Biomedical subjects

A Beck

Publications and source records attributed to A Beck.

At least 91 records · Page 5Linked to original sources

PubMed2001

[Fractures involving the distal femoral epiphysis. Long-term outcome after completion of growth in primary surgical management].

During a period of 12 years (1983-1994) we operated 13 patients with fractures involving the distal epiphyseal cartilage of the femur. All patients could be followed up in clinical and radiological examination following the completion of growth. By examination no patients had any complaints. The clinical examination revealed no limitation in range of motion of the hip or knee joint compared to the other side in any of the patients. 5 patients out of 13 (38%) were found to have a correct axial alignment with no axis deviation, shortening or lengthening of the leg. The other 8 patients (62%) presented the following one- or multidimensional deformities (compared to the contralateral, uninjured femur): 2 patients had varus deformities, 5 patients had valgus deformities, the axial malalignment in the frontal plane was always less than 10 degrees in all cases. 5 patients were found to have a shortened femur (between 8 and 19 mm), while an elongation of the primarily injured femur (10 and 15 mm) was established in 2 patients. On the basis of this study, we recommend that clinical and, if necessary, radiological and/or sonographic examinations are performed following the completion of growth in all patients with injuries involving the epiphyseal plate of the distal femur.

Adolescent↗

PubMed2001

[Evaluation of cartilage changes within the scope of second-look arthroscopy 12 months after surgical reconstruction of anterior cruciate ligament rupture].

The anterior cruciate ligament (ACL) rupture is among the most frequent injuries of the joints. Actually, there is no doubt regarding the necessity for surgical treatment. However, little is known about the progression of osteochondral damages and their distribution following reconstruction of the ACL. We treated 150 tears of the ACL either acute (median 7d) with augmented reinsertion (n = 41) and with autologous bone patella tendon graft (n = 24) or chronic (median 369d) with autologous bone patella tendon graft (n = 85). The study design was prospective. All osteochondral defects were documented in the six compartments. Second look arthroscopy and clinical examination were performed after twelve months in the course of removal of implants and possible changes of the osteochondral state were evaluated. Detoriation of osteochondral state was seen in 86 (57%) of 150 patients, while there was no statistical difference between the three groups. The time of operation had no influence on the osteochondral damage. There was a significant increase of chondral damages in the medial and retropatellar compartment after autologous bone patella tendon graft, while the changes after augmented reinsertion were diffuse. There were no significant differences in the clinical examination between the three groups regarding the Lysholm score and the functional and subjective outcome. However, postoperative instability was frequently observed (positive pivot-shift 25%, positive Lachmann test 57%). We suggest that postoperative instability should have led to the increased osteochondral damages.

Adult↗

PubMed2001

MRI in isolated sixth nerve palsies.

In previous studies the origin of the majority of isolated sixth nerve palsies was not clear or was ascribed to vascular disease. Our purpose was determine how frequently a causative lesion was demonstrated on MRI in patients with an acute unilateral sixth nerve palsy. We performed a prospective study of 43 patients using a standardised protocol. In 27 patients (63%) a lesion was identified on the initial MRI relevant to the sixth nerve palsy; 21 (49%) were found to have a tumour or tumour-like lesion; the frequency of presumed vasculopathy in this group was 15%. There were 16 patients (37%) with an initially normal MRI, of whom 10 (62%) had a history of vasculopathy, a significantly different proportion from the group of patients with a visible causative lesion. MRI after 3-6 months was normal in all patients with a normal initial MRI. We suggest that MRI should routinely be performed in patients presenting with an acute sixth nerve palsy, even those with evidence of a vasculopathy. If the symptoms regress spontaneously and there is a history of vasculopathy, follow-up MRI is not necessary.

Abducens Nerve↗

PubMed2001

Excimer laser-assisted recanalisation of femoral arterial stenosis or occlusion caused by the use of Angio-Seal.

