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Biomedical subjects

M Klein

Publications and source records attributed to M Klein.

At least 91 records · Page 5Linked to original sources
PubMed2000

The free release of dismantled materials. The practical case of the BR3 reactor

The dismantling of a nuclear power reactor produces a large quantity and variety of obsolete materials. Besides the activated materials which must be evacuated as radioactive waste, a large quantity of materials can either be recycled in the nuclear sector or free released as non-radioactive materials. Dismantling is a complex task so that to achieve our main goal of minimisation of radioactive waste production, it requires the set-up of procedures and free release criteria, a strict follow-up and a traceability at all steps. The free release of obsolete materials can be achieved by several processes such as, melting in a nuclear foundry, or by various physical and chemical decontamination processes. The final key point is the measurement of a very low level radioactivity for large items or for a high throughput.

Journal Article↗
PubMed2000

A phase II study of paclitaxel in chemonaïve patients with recurrent high-grade glioma.

BACKGROUND: The prognosis of malignant gliomas remains poor. In recurrent disease, chemotherapy can be considered. PATIENTS AND METHODS: In this phase II study we determined the anti-tumour efficacy of paclitaxel 200 mg/m2 in a three-hour intravenous infusion every three weeks in chemonaïve patients with recurrent high-grade glioma in terms of response, survival, and quality of life. RESULTS: In 17 patients (14 glioblastoma multiforme, 3 anaplastic astrocytoma) 69 paclitaxel cycles were administered. Partial or complete responses were not observed. Stable disease for four to six months was observed in five patients (29%). Median time to progression and median survival were two and 10 months, respectively. Toxicity due to paclitaxel was as to be expected and minor in most cases. Quality of life and mood estimates appeared rather stable over time. CONCLUSIONS: We conclude that three-weekly 200 mg/m2 paclitaxel chemotherapy for patients with recurrent high-grade gliomas did not lead to major complications or adverse effects on quality of life and mood. However, this therapy is of only very limited value in terms of response and survival in such patients.

Adult↗
PubMed2000

A membrane-potential dependent ABC-like transporter mediates the vacuolar uptake of rye flavone glucuronides: regulation of glucuronide uptake by glutathione and its conjugates.

In this paper we present results on the vacuolar uptake mechanism for two flavone glucuronides present in rye mesophyll vacuoles. In contrast to barley flavone glucosides (Klein et al. (1996) J. Biol. Chem. 271, 29666-29671), the flavones luteolin 7-O-diglucuronyl-4'-O-glucuronide (R1) and luteolin 7-O-diglucuronide (R2) were taken up into vacuoles isolated from rye via a directly energized mechanism. Kinetic studies suggested that the vacuolar glucuronide transport system is constitutively expressed throughout rye primary leaf development. Competition experiments argued for the existence of a plant MRP-like transporter for plant-specific and non-plant glucuronides such as beta-estradiol 17-(beta-D-glucuronide) (E217G). The interaction of ATP-dependent vacuolar glucuronide uptake with glutathione and its conjugates turned out to be complex: R1 transport was stimulated by dinitrobenzene-GS and reduced glutathione but was inhibited by oxidized glutathione in a concentration-dependent manner. In contrast, R2 uptake was not increased in the presence of reduced glutathione. Thus, the transport system for plant-derived glucuronides differed from the characteristic stimulation of vacuolar E217G uptake by glutathione conjugates but not by reduced glutathione (Klein et al. (1998) J. Biol. Chem. 273, 262-270). Using tonoplast vesicles isolated with an artificial K+ gradient, we demonstrate for the first time for plant MRPs that the ATP-dependent uptake of R1 is membrane-potential dependent. We discuss the kinetic capacity of the ABC-type glucuronide transporter to explain net vacuolar flavone glucuronide accumulation in planta during rye primary leaf development and the possibility of an interaction of potential substrates at both the substrate binding and allosteric sites of the MRP transporter regulating the activity towards a certain substrate.

ATP-Binding Cassette Transporters↗
PubMed2000

The pediatric trauma C-spine: is the 'odontoid' view necessary?

