Redimune NF Liquid, a ready-to-use, high-concentration intravenous immunoglobulin therapy preparation, is safe and typically well tolerated in the routine clinical management of a broad range of conditions.

In clinical practice, intravenous immunoglobulin therapy (IVIG) is used in the management of a wide variety of medical conditions. Observational studies examining IVIG use in routine clinical practice are therefore an important means of validating findings from more strictly randomized controlled trials of patients with specific conditions. In this observational study, we examined the tolerability of a high-concentration (12%) ready-to-use liquid IVIG (Redimune NF Liquid) when used in the standard management of a diverse range of conditions (including primary immunodeficiency diseases, neurology conditions, oncology conditions and immune thrombocytopaenic purpura). IVIG regimen and dose were selected by the physician based on the summary of product characteristics. During the study, 193 infusions were administered to 51 patients in 153 infusion cycles (per infusion cycle: one to five infusions; mean dose, 347.6 mg/kg; mean duration, 202.4 min). The mean maximum infusion rate per cycle was 2.9 mg/kg/min, demonstrating that the infusion rate was often higher than that recommended in the summary of product characteristics. Redimune NF Liquid was well tolerated: there were 36 adverse reactions (at least probably associated with IVIG) in 10 patients (19.6% of sample, 0.24 per infusion cycle, 0.19 per infusion). The most common adverse reaction was headache (50% of reactions), followed by chills (13.8%). Most reactions (69%) were mild and there were no serious or unexpected reactions. In conclusion, in routine clinical practice involving patients with many different conditions, Redimune NF Liquid was well tolerated by the majority of patients.

Effects of midazolam on cerebral hemodynamics and cerebral vasomotor responsiveness to carbon dioxide.

Although it is known that hypercarbia increases and benzodiazepines decrease cerebral blood flow (CBF), the effects of benzodiazepines on CBF responsiveness to CO2 are not well documented. The influence on CBF and CBF-CO2 sensitivity of placebo or midazolam, which is a new water-soluble benzodiazepine, was measured in eight healthy volunteers using the noninvasive 133Xe inhalation method for CBF determination. Under normocarbia, midazolam decreased CBF from 40.6 +/- 3.2 to 27.0 +/- 5.0 ml 100 g-1 min-1 (means +/- SD). At a later session under hypercarbia, CBF was 58.8 +/- 4.4 ml 100 g-1 min-1 after administration of placebo, and 49.1 +/- 10.2 ml 100 g-1 min-1 after midazolam. The mean of the slopes correlating PaCO2 and CBF was significantly steeper with midazolam (2.5 +/- 1.2 ml 100 g-1 min-1 mm Hg-1) than with placebo (1.5 +/- 0.4 ml 100 g-1 min-1 mm Hg-1). Our results suggest that midazolam may be a safe agent to use in patients with intracranial hypertension, since it decreases CBF and thus cerebral blood volume; however, it should be administered with caution in nonventilated patients with increased intracranial pressure, since its beneficial effects on cerebrovascular tone can be readily counteracted by the increase in arterial CO2 tension induced by this drug.

[Development of a neurological score for the clinical evaluation of sylvian infarctions]. / Mise au point d'un score neurologique pour l'évaluation clinique des infarctus sylviens.

Among the main methodological problems raised by clinical trials in cerebral vascular accidents, one of the most serious is the lack of well-established and widely accepted criteria to evaluate the course of the disease. On the basis of published scores and of several trials carried on by us in three different centres during the last few years, we have developed a neurological score devised to reflect, as accurately as possible, deficits due to infarctions in the Sylvian territory, yet rapid and simple enough to provide an objective and reproducible rating. We report here the results of a prospective study concerning the inter-rater variations of the score from one centre to the other (inter-centre study) and within each centre (intra-centre study). These results have led us to withdraw three items with insufficient response rate and poor agreement, viz, "mental confusion", "visual field" and "sensory disorders". With the remaining 10 items the mean agreement between individual items varied from 85% to 90% and the global score agreement exceeded 90%. A study comparing our score with the Barthel index showed close correlation up to the autonomy threshold (Barthel index = 60) and divergent results beyond that point. The good agreement observed between inter-rater variations suggests that the score is reliable but does not inform on its sensitivity. In view of their relative independence, the neurological and the functional score should be regarded as complementary and should be used together as criteria of clinical assessment.

[Physiopathology of brain edema]. / Physiopathologie de l'oedème cérébral.

Cerebral edema is by definition an increase in the water content of the brain. Because of the rigidity of the skull, every increase in brain volume invariably causes intracranial hypertension which, in turn, has two major consequences: firstly, cerebral perfusion pressure is reduced, thus promoting ischemia; secondly, cerebral structures are displaced toward places of lesser resistance, thus causing brain herniation. In consequence, medical treatment of intracranial hypertension should be chiefly directed against brain edema. Recent research in the field demonstrates that there are different forms of edema, the underlying mechanisms of which are discussed.

Detection of carotid artery stenosis and obstruction by cerebral radionuclide angiography.