The aim of this study was to demonstrate the effect of excimer laser and balloon angioplasty of femoral artery stenosis and occlusion after use of a haemostatic puncture closure device. A haemostatic puncture closure device (Angio-Seal) was used in 6000 patients after diagnostic or therapeutic artery catheterisation. In 34 of those patients symptoms of peripheral artery disease occurred. Sixteen of those 34 cases were transferred to our clinic for excimer laser angioplasty. All 16 patients presented with symptoms of acute peripheral artery disease within 1-14 days: superficial femoral artery (SFA) occlusions (4 cases); superficial femoral artery stenosis (3 cases); high-grade stenosis of the common femoral artery (CFA; 3 cases); high-grade stenosis of CFA; SFA and profund femoral artery (PFA; 3 cases); and occlusions of CFA, SFA and PFA (3 cases). Before any procedure was performed, informed consent was given by the patient, which included the use of the Angio-Seal closure device. Every patient who had to undergo recanalisation procedures gave additional informed consent which especially included the usage of the excimer laser for recanalisation. A measurement of the walking distance, ankle-brachial systolic pressure index (ABI) and diagnostic angiography was performed in 13 cases before and immediate after as well as 3 and 6 months after therapeutic percutaneous transluminal laser angioplasty followed by balloon angioplasty (PTLA/PTA). In 3 patients the risks of PTLA/PTA was considered too high; those patients underwent surgical repair. Angiographic and clinical improvement was achieved in 13 of 13 patients. The mean walking distance increased from 81 to > 400 m. The average ankle-brachial systolic pressure index (ABI) increased from 0.47 to 0.84. One patient developed a dissection of the SFA, and in 1 case a peripheral embolisation was seen. The PTLA/PTA technique is a successful therapeutic option for patients with femoral artery occlusion or high-grade stenosis after Angio-Seal application.

Angioplasty, Balloon, Laser-Assisted↗

PubMed2001

The nail-insertion point in unreamed tibial nailing and its influence on the axial malalignment in proximal tibial fractures.

The consequence of choosing a point of insertion for the nail (i.e. medial or lateral of the lig. patellae) in unreamed tibial nailing (AO unreamed tibial nail, UTN) was studied in 22 formaldhyde-fixed tibiae. A lateral osteotomy at the transition from the first to the second fifth of the tibia was used as a model for the fracture. A nail insertion point medial of the lig. patellae caused a valgus deformity, combined with a shift of the distal fragment to the medial side. A lateral point of entry resulted in a varus deformity, together with a lateral shift of the distal fragment. Our results show that the insertion point of the nail is important for the alignment of the axis. Choosing a different point for the insertion of the nail can be useful in operative correction of malalignment of the tibia.

Biomechanical Phenomena↗

PubMed2001

Bursting activity in leech Retzius neurons induced by low external chloride.

We have investigated the bursting activity of Retzius neurons in the central nervous system of the leech Hirudo medicinalis as induced in Cl(-)-free saline by measuring membrane potential, membrane current and the intracellular calcium concentration ([Ca2+]i), using fura-2 or Oregon-Green488-Bapta-1. The Retzius neurons changed their low tonic firing to rhythmical bursting activity when the extracellular Cl- concentration ([Cl-]o) was lowered to 1 mM or less. In Cl(-)-free saline (Cl- exchanged by gluconate), bursting was accompanied by a rise in intracellular Ca2+ in both cell body and axon, which oscillated in synchrony with the bursts. The Ca2+ transients depended on the amplitude and duration of the depolarization underlying the burst, and were presumably due to Ca2+ influx through voltage-dependent Ca2+ channels. In Ca(2+)-free, EGTA-buffered saline or in the presence of Ca2+ channel blockers verapamil (1 mM) or diltiazem (500 microM) the depolarizations underlying the bursts in Cl(-)-free saline were enhanced in amplitude and duration. Bursting was not affected by depleting the intracellular Ca2+ stores with cyclopiazonic acid. The depolarization in Cl(-)- and Ca(2+)-free saline did not evoke intracellular Ca2+ changes. The burst-underlying membrane depolarization induced by Cl- removal was found to be due to a Na(+)-dependent persistent inward current and could be inhibited by saxitoxin (25-50 microM). The results suggest that a persistent Na+ current is generated in Cl(-)-free saline and induces the depolarization underlying rhythmic activity, and that presumably Ca(2+)-induced K+ currents modulate the bursting behaviour.