BACKGROUND/PURPOSE: The "odontoid view" is a difficult and often hazardous film to obtain in young children. The aim of this study was to determine if the transoral roentgenogram is necessary in the evaluation of the pediatric cervical spine. METHODS: A retrospective, multiinstitutional review was performed of all patients 16 years of age and under with documented cervical spine injury in a large metropolitan area during the past decade. Fifty-one children with cervical spine injury were identified from the medical records at 4 hospitals. RESULTS: The 0- to 8-year-old age group had a significantly higher incidence of upper (occiput to C3) cervical injury than the 9- to 16-year-old age group (67% v 39%; P < .05). In the 0- to 8-year-old group the initial lateral/anteroposterior radiograph made the diagnosis of cervical spine injury in 13 of 15 patients (87%), and in no patients was the transoral odontoid view used to make the diagnosis of cervical spine injury. In only 1 patient in the 9- to 16-year-old age group with a type III odontoid fracture was this view deemed useful. The overall mortality rate in this series was 7.8% with all deaths secondary to associated head injury. CONCLUSIONS: In the 0- to 8-year-old age group in whom the incidence of cervical spine injury is rare but frequently involves the upper cervical spine, the transoral odontoid roentgenogram may be of little value in the evaluation of the spine and should not be considered necessary in "clearing" the pediatric cervical spine. An alternative evaluation of these patients would include an initial lateral and AP radiograph, followed by computed tomography scan.

Cervical Vertebrae↗
PubMed2000

Optical coherence tomography: advanced technology for the endoscopic imaging of Barrett's esophagus.

BACKGROUND AND STUDY AIMS: Endoscopic optical coherence tomography (OCT) is an emerging medical technology capable of generating high-resolution cross-sectional imaging of tissue microstructure in situ and in real time. We assess the use and feasibility of OCT for real-time screening and diagnosis of Barrett's esophagus, and also review state-of-the-art OCT technology for endoscopic imaging. MATERIALS AND METHODS: OCT imaging was performed as an adjunct to endoscopic imaging of the human esophagus. Real-time OCT (13-microm resolution) was used to perform image-guided evaluation of normal esophagus and Barrett's esophagus. Beam delivery was accomplished with a 1-mm diameter OCT catheter-probe that can be introduced into the accessory channel of a standard endoscope. Different catheter-probe imaging designs which performed linear and radial scanning were assessed. Novel ultrahigh-resolution (1.1-microm resolution) and spectroscopic OCT techniques were used to image in vitro specimens of Barrett's esophagus. RESULTS: Endoscopic OCT images revealed distinct layers of normal human esophagus extending from the epithelium to the muscularis propria. In contrast, the presence of gland- and crypt-like morphologies and the absence of layered structures were observed in Barrett's esophagus. All OCT images showed strong correlations with architectural morphology in histological findings. Ultrahigh-resolution OCT techniques achieved 1.1-microm image resolution in in vitro specimens and showed enhanced resolution of architectural features. Spectroscopic OCT identified localized regions of wavelength-dependent optical scattering, enhancing the differentiation of Barrett's esophagus. CONCLUSIONS: OCT technology with compact fiberoptic imaging probes can be used as an adjunct to endoscopy for real-time image-guided evaluation of Barrett's esophagus. Linear and radial scan patterns have different advantages and limitations depending upon the application. Ultrahigh-resolution and spectroscopic OCT techniques improve structural tissue recognition and suggest future potential for resolution and contrast enhancements in clinical studies. A new balloon catheter-probe delivery device is proposed for systematic imaging and screening of the esophagus.

Barrett Esophagus↗
PubMed2000

Esophagobronchial fistula combined with a peptic esophageal stenosis.

Peptic strictures are a rare complication of severe gastroesophageal reflux disease. An esophagobronchial fistula as a complication of a severe long-term reflux esophagitis with peptic stenosis is here described for the first time: A 43-year-old mentally disabled patient suffered from recurrent bronchopneumonia. Endoscopy revealed an esophagobronchial fistula originating in a peptic stricture. Under short-term fasting, intravenous feeding and application of a proton pump inhibitor (PPI) closure of this fistula was achieved within 4 days. Subsequently, dilatation was carried out. The case demonstrates that pulmonary complications in patients with peptic esophageal strictures may not only be due to aspiration of refluxate but--rarely--also to fistulae between the esophagus and the bronchial tree.

Adult↗
PubMed2000

Energy metabolism and thyroid hormone levels of growing rats in response to different dietary proteins--soy protein or casein.

