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Biomedical subjects

Y Lazorthes

Publications and source records attributed to Y Lazorthes.

At least 19 recordsLinked to original sources

Does intrathecal morphine in the treatment of cancer pain induce the development of tolerance?

OBJECTIVE: This retrospective study was designed to investigate whether chronic lumbar intrathecal administration of morphine leads to the development of opioid tolerance in patients suffering from intractable cancer pain. METHODS: Between 1978 and 1995, 159 patients with refractory cancer pain were treated with intrathecal morphine in our Multidisciplinary Pain Center. The treatment consisted of preservative-free morphine administered through an access port as a single bolus. In this series of patients (n = 159), the daily doses of intrathecal morphine were determined as a function of duration of follow-up. RESULTS: The mean follow-up period was 95 days (range, 5-909 d), the mean starting daily dose of intrathecal morphine was 2.69 mg (range, 1-7.5 mg), and the mean terminal dose was 7.82 mg (range, 1-80 mg). The results demonstrated that only a moderate increase in daily dose of intrathecal morphine was required during the course of treatment (a two- to threefold increase for a 3-mo period). Furthermore, the dose increment was similar for patients followed up for more or less than 60 days. This increase did not result in any central opioid-related side effects, and the pain was managed satisfactorily. CONCLUSION: The requirement for a moderate increase in intrathecal opioid doses reflects the development of tolerance but did not limit the patients' ability to obtain adequate analgesia during the course of their painful disease.

Adult

Effect of gamma knife on secondary trigeminal neuralgia.

The following study was conducted to evaluate the results of Gamma Knife stereotactic radiosurgery in the management of secondary trigeminal neuralgia. 53 patients suffering from secondary trigeminal neuralgia were studied and the results reported. We defined four therapeutic groups: group I correspond to essential trigeminal neuralgia. The primary aim was tumor control in group IV and pain cessation in group III and II (visualization of the fifth nerve root was possible in group II but not in group III). The target dose of the radiosurgery used in the current study varied from 20 to 40 Gy in group III and IV and from 70 to 90 Gy in group I and II. At short-term follow-up, 37 patients (74%) were pain-free, 9 patients (18%) were improved (50%-90% relief) and only 4 patients (8%) experienced treatment failure. Among the patients with early treatment success, 10 patients experienced a complete recurrence of pain in the four succeeding years, and 11 initially pain-free patients deteriorated to partial pain relief. The median time to pain relief was three months (range 1 day to 1 year). The mean follow-up was 32 months (range 7 to 60 months). No patient developed increased facial pain or deafferentation pain. Among the 53 patients, only two exhibit a slight facial hypesthesia and one patient described motor fasciculation related to Gamma Knife treatment. In our experience Gamma Knife surgery appears a safe and effective method for the treatment of secondary trigeminal neuralgia.

Adult

Hearing restoration in posterior fossa tumors.

OBJECTIVE: This study aimed to assess the results of hearing restoration with a cochlear or a brainstem implant in posterior fossa tumors. PATIENTS: Six patients were selected. Two patients with an acoustic neuroma in the only-hearing ear (cases 1 and 2), one patient with a posterior fossa meningioma (case 3), one patient with bilateral facial neuroma (case 4), and two patients with bilateral acoustic neuroma (cases 5 and 6) participated. INTERVENTION: In cases 1 and 2, the patients had a cochlear implant inserted on the only-hearing ear opposite the acoustic neuroma. In case 3, the patient presented with total deafness on the left side and a 10-mm meningioma on the right side. A cochlear implantation was performed after removal of the meningioma on the right side. In case 4, the patient was operated on on both sides with bilateral postoperative deafness. A cochlear implantation was performed on the better hearing ear. In cases 5 and 6, patients underwent an auditory brainstem implantation after the exeresis of the second tumor. RESULTS: Promontory test results were positive for patients 1, 2, 3, and 4. After implantation, patients 1, 2, 3, and 4 scored 98%, 13%, 70%, and 30%, respectively, in open-set sentence recognition tests, whereas patients 5 and 6 scored 0% and 20%, respectively. CONCLUSIONS: In case of nonfunctional cochlear nerve, in acoustic neuroma, either bilateral and in the only-hearing ear, promontory test should be performed. If positive results, a cochlear implantation should be performed, because successful results could be expected. Overall results of cochlear implantation on speech discrimination are better than those obtained with a brainstem implant.

