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Biomedical subjects

A Forster

Publications and source records attributed to A Forster.

At least 55 records · Page 3Linked to original sources

The LMO1 and LDB1 proteins interact in human T cell acute leukaemia with the chromosomal translocation t(11;14)(p15;q11).

The ectopic expression of LMO1 or LMO2 in T cell acute leukaemias resulting from chromosomal translocations t(11;14)(p15;qll) or t(11;14)(p13;q11) respectively in a causal factor in tumorigenesis. LMO1 has been found as a heterodimer with a 46 Kd protein in a T cell line derived from a childhood T-acute leukaemia. This 46 Kd protein is the LIM-binding protein LDB1/NLI. The latter is a phosphoprotein and binds to LMO1 in its phosphorylated state and essentially all the LMO1 and LDB1 protein in the T cell line is part of the complex. Therefore, the LMO1-LDB1 interaction is likely to be involved in tumorigenesis after LMO1 is ectopically expressed following chromosomal translocation in T cells prior to development of acute leukaemias.

Chromosomes, Human, Pair 11↗

Identification of the LMO4 gene encoding an interaction partner of the LIM-binding protein LDB1/NLI1: a candidate for displacement by LMO proteins in T cell acute leukaemia.

The T cell oncogenes LMO1 and LMO2 are activated by distinct chromosomal translocations in childhood T cell acute leukaemias. Transgenic mouse models of this disease demonstrate that enforced expression of Lmo1 and Lmo2 cause T cell leukaemias with long latency and that Lmo2 expression leads to an inhibition of the T cell differentiation programme, prior to overt disease. These functions appear to be partly mediated by interaction of LMO1 or LMO2 with the LIM-binding protein LDB1/ NLI1. We have now identified a new member of the Lmo family, designated Lmo4, via its interaction with Ldb1. Lmo4 is widely expressed in mouse tissues, including adult thymus (mainly CD4, CD8-double positive T cells) and embryonic thymus (mainly CD4, CD8-double negative T cells). These characteristics imply that Ldb1-Lmo4 interaction may function in the T cell developmental programme and that enforced expression of LMO1 or LMO2 by chromosomal translocations or transgenesis may displace Lmo4 from this complex and thereby influence T cell differentiation prior to T cell tumour occurrence.

Adaptor Proteins, Signal Transducing↗

[Recurrent cerebrovascular insult--manifestation of POEMS syndrome?].

The POEMS syndrome is a multisystem disorder characterised by polyneuropathy, organomegaly endocrinopathy, plasma cell dyscrasia and skin changes. Along with many further manifestations this rare syndrome may also include macroangiopathy and acute vascular obliteration. In the literature such vascular problems have received only little attention and most case reports refer to involvement of the coronary and lower limb arteries. To our knowledge, the association with recurrent strokes has not been described. We report on a 59-year-old male with a complete form of POEMS syndrome associated with multicentric Castleman's disease. Despite absence of vascular risk factors, myocardial infarctions and ischemic necroses of toes occurred, and recurrent ischemic strokes appeared during oral anticoagulation. Recurrent strokes may therefore represent a further complication of the POEMS syndrome.

Castleman Disease↗

The T cell leukemia LIM protein Lmo2 is necessary for adult mouse hematopoiesis.

The LIM-finger protein Lmo2, which is activated in T cell leukemias by chromosomal translocations, is required for yolk sac erythropoiesis. Because Lmo2 null mutant mice die at embryonic day 9-10, it prevents an assessment of a role in other stages of hematopoiesis. We have now studied the hematopoietic contribution of homozygous mutant Lmo2 -/- mouse embryonic stem cells and found that Lmo2 -/- cells do not contribute to any hematopoietic lineage in adult chimeric mice, but reintroduction of an Lmo2-expression vector rescues the ability of Lmo2 null embryonic stem cells to contribute to all lineages tested. This disruption of hematopoiesis probably occurs because interaction of Lmo2 protein with factors such as Tal1/Scl is precluded. Thus, Lmo2 is necessary for early stages of hematopoiesis, and the Lmo2 master gene encodes a protein that has a central and crucial role in the hematopoietic development.

