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Biomedical subjects

A Muller

Publications and source records attributed to A Muller.

At least 109 records · Page 6Linked to original sources
PubMed1994

Protection by prostaglandins from glutamate toxicity in cortical neurons.

The growing evidence that glutamate may be an important agent mediating ischemic damage to neurons, led us to investigate the possible protective effects of pharmacological agents against glutamate in a model system of cortical neurons. In this study we examined, in particular, the cytoprotective effect of prostaglandins. Experiments were carried out in vitro by using rat cortical neurons in culture for 10 days. They were incubated for 3h with glutamate (10 microM) in the presence or absence of various pharmacological agents including prostaglandins (PGD2, PGE1, PGE2, PGF2 alpha, PGI2, 6-Keto-PGF1 alpha, carba-TXA2, carba-PGI2 and PGF2 alpha-methylester). Increase in lacticodehydrogenase (LDH) release into the culture medium has been measured as an index of cell injury. When neurons were incubated with glutamate they released LDH due to NMDA-receptor activation since D-L-2-amino-5-phosphonovaleric acid, a specific receptor antagonist, protected the cells. The protective activity of oxypurinol, amflutizole, superoxide dismutase, NG nitro-L-arginine and quinacrine, also suggests that xanthine oxidase activation, the generation of superoxide radical, and nitrix oxide, as well as phospholipase A2 stimulation are responsible for neuron injury (i.e. LDH release). All the tested prostaglandins, except PGF2 alpha-methylester, afforded significant protection at concentrations between 0.1 and 10 microM. The order of potency of the prostanoids was: PGF2 alpha = PGE2 > Carba-TXA2 > PGE1 > PGD2 > PGI2 = Carba-PGI2 > 6-Keto-PGF1 alpha. Additional experiments showed that prostaglandins did not compete for the NMDA binding site and that they did not inhibit free radical-related membrane damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Prostacyclin (PGI2) protects rat cortical neurons in culture against hypoxia/reoxygenation and glutamate-induced injury.

Arachidonic acid and its metabolites are released in brain extracellular fluids as a result of ischemia and may participate in either damaging or protecting neural tissues. This study investigates the neuroprotective effect of prostacyclin (PGI2) on hypoxia (5 h)/reoxygenation (3 h) and on the excitotoxic neurotransmitter, glutamate (10 microM), in rat cortical neuron cultures. At microM concentrations, PGI2 inhibits lactate dehydrogenase release, a cell-injury marker. These results, showing a direct cytoprotective effect of PGI2 on brain cells, reinforce its beneficial properties on vessels and circulating cells in cerebral ischemia.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Superoxide and nitric oxide cooperation in hypoxia/reoxygenation-induced neuron injury.

Oxygen-derived free radicals are implicated in hypoxia- and reoxygenation-related brain injury. In addition, excitatory amino acid neurotransmitters seem to be involved in this neurotoxicity and could act through the L-arginine/nitric oxide (NO) synthase pathway. In the present study we have used rat forebrain neurons in culture submitted to hypoxia/reoxygenation to investigate the relative role of free radicals, glutamate, and nitric oxide in hypoxic neuronal injury. Hypoxia (5 h) followed by reoxygenation (0-24 h) induced cell damage assessed by lacticodehydrogenase release into culture medium. Superoxide dismutase (SOD, 500 U/mL), D-L-2-amino-5-phosphonovaleric acid (100 microM), a glutamate receptor antagonist, and NG-nitro-L-arginine (100 microM), an NO synthase inhibitor, protected the neurons. The effect of NG-nitro-L-arginine was reversed by adding L-arginine (10 mM) in the culture medium, and hemoglobin, which scavenges NO, also afforded protection. Hypoxia (5 h) provoked glutamate release from neurons, and this effect was inhibited by SOD. Exogenous glutamate (1-100 microM) induced lacticodehydrogenase release, and this effect was inhibited by glutamate antagonism, NO synthase inhibition, or superoxide radical scavenging. These data are consistent with the following sequence of events in hypoxia-related neurotoxicity: free radical formation, glutamate release, and activation of NO synthase leading to superoxide and NO cooperative toxicity.

Animals↗
PubMed1993

[Is the immunologic evaluation in endocarditis of value?].

Forty-seven patients were included in a prospective trial to define the interest for searching immunologic abnormalities during endocarditis. No specific abnormalities were found, aside some patients with endocarditis who have a high levels of immune complexes. These results suggest that the interesting immunologic abnormality is the presence of an high level of immune complexes could be of interest in endocarditis.

