Unusual pseudoaneurysm of an axillofemoral bypass caused by seat belt trauma: case report.
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Accidents, Traffic↗
Biomedical subjects
K Krüger
Publications and source records attributed to K Krüger.
New modular delivery system for diagnostic and therapeutic pre-targeting using tautomer-specific monoclonal antibody EM-6-47 and 3-substituted adenines.
We have developed a new modular affinity system for the 2-step delivery of functional molecules to target cells. The system is based on the tautomer-specific monoclonal antibody (MAb) EM-6-47, which binds to 3- and 3,8-substituted adenines with high affinity (Ka > 10(9) l/mol) without cross-reacting with naturally occurring purine derivatives. This MAb serves as the hapten-specific fusion partner to produce bispecific MAbs (bs-MAbs) recognizing a target cell antigen and a low-m.w. hapten as carrier molecule for, e.g., radionuclides. Either the C-8 or the N-3 position of adenines can be used for conjugation with effector molecules; the remaining position may be substituted with different moieties to modulate the pharmacokinetics of the haptens. Different 3- and 3,8-substituted adenines conjugated to the chelates DOTA and DTPA or to the drug daunomycin were synthesized. Adenine-chelate derivatives were efficiently labeled with (111)In and 90Y, while high-affinity binding of 3-substituted adenines to MAb EM-6-47 remained almost unaffected by the conjugation to radiochelates. To confirm the validity of the delivery system, a prototype bs-MAb, EM-168-47, was generated by somatic cell fusion of MAb EM-6-47 and MAb EM-168-2, the latter recognizing a surface antigen on canine hematopoietic cells. Two-step targeting assays in vitro verified the bs-MAb-mediated, dose-dependent delivery of (111)In-labeled adenine-chelate derivatives to myeloid cells. This system represents a powerful tool for new pre-targeting approaches relying on bs-MAbs and low-m.w. haptens. Suitable cellular antigens can be targeted by fusing the appropriate MAbs with hapten-specific MAb EM-6-47, and tailor-made 3-substituted adenines may be labeled with diagnostic or therapeutic radionuclides, cytotoxic drugs or other functional molecules.
Adenine↗
The transcriptional activator GvpE for the halobacterial gas vesicle genes resembles a basic region leucine-zipper regulatory protein.
The GvpE protein involved in the regulation of gas vesicles synthesis in halophilic archaea has been identified as the transcriptional activator for the promoter located upstream of the gvpA gene encoding the major gas vesicle structural protein GvpA. A closer inspection of the GvpE protein sequence revealed that GvpE resembles basic leucine-zipper proteins typically involved in the gene regulation of eukarya. A molecular modelling study of the C-terminal part implied a cluster of basic amino acid residues constituting the DNA-binding site (DNAB) followed by an amphiphilic helix, suitable for the formation of a leucine-zipper structure within a GvpE dimer. The model of a GvpE dimer docked onto DNA indicated that the side-chains of the basic residues could perfectly interact with the negatively charged phosphate groups of the DNA backbone. Substitution of three basic amino acid residues of this putative DNAB by alanine and/or glutamate generated mutated GvpE proteins. None of these was able to activate the c-gvpA promoter in vivo, indicating that these basic residues are required for GvpE activity. This identification of an archaeal gene regulator displaying similarity to eukaryal regulatory proteins implies that the basic transcription machinery of eukarya and archaea are closely related, and that the regulatory proteins have evolved according to common principles.
Amino Acid Sequence↗
Reproductive outcome in offspring of parents occupationally exposed to lead in Norway.
In Norway, great efforts have been made to protect both male and female employees against teratogenic exposures. Associations between occupational lead exposure and reproductive outcome in the offspring were studied. All births in Norway 1970-1993 with possible maternal or paternal occupational lead exposure were compared with a reference population of offspring of parents without occupational lead exposure. Offspring of lead exposed mothers had an increased risk of low birth weight (RR = 1.34; CI = 1.12-1.60) and neural tube defects (RR = 2.87; CI = 1.05-6.38). Effects on birth weight and gestational age showed significant dose-response associations. Offspring of lead exposed fathers had no increased risks of any of the analyzed reproductive outcomes. However, decreased risks were observed of low birth weight (RR = 0.91; CI = 0.86-0.96) and preterm birth (RR = 0.89; CI = 0.86-0.93). Further efforts seem to be needed to protect the offspring of lead-exposed mothers.