Adaptor Proteins, Signal Transducing↗

Postoperative analgesia with "3-in-1" femoral nerve block after prosthetic hip surgery.

PURPOSE: To evaluate the efficacy of a single shot "3-in-1" femoral nerve block for prosthetic hip surgery in association with general anaesthesia on post-operative analgesia. METHODS: Forty patients, ASA 1 to 3, received sham block or "3-in-1" femoral nerve block, following Winnie's landmarks with a nerve stimulator, and 40 ml bupivacaine 0.5% with epinephrine were injected after induction of anaesthesia. Vecuronium, 0.1 mg.kg-1, was added after performing the block and anaesthesia was maintained with isoflurane, oxygen 40% and nitrous oxide 60%. Fentanyl, 1.5 microgram.kg-1, was administered before incision to all patients. Heart rate, blood pressure, fentanyl requirements and FETiso were measured throughout surgery. During the post-operative period, 75 mg diclofenac i.m. and/or 0.1 mg.kg-1 morphine s.c. were administered when pain score was > 3/10 and repeated when necessary. Pain scores at first analgesic intervention, at 24 hr and 48 hr as well as diclofenac and morphine requirements after surgery were recorded. RESULTS: There was no difference in anaesthetic requirements during surgery. The time from performance of sham or "3-in-1" femoral nerve block to the first analgesic intervention (261 +/- 49 min versus 492 +/- 40 min, P < 0.05) and time from extubation to the first analgesic intervention (61 +/- 44 min vs 298 +/- 39 min, P < 0.05) were prolonged in the study group. However, pain scores and the analgesic requirements in the postoperative periods (24 and 48 hr) were similar. CONCLUSION: There is a short-term benefit during the first few postoperative hours in using a single shot "3-in-1" femoral nerve block to complement general anaesthesia for elective hip surgery.

Adjuvants, Anesthesia↗

Comparison of clonidine, morphine or placebo mixed with bupivacaine during continuous spinal anaesthesia.

PURPOSE: To compare intraoperative anaesthetic and haemodynamic effects of clonidine-bupivacaine, morphine-bupivacaine and placebo-bupivacaine combinations during continuous spinal anaesthesia. METHODS: Thirty six geriatric patients, undergoing knee replacement using continuous spinal anaesthesia were randomly assigned to: Placebo (n = 12), clonidine (n = 12) and morphine (n = 12), where 1 ml saline, 0.15 mg clonidine or 0.15 mg morphine were mixed with 10 mg bupivacaine 0.5%. Anaesthetic variables studied were maximal sensory level and degree of motor block, duration of surgical analgesia and duration of anaesthesia. Changes in systolic arterial pressure and vasopressor requirements were evaluated. RESULTS: Maximal sensory level and degree of motor block were comparable among the groups. Before surgery two patients in the placebo group, three in the clonidine and one in the morphine group received one additional ml bupivacaine 0.5% because of inadequate anaesthesia and were not considered for determination of duration of surgical analgesia. In the remainder, 1/9 in the clonidine group, 8/10 in placebo and 8/11 in morphine (P < 0.05) received reinjection of bupivacaine for surgical pain. These injections were given about 2 1/2 hr after the initial intrathecal injection, the duration of anaesthesia being about four hours. During the first 30 min after the initial injection the decrease in systolic pressure was greater in the clonidine and morphine than in the placebo group (P < 0.05). Thereafter, vasopressor requirements were higher only in the clonidine group (P < 0.05). CONCLUSION: In elderly patients 0.15 mg clonidine but not 0.15 mg morphine prolonged surgical analgesia when added to 10 mg plain bupivacaine.

Aged↗

[Halogenated anesthetic vaporizers: importance of maintenance regulations].

