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Biomedical subjects

A Cahana

Publications and source records attributed to A Cahana.

At least 19 recordsLinked to original sources
PubMed2006

[Novelties in interventional pain techniques].

The clinical application of new interventional technology begins with its conception, passes through a scientific validation and finally should be accepted as part of current clinical practice. One way of scientifically validating these techniques is analyzing present practice, available resources and patient outcome. The first part of this article describes the stages in the creation of a quality management system (ISO 9001) which we carried out, in order to judiciously realize these novel interventions. In the second part two techniques indicated in low back and leg pain are described. The first is spinal endoscopy, a three dimensional procedure designed to diagnose and treated painful lumbar radiculopathy. The second is intra-discal electro-therapy (IDET), indicated in discogenic pain. Albeit novel, these techniques are of promising nature, and their qualitative analysis, via rigorous certification is, we think, of interest.

Chronic Disease↗
PubMed2006

Minimally invasive procedures for the treatment of failed back surgery syndrome.

Failed back surgery syndrome has become unfortunately a common clinical entity. FBSS does not have one specific treatment because it does not have one specific cause. Some features are shared with chronic low back pain (CLBP) and some pathological processes are specific. Both pathologies are leading causes of disability in the industrialized world and costly medical and surgical treatments are continuously used despite their limited efficacy. Nonetheless, evidence based practice guidelines are systematically developed. In this chapter we cautiously review the vast, complex and at times contradictory literature regarding the treatment of FBSS. Interventional Pain literature suggests that there is moderate evidence (small randomized or non randomized or single group or matched case controlled studies) for medial branch neurotomy and limited evidence (non experimental one or more center studies) for intra-discal treatments in mechanical low back pain. There is moderate evidence for the use of transforaminal epidural steroid injections, lumbar percutaneous adhesiolysis and spinal endoscopy for painful lumbar radiculopathy and spinal cord stimulation and intrathecal pumps mostly after spinal surgery. In reality there is no gold standard for the treatment of FBSS but, these results seem promising.

Adrenal Cortex Hormones↗
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↗
PubMed2004

Trophic signals acting via phosphatidylinositol-3 kinase are required for normal pre-implantation mouse embryo development.

The growth and survival of the preimplantation mammalian embryo may be regulated by several autocrine trophic factors that have redundant or overlapping actions. One of the earliest trophic factors to be produced is embryo-derived platelet-activating factor (1-O-alky-2-acetyl-sn-glyceryl-3-phosphocholine). The addition of platelet-activating factor to embryo culture media exerted a trophic effect, but structurally related lipids (3-O-alky-2-acetyl-sn-glyceryl-1-phosphocholine, 1-O-alky-sn-glyceryl-3-phosphocholine, octadecyl-phosphocholine) had no effect. Platelet-activating factor induced a pertussis toxin-sensitive [Ca(2+)](i) transient in two-cell embryos that did not occur in platelet-activating factor-receptor null (Pafr-/-) genotype embryos. Fewer Pafr-/- mouse zygotes developed to the blastocyst stage in vitro compared with Pafr+/+ zygotes (P<0.02), those that developed to blastocysts had fewer cells (P<0.001) and more cells with fragmented nuclei (P<0.001). The inhibition of 1-O-phosphatidylinositol 3-kinase (LY294002 (3 microM and 15 microM) and wortmannin (10 nM and 50 nM)) caused a dose-dependent inhibition of platelet-activating factor-induced [Ca(2+)](i) transients (P<0.001). The two-cell embryo expressed 1-O-phosphatidylinositol 3-kinase catalytic subunits p110 alpha, beta, gamma and delta, and regulatory subunits p85 alpha and beta. LY294002 and wortmannin each caused a significant reduction in the proportion of embryos developing to the morula and blastocyst stages in vitro, reduced the number of cells within each blastocyst, and significantly increased the proportion of cells in blastocysts with fragmented nuclei. The results indicate that embryo-derived platelet-activating factor (and other embryotrophic factors) act through its membrane receptor to enhance embryo survival through a 1-O-phosphatidylinositol 3-kinase-dependent survival pathway.

