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Biomedical subjects

P Wolf

Publications and source records attributed to P Wolf.

At least 19 recordsLinked to original sources

Language lateralization by Wada test and fMRI in 100 patients with epilepsy.

Comparing the determination of language dominance using fMRI with results of the Wada test in 100 patients with different localization-related epilepsies, the authors found 91% concordance between both tests. The overall rate of false categorization by fMRI was 9%, ranging from 3% in left-sided temporal lobe epilepsy (TLE) to 25% in left-sided extratemporal epilepsy. Language fMRI might reduce the necessity of the Wada test for language lateralization, especially in TLE.

Adult↗

[Sunscreens. Protection against skin cancers and photoaging].

Experimental animal studies have unambiguously demonstrated that topical sunscreens can prevent squamous cell carcinoma and photoaging (damage of collagen and elastic fibers of the skin). Although data from clinical studies and surrogate markers also indicate such photoprotective effects in man, there is a lack of controlled, prospective clinical trials to provide definite evidence in man. Because of inadequate data, no definite conclusions can be drawn about the cancer-preventive activity of topical use of sunscreens against basal cell carcinoma and malignant melanoma.

Administration, Topical↗

[Animal nutrition for veterinarians--actual cases: tulip bulbs with leaves (Tulipa gesneriana)--an unusual and high risk plant for ruminant feeding].

14 cattle (mainly younger ones) of a total of 50 extensively kept Galloways died within 6 weeks in late winter 2001/02. According to the owner's report, grass growth had been rather poor; therefore, the herd was fed additionally hay as well as large amounts of tulip onions. In the microbiological examination a highly reduced hygienic quality of the roughage could be detected. In the rumen contents of two dissected young cattle parts of tulip onions were found. According to pertinent literature, tulip onions (in particular their external layers) contain variant-specific amounts of anti-nutritive substances; main active agents are tulipin (a glycoprotein), tuliposid A and B, and lectins. They may cause intensive mucosal irritation, accompanied by reduced feed digestion and body-weight gains, drooling, vomiting and diarrhea. This case report underlines risks caused by feeding of plants originally not destined as forage, if their active ingredients and effects are unknown or remain unconsidered.

Animal Feed↗

[The epileptic patient in general practice. What the family physician must attend to].

Some 25% of patients with epilepsy are under the sole care of their family doctors. Treatment is applied in accordance with clear guidelines. The leading aim of therapy is always freedom from seizures. The gold standard is monotherapy, with combination treatment taking second place. In focal epilepsy, the drug of first choice is still carbamazepine, and in generalized epilepsy valproic acid. The use of the new antiepileptics should be given careful consideration, not least on account of their high price. Switch-over from a proprietary to a generic drug may be associated with the problem of differences in bioavailability. Routine monitoring of serum levels is not useful, but is always necessary when a seizure occurs unexpectedly. On account of their disease, many people with epilepsy are discriminated against. Questions regarding the advisability of having children or driving a car, should, however, not automatically elicit a negative response.

Anticonvulsants↗

Cryopreservation of adult human hepatocytes obtained from resected liver biopsies.