Adolescent

[Treatment of spasticity with the intrathecal administration of baclofen].

Direct intrathecal administration of baclofen in the treatment of severe spasticity was proposed in 1984 by Richard Penn with the objective to carry out a selective spinal distribution of the active principle thus avoiding supraspinal side effects. We presented our first results at the French Language Association of Neurosurgery in 1985 within the framework of a report on "Functional neurosurgery of cerebral palsy" (Neurochirurgie, 1985, 31 (suppl 1): 1-118). This study aims to specify the selection criteria and current indications of this method for the treatment of severe chronic diffused spasticity of spinal and cerebral origin in adults and in children. This report relates to our experience concerning 60 patients (10 children) that benefit from the use of a totally implantable system for chronic administration. The total follow-up of all patients was 48 months (from 3 to 140 months). The initial effective daily amount of baclofen was 156 micrograms/24 hours and progressed in time to reach in the long run 280 micrograms/24 hours, with a very broad interindividual variability from 36 to 1050 micrograms/24 hours. All the patients benefited from a reduction in muscular hypertonicity as well as painful muscular spasms. On the other hand, the functional improvement was very variable from one patient to another and depended primarily on the initial clinical state and the etiology of the spasticity. The results observed were more significant in post-traumatic paraplegia than those secondary to demyelination disease even if they were stabilized with regard to spasticity of spinal origin. This mode of administration currently plays a significant role in the treatment of spasticity of cerebral origin, in particular in children presenting a motor disorder of cerebral origin with spastic prevalence. The current limitations of this type of treatment are technical because of the frequent catheter malfunctions, but are due essentially to the importance and constraint of the multi-disciplinary organization needed for the out-patient follow-up.

Baclofen

Relief of intractable cancer pain by human chromaffin cell transplants: experience at two medical centers.

In addition to its possible role as a replacement source in CNS degenerative diseases, neural transplantation may be used to augment the normal production of neuroactive substances. Our laboratory at the University of Illinois at Chicago has shown, in both acute and chronic pain models, that transplantation of adrenal medullary tissue or isolated chromaffin cells into CNS pain modulatory regions can reduce pain sensitivity in rodents. Chromaffin cells were chosen as the donor source since they produce high levels of both opioid peptides and catecholamines, substances which reduce pain sensitivity when injected locally into the spinal subarachnoid space. The analgesia produced by these transplants probably results from the release of both opioid peptides and catecholamines since it can be blocked or attenuated by both opiate and adrenergic antagonists. Studies indicate that even over long periods there is no apparent development of tolerance. Promising results have been obtained in preliminary clinical studies using allografts of adrenal medulla to relieve cancer pain. This clinical review encompasses results at two Medical Centers-University of Illinois at Chicago and University Paul Sabatier, Toulouse, France-in assessing efficacy of subarachnoid adrenal medullary transplantation for alleviating cancer pain. Our clinical and autopsy data strongly support our previous laboratory studies, i.e., that chromaffin cell transplants into the subarachnoid space represent a promising new approach to the alleviation of chronic pain. It is suggested that further clinical studies are now warranted.

Acute Disease

Oxytocin increases thresholds of colonic visceral perception in patients with irritable bowel syndrome.

