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M Becker

Publications and source records attributed to M Becker.

At least 73 records · Page 4Linked to original sources
PubMed1999

Internal carotid artery dissection following rigid esophagoscopy.

A case of internal carotid artery dissection that developed after rigid esophagoscopy is described. The diagnosis was suggested by the clinical presentation and confirmed by the findings of radiological examinations. Internal carotid artery dissection is a rare condition of controversial etiology. Most frequently, the cause is unknown and the condition is termed idiopathic. A few cases have occurred after forceful cervical extensions and manipulations. The pathogenesis in our case is uncertain: while the rigid esophagoscopy is the most probable cause, the intubation and spontaneous carotid artery dissection cannot be ruled out.

Adult↗
PubMed1999

Viability of cultured nerve grafts: An assessment of proliferation of Schwann cells and fibroblasts.

Previous studies demonstrated that the viability of nerve grafts had a positive effect on nerve regeneration, while the cold storage of nerve grafts obtained few viable cells at the later stage. The purpose of this study was to examine the cellular activities of Schwann cells and fibroblasts in cultured nerve grafts prior to transplantation. 2.5-cm long sciatic nerve grafts were harvested from 75 male Lewis rats. Two different media were utilized to culture the nerve grafts up to 3 weeks: Dulbecco's modified eagle medium (DMEM) only or DMEM supplemented with 2 microM forskolin and 10 microg/ml pituitary exact (mitogen medium for Schwann cells). In vivo predegenerated and normal nerve grafts were used as positive and negative controls, respectively. We employed a 5-bromo-2'-deoxyuridine (BrdU) incorporation method to evaluate the proliferating cells in the cultured nerve grafts. S-100 and vimentin immunostaining were used to estimate the presence of Schwann cells and fibroblasts in all nerve grafts at different intervals. The results showed that the proliferating cells increased progressively under culture conditions. The proliferating cells distributed evenly in small fascicles (average diameter 251 +/- 71.5 microm), whereas they appeared mainly in the margin of large fascicles (average diameter 624 +/- 87.3 microm). The mitogen medium stimulated Schwann cell multiplication more significantly in comparison with DMEM after 3 days of culture (P < 0.01), however, there were fewer fibroblasts present in the mitogen medium than in DMEM after 2 days of culture (P < 0.01). It is suggested that the viability of nerve grafts can be preserved under culture conditions. Furthermore, the cellular activity of the Schwann cells and fibroblasts in nerve grafts can be manipulated in in vitro Wallerian degeneration.

Animals↗
PubMed1999

Differential kinetics of primitive hematopoietic cells assayed in vitro and in vivo during serum-free suspension culture of CD34+ blood progenitor cells.

So far, blood progenitor cells (BPC) expanded ex vivo in the absence of stromal cells have not been demonstrated to reconstitute hematopoiesis in myeloablated patients. To characterize the fate of early hematopoietic progenitor cells during ex vivo expansion in suspension culture, human CD34(+)-enriched BPC were cultured in serum-free medium in the presence of FLT3 ligand (FL), stem cell factor (SCF) and interleukin 3 (IL-3). Both CD34 surface expression levels and the percentage of CD34+ cells were continuously downregulated during the culture period. We observed an expansion of colony-forming units granulocyte-macrophage (CFU-GM) and BFU-E beginning on day 3 of culture, reaching an approximate 2-log increase by days 5 to 7. Limiting dilution analysis of primitive in vitro clonogenic progenitors was performed through a week 6 cobblestone-area-forming cell (CAFC) assay, which has previously been shown to detect long-term bone marrow culture-initiating cells (LTC-IC). A maintenance or a slight (threefold) increase of week 6 CAFC/LTC-IC was found after one week of culture. To analyze the presence of BPC mediating in vivo engraftment, expanded CD34+ cells were transplanted into preirradiated NOD/SCID mice at various time points. Only CD34+ cells cultured for up to four days successfully engrafted murine bone marrow with human cells expressing myeloid or lymphoid progenitor phenotypes. In contrast, five- and seven-day expanded human BPC did not detectably engraft NOD/SCID mice. When FL, SCF and IL-3-supplemented cultures were performed for seven days on fibronectin-coated plastic, or when IL-3 was replaced by thrombopoietin, colony forming cells and LTC-IC reached levels similar to those of control cultures, yet no human cell engraftment was recorded in the mice. Also, culture in U-bottom microplates resulting in locally increased CD34+ cell density had no positive effect on engraftment. These results indicate that during ex vivo expansion of human CD34+ cells, CFC and LTC-IC numbers do not correlate with the potential to repopulate NOD/SCID mice. Our results suggest that ex vivo expanded BPC should be cultured for limited time periods only, in order to preserve bone-marrow-repopulating hematopoietic stem cells.