Isolated human hepatocytes have been shown to represent a valuable in vitro model to investigate the metabolism and cytotoxicity of xenobiotics. In addition, human hepatocyte transplantation and artificial liver support systems using isolated human hepatocytes are currently investigated as treatment for acute and chronic hepatic failure. In this regard, human hepatocyte banking by cryopreservation would be of great interest. In the present study, freshly isolated hepatocytes from resected liver biopsies of 28 separate donors (viability: 88 +/- 2%; plating efficiency: 79 +/- 5%) were cryopreserved using two different protocols, stepwise freezing (SF) or progressive freezing (PF), in combination (PF(+), SF(+)) or not (PF(-), SF(-)) with a 30 min preincubation in culture medium at 37 degrees C. Total recovery was higher after PF (38 +/- 3%) than after SF (12 +/- 2%). Preincubation prior to SF had no effect on plating efficiency of thawed hepatocytes (SF(-): 38 +/- 6% versus SF(+): 46 +/- 7%) while preincubation prior to PF increased plating efficiency of thawed hepatocytes (PF(-): 42 +/- 6% versus PF(+): 64 +/- 4%, p < 0.05). In attached cultured human cryopreserved/thawed hepatocytes (CH) from the PF(+) group, albumin production and glutathione content were not significantly different from those of the freshly isolated hepatocyte (FIH) cultures. Cells in CH monolayers appeared smaller than cells in FIH monolayers. In addition, the pattern of cytochrome P450- and UDP-glucuronosyl transferase-dependent isoenzyme activities and GST activity were different, suggesting a variability in the resistance to cryopreservation of the various liver hepatocyte populations. Taken all together, the results of the present study suggest that recovery of human hepatocytes after isolation prior to progressive freezing should allow human hepatocyte banking for use in pharmacotoxicology and cell therapy research purposes.

Adult↗

[Physical activity after shoulder arthroplasty].

A hemi- or total shoulder arthroplasty was performed in 171 patients between 1992 and 1997. We examined 118 patients under the age of 70 regarding their level of physical activity. For a pre- and postoperative comparison we divided the patients in two groups. Group one included all patients with osteoarthritis, rheumatoid arthritis, instability associated arthritis, avascular necrosis and other arthropathies. Group two included acute fractures and fracture sequelae. The postoperative outcome was functionally assessed by using the Constant score. There was an average Constant score of 60,9 for group one and 67,1 for group two. Both groups showed a domination of activities with motion patterns unspecific for the shoulder. There were more patients in group two reporting activities which depend on a good or very good shoulder function. There is no general estimation for the ability to be active in sports after shoulder arthroplasty. An individual assessment of the shoulder function is essential. Important criterias beside motivation and age are the status of the rotator cuff and the soft tissue balancing. The correct indication for shoulder arthroplasty as well as the preoperative planning and the postoperative rehabilitation program are essential for a good functional outcome and the key for physical activity after shoulder arthroplasty.

Adult↗

O(6)-Methylguanine-DNA methyltransferase promoter hypermethylation shifts the p53 mutational spectrum in non-small cell lung cancer.

The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) removes mutagenic adducts from the O6 position of guanine, thereby protecting the genome against G to A transition mutations. MGMT is inactivated by promoter hypermethylation in many human cancers and has been associated with G to A mutations in K-ras in colorectal cancer. We hypothesized that MGMT promoter hypermethylation would be associated with an increase in G to A transitions in the p53 gene in non-small cell lung cancer (NSCLC). p53 mutations were detected by both dideoxy sequencing and p53 GeneChip analysis in 92 patients with primary NSCLC. Methylation of the promoter region of the MGMT gene was determined using methylation-specific PCR and was present in 27 of 92 (29%) tumors. Hypermethylation of the MGMT promoter was more common in adenocarcinoma than in other histological types of NSCLC and was also more common in poorly differentiated tumors. MGMT promoter hypermethylation was present significantly more often in tumors with a G to A mutation in p53 (9 of 14; 64%) than in tumors with other types of p53 mutations (11 of 41; 27%; P = 0.02) or in tumors with wild-type p53 (7 of 37; 18%; P = 0.006). MGMT promoter hypermethylation was also strongly associated with G to A transitions at CpG sites. Inactivation of the MGMT gene by promoter hypermethylation alters the pattern of p53 mutation in NSCLC.

Carcinoma, Non-Small-Cell Lung↗

Spreading depression in human neocortical slices.

