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Biomedical subjects

S Hofer

Publications and source records attributed to S Hofer.

At least 19 recordsLinked to original sources
PubMed2000

High prevalence of Echinococcus multilocularis in urban red foxes (Vulpes vulpes) and voles (Arvicola terrestris) in the city of Zürich, Switzerland.

Over a period of 26 months from January 1996 to February 1998, 388 foxes from the city of Zürich, Switzerland, were examined for intestinal infections with Echinococcus multilocularis and other helminths. The prevalence of E. multilocularis in foxes sampled during winter increased significantly from 47% in the urban to 67% in the adjacent recreational area, whereas prevalence rates of other helminths were similar in both areas. Seasonal differences in the prevalence of E. multilocularis were only found in urban subadult male foxes which were significantly less frequently infected in summer than in winter. The distribution of the Echinococcus biomass, as expressed by worm numbers per fox was overdispersed in 133 infected foxes randomly sampled in winter. Ten of these foxes (8%) were infected with more than 10,000 specimens and carried 72% of the total biomass of E. multilocularis (398,653 worms). Prevalences did not differ significantly in these foxes in regard to age and sex but worm burdens were significantly higher in subadult foxes as compared with adult foxes. In voles (Arvicola terrestris) trapped in a city park of Zürich, E. multilocularis metacestodes were identified by morphological examination and by PCR. The prevalence was 20% among 60 rodents in 1997 and 9% among 75 rodents in 1998. Protoscoleces occurred in 2 of the cases from 1997. The possible risk for human infection is discussed with respect to the established urban E. multilocularis cycle.

Animals↗
PubMed2000

Treatment of solid tumors following allogeneic bone marrow transplantation.

Second solid tumors are well known late complications after bone marrow transplantation. Treatment strategies are ill defined. We retrospectively evaluated treatment and outcome in a single institution. From August 1974 to July 1996, six solid tumors were observed in five of 387 patients 2 to 13 years after BMT, corresponding to a probability of developing a second solid tumor of 9% (1-17%, 95 CI) at 15 years: these comprised endometrial carcinoma, carcinoma of the thyroid gland, cervical carcinoma, sarcoma of the small intestine, osteosarcoma of the tibia and ovarian carcinoma. All five patients were treated as intensively as they would be without a history of BMT. At last follow-up four of the five patients were alive and without signs of tumor. We postulate that second solid tumors after BMT should be treated as de novo tumors. Early detection based on consequent clinical follow-up of the transplant patients might explain the relatively good outcome.

Adenocarcinoma↗
PubMed1999

[New aspects of interdisciplinary therapy for malignant gliomas in adults].

Malignant gliomas are the most frequent primary brain tumours in adults. Their histopathological grade (WHO) and histological subtype (astrocytoma, oligodendroglioma, mixed tumour) is associated with biological behaviour and clinical outcome. Throughout the course of glioma an interdisciplinary approach is mandatory. Surgery and radiation therapy are standard procedures. Oligodendroglial tumours are chemosensitive and molecular biological markers can predict this sensitivity. Prediction of chemosensitivity in astrocytic tumors is not available yet. We propose a multimodal therapeutic approach and refer to ongoing clinical trials.

Adult↗
PubMed1999

M1204, a novel 2',5' oligoadenylate synthetase with a ubiquitin-like extension, is induced during maturation of murine dendritic cells.

A novel molecule expressed by spleen dendritic cells (DC) was isolated using a subtractive hybridization approach. The full-length M1204 clone has 3063 bp, with 1415 bp spanning a single open reading frame, coding for a protein of a predicted size of about 50 kDa. This sequence has strong homology to 2', 5' oligoadenylate synthetase and contains a ubiquitin-like domain. In Northern blot analyses the mRNA is strongly expressed in spleen DC, whereas, in bone marrow-derived DC, the amount of mRNA increases during the maturation process. None of the other leukocytes nor several hemopoietic cell lines tested express this mRNA, but clear expression occurs in many organs, the highest levels being in thymus, lung, and bone marrow. In situ hybridization, combined with immunocytochemical staining of tissue sections of lung and spleen, shows colocalization of M1204 with the 2A1 and NLDC DC markers. In Western blot experiments, an antiserum raised against the recombinant M1204 recognizes a single band in bone marrow-derived DC and in the lung. The expressed oligoadenylate synthetase domain is active in synthesizing 2',5' diadenylate, which by itself may inhibit viral protein synthesis and may also function as a substrate for 2',5' oligoadenylate synthetase. Since the oligoadenylate/RNase L system provides early protection against virus infection, we hypothesize that M1204 prevents virus-induced cell death in DC.

