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Biomedical subjects

M Dumas

Publications and source records attributed to M Dumas.

At least 127 records · Page 7Linked to original sources

[The causes of intracranial hemorrhagic complications induced by antivitamins K].

Cerebral haemorrhage is the main life-threatening complication of oral anticoagulant therapy. In order to identify a means of prevention, the authors undertook a retrospective study of 68 consecutive cases of anticoagulant-related intracerebral haemorrhage. The mortality was 38.5%. The respective frequency of intracerebral haemorrhage, subarachnoid haemorrhage, acute and chronic subdural haematomas was 63.2, 16.2, 10.3 and 10.3%, respectively. On admission, nearly half the patients (53%) had prothrombin ratios inferior to 25%. A predisposing factor was found in 58% of cases: hypertension (30.6%), head injury (14.5%), alcoholism or drug interaction (11.2%), and one case of intracerebral aneurysm. A history of a transient ischaemic attack or of a cerebrovascular accident was found in 10.2% of cases and 11.7% had a previous anticoagulant related extracranial haemorrhage. The initial indications for oral anticoagulation were ischaemic heart disease (32%), atrial fibrillation (20.5%), secondary prevention of venous thromboembolic disease (17.6%) and primary prevention of venous thrombosis (11.7%). The duration of treatment for isolated ischaemic heart disease was over 6 months in all cases: the average duration of treatment was 12.4 months in phlebitis and pulmonary embolism. A critical review of the indications of treatment in the light of recent recommendations showed that if inappropriate indications were rare, the sometimes unnecessary prolongation of treatment was more common. Nearly half of these cases were receiving anticoagulants when the potential benefits were questionable at the time of the haemorrhagic complication. Clinical and biological follow-up is necessary for patients on anticoagulants; minor bleeding complications may be the prelude to major haemorrhage. Biological follow-up is based on control of the international normalised ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Hydroxycoumarins↗

Effects of three K+ channel openers on airways and pulmonary circulation in the isolated guinea-pig lung.

The antispasmodic and spasmolytic effects of levcromakalim (BRL 38227), aprikalim (RP 52891) and pinacidil were investigated in airways and pulmonary vessels of the isolated guinea-pig perfused lung. In airways, the three drugs exhibited modest antispasmodic properties, and pinacidil was more potent than levcromakalim and aprikalim against the contractions induced by carbachol (0.001-10 microM) or K+ (5-50 mM). Whereas levcromakalim and aprikalim acted only at low concentrations of K+, the rightward shift of the K+ concentration-effect curve produced by pinacidil was observed at all K+ concentrations (5-50 mM), suggesting that a mechanism of action other than K+ channel opening is involved in the effects of pinacidil. Pinacidil (0.3-100 microM) had the greatest spasmolytic effect in airways precontracted by carbachol (0.3 microM). The three K+ channel openers were equipotent against the sustained contractions of airways induced by 25 or 30 mM K+ and their spasmolytic activity was more marked against contractions induced by low rather low than high K+ concentrations. Levcromakalim and aprikalim were more effective as relaxant than as antispasmodic drugs. In K(+)-precontracted pulmonary vessels, the relaxant activity of pinacidil and levcromakalim was more pronounced than that observed in airways, suggesting a vascular selectivity of these drugs.

Animals↗

Cell culture evidence for neuronal degeneration in amyotrophic lateral sclerosis being linked to glutamate AMPA/kainate receptors.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motor neurons. Glutamate, a potent central-nervous-system toxin, has been proposed as one possible factor in this motoneuron disease. Serum from patients with ALS is known to be toxic when added to neurons in culture. We report on the toxicity to rat neurons in culture of cerebrospinal fluid (CSF) from patients with ALS. CSF were obtained from 10 ALS patients, 10 neurological controls, and 10 other controls. ALS CSF was added at dilutions of 50%, 20%, or 10% and neuron survival was assessed after 24 h. The neuroprotective effects of antagonists to two glutamate receptors were also assessed. ALS CSF was significantly neurotoxic, with a neuronal survival rate of only 47% compared with 80% or so for control CSF. This neurotoxicity was blocked by CNQX, an antagonist to the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptor but not by two N-methyl-D-aspartate (NMDA) antagonists. ALS CSF contains a specific neurotoxic factor which is AMPA/kainate-like which could have a role in the neuronal degeneration of this disease.

2-Amino-5-phosphonovalerate↗

Lack of association between peripheral neuropathy and HTLV-I infection in west Africa. Epidemiological, serological and nerve biopsy study.