Cortical spreading depression (CSD) occurrence has been suggested to be associated with seizures, migraine aura, head injury and brain ischemia-infarction. Only few studies identified CSD in human neocortical slices and no comprehensive study so far evaluated this phenomenon in human. Using the neocortical tissue excised for treatment of intractable epilepsy, we aimed to investigate CSD in human. CSD was induced by KCl injection and by modulating T-type Ca(2+) currents in incubated human neocortical tissues in an interphase mode. The DC-fluctuations were recorded by inserting microelectrodes into different cortical layers. Local injection of KCl triggered single CSD that propagated at 3.1+/-0.1 mm/min. Repetitive CSD also occurred spontaneously during long lasting application (5 h) of the T-type Ca(2+) channel blockers amiloride (50 microM) or NiCl(2) (10 microM) which was concomitant with a reversible extracellular potassium increase up to 50 mM. CSD could be blocked by the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovaleric acid in all cases. The results demonstrate that modulation of the Ca(2+) dynamics conditioned human neocortical slices and increased their susceptibility to generate CSD. Furthermore, these data indicate that glutamatergic pathway plays a role in CSD phenomenon in human.

Adolescent↗

Comparative evaluation of Celsior solution versus Viaspan in a pig liver transplantation model.

BACKGROUND: In a pig liver transplantation model, we compared the effects of Celsior solution (CS), an extracellular preservation solution, with Viaspan (University of Wisconsin solution, UW) on graft function and animal survival. METHODS: Pig livers were flushed with either CS or UW solution and cold-stored for 12 hr (group 1) or for 8 to 10 hr (group 2). Grafts were transplanted orthotopically. Intrahepatic reduced and oxidized glutathione and adenine nucleotides were evaluated 1 hr after reperfusion. Liver function of transplanted animals was monitored for up to 6 days by serum transaminases, total bilirubin, purine nucleoside phosphorylase, and prothrombin levels. RESULTS: In group 1, all animals died within 24 hr after reperfusion regardless of the preservation solution used. In group 2, no significant difference was seen in survival between the CS (72%) and the UW (67%) groups 6 days after transplantation, and there were no statistically significant differences in the biochemical data. There were no differences in histological evaluation of the livers at the time of death or killing of the animals between the CS and UW groups. CONCLUSION: Within the limits of this pilot study, CS is equivalent to UW in terms of graft function and animal survival.

Adenosine↗

Effect of topically applied T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum: a randomised study. Xeroderma Pigmentosum Study Group.

BACKGROUND: In patients with xeroderma pigmentosum the frequency of all forms of skin cancer is higher than in the general population, owing to a genetic defect in DNA repair. The bacterial DNA repair enzyme, T4 endonuclease V, delivered intracellularly, increases the rate of repair of sunlight-induced DNA damage in human cells. We tested the ability of this enzyme in a liposomal delivery vehicle applied topically (T4N5 liposome lotion) to lower the rate of new skin cancers in patients with xeroderma pigmentosum. METHODS: 30 patients were enrolled in this prospective, multicentre, double-blind study. Patients were randomly assigned T4N5 liposome lotion or a placebo liposome lotion, to be applied daily for 1 year. At 3-monthly visits, new actinic keratoses and basal-cell carcinomas were identified and removed. Analyses were by intention to treat. FINDINGS: 20 patients were assigned T4N5 liposome lotion and ten placebo lotion; one placebo-group patient withdrew before treatment and one withdrew with progressive disease at 9 months. The annualised rate of new actinic keratoses was 8.2 among the patients assigned T4N5 liposome lotion and 25.9 among those assigned placebo (difference 17.7 [95% CI 11.8-26.5]; p=0.004 by Poisson modelling). For basal-cell carcinoma, the annualised rates of new lesions were 3.8 in the treatment group and 5.4 in the placebo group (difference 1.6 [0.38-2.82]). No significant adverse effects were found among any of the patients. INTERPRETATION: DNA damage has an important role in the development of skin cancer and precancerous skin lesions. The topical application of DNA repair enzymes to sun-damaged skin of patients with xeroderma pigmentosum lowered the rate of development of two forms of these lesions during a year of treatment.

Administration, Topical↗

Syngeneic consecutive rat spleen transplantation bearing infantile testis.

