The effect of direction of force to the craniofacial skeleton on the severity of brain injury in patients with a fronto-basal fracture.

The skull base is uniquely positioned to absorb force imparted to the craniofacial skeleton, thereby reducing brain injury. Less well understood is the effect of the direction of force imparted to the craniofacial skeleton on the severity of brain injury. Eighty-one patients from two UK major trauma centres who sustained a fronto-basal fracture were divided into two groups: those struck with predominantly anterior force and those by predominantly lateral force. The first recorded Glasgow Coma Score (GCS), requirement for intubation, and requirement for decompressive craniectomy were used as markers of the severity of brain injury. An average GCS of 5 was found in the lateral group and 14 in the anterior group; this difference was statistically significant (P<0.001). There was an increased need for both intubation and decompressive craniectomy in the lateral group compared to the anterior group (absolute risk difference 46.6% and 15.8%, respectively). These results suggest that the skeletal anatomy of the fronto-basal region influences the severity of head injury. The delicate lattice-like structure in the central anterior cranial fossa can act as a crumple zone, absorbing force. Conversely in the lateral aspect of the anterior cranial fossa, there is a lack of collapsible interface, resulting in an increased energy transfer to the brain.

Applied anatomy of the anterior cranial fossa: what can fracture patterns tell us?

The skull base is uniquely placed to absorb anteriorly directed forces imparted either via the midfacial skeleton or cranial vault. A variety of skull base fracture classifications exist. Less well understood, however, is fracture extension beyond the anterior cranial fossa (ACF) into the middle and posterior cranial fossae. The cases of 81 patients from two UK major trauma centres were studied to examine the distribution of fractures across the skull base and any relationship between the vector of force and extent of skull base injury. It was found that predominantly lateral force to the craniofacial skeleton produced a fracture that propagated beyond the ACF into the middle cranial fossa in 77.4% of cases, significantly more (P<0.001) than for predominantly anterior force (12.0%). Fractures were significantly more likely to propagate into the posterior fossa with a lateral vector of impact compared to an anterior vector (P=0.049). This difference in energy transfer across the skull base may, in part, be explained by the local anatomy. The more delicate central ACF acts as a 'crumple zone' in order to absorb force. Conversely, no collapsible interface exists in the lateral aspect of the ACF, thus the lateral ACF behaves like a 'buttress', resulting in increased energy transfer.

Current HIV treatment guidelines--an overview.

Use of highly active antiretroviral therapy has resulted in significant reductions in HIV-related morbidity and mortality. Current therapeutic approaches target cellular entry, viral transcription, and maturation of newly formed virus. Combination therapy is necessary to provide durable suppression of viral replication and immune reconstitution. A variety of consensus treatment guidelines addressing prophylaxis and treatment of HIV infection and opportunistic infections have been developed to serve as resources for clinicians. A summary of U.S. Department of Health and Human Services Guidelines for Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents and International AIDS Society-USA Panel recommendations for Treatment of Adult HIV infection are presented. Considerations for selection of antiretroviral therapy in special populations (e.g., pregnancy, coinfection with tuberculosis, hepatitis B and C virus) are highlighted. U.S. Public Health Service guidelines for management of occupational exposure to HIV and initiation of postexposure prophylaxis are discussed as well as World Health Organization recommendations for use of antiretroviral therapy in resource-limited settings. The pathophysiology of HIV infection, viral load testing methods, viral dynamics, and classification of antiretrovirals are also briefly reviewed.

Cytotoxicity induced by the combination of valproic acid and tumor necrosis factor-alpha: implication for valproic acid-associated hepatotoxicity syndrome.