Androstadienes↗
PubMed2003

A study of the nature of embryonic lethality in LIS1-/- mice.

Homozygous deletion of the Lis1 gene (Lis1(-/-)) in mouse resulted in early embryonic lethality immediately after embryo implantation by an undefined mechanism. We seek to define the nature of this demise. LIS1 (pafah1b1) is a 46 kDa protein with seven tryptophan-aspartate (WD) repeats. It docks with many proteins and has been implicated in microtubular function, cell division, intercellular transport, and nuclear and cellular motility. Combined Western and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analyses showed that LIS1 expression from the blastocyst stage required new transcription from the embryonic genome. Consequently, the death of post-implantation embryos may not reflect the first time during development that LIS1 was required, rather, it may reflect the first time following depletion of gametic stores that its actions were essential. Following culture of blastocysts in vitro for 96 hr the inner cell mass (ICM) of null embryos were significantly smaller than ICM of wild-type siblings. Normal blastocyst outgrowths after 96-hr culture had high levels of LIS1 expression in the outer cells of developing ICM and extensive expression in trophoblast cells. Lis1(-/-) embryos had significantly smaller trophoblast nuclei than wild-type embryos. The results show that LIS1 expression is required for the continued normal development of the ICM and optimal trophoblast giant cell formation.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2003

Subdural catheter migration may lead to baclofen pump dysfunction.

OBJECTIVES: To report an unusual cause of intrathecal drug delivery failure in baclofen pump device. STUDY DESIGN: A case report of an SCI patient treated with intrathecal baclofen, presenting a drug withdrawal. SETTING: Regional spinal cord injuries centre in Geneva (Switzerland). METHODS: We present a case of a 38-year-old male with complete T9 spastic paraplegia for 15 years, treated with intrathecal baclofen for 11 years. He recently presented to our centre with a spastic hypertonic episode, associated with rhabdomyolysis. RESULTS: Standard investigations were unrevealing. However, a CT scan performed after injecting a radio-opaque solution by the side port of the pump, showed an unexpected catheter migration into the subdural space. Surgical revision reversed withdrawal symptoms. CONCLUSIONS: Subdural catheter migration must be considered in the differential diagnosis of intrathecal drug delivery system failures. We recommend the use of the CT scan after contrast injection, to detect the localization of the distal catheter tip and confirm the normal diffusion into the subarachnoid space.

Accidental Falls↗
PubMed2002

LIS1-no more no less.

LIS1 is one of the genes that has a principle role in brain development since hemizygote mutations in LIS1 result in a severe brain malformation known as lissencephaly ('smooth brain'). LIS1 is a WD repeat protein and is known to be involved in several protein complexes that are likely to play a functional role in brain development. We discuss here the brain developmental phenotype observed in mice heterozygote for an N-terminal truncated LIS1 protein in view of known LIS1 protein interactions.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2001

Targeted mutagenesis of Lis1 disrupts cortical development and LIS1 homodimerization.

Lissencephaly is a severe brain malformation in humans. To study the function of the gene mutated in lissencephaly (LIS1), we deleted the first coding exon from the mouse Lis1 gene. The deletion resulted in a shorter protein (sLIS1) that initiates from the second methionine, a unique situation because most LIS1 mutations result in a null allele. This mutation mimics a mutation described in one lissencephaly patient with a milder phenotype. Homozygotes are early lethal, although heterozygotes are viable and fertile. Most strikingly, the morphology of cortical neurons and radial glia is aberrant in the developing cortex, and the neurons migrate more slowly. This is the first demonstration, to our knowledge, of a cellular abnormality in the migrating neurons after Lis1 mutation. Moreover, cortical plate splitting and thalomocortical innervation are also abnormal. Biochemically, the mutant protein is not capable of dimerization, and enzymatic activity is elevated in the embryos, thus a demonstration of the in vivo role of LIS1 as a subunit of PAF-AH. This mutation allows us to determine a hierarchy of functions that are sensitive to LIS1 dosage, thus promoting our understanding of the role of LIS1 in the developing cortex.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1999

LIS1 is a microtubule-associated phosphoprotein.