Animals↗

PubMed2001

Stability and CTL activity of N-terminal glutamic acid containing peptides.

Several cytotoxic T lymphocyte peptide-based vaccines against hepatitis B, human immunodeficiency virus and melanoma were recently studied in clinical trials. One interesting melanoma vaccine candidate alone or in combination with other tumor antigens, is the decapeptide ELA. This peptide is a Melan-A/MART-1 antigen immunodominant peptide analog, with an N-terminal glutamic acid. It has been reported that the amino group and gamma-carboxylic group of glutamic acids, as well as the amino group and gamma-carboxamide group of glutamines, condense easily to form pyroglutamic derivatives. To overcome this stability problem, several peptides of pharmaceutical interest have been developed with a pyroglutamic acid instead of N-terminal glutamine or glutamic acid, without loss of pharmacological properties. Unfortunately compared with ELA, the pyroglutamic acid derivative (PyrELA) and also the N-terminal acetyl-capped derivative (AcELA) failed to elicit cytotoxic T lymphocyte (CTL) activity. Despite the apparent minor modifications introduced in PyrELA and AcELA, these two derivatives probably have lower affinity than ELA for the specific class I major histocompatibility complex. Consequently, in order to conserve full activity of ELA, the formation of PyrELA must be avoided. Furthermore, this stability problem is worse in the case of clinical grade ELA, produced as an acetate salt, like most of the pharmaceutical grade peptides. We report here that the hydrochloride salt, shows higher stability than the acetate salt and may be suitable for use in man. Similar stability data were also obtained for MAGE-3, another N-terminal glutamic acid containing CTL peptide in clinical development, leading us to suggest that all N-terminal glutamic acid and probably glutamine-containing CTL peptide epitopes may be stabilized as hydrochloride salts.

Animals↗

PubMed2001

A candidate prostate cancer susceptibility gene at chromosome 17p.

It is difficult to identify genes that predispose to prostate cancer due to late age at diagnosis, presence of phenocopies within high-risk pedigrees and genetic complexity. A genome-wide scan of large, high-risk pedigrees from Utah has provided evidence for linkage to a locus on chromosome 17p. We carried out positional cloning and mutation screening within the refined interval, identifying a gene, ELAC2, harboring mutations (including a frameshift and a nonconservative missense change) that segregate with prostate cancer in two pedigrees. In addition, two common missense variants in the gene are associated with the occurrence of prostate cancer. ELAC2 is a member of an uncharacterized gene family predicted to encode a metal-dependent hydrolase domain that is conserved among eukaryotes, archaebacteria and eubacteria. The gene product bears amino acid sequence similarity to two better understood protein families, namely the PSO2 (SNM1) DNA interstrand crosslink repair proteins and the 73-kD subunit of mRNA 3' end cleavage and polyadenylation specificity factor (CPSF73).

Amino Acid Sequence↗

PubMed2001

[Gastrointestinal autonomic nerve tumor].

Gastrointestinal autonomic nerve tumors (GAN-tumor) are rare malignant neurogenic stromal tumors of the intestinal tract. The origin is suspected in the autonomic nerve plexus Meissner or Auerbach with the interstitial cells of Cajal as precursors. We report on a 53-year-old patient with a clinical apparent and radiological 5 cm measuring tumor of the jejunum, which was resected and immunohistochemically verified as GAN-tumor. Within the follow-up of 29 months metastases appeared within the omentum majus with a diffuse peritoneal spreading. Several trials of adjuvant chemotherapy (adriamycine/ifosamide, taxotere, gemcitabine/xyloda) were ineffective. 15 months after the second operation the patient died. Since the first description of the GAN-tumor in 1984 87 patients were reported in the literature. No recurrences or metastasis were seen in tumors with a seize less than 5 cm. A tumor seize of more than 10 cm is associated with recurrences in 64% of the cases within 2 years. Since there is no option for medical treatment, surgical resection is the treatment of choice and has to be considered also in the case of recurrence.

