Encephalopathy with seizures after use of aluminium-containing bone cement.
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Biomedical subjects
Publications and source records attributed to P Mahieu.
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Glomerular mesangial cells play a major role in the structure of capillary loops, generation of mediators of inflammation, and uptake of macromolecules. We demonstrate here that isobutylcyanoacrylate nanoparticles loaded with actinomycin D (ADNP) concentrate in rat mesangial cells in vitro and in vivo, as compared to the free drug (AD). In normal rats injected with 20 micrograms of 3H-ADNP or 3H-AD, the uptake ratios 3H-ADNP/3H-AD measured in whole kidneys at 30 and 120 min were 2.2 +/- 1.0 and 2.3 +/- 0.9, respectively. The same ratios calculated for isolated rat glomeruli and tubules, were 4.1 +/- 0.5 and 0.8 +/- 0.2 at 30 min, and 2.6 +/- 0.5 and 0.6 +/- 0.3 at 120 min, respectively. In the glomeruli, the absolute uptake of 3H-ADNP corresponded to 7.5 (30 min) and 1.8 (120 min)% I.D./100 mg of protein. In rats with experimental glomerulonephritis, the uptakes of 3H-ADNP and 3H-AD by the glomeruli were 6.9 and 4.0 times higher than in normal rats, respectively. In vitro experiments demonstrated up to 5 times higher uptake by glomerular mesangial cells than by epithelial cells. Uptake was maximum after 60 min, higher at 37 degrees C than at 4 degrees C, dependent on the presence of fresh serum and inhibited by cytochalasin-B. Drug targeting by nanoparticles is thus possible to renal cells involved in inflammatory processes, especially mesangial cells and macrophages. Nanoparticles could also be useful for lowering drug concentration in tubular cells, to reduce any tubular toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: To determine the main characteristics of gastroduodenal motility in mechanically ventilated, critically ill patients. DESIGN: Case series; comparison with a parallel control group. SETTING: Intensive care unit in a university teaching hospital. PATIENTS: Twelve adult critically ill patients who required > 2 days of mechanical ventilation as a consequence of neurologic or respiratory disease. Control sample of 12 overnight, fasting, healthy volunteers. MEASUREMENTS AND MAIN RESULTS: Pressure changes in the gastric antrum, proximal duodenum, and distal duodenum were simultaneously recorded during a 4-hr period by a multilumen tube (perfused catheter technique). The migrating motor complex and its three successive phases were identified according to usual definitions (phase 1, period of quiescence; phase 2, period of irregular contractile activity; phase 3 or activity front, period of high-frequency, regular contractions). Contractions and activity fronts at each site were quantified. The mean duration of the migrating motor complex was determined in the duodenum, as well as the contribution of each phase (phases 1, 2, 3) to the length of the complete cycle. The propagation characteristics of each activity front were assessed visually. In the patients, the number of contractions was markedly decreased in the antrum, where activity fronts were totally absent. In the duodenum (proximal and distal), the number of contractions and the occurrence of activity fronts were comparable in both groups. Although the duration of the duodenal migrating motor complex was similar in the two groups, the relative contribution of the quiescence period (phase 1) to the total cycle length increased and the contribution of phase 2 decreased in the patients. Three patients exhibited abnormally propagated (retrograde or stationary) activity fronts in the duodenum. CONCLUSIONS: Gastroduodenal motility is severely impaired in this group of mechanically ventilated patients. Activity fronts of the migrating motor complex never originated in the stomach, which was hypokinetic; qualitative disorders of the migrating motor complex were present in the duodenum. The loss of peristaltic activity in the stomach and, to a lesser degree, in the duodenum is consistent with an important role for motility disorders in the occurrence of digestive microbial overgrowth in such patients.
We report a case of organophosphate poisoning with a commercial preparation of malathion (deliberate ingestion of Malathane Garden Spray: malathion 15% in isopropyl alcohol) in which the initial cholinergic crisis was followed by cardiac, pulmonary, neurological and renal manifestations. They occurred when erythrocyte and plasma cholinesterases were reactivating. A chemical analysis of the pesticide preparation revealed, apart from malathion itself, the presence of isopropylmalathion and O,O,S-trimethylphosphorothioate. Although pure malathion is regarded as one of the safest organophosphate insecticides, this observation underlines the possibility of severe complications after exposure to a preparation which has been stored for a long period of time.
Three-modality evoked potentials (TMEPs) were recorded in 184 comatose patients (52 anoxic, 132 traumatic). Both types of comas were associated with different TMEP patterns. Anoxic comas were associated with prognostically relevant abnormalities of cortical (visual and somatosensory) evoked potentials (EPs), while brainstem (auditory and somatosensory) EPs were not specifically altered. The prognostic value of TMEPs in anoxic comas depended on the time elapsed from the acute episode: mildly altered EPs were associated with a better prognosis in the first 10 days; strongly altered TMEPs were associated with a poorer prognosis from the first day; no definite conclusion could be drawn from mildly altered EPs after the 10th day, or from strongly altered TMEPs in the first 24 h. By contrast, both the cortical and the brain-stem activities were altered in head trauma. The abnormalities were clustered into four patterns: hemispheric damage without brain-stem involvement (pattern 1), mesencephalic lesion (pattern 2), transtentorial herniation (pattern 3), and brain death (pattern 4). Patterns 3 and 4 were uniformly associated with death. The prognostic value of pattern 1 was similar to that observed in anoxic comas. The outcome of patients presenting pattern 2 depended on the extent of hemispheric damage associated with the mesencephalic lesion; we thus suggest to systematically perform magnetic resonance imaging (MRI) in patients presenting TMEP pattern 2. We finally demonstrated that a few patients presenting absent cortical activities in the very acute stage of coma can eventually recover a good neurological function.