Energy balances were measured by indirect calorimetry in four experiments on male growing rats, fed restrictively on isoenergetic and isonitrogenous (10% CP) diets based on either casein supplemented with methionine, or soy protein isolate (experiments 1, 2 and 3) and soy protein isolate supplemented with methionine (experiment 0), respectively. At the end of experiments the rats were killed for body analysis and determination of thyroid hormones and lipids in blood as well as mitochondrial respiration in liver and heart. Feeding of non-supplemented soy protein resulted in a lower efficiency of energy utilisation as well as a lower protein utilisation compared to casein-fed and supplemented soy protein-fed rats. Chemical body composition was not markedly different between the dietary groups. After long-term feeding of soy protein (experiment 3) mass and mitochondrial protein content of the interscapular brown adipose tissue were increased compared to casein-fed rats. Serum thyroid hormone levels were not changed (T3 and free T3) or were significantly lowered (T4 and free T4) following soy protein feeding in comparison with casein feeding (except for experiment 2). Cholesterol and triglycerides were decreased on an average in response to soy protein or supplemented soy protein feeding. In two of three experiments a significant lower efficiency of hepatic mitochondrial respiration with succinate as substrate, expressed by the ratio of added ADP to oxygen consumed, was observed in soy protein-fed rats compared to casein-fed rats.

Animals↗
PubMed2000

Research note: is starch utilization for fat deposition in man different from that in animals?

Utilization of starch for fat deposition in humans was investigated by means of the nitrogen-carbon-balance method in a respiration chamber using the difference principle with a basal and a supplemental period. The basal diet was designed to maintain an adequate energy balance of the volunteer and to meet the maintenance requirements of protein, minerals and vitamins. The dietary fat content was minimized to 2.7% of DM. The digestibility of starch energy was determined to be 97%. The estimated efficiency of ME utilization of starch for energy deposition in humans amounted to 75.8%, which was in accordance with former results in pigs and rats. This suggests that in case of an intake of diets rich in carbohydrates and low in fat the utilization of carbohydrates for lipogenesis in humans is similar to that in monogastric mammal animals.

Adipose Tissue↗
PubMed2000

Polarization of Na(+)/H(+) and Cl(-)/HCO (3)(-) exchangers in migrating renal epithelial cells.

Cell migration is crucial for processes such as immune defense, wound healing, or the formation of tumor metastases. Typically, migrating cells are polarized within the plane of movement with lamellipodium and cell body representing the front and rear of the cell, respectively. Here, we address the question of whether this polarization also extends to the distribution of ion transporters such as Na(+)/H(+) exchanger (NHE) and anion exchanger in the plasma membrane of migrating cells. Both transporters are required for locomotion of renal epithelial (Madin-Darby canine kidney, MDCK-F) cells and human melanoma cells since their blockade reduces the rate of migration in a dose-dependent manner. Inhibition of migration of MDCK-F cells by NHE blockers is accompanied by a decrease of pH(i). However, when cells are acidified with weak organic acids, migration of MDCK-F cells is normal despite an even more pronounced decrease of pH(i). Under these conditions, NHE activity is increased so that cells are swelling due to the accumulation of organic anions and Na(+). When exclusively applied to the lamellipodium, blockers of NHE or anion exchange inhibit migration of MDCK-F cells as effectively as when applied to the entire cell surface. When they are directed to the cell body, migration is not affected. These data are confirmed immunocytochemically in that the anion exchanger AE2 is concentrated at the front of MDCK-F cells. Our findings show that NHE and anion exchanger are distributed in a polarized way in migrating cells. They are consistent with important contributions of both transporters to protrusion of the lamellipodium via solute uptake and consequent volume increase at the front of migrating cells.

Amiloride↗
PubMed2000

SPECT attenuation artifacts in normal and overweight persons: insights from a retrospective comparison of Rb-82 positron emission tomography and TI-201 SPECT myocardial perfusion imaging.

PURPOSE: Myocardial perfusion imaging can be performed using SPECT or positron emission tomography (PET). SPECT has lower specificity than PET, largely as a result of attenuation artifacts; however, it is more widely available. The authors describe a study of the effect of sex and body weight on the incidence of SPECT attenuation artifacts using a retrospective comparison of TI-201 SPECT and Rb PET. METHODS: One hundred sixty-one persons (101 men, 60 women; 81 normal weight, 80 overweight) underwent TI-201 SPECT and Rb PET. The incidence of observed perfusion defects was studied in territories of the three major coronary arteries. SPECT and PET results were also compared with those of angiography in a subset of 75 patients. RESULTS: One hundred fourteen defects were reported on Rb PET compared with 176 defects with TI-201 SPECT. Excess TI-201 SPECT defects occurred in male and female, normal-weight and overweight persons. The average specificity was 64% for TI-201 SPECT and 84% for Rb PET, reflecting this difference. CONCLUSIONS: Attenuation artifacts in TI-201 SPECT occur frequently and are not confined to easily identifiable subgroups of patients. Therefore, measures to improve specificity of SPECT (e.g., prone or gated imaging) or alternative imaging techniques such as PET have potential advantages for everyone, not simply for obese patients and women with large breasts. In addition, awareness of the prevalence of SPECT attenuation artifacts, in both sexes and all weight categories, may contribute to improved accuracy of interpretation.