Animals↗
PubMed1999

Local disposition kinetics of floxuridine after intratumoral and subcutaneous injection as monitored by [19F]-nuclear magnetic resonance spectroscopy in vivo.

PURPOSE: To test the utility of [19F]-nuclear magnetic resonance (NMR) spectroscopy for studying the kinetics of local drug disposition after interstitial application in vivo. METHODS: Floxuridine at 30 micromol (2.5% of the reported i.p. 50% lethal dose, LD50) was injected into rats either intratumorally (Morris hepatoma M3924A) or s.c. [19F]-NMR spectra were obtained at the site of administration for up to 5 h after injection using a 2-cm diameter surface coil at 2.0 T. Signal-time data obtained for floxuridine and the metabolite 5-fluorouracil were analyzed using linear compartment models. RESULTS: The lower limit for the quantitation of drug remaining at the site of administration was 1 micromol for tumors and 0.2 micromol for the s.c. injection site. Local drug disposition was biexponential in four of six tumors where the half-lives of the fast and slow components of disposition ranged from 4 to 26 and from 33 to 289 min, respectively. It was monoexponential in the remaining two tumors (half-lives 49 and 128 min) and in the s.c. injection experiments (n = 4, half-life 6-9 min). 5-Fluorouracil could be quantitated in three of six tumors; the estimated fraction of floxuridine converted intratumorally into 5-fluorouracil was 11-23%. Alpha-fluoro-beta-alanine was detected in the sum spectra of three of the six tumours. CONCLUSIONS: Local drug-disposition kinetics after interstitial application can be monitored noninvasively by in vivo [19F]-NMR spectroscopy. Disposition kinetics after local injection is highly variable and has a slow component in this tumor, whereas it is much less variable and relatively fast in subcutaneous tissue. The results suggest that NMR spectroscopy may be useful for in vivo studies of drug release from depot preparations designed for interstitial application.

Animals↗
PubMed1999

A signal peptide cleavage site mutation in the cationic trypsinogen gene is strongly associated with chronic pancreatitis.

BACKGROUND & AIMS: In pancreatitis, a key role has been attributed to the inappropriate conversion of trypsinogen to trypsin. Recently, two mutations of the cationic trypsinogen gene were found in families with hereditary pancreatitis. This study was conducted to determine the spectrum and frequency of cationic trypsinogen mutations in unrelated patients with idiopathic or hereditary chronic pancreatitis (CP). METHODS: DNA samples from 44 unrelated children and adolescents with CP (30 patients with idiopathic CP and 14 with hereditary CP) and from 56 family members were investigated. The cationic trypsinogen gene was screened for mutations by single-strand conformation polymorphism analysis and DNA sequencing. RESULTS: A mutation in the cationic trypsinogen gene was detected in 5 patients: in 2 patients with a family history of CP and in 3 patients with idiopathic CP. In 1 patient the formerly described R122H mutation was detected. In 4 patients a hitherto unknown mutation was found at the signal peptide cleavage site leading to an alanine to valine exchange in codon 16. The mutations were inherited in all cases. In 95 unrelated control individuals the A16V mutation was not found. CONCLUSIONS: Heterozygosity for the A16V mutation is strongly associated with CP. These results indicate that a significant percentage of patients with idiopathic CP may have a genetic basis for their disorder; therefore, genetic testing should be included in the diagnostic evaluation of these patients.

Adolescent↗
PubMed1999

Treatment of ataxia in isolated vitamin E deficiency caused by alpha-tocopherol transfer protein deficiency.

Dysfunction of the alpha-tocopherol transfer protein causes ataxia with isolated vitamin E deficiency. A 14-year-old male patient presented with ataxia and mental symptoms caused by a homozygous (552G-->A) alpha-tocopherol transfer protein mutation. After initiation of high-dosage alpha-tocopherol therapy, the organic mental syndrome disappeared and cognitive function improved rapidly. Neurologic recovery, however, was slow and incomplete.

Adolescent↗
PubMed1999

Surgical treatment of Zenker's diverticulum: transcutaneous diverticulectomy versus microendoscopic myotomy of the cricopharyngeal muscle with CO2 laser.

