Biomedical subjects

S Albrecht

Publications and source records attributed to S Albrecht.

At least 37 records · Page 2Linked to original sources

PubMed2001

Promoter-specific transcription of the IGF2 gene: a novel rapid, non-radioactive and highly sensitive protocol for mRNA analysis.

The human insulin-like growth factor-II (IGF2) is a regulatory peptide which is critical in normal fetal growth. IGF2 gene transcription is controlled by the usage of four promoters P1-P4 of which promoters P2-P4 are genomically imprinted. Disruption of imprinting and the resulting increase of gene dosage have been shown to be implicated in tumor progression in a variety of human tumors. Due to the need for high amounts of tissue material for conventional methods such as Northern blotting or ribonuclease protection assay (RPA), studies on IGF2 expression have most often been limited to the detection of total IGF2 transcript, though different dysregulatory events can be responsible for the abundance of IGF2 mRNA found in many tumors. We established a highly sensitive competitive RT-PCR assay for the four different transcripts of the IGF2 gene with transcript-specific external RNA competitors in which we take advantage of fluorescence-based quantification on a semiautomated sequencer. The amount of total RNA needed is approximately 100 times lower than the amounts required for Northern blotting or RPA, so that even cytological samples can be analyzed. We applied the assay to a series of eleven hepatoblastomas (HB) in which normal adjacent liver tissue could also be analyzed.

Child, Preschool↗

PubMed2001

Topographic relations between the neural and ligamentous structures of the lumbosacral junction: in-vitro investigation.

Transient or persistent alterations in the L5 lumbar nerve root have been described as a complication after the reduction of spondylolistheses. In a retrospective analysis of our own patients, we observed a higher incidence of transient motor and sensomotor deficits after single-sitting anatomic correction of May-erding grade IV anterolistheses and spondyloptoses. These findings are consistent with those of other authors. The deficits pertained to muscles in the innervation range of the L5 nerve root, without there being any evidence of intradural root damage or nerve compression. In vitro studies have shown distraction and translation of the nerve root to be pathogenetically relevant mechanisms, leading to damage during intraoperative reduction. Additional alteration of neuronal structures may be caused by ventral parts of the iliolumbar ligament complex during the reduction maneuver. In order to reveal extradural constrictions of the L5 nerve root that might predispose towards intra- or perioperative damage, we examined anatomic specimens to determine the course and neighboring relationships of the lumbosacral plexus, especially in relation to pelvivertebragenic ligamentous connections. In addition to the morphologic considerations, we conducted translation tests, which were designed to simulate changes in shape and size of the epineural layer, as well as in vitro measurements of the resulting pressure on the nerve. In addition to a range of variations in the attachment of the iliolumbar ligament complex, which was always located dorsally to the nerve roots, we found a ligamentous connection formed by connective tissue between the sacrum and the fifth lumbar vertebral body on the caudal margin of the ligament apparatus in 14 out of 30 specimens. Its course was constantly ventral to the L5 nerve root, which was also adherent to the periosteum of the sacrum distal to this constriction in one-fifth of the specimens. The average pressure exerted on the nerve root during the distraction and translation process was over 30 mmHg in the area of this lumbosacral ligamentous connection, at a distance of greater than 20 mm. When the translation distance was further increased, perineural fatty tissue was discharged, due to increasing perineural pressure.

Aged↗

PubMed2001

Rathke's cleft cyst presenting as sphenoid sinusitis.

Rathke's cleft cysts are developmental abnormalities of the craniopharyngeal duct composed of retained stratified ciliated cuboidal cells of the respiratory type. Incidentally found in the pars intermedia in 13% to 33% of routine autopsies, they are discovered in growing numbers on CT and MRI scans. From 1991 to 1999, 9 cases of Rathke's cleft cysts were encountered by the senior authors, 4 of which were treated surgically (3 by using a transsphenoidal approach and one by using a transcranial subfrontal approach). Of the 3 patients treated with a transsphenoidal approach, 2 presented with symptoms mimicking sphenoid sinusitis and were initially referred for otolaryngologic evaluation. The clinical, pathologic, and radiologic features, as well as management and follow-up of those 2 patients, are reviewed. There has been only one previous case report of Rathke's cleft cysts presenting as sinusitis. Nevertheless, the otolaryngologist should be aware of this condition because it may present with other significant symptomatic extracranial extensions.