Autonomic Nervous System↗

PubMed2001

Targeting of nasal mucosa-associated antigen-presenting cells in vivo with an outer membrane protein A derived from Klebsiella pneumoniae.

Administration of vaccines by the nasal route has recently proven to be one of the most efficient ways for inducing both mucosal and systemic antibody responses in experimental animals. Our results demonstrate that P40, a well-defined outer membrane protein A from Klebsiella pneumoniae, is indeed a carrier molecule suitable for nasal immunization. Using fragments from the respiratory syncytial virus subgroup A (RSV-A) G protein as antigen models, it has been shown that P40 is able to induce both systemic and mucosal immunity when fused or coupled to a protein or a peptide and administered intranasally (i.n.) to naive or K. pneumoniae-primed mice. Confocal analyses of nasal mucosa-associated lymphoid tissue after i.n. instillation of P40 showed that this molecule is able to cross the nasal epithelium and target CD11c-positive cells likely to be murine dendritic cells or macrophages. More importantly, this targeting of antigen-presenting cells following i.n. immunization with a subunit of the RSV-A molecule in the absence of any mucosal adjuvant results in both upper and lower respiratory tract protection against RSV-A infection.

Adjuvants, Immunologic↗

PubMed2001

Increase in mortality rates from intrahepatic cholangiocarcinoma in England and Wales 1968-1998.

BACKGROUND: The age standardised mortality rate per 100 000 population for all causes of liver tumours (International Classification of Disease 9 (ICD-9) 155) has almost doubled in England and Wales during the period 1979-1996. We further analysed the mortality statistics to determine which anatomical subcategories were involved. METHODS: Mortality statistics for liver tumours of ICD-9 155, 156, and subcategories, and for tumours of the pancreas (ICD-9 157), in England and Wales were investigated from the Office for National Statistics, London, from 1968 to 1996 inclusive. Data for 1997 and 1998 were also available on intrahepatic cholangiocarcinomas. RESULTS: There has been a marked rise in age standardised mortality rates for intrahepatic cholangiocarcinoma. Since 1993, it represents the commonest recorded cause of liver tumour related death in England and Wales. This is evident in age groups older than 45 years. In contrast, mortality trends from other primary liver tumours, including hepatocellular carcinoma, were unremarkable. CONCLUSIONS: The observed increase in mortality from intrahepatic cholangiocarcinoma may represent better case ascertainment and diagnosis due to improved diagnostic imaging, use of image guided biopsies, or increased use of ERCP. However, the trend started before ERCP was introduced nationally, mortality rates have continued to increase steadily thereafter, and there is no clear evidence that diagnostic transfers easily explains the findings. Alternatively, these observations may represent a true increase in intrahepatic bile duct tumours. Epidemiological studies are required to determine whether there is any geographical clustering of cases around the UK.

Adult↗

PubMed2001

Nurse caregiver feelings about agitation in Alzheimer's disease.

This study examines the feelings of nurse caregivers of patients with Alzheimer's disease (AD) who are agitated. Methods included participant observation, examination of medical records, and ethnographic interviews of 17 nurse caregivers from one inpatient setting. Two patterns of feelings emerged from the data. One pattern was associated with caregiver expressions of personal identification with and vulnerability to AD. These nurses endorsed feelings of helplessness, men hopelessness, and frustration when providing care to agitated AD patients. A second pattern situated nursing interactions within the realistic context of the patient's response to the illness. Caregiver feelings of confidence, competence, and satisfaction were associated with the second pattern. The relationship between the feeling states of nurse caregivers and their reported management of agitation in AD is discussed. Recognition and awareness of distressing feelings is a necessary first step for nurses to learn less personalized reactions to patients and respond more objectively to agitated behaviors.

