Pediatric intracranial pressure monitoring in hypoxic and nonhypoxic brain injury

We reviewed the results of all pediatric patients undergoing intracranial pressure (ICP) monitoring in a 2-year period at our institution. The outcome of patients suffering hypoxia or ischemic injuries (HII) is compared to those suffering non-hypoxic or non-ischemic injuries (NHII). Thirty-four patients had ICP monitors placed during the study period. Inconplete patient information led to the exclusion of 5 patients. An additional 5 patients were excluded because no measures to control ICP were taken after the monitor was placed. Twenty-four patients required treatment for raised ICP (hyperventilation, 24; mannitol, 19; barbiturate coma, 6). Admission Glasgow Coma Score in patients suffering HII (median score 5) and NHII (median score 6) were not significantly different (Mann-Whitney U Test). Only 2 of 8 patients with HII were near-drowning vietims. The remaining 6 had HII from other causes (5 survivors of various forms of asphyxia and 1 of cardiac arrest). All 8 patients had poor outcomes (1 severely disabled; 7 died). The 16 patients with NHII had a variety of diagnoses (6 trauma, 5 encephalitis, 4 bacterial meningitis, 1 diabetic ketoacidosis). Among these, 6 had good outcomes and 10 poor outcomes (2 severely disabled, 2 vegetative, and 6 died). The difference in outcome between patients with NHII and HII is significant at P=0.059 (Fischer Exact test). Patients with NHII may benefit from ICP monitoring. Patients with HII from near-drowning and other causes did not appear to benefit from ICP monitoring and interventions directed at controlling ICP.     

Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies

Summary Cytosine arabinsodie (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m² as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9–12 and 21–24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m²×2 doses of ara-C and 50 mg/m² of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.Supported in part by grants from the National Cancer Institute (CA-12197 and CA-09422) and the American Cancer Society CF-85-182     

Postprandial induction of chaperone gene expression is rapid in mice.

Molecular chaperones assist in the biosynthesis and processing of proteins. Most chaperones are induced by physiological stresses. We have shown that dietary energy restriction decreases the mRNA and protein levels of many endoplasmic reticulum chaperones in the livers of mice. Here, we have investigated the response of chaperone mRNA to feeding. Control and 50% energy-restricted C3B10RF1 mice were deprived of food for 24 h, fed, and killed 0, 1.5, 5 or 12 h after feeding. Chaperone mRNAs were strongly induced as early as 1.5 h after feeding in control and energy-restricted mice. The integrated levels of these mRNA over 24 h were significantly lower in energy-restricted mice. The mRNA response to energy intake was mirrored over the course of days in the level of chaperone protein. A similar but smaller response to feeding was found in kidney and muscle. Puromycin and cycloheximide failed to inhibit the feeding response, suggesting that feeding releases chaperone expression from an unstable inhibitor. Studies with dibutyryl-cAMP- and glucagon-supplemented, normal and streptozotocin-diabetic mice suggest that glucagon and insulin may be mediators of the feeding response. Adrenalectomy enhanced the feeding induction, but dexamethasone administration had no effect. Thus, postprandial changes in insulin and glucagon may link chaperone gene expression to feeding, possibly in several tissues including liver.     

A novel hemostatic agent: the potential role of recombinant activated factor VII (rFVIIa) in anesthetic practice.

PURPOSE: To review the role of recombinant factor VIIa in anesthetic practice. SOURCE: A review of the published literature. MAIN FINDINGS: The mechanism of action of rFVIIa suggests enhancement of hemostasis limited to the site of injury without systemic activation of the coagulation cascade. In addition to its indication for use in patients with hemophilia, use of rFVIIa for treatment of uncontrolled massive hemorrhage in various peroperative settings appears to be rational, safe, and effective. Published results suggest that in trauma patients rFVIIa may play a role as an adjunctive hemostatic measure in addition to surgical hemostatic techniques There is preliminary evidence that hemorrhagic complications (eg. epistaxis, vaginal bleeding) associated with profound thrombocytopenia can be reversed with rFVIIa even at platelet counts below 10,000 per microL. Various case reports outlining the successful treatment with recombinant factor VIIa of patents experiencing intractable bleeding after valve replacement surgery, and with severe hemorrhage during therapy with left ventricular assist device, indicate the potential therapeutic efficacy of this agent in cardiac surgical procedures. Additionally, rFVIIa has been used successfully for treatment of massive postoperative bleeding following general surgery. CONCLUSIONS: rFVIIa is a novel hemostatic agent that shows promise in non-hemophiliac patents of a significant therapeutic role in variety of coagulopathic and hemorrhagic conditions in clinical situations ranging from thrombocytopenia, disseminated intravascular coagulation and transfusion-related coagulopathy, as well as in patients experiencing massive blood loss undergoing orthotopic liver transplantation, cardiac, orthopedic and genitourinary surgery.     

Economic efficiency versus social equality? The U.S. liberal model versus the European social model.

This article begins by challenging the widely held view in neoliberal discourse that there is a necessary trade-off between higher efficiency and lower reduction of inequalities: the article empirically shows that the liberal, U.S. model has been less efficient economically (slower economic growth, higher unemployment) than the social model in existence in the European Union and in the majority of its member states. Based on the data presented, the authors criticize the adoption of features of the liberal model (such as deregulation of their labor markets, reduction of public social expenditures) by some European governments. The second section analyzes the causes for the slowdown of economic growth and the increase of unemployment in the European Union--that is, the application of monetarist and neoliberal policies in the institutional frame of the European Union, including the Stability Pact, the objectives and modus operandi of the European Central Bank, and the very limited resources available to the European Commission for stimulating and distributive functions. The third section details the reasons for these developments, including (besides historical considerations) the enormous influence of financial capital in the E.U. institutions and the very limited democracy. Proposals for change are included.     

Cosolvency of Dimethyl Isosorbide for Steroid Solubility

Dimethyl isosorbide (DMI), which is currently under investigation for its potential use as a pharmaceutical vehicle and drug permeation enhancer, is a water-miscible liquid with relatively low viscosity. The solubilization behavior of DMI as a cosolvent for nonpolar drugs was characterized via dielectric constant measurements of binary solvent systems containing DMI and either water, propylene glycol (PG), or polyethylene glycol (PEG). Evidence from the dielectric constant profiles and NMR studies suggest that DMI undergoes complexation with water and PG, but not with PEG, through hydrogen bonding interactions. The solvent complexation exhibited a major effect on the solubilities of prednisone, dexamethasone, and prednisolone in the mixed solvent systems. Maximum solubility of each drug was found to occur near a DMI/water or DMI/PG concentration ratio of 1:2. In the DMI–PEG mixed system, while there is no apparent interaction between DMI and PEG molecules, the solubility of prednisone was found to increase with decreasing dielectric constant.     

Peri-ventricular grey stimulation versus motor cortex stimulation for post stroke neuropathic pain.

Central post stroke pain is often difficult to manage satisfactorily with conventional treatment modalities for pain. In the last decade functional neurosurgery has offered hope with motor cortex stimulation achieving significant alleviation of pain in some patients. Unfortunately this has led to the neglect of chronic stimulation of deep grey matter as another modality of treating this condition. In this article we present our experience with motor cortex stimulation and that with deep grey matter stimulation in patients with post stroke pain. We argue that both modalities have a significant role and that what is required are better methods of identifying particular patients who are more likely to respond to one or the other.