Birth Weight↗
[Severe toe gangrene as an early manifestation of Wegener granulomatosis in a young patient].
Gangrene of digits is a very rare manifestation of Wegener's granulomatosis (WG). We report a case of a 29-year-old woman with nonspecific symptoms like fever, weight loss, arthralgia, arthritis and high systemic inflammatory signs. On the grounds of a presumed infection the patient was treated with antibiotics which showed no effect. Within short she complained of pain and paresthesia of the right foot with a rapid lividity. Angiography demonstrated multiples stenoses and multisegmental occlusions of the lower leg arteries. Together with renal and pulmonal symptoms a WG was suspected, the diagnosis being confirmed by kidney biopsy and positive cANCAs. A few months after starting a combined therapy with cyclophosphamide and corticosteroids the patient showed a partial remission with a residual toe gangrene. Comparing the five worldwide reported cases with digital gangrene and our presentation there is a concordance of all in the occurrence of an extremely high disease activity together with a glomerulonephritis. The findings of p-ANCAs in our patient and positive Hbs antigen in another case of WG with digital gangrene suggests a relation to panarteriitis nodosa, where gangren is more common.
Adult↗
[Need and possibilities for quality management in drug therapy of patients with rheumatic diseases].
Only during recent years have intensive attempts been made to install a program for more objectively based quality criteria instead of the traditional subjectively and empirically determined therapeutic decisions for the application of DMARDs. The optimized quality management for this treatment should focus on factors such as: diagnosis as early as possible (basic for the introduction of DMARD therapy), reliable assessment of the individual long-term prognosis (as an important aid in the choice of the appropriate drug), prompt determination and establishment of the chosen therapy, and an optimal long-term application of this treatment (including competent control of effectiveness, tolerance, and compliance). Instrumentation for these purposes have been so far only partly available, e.g., diagnostic criteria and control guidelines. Besides the partially missing appropriate measures, maximum quality management is presently opposed by insufficient rheumatological specialist care for many RA patients--caused by the lack of specialists and a dilatory attitude towards involving them, respectively. Nevertheless, there is hope that in the course of new developments the gap between needs and benefits of quality management will grow smaller.
Antirheumatic Agents↗
Lactate in scalp and cord blood from fetuses with ominous fetal heart rate patterns.
OBJECTIVE: We investigated lactate concentrations in fetal scalp and cord blood to determine the sources of fetal lactacidosis in fetuses with ominous heart rate patterns. METHODS: Cord blood was collected from newly delivered infants who had been monitored by fetal scalp blood sampling during labor. In 250 cases umbilical arterial and venous cord blood lactate levels were measured. We assessed the umbilical arterial lactate concentrations in relation to the venous lactate levels, the arterial pH level, base excess, and arteriovenous lactate differences in cord blood. In 103 cases the levels of lactate in fetal scalp blood, sampled within 60 minutes of delivery, were compared with those in the umbilical artery and vein and the pH level and base excess immediately after birth. RESULTS: Lactate level in the umbilical artery showed a significant correlation to that in umbilical venous blood (r = .84, P < .001), to arteriovenous lactate differences (r = .52, P < .001), as well as to pH (r = -.55, P < .001) and base excess (r = -.63, P < .001) in arterial cord blood. Lactate concentrations in fetal scalp blood shortly before delivery showed a significant correlation to lactate levels in the umbilical arterial (r = .65, P < .001) and venous blood (r = .62, P < .001). CONCLUSION: The study indicates a close correlation between lactate levels in arterial and venous cord blood, as well as between the lactate levels and pH and base excess in cord arterial blood in patients with ominous fetal heart rate patterns. We also found an increased fetal contribution with increasing lactacidemia. Lactate concentrations in fetal scalp blood correlated well with those in cord arterial and venous blood.
Female↗
Anisotropy of chemical shift and J coupling for P-31 and Se-77 in trimethyl and triphenyl phosphine selenides.