We report a serious dysfunction of 19 halothane vaporisers Vapor 19.3 (Dräger) which delivered a much higher concentration of agent than indicated on the dial. This inaccuracy was linked to a major corrosion of the inner layers of the vaporiser, with a deposit of zinc bromide and chloride in the bypass channel. The main cause for this dysfunction was the absence of an adequate maintenance of the vaporisers since their purchase 3 years before.

Anesthesia, Inhalation↗

Motor pathway analysis in HAM/TSP using magnetic stimulation and F-waves.

BACKGROUND: Tropical Spastic Paraparesis/HTLV-I Associated Myelopathy (HAM/TSP) is a chronic, progressive myelopathy endemic to the Caribbean. In HAM/TSP, peripheral motor pathways have been assessed using electromyography and nerve conduction studies; central motor pathways have been assessed to a limited extent using electrocortical stimulation. We used magnetic cortical stimulation (a painless alternative to electrocortical stimulation) and F-wave analysis to study conduction in the central and peripheral motor pathways in 18 HTLV-I seropositive, Jamaican TSP patients (ages 29-70 years; duration of symptoms 3-20 years) and 22 normal controls. METHODS: Magnetic cortical stimulation was effected using a 9 cm diameter undamped MES10 coil. F-waves and M-responses were elicited by electrical stimulation of the ulnar nerve at the wrist, and deep peroneal stimulation at the knee. Stimulation and recording of response latencies in abductor digitii minimi (ADM) and tibialis anterior (TA) were carried out using a Cadwell Excel system. RESULTS: With cortical stimulation, response latencies (TMCTs) to ADM and TA were prolonged in the patients relative to controls. F-wave and M-response latencies were unaffected, suggesting no peripheral pathology. Latency (CMCT) between cortex and lumbar cord was significantly prolonged; that between cortex and C7/T1, also, but less markedly (P < 0.0005). Amplitudes of cortically evoked responses were significantly reduced only in the lower limbs (TA). CMCT increased as the disease progressed from mild to moderate, thereafter remaining largely unchanged. CONCLUSIONS: Meta-analysis of interlaboratory control data revealed no significant differences in TMCTs between our controls and others studied using similar techniques. The observations are consistent with pathology affecting mainly the thoracolumbar cord in HAM/TSP.

Adult↗

Checking the anaesthetic machine: self-reported assessment in a university hospital.

Checking the anaesthetic machine before its daily use is essential. The aim of our study was to evaluate, through the use of an anonymous questionnaire, how the anaesthetists of our institution (physicians and nurses) report their daily checking. Sixty-three questions were used to ask the participants how frequently they checked the main components of the anaesthetic machine; the answers were evaluated with a score (0-3). The overall response rate was 78%, nurses; rate being lower than physicians' rate. Nurses obtained a higher global score, which raises the question of different adherence to guidelines by nurses and physicians. Moreover, questions in relation to gas supply were badly scored by all participants, which should alert us to reinforce theoretical and practical training in these items. Finally, although the methodology used in this survey could raise the question of the best way to evaluate the actual checkout procedure, self-reported assessment remains an alternative to more complex and expensive methods, such as an observer or a video evaluation.

Analysis of Variance↗

The influence of an aging surgical population on the anesthesia workload: a ten-year survey.