We report two cases of severe acetaminophen poisoning with favorable outcome after delayed medical treatment with N-acetylcysteine, despite severe hepatic disturbances. We briefly review the most commonly accepted prognostic criteria and the role of liver transplantation.
A 48-year-old woman was referred from Zaire with suspected rabies encephalitis. Survival was 34 days after the onset of symptoms and the diagnosis of rabies was ultimately proven after brain autopsy. Serial neurophysiological investigations, including EEG and multimodality evoked potentials and radiological examinations (cerebral magnetic resonance imaging and computed tomodensitometry) were performed. Whereas the clinical findings and EEG were compatible with brain death at the end of the course, this diagnosis could be definitely ruled out by multimodality evoked potentials, magnetic resonance imaging and autopsy. The validity of multimodality evoked potentials is discussed in this particular setting.
A 61-year-old man without previous medical history was admitted for Guillain-Barré syndrome (GBS). Carbamazepine was prescribed on day 72 for dysesthesia occurring at the time of recovery. Subsequently, severe cardiac conduction disturbances (asystole, atrioventricular block) were observed and a permanent pacemaker had to be inserted. The possible relationship between carbamazepine therapy and cardiac side effects is discussed in this condition, as GBS itself is often complicated by cardiac arrhythmias.
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Severe Guillain-Barré syndrome (GBS) usually results in life-threatening autonomic disturbances requiring a close monitoring of the patient in an Intensive Care Unit. Besides dangerous cardiac manifestations, neuroendocrine changes are also reported and could induce electrolytes and fluid balance impairments. Polyuria has been observed in a severe case of GBS occurring in a 16-year-old boy. Consecutive blood samples were obtained for renin, aldosterone, antidiuretic hormone and atrial natriuretic factor measurements. Polyuria in GBS is multifactorial and would be partly due to a dysregulation of osmoreceptors.
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A solid-phase ELISA was set up to measure the direct binding capacity (BC) of different, commercially available, purified human IgA preparations to plates coated with human fibronectin (FN). It was found that secretory, polymeric, and, to a much lesser extent, monomeric IgA exhibited elevated FN-BC as compared to their BC to plates coated with bovine serum albumin. This binding was specific since not observed with human IgG or IgM antibodies. In addition, we noted that this interaction was dose dependent, Ca2+ dependent, saturable, and not covalent, was inhibited by soluble FN, but not by a prior incubation of FN-coated plates with anti-human fibronectin antibodies, and appeared to involve on the dimeric FN other structures than its heparin-binding, collagen-binding, or C1q-binding domains. Similar experiments conducted with normal plasma indicated that plasma IgA, but not plasma IgG or IgM, was also capable of significant binding to FN-coated plates. In contrast, serum IgA did not significantly bind to those plates under otherwise identical experimental conditions. Thus, the coagulation process induces a strong decrease in the FN-BC of circulating IgA, which implies the necessity of using plasma rather than serum to study such interactions. The apparent molecular weight of plasma IgA interacting with FN-coated plates ranged between 450 and 900 kd, and its major binding characteristics were quite similar to those observed with purified polymeric IgA. The FN-BC of plasma IgA was then measured by the same ELISA in 30 patients with primary IgA nephropathy (IgAN) and in 23 healthy controls. The mean FN-BC of plasma IgA was significantly higher in patients than in normal controls. This enhancement was due mainly to the augmentation in the concentration of circulating "macromolecular" IgA and was significantly correlated with the plasma levels of IgA-FN complexes. However, the pathogenetic role of these findings was probably not determinant since similar observations were made in alcoholic liver cirrhosis without urinary abnormalities and since the FN-BC of plasma IgA or the plasma levels of IgA-FN complexes were not correlated with the various biological parameters of evolutivity of primary IgAN. In conclusion, these studies suggest that the ability of polymeric IgA to directly bind to FN is involved in the formation of circulating IgA-FN complexes and that this normal binding process, although enhanced in IgAN, is probably not responsible for kidney injury, at least in the patients studied.
Cardiac arrhythmias and circulatory collapse account for the high mortality reported after severe chloroquine poisoning. We have recently observed a 17-year-old man who ingested an 8 g chloroquine overdose. Cardiac arrest occurred within 1 h. Cardiogenic shock was refractory to epinephrine, dopamine and molar sodium lactate. Amrinone, a bipyridine analog, was then successfully used to improve haemodynamic conditions.