Patients (n = 1166) with various neurological disorders hospitalized in Dakar, Abidjan, Lomé and Ouagadougou were examined prospectively over a 42-month period. Seropositivity for HTLV-I alone was found to be 1.8%, which is comparable to that estimated for the general population in Africa. Eighteen of the patients with TSP and only 5 with PN were HTLV-I positive, but co-infections were found in 30-40% of cases. Discrete and unspecific lesions were observed on light and electron microscopic examination of peripheral nerve biopsies from 11 patients. Since spastic paraparesis emerges as the disorder containing the largest number of HTLV-I-positive individuals, it may be premature to conclude that HTLV-I is a causal agent in PN. Nevertheless, their rarity and the frequency of retroviral co-infections distinguish these cases of African HTLV-I-associated myelopathy from comparable cases observed in other parts of the world.

Adolescent↗

HTLV-1 antibody class and subclass distribution in African TSP and control populations.

The humoral immune responses in 44 sera from HTLV-1 seropositive African subjects were compared. The sample population was composed of 12 patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), 12 patients with other neurological conditions and 20 asymptomatic carriers. Samples HTLV-1 antigens were tested against all immunoglobulin classes and IgG subclasses, using the Western blot technique with polyclonal and monoclonal antibodies. Whilst IgG reacted with gag, env and tax products for the three groups studied, IgM and IgA were found to react more frequently with HTLV-1 in HAM/TSP patients. For these patients, IgM and IgA were particularly directed against tax and env proteins. Among IgG subclasses, IgG1 was most sensitive to gag, env and tax products reacting in similar proportions in all three groups. IgG2 and IgG4 were apparently not involved. IgG3 was most responsive in HAM/TSP patients. These data are similar to those observed in AIDS patients, LAS and HIV asymptomatic carriers and emphasize the role of HTLV-1 in HAM/TSP.

Acquired Immunodeficiency Syndrome↗

Sleep-wake cycle in human African trypanosomiasis.

Sleeping sickness patients are classically described as sleepy by day and restless by night. Prior to this study, we had objectively confirmed this description by recording 24-h sleep patterns in a patient with human African trypanosomiasis. We report 24-h polysomnographic recordings (EEG, electrooculogram, electromyogram, electrocardiogram, and nasal, buccal, and thoracic respiratory traces) performed on two eight-channel electroencephalographs in eight patients with untreated sleeping sickness at an early stage of meningoencephalitis. As in our previously reported patient, there was no hypersomnia. The patients presented mainly a disorganization of the circadian alternation of sleeping and waking, with no or little alteration in the states of vigilance at this early stage of the disease. The disorganization was proportional to the degree of severity of the clinical symptoms. It may be due to an alteration in biological clock mechanisms.

Adolescent↗

Monitoring of the motor pathway during spinal surgery.

Paraplegia caused by irreversible lesions of the spinal cord is one of the major possible complications after scoliosis surgery. Several monitoring methods have been proposed but none are completely satisfactory. Since 1986 the authors assessed motor pathways during scoliosis surgery, using electrical stimulation of the motor cortex and lower limb muscle recordings (tibialis anterior muscle). Twenty-seven patients were included in this study: 25 with idiopathic scoliosis and 2 with dorsal kyphosis. Recordings in anesthetized patients with hypothermia were performed before and after spinal derotation during the surgical procedure. Magnetic cortical stimulation was carried out in ten awake patients before and after surgery. Reproducible responses were obtained in 22 patients under anesthesia. In eight patients no difference of the latency of the muscle response was detected before and after the correction of the spinal angulation. In 14 patients the increase of latency ranged from 0.4 ms to 5.2 ms. No correlation was found between the slowing of motor conduction and the magnitude of spine correction. No central neurologic complications were seen after surgery. The authors concluded that their study demonstrated that motor pathway assessment in anesthetized patients can be performed at different times during the surgical procedure. This technique should help in the future monitoring spinal function during scoliosis surgery.

Adolescent↗

[Peritoneal tuberculosis and continuous ambulatory peritoneal dialysis].

Depressed immunity in uremic patients increases by ten the risk of tuberculosis. In such patients, 40% of tuberculosis manifestations are extrapulmonary, and peritoneum is involved in about 6% of the cases. Seventeen cases of peritoneal tuberculosis have been so far reported in CAPD patients, and we add a new case. The prognosis of the disease is severe since 8 patients died. Three deaths out of 8 are directly linked to tuberculosis. Indeed, peritoneal tuberculosis diagnosis is hard and often late, at least for two main reasons: at first, it can be difficult to exclude the other causes of lymphocytic peritonitis (viral, fungal, bacterial, etc.), secondly, growth of mycobacteria in dialysate effluent cultures is late and inconstant. Omental biopsy in lymphocytic peritonitis of unknown origin could be of great value for an early diagnosis. Despite the adaptation of antituberculous drugs doses, side-effects are not so rare: optical neuritis and liver toxicity in our case. In spite of ultrafiltration loss, stopping CAPD is not always necessary, as in the reported case.