Seventy-seven Lewis adult rats received autologous testicular implants in the spleen. These spleens were retransplanted in a consecutive transplant fashion as we described earlier. Some were observed as long as 26 to 27 months. Although earlier splenic-testicular transplants showed benign granulosa cell tumors, some of the long-term follow-ups showed a seminoma-like transformation.

Animals↗

Hepatic metastases of gastroenteropancreatic neuroendocrine tumors: safe hepatic surgery.

Liver metastases of neuroendocrine tumors are usually slow-growing, and cytoreductive hepatectomy can help reduce the effects of endocrinopathies and increase life expectancy and symptom-free survival. However, it has yet to be fully investigated how hepatectomy for metastatic neuroendocrine tumors can be performed safely. Here we report the results of 13 patients with neuroendocrine liver metastases operated on in our institution and those of a French multicentric study that included 131 patients. Preoperative patient selection and appropriate surgical technique, sometimes combined with preoperative portal embolization and local tumor destruction (radiofrequency and cryotherapy), may increase the resectability and the safety of the procedure. The mortality rate after hepatectomy was 0% (2.3% in the French study); the 3- and 6-year survival rates were 91% and 68%, respectively, in our institution (the mean survival time was 66 months in the French multicentric survey). Significant prolonged survival with complete palliation of symptoms can be obtained after liver metastases resection with low mortality.

Adult↗

Surgical repair after bile duct and vascular injuries during laparoscopic cholecystectomy: when and how?

Recent collective reviews have outlined when and how surgeons should treat patients with bile duct injuries after laparoscopic cholecystectomy (LC). However, little is described about other injuries combined with bile duct injuries, for example, hepatic arterial injury and secondary biliary cirrhosis. Fifteen patients with bile duct injuries following LC were referred and surgically treated from 1990 to 1998 in our institution. We report how patients with hepatic arterial injury combined with bile duct injuries during LC were treated. The present study also reports unusual complicated situations: one patient with biliary cirrhosis referred 4 years after LC, another treated with internal biliary metallic stent referred 2.5 years after LC, and another with isolated right hepatic ductal injury. Short- and long-term surgical outcomes after biliary repair were compared between simply referred patients and those with complicated history. Patients who were referred several years after LC and who were referred after primary hepaticojejunostomy were included with patients with complicated history (n = 4, group B), and the other patients were included with patients with simple history (n = 11, group A). Simultaneous right hepatic arterial occlusion was observed in 3 of these 15 patients, and arterial reconstruction was performed in 2 of the 3 patients in addition to biliary reconstruction. No postoperative complication occurred in these three patients. The patient with isolated injury of the right hepatic duct and the other with biliary cirrhosis were successfully treated with hepaticojejunostomy. The other patient treated with biliary stent underwent hepaticojejunostomy but a second operation was required because of later stenosis. Mean hospital stay was significantly longer in group B (30.3 +/- 6.9 days) than in group A (18.5 +/- 2.5 days, p< 0.05). Rehospitalization was more frequent in group B than in group A (p < 0.01). However, long-term outcome was successful in both groups. The present results showed that arterial reconstruction should be performed when the distal right hepatic artery can be exposed and reconstructed, and suggested that patients with bile duct injuries during LC should be immediately referred to surgical institutions in which surgeons have adequate experience of bile duct repair and hepatic arterial reconstruction.

Adult↗

Is a proliferation index of cancer cells a reliable prognostic factor after hepatectomy in patients with colorectal liver metastases?

