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Biomedical subjects

W Wolf

Publications and source records attributed to W Wolf.

At least 37 records · Page 2Linked to original sources
PubMed2000

Enhancement of 5-fluorouracil anabolism by methotrexate and trimetrexate in two rat solid tumor models, Walker 256 carcinosarcoma and Novikoff hepatoma, as evaluated by 19F-magnetic resonance spectroscopy.

Although 5-fluorouracil (5-FU) is one of the most effective single agents in treating solid tumors, its low effectiveness as a single agent has led to development of a number of modulators intended to enhance its therapeutic effectiveness. Of these, methotrexate (MTX) and trimetrexate (TMTX) have been shown to have synergistic anticancer activity with 5-FU. The effect of these two drugs on the uptake and the intratumoral metabolism of 5-FU was studied in two rat tumor models using 19F-nuclear magnetic resonance spectroscopy: on excised samples of Walker 256 carcinosarcoma and noninvasively (in vivo) in Novikoff hepatoma. In the rats bearing the Walker 256 tumor, a 4-hr pretreatment with MTX showed the maximal increase in the rate of conversion from 5-FU to its fluorinated nucleotides/nucleosides. In the rats bearing the Novikoff hepatoma, both modulators increased the amounts of cyctotoxic anabolites of 5-FU, but at the doses administered, the cumulative amounts of 5-FU anabolites formed after MTX were significantly higher than those formed after TMTX or after saline control. On the other hand, the increase in the levels of the fluorinated nucleotides/nucleosides after TMTX peaked at a later time. The possible significance of these findings is that timing of administration of a modulator is important because it affects both transport and metabolism of 5-FU. The two modulators studied, both antifolates, act differently on transport and on metabolism: MTX affects both, whereas TMTX, at the level studied, appears to affect predominantly the metabolic process. In addition, significant differences exist between tumor models. These data suggest possible mechanisms and processes that should be studied further in humans, using these noninvasive pharmacokinetic imaging methods for monitoring 5-FU targeting and metabolism.

Animals↗
PubMed1999

Chronic poisoning by copper in tap water: I. Copper intoxications with predominantly gastointestinal symptoms.

Copper can induce acute and chronic intoxications in humans. Copper in tap water has caused a series of severe systemic diseases in Germany in recent years (copper induced liver cirrhosis). Besides cirrhosis, another type of disease with predominantly gastrointestinal symptoms has occurred which likewise appeared to be induced by copper in tap water. - In a retrospective investigation we looked for additional indications and proof that chronic copper poisoning has been the cause of the observed gastrointestinal diseases. All patients suffering from this type of disease had copper plumbing in their houses. - The patients (children and adults) suffered from nausea, vomiting, colic, and diarrhoea. In the group of infants, one refused formula milk (prepared with tap water) and the others suffered from persistent restlessness, unexplainable screaming (especially at night) and/or long lasting diaper rash. - We accept the diagnosis of chronic copper intoxication as the cause of the gastrointestinal symptoms when at least one of the following criteria were fulfilled: 1. first manifestation, remission and relapse of the disease depend on intake and a non-intake of water containing copper, respectively. 2. hypercupric state of the patients (i.e. pathological high concentrations of the non-ceruloplasmin-bound copper in serum and/or elevated copper levels in urine) 3. signs of systemic copper intoxication in the same patient 4. signs of systemic copper intoxication or hypercupric states in members of the patient s family or in his neighbourhood (non-relatives) - We found that the disease can even be caused by copper concentrations below the allowed concentration given by the German Guidelines for Drinking Water (Trinkwasserverordnung). - The data prove that copper in drinking water can cause gastrointestinal diseases and not only the better known systemic diseases (i.e. copper induced liver cirrhosis). Copper poisoning must be considered as a possible cause of chronic gastrointestinal diseases in those countries in which copper plumbing is common.

Adolescent↗
PubMed1999

Chronic poisoning by copper in tap water: II. Copper intoxications with predominantly systemic symptoms.

Copper can induce acute and chronic intoxications in humans. Copper in tap water has caused a series of severe systemic diseases in Germany in recent years (chronic copper poisoning, CCuP). From the clinical point of view it has been difficult to establish the diagnosis on the basis of clinical and laboratory methods. In a retrospective study, we therefore looked for essential clinical signs as well as laboratory findings which might be typical and essential for the diagnosis of CCuP. - We observed that in patients with severe systemic CCuP not only the liver but also several other organs have been the target of copper. As a proof copper overload has been measured. The latter results are presented here. - During or shortly after exposure "free" serum copper (= non-ceruloplasmin-bound copper) was significantly elevated in all patients (range 5.1 to 47.1 micromol/l, or 25.7 to 56.2 % of total serum copper). The normal upper limits in infants according to Salmenperä (8) are: 0.3 micromol/l, or 1.6 % of total serum copper. - Total serum copper was elevated in 14/16 patients: 13.7 to 30.1 micromol/l in sick infants (normal upper level: 12.6 micromol/l), and 17.0 to 27.2 in sick children (normal upper level for children and adults: 21.4 micromol/l). - Urine copper excretion was found elevated in 9/10 patients, with a range of 11 to 456 microg/dl (normal upper level in adults: 15 microg/dl). - Our results show that patients with systemic CCuP are in a "hypercupric" state. The data thus firstly prove that indeed the putative agent copper is found in excess in the patients and secondly show that the estimation of "free" copper in serum and the measurement of copper in urine are reliable diagnostic methods. Elevation of total serum copper (even though not specific) can give a first hint to the diagnosis. - The hypercupric state of systemic CCuP can be differentiated from that of Wilson's disease by (1) normal levels of ceruloplasmin and (2) the observation that values for free copper in serum or urinary copper normalize in an environment without copper in tap water, for instance in a hospital.