Adult↗

PubMed2001

A new model of electrically evoked pain and hyperalgesia in human skin: the effects of intravenous alfentanil, S(+)-ketamine, and lidocaine.

BACKGROUND: The authors used the analgesics alfentanil, S(+)-ketamine, and systemic lidocaine to examine a new human model of experimental pain and hyperalgesia. METHODS: Transcutaneous electrical stimulation at a high current density (5 Hz, 67.5+/-6.6 mA) was used to provoke acute pain (numeric rating scale, 5 of 10), stable areas of secondary mechanical hyperalgesia to pin prick (43.6+/-32.1 cm2), and light touch (27.5+/-16.2 cm2) for 2 h. Alfentanil, S(+)-ketamine, and lidocaine were applied for 20 min in a double-blind, placebo-controlled, crossover design in 12 subjects using target controlled infusions. RESULTS: In the placebo session, pain ratings and areas of hyperalgesia were stable during the stimulation period, which facilitated the assessment of analgesic effects. Alfentanil effectively inhibited electrically evoked pain and reduced pin prick hyperalgesia and allodynia during its infusion. S(+)-ketamine-induced inhibition of secondary hyperalgesia was more pronounced and lasted for the whole experimental protocol. Therapeutic levels of systemic lidocaine showed only marginal analgesic effects, but lasting antihyperalgesic effects. CONCLUSIONS: A new model of electrically induced pain and hyperalgesia was established, which enabled assessment of the time course of analgesic and antihyperalgesic effects with high temporal resolution and minimum tissue damage and which was further validated by use of common intravenous anesthetics.

Adult↗

PubMed2001

Mycotic aneurysm of the carotid bifurcation in the neck: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Mycotic aneurysms of the extracranial carotid artery are rare and difficult to diagnose. A search of the world literature published since 1966 reveals at least six cases of mycotic carotid aneurysms due to a Salmonella septicemia. We present an exceptional case of mycotic pseudoaneurysm of the bifurcation of the carotid artery due to Salmonella septicemia and discuss the pathogenesis as well as various aspects of the diagnosis and surgical management. CLINICAL PRESENTATION: A 68-year-old man presented in Poland with Salmonella sepsis; 1 month later, he was admitted to the emergency department of the Sir Mortimer B. Davis-Jewish General Hospital in Montreal with a bulky and pulsatile right cervical mass. An angiogram and a computed tomographic scan revealed a voluminous and partially thrombosed aneurysm the size of a tangerine originating from the posterior aspect of the carotid junction. INTERVENTION: Balloon trapping was attempted at the Montreal Neurological Hospital. Subsequently, the patient developed a significant neurological deficit, which was quickly reversed by the administration of hypertensive, hypervolemic, and hemodilution therapy. Thereafter, the pseudoaneurysm was resected surgically, and the internal and external carotid arteries were sacrificed. Pathological examination of the excised specimen of the carotid junction revealed a pseudoaneurysm. Bacterial culture of the lesion showed growth of Salmonella. CONCLUSION: The postoperative course was satisfactory except for laryngeal paralysis due to involvement of the vagus nerve. Four months later, a computed tomographic scan showed only small lacunae in both centra semiovale.

Aged↗

PubMed2001

Implementing a community-based social marketing project to improve agricultural worker health.