In a retrospective study, we analyzed 97 patients who were treated by either transcutaneous diverticulectomy (n = 66) or microendoscopic myotomy of the cricopharyngeal muscle with CO(2) laser (n = 31). Two (6.4%) of 31 patients in the microendoscopic myotomy group had complications, compared with 10 (15%) of 66 patients in the diverticulectomy group. In addition, the complications observed in the microendoscopic myotomy group were less severe than those observed in the transcutaneous diverticulectomy group. The average length of hospitalization was shorter in the microendoscopic myotomy group than in the diverticulectomy group (8 days versus 11.4 days). We conclude that microendoscopic CO(2)-laser myotomy is a less invasive, more precise, and safer procedure, which results in a shortened period of hospitalization and complete relief of symptoms in the vast majority of cases.

Adult↗
PubMed1999

The copper chaperone CCS is abundant in neurons and astrocytes in human and rodent brain.

Copper trafficking in mammalian cells is highly regulated. CCS is a copper chaperone that donates copper to the antioxidant enzyme copper/zinc superoxide dismutase 1 (SOD 1). Mutations of SOD1 are responsible for approximately 20% of familial amyotrophic lateral sclerosis (FALS). Monospecific antibodies were generated to evaluate the localization and cellular distribution of this copper chaperone in human and mouse brain as well as other organs. CCS is found to be ubiquitously expressed by multiple tissues and is present in particularly high concentrations in kidney and liver. In brain and spinal cord, CCS was found throughout the neuropil, with expression largely confined to neurons and some astrocytes. Like SOD1, CCS immunoreactivity was intense in Purkinje cells, deep cerebellar neurons, and pyramidal cortical neurons, whereas in spinal cord, CCS was highly expressed in motor neurons. In cortical neurons, CCS was present in the soma and proximal dendrites, as well as some axons. Although the distribution of CCS paralleled that of SOD1, there was a 12-30-fold molar excess of SOD1 over CCS. That both SOD1 and CCS are present, together, in cells that degenerate in ALS also emphasizes the potential role of CCS in mutant SOD1-mediated toxicity.

Amyotrophic Lateral Sclerosis↗
PubMed1999

Computing data about patients with cleft lip and palate.

For clinical research and quality control in the treatment of patients with cleft lip and palate (CLP) we created a register based on commercially available computer components. In this report we present the logical organisation of the system and give some representative examples of its applicability. There is great potential for easy access to data, and presentation.

Adult↗
PubMed1999

Novel four-drug salvage treatment regimens after failure of a human immunodeficiency virus type 1 protease inhibitor-containing regimen: antiviral activity and correlation of baseline phenotypic drug susceptibility with virologic outcome.

Twenty human immunodeficiency virus-infected patients experiencing virologic failure of an indinavir- or ritonavir-containing treatment regimen were evaluated in a prospective, open-label study. Subjects received nelfinavir, saquinavir, abacavir, and either another nucleoside analog (n=10) or nevirapine (n=10). Patients treated with the nevirapine-containing regimen experienced significantly greater virologic suppression at week 24 than those not treated with nevirapine (P=.04). Baseline phenotypic drug susceptibility was strongly correlated with outcome in both treatment arms. Subjects with baseline virus phenotypically sensitive to 2 or 3 drugs in the salvage regimen experienced significantly greater virus load suppression than those with baseline virus sensitive to 0 or 1 drug (median week-24 change=-2.24 log and -0.35 log, respectively; P=.01). In conclusion, non-nucleoside reverse transcriptase inhibitors may represent a potent drug in salvage therapy regimens after failure of an indinavir or ritonavir regimen. Phenotypic resistance testing may provide a useful tool for selecting more effective salvage regimens.

Adult↗
PubMed1999

An automatic method for the identification and interpretation of clustered microcalcifications in mammograms.

We investigated a method for a fully automatic identification and interpretation process for clustered microcalcifications in mammograms. Mammographic films of 100 patients containing microcalcifications with known histology were digitized and preprocessed using standard techniques. Microcalcifications detected by an artificial neural network (ANN) were clustered and some cluster features served as the input of another ANN trained to differentiate between typical and atypical clusters, while others were fed into an ANN trained on typical clusters to evaluate these lesions. The measured sensitivity for the detection of grouped microcalcifications was 0.98. For the task of differentiation between typical and atypical clusters an Az value of 0.87 was computed, while for the diagnosis an Az value of 0.87 with a sensitivity of 0.97 and a specificity of 0.47 was obtained. The results show that a fully automatic computer system was developed for the identification and interpretation of clustered microcalcitications in mammograms with the ability to differentiate most benign lesions from malignant ones in an automatically selected subset of cases.