Adult↗
PubMed1993

Medicare prospective payment reforms and hospital utilization. Temporary or lasting effects?

Early evaluations of the Medicare prospective payment reforms found them very effective in reducing hospital utilization. In this study, the author investigated whether the reforms remained effective throughout the first decade of implementation. Seasonal autoregressive-integrated-moving average (ARIMA) models with intervention components were applied to age-specific national times series of hospital admissions, average length of stay, inpatient days, and adjusted inpatient days. Three alternative regulatory impact patterns were tested using quarterly data collected by the National Hospital Panel Survey spanning the period 1970:1 to 1992:1 (n = 89). The reimbursement reforms seem to have reduced hospital admissions, average length of stay and patient days during fiscal years 1983-1984, but significant readjustments relative to projected levels occurred for all four utilization measures during fiscal years 1985-1986. Similar, yet less pronounced readjustments, were found in the analysis of non-Medicare time series suggesting regulatory spill-over effects. Sicker patients and hospital diversification efforts are two plausible reasons for the relative increase in hospital utilization during 1985-1986. The Medicare reimbursement reforms appear to remain effective in reducing hospital utilization, but at a reduced rate.

Aged↗
PubMed1993

Oncogenic activation of c-ABL by mutation within its last exon.

The c-ABL proto-oncogene is a predominantly nuclear localized tyrosine kinase. A random mutagenesis scheme was used to isolate c-ABL mutants whose expression produced a transformed phenotype in rodent fibroblast cells. An in-frame deletion within the central region of the last exon was identified in one ABL mutant. The mechanism of c-ABL oncogenic activation by mutation within the last exon differs both functionally and structurally from those of v-ABL and BCR/ABL. This class of ABL mutants shows increased tyrosine phosphorylation of cellular proteins in vivo but low levels of autophosphorylation. Last-exon ABL mutants are distinguished from v-ABL or BCR/ABL by their inability to transform primary bone marrow cells or support the growth of transformed pre-B cells. These findings define a new mechanism of oncogenic activation for the ABL kinase through mutations in the last exon which do not require amino-terminal deletions or mutations within the src homology regions.

3T3 Cells↗
PubMed1993

Evaluation of the "Auto-Stat 6010" automatic osmometer and its comparison with the "digimatic-advanced 3DII" manual osmometer.

The results are presented of a comparative study between two osmometers, a manual one, Digimatic-Advanced 3DII (Advanced Instruments, Medical Europa, Barcelona), and an automatic one, Auto-Stat 6010 (Kyoto, Daiichi, Kagaku, Menarini, Firenze). Both osmometers have the same operation principle, but they employ different systems for determination of the freezing point depression. Both instruments showed good precision (CV < 1%), accuracy, and a wide range of linearity. In the assay of 133 sera and 101 24-h urines, the methods showed a good correlation (r = 0.945 and r = 0.999) and the Anova test showed no statistical difference between the means (p > 0.05). The carry over effect in the Auto-Stat was statistically significant (p < 0.001) but within the range of imprecision of the osmometers. Variation due to evaporation is lower than 0.8%. In conclusion, we are sure that both osmometers are useful in the laboratory, although the Auto-Stat 6010 osmometer has the advantage over the Digimatic-Advanced 3DII of automatic sample processing.

Calibration↗
PubMed1992

Ca2+ homeostasis and fast-type sarcoplasmic reticulum Ca(2+)-ATPase expression in L6 muscle cells. Role of thyroid hormone.