The Together for Agricultural Safety project is a community-based social marketing project working to reduce the adverse health effects of pesticide exposure among fernery and nursery workers in Florida. In 3 years, the collaboration between university and community researchers has embodied many of the principles of community-based research while completing multiple stages of formative data collection required for a social marketing project. This hybrid approach to developing a health intervention for a minority community has been successful in its early stages because the community partners are organized, empowered, and motivated to execute research activities with the assistance of academic partners. However, this work has also been labor intensive and costly. This article describes the lessons learned by project partners and considers the limitations of this approach for agricultural health research.

Adult↗

PubMed2001

Prion disease resembling frontotemporal dementia and parkinsonism linked to chromosome 17.

OBJECTIVE: To compare the clinical features of a familial prion disease with those of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). BACKGROUND: Prion diseases are not usually considered in the differential diagnosis of FTDP-17, since familial Creutzfeldt-Jakob disease (CJD), the most common inherited prion disease, often manifests as a rapidly progressive dementia. Conversely, FTDP-17 usually has an insidious onset in the fifth decade, with abnormal behavior and parkinsonian features. METHOD: We present the clinical features of 12 patients from a family with CJD associated with a point mutation at codon 183 of the prion protein gene. RESULTS: The mean age at onset was 44.0 +/- 3.7; the duration of the symptoms until death ranged from two to nine years. Behavioral disturbances were the predominant presenting symptoms. Nine patients were first seen by psychiatrists. Eight patients manifested parkinsonian signs. CONCLUSION: These clinical features bear a considerable resemblance to those described in FTDP-17.

Adult↗

PubMed2000

Functional implications of tissue factor localization to cell-cell contacts in myocardium.

Recently published studies suggest that the procoagulant receptor protein tissue factor (TF) is involved in vitro in cell adhesion and migration, via an interaction of its cytoplasmic domain with cytoskeletal proteins. Interestingly, TF is abundantly expressed in myocardium, but not in skeletal muscle. To elucidate the possible roles of TF in the myocardium, this study examined the cellular distribution of TF in relation to cytoskeletal proteins, as well as its relative amounts in different segments of premature, mature, and pathologically altered cardiac muscle. In juvenile and adult hearts, TF was predominantly detectable in the transverse part of the intercalated discs, where it co-localized with cytoskeletal proteins such as desmin and vinculin. The lowest amount of TF was observed in right atrial and the highest in left ventricular myocardium, which correlated with the number of contact sites of cardiomyocytes in these segments of the cardiac muscle. Lower levels of TF were present in structurally altered myocardium from patients with hypertension or ventricular hypertrophy. In addition, TF expression was decreased in human heart during sepsis and transiently decreased in rabbit heart in an endotoxaemia model, which indicates that a reduction in TF may contribute to cardiac failure in sepsis. The microtopography of TF at cardiomyocyte contact sites indicates that TF may play a structural role in the maintenance of cardiac muscle.

Adolescent↗

PubMed2000

p57(KIP2) is not mutated in hepatoblastoma but shows increased transcriptional activity in a comparative analysis of the three imprinted genes p57(KIP2), IGF2, and H19.

Hepatoblastomas (HBs), representing malignant liver tumors of childhood, show frequent loss of heterozygosity (LOH) in the chromosomal region 11p15.5. This loss is of maternal origin suggesting the presence of a monoallelically expressed tumor suppressor gene in this region. p57(KIP2) (KIP2) located at 11p15.5 is predominantly expressed from the maternal allele and encodes a cyclin-dependent kinase inhibitor. We screened a series of 56 HB tumors and five HB cell lines for allelic loss (LOH) of the KIP2 locus by microsatellite analysis and KIP2 coding sequence mutations by single-strand conformation polymorphism analysis. Although LOH at the KIP2 locus occurred in 25% of the cases, no mutations were found. Analysis of KIP2 mRNA expression by competitive reverse transcriptase-polymerase chain reaction revealed up-regulation in nine of 12 HBs compared to matching liver samples. In contrast, mRNA levels of the putative suppressor gene H19 on 11p15.5 were decreased in 10 of 12 tumors, indicating that KIP2 and H19 are not co-regulated in HBs. IGF2 mRNA expression was increased in 11 of 12 HB samples. All HBs showed monoallelic KIP2 expression. However, the overexpression of KIP2 in HBs with maternal loss of 11p15.5 suggests a reactivation of the paternal allele in these cases. Overexpression of KIP2 in HBs argues against a role as a HB suppressor gene.