UNLABELLED: To assess the evolution of the anesthetic workload related to elderly population (> or = 65 yr) at the University Hospital of Geneva, the total number of anesthesia cases, high-risk patients, and emergency procedures, as well as the total duration of anesthesia and incidence of perianesthetic complications, were retrospectively analyzed over 10 yr. The squared correlation coefficient was used to assess the proportion of variance explained by the linear regression of the absolute and the relative number of events over time. More than 165,000 anesthesia procedures were analyzed, and the data were separated into two groups: the younger population (<65 yr) and the elderly population (> or = 65 yr). From 1985 to 1994, the elderly surgical population grew significantly faster (P < 0.001) than the elderly resident population (from 20.3% to 25.1% versus from 12.5% to 13.6%). Half of the increased number of anesthesia cases during this period were administered to elderly patients. The number of high-risk elderly patients increased by 48.3% (P < 0.0001). The number of emergency procedures in elderly patients increased only until 1991, and a significant decrease in the incidence of perianesthetic complications was observed. Because the mean duration of each procedure remained constant, the increased anesthetic workload in our institution was mainly due to increased geriatric surgical activity. IMPLICATIONS: During a study period of 10 yr, the increased anesthetic workload (defined as the number of anesthesia cases, high-risk patients, emergency procedures, and complication rate) at the University Hospital of Geneva was mainly due to the increased geriatric (patients > or = 65 yr) surgical activity, not to the aging of the resident population.

Age Factors↗

Patient evaluation and comparison of the recovery profile between propofol and thiopentone as induction agents in day surgery.

The patient's subjective perception of the quality of his/her recovery after day case anaesthesia with propofol or thiopentone as induction agents is still controversial. The authors investigated the perception and quality of awakening after anaesthesia during the recovery period and at 24 hours and 72 hours, in outpatients undergoing anaesthesia induced either with propofol or thiopentone and maintained with a volatile anaesthetic. In a double-blind study in adults undergoing knee arthroscopy in a day surgery unit, propofol and thiopentone were compared as induction agents in 60 randomized outpatients. A Critical Flicker Fusion Threshold test (CFFT), verbal test for anxiety, visual analog scale for anxiety and pain, and questionnaires were used to assess objectively and subjectively the quality of anaesthesia and awakening during the postoperative period. Demographic data and mean duration of anaesthesia were similar. In the propofol group, patients awoke more rapidly (9.2 +/- 5.8 vs 12.3 +/- 5.8 min) (P < 0.05); however, the CFFT measurements did not show any significant difference between the groups, except at time = 0 min, when 17 patients in the propofol group were able to perform the test versus only 10 patients in the thiopentone group (P < 0.05). At 4, 24, and 72 hours postoperatively, the authors were unable to detect any difference between the two groups. Except for early recovery, there were no differences between the intermediate and late recovery profiles, when propofol or thiopentone was used as the anaesthetic induction agent in day surgery.

Adolescent↗

The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-binding complex which includes the TAL1, E47, GATA-1 and Ldb1/NLI proteins.

The LIM-only protein Lmo2, activated by chromosomal translocations in T-cell leukaemias, is normally expressed in haematopoiesis. It interacts with TAL1 and GATA-1 proteins, but the function of the interaction is unexplained. We now show that in erythroid cells Lmo2 forms a novel DNA-binding complex, with GATA-1, TAL1 and E2A, and the recently identified LIM-binding protein Ldb1/NLI. This oligomeric complex binds to a unique, bipartite DNA motif comprising an E-box, CAGGTG, followed approximately 9 bp downstream by a GATA site. In vivo assembly of the DNA-binding complex requires interaction of all five proteins and establishes a transcriptional transactivating complex. These data demonstrate one function for the LIM-binding protein Ldb1 and establish a function for the LIM-only protein Lmo2 as an obligatory component of an oligomeric, DNA-binding complex which may play a role in haematopoiesis.

Adaptor Proteins, Signal Transducing↗

Effect on postoperative analgesia of small-dose lysine acetylsalicylate added to prilocaine during intravenous regional anesthesia.

