into cynomolgus monkeys showed longer survival (15.2 +/- 7 min and >4.5 hr, respectively) than controls (5.5 +/- 1.4 min). In contrast to hyperacutely rejected control hearts, rejected homozygous DAF hearts showed signs of acute vascular rejection (AVR) characterized by edema, hemorrhage, and an intense PMN infiltration. CONCLUSIONS: We demonstrate that endothelial-specific DAF expression increased heart transplant survival in a rat-to-primate model of xenotransplantation. This will aid in the analysis of AVR and of new genes that may inhibit this form of rejection, thus helping to define strategies for the production of transgenic pigs.

Animals↗
PubMed1998

Invariant chain can bind MHC class II at a site other than the peptide binding groove.

Invariant chain binds to class II molecules and guides them to the cell surface via the endosomes. Class II-associated invariant chain peptide (CLIP), a conserved sequence in an unstructured region of invariant chain, binds in the peptide binding groove of class II and is thought to be the major contributor to the interaction between invariant chain and class II molecules. However, other interaction sites between the two proteins may exist. The published data on this subject are conflicting. We have studied the ability of invariant chain to interact with a class II molecule in which the peptide binding groove of the protein is already occupied by a covalently attached peptide. Precipitation of these class II/peptide complexes with an Ab specific for this particular combination also precipitates invariant chain. This binding between class II/peptide and invariant chain is weak, and coprecipitation is only apparent in mild detergents. Thus, when the class II peptide binding groove is occluded by peptide and is not free to interact with CLIP, invariant chain can still bind the class II molecule at other lower affinity sites.

Animals↗
PubMed1998

Long-term follow-up and histological changes of superficial nonmelanoma skin cancers treated with topical delta-aminolevulinic acid photodynamic therapy.

OBJECTIVE: To investigate the immediate and long-term effects of photodynamic therapy with delta-aminolevulinic acid (ALA-PDT) on superficial basal cell carcinomas (BCC) and superficial squamous cell carcinomas (SCC). DESIGN: Retrospective study with 60 months of maximal follow-up. SETTING: University-based hospital in Graz, Austria. PATIENTS: Forty-seven subjects with a total of 95 superficial BCC and 35 superficial SCC. INTERVENTIONS: A compound of 20% delta-aminolevulinic acid was topically applied under an occlusive and light-shielding dressing before exposure to either UV-A or different wave bands of polychromatic visible light (full-spectrum visible light, >515, >570, or >610 nm). MAIN OUTCOME MEASURES: Primary tumor responses and recurrence rates in the long-term follow-up, as well as histological changes associated with ALA-PDT, were studied. RESULTS: The complete primary response rate for all wave bands of light was 86% (82/95) for superficial BCC and 54% (19/35) for superficial SCC. There was no statistically significant difference among the response rates to the different wave bands of light. After a median follow-up of 19 months (range, 3-60 months) for BCC and 8 months (range, 3-47 months) for SCC, the overall recurrence rate was 44% (36/81) and 69% (11/16), respectively. At 36 months after therapy, the projected disease-free rate was 50% (95% confidence interval, 43%-57%) for BCC vs 8% (95% confidence interval, 7%-9%) for SCC (P<.001, log-rank test). Histopathologic studies revealed a significant increase of fibrosis in the dermis after ALA-PDT and appearance of a sharp border between fibrotic and nonfibrotic tissue. In 15 of 16 BCC examined, the border between fibrotic and nonfibrotic tissue was deeper in the dermis than the maximum tumor thickness before therapy (P<.001, Wilcoxon signed rank test). Similar histopathologic observations were made in SCC. CONCLUSIONS: Our study revealed poor long-term cure rates for superficial BCC and SCC treated with topical ALA-PDT and visible light. The histopathologic observations showing remarkable fibrosis in the dermis indicated that the effect of ALA-PDT reached deeper than the initial depth of invasiveness of the neoplastic tissue, suggesting in turn that the poor long-term results of ALA-PDT cannot be explained by insufficient penetration of the therapy effect.

Administration, Topical↗