AIM: The effects of oxytocin on colonic perception of intraluminal distension were evaluated in 26 patients with irritable bowel syndrome (IBS), using a flaccid bag placed in the descending colon and connected to a computerised barostat. METHOD: Symptomatic responses (first sensation and pain) were evaluated during isobaric distensions (4 mm Hg increments, five minute duration, five minute interval with return to zero pressure between each step), performed automatically by the barostat, during a continuous infusion of placebo or various doses of oxytocin (10, 20, 30, and 50 mU/min). RESULTS: The distension pressure (mean (SD)) required to induce a first abdominal sensation was 17.3 (5.5) mm Hg on placebo, 19.9 (5.8) on oxytocin 10 mU/min (NS), 22.3 (6.0) mm Hg on oxytocin 20 mU/min (p < 0.01), 23.1 (6.6) mm Hg on oxytocin 30 mU/min (p < 0.01), and 24.0 (7.1) mm Hg on oxytocin 50 mU/min (p < 0.01). The distension pressure required to induce pain was 24.8 (6.3) mm Hg on placebo, 26.0 (5.8) on oxytocin 10 mU/min (NS), 33.3 (7.8) mm Hg on oxytocin 20 mU/min (p < 0.01), 34.2 (7.6) mm Hg on oxytocin 30 mU/min (p < 0.01), and 34.3 (7.9) mm Hg on oxytocin 50 mU/ min (p < 0.01). Compliance curves were not different after placebo and oxytocin injection at the different doses. Naloxone did not inhibit the effect of oxytocin. Oxytocin also did not alter somatic perception, characterised by the RIII reflex at the level of the biceps femori. CONCLUSIONS: Oxytocin significantly increases thresholds for visceral perception in IBS patients at doses equal or to greater than 20 mU/min, possibly by acting at the level of visceral afferents.

Adult

Transplantation of human chromaffin cells for control of intractable cancer pain.

Adrenal medullary chromaffin cells produce high levels of endogenous opioid peptides. Recent data suggest that transplantation injected locally into the spinal subarachnoid space reduced intractable malignant pain. In order to determine the feasibility, the efficacy and the risks of using adrenal medullary tissue for control of irreducible pain, we have developed a transplantation protocol on cancer pain patients selected when they required chronic intrathecal injection of morphine and progressively increasing doses to maintain the level of analgesic effects. At the present time, our clinical trial involves 8 patients. We report here our initial results (mean follow-up: 5 months). The various data collected before and after the intrathecal administration of chromaffin cells included: 1) Pain evaluation over time, with concomitant narcotic intake, 2) CSF sampling through an implanted access port to determine the following biological parameters: biochemical assay for opioid peptides, cell count and phenotyping of lymphocytes, 3) peripheral blood samples for lymphocyte typing. The results confirm the efficacy of adrenal medullary transplantation into spinal CSF for controlling irreducible cancer pain. Complementary intrathecal and oral morphine were totally stopped in 2 cases and stabilized in 5 others. It seems essential to have an important volume of grafted tissue to achieve analgesia with high levels of metenkephalin in CSF. A progressive decrease in metenkephalin release was observed from 2 to 4 months after the transplantation. Two patients with a long-term follow-up (8 and 12 months) needed another intrathecal chromaffin cell graft.

Adrenal Medulla

[Chronic spinal cord stimulation in the treatment of neurogenic pain. Cooperative and retrospective study on 20 years of follow-up].

The aim of this investigation is to evaluate the long-term spinal cord stimulation (SCS) efficacy and safety, with a 20-years study concerning 692 patients (series I: 279, series II: 413). The series concern 304 arachno-epidural fibrosis, 152 peripheral nerve lesions, 25 amputations pain, 17 plexus brachial lesions, 101 spinal cord lesions, 22 cancer pain, and 71 vascular pain. A multidisciplinary chronic pain evaluation must exclude contra-indications (nociceptive pain, serious drug habituations, psychological problems, unresolved issues or secondary pain). Percutaneous epidural SCS is a screening method if the trial is sufficiently prolonged (3 to 14 days) and if the pain topography is overlapped by induced paresthesias. The immediate global results of the 2 series are similar: respectively 86% and 85% of success one month after implantation. With the same longterm follow-up (mean: 10 yrs, range: 2-20), and the same evaluation criteria, the percentage of long-term global success rate is 54% in series I, and 52% in series II. In the most recent period (1984-1990) concerning 301 patients, the success rate are respectively 68% and 60%. Analysing the results etiologically confirms the therapeutic value of SCS for neurogenic pain secondary to partial deafferentation. For upper limb pain, ipsilateral radicular stimulation is preferable. When the nerve lesion extends to the pre-ganglionic portion (brachial plexus avulsion, herpes zoster) or in cases of pain of spinal or cerebral origin, thalamic stimulation must be considered, after failure of SCS.