Nonsteroidal antiinflammatory drugs act largely peripherally by blocking the local synthesis of prostaglandins. The aim of this study was to evaluate whether the addition of a small dose of lysine acetylsalicylate (LA) to the prilocaine used for intravenous regional anesthesia (IVRA) would improve the quality of postoperative analgesia. Sixty patients undergoing lower extremity IVRA for foot or ankle surgery were randomly assigned to three double-blind groups: LA-IVRA where 90 mg of LA was mixed with prilocaine 0.5% for IVRA and 1 mL of 0.9% NaCl administered intravenously (IV) through the forearm catheter after tourniquet inflation; LA-IV where 1 mL of 0.9% NaCl was mixed with prilocaine and 90 mg of LA administered IV; and placebo where 1 mL of 0.9% NaCl was administered both with prilocaine for the IVRA and IV. Duration of analgesia (time elapsed between tourniquet release and first injection of morphine, expressed as mean +/- SD) was significantly longer (P < 0.05) in LA-IVRA (387 +/- 216 min) when compared with LA-IV (175 +/- 264 min) and placebo (126 +/- 201 min). Analgesic requirements remained significantly lower in LA-IVRA when compared with placebo only during the first six postoperative hours, LA-IV being in an intermediate position. Pain scores were significantly lower in LA-IVRA during the first postoperative hour when compared with LA-IV and during the first 3 postoperative hours when compared with placebo. We conclude that 90 mg of LA (corresponding to 50 mg of acetylsalicylic acid) added to prilocaine 0.5% during IVRA improves the quality of postoperative analgesia in the early postoperative period.

Analgesia↗

A qualitative study of specialist nurse support for stroke patients and care-givers at home.

BACKGROUND: The involvement of five specialist nurses in providing a stroke support service was evaluated quantitatively in a recent randomized controlled trial. This complementary study used qualitative methods to evaluate trial outcomes more comprehensively. AIMS: To identify whether the nurses' intervention may have influenced the process of stroke recovery. METHOD: A purposefully selected subsample of 30 patients and 15 care-givers were interviewed within 1-3 months of their final quantitative assessment (12 months after recruitment to the randomized trial). Fifteen of the patients and eight of the care-givers had received visits from a specialist nurse. A semistructured interview was designed to include questions on perceptions of the recovery process and evaluation of services received. RESULTS: Some differences were evident between the accounts of control and intervention group subjects. The less tangible aspects of nurses' interventions--concern, attention, empathy and interest, when combined with sound professional knowledge, had identifiable value to the patients and care-givers. It appeared that the nurses had employed considerable sensitivity and skill in identifying and responding to particular needs at appropriate times. CONCLUSION: The qualitative evaluation offers a different picture to the quantitative results of the randomized controlled trial. In general, the findings of the qualitative study are more positive and encouraging than the quantitative results. The majority of patients and care-givers in the intervention group believed that they had benefited from the specialist nurse's visits.

Caregivers↗

Chromosomal translocations and leukaemia: a role for LMO2 in T cell acute leukaemia, in transcription and in erythropoiesis.

The LMO2 gene associated with T cell acute leukaemia has been used as an example of a gene activated by association with the T cell receptor genes after chromosomal translocations. The gene is shown to encode a LIM protein which is involved in protein interactions and during normal haematopoiesis is necessary for erythroid development. LMO2 has been shown to cause tumours when aberrantly expressed and to be able to heterodimerise with TAL1 to facilitate tumour development.

Adaptor Proteins, Signal Transducing↗

LIM-only protein Lmo2 forms a protein complex with erythroid transcription factor GATA-1.

The LIM-only protein Lmo2, originally identified as an oncogenic protein in human T cell leukemia, is essential for erythropoiesis. A possible role for Lmo2 in transcription during erythropoiesis has been investigated. Direct interaction of Lmo2 was observed in vitro and in vivo with the zinc finger transcription factor GATA-1, as well as with the basic helix-loop-helix (bHLH) transcription factor Tall. By using mammalian two-hybrid analysis, E47/Tall/Lmo2/GATA-1 protein complex could be demonstrated. Thus, a molecular link exists between three proteins crucial for erythropoiesis. This data suggest that variations in amounts of complexes involving Lmo2, Tall, and GATA-1 could be important for erythroid differentiation.

Adaptor Proteins, Signal Transducing↗