Child, Preschool↗

PubMed2000

Generalized radial basis function networks for classification and novelty detection: self-organization of optimal Bayesian decision.

By adding reverse connections from the output layer to the central layer it is shown how a generalized radial basis functions (GRBF) network can self-organize to form a Bayesian classifier, which is also capable of novelty detection. For this purpose, three stochastic sequential learning rules are introduced from biological considerations which pertain to the centers, the shapes, and the widths of the receptive fields of the neurons and allow ajoint optimization of all network parameters. The rules are shown to generate maximum-likelihood estimates of the class-conditional probability density functions of labeled data in terms of multivariate normal mixtures. Upon combination with a hierarchy of deterministic annealing procedures, which implement a multiple-scale approach, the learning process can avoid the convergence problems hampering conventional expectation-maximization algorithms. Using an example from the field of speech recognition, the stages of the learning process and the capabilities of the self-organizing GRBF classifier are illustrated.

Artificial Intelligence↗

PubMed2000

Postoperative pain control following remifentanil-based anaesthesia for major abdominal surgery.

Eighty patients undergoing major abdominal surgery using remifentanil-based anaesthesia were randomly allocated in a double-blind manner to receive an intravenous bolus of fentanyl, buprenorphine, morphine or piritramide 20 min before the end of surgery. A reduced dose was administered postoperatively when patients reported moderate pain. Subsequent analgesia was provided by patient-controlled analgesia (PCA). The mean time from the end of anaesthesia to spontaneous respiration was 9 +/- 5 min. At first pain assessment, 63% of patients reported no or mild pain; 80% of patients required the second opioid bolus, those receiving piritramide needed the bolus significantly later than patients receiving buprenorphine or fentanyl. First PCA requirement also occurred significantly later in the piritramide group. This technique provided effective postoperative pain relief and transition to routine PCA and did not compromise recovery.

Abdomen↗

PubMed2000

Validation of immunolocalization of the urokinase receptor expression in ductal carcinoma in situ of the breast: comparison with detection by non-isotopic in-situ hybridization.

AIMS: Ductal carcinoma in situ (DCIS) is a pre-invasive form of mammary carcinoma with no microscopic evidence of cancer cell invasion through the basement membrane. However, for initiation of invasion, tumour cells have to acquire and focus proteolytic activity on to the cell surface in order to infiltrate the surrounding extracellular matrix. The receptor (uPA-R or CD87) for the serine protease urokinase-type plasminogen activator (uPA) plays a central role in invasion and metastasis. This study was performed to determine and localize m-RNA and protein of uPA-R in ductal carcinoma in situ of the breast. METHODS AND RESULTS: We analysed uPA-R mRNA and protein expression by in-situ hybridization and immunohistochemistry, respectively, in 50 formalin-fixed, paraffin-embedded specimens of DCIS. Three different antibodies were used to stain cell-associated uPA-R; chicken polyclonal antibody (pAb) HU277 and monoclonal antibodies (mAb) IID7 and 3936. In all cases, myoepithelial and stromal cells reacted with either antibody. Especially, reaction of macrophage-like cells with mAb 3936 resulted in a well-marked and bright staining. Applying mAb IID7, in 46 of the 50 breast specimens tumour cells showed a positive immunoreaction. Likewise pAb HU277 stained tumour cells in 40 of the 50 cases, whereas mAb 3936 reacted with only 24 of the 50 tissue sections. Endothelial cells were marked by both mAb IID7 and pAb HU277 (46/50 and 35/50, respectively); mAb 3936 did not label at all. All of the cell types stained by mAb IID7 and pAb HU277 also displayed reactivity with uPA-R mRNA-specific antisense oligonucleotides in in-situ hybridization. CONCLUSIONS: Our results reveal the presence of the tumour invasion-related receptor for the protease uPA not only in invasive ductal breast carcinoma but also in different types of DCIS.