Artifacts↗
PubMed2000

The picornavirus replication inhibitors HBB and guanidine in the echovirus-9 system: the significance of viral protein 2C.

HBB [2-(alpha-hydroxybenzyl)-benzimidazole] and guanidine are potent inhibitors of picornavirus replication. Among other evidence, limited cross-resistance and a synergistic effect of both inhibitors suggest similar but not identical mechanisms of antiviral action. Echovirus-9 variants resistant to each of these drugs were characterized and sequenced. Complete resistance to HBB or guanidine was shown to be due to single but different point mutations in the non-structural protein 2C. Protein 2C was expressed as GST fusion and His-tagged proteins for the wild-type and various mutants. Although three mutations were located in or near conserved NTP binding motifs, NTPase activity was not altered in the presence of HBB or guanidine.

Animals↗
PubMed2000

A human immunodeficiency virus prime-boost immunization regimen in humans induces antibodies that show interclade cross-reactivity and neutralize several X4-, R5-, and dualtropic clade B and C primary isolates.

A human immunodeficiency virus (HIV) vaccine that will be useful in diverse geographic regions will need to induce a broad immune response characterized by cross-clade immunity. To test whether a clade B-based HIV candidate vaccine could induce interclade humoral responses, including neutralizing activity against primary HIV-1 isolates, sera were tested from recipients of a vaccine consisting of recombinant canarypox virus vCP205 and recombinant gp120(SF2). Serum antibodies exhibited strong immunochemical cross-reactivity with V3 peptides from clades B, C, and F, with weaker activity for several V3 peptides from clades A, D, G, and H; essentially no reactivity could be demonstrated with V3 peptides from clades E and O. Extensive cross-clade reactivity was also documented by enzyme-linked immunosorbent assay with all nine recombinant HIV envelope glycoproteins tested from clades B, D, and E. In addition, vaccinees' sera displayed significant neutralizing activity against 5 of 14 primary isolates tested, including one X4 virus and two dualtropic viruses (from clade B) and two R5 viruses (from clades B and C). This is the first demonstration of the induction by a candidate HIV vaccine constructed from clade B laboratory strains of HIV of neutralizing activity against R5 and clade C primary isolates. The data suggest that, by virtue of their ability to induce cross-clade immune responses, appropriately formulated HIV vaccines based on a finite number of HIV isolates may ultimately be able to protect against the wide range of HIV isolates affecting the populations of many geographic regions.

AIDS Vaccines↗
PubMed2000

[Frequency of cesarean sections in Austria].

OBJECTIVE: While there exist detailed reports on the frequency of cesarean sections in many European countries, there are only selective data of single centers available in Austria. Thus this study aims at evaluating the present frequency of cesarean sections in Austria. METHODS: To achieve this aim, we analyzed all births during the years 1996 (n = 89,208), 1997 (n = 84,408) and 1998 (n = 81,568). Along with the general mean rate of sections, we also describe the influences of the duration of pregnancy, of the birth weight, and of the number of paturitions. The data were statistically evaluated by chi-square test. RESULTS: During the study period, the frequence of sections rose from 13.08% (1996) to 14.0% (1997) and to 14.55% (1998). This rise proved to be statistically significant (p = 0.0001). 47% of premature births (< or = 35th week of gestation) are delivered by cesarean section. This rate drops to only 13.24% after the 35th week of gestation. Yet, more than half of pregnancies with dystrophic children (<2,000 g) are delivered by cesarean section even after the 35th week of gestation. Primigravidae have to expect section in 17% of the cases (1998); the section rate diminishes continuously, however, with increasing number of pregnancies. CONCLUSIONS: Following the general trend, the frequency of cesarean sections is continuously rising in Austria too. The present study can serve as a basis for international comparisons as well as for measures of intradepartmental quality control.

Austria↗
PubMed2000

The thioredoxin boxes of thyroglobulin: possible implications for intermolecular disulfide bond formation in the follicle lumen.

