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Biomedical subjects

A Forster

Publications and source records attributed to A Forster.

At least 19 recordsLinked to original sources
PubMed2006

Sedating effects of Humulus lupulus L. extracts.

It was the aim of the study to check ethanolic and CO2 extracts from Humulus lupulus for sedating activity. Both preparations reduced the spontaneous locomotor activity, increased the ketamine-induced sleeping time and reduced body temperature, confirming a central sedating effect. No indications of anxiolytic activity were found in the elevated plus maze test for any of the test preparations. This sedating activity could be attributed to three categories of constituents of lipophilic hops extracts. Though the alpha-bitter acids proved to the be most active constituents, the beta-bitter acids and the hop oil clearly contributed to the sedating activity of lipophilic Humulus extracts.

Animals↗
PubMed2006

A conditional model of MLL-AF4 B-cell tumourigenesis using invertor technology.

MLL-AF4 fusion is the most common consequence of chromosomal translocations in infant leukaemia and is associated with a poor prognosis. MLL-AF4 is thought to be required in haematopoietic stem cells to elicit leukaemia and may be involved in tumour phenotype specification as it is only found in B-cell tumours in humans. We have employed the invertor conditional technology to create a model of MLL-AF4, in which a floxed AF4 cDNA was knocked into Mll in the opposite orientation for transcription. Cell-specific Cre expression was used to generate Mll-AF4 expression. The mice develop exclusively B-cell lineage neoplasias, whether the Cre gene was controlled by B- or T-cell promoters, but of a more mature phenotype than normally observed in childhood leukaemia. These findings show that the MLL-AF4 fusion protein does not have a mandatory role in multi-potent haematopoietic stem cells to cause cancer and indicates that MLL-AF4 has an instructive function in the phenotype of the tumour.

Animals↗
PubMed2006

[Mechanisms by which acute orofacial pain becomes chronic].

Pain is a complex, multidimensional experience encompassing sensory-discriminative, cognitive, emotional and motivational dimensions. These dimensions in the orofacial region have particular expression since the face and mouth have special biological, emotional and psychological meaning to each individual. Orofacial pain is frequent. Epidemiological studies reveal a high prevalence of severe pain in syndromes such as temporomandibular disorders (TMD), burning mouth syndrome and toothaches, as well as an important role of psychosocial influences, contributing to the persistence of these syndromes. Many of the difficulties experienced by clinicians with the diagnosis and management of acute and chronic orofacial pain stem from a lack of recognition and understanding of these complex conditions, the various intricate bio-psycho-social interactions and the neurobiology behind the chronicisation of acute pain. This text strives to review the important advances and insights into the peripheral processes by which noxious stimuli activates or modulates nociceptive afferent input into the brainstem, the neural pathways in the brainstem and higher levels of the trigeminal (V) somatosensory system and the mechanisms involved in the plasticity of nociceptive transmission. We shall link this knowledge to clinical correlates and suggest a therapeutic approach in acute orofacial pain, in the attempt to avoid the development of chronic pain.

Acute Disease↗
PubMed2005

Chromosomal translocation engineering to recapitulate primary events of human cancer.

Mouse models of human cancers are important for understanding determinants of overt disease and for "preclinical" development of rational therapeutic strategies; for instance, based on macrodrugs. Chromosomal translocations underlie many human leukemias, sarcomas, and epithelial tumors. We have developed three technologies based on homologous recombination in mouse ES cells to mimic human chromosome translocations. The first, called the knockin method, allows creation of fusion genes like those typical of translocations of human leukemias and sarcomas. Two new conditional chromosomal translocation mimics have been developed. The first is a method for generating reciprocal chromosomal translocations de novo using Cre-loxP recombination (translocator mice). In some cases, there is incompatible gene orientation and the translocator model cannot be applied. We have developed a different model (invertor mice) for these situations. This method consists of introducing an inverted cDNA cassette into the intron of a target gene and bringing the cassette into the correct transcriptional orientation by Cre-loxP recombination. We describe experiments using the translocator model to generate MLL-mediated neoplasias and the invertor method to generate EWS-ERG-mediated cancer. These methods mimic the situation found in human chromosome translocations and provide the framework for design and study of human chromosomal translocations in mice.