BACKGROUND: In spite of many reports focusing on prognostic factors after hepatectomy in patients with colorectal liver metastases, few studies have investigated pathological factors, eg, fibrous pseudocapsulation, growth pattern at the tumor margin, and proliferation activity of cancer cells, other than histological type and surgical margin. The aim of the present study was to investigate whether absence of pseudocapsulation, infiltrative growth pattern of metastases, and higher proliferation of cancer cells shown by Ki-67 immunohistochemical reactivity were associated with poorer survival after hepatectomy among patients with colorectal liver metastases. METHODS: Between 1988 and 1998, 221 patients underwent hepatic resection of colorectal metastases with curative intent in our institution. Pathology analyses were focused on pseudocapsulation of liver metastases, growth pattern at the tumor edge, and Ki-67 labelling index (Ki-67 LI) of cancer cell nuclei. Univariate analyses of survival and of disease-free survival were performed for several clinicopathological factors, and multivariate analyses of survival and disease-free survival were also performed. RESULTS: The univariate survival analyses showed that pseudocapsulation, growth pattern, and Ki-67 LI were significant prognostic factors, besides synchronous versus metachronous occurrence of metastases, carcinoembryonic antigen level before hepatectomy, and number of metastases. A multivariate analysis showed that Ki-67 labeling index was the most reliable prognostic factor of survival. In addition, Ki-67 LI and microscopic growth pattern were multivariately predictive factors of disease-free survival. CONCLUSIONS: This large single-institution study showed that investigation of cancer cell proliferation and pathologic characteristics of the tumor margin are major prognostic factors.

Analysis of Variance↗

Role of anti-Gal alpha13Gal and anti-platelet antibodies in hyperacute rejection of pig lung by human blood.

BACKGROUND: Previous work has shown that antibodies against porcine antigens are an important trigger of hyperacute lung rejection (HALR). The relative importance of Gal alpha1,3Gal epitopes and other antigens, such as those expressed on pig platelet membranes or lung itself, has not been defined. This study compares the efficiency of three anti-pig antibody depletion strategies, and their efficacy with regard to attenuation of HALR. METHODS: Plasma pooled from three human donors was adsorbed against Gal alpha1,3Gal disaccharide or porcine platelet extract (PPE), or passed through pig lung vasculature. Whole blood reconstituted using adsorbed plasma was then used to perfuse piglet lung, and results were compared with unmodified human blood. RESULTS: Depletion of lung-reactive anti-Gal alpha1-3Gal antibodies was most efficient with the alphaGal column (99% +/- 0.5% vs 87% to 93% +/- 11% for PPE and 92% to 95% +/- 8% for lung, p < 0.01 vs alphaGal column). PPE column tended to be more efficient (77% to 84% +/- 12%) in removing anti-PPE antibodies than pig lung (66% to 70% +/- 14%) or the alphaGal column (56% to 63% +/- 16%, p < 0.05). Lung survival and function with each antibody depletion strategy was improved relative to unmodified controls (mean survival > or = 146 minutes vs 8 minutes for controls). Although alphaGal and lung adsorption yielded more consistent lung protection (survival beyond 2 hours) than did PPE, no approach proved significantly superior. Complement C3a elaboration at 10 minutes was attenuated > 80% by each adsorption strategy, an effect that was most pronounced in the lung adsorption group (95%, p < 0.01). Histamine elaboration was blunted significantly by PPE adsorption but not in other groups (p < 0.05). Platelet but not leukocyte sequestration was decreased with antibody depletion compared with the nondepleted group (44% to 50% vs 82%, p < 0.01). CONCLUSIONS: Each antibody depletion strategy tested significantly prolongs lung xenograft survival and function compared with unmodified human blood, but none was sufficient to reliably prevent HALR. Depletion of antibodies against both alphaGal and additional cell membrane antigens, or control of antibody-independent pathogenic pathways, may be necessary to consistently prevent HALR.

Acute Disease↗

[Liver transplantation in a patient with hemophilia A and end stage liver failure].

We report the case of a 50 year-old man factor VIII deficient haemophiliac and hepatitis C cirrhosis. The patient underwent orthotopic liver transplantation because of episodes of variceal bleeding and encephalopathy. He received factor VIII replacement therapy perioperatively. Factor VIII returned to normal within 24 hours postoperatively and factor VIII replacement was stopped. Liver transplantation can be considered as definitive therapy for haemophilia.

Hemophilia A↗