Breast Diseases↗
PubMed1999

Endoscopic ultrasound cannot determine suitability for esophagectomy after aggressive chemoradiotherapy for esophageal cancer.

OBJECTIVE: Endoscopic ultrasound (EUS) provides important information in the initial staging of patients with esophageal cancer. With recent modifications in chemoradiotherapy protocols, a significant number of patients have no residual tumor at esophagectomy. The high surgical morbidity and mortality might be avoided if complete response to chemoradiotherapy could be predicted. Previously published clinical trials, with relatively small patient numbers, have suggested that EUS may accurately stage esophageal cancer after chemoradiotherapy. The aim of this study was to verify the accuracy of EUS in staging esophageal cancer after effective chemoradiotherapy. METHODS: EUS staging was performed before and after concurrent cisplatin, 5-fluorouracil, and hyperfractionated radiotherapy in 59 patients with newly diagnosed esophageal cancer. All patients underwent subsequent esophagectomy and pathological staging. The accuracy of preoperative, postchemoradiotherapy EUS was evaluated in a retrospective fashion by comparison to pathological staging. RESULTS: After chemoradiotherapy, 18 patients (31%) had no residual disease at pathological staging (T0N0). However, EUS correctly predicted complete response to chemoradiotherapy (T0N0) in only three patients (17%). The accuracy of postchemoradiotherapy EUS for pathological T stage was only 37%, and its sensitivity for N1 disease was only 38%. EUS was unable to distinguish postradiation fibrosis and inflammation from residual tumor. CONCLUSION: When aggressive preoperative chemoradiotherapy is provided to patients with esophageal cancer, the predictive value of postchemoradiotherapy EUS is inadequate for use in clinical decision making.

Adenocarcinoma↗
PubMed1999

Identification of human herpesvirus 8-specific cytotoxic T-cell responses.

Human herpesvirus 8 (HHV-8) (or Kaposi's sarcoma-associated herpesvirus) is implicated in the etiopathogenesis of Kaposi's sarcoma (KS) and certain lymphoproliferations. The introduction of more effective therapies to treat human immunodeficiency virus infection has led to a decline in the incidence of KS and also in the resolution of KS in those already affected. This suggests that cellular immune responses including cytotoxic T lymphocytes (CTLs) could play a vital role in the control of HHV-8 infection and in KS pathogenesis. Here we elucidate HLA class I-restricted, HHV-8-specific cellular immune responses that could be important in the control of HHV-8 infection and subsequent tumor development. We show the presence of CTLs against HHV-8 latent (K12), lytic (K8.1), and highly variable (K1) proteins in infected individuals.

AIDS-Related Opportunistic Infections↗
PubMed1999

Dual versus triple therapy of Helicobacter pylori infection: results of a multicentre trial.

OBJECTIVE: To compare dual therapy (omeprazole and amoxicillin) with triple therapy (omeprazole, amoxicillin, and clarithromycin) in the treatment of Helicobacter pylori infection. The efficacy of 1 mg/kg/day omeprazole was randomly compared with 2 mg/kg/day. STUDY DESIGN: 252 patients (median age, 11.0 years; range, 3-18) presenting with chronic abdominal pain underwent endoscopy and a 13C-urea breath test. Gastric biopsy specimens were taken for histological examination and for the rapid urease test. Patients were treated for two weeks: group A (n = 63) received amoxicillin (50 mg/kg; maximum, 2 g/day), group B (n = 73) received amoxicillin and clarithromycin (20 mg/kg; maximum, 1 g/day). Both groups were randomly treated with either 1 or 2 mg/kg omeprazole (maximum, 80 mg/day). Diagnostic procedures were repeated four weeks after the end of treatment. RESULTS: 11 patients were excluded; 136 patients were H pylori positive (56%), 105 of whom were re-examined after treatment. Helicobacter pylori was eradicated in 52% of group A and 83% of group B. The dose of omeprazole had no influence on the eradication rate. Specificity and sensitivity of the rapid urease test were 94% and 93%, respectively. Specificity and sensitivity of the 13C-urea breath test were 93% and 95%, respectively. CONCLUSIONS: Dual therapy can no longer be recommended. Triple therapy is more effective than dual therapy in the eradication of H pylori infection. The lower dose of 1 mg/kg omeprazole was as effective as 2 mg/kg.