Lissencephaly, a severe brain malformation, may be caused by mutations in the LIS1 gene. LIS1 encodes a microtubule-associated protein (MAP) that is also part of the enzyme complex, platelet-activating factor acetylhydrolase. LIS1 is also found in a complex with two protein kinases; a T-cell Tat-associated kinase, which contains casein-dependent kinase (CDK) activating kinase (CAK), as well as CAK-inducing activity, and with a spleen protein-tyrosine kinase similar to the catalytic domain of p72syk. As phosphorylation is one of the ways to control cellular localization and protein-protein interactions, we investigated whether LIS1 undergoes this post-translational modification. Our results demonstrate that LIS1 is a developmentally regulated phosphoprotein. Phosphorylated LIS1 is mainly found in the MAP fraction. Phosphoamino acid analysis revealed that LIS1 is phosphorylated on serine residues. Alkaline phosphatase treatment reduced the number of visible LIS1 isoforms. In-gel assays demonstrate a 50-kDa LIS1 kinase that is enriched in microtubule-associated fractions. In vitro, LIS1 was phosphorylated by protein kinase CKII (casein kinase II), but not many other kinases that were tested. We suggest that LIS1 activity may be regulated by phosphorylation.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1999

Platelet-activating factor (PAF) acetylhydrolase activity, LIS1 expression, and seizures.

Lissencephaly patients are born with severe brain malformations and suffer from recurrent seizures. LIS1, the gene mutated in isolated lissencephaly patients, is a subunit of the heterotrimeric cytosolic enzyme platelet-activating factor acetylhydrolase (PAF-AH), interacts with tubulin, and affects microtubule dynamics. In order to gain molecular insights into the possible involvement of LIS1 in seizures in lissencephaly patients, we induced seizures in rats by injection of kainate. PAF-AH activity was markedly reduced as early as 30 min following initiation of seizures, making this parameter a sensitive indicator of seizure events. PAF-AH activity returned to and surpassed control values 1 week following initiation of seizures. Expression of LIS1 in the dentate gyrus changed significantly in a manner similar to that of PAF-AH enzymatic activity. This is the first correlation found between LIS1 expression and PAF-AH activity. Furthermore, the expression of the alpha2 catalytic subunit, which is the major PAF-AH catalytic subunit in rat adult brain, changed in a dramatic fashion. An additional higher-mobility LIS1 cross-reactive band was detected in samples isolated a week following seizure occurrence. This LIS1 isoform was enriched in the microtubule-associated fraction. We propose that LIS1 expression is an important factor in regulation of PAF-AH activity. We postulate that reductions in LIS1 protein levels found in lissencephaly patients may render them more susceptible to seizures.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1999

LIS1 and platelet-activating factor acetylhydrolase (Ib) catalytic subunits, expression in the mouse oocyte and zygote.

Platelet-activating factor is a phospholipid with several documented roles in the pre-implantation embryo. Enzymes that belong to the platelet-activating factor acetylhydrolases family inactivate platelet-activating factor. Cytosolic platelet-activating factor acetylhydrolase (Ib) is a heterotetramer composed of two catalytic subunits (alpha1/alpha2) and two regulatory LIS1 subunits. The expression of these components was monitored in the mouse oocytes and zygotes using reverse-transcribed PCR and Western blot analysis. Interestingly, these proteins are expressed in the oocyte and zygote and their expression increases after fertilization, probably due to stabilization of maternal RNA. Lis1 mRNA transcription also increases after fertilization. However, assaying for expression of a specific paternal LIS1 isoform detected no zygotic translation in the one cell stage. These findings suggest a potential role for platelet-activating factor acetylhydrolase (Ib) components in the early mouse embryo.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1999

Analysis of lissencephaly-causing LIS1 mutations.