Adult↗

PubMed2000

Expression of the neurotrophin receptor p75NTR in medulloblastomas is correlated with distinct histological and clinical features: evidence for a medulloblastoma subtype derived from the external granule cell layer.

Medulloblastomas (MBs) are primitive neuroectodermal tumors (PNET) of the cerebellum. They represent the most frequent malignant pediatric brain tumors, but their origin still remains unresolved and controversial. MB cells correspond to different stages of neural development and differentiation as illustrated by their expression of neuronal and glial markers. In the present study, we examined the expression pattern of the common low-affinity neurotrophin receptor p75NTR in a series of 167 MBs by immunohistochemistry. While p75NTR was present in only 17% of classic MBs (CMB), we found expression of p75NTR in all desmoplastic (nodular) MBs (DMB) examined, and in 71% of those MBs with a significant desmoplastic component. Furthermore, both desmoplastic histology and p75NTR expression were present preferentially in those tumors of adolescents and adults that are frequently located laterally in the cerebellar hemispheres. In DMBs, p75NTR was expressed predominantly in the proliferative, reticulin-rich areas, which may show coexpression of GFAP. In the pale islands of DMB, p75NTR was expressed only weakly or was absent. The expression pattern showed an inverse relation to that of the synaptic vesicle protein synaptophysin that was predominant in p75NTR negative classic MBs. Since the neurotrophin receptor p75NTR is expressed in cells of the external granule cell layer (EGL) of the fetal cerebellum, our findings suggest that progenitor cells of the EGL are the cellular origin of a distinct subset of MB, namely the desmoplastic variant and MBs with a significant desmoplastic component.

Adult↗

PubMed2000

Radionuclide imaging in patients with amputations of the lower leg: typical imaging patterns in five cases.

Amputation of the lower leg is not uncommon in elderly patients with chronic infections or vascular problems of the leg and foot, and most often it is performed below the knee or on the distal part of the lower leg (i.e., Syme's amputation). After operation, healing disorders with or without infection can occur, and usually structural imaging methods are performed for diagnosis. Radionuclide imaging using a combination of bone scans and infection scintigraphy can help to identify bone and soft tissue infection. Interpreting radionuclide scans is difficult, because imaging findings after amputation may depend not only on the level of resection and the disease investigated but also on the time that has elapsed since surgery. Typical imaging patterns of bone or infection scintigraphy of five patients are described

Adult↗

PubMed2000

New ELISA for quantitation of human urokinase receptor (CD87) in cancer.