Adult↗
PubMed1999

Nonsurgical reconstruction of thoracic aortic dissection by stent-graft placement.

BACKGROUND: The treatment of thoracic aortic dissection is guided by prognostic and anatomical information. Proximal dissection requires surgery, but the appropriate treatment of distal thoracic aortic dissection has not been determined, because surgery has failed to improve the prognosis. METHODS: We prospectively evaluated the safety and efficacy of elective transluminal endovascular stent-graft insertion in 12 consecutive patients with descending (type B) aortic dissection and compared the results with surgery in 12 matched controls. In all 24 patients, aortic dissection was diagnosed by magnetic resonance angiography. In each group, the dissection involved the aortic arch in 3 patients and the descending thoracic aorta in all 12 patients. With the patient under general anesthesia, either surgical resection was undertaken or a custom-designed endovascular stent-graft was placed by unilateral arteriotomy. RESULTS: Stent-graft placement resulted in no morbidity or mortality, whereas surgery for type B dissection was associated with four deaths (33 percent, P=0.09) and five serious adverse events (42 percent, P=0.04) within 12 months. Transluminal placement of the stent-graft prosthesis was successful in all patients, with no leakage; full expansion of the stents was ensured by balloon inflation at 2 to 3 atm. Sealing of the entry tear was monitored during the procedure by transesophageal ultrasonography and angiography, and thrombosis of the false lumen was confirmed in all 12 patients after a mean of three months by magnetic resonance imaging. There were no deaths or instances of paraplegia, stroke, embolization, side-branch occlusion, or infection in the stent-graft group; nine patients had postimplantation syndrome, with transient elevation of C-reactive protein levels and body temperature plus mild leukocytosis. All the patients who received stent-grafts recovered, as did seven patients who underwent surgery for type B dissection (58 percent) (P=0.04). CONCLUSIONS: These preliminary observations suggest that elective, nonsurgical insertion of an endovascular stent-graft is safe and efficacious in selected patients who have thoracic aortic dissection and for whom surgery is indicated. Endoluminal repair may be useful for interventional reconstruction of thoracic aortic dissection.

Adult↗
PubMed1999

Modulation of motor evoked potentials by muscle vibration: the role of vibration frequency.

Augmentation of motor evoked potentials (MEPs) by muscle vibration (MV) was studied in 10 healthy subjects with regard to the vibration frequency (VF). The extensor carpi radialis muscle (ECR) was vibrated using VFs of 80, 120, and 160 Hz. Motor evoked potentials following transcranial magnetic stimulation were recorded simultaneously from the vibrated ECR and the antagonist flexor carpi radialis muscle (FCR) without MV, 0.5 s and 3 s after onset of MV and 1 s after offset. Only the VFs of 80 Hz and 120 Hz caused MEP augmentation and latency shortening in ECR, whereas depression of MEPs in FCR was induced by all VFs used. It appears that MEP augmentation and latency shortening in ECR are mediated by the primary muscle spindle endings which respond with optimal discharge rates to VFs of up to 100 Hz. Motor evoked potential depression in FCR, being well expressed also with VF 160 Hz, seems to involve other dynamic mechanoreceptors.

Adult↗
PubMed1999

Voluntary motor reactions: does stimulus appearance prolong the actual tremor period?

Entrainment of voluntary motor responses by ongoing tremors demonstrates the interaction of motor actions simultaneously performed by the same muscle. In the case of physiological tremor, based on experimental data, Kogan (Determining the influence of a bright stimulus on the ultramicrostructure of the movement control process in highly qualified wrestlers, Tesisi 7, Nautschnometoditscheskoi konferenzii respublik Pribaltiki i Belorussi po woprosam sportivnoi trenirovki, Riga, 1978:56-57) postulated a direct and immediate impact of a 'go' stimulus on the actual tremor cycle. This paper represents a critical replication of this investigation, showing that the effect reported can be simply explained as an inherent statistical consequence of the experimental paradigm.

Adult↗
PubMed1998

Non-invasive 19F-NMRS of 5-fluorouracil in pharmacokinetics and pharmacodynamic studies.