The 31P and 77Se magic angle spinning (MAS) nuclear magnetic resonance (NMR) experiments for selenium-77 enriched (70%) trimethylphosphine selenide 1 and triphenylphosphine selenide 2 were carried out in order to determine the nuclear magnetic shielding tensors of both nuclei and to establish values of the phosphorus-selenium indirect spin-spin coupling anisotropy delta J. The m = +1/2 and m = -1/2 subspectra were analysed by the dipolar-splitting-ratio method of Eichele and Wasylischen. For the C(S) molecule 1, delta J was obtained to be +640 +/- 260 Hz from the 31P spectrum and +550 +/- 140 Hz from the 77Se spectrum. Density functional theory (DFT) calculations give a delta J value of about +705 Hz. The value of delta J could not be determined unambiguously by analysis of the 31P spectra for the C1 molecules 2; nevertheless, an estimation of delta J was possible. The principal axis 3 of the phosphorus shielding tensor was determined to be nearly parallel to the PSe bond in 1 and 2. For the selenium shielding of 1, the same orientation was found, whereas in 2, the principal axis 2 of the selenium shielding was found to be oriented nearly along the PSe bond. The experimentally determined phosphorus nuclear magnetic shielding tensors agree well with those calculated by the IGLO method. For those two principal values of the selenium-shielding tensors corresponding to directions nearly perpendicular to the SeP bond, the agreement between calculated and experimental values is satisfactory. For the third one, corresponding to the principal axis close to the SeP bond, the calculated deshielding contributions are distinctly too small for both compounds investigated. Trends observed for the calculated molecular orbital (MO) contributions to the shielding as well as possible reasons for the underestimation of the deshielding contributions along the SeP bond are discussed.
Anisotropy↗
[Direct-current treatment of chemically induced mammary carcinoma in an animal model: MR volumetric assessment of the effect of the therapy].
PURPOSE: To investigate the effect of direct current treatment (DCT) on the growth of mammary carcinomas in rats by MR-volumetry. METHODS: Chemically induced mammary adenocarcinomas in a control group (n = 17) were compared with treated tumours (18 C/cm3 in group A: n = 7 or 36 C/cm3 in group B: n = 12). 31 untreated tumours were situated near a treated tumour (group C). Experiments were carried out using one positive electrode in the tumour centre and three negative electrodes in the periphery. The tumour volume was measured by MRI before, and 1, 3, 6, 9 and 12 weeks after treatment. RESULTS: 12 weeks after DCT, the mean tumour volume in group A (164% +/- 158%, p < 0.05) and group B (13% +/- 24%, p < 0.001) was significantly reduced compared to the control group (434% +/- 230, Mann-Whitney U-Test). Complete tumour regression occurred in 42% of tumours in group B and was not achieved in group A, C and control group. Tumour growth in group C was decreased compared to the control group. CONCLUSIONS: The effectiveness of DCT was found to depend on the applied dosage -36 C/cm3 was more effective than 18 C/cm3. The effect of DCT is not limited to the area between the electrodes.
9,10-Dimethyl-1,2-benzanthracene↗
Reperfusion after thrombolytic therapy of embolic stroke in the rat: magnetic resonance and biochemical imaging.
The effect of thrombolytic therapy was studied in rats submitted to thromboembolic stroke by intracarotid injection of autologous blood clots. Thrombolysis was initiated after 15 minutes with an intracarotid infusion of recombinant tissue-type activator (10 mg/kg body weight). Reperfusion was monitored for 3 hours using serial perfusion- and diffusion magnetic resonance imaging, and the outcome of treatment was quantified by pictorial measurements of ATP, tissue pH, and blood flow. In untreated animals, clot embolism resulted in an immediate decrease in blood flow and a sharp decrease in the apparent diffusion coefficient (ADC) that persisted throughout the observation period. Thrombolysis successfully recanalized the embolized middle cerebral artery origin and led to gradual improvement of blood flow and a slowly progressing reversal of ADC changes in the periphery of the ischemic territory, but only to transient and partial improvement in the center. Three hours after initiation of thrombolysis, the tissue volume with ADC values less than 80% of control was 39 +/- 22% as compared to 61 +/- 20% of ipsilateral hemisphere in untreated animals (means +/- SD, P = .03) and the volume of ATP-depleted brain tissue was 25 +/- 31% as compared to 46 +/- 29% in untreated animals. Recovery of ischemic brain injury after thromboembolism is incomplete even when therapy is started as early as 15 minutes after clot embolism. Possible explanations for our findings include downstream displacement of clot material, microembolism of the vascular periphery, and events associated with reperfusion injury.
Adenosine Triphosphate↗
Improved model of thromboembolic stroke and rt-PA induced reperfusion in the rat.