The serine protease urokinase-type plasminogen activator (uPA), its inhibitor (PAI-1), and its receptor (uPAR; CD87) facilitate cancer cell invasion and metastasis. Whereas uPA and PAI-1 antigen levels determined in tumor tissue extracts of breast cancer patients correlate with disease recurrence and overall survival, the prognostic relevance of uPAR is still a matter of debate. We established two new sandwich-type enzyme-linked immunosorbent assay (ELISA) formats (HU/IIIF10-ELISA and HU/HD13-ELISA) using the epitope-defined monoclonal antibody (mAb) IIIF10 or the conformation-dependent mAb HD13.1, a polyclonal chicken antibody (HU277), and recombinant soluble uPAR (CHO-suPAR) as the standard. The lower detection limit of the assays was at 0.16 ng/ml, with a linear dose-response up to 5 ng/ml of uPAR antigen. Both ELISA formats showed good reproducibility and recovery. The intra-assay and the inter-assay variation coefficients were respectively 4.3% and 11.7% (HU/IIIF10-ELISA) and 4.0% and 10.7% (HU/HD13-ELISA). The recovery rate of uPAR in cell lysates spiked with CHO-suPAR was above 82% and 88%, respectively. With these new ELISA formats, uPAR antigen content in breast cancer tissue extracts and tumor cell lysates was determined and compared to a commercially available ELISA (ADI-ELISA). By all of the three uPAR ELISA formats CHO-suPAR and uPAR present in lysates of non-malignant epithelial cells and stimulated monocytes were quantified with similar sensitivity. Interestingly, in breast cancer cell lines of epitheloid origin a higher uPAR antigen content was determined by the HU/IIIF10-ELISA than the HU/HD13- or ADI-ELISA formats. In lysates of fibroblastic breast cancer cell lines similar uPAR values were obtained with the HU/IIIF10- and ADI-ELISA formats, whereas with the HU/HD13-ELISA significantly lower uPAR concentrations were determined. The prognostic relevance of tumor uPAR antigen was evaluated in 199 primary breast cancer patients with a median follow-up of 24 months. uPAR antigen values above the cut-off of 3.33 ng/mg protein as determined by the HU/IIIF10-ELISA were significantly correlated with short disease-free survival (p=0.025). Results obtained by the other two ELISA formats (HU/HD13-ELISA and ADI-ELISA) were not associated with prognosis. Our findings stress the need of well-characterized antibodies, which detect both uPAR of non-malignant and tumor cells, in setting up a uPAR-ELISA useful for assessing breast cancer patient prognosis.

Animals↗

PubMed2000

[Follow-up after histologically verified radical resection of early cancers of the mouth cavity: results of a prospective multicenter study].

INTRODUCTION: Early stage oral cavity carcinoma is curable in most cases. This study follows the course of early stage squamous cell carcinoma of the oral cavity after radical surgical resection, in order to assess the necessity of further treatment modalities. MATERIAL AND METHODS: In a prospective multicentric study, 110 patients with T1-T2 and N0-N1 (without capsular invasion) squamous cell carcinoma of the oral cavity were enrolled. All patients were treated exclusively by surgical resection with histopathologically proven negative margins. RESULTS: Among 96 patients (14 excluded because of positive margins), followed-up for 3 years, 18 presented a local or regional recurrence. In 12 of these 18 loco-regional control was reestablished by second treatment. Overall, the 4-year disease-specific survival probability was 94%. Patients treated initially by selective neck dissection had significantly lower recurrence rates than those without neck surgery. CONCLUSION: Early (T1-2, N0-1) squamous cell carcinoma of the oral cavity is adequately treated by surgery alone. The surgical procedure should include margin-free resection of the primary combined with selective neck dissection. Systematic postoperative radiotherapy does not appear necessary. Neck dissection is advocated in N0 patients as well.

Carcinoma, Squamous Cell↗

PubMed1999

[Molecular biology studies of a multicenter phase III study (SIC Study)].

Transcription factors adjust the up- and downregulation of inflammatory genes. Within the bounds of the SIC-study (Selenium in Intensive Care) the authors will investigate the role of transcription factors NF-kappa B and AP-1 in S.I.R.S/septic patients. The goal of these investigations is the corroboration of therapy of septic patients with sodium selenite at the molecular biological level.

Critical Care↗

PubMed1999

[Significance of selenium in regulation of inflammatory response by transcription factors in polytrauma patients. A clinical study].

The authors have investigated the relationship between selenium and transcription factors (NF-kappa B and AP-1) in the field of pathogenesis of polytrauma. Correlations between plasma selenium content and transcription factor binding activity have been found. The measured connecting capacitances of transcription factors have been associated with the severity of disease. To harden the results of this research a randomized double blind study with sodium selenite substitution is necessary next. This study will be to establish the therapy with sodium selenite in the treatment of polytrauma.

APACHE↗