Knowledge of the exact dose and rate at which an antitumor agent is delivered to its target site is postulated to be crucial to proper patient management. It is now possible to obtain such information using non-invasive 19F-NMRS (nuclear magnetic resonance spectroscopy) following the administration of 5-fluorouracil (5-FU). We have performed such studies in 103 patients with breast, colorectal and other tumors. Measurable 19F signals were detected in 99 of these patients (92.5%). Estimation of the tumoral t1/2 of 5-FU in these patients revealed that 51 of them (51.5%) exhibited a tumoral t1/2 greater than 20 min, a value we had characterized as indicating drug trapping in the tumor. Of these patients, 46 who received regimen bolus 5-FU 600 mg/m2 with leucovorin for their treatment have been evaluated. In these patients, the association between trapping and response remains very high (p<.000001). None of the non-trappers responded to chemotherapy, whereas 70% of the evaluable trappers responded. Details are presented here on the methodology of NMRS data acquisition and on their pharmacokinetic analysis. The potential mechanisms underlying the trapping effect appear to be predicated primarily on transport processes. Suggestions are presented on how such pharmacokinetic imaging studies may extend both our understanding of the mechanism of action of 5-FU, and how they could be used to optimize patient treatment.

Antimetabolites, Antineoplastic↗
PubMed1997

[Femoral arteriovenous fistula and transplant malfunction after allogeneic kidney transplantation. A case report].

This case report deals with the clinical history of a 52-year-old woman who suffered from delayed graft function and ischaemic pain after a technically successful renal transplantation. The past history of the patient revealed that coronary catheters had repeatedly been used for investigation and treatment of myocardial infarctions. The clinical investigation reported here revealed a typical auscultatory result with an arteriovenous (AV) fistula in the right upper limb. After performing a digital arterial angiography, an AV fistula between the femoral artery and vein was demonstrated. Operative occlusion of the fistula increased the perfusion of the kidney graft and the right limb. The patient recovered without wound infection and could leave the hospital with the transplanted kidney functioning well. This case report demonstrates that persistence of AV fistulas after angiographic investigations is rare. Operative occlusion of these lesions should be performed before kidney transplantation to avoid steal phenomena and disturbed would healing.

Angiography, Digital Subtraction↗
PubMed1997

The effects of anesthesia on the biodistribution of drugs in rats: a carboplatin study.

PURPOSE: Anesthetics can alter the biodistribution profile of drugs and, consequently, the regional pharmacokinetics of antineoplastic drugs at the tumor site. The effect of coadministered anesthetics on the biodistribution profile of carboplatin was studied in rats. METHODS: Female Wistar rats were used to compare the effects of ketamine/xylazine, thiopental and pentobarbital on the biodistribution of 30 mg/kg radiolabelled 195mPt-carboplatin administered intravenously, with conscious rats as the control group. Blood and urine samples were collected between 5 and 120 min. RESULTS: The percentage values of the injected dose of platinum per ml (%ID/ml) in plasma at the final time-point were respectively, 0.557%, 0.156%, 0.115% and 0.086%, in pentobarbital-, ketamine/xylazine- and thiopental-injected rats, and in conscious animals. Following the same sequence of groups, the %ID/ml values of platinum in the cumulative urine were 0.001%, 0.619%, 0.184% and 0.118%, respectively. Urine output varied from very little in the pentobarbital group, to several milliliters in the other groups. CONCLUSIONS: There was an increase of almost 100-fold in total platinum uptake in the kidneys, cerebrum and cerebellum of rats receiving pentobarbital over the uptake in the control rats, whereas the biodistribution profile of the thiopental group had the least variance. These results demonstrate the importance of anesthetic selection in animal pharmacokinetic studies, as it influences the biodistribution and pharmacokinetic profile of the drug being studied.

Anesthetics↗
PubMed1997

P31 phosphor persistence at photopic mean luminance level.

P31 phosphor screens are frequently used for short-term presentation of dot and grating patterns, but experimental data obtained with this technique have been criticized because of possible parasitic effects of phosphor persistence on subjects visual performance. Recently, this issue provoked a controversial discussion in Vision Research (Groner et al., 1993; Westheimer, 1993, 1994; Irwin, 1994; Di Lollo et al., 1994) which was concerned with persistence effects of P31 screens for dot patterns. Supplementing this discussion, the present work deals with the effects of different types of patterns (dot pattern vs. gratings) and background mean-luminance levels (scotopic vs. phototopic) on phosphor persistence. Physical measurements of P31 persistence occurring with grating patterns of a mean luminance of 20 cd m-2 (i.e. photopic range) were obtained by using an extremely linear photometer with high temporal resolution. Under this photopic condition, the measurements demonstrate a fast decay of residual grating contrast to 1.4% of its original value within 50 ms after pattern offset. This phosphor behavior must be considered when designing an experiment with a P31 screen though it certainly embodies no problems in many applications.

Computer Terminals↗