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Biomedical subjects

B Schott

Publications and source records attributed to B Schott.

At least 37 records · Page 2Linked to original sources

Comparative activity of anthracycline 13-dihydrometabolites against rat glioblastoma cells in culture.

We have studied the growth inhibition, DNA synthesis inhibition and cell incorporation of five 13-dihydrometabolites of anthracyclines in a model of doxorubicin-sensitive and -resistant rat C6 glioblastoma cells. These compounds were major metabolites for doxorubicin, epirubicin, daunorubicin, idarubicin and the new anthracycline 4'-deoxy-4'-iododoxorubicin and are known to be present in appreciable amounts in the plasma of patients treated with these drugs. We have shown that in vitro growth inhibition in sensitive cells was either much lower than that of the parent drug (doxorubicinol, epirubicinol, daunorubicinol), or similar to it (idarubicinol, 4'-iodoxorubicinol). In resistant cells, growth inhibition was about 100 times lower than in wild cells, and was always lower than that of the parent anthracycline. DNA synthesis inhibition occurred in sensitive cells for doses about 100 times higher than those required for growth inhibition, but in resistant cells, similar doses provided growth inhibition and DNA synthesis inhibition. Metabolite incorporation was always lower than that of the corresponding parent anthracycline; it was greatly reduced in resistant cells as compared to sensitive ones. The calculated intracellular concentrations obtained for the same growth inhibition are higher in resistant cells than in sensitive cells; in contrast, the calculated intracellular concentrations obtained for the same DNA synthesis inhibition are similar in resistant and sensitive cells, and similar for all the metabolites studied. These results suggest that the amount of drug incorporated is primarily responsible for DNA synthesis inhibition, which is directly correlated to growth inhibition in resistant cells, but not in sensitive cells.

Animals↗

Comparative cytotoxicity, DNA synthesis inhibition and drug incorporation of eight anthracyclines in a model of doxorubicin-sensitive and -resistant rat glioblastoma cells.

We have compared the growth inhibition, DNA synthesis inhibition and cell incorporation of eight anthracyclines in a model of doxorubicin-sensitive and -resistant rat C6 glioblastoma cells. The anthracyclines studied were both the reference molecules (daunorubicin, doxorubicin) and the new drugs recently introduced in clinical use or in trials (epirubicin, idarubicin, pirarubicin, esorubicin, rubidazone, 4'-deoxy-4'-iododoxorubicin). We have shown that the in vitro growth inhibition was correlated with the LD50. The new anthracyclines were more potent than the reference drugs in the sensitive cells and the resistance patterns revealed a reduced cross resistance of idarubicin, pirarubicin and 4'-deoxy-4'-iododoxorubicin towards the doxorubicin-resistant line. DNA synthesis inhibition occurred for much higher doses than growth inhibition in sensitive cells, but for similar doses in resistant cells. This suggests that different mechanisms could be involved in the mechanism of growth inhibition in sensitive and resistant cells. For similar exposures, reduction of drug incorporation was a general feature in the resistant line when compared to the sensitive one. However, no correlation was shown, for the various drugs, between the reduction of incorporation and the resistance factor. Moreover, the intracellular concentration required for growth inhibition is much higher in resistant cells than in sensitive cells, suggesting that increased drug efflux might not be the only mechanism to explain drug resistance.

Animals↗

[Lexical agraphia caused by left temporoparietal hematoma].

A patient presented with dysorthographia associated with amnestic aphasia due to a left temporo-parietal hematoma. Reading, copying, graphism of letters were normal. Dictation showed better results for logatomes and regular words, without orthographical difficulty, than for those with orthographical problems (ambiguous and irregular words). The overall features suggested a disorder of the lexical system in which orthography of words known to patients is present. The phonological pathway of phoneme-grapheme conversion was preserved since errors were usually phonologically correct. Initially it was possible to conclude to a disorder of the semantic value of words in their visual form. Oral spelling, auditory reading and written denomination also showed more errors for words of difficult orthography. This patient presented a disorder of visual representation of words. Comparison of this case with the few reported ones showed that the latter often had amnestic aphasia and differed from our case in the associated lexical or phonologic alexia. A common feature of the lesions is involvement of the left angular gyrus is right-handed patients.

Aged↗

[Early somesthetic evoked potentials and sensory deficits in thalamic and juxta-thalamic lesions. Clinical, electrophysiological and x-ray computed tomographic study in 70 patients].