We report the technical details and validation of an improved rat model for thromboembolic stroke and rt-PA induced reperfusion, which closely resembles clinical embolic stroke. The middle cerebral artery (MCA) was proximally occluded by injection of twelve medium sized (1.5 x 0.35 mm), fibrin-rich autologous blood clots. On inspection, densely packed clot material was found at the ipsilateral MCA origin in all untreated animals. Autoradiographic rCBF measurements showed severe ischemic deficit throughout the ipsilateral MCA territory in untreated animals. The volume in which flow values fell below 30 ml/100 g per min was 54 +/- 14% of the hemispheric volume. In all rt-PA treated animals the proximal MCA was recanalised, and the volume with flow values below 30 ml/100 g per min was reduced to 29 +/- 17%. Histological findings paralleled the spatial spread of the CBF deficit. The rat model presented is well-suited for investigations of the specific pathophysiology of thromboembolic stroke. Furthermore it allows detailed studies of thrombolytically induced reperfusion, beyond the question of successful recanalisation.
Animals↗
Male proportion in offspring of parents exposed to strong static and extremely low-frequency electromagnetic fields in Norway.
Reduced male proportion in offspring of male carbon setters prompted a study into whether offspring of workers exposed to strong static and extremely low-frequency electromagnetic fields (ELF) had a deviant sex ratio. The study was based on all births in Norway 1970-1993. The reference population was offspring of parents not exposed to ELF. The male proportion in offspring of men in aluminum works was 50.38%, RR 0.98 (0.94-1.03), in manganese works 47.32%, RR 0.92 (0.83-1.02), in factories producing iron 50.03%, RR 0.97 (0.93-1.02), in nickel works 48.27%, RR 0.94 (0.84-1.05), and in electric wire production 47.20%, RR 0.92 (0.80-1.05). In the offspring of women in aluminum works, the male proportion was 37.04%, RR 0.72 (0.59-0.90), in all smelter works grouped together, 45.13%, RR 0.88 (0.79-0.99). The male proportion in the reference population was 51.42%. The male proportion in offspring of men in industries with ELF, was slightly reduced, while offspring of women was significantly reduced.
Aluminum↗
Blood-brain barrier disturbances after rt-PA treatment of thromboembolic stroke in the rat.
We studied the effects of rt-PA (recombinant tissue type-plasminogen activator) treatment on the blood-brain barrier (BBB) after thromboembolic stroke in rat. New MRI methods of diffusion and perfusion imaging to observe the hemodynamic and biophysical effects of thrombolysis were combined with methods for assessment of BBB disturbances. In untreated animals clot embolism produced a rapid drop in MRI perfusion values and the ADC (apparent diffusion coefficient), with subsequent infarction. BBB disturbances, visualised as extravasation of serum proteins on cryostat sections, were manifest in nearly all animals in the borderzone of infarcts. In animals treated with rt-PA 15 min after clot embolism thrombolysis resulted in reperfusion of affected brain regions with subsequent improvement of ADC values. Final lesion size on ADC maps was reduced by 36% relative to untreated animals. However, BBB disturbances were not improved after treatment. To the contrary, rt-PA treated animals showed further regions with serum protein extravasation in the infarcted territories and in distant non-ischemic brain regions. MR imaging with the BBB tracer GdDTPA showed more pronounced and widespread contrast enhancement in the rt-PA treated than in the untreated group. Increased blood-brain barrier disturbances have to be taken into account even when thrombolytic therapy is started very early after the onset of stroke.
Animals↗
[Juvenile Adamantiades-Behçet disease in decreased stimulation with anti-CD3 monoclonal antibody].
A 12 year old boy developed the complete symptom complex of Adamantiades-Behçet's disease over a two-year period. He presented with the mucocutaneous variant with recurrent to persistent oral ulcers which extended into the pharynx, recurrent genital ulcers, perianal lesions, and a positive pathergy test. Ocular involvement and other symptoms associated with the disease were absent. However, the early onset of the disease and the male gender indicated a bad prognosis. The patients father deficiency of suffered from bronchial asthma with recurrent respiratory infections. An IgG-3 subclass was detected. Lymphocyte transformation tests showed markedly diminished response to stimulation with anti-CD3 monoclonal antibody in both patients, while response to PWM, CoA and PHA was normal. In addition, the concentration of serum soluble interleukin 6 receptor was reduced in both patients.
Antibodies, Monoclonal↗
Gas vesicle formation in halophilic Archaea.