CA and RA were performed in 140 patients suffering either from TIAs (n = 43; mean age 59 +/- 9.7 years) or from RIND (n = 97; mean age 58 +/- 13 years). Completed stroke was excluded from this study. Criteria of abnormality of RA were determined from a normal control group (n = 100; mean age 37 +/- 17 years). Overall detection rate of extracranial carotid artery lesions of any size was 63% (42:66). False negative results were reviewed. Within the same group of patients, DU was positive in 76%. The addition of RA and DU enhanced the detection rate to 88%. In the subgroup with normal extracranial carotid arteries, RA accounted for 6.7% of false positive results. Intracranially, RA was able to demonstrate a significant asymmetry of perfusion in good correlation with clinical examination in 65% of the cases (91: 140), whereas CA was found positive in only 26% of the patients. It is concluded that RA is best suited for documentation of intracranial carotid artery territory disease and for studying intracranial consequences of extracranial lesions. In contrast, DU is preferred for detection of extracranial lesions. However, the addition of both techniques enhances the power of non-invasive detection of carotid artery stenosis and obstruction.

[Measures of regional cerebral blood deficit by inhalation of xenon 133: clinical applications]. / Mesures de débit sanguin cérébral régional (DSR) par inhalation de xénon 133: applications cliniques.

Multiple measurements of regional cerebral blood flow (rCBF) after 133 xenon inhalation allowed us to compare results obtained during different forms of migraine and during transient ischaemic attacks, as opposed to a group of normal controls. In normal healthy volunteers (N = 65) classified in decades, there is a stepwise reduction in cortical blood flow (F1) with advancing age (r = .97, p < .0001). The reduction in the slow component of blood flow (F2 congruent to white matter flow) is not significant. In common and classical form of migraine (N = 23)F1 is signifcantly increased during the cephalalgic phase and during the two consectuvie days (p < .01). On the contrary, in accompanied migraine (N = 17), F1 is significantly decreased during the first four days (p < .001) and to a lesser extent from the 4th to the 10th day (N = 5; p < .05). In transient ischaemic attacks (T.I.A.; N = 12) F1 is significantly increased until three weeks after the attack (p < .01). The differences in rCBF in accompanied migraine versus T.I.A. appears to help in the differential diagnosis of clinically difficult cases.

Effects of midazolam on cerebral blood flow in human volunteers.

The effects of intravenously administered midazolam on cerebral blood flow were evaluated in eight healthy volunteers using the 133Xe inhalation technique. Six minutes after an intravenous dose of 0.15 mg/kg midazolam, the cerebral blood flow decreased significantly (P less than 0.001) from a value of 40.6 +/- 3.3 to a value of 27.0 +/- 5.0 ml . 100 g-1 . min-1. Cerebrovascular resistance (CVR) increased from 2.8 +/- 0.2 to 3.9 to 0.6 mmHg/(ml . 100 g-1 . min-1)(P less than 0.001). Mean arterial blood pressure decreased significantly (P less than 0.05) from 117 +/- 8 to 109 +/- 9 mmHg and arterial carbon dioxide tension increased from 33.9 +/- 2.3 to 38.6 +/- 3.2 mmHg (P less than 0.05). Arterial oxygen tension remained stable throughout the study, 484 +/- 95 mmHg before the administration of midazolam and 453 +/- 76 mmHg after. All the subjects slept after the injection of the drug and had anterograde amnesia of 24.5 +/- 5 min. The decrease in mean arterial blood pressure was probably not important since it remained in the physiologic range for cerebral blood flow autoregulation. The increase in arterial carbon dioxide tension observed after the midazolam injection may have partially counteracted the effect of this new benzodiazepine on cerebral blood flow. Our data suggest that midazolam might be a safe agent to use for the induction of anethesia in neurosurgical patients with intracranial hypertension.

Effects of a specific benzodiazepine antagonist (RO 15-1788) on cerebral blood flow.

RO 15-1788, a specific benzodiazepine antagonist, although it effectively antagonizes the clinical effects of benzodiazepines (i.e., sedation and amnesia), can also induce subjective agonist effects such as sedation or inverse agonist effects such as anxiety. The purpose of this study was to investigate in seven healthy volunteers the effect of RO 15-1788 on cerebral blood flow when intravenously injected alone or with midazolam and to compare its effects with midazolam administered alone. Cerebral blood flow was measured with the 133xenon inhalation technique and the drugs were administered simultaneously in a double-blind, randomized fashion during the four following sessions: placebo-placebo; midazolam-placebo; RO 15-1788-placebo; midazolam-RO 15-1788. No difference in cerebral blood flow was noted between the placebo-placebo, the RO 15-1788-placebo, and the RO 15-1788-midazolam sessions--although midazolam injected alone decreased cerebral blood flow by 30%. The sedation, amnesia, and the electroencephalograph (EEG) and muscle tone changes observed with midazolam-placebo were not present during the RO 15-1788-placebo and RO 15-1788-midazolam sessions. This study demonstrates the absence of effects of RO 15-1788 on cerebral blood flow when injected alone and the efficacy of this new drug in antagonizing the depressant effects of midazolam on cerebral hemodynamics.

Critical appraisal of cerebral blood flow measured from brain stem and cerebellar regions after 133 Xe inhalation in humans.

Validity of regional blood flow (rCBF) measurements recorded over the human posterior fossa after 133Xe inhalation was tested. Recording of counts from both brain stem and cerebellum (BSC) was reproducible and contamination by counts derived from surrounding anatomical structures was low and no greater than that found over hemispheres. BSC values were F1 = 99 +/- 19 ml/100g brain/min, F2 = 17 +/- 4 in reasonable agreement with data reported from experimental animals. BSC flow values showed significant correlation with the state of awareness as judged by clinical and EEG evaluation with lowest F1 values in semicoma and step increases in stupor, non-REM sleep, drowsiness, rest, activation, REM sleep and highest values during focal and generalized epileptic seizures.