The effect of thyroid hormone (L-tri-iodothyronine; T3) on the cytosolic free Ca2+ concentration ([Ca2+]i) in L6 myotubes was studied at rest and during activation to explore the possible mediating role of [Ca2+]i in the T3-induced net synthesis of fast-type sarcoplasmic reticulum (SR) Ca(2+)-ATPase. The mean [Ca2+]i at rest was approx. 115 nM in myoblasts, control myotubes and T3-treated myotubes. Therefore it is unlikely that the T3-induced elevation of Ca(2+)-ATPase levels is mediated by [Ca2+]i changes. To investigate the influence of the 4-fold higher Ca(2+)-ATPase levels in T3-treated myotubes (compared with controls) on [Ca2+]i, interventions with caffeine (10 mM) and a high extracellular K+ concentration ([K+]o) (30 mM) were applied which initially mobilize Ca2+ predominantly from the SR. The results showed a lower (caffeine) or not significantly different (high [K+]o) increase in [Ca2+]i in T3-treated myotubes compared with controls. No rise in [Ca2+]i was found in myoblasts with caffeine or high [K+]o. The role of [Ca2+]i in the regulation of Ca(2+)-ATPase levels was investigated by varying [Ca2+]i through exposure of cells to different concentrations of extracellular Ca2+ (0.2-1.8 mM) and ionomycin (0.1-0.25 microM). At subnormal [Ca2+]i (55 nM) the T3-induced net synthesis of Ca(2+)-ATPase was virtually abolished, and at supranormal [Ca2+]i (195 nM) it was greatly depressed. Intermediate stimulation of net Ca(2+)-ATPase synthesis was found at [Ca2+]i of 95 and 165 nM, with an optimum at approx. 125 nM. Similar but less pronounced effects were found for the basal Ca(2+)-ATPase levels. In contracting primary rat myotubes, Ca(2+)-ATPase levels were significantly lower than in tetrodotoxin-arrested myotubes. The same results were obtained in the presence of T3. Since the mean [Ca2+]i in contracting cells is higher than in resting cells, these data agree with those obtained in the L6 cells with ionomycin. A major conclusion of this study is the existence of a [Ca2+]i optimum, near resting levels, for the expression of the fast-type Ca(2+)-ATPase in the L6 muscle cell line.

Animals↗
PubMed1992

Blood eosinophilia in Hodgkin's disease. A follow-up of 25 cases in Venezuela.

Twenty-five patients with Hodgkin's disease and high eosinophil counts were observed for an average of 90 months. Fluctuations in the levels of eosinophils were important in the course of observation. No relation with stages, histologic type, or evolution was noticed. Steroid-containing regimens and severe premortem conditions seemed to lower the counts. Relapse-free survival was shorter in our 25 patients than in a control group of 50 patients with Hodgkin's disease and no eosinophilia who had approximately the same stage, histologic type, and treatment of disease. However, the overall survival was somewhat better for the eosinophilic patients with stages IIIB and IV (0.1 greater than P greater than 0.05).

Adolescent↗
PubMed1992

Synthesis and contractile activity of new pseudopeptido and thioaromatic analogues of leukotriene D4.

Seven new pseudopeptido and thioaromatic leukotriene analogues were synthesized and their agonist-antagonist and binding activities investigated. The synthesis led to the pleasing observation that the analogue in which the cysteinyl-glycine moiety was replaced by a 6-mercapto-3-(E)-hexenoic acid, not only exhibited potent affinity (guinea-pig lung parenchyma, IC50: 5 x 10(-9) M) but also showed 30% of the LTD4 agonist activity (guinea-pig ileum, ED 50: 2.7 x 10(-9)) giving very important key information on LTD4 geometry to the receptor. This compound was the first stable new pseudopeptido-leukotriene with such agonist activity and should contribute to the understanding of the metabolism of leukotriene D4. In addition, inversion of chirality at C5 and C6 carbon atoms of the leukotriene chain or replacement of the cysteinyl-glycine moiety by a thioaromatic acid led to new weak antagonists of the LTD4.

Animals↗
PubMed1992

[Treatment of algodystrophy of the knee: diagnostic error and misplacement of the peridural catheter].

A fifty-year-old female patient, with a history of reflex sympathetic dystrophy of the left hand and right ankle, complained of pain in her right knee. The skin was slightly oedematous and red, whereas the knee X-ray was quite normal. These findings were thought to be related to another episode of reflex sympathetic dystrophy, and treatment with continuous epidural morphine and lidocaine was prescribed. Catheter insertion was uneventful. However, the lack of pain relief led to the suspicion of femoral neuralgia. Plain X-ray films of the lumbar spine showed the epidural catheter to be passing through the L2-3 foramen. The catheter was removed. The development of fever and major inflammatory signs of the knee revealed gout arthritis. This case stresses the need for careful repeated clinical examination in order to make the right diagnosis. On the other hand, when the expected effect of drugs administered by the epidural route fails to appear, the catheter's position should be promptly checked by X-ray.

Analgesia, Epidural↗
PubMed1992

[Spinal administration of analgesic substances in the treatment of chronic pain].

The various forms of chronic pain conditions are described and related to recent knowledge of their neurophysiology. The pharmacology and mode of action of substances used for pain relief by intrathecal, subdural or peridural injection is presented. The modalities of their application, the results obtained and the complications encountered are detailed.

Analgesics↗
PubMed1992

[Fractures of the humeral shaft: role of fasciculated nailing using Hackethal's method. Apropos of 129 cases].