Gas vesicles are intracellular, microbial flotation devices that consist of mainly one protein, GvpA. The formation of halobacterial gas vesicles occurs along a complex pathway involving 14 different gvp genes that are clustered in a genomic region termed the "vac region". Various vac regions found in Halobacterium salinarum (p-vac and c-vac), Haloferax mediterranei (mc-vac), and Natronobacterium vacuolatum (nv-vac) have been investigated. Except for the latter vac region, the arrangement of the gvp genes is identical. Single gvp genes have been mutated to study the effect on gas vesicle synthesis in transformants and to determine their possible function. Each vac region exhibits a characteristic transcription pattern, and regulatory steps have been observed at the DNA, RNA, and protein level, indicating a complex regulatory network acting during gas vesicle gene expression.
Archaeal Proteins↗
Low-frequency oscillations of visual, auditory and somatosensory cortical neurons evoked by sensory stimulation.
Low-frequency oscillations-LFOs-below 20 Hz in the activity of cortical neurons are a commonly observed property across all sensory modalities. However, the functional significance and potential role of these intrinsic oscillations are not well understood. Here, we attempt to provide a general framework for the interpretation of this phenomenon by considering its properties across several sensory modalities. In the first part, we provide a survey and a general description of low-frequency oscillations (LFOs) at a cellular level observed following adequate [Basar, and Schürmann, 1994]. Sensory stimulation of neurons recorded in three sensory modalities of neocortices in higher mammals. The second part will address some functional aspects of low-frequency oscillations (LFOs) such as stimulus selectivity and so-called 'interference' phenomena, specifically with findings related to 'resetting' and 'gating' of sensory processing streams. Finally, a hypotheses is outlined in which the low-frequency oscillations are regarded as an organizational principle by which continuity of sensory and motor states over time could be accomplished.
Acoustic Stimulation↗
[A proposal for the MR staging of early rheumatoid arthritis in the metacarpophalangeal and proximal interphalangeal joints].
PURPOSE: MRI can demonstrate pathology of joint disease in the early course of rheumatoid arthritis prior to destructions seen on conventional radiographs. In a prospective study, we tried to develop a systematical classification of joint pathology demonstrated by MRI, which would be essential for scoring the course of the disease. PATIENTS AND METHOD: Metacarpophalangeal and interphalangeal joints of 48 patients suffering from early rheumatoid arthritis (mean disease duration: 6.4 months) were evaluated by MRI using a high-resolution transmitter-receiver coil. Examinations included 2 mm sliced T2-, T1- and gadolinium enhanced T1-SE sequences in coronal and axial orientation. In consideration of pathological findings on MRI and histopathogenetical pathways of destruction in rheumatoid arthritis a MR-score (0-5) was established. RESULTS: This allowed to score each joint examined: score 0 (normal) in 47.8%/49.5%, score 1 in 35.5%/50.5%, score 2 in 4.2%/0%, score 3 in 10.8%/0%, score 4 in 1.5%/0% of the metacarpophalangeal/interphalangeal joints, respectively. CONCLUSIONS: Using the MR-score a relative individual destruction number can be calculated, which may be used to follow up patients in the early course of rheumatoid arthritis (e.g. drug therapy studies). The presented MR scoring system has to be evaluated further in longitudinal studies and must be correlated to radiographical and clinical findings.
Adult↗
Nontraumatic subarachnoid hemorrhage: value of repeat angiography.
PURPOSE: To evaluate the benefits and risks of repeat cerebral angiography in patients with subarachnoid hemorrhage of unknown cause. MATERIALS AND METHODS: Findings from 391 angiographic examinations (323 initial, 68 repeat) were retrospectively reviewed in 323 patients with nontraumatic subarachnoid hemorrhage to determine the cause of bleeding and the frequency of complications with neurologic deficit. RESULTS: At the initial angiographic examination, aneurysms were found in 195 patients (60.4%), and arteriovenous malformations were found in 11 patients (3.4%). Sixty-six patients with negative findings at initial examination underwent repeat cerebral angiography. Three additional aneurysms were detected, all of which could be seen retrospectively on the initial angiogram. In 63 patients, the cause of bleeding remained unexplained. Complications of the 391 angiographic examinations were definitive neurologic deficits in one patient (0.2%) and transient deficits in seven patients (1.8%). CONCLUSION: Repeat angiography is not necessary in patients with subarachnoid hemorrhage if technically good, carefully evaluated digital subtraction angiography was performed initially. Repeat angiography seems to be justified only when the initial examination is technically inadequate, when vasospasm is present, or if further bleeding occurs.
Adolescent↗