Somatosensory Evoked Potentials (SEPs) have been recorded in 70 patients presenting a thalamic or capsular CT scan lesion. The loss of SEP parietal components confirmed the deafferentation of somatosensory cortex in infarctions of geniculothalamic or anterior choroidian arteries territory. SEPs were found to be normal in infarctions of other arterial territories, in agreement with the clinical evidence of normal somatosensory performances. In patients with haematomas, especially when located in the thalamus, there was no clear correlation between lesion sites and SEP data. Abnormal parietal responses were always associated to impaired tactile and joint sensations. The correlation was less significant for vibration sense. In four cases of selective loss of pain sensation SEPs were normal. In seven patients with abnormal parietal responses sterognosis was normal, a situation which is never encountered in cortical lesions. SEPs reliably documented the degree of somatosensory loss in patients with tactile extinction phenomenon. Contralateral parietal responses were reduced in four patients with tactile extinction but no attentional deficit for other sensory modalities. Thus normal SEPs are a prerequisite to consider thalamic neglect syndrome as a pure attentional disorder. Moreover SEPs demonstrated that there was no long-lasting deafferentation of somatosensory cortex in ataxic hemiparesis. It was found that selective loss of post-or prerolandic SEP components could occur in capsular lesions. This finding favors the hypothesis of parallel and independant thalamo-parietal and thalamo-frontal somatosensory projections that may be selectively damaged in lesions of thalamocortical radiations.

Adolescent↗

Cerebrospinal fluid and serum immune complex in acute inflammatory polyneuritis. Detection by Clq binding assay.

Immune complexes (IC) were assessed in serum and CSF from 11 patients with acute inflammatory polyneuritis (AIP). An 125 I-labeled Clq binding assay (Clq BA) was used. IC were present in the sera of four patients and in the CSF of six. CSF-Clq BA of AIP (Group 1) were compared with 12 patients with other inflammatory neurological diseases (Group 2) and 22 patients with non-inflammatory neurological diseases (Group 3). There was only a significant difference between Group 1 compared to Group 3 (p less than 0.05). Serum and CSF IC did not correlate either with blood-brain barrier lesions or with immunoglobulin deposits in sural nerve biopsy.

Acute Disease↗

[Thalamic pain: critical study of 43 cases].

Apart from hyperpathia, which is an entity in itself, thalamic pain presents a clinical spectrum of variable quality and intensity that justifies the description of "thalamic pains". Their mechanisms can be related to two basic mechanisms. The first involves the dependence of the thalamus to the afferent spinothalamic system. A lesion of the lemniscal system resulting from lesions of the thalamic sensory nuclei--capable of provoking a syndrome of paresthesia-hyperpathia (P-HI)--provokes a loss of gate control normally ensured by this discriminatory system and thus releases the pathologic nociceptive reactivity. Some authors think that the thalamic lesion alters the activity of control of the VPL nucleus on the lumbosacral spinothalamic tract. This concept considers thalamic pain as identical with brain stem spinothalamic pain provoked by exclusion of the control system arising in the giant-cell reticular nucleus and projecting onto onto the posterior horns. However, most cases of thalamic pain appear to be dependent on another mechanism involving the thalamocortical loop. In this case the thalamic sensory nucleus lesion is involved insofar as it implicates the reciprocal thalamocortical connections and the reticular nucleus. Involvement of the Th-C-Th loop as the ultimate representative of the lemniscal gate control is supported by "pseudo-thalamic" pains related to cortico-subcortical lesions with abolished SEP. But the numerous cases of painful thalamic syndromes with lemniscal sparing and normal SEP lead to incriminate a lesion of a specific thalamocortical control system for pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

[Lymphocyte subpopulations of the blood and cerebrospinal fluid in acute polyradiculoneuritis. Study of 14 cases using monoclonal antibodies].

The T lymphocytes in blood and CSF of 14 patients with acute polyradiculoneuritis were studied using the OKT series of monoclonal antibodies. Results were compared with findings in two control groups. Three patients with cytomegalovirus infection showed elevation of circulating OKT 8. A significant increase in the mean ratio OKT 4/OKT 8 was noted in all other cases, corresponding in 4 of the 11 patients to a reduction in number of OKT 8 lymphocytes. The CSF was normal in 3 of the 14 cases.

Acute Disease↗

[Familial paroxysmal ataxia sensitive to acetazolamide. 3 cases in a new European family].

UNLABELLED: This family is the tenth reported world-wide and the second reported in Europe. Two of 3 brothers, their mother and probably their maternal grandmother were affected. CLINICAL FEATURES: paroxysmal bouts of ataxia and dysarthria, nystagmus of permanent gaze, the dominant autosomal transmission, the benign nature of the affection and the remarkable efficacy of acetazolamide were typical of familial paroxysmal ataxia. Specific points emphasized are the presence of a mild pyramidal syndrome as a permanent finding in 2 of these patients, and the anomalies of visual (longer lag period) and somesthetic (slowed conduction rate in the lemniscus medialis) evoked potentials probably the result of extension into other pathways than the cerebellar system. The finding of some degree of glucose intolerance, noted previously (Aimard, Vighetto et al., 1983) raises the question of the place of this disease in the group of paroxysmal ataxias due to pyruvic metabolism disorders.

Acetazolamide↗

[Treatment of morning migraine. Clinical and biokinetic correlation of programmed-release dihydroergotamine].

The authors have tested a new preparation of dihydroergotamine (microgranules in a capsule) by comparing the clinical results obtained in 30 patients suffering from morning migraine with the plasma levels of the active substance measured in 8 healthy subjects. The microgranules were administered in doses of 30 mg/24 hours and compared with a similar dose of a dihydroergotamine solution. The close correlation observed between sustained plasma levels and prolonged therapeutic effects indicates a truly programmed delivery of dihydroergotamine by the microgranule preparation.