Multimerization of thyroglobulin (TG) takes place extracellularly in the thyroid follicle lumen and is regarded as a mechanism to store TG at high concentrations. Human thyroglobulin (hTG) has been shown to multimerize mainly by intermolecular disulfide cross-links. We recently noted that TG of various mammalian species contains three highly conserved thioredoxin boxes (CXXC). This sequence is known to underlie the enzymatic activity of protein disulfide isomerase (PDI). As hTG formed intermolecular disulfide bonds in the absence of other proteins depending on the redox conditions and hTG concentration, the CXXC-boxes of TG might provide the structural basis for self-assisted intermolecular cross-linking. To test this hypothesis we prepared a recombinant TG fragment containing the three thioredoxin boxes. This fragment exhibited a redox activity amounting to about 10% of the activity of PDI at redox conditions supposed to be present in the extracellular space. This activity might be supplemented by the oxidizing system of the apical cell surfaces of thyrocytes facing the follicle lumen. Indeed, incubation of hTG with peroxidase and H202 resulted in intermolecular disulfide bridge formation. Our results suggest a combined mechanism of self-assisted and peroxidase-mediated disulfide bond formation leading to the intermolecular cross-linking of lumenal hTG.

Animals↗
PubMed2000

Prospective analysis after coronary-artery bypass grafting: platelet GP IIIa polymorphism (HPA-1b/PIA2) is a risk factor for bypass occlusion, myocardial infarction, and death.

Recently, we have demonstrated that human platelet antigen 1b (HPA-1b or P1A2) is a hereditary risk factor for platelet thrombogenicity leading to premature myocardial infarction in preexisting coronary artery disease. However, HPA-lb does not represent a risk factor for coronary artery disease itself. The aim of our present study was to evaluate the role of HPA-lb on the outcome in patients after coronary-artery bypass surgery. We prospectively determined the HPA-1 genotype in 261 consecutive patients prior to saphenous-vein coronary-artery bypass grafting. The patients were followed for one year. Among patients with bypass occlusion, myocardial infarction, or death more than 30 days after surgery, the prevalence of HPA-lb was significantly higher than among patients without postoperative complications (60 percent, 6/10, vs. 24 percent, 58/241, p <0.05, odds ratio 4.7). Using a stepwise logistic regression analysis with the variables HPA-1b, age, sex, body mass index, smoking (pack-years), hypertension, diabetes, cholesterol and triglyceride concentration, only HPA-lb had a significant association with bypass occlusion, myocardial infarction, or death after bypass surgery (p = 0.019, odds ratio 4.7). This study shows that HPA-1b is a hereditary risk factor for bypass occlusion, myocardial infarction, or death in patients after coronary-artery bypass surgery.

Aged↗
PubMed2000

Reconstruction of the contracted ocular socket with free full-thickness mucosa graft.

Patients who have undergone enucleation of the eye can be treated with glass eye prostheses, provided retention is adequate. Inadequate retention due to contraction of the conjunctival mucosa is a common problem which frequently affects the lower fornix first. This can be corrected using a free full-thickness buccal mucosa graft. Indications, operative procedures and postoperative results are presented.

Adult↗
PubMed2000

Contribution of whole body F-18-FDG-PET and lymphoscintigraphy to the assessment of regional and distant metastases in cutaneous malignant melanoma. A pilot study.

AIM: This pilot study describes use of whole body PET (WB PET) for staging of melanoma. WB PET in conjunction with lymphoscintigraphy (LS) for evaluating status of the sentinel lymph node (SLN) in primary melanoma was investigated with comparison to histopathological results. WB PET was also used both for primary and metastatic melanoma for screening for distant metastases, restaging and follow-up. METHODS: Group I: 17 patients with primary cutaneous melanoma underwent LS, WB PET and SLN dissection. WB PET findings were compared with biopsy results at the SLN site and were used for screening for distant metastases. Group II: 17 patients with a history of melanoma underwent WB PET for follow-up and/or restaging. Results were confirmed or refuted by other radiological modalities or by biopsy or clinical follow-up. RESULTS: Group I: out of 20 SLNs identified by LS in the 17 patients, 18 were negative on WB PET and 2 were positive. 19/20 WB PET findings were confirmed either by histopathology or by clinical follow-up (20 mo). Accuracy was 94% for the assessment of the status of the SLN. Group II: WB PET findings altered staging and treatment in 12/17 patients and confirmed the validity of treatment in 3/17 patients. Overall, in 15/17 patients (88%), WB PET had an impact on treatment strategy. CONCLUSION: Further studies are required to demonstrate if WB PET can become a reliable non-invasive alternative to surgery in the characterization of the SLN. WB PET is important as a baseline in primary localized melanoma and decisively impacts patient management in metastatic melanoma.

Adult↗