2',5'-Oligoadenylate Synthetase↗
PubMed1998

[ 40 years of 5-fluorouracil--still an attractive cytostatic].

On its 40th birthday 5-fluorouracil (FU) is still an attractive drug frequently employed in adjuvant and palliative treatment of colorectal and breast cancer, head and neck cancer, oesophageal cancer and anal cancer. After all this time it is still not known what the optimal schedule or the best form of administration is, and whether or not modulation of the drug is of any benefit. This article deals with the drug's different modes of action depending on the schedule of administration. An overview of the literature on drug modulation is given. We introduce the less well-known side effects of the drug and the newly developed orally administered prodrugs of FU.

Antimetabolites, Antineoplastic↗
PubMed1998

Characterization of the human gene coding for the swelling-dependent chloride channel ICln at position 11q13.5-14.1 (CLNS1A) and further characterization of the chromosome 6 (CLNS1B) localization.

Expression cloning revealed a chloride channel (ICln) that we found to be fundamental for the regulatory volume decrease in a variety of cells. The chromosomal localization of the human ICln-gene showed two loci, one at chromosome 11 in position q13.5-q14.1, termed CLNS1A, and a second one at chromosome 6 at position p12.1-q13, termed CLNS1B. In this study, we offer a detailed characterization of the CLNS1A gene and provide the exact position (6p12) and sequence data of CLNS1B, an intronless gene 91.3% homologous to the coding region of CLNS1A.

Amino Acid Sequence↗
PubMed1998

Dexamethasone treatment and plasma glucose levels: relevance for fluorine-18-fluorodeoxyglucose uptake measurements in gliomas.

UNLABELLED: Dexamethasone (DEX) is frequently used in brain tumor management. This study investigated the effect of DEX treatment and plasma glucose levels on 18F-fluorodeoxyglucose (FDG) uptake in patients with malignant gliomas (16 glioblastoma, 3 anaplastic astrocytoma). METHODS: Fifteen DEX-treated patients (mean relative dose 0.23 +/- 0.15 mg(-1) x kg(-1) x day(-1), range 0.07-0.53), four patients not treated with DEX and nine healthy subjects were studied using PET and FDG. PET data obtained from tumors and the contralateral cortex were fitted to a standard two-tissue compartment model. The FDG transport and phosphorylation rates, distribution volume (DV), steady-state accumulation (Ki), deoxyglucose metabolism (R), plasma volume as well as standardized uptake values (SUVs) and tumor-to-brain ratios were determined. In addition, the tumor size was estimated from the maximal area of contrast-enhancing tumor on computed cranial tomography (CCT) scans or MRI. RESULTS: FDG uptake was depressed in the contralateral cortex of patients and was related to tumor size. With increasing relative DEX dose, a decrease in the DV of tumors (linear regression p = 0.021) and in the DV (p = 0.109) and plasma volume (p = 0.010) of contralateral cortex was found. R, Ki and SUVs in tumors and contralateral cortex were not related to the relative DEX dose. With increasing plasma glucose levels, differential decreases in Ki and SUVs in tumors (p = 0.057 and p = 0.733, respectively) and contralateral cortex (p = 0.001 and p = 0.029, respectively) were observed. CONCLUSION: The data suggest that DEX affects FDG uptake in malignant gliomas through interaction with cerebral blood vessels and extracellular space, whereas FDG metabolism in tumors is not influenced substantially. This is of practical importance for patients having serial brain tumor imaging for treatment evaluation because patients may receive different DEX doses at different time points in the course of their disease. By contrast, the plasma glucose level must be considered a confounding variable when SUVs, tumor-to-brain ratios or Ki are used for treatment evaluation.

Antineoplastic Agents, Hormonal↗
PubMed1997

[The "pinch off" syndrome: a complication of implantable catheter systems in the subclavian vein].

We report the case of a 63-year-old male patient who received a subcutaneous Port-a-cath system in the right subclavian vein for administration of chemotherapy. Five weeks after successful use, flushing with NaCl 0.9% caused a painless subcutaneous swelling. Fluoroscopy confirmed a leakage below the right clavicle. The catheter was explanted and replaced by a new catheter via Seldinger technique. Two weeks later another leakage occurred and the catheter was removed definitively. Defective equipment was ruled out by the catheter producing company. The "pinch off" syndrome, a rare phenomenon of catheter compression and consecutive catheter fracture, is described, together with the diagnostic signs, the incidence and preventive measures suggested in the literature.