Aged↗

PubMed2001

Stress analysis of the aortic valve with and without the sinuses of valsalva.

BACKGROUND AND AIM OF THE STUDY: In some patients with dilated aortic root, attempts have been made to replace the aorta and preserve the anatomically normal leaflets. The tubular Dacron graft used in the valve-sparing procedure does not have the sinuses of Valsalva, and therefore might adversely affect the valve. The effect of the presence or absence of the sinuses was investigated on stresses in the leaflets. METHODS: Finite element models of the tubular aortic root and the root with the sinuses were constructed. The model dimensions were: aorta radius 13 mm; valve height 18 mm; leaflet thickness 0.5 mm; aorta and sinus wall thickness 1.3 mm. In the root with the sinuses, each leaflet-sinus unit formed a cylindrical geometry. The model was loaded with an internal pressure of 80 mmHg (0.01 N/mm2) and the stress determined. RESULTS: The stress in the leaflet belly was 0.26 N/mm2, and not affected by the geometry and stiffness of the root. In the tubular root there was a stress concentration along the leaflet attachment, and the stress reached 0.65 N/mm2; in contrast, in the sinus root there was no stress concentration and maximum stress was only 0.3 N/mm2. Under pressure, the leaflet-sinus assembly expanded in a uniform manner, whereas in a tubular root large deformations occurred along the leaflet attachment. CONCLUSION: The sinuses of Valsalva play a very important role in minimizing stress in the leaflets; thus, use of the sinus graft is expected to enhance the longevity of the spared valve.

Aortic Valve↗

PubMed2000

Spanning or looping? The order and conformation of bipolar phospholipids in lipid membranes using 2H NMR spectroscopy.

Solid-state 2H NMR spectroscopy was used to study and characterize the conformation and order of bolaform lipid membranes. A series of 2H-labeled bolaform phosphatidylcholines has been synthesized and their properties compared to a [D4]dimyristoylphosphatidylcholine (DMPC) and a [D8]-32 macrocyclic phosphatidylcholine. 31P NMR measurements establish that the aqueous dispersions of these lipids adopt lamellar phases. Computational dePakeing was used to extract the spectrum of the oriented system from spectra consisting of a superposition of randomly oriented domains in an unoriented sample. A large (> 90 %) and constant value for the normalized segmental order parameter (Smol) was observed for all positions along the diacyl chain of the bolaform lipids and only a small population (< 10%) of a less ordered conformer was observed. The less ordered conformer is assigned to the looping conformation on the basis of comparison with the deuterated macrocyclic phospholipid which has an enforced loop in its diacyl chain. The predominant population(> 90%) of the bolaform lipids is assigned to a highly ordered, spanning conformer.

Deuterium↗

PubMed2000

Priming by microbial antigens from the intestinal flora determines the ability of CD4+ T cells to rapidly secrete IL-4 in BALB/c mice infected with Leishmania major.

Infection of BALB/c mice with Leishmania major results in the rapid accumulation of IL-4 transcripts within CD4(+) T cells that react to the parasite Leishmania homologue of mammalian RACK1 (LACK) Ag. Because memory/effector cells secrete IL-4 more rapidly than naive cells, we sought to analyze the phenotype of these lymphocytes before infection. Indeed, a fraction of LACK-specific CD4(+) T cells expressed a typical CD62 ligand(low)CD44(high)CD45RB(low) phenotype in uninfected mice. LACK-specific T cells were primed in gut-associated lymphoid tissues by cross-reactive microbial Ags as demonstrated by their reactivity with bacterial extracts and by the ability of APCs from the mesenteric LN of BALB/c mice to induce their proliferation. Also, mice in which the digestive tract has been decontaminated exhibited a reduced proportion of LACK-specific T cells expressing a memory/effector phenotype and did not exhibit the early accumulation of IL-4 transcripts induced by L. major. Thus, LACK-specific T cells represent a subset of CD4(+) T cells which have acquired the ability to rapidly secrete IL-4 as the result of their priming by cross-reactive microbial Ags. Tracking the fate of these cells may provide information about the regulation of cell-mediated immune responses to gut Ags in physiological and pathological situations.