Animals↗
PubMed2004

[Arthralgia, eosinophilia, proteinuria and diuretics-resistant leg edemas].

We report the case of a patient with eosinophilic fasciitis, a rare disease related to systemic sclerodermia and other fibrosing disorders. An involvement of the kidneys--like in this patient with proteinuria and hypoproteinemia--has been described in the literature but is very rare. We discuss diagnostic procedures and novel therapeutic options as combination therapies with steroids, methotrexate and ciclosporine A.

Adult↗
PubMed2004

Are there reliable predictors of postoperative pain?

BACKGROUND: The purpose of this study was to identify the preoperative determinants of severe postoperative pain. METHODS: Potential predictors were assessed using a questionnaire submitted on the day before surgery. Pain at rest, and pain during coughing/mobilization, were measured using visual analog scales on the day of surgery and on the following 2 days. The type of postoperative pain management was not standardized and was prescribed by the anesthesiologist in charge. Multivariate logistic regression models explaining postoperative pain were developed in Group I, comprising 304 consecutive patients undergoing orthopedic or intraperitoneal surgery, and validated in Group II, comprising 145 independent patients. RESULTS: Of the 62 variables examined by univariate analysis, only five were found to increase the risk of severe postoperative pain in Group I at rest and six factors during cough/mobilization. In the multivariate model for pain at rest, general anesthesia, expectation of postoperative pain, and chronic sleeping difficulties increased the risk of severe postoperative pain. In Group II, only chronic sleeping difficulties remained (OR: 3.97, 95% Cl: 1.69-9.29). In the multivariate model during cough/mobilization, intraperitoneal surgery, fear of postoperative pain, and having a relative with a history of pain increased the risk of severe postoperative pain in Group I. Intraperitoneal surgery OR 2.45 (95% Cl = 1.01-4.50) and having a relative with a history of pain OR 2.06 (95% Cl = 1.005-4.50) remained in Group II. CONCLUSION: Of the many factors that may influence postoperative pain, chronic sleeping difficulties emerge in this population of patients as the strongest determinant of pain at rest. Intraperitoneal surgery and having a relative with a history of pain are the strongest determinants of pain during cough/mobilization. These findings make physiological sense and deserve more attention by anesthesiologists.

Adolescent↗
PubMed2004

Null mutation of the Lmo4 gene or a combined null mutation of the Lmo1/Lmo3 genes causes perinatal lethality, and Lmo4 controls neural tube development in mice.

The LIM-only family of proteins comprises four members; two of these (LMO1 and LMO2) are involved in human T-cell leukemia via chromosomal translocations, and LMO2 is a master regulator of hematopoiesis. We have carried out gene targeting of the other members of the LIM-only family, viz., genes Lmo1, Lmo3 and Lmo4, to investigate their role in mouse development. None of these genes has an obligatory role in lymphopoiesis. In addition, while null mutations of Lmo1 or Lmo3 have no discernible phenotype, null mutation of Lmo4 alone causes perinatal lethality due to a severe neural tube defect which occurs in the form of anencephaly or exencephaly. Since the Lmo1 and Lmo3 gene sequences are highly related and have partly overlapping expression domains, we assessed the effect of compound Lmo1/Lmo3 null mutations. Although no anatomical defects were apparent in compound null pups, these animals also die within 24 h of birth, suggesting that a compensation between the related Lmo1 and 3 proteins can occur during embryogenesis to negate the individual loss of these genes. Our results complete the gene targeting of the LIM-only family in mice and suggest that all four members of this family are important in regulators of distinct developmental pathways.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Effects of CaCl2 and MgCl2 on Fourier transform infrared spectra of lung cancer cells.