Antineoplastic Agents↗
PubMed1997

Resistance to the new anti-cancer phospholipid ilmofosine (BM 41 440).

The thioether phospholipid ilmofosine (BM 41 440) is a new anti-cancer drug presently undergoing phase II clinical trials. Because resistance to anti-tumour drugs is a major problem in cancer treatment, we investigated the resistance of different cell lines to this compound. Here we report that the multidrug-resistant cell lines MCF7/ADR, CCRFNCR1000, CCRF/ADR500, CEM/VLB100 and HeLa cell lines transfected with a wild-type and mutated (gly/val185) multidrug resistance 1 gene (MDR1) are cross-resistant to ilmofosine compared with the sensitive parental cell lines. In CEMNM-1 cells, in which the resistance is associated with an altered topoisomerase II gene, no cross-resistance to ilmofosine was observed. Ilmofosine is not capable of modulating multidrug resistance and neither does it reduce the labelling of the P-glycoprotein (P-gp) by azidopine nor alter ATPase activity significantly. The resistance to ilmofosine in multidrug-resistant CCRF/VCR1000 cells cannot be reversed by the potent multidrug resistance modifier dexniguldipine-HCI (B8509-035). A tenfold excess of ilmofosine does not prevent the MDR-modulating effect of dexniguldipine-HCl. Treatment of cells with ilmofosine does not alter the levels of MDR1 mRNA. Long-term treatment of an ilmofosine-resistant Meth A subline with the drug does not induce multidrug resistance, indicating that ilmofosine does not increase the level of P-gp. Determination of the MDR2 mRNA levels in the cells revealed that the resistance pattern to ilmofosine is not correlated with the expression of this gene. It is concluded, therefore, that multidrug-resistant cells are cross-resistant to ilmofosine and that the compound is not a substrate of Pgp. No association between the expression of the MDR2-encoded P-gp and resistance to ilmofosine was observed. It is supposed that MDR1-associated alterations in membrane lipids cause resistance to ilmofosine.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Fluorescence-optical measurements of chloride movements in cells using the membrane-permeable dye diH-MEQ.

Fluorescence-optical measurements of the intracellular chloride concentration facilitate identification of chloride movements across the cell membrane of living cells. The two main dyes used for this purpose are 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ) and 6-methoxy-quinolyl acetoethyl ester (MQAE). The use of both substances is impaired by their poor membrane permeability and therefore limited loading of the cells to be studied. Here we report the use of 6-methoxy-N-ethylquinolinium iodide (MEQ), a chloride-sensitive dye for which a membrane-permeable form is easily prepared. This makes the loading procedure as easy as with the acetoxymethyl (AM) forms of other dyes for sensing intracellular ions. In addition, the original method, which described absolute concentration measurements of chloride in the cytosol, was modified in so far as only relative measurements were made. This avoids the known limitations of single wavelength excitation and emission dyes with respect to exact concentration measurements. Moreover, to enhance the signal-to-noise ratio the driving force for chloride was considerably increased by changing the original direction of the anion flux in the cells under investigation. We verified the method by using fibroblasts and activating ICln, a putative chloride channel cloned from epithelial cells and of paramount importance in the regulatory volume decrease in these cells. In the presence of SCN- the MEQ quench measured in NIH 3T3 fibroblasts is dramatically enhanced in hypotonically challenged cells compared with cells under isotonic conditions. Antisense oligodeoxynucleotides sensing ICln considerably impeded the swelling-induced chloride current (ICl) in NIH 3T3 fibroblasts. Accordingly, the chloride movement measured by the SCN- quench of the MEQ signal was significantly reduced. Similar results can be obtained in the presence of 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) or 4, 4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), two known blockers of chloride transport in the plasma membrane of a variety of cells. In conclusion, fluroscence-optical measurements using MEQ as the chloride-sensitive dye provide a reliable and easy-to-use method for measuring changes of the chloride flux across the cell membrane of living cells.

3T3 Cells↗
PubMed1996

The influence of lung volume reduction surgery on ventilatory mechanics in patients suffering from severe chronic obstructive pulmonary disease.