ATP-Binding Cassette Transporters↗

PubMed2000

Local permutations in the glomerular array of the mouse olfactory bulb.

Olfactory sensory neurons expressing a given odorant receptor gene project their axons with great precision to a few specific glomeruli in the olfactory bulb. It is not clear to which extent the positions of these glomeruli are fixed. We sought to evaluate the constancy of the glomerular array in the mouse by determining the relative positions of glomeruli for various odorant receptors, using a method that affords single-axon resolution, and in a large number of bulbs. We used a genetic strategy to visualize neuronal populations that express one of three members of the mOR37 subfamily. We generated by gene targeting five strains of mice in which expression of a given mOR37 gene is linked to expression of an axonal maker, which is either taulacZ or tauGFP. The patterns of marker expression faithfully mimic those of the cognate receptors. Axons of neurons expressing a given mOR37 gene converge onto one or two glomeruli per bulb. Each mOR37 gene has its own glomeruli, and the mOR37 glomeruli are grouped within a restricted domain of the bulb. Serial sectioning of 214 bulbs reveals that the relative positions of the three types of glomeruli are not fixed but display local permutations. Importantly, this is also the case among the two bulbs from one individual, ruling out the genetic manipulation itself and differences in genetic background or olfactory experience as causes for the observed variability. These local permutations may reflect the developmental history of the glomeruli and are relevant for the construction of spatial odor maps.

Alleles↗

PubMed2000

Sequence analyses of the olfactory receptor gene cluster mOR37 on mouse chromosome 4.

The olfactory receptor multigene family is organized in clusters spread throughout the genome. In the present study, we have sequenced two subregions of the mOR37 gene cluster on mouse chromosome 4. The resulting 100 kb of sequence revealed seven odorant receptor coding regions and one gene fragment. Sequence analyses reveal that the mOR37 gene cluster may represent a rather ancient cluster. The mOR37 genes exhibit a complex intron/exon structure, and some appear to be differentially spliced. All genes in the cluster share conserved sequence motifs 5' of their putative initial exons, which represent potential binding sites for transcription factors. The clustered organization and conserved sequence motifs suggest common expression control mechanisms for these genes.

5' Untranslated Regions↗

PubMed2000

Influence of administration dose and route on the immunogenicity and protective efficacy of BBG2Na, a recombinant respiratory syncytial virus subunit vaccine candidate.

The immunogenicity and protective efficacy of BBG2Na, a novel recombinant respiratory syncytial virus subunit vaccine candidate, was assessed in BALB/c mice under various conditions of dose, administration route and number of immunisations. A single intra-peritoneal (i.p.) dose of 2 microg, or two doses of 0.2 microg, were sufficient to induce elevated RSV-A serum antibodies and sterilising lung protective immunity. Serum antibody titres were significantly boosted following second immunisations, but not a third. Of three routes of immunisation, i.p. induced the highest RSV-A antibody titres, followed in efficacy by the intra-muscular (i. m.) and subcutaneous (s.c.) routes. Nonetheless, all three routes induced comparable and sterilising lung protection. In contrast, upper respiratory tract protection was observed only after i.p. vaccination, although significant viral titre reductions were evident following i.m. or s.c. immunisations. Interestingly, Pepscan analyses indicated that antibody epitope usage was highest in i.p. and lowest in i.m. immunised mice, respectively. Nonetheless, all routes resulted in antibody responses to known lung protective epitopes (protectopes). Thus, the prevention of serious lower respiratory tract disease, the principle goal of a RSV vaccine, but not URT infection, is dose dependent but unlikely to be influenced by the route of BBG2Na administration.

Animals↗