This retrospective study was based on 141 diaphyseal fractures of the humerus, treated by Hackethal fasciculated pinning, among 371 fractures followed up during 10 years in our department. There were six preoperative radial paralyses. The mean consolidation delay was 65 days. Six fractures did not unite and there was no sepsis. The only immediate neurological postoperative complication was a regressive cubital paralysis. 72 fractures could be followed-up with a mean of 4 years, to establish a functional result chart. 94.4 per cent of the results were good and very good, 2 shoulder stiffness and only one elbow stiffness. The displaced fractures of the humeral diaphysis on D2 to D5 zones, as well as pathological fractures are good indications for Hackethal fasciculated pinning.

Bone Nails↗
PubMed1991

The elevation of sarcoplasmic reticulum Ca2(+)-ATPase levels by thyroid hormone in the L6 muscle cell line is potentiated by insulin-like growth factor-I.

Net synthesis of the fast-type sarcoplasmic reticulum (SR) Ca2(+)-ATPase was studied in the muscle cell line L6AM using an immunochemical assay (e.l.i.s.a.). In addition, Ca2+ uptake by SR was monitored in muscle cell homogenates by a method employing the fluorescent Ca2+ indicator fura-2. Measurements were done both in differentiating myoblasts and in myotubes. Ca2(+)-ATPase levels were low (1 pmol/mg of protein) in undifferentiated myoblasts (controls) and only doubled over a period of 8 days in the absence of thyroid hormone (L-triiodothyronine; T3). This corresponded to a similar increase in Ca2+ uptake activity. Only half of the myoblasts fused under these conditions. Fusion was not increased in the presence of T3 (5 nM), but Ca2(+)-ATPase levels increased 4-fold and the Ca2+ uptake activity doubled compared with controls. In contrast, insulin-like growth factor-I (IGF-I) induced almost complete myotube formation (greater than 90% fusion), but only slightly stimulated (50%) net Ca2(+)-ATPase synthesis above control levels. However, the doubling of the Ca2+ uptake stimulation by IGF-I was comparable with that caused by T3. The effects of T3 plus IGF-I on Ca2(+)-ATPase levels and Ca2+ uptake activity were more than additive. Furthermore, the temporal relationship between the induction of Ca2(+)-ATPase net synthesis and Ca2+ uptake activity was identical with the two hormones. Qualitatively similar results were obtained when T3 and IGF-I were added to maximally fused cell cultures. The enhanced effect of T3 on Ca2(+)-ATPase net synthesis and Ca2+ uptake activity in the presence of IGF-I cannot therefore be explained by an increased myotube formation stimulated by the latter. In both differentiating myoblasts and myotubes the effect of T3 was more prominent on Ca2(+)-ATPase net synthesis than on Ca2+ uptake activity, whereas in myotubes the opposite was observed for IGF-I. This could imply complementary actions of the two agents in the development of a functional SR.

Animals↗
PubMed1991

[Back pain after epidural anesthesia].

A 24-year-old female patient underwent a minor orthopaedic procedure under epidural anaesthesia. She had a past history of lumbar backache. The epidural anaesthetic was carried out with the patient sitting. However, she had an acute vagal reaction, with loss of consciousness and forward headfall. Thirty-six hours later, the patient complained of severe pains diffusing all over her vertebral column, together with sciatica and paravertebral muscle contraction which did not respond to drug treatment. An epidural abscess or haematoma was ruled out. The pain finally disappeared after a few days of wearing a cervical collar, taking anti-inflammatory drugs, and a few vertebral manipulations. The back pain was probably due to a posterior articular joint syndrome, worsened by the forward headfall. In view of the past history, an epidural anaesthetic should probably have been best avoided.

Abscess↗
PubMed1991

[Sympathetic nervous system, pain and epidural administration of morphine].

There are multilevel intrications between nociceptive afferences and sympathetic efferences: anatomical vicinity in visceral innervation; systemic and local activation of the sympathetic efferences in response to nociceptive stimulation; major role of sympathetic activation in the perpetuation of sympathetic dystrophies. The analysis of a retrospective series of 10 patients suffering from algodystrophia revealed that epidural morphine administration had a beneficial effect only in those which were treated at an early stage of their illness. Despite epidural morphine has been claimed to be without effect on the efferent sympathetic tone in normal animals and individuals, it seems that in some pathologic states, the sympathetic output can be depressed. Recent anatomical and neurophysiological evidences argue for such a possibility.

Analgesia, Epidural↗