Recently, lung volume reduction [LVR] removal of about 20% of lung volume), has been performed to treat severe emphysema. Little is known, however, about the mechanism and time course of functional improvement, and the reasons that such patients can be tracheally extubated very early. Therefore, we studied changes in ventilatory mechanics in 12 patients after LVR. Measurements of work of breathing (WOB), intrinsic positive end-expiratory pressure (PEEPi), dynamic compliance (Cdyn), and mean airway resistance (Rawm) were performed the day before surgery, early postoperatively, and 1 and 3 mo after surgery. All measurements were performed on tracheally extubated patients, simultaneously assessing esophageal pressure via esophageal balloon catheter and air flow via tightly adjusted mask. Standard spirometry was assessed pre-operatively and 1 and 3 mo postoperatively. The patients presented with forced expiratory volume in 1 s (FEV1), of 670 +/- 50 mL and pathological values of WOB and PEEPi. All patients were successfully tracheally extubated within 5 h postoperatively. Immediately thereafter, a marked and sustained decrease in WOB, PEEPi, and Rawm was noted, as well as an increase in Cdyn. Ventilatory mechanics improved immediately after LVR, probably due to decompression of lung tissue, thereby enabling successful tracheal extubation.

Adult↗
PubMed1996

Blockade of swelling-induced chloride channels by phenol derivatives.

1. In NIH3T3 fibroblasts, the chloride channel involved in regulatory volume decrease (RVD) was identified as ICln, a protein isolated from a cDNA library derived from Madin Darby canine Kidney (MDCK) cells. ICln expressed in Xenopus laevis oocytes gives rise to an outwardly rectifying chloride current, sensitive to the extracellular addition of nucleotides and the known chloride channel blockers, DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) and NPPB (5-nitro-2-(3-phenylpropylamino)-benzoic acid). We set out to study whether substances structurally similar to NPPB are able to interfere with RVD. 2. RVD in NIH3T3 fibroblasts and MDCK cells is temperature-dependent. 3. RVD, the swelling-dependent chloride current and the depolarization seen after reducing extracellular osmolarity can be blocked by gossypol and NDGA (nordihydroguaiaretic acid), both structurally related to NPPB. 4. The cyclic AMP-dependent chloride current elicited in CaCo cells is less sensitive to the two substances tested while the calcium-activated chloride current in fibroblasts is insensitive. 5. The binding site for the two phenol derivatives onto ICln seems to be distinct but closely related to the nucleotide binding site identified as G x G x G, a glycine repeat located at the predicted outer mouth of the ICln channel protein.

3T3 Cells↗
PubMed1996

Early postoperative stress: video-assisted wedge resection/lobectomy vs conventional axillary thoracotomy.

Postoperative pain is a major cause of ineffective breathing after lung surgery, predisposing patients to hypoxemia. Because potent analgesics like opioids depress ventilation and other analgesic techniques are time-consuming, efficient postoperative pain therapy is difficult. Therefore, a less painful surgical approach could be beneficial. Forty-seven patients with diagnosis of a pulmonary nodule were prospectively studied. Patients were assigned to a video-assisted thoracic surgery (VATS) group (n=22) or a group undergoing axillary thoracotomy (n=25). Visual analogue scale (VAS) scores, plasma glucose levels, plasma epinephrine and plasma norepinephrine levels, as well as arterial oxygen (PaO2) and carbon dioxide (PaCO2) tension were determined the day before surgery, and 3, 15, 24, 48, and 72 h after surgery. Postoperative piritramide (a synthetic morphine compound) demand was recorded. VAS values were significantly lower (p<0.05) during the whole observation period in the VATS group. Significantly higher epinephrine levels were observed 3 and 15 h after surgery (267.4 +/- 28 vs 111.8 +/- 13 ng/L; p<0.01; and 176.6 +/- 46.5 vs 96 +/- 14.5 ng/L; p<0.05) in the thoracotomy group, whereas there was no significant difference in norepinephrine (correction of norephinephrine) levels. Piritramide demand was significantly (p<0.05) reduced in the VATS group throughout the whole observation period. There was no difference in PaCO2 values but PaO2 Values were higher in the VATS group over 72 h, with maximum differences occurring at 15 h after operation: 60.9 +/- 1.9 vs 49.2 +/- 2.4 mm Hg (p<0.01). In conclusion, the videoendoscopic approach is associated with less postoperative pain and better oxygenation than traditional surgical approaches.

Analgesics, Opioid↗