Electric Stimulation Therapy

[Monitoring of somatosensory evoked potentials during surgery for aneurysms of the sylvian artery].

Per-operative use of S.E.P.s for vascular disease is based on: 1. The relationship between electrical cortical responses and cerebral blood flow. 2. The existence of a reversible threshold of cerebral ischemia. Intra-operative monitoring S.E.P.s were used during 30 procedures for aneurysms of the middle cerebral artery (M.C.A.). In 18 cases, a temporary occlusion of M.C.A. was necessary. Occlusion times ranged from 1 to 30 minutes. The central conduction time delay (C.C.T.), i.e. the delay N14-N20 and the cortical peak (N20) amplitude, elicited by median nerve stimulation was bilaterally monitored. A prolongation of the C.C.T. by 1 millisecond (compared with the baseline induction value) and a progressive decrease or a disappearance of the N20 peak were considered as "significant" changes. In response to these changes, immediate corrective actions (interruption of temporary M.C.A. occlusion (T.O.), repositioning of brain retractors, reapplication of aneurysm clips ...) were implemented. The reversibility of the S.E.P.s alterations during surgery was correlated with the post-operative outcome. Significant changes were found in 20 cases (including 13 T.O.). They were totally reversible in 11 cases: 5 of them developed a new but transient immediate post-operative deficit, none had a definitive deficit, and 6 patients had no new deficit. In 9 cases, the per-operative S.E.P.s alterations were not reversible: 3 cases (including 1 T.O.) had a transient deficit, 4 a permanent deficit, and 1 died (aneurysm rupture during craniotomy). An irreversible N20 peak disappearance predicted a permanent post-operative deficit in 4 of 4 patients (100%), whereas an isolated irreversible C.C.T. increase was only followed by a transitory deficit. Only 1 of 9 patients with no change in S.E.P.s (during a 15 min. T.O.), had a transient hemiparesis: this "false-negative" case will be discussed. This study confirms that S.E.P.s monitoring provides useful warning during aneurysm surgery. Median nerve S.E.P.s reflect the functional integrity of cortical M.C.A. territory; it is the pathway a risk during M.C.A. aneurysm surgery. S.E.P.s changes are not real-time information (an average of 500 responses need about 2 min), but these delays allow the surgeon to reverse the situation by immediate intra-operative adjustment, especially during temporary M.C.A. occlusion.

Adult

[ENT and neurosurgical team approach to malignant ethnoido-frontal tumors].

The authors describe a surgical technique of total ethmoidectomy by mixed frontal and paralateronasal duct for excision of the ethmoidal bloc tumors. This technique requires a surgical team aware of neurosurgical and ORL problems. The authors report their experience on a series of six patients, surgically managed from 1983 to 1990.

Adolescent

[Mechanisms of action of medullary neurostimulation in the treatment of limb arteriopathy].

Despite 25 years of clinical practice, concerning chronic epidural spinal cord stimulation (SCS) for pain control, the mechanisms underlying the beneficial effects are still poorly understood. The main indications for SCS are intractable chronic pain secondary to neurogenic origin (essentially neuropathies by lesion of peripheral nerve or roots) or to ischemic origin. Several observations suggest that mechanisms by which SCS alleviate these two types of pain are different. In peripheral vascular disease, the analgesic effect appears as the consequence of the vasodilatory effect of SCS. The actual experimental data indicate that SCS produce its influence on peripheral microcirculation via a transitory suppression of the sympathetic vasoconstrictor control.

Arteries

CSF baclofen levels after intrathecal administration in severe spasticity.

The pharmacokinetic parameters in the CSF of baclofen given to 4 patients as an intrathecal bolus are reported. Considerable inter-individual variability in the parameters was observed. The elimination half-life ranged from 0.9 to 5 h and the clearance from 0.013 to 0.08 l.h-1. In order to optimize treatment, it is suggested that CSF baclofen levels be matched to changes in Hoffman's monosynaptic reflex (H reflex).