The cations Ca2+ and Mg2+ are two important factors in the growth and maintenance of living cells. The addition of Ca2+ to living cells can cause a change in the three-dimensional (3D) structure of calcium binding proteins. Therefore, we decided to study whether the addition of CaCl2 and MgCl2 to three in vitro growing lung cancer cell lines could cause changes that could be measured by Fourier Transform Infrared Spectroscopy. The addition of CaCl2 or MgCl2 to lung cancer cells caused an increase in absorbance of the trough at 1410 cm(-1). This translated into an inversion of the 1410/1395 cm(-1) ratio following the addition of CaCl2 or MgCl2 for all three lung cancer cell lines. Also, the amide I peak shifted from around 1631 cm(-1) to lower wavenumbers when CaCl2 or MgCl2 was added to cancer cells. Furthermore, the addition of these two substances caused a shift of the peak between 3290 and 3395 cm(-1). Finally, while the addition of CaCl2 to lung cancer cells was associated with an increased cell death, this was not the case following the addition of MgCl2. This would confirm that the changes seen in the spectra of all three cell lines are due to metabolic and ionic shifts rather than cell death.

Apoptosis↗
PubMed2003

LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1.

We have previously shown correction of X-linked severe combined immunodeficiency [SCID-X1, also known as gamma chain (gamma(c)) deficiency] in 9 out of 10 patients by retrovirus-mediated gamma(c) gene transfer into autologous CD34 bone marrow cells. However, almost 3 years after gene therapy, uncontrolled exponential clonal proliferation of mature T cells (with gammadelta+ or alphabeta+ T cell receptors) has occurred in the two youngest patients. Both patients' clones showed retrovirus vector integration in proximity to the LMO2 proto-oncogene promoter, leading to aberrant transcription and expression of LMO2. Thus, retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter.

Adaptor Proteins, Signal Transducing↗
PubMed2003

[New therapies in rheumatoid arthritis].

In the treatment of rheumatoid arthritis great progress was made by new disease modifying antirheumatic drugs such as leflunomide, the use of combination therapies and especially the introduction of the TNF blockers. These agents are produced by the means of genetic engineering and allow excellent suppression of the disease activity and inhibition of radiographic progression. Their major advantages are the fast response and good overall tolerability. Because of the involved risk for infections and the high costs TNF blocking agents should be reserved for patients who respond poorly to conventional disease modifying antirheumatic drugs or do not tolerate them.

Antirheumatic Agents↗
PubMed2003

Deep brain stimulation of the subthalamic nucleus: effectiveness in advanced Parkinson's disease patients previously reliant on apomorphine.

OBJECTIVES: To assess the efficacy of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with advanced Parkinson's disease previously reliant on apomorphine as their main antiparkinsonian medication. METHODS: Seven patients with motor fluctuations despite optimal medical treatment given as predominantly apomorphine infusion (n=6), or intermittent apomorphine injections (n=1) underwent bilateral STN DBS using frameless stereotactic surgery. Standard assessments of parkinsonism and motor fluctuations, using Unified Parkinson's Disease Rating Scale (UPDRS) were performed before and six months after surgery. Assessments were performed both on and off medication, and postoperative with the stimulators switched on and off. RESULTS: Bilateral STN DBS improved motor scores (UPDRS III) by 61% when off medication (p<0.05). Clinical fluctuations (UPDRS IV items 36-39) were reduced by 46.2% (p<0.05). Total daily apomorphine dose was reduced by 68.9% (p<0.05) and apomorphine infusion via a pump was no longer required in four patients. There were no operative complications. Two patients required treatment for hallucinations postoperatively but there was no significant change in mini-mental state examination. CONCLUSIONS: In patients with advanced Parkinson's disease, previously reliant on apomorphine, bilateral STN DBS is an effective treatment to reduce motor fluctuations and enable a reduction in apomorphine use.

Aged↗
PubMed2003

Variability in position of the subthalamic nucleus targeted by magnetic resonance imaging and microelectrode recordings as compared to atlas co-ordinates.