Adolescent↗
PubMed1999

Resectable esophageal carcinoma: local control with neoadjuvant chemotherapy and radiation therapy.

PURPOSE: To evaluate the usefulness of neoadjuvant chemotherapy and radiation therapy before esophagectomy for invasive cancer of the esophagus or gastroesophageal junction (GEJ). MATERIALS AND METHODS: The authors conducted a retrospective analysis of 154 patients who underwent esophagectomy for invasive cancer between September 1, 1991, and December 31, 1995. The end points evaluated were overall, disease-free, local-regional relapse-free, and systemic relapse-free survival. RESULTS: Seventy of the 154 patients received neoadjuvant combined-modality therapy (CMT) consisting of concurrent cisplatin and fluorouracil administration and accelerated, hyperfractionated radiation therapy. The remaining 84 patients underwent immediate esophagectomy. With a median follow-up of 34.7 months, the 3-year overall, disease-free, and distant metastatic relapse-free survival rates were 38.0%, 41.9%, and 56.0%, respectively. Although neoadjuvant therapy did not appear to prevent distant metastases, there was a dramatic effect on local control. After CMT, the 5-year local control rate was 90% compared to 64% after surgery (P < .001). Tumors in the GEJ recurred more frequently (P = .01); however, multivariate analysis showed CMT was the only independent predictor of local control. Postoperative mortality was 15.7% after CMT versus 5.9% without CMT (P = .05). CONCLUSION: Local control of esophageal cancer is excellent following neoadjuvant chemotherapy and radiation therapy. However, the effects of CMT on overall and disease-free survival are less clear due to significant differences between the treatment groups.

Adenocarcinoma↗
PubMed1999

The Wisconsin Quality of Life Index: a multidimensional model for measuring quality of life.

The Wisconsin Quality of Life Index (W-QLI) is a multidimensional model for measuring quality of life. This model assumes that quality of life is comprised of 9 dimensions: life satisfaction, occupational activities, psychological well-being, physical health, social relations, economics, activities of daily living, symptoms, and the patient's own goals. The W-QLI takes into account the different perspectives of the patient, the patient's family, and the clinician, both currently and over time. An accompanying taxonomy and patient outcome report can be used in clinical practice to group the patient's goals and to track the attainment of the goals over time, as well as to show the agreements and disagreements between the patient and clinician in terms of how satisfied each is with the patient's progress. The W-QLI, taxonomy, and outcome report can also incorporate the service provider's goals and can be used to examine program results.

Activities of Daily Living↗
PubMed1999

Anticancer drug sensitivity and expression of multidrug resistance markers in early passage human sarcomas.

We have established new human sarcoma lines and examined their sensitivity to common antitumor drugs and expression of putative multidrug resistance (MDR) proteins. Eighty-two sarcoma samples were transplanted in nude mice. Fourteen of these sarcomas were established as tumor cell lines. We determined a chemosensitivity profile to antitumor drugs (MDR drugs = doxorubicin, mitoxantrone, and vincristine; non-MDR drugs = cisplatin, ifosfamide, and bleomycin) for each tumor line in vivo. Response to chemotherapy with doxorubicin and ifosfamide was observed in 30-50% of these tumor lines. Our results obtained with xenotransplants are similar to the results documented in clinical trials in which doxorubicin and ifosfamide are effective in 30-50% of the patients. Furthermore, we examined expression of MDR-relevant markers like P-glycoprotein, MDR-associated protein, lung resistance protein, and mdr1 mRNA in these xenotransplants. A relationship between mdr1 mRNA expression and response to doxorubicin was demonstrated in >90% of our tumor lines. In six sarcomas with mdr1 mRNA expression, five were resistant against doxorubicin and cross-resistant against several other drugs, whereas from eight sarcomas, which lacked detectable mdr1 mRNA, seven were sensitive to doxorubicin and other drugs. We found lung resistance protein or MDR-associated protein expressed in three resistant and mdr1 mRNA-positive sarcomas. These results demonstrate that mdr1 mRNA expression is a putative marker for drug resistance in our sarcoma lines. We conclude, therefore, that inherent P-glycoprotein expression might be also responsible for drug resistance occurring in treatment of patients with sarcomas. The established tumor lines are useful for additional investigations on mechanisms of drug resistance in sarcomas and as models for preclinical screening of new antitumor drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