Adult

[Analysis of the results of surgery and nucleolysis using papain in 1085 cases of lumbar disk hernias].

1,085 patients have been treated for intervertebral disc herniation with lombo-sciatica: in 751 cases surgical discectomy without laminectomy has been performed with or without microscope; 334 underwent papain nucleolysis. The two clinical groups were separated on clinical and radiographic backgrounds: nucleolysis was performed in patients with no motor disturbance, no stenosis of the lumbar canal, no displaced fragment; the other patients received surgical treatment. The results were evaluated according to MacNab's criteria with a follow-up of 12 to 84 months (mean 17.2 months). The results after surgical treatment were excellent in 53.8% and good in 36.8% of the cases. For papain treatment they were excellent in 32.7% and good in 38.8% of the cases. Papain nucleolysis therefore appears to be an efficient method for the treatment of intervertebral disc herniations associated with lombo-sciatica but, overall, gives poorer results than surgery in spite of a strict selection procedure. In this study, complications due to papain nucleolysis were restricted to chemical spondylodiscitis (5 cases) and to 2 benign allergic syndromes. Statistical analysis of all the cases and multifactorial correlation research pointed out the importance of "workmen's compensation" as prognostic factor. Since this study, 90% of the patients presenting with disc herniation associated with lombo-sciatica recalcitrant to medical treatment undergo surgical discectomy; papain nucleolysis is reserved for sub-ligamentary and non-displaced forms without stenosis of the lumbar canal and represent 10% of our current population.

Adolescent

Chronic intrathecal baclofen administration for control of severe spasticity.

Baclofen, the most effective drug for treating spasticity, is a specific agonist of gamma-aminobutyric acid-B receptors, and is very abundant in the superficial layers of the spinal cord. Given orally, baclofen does not easily penetrate the blood-brain barrier, and is distributed equally to the brain and spinal cord. Direct intrathecal administration was given in order to change the distribution of the drug by preferentially perfusing the spinal cord. Eighteen patients presenting a severe spastic syndrome were treated with chronic intrathecal infusion of baclofen in the lumbar cerebrospinal fluid. After clinical preselection, 38 patients were implanted with a lumbar access port allowing long-term trials in order to determine the efficacy of baclofen therapy and the effective 12-hour dose. The 18 patients selected for chronic administration were implanted with a programmable pump. The pathology in these cases was: multiple sclerosis (6 cases), posttrauma spastic syndrome (eight cases), and (one case each) cerebral palsy, ischemic cerebral lesion, spinal ischemia, and transverse myelitis. The mean follow-up period was 18 months (range 4 to 43 months). The clinical results were evaluated according to muscular hypertony on Ashworth's scale (changed for occurrence of painful spasms) and functional improvement. Results were better for spastic syndrome secondary to traumatic medullary lesion than for demyelinating disease. Hypertonia was improved in all cases as confirmed by the registration of the Hoffman (H) reflex. Painful muscular spasms disappeared in 14 of the 16 affected patients. Significant functional improvement was noted in nine patients and was considerable in three. The risk of side effects secondary to overdose (such as excessive hypotonia or central depression) and the absence of a specific baclofen antagonist stresses the necessity for accurate determination of the efficient dose. After an initial titration period and adjustment of the therapeutic dose, the individual doses were from 21 to 500 micrograms/24 hrs (mean 160 micrograms/24 hrs). This new conservative method is very effective, perfectly reversible, and safe when administered in conditions favorable to its use.

Baclofen

[Monitoring management of nosocomial infections in a neurosurgical department].

Fulfilling a nosocomial infection watch program in a neurosurgery department lead to assess the basic situation i.e. the same characteristics related to both surgery and I.C.U. (incidence rate of wound infections 3%, of bronchopulmonary tract infections 20.8% and of urinary tract infections 9.1%). To ensure feasibility of data collection and data accuracy, strategy was based on weekly passive epidemiological data collection, laboratory data and monthly confrontation with neurosurgery's practitioners.

Bacteriological Techniques