HPLC/MS findings in a fatality involving sustained-release verapamil.

A fatality involving verapamil, a calcium channel blocker agent, is presented. A 51-year old male ingested 7200 mg of sustained-release (SR) verapamil at T0 and died 40 hours later of refractory, mixed shock and multiorgan failure. The symptoms displayed during hospitalization were quite typical and involved altered consciousness, hypotension, bradycardia, atrioventricular block, metabolic acidosis and renal failure. Verapamil and its primary metabolite, norverapamil, were assayed on eight plasma and two urine samples, successively taken between the admission to the ICU (T0 + 4 hours) and time of death, using an original high-performance liquid chromatography/mass spectrometry (HPLC/MS) procedure with verapamil-d3 as internal standard. Plasma verapamil and norverapamil levels on admission were 0.94 and 1.36 microg/mL, respectively, then verapamil remained practically unchanged throughout the hospitalization (0.85 microg/mL at T0 + 40 hours). The discussion focuses on the detrimental role of SR formulations in overdose, with special emphasis on the risk of pharma-cobezoar development already reported with SR-verapamil. To our knowledge, this is the first report of a verapamil fatality documented by repeated plasma measurements of the drug during the antemortem period.

Neurological complications and pleural lavage with a fibrinolytic agent. A two-case report.

We report on an unusual, albeit potentially severe, complication of the performance of a pleural lavage with streptokinase in two patients demonstrating parapneumonic pleural effusion. During the time they underwent repeated pleural lavages with saline and streptokinase, they suddenly demonstrated focal neurological signs. As a result of early diagnosis and emergency hyperbaric oxygenation, both patients recovered without delayed sequelae. Air embolism is a potentially severe complication which can occur during pleural lavage. Whether streptokinase increases the risk of opening a latent vascular breach cannot be definitely established, but clinicians should be aware of this risk. In this context, the onset of acute focal neurological signs should suggest the possibility of air embolism and lead to the transfer of the patient close to a hyperbaric facility within a few hours.

[Polyneuropathy and neuromyopathy in intensive care. 4 new cases]. / Polyneuropathie et neuromyopathie de réanimation. Quatre nouveaux cas.

Neuromuscular complications acquired in the intensive care unit form a new clinical entity. Three neuromuscular deficits are described: so-called critical illness polyneuropathy where neuromyopathic changes are associated with corticosteroid and/or neuromuscular blocking agents, and catabolic myopathy. We report four new cases: three of them concerning polyneuropathy and one neuromyopathic change.

Polyamines and the recovery of intestinal morphology and function after ischemic damage in rats.

We have followed the time-course of the morphological and functional recovery of intestinal mucosa after 90 min of mesenteric vascular occlusion. At the end of the ischemic period the villi were smashed, but crypts were preserved. Microvillous hydrolase activities showed a dramatic drop when compared with sham-operated controls. Reperfusion was followed by an immediate upsurge of ornithine decarboxylase activity and a significant (p < 0.01) enhancement of putrescine and N1-acetyl-spermidine concentrations, while spermidine and spermine concentrations in mucosal cells decreased. This indicated that, both, de novo synthesis and degradation rates of the polyamines were increased. Treatment with alpha-difluoromethyl-ornithine, a selective inactivator of ornithine decarboxylase prevented the accumulation of active enzyme, but did not prevent morphological healing. It delayed however the recovery of sucrase and aminopeptidase-specific activities. Our results suggest that in addition to de novo synthesis, other sources of polyamines are mobilized to an extent that growth at a normal rate is supported. This indicates that the presence of active ornithine decarboxylase enzyme is not a prerequisite for the restitution of intestinal integrity after ischemia. We suggest that in a situation of inadequate polyamine supply the restoration of vital processes (mucosal regeneration) has priority over the restoration of specific functions.

[Regression of IgA kappa monoclonal gammopathy in IgA lambda Kahler's disease]. / Régression d'une gammapathie monoclonale à IgA kappa lors du développement d'une maladie de Kahler à IgA lambda.

The authors report the case of a patient with a stable IgA kappa gammapathy over several years which finally evolved to an IgA lambda myeloma during which the initial gammapathy regressed. As the two gammapathies probably arose from two different cellular populations, the regression of the IgA kappa dysglobulinaemia is an additional argument in favour of the hypothesis that benign monoclonal gammapathies are the result of cellular hyperplasia.