BACKGROUND: Traditional methods for localisation of target nuclei for deep brain stimulation (DBS) have used brain atlas co-ordinates for initial targeting. It is now possible to visualise the subthalamic nucleus (STN) on magnetic resonance imaging (MRI) and determine the individual variability of its position. METHODS: The present study was performed in patients undergoing STN DBS for Parkinson's disease. The STN was directly targeted from axially obtained MRI and verified with microelectrode recordings. Postoperatively, the most effective contact was identified for each patient, and its position was calculated. RESULTS: Fifty electrodes were inserted in 25 patients. The target position varied considerably in relation to the mid-commissural point. The mean effective contact position lies just dorsal to the location of the STN in a standard brain atlas. CONCLUSION: The STN varies in position, and can be accurately targeted from MRI alone.

Adult↗
PubMed2003

Use of the NeuroMate stereotactic robot in a frameless mode for movement disorder surgery.

BACKGROUND/AIMS: To evaluate the use of the NeuroMate stereotactic robot with a novel ultrasound registration system for movement disorder surgery (MDS). METHODS: Using the robot in a frameless mode, 51 patients underwent MDS. Surgical planning was carried out using MRI data obtained more than 24 h before surgery. RESULTS: 37 out of 50 targets in the subthalamic nucleus were satisfactorily identified with a single microelectrode trajectory and the final electrode positions were at a mean distance of 1.7 mm from the calculated target. There was a significant improvement in motor scores of the Unified Parkinson's Disease Rating Scale III (off medication) at 6 (43%) and 18 months (51.7%) compared to pre-operative scores (p < 0.05). CONCLUSIONS: The frameless robot using only MRI data can be used for MDS. The temporal separation of imaging from the surgical procedure provides additional time for detailed image analysis and planning.

Humans↗
PubMed2002

The anatomical and neurophysiological basis of the sensate free TRAM and DIEP flaps.

Recent developments in autogenous breast reconstruction using the rectus abdominis myocutaneous free flap include attempts to reinnervate the flap tissue. We have carried out anatomical studies to determine the nature of abdominal-wall cutaneous innervation, with particular emphasis on the harvesting of sensate flaps. Dissections were performed on four embalmed and 12 fresh human cadavers (32 sides). The lowest five intercostal nerve trunks were identified and traced to the lateral border of the rectus sheath. A detailed dissection of the intramuscular course of the nerves and associated vasculature was performed. The relationship of the nerves to the vascular perforators used for rectus abdominis myocutaneous flaps was determined visually, and confirmed histologically. In contrast to previous studies, we show that nerves supplying cutaneous sensation can travel with both medial and lateral vascular perforators. In order to confirm clinically useful innervation, the abdominal flap skin of five patients undergoing TRAM flap reconstruction was stimulated electrically, and sensory recordings were made directly from the related intercostal nerve just prior to flap harvest. These studies represent, to our knowledge, the first clinical application of neurophysiological techniques to outline the perforator neurosomes of flaps based on the deep inferior epigastric vascular axis. We provide the first comprehensive study of abdominal-wall innervation with regard to sensate free-flap harvest. Our dissections show complex patterns of abdominal skin innervation that have not been previously described. The implications for sensate free TRAM and DIEP flap reconstructions, as well as the potential for more accurate inclusion of innervated flap skin, are discussed.

Abdominal Muscles↗
PubMed2002

Generalised pustular psoriasis induced by cyclosporin a withdrawal responding to the tumour necrosis factor alpha inhibitor etanercept.

We report a 50-year-old male patient with a 15-year history of psoriasis including mutilating psoriatic arthritis, in whom the withdrawal of cyclosporin A induced a generalised pustular exacerbation and a aggravation of the joint condition. Two weekly injections of 25 mg of the tumour necrosis factor alpha inhibitor etanercept led to a rapid improvement of his psoriatic arthritis, as well as regression of the pustular eruption, while residual erythema was still present. The clinical response was reflected by an increase in circulating interleukin (IL) 10 and a decrease in IL-6 and IL-8 serum levels during treatment. We conclude that etanercept may be a safe and effective therapy not only in severe psoriatic arthritis, but also in cases of pustular rebound after withdrawal of immunosuppressive agents.

Antirheumatic Agents↗