Mutations in the LIS1 gene may result in severe abnormalities of brain cortical layering known as lissencephaly. Most lissencephaly-causing LIS1 mutations are deletions that encompass the entire gene, therefore the mechanism of the disease is regarded as haploinsufficiency. So far, 13 different intragenic mutations have been reported: one point mutation, H149R; deletion of exon 9, which results in deleted acids Delta301-334; deletion of exon 4, which results in deleted amino acids Delta40-64; 10 mutations resulting in truncated proteins and one predicted to result in extra amino acids. We studied the consequences of the point mutation, deletion mutation and one of the reported truncations. In order to study LIS1 structure function, we introduced an additional point mutation and other truncations in different regions of the protein. The consequences of these mutations to protein folding were studied by gel filtration, sucrose density gradient centrifugation and measuring resistance to trypsin cleavage. On the basis of our results, we suggest that all truncation mutations and lissencephaly-causing point mutations or internal deletion result in a reduction in the amount of correctly folded LIS1 protein.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1999

A comparison of the placental transfer of ropivacaine versus bupivacaine.

UNLABELLED: This study compares the placental transfer of ropivacaine and bupivacaine using the dual perfused, single cotyledon human placental model. We studied the effects of maternal/fetal protein binding, maternal ropivacaine concentration, and fetal pH on ropivacaine transfer. At a clinically relevant maternal concentration (1 microg/mL), the calculated transfer ratios (local anesthetic percent transfer/antipyrine percent transfer) of ropivacaine (0.82 +/- 0.03) and bupivacaine (0.74 +/- 0.01) were comparable at the completion of the perfusion experiment (120 min). When the perfusates were modified to simulate actual in vivo plasma protein binding values, the maternal-to-fetal transfer of ropivacaine and bupivacaine decreased significantly (P < 0.05) as indicated by transfer ratios of 0.42% +/- 0.07% and 0.40% +/- 0.03%, respectively. No saturation of the transfer process was observed for either drug at the maternal concentrations investigated. The placental transfer of both local anesthetic agents increased significantly as the fetal pH decreased. This investigation shows that ropivacaine and bupivacaine cross the human placenta at a similar rate, despite their differences in lipophilicity and stereochemistry. Placental transfer of both compounds is highly influenced by maternal and fetal protein concentration and the fetal pH. IMPLICATIONS: The placental transfer of ropivacaine was shown to be similar to that of bupivacaine, and is thus highly influenced by the degree of maternal and fetal protein binding and fetal pH.

Adult↗
PubMed1998

[Intravenous lignocaine for chronic pain: an 18-month experience].

Intravenous injection of lignocaine relieves pain in animals with experimentally induced pain, and in man, mainly those with neuropathic pain. 106 patients were treated with intravenous lignocaine during a period of 18 months (212 treatment sessions). Blood pressure, heart rate and pain scores were continuously monitored after an intravenous bolus of lignocaine, 1 mg/kg, followed by continuous infusion of lignocaine, 5 mg/kg during 1 hour. There was significant pain relief after each session in most patients, lasting from a few hours to 4 weeks. There were no significant side effects. We present 2 of our patients. Due to its simplicity, efficacy and safety, intravenous lignocaine injection is recommended for those with neuropathic pain unrelieved by other therapeutic modalities.

Adult↗
PubMed1997

Malignant hyperthermia susceptibility: anaesthetic implications and risk stratification.

Malignant hyperthermia (MH) is a rare autosomal dominant trait that predisposes individuals to great danger when exposed to certain anaesthetic triggering agents, such as potent volatile anaesthetics and succinylcholine. Sudden hypermetabolic reaction occurs in skeletal muscle, leading to hyperthermia and massive rhabdomyolysis. Precautions must be taken before the anaesthesia of MH-susceptible patients. No triggering agents should be administered, central body temperature and ETCO2 should be carefully monitored, and dantrolene must be immediately available. In addition, the anaesthesia machine should be carefully washed to remove traces of halogenated agents, and the use of fresh disposable anaesthetic circuits is recommended. Early diagnosis of the syndrome by alert, informed anaesthesiologists, and the immediate administration of dantrolene and other supportive measures, has reduced mortality. Patients with MH susceptibility should be instructed to alert the anaesthesiologist about their condition whenever anaesthesia is needed. Although people diagnosed with MH susceptibility should not change their lifestyle in general, military service is limited.

Adolescent↗