Adolescent↗

A chronobiological study of melatonin, cortisol growth hormone and prolactin secretion in cluster headache.

The temporal organization of plasma melatonin, cortisol, growth hormone (GH) and prolactin secretion was examined in healthy rested controls and in patients suffering from episodic cluster headache. Eleven patients with typical cluster headache (10 men, 1 female) and 8 male controls were studied over a 24-h period: blood was collected at 2-h intervals during the day and at 1-h intervals at night. Plasma melatonin, cortisol, GH and prolactin levels were determined by radioimmunoassay. Most of the cluster headache patients showed a decrease in nocturnal melatonin secretion and the melatonin rhythm was even completely abolished in one patient. Chronobiological analysis of the cluster headache patients' 24-h plasma melatonin profile showed a significant decrease in amplitude and mesor: these were 58.7 pg/ml and 34.4 pg/ml respectively in control subjects, versus 18.7 pg/ml and 17.6 pg/ml for the patients. In addition, patients showed a significant phase-advance in their melatonin rhythm. For cortisol, the rhythm appeared slightly blunted in the cluster headache group and was significantly phase-advanced. The plasma prolactin profile showed no significant alteration, but for plasma GH the nocturnal peak was advanced in some patients; in the absence of sleep recording, however, no conclusion could be drawn. Results from this study suggest a neuroendocrine dysregulation in cluster headache in the endogenous clock which controls the pineal rhythmicity.

Adult↗

[Acute necrotizing herpetic encephalitis with a spontaneously improving clinical course].

A 70 year-old-man with recurrent herpetic keratitis had a meningo-encephalitis with transient left hemiplegia and disorders of consciousness. EEG disclosed periodic slow waves on the right temporal region. Isotope and CT scans showed focal abnormalities in the same region. Antibodies to herpes simplex virus were demonstrated by complement fixation in serum and specific antiherpes IgG and IgM by immunofluorescence assay in serum and CSF. A year later the patient had a status epilepticus. CT scan showed a large right temporal hypodense area. CSF was abnormal with pleiocytosis, increased protein and IgG levels. High titers of antiherpes IgG persisted in serum and CSF. Neuropsychological tests did not demonstrate any memory impairment. The occurrence of persistent inflammation after herpes simplex encephalitis is discussed. The unusual benign course without antiviral therapy, may be related to the reactivation of a latent infection with an efficient immunological response. The unilateral temporal necrosis may explain the absence of amnestic sequelae.

Acute Disease↗

[Deafness and tinnitus in flare-ups in 10 cases of multiple sclerosis].

Deafness in multiple sclerosis is rare, being reported in less than 1 p. 100 of the cases. Ten cases of deafness associated with tinnitus during acute episodes of multiple sclerosis are presented, the diagnosis being definite in 9 patients and probable, according to McAlpine's criteria, in the tenth case. These were not cases where routine examinations demonstrated a latent hearing defect, but were all patients with sudden, often unilateral, incapacitating deafness during an acute episode of the disease, with regression usually after less than 3 months. Deafness recurred in 3 patients and was the initial symptom in 5 cases. Serial audiometric examinations were performed in most cases together with recordings of various evoked potentials, including early auditory evoked potentials during or after the onset of deafness in all 10 patients. BAEPs abnormalities were noted in 8 and appeared to be correlated more with brain stem demyelinization, as it has been established for a few years, than with the deafness itself. Severe anomalies of auditory evoked potentials regressed after the acute episode in only 1 patient. Lesions of the auditory pathways within the brain stem appear to be the cause of the deafness, as shown by results of auditory tests, which pointed to a central origin. The onset of deafness did not indicate a particular progression of multiple sclerosis.

Adult↗

[Cataplectic falls disclosing hypercalcemia].

Clinical manifestations of hypercalcaemic encephalopathy were heralded in three patients by isolated cataplexy-like falls without loss of consciousness. In one patient the falls with global hypotonia occurred every 5 to 10 seconds and were unaccompanied by changes in E.E.G. The falls disappeared after hypercalcaemia was corrected by excision of a parathyroid adenoma in two patients and by calcitonin injections in one. For this reason, there is little doubt that they were due to the hypercalcaemia, but their mechanism is poorly understood; it probably involves metabolic disturbances in the reticular systems of the brain stem. The connections between calcium metabolism and neuromediators in the brain stem are discussed.

Adenoma↗

Dissociation of early SEP components in unilateral traumatic section of the lower medulla.

Spinal and scalp early SEPs were recorded, using a noncephalic reference electrode, in a patient with a traumatic cervicomedullary lesion causing unilateral loss of position sense. Cervical N11 and N13 and scalp-recorded far-field P14 SEPs were clearly dissociated following stimulation of the affected side. The findings suggest that the P14 component is generated above the foramen magnum, whereas the cervical N13 has a spinal generator.

Adult↗