Aged↗

Improvement in motor evoked potentials and clinical course post-steroid therapy in multiple sclerosis.

Motor evoked potentials (MEP) were recorded in 23 patients with definite relapsing multiple sclerosis before and after treatment with a short course of high dose of methylprednisolone. MEP were performed together with clinical examination just before treatment, and 6 and 60 days later. The following results were observed: (1) a statistically significant relationship between the corticospinal deficit and the alteration in MEP, (2) a significant improvement in latency of MEP by day 6, (3) a significant correlation between the change in the Kurtzke disability scale rating and the improvement in MEP. The results provide further evidence for the possible effectiveness of short courses of high dose corticosteroids in the treatment of relapses of multiple sclerosis and the usefulness of MEP in its assessment.

Adult↗

Comparative pharmacokinetics of tetrahydropyranyl-doxorubicin and doxorubicin in rat isolated lung.

Rat isolated perfused lungs (Sprague-Dawley rats, n = 20) were studied to compare the pulmonary uptake of a new anthracycline, tetrahydropyranyl-doxorubicin (THP-DXR) with that of doxorubicin (DXR). Lung perfusions were initiated with a constituted medium containing either drug at concentrations of 1, 10 or 100 microM. Lungs were perfused by recirculation for 60 min. Thirteen perfusate samples were collected over 60 min and subjected to HPLC for assay. The perfusate concentration of THP-DXR decreased to 24 +/- 5% of the initial concentration and to 8 +/- 2%, 20 and 60 min after the beginning of the infusion, respectively. Corresponding values for DXR were 77 +/- 16 and 52 +/- 15%, respectively (P less than 0.05). During the THP-DXR perfusion, the area under the perfusate concentration vs time curve (AUC) was decreased to one-third and the clearance was increased 3-fold (P less than 0.05). The pulmonary concentration of THP-DXR reached 0.032 +/- 0.01 mumol g-1 60 min after the beginning of a perfusion of 1 microM of the drug. This concentration increased to 0.379 +/- 0.11 mumol g-1 when the initial dose concentration was 10 microM. Corresponding lung concentrations for DXR were 0.013 +/- 0.001 and 0.150 +/- 0.04 mumol g-1, respectively (P less than 0.05). The perfusate concentration/initial concentration ratio decreased by the same amount whether a 1 or 10 microM initial concentration of either drug was used. An initial concentration of 100 microM of THP-DXR, unlike DXR, consistently induced oedema in the perfused lung. No metabolite of either drug was revealed during the course of our study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Myelin palingenesis. 2. Immunocytochemical localization of myelin/oligodendrocyte glycolipids in multilamellar structures.

Myelin is a membrane with unique characteristics that set it apart from any other membrane. It has a very high lipid:protein ratio (approximately 75:25) not found in other multilamellar membranes; it has a high content of two glycolipids--galactocerebrosides and sulfatides--which account for 26.5% of its lipids. The physiological role of these glycolipids in myelin and/or oligodendrocytes is unknown, but evidence that Abs directed against them interfere with myelination has been presented. Moreover, one of the early events in the process of oligodendrocyte differentiation prior to myelination is the acquisition of galactocerebroside on their surface. In earlier work, we have demonstrated that adhesion of oligodendrocytes to a positively charged substratum signals the commencement of myelinogenesis. Among the events that take place following adhesion are the rapid synthesis of glycolipids. Since over time in culture, oligodendrocytes elaborate multilamellar membranes that contain all the myelin characteristic proteins, we undertook to investigate whether these structures also accumulate myelin characteristic glycolipids. We have used three monoclonal antibodies--two are directed against galactocerebroside, the third one is an antisulfatide--in conjunction with the immunogold method, at the electron microscopic level, to examine the distribution of these glycolipids in the multilammelar structures that accumulate in long-term oligodendrocyte cultures. Our data show that galactocerebrosides and sulfatides are present in the multilamellar structures. Staining is easily demonstrated on the outermost membrane. However, as was the situation with myelin proteins, detection of these glycolipids on the inner lamellae is only achieved at the expense of destroying the ultrastructure. This is so, independent of whether the structures are compact or not.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