A previous study showed that valproic acid (VPA) and tumor necrosis factor-alpha (TNF-alpha) exhibit synergistic toxicity (lethality) in Sprague-Dawley and Wistar rats. The present study investigated a possible mechanism for this synergy using an in vitro system. Incubation of human U937 cells with 1 mM VPA or with 0.001 ng/mL of TNF-alpha alone had a negligible effect on cytotoxicity (less than 7%). However, the combination of the two drugs significantly increased the cytotoxicity up to 34%. Chronic treatment of U937 cells with VPA or TNF-alpha for 48 hr reduced protein kinase C (PKC) activity. Further, the PKC selective inhibitor Gö6976 potentiated VPA-induced cytotoxicity and TNF-alpha-induced cytotoxicity, whereas the PKC activator phorbol-12-myristate-13-acetate provided a significant protection against the cytotoxicity associated with VPA or TNF-alpha. These results suggest that the synergism in cytotoxicity exhibited by the combination of VPA and TNF-alpha may be mediated through attenuation of PKC activity.

Effects of citrulline malate on bacterial lipopolysaccharide induced endotoxemia in rats.

The administration of endotoxins to rats as lipopolysaccharides (LPS) induces a state of exhaustion, in which the main symptoms are febrile hyperthermia, reduced food intake, decreased body weight, and reduced muscle performance in treadmill tests. Underlying the physiological and behavioral disturbances due to the LPS is the activation of macrophages that release cytokines (interleukin-1, tumor necrosis factor a) and NO. The cellular responses are intended to maintain homeostasis. Provision of citrulline as citrulline malate (CAS 54940-97-5, Stimol), an antifatigue substance, improved muscle performance, but had no effect on the body temperature or on the body weight of these animals weakened by LPS. The presence of citrulline in the NO synthesis pathway, or its participation in the speeded up elimination of ammonia and lactates, the main products of muscle metabolism, might explain the effects of citrulline malate in rats treated with LPS.

Cosmic dust analog simulation in a microgravity environment: the STARDUST program.

We have undertaken a project called STARDUST which is a collaboration with Italian and American investigators. The goals of this program are to study the condensation and coagulation of refractory materials from the vapor and to study the properties of the resulting grains as analogs to cosmic dust particles. To reduce thermal convective currents and to develop valuable experience in designing an experiment for the Gas-Grain Simulation Facility aboard Space Station Freedom we have built and flown a new chamber to study these processes under periods of microgravity available on NASA's KC-135 Research Aircraft. Preliminary results from flights with magnesium and zinc are discussed.

Effects of valproate and citrulline on ammonium-induced encephalopathy.

Hyperammonemia is a recognized side effect of treatment with the antiepileptic drug (AED) valproate (VPA). Encephalopathic complications have also been observed in some patients receiving VPA therapy. The relation between VPA-induced hyperammonemia and encephalopathy is not clear, however. A model of ammonium (NH4+)-induced coma was used to investigate the contribution of VPA and to assess the efficacy of citrulline (a urea cycle intermediate) on hyperammonemia and encephalopathy. In groups of 6-12 rats, administration of VPA (2.5 mmol/kg) was associated with (a) a decrease in the dose of NH4+ that produces coma in 50% of the animals (CD5) from 6.1 to 3.6 mmol/kg, and (b) significant increases in blood ammonia concentrations in NH(4+)-treated animals. In addition, clear evidence also showed that in the presence of VPA, a lesser concentration of ammonia produced coma. Citrulline treatment (5.0 mmol/kg) was associated with (a) an increase in the CD50 value of NH(4+)-treated animals from 6.1 to 8.6 mmol/kg, (b) a statistically significant decrease in ammonia concentration at all doses examined, (c) complete protection from encephalopathic effects of NH4+ at citrulline concentrations three- to tenfold greater than basal levels; and (d) a 24% increase in the CD50 value and a statistically significant decrease in ammonia concentration of VPA/NH(4+)-treated animals. These findings indicate that VPA has a dual effect on encephalopathy and that citrulline should benefit those patients treated with VPA who experience adverse encephalopathic effects.

An overview of the cosmic dust analogue material production in reduced gravity: the STARDUST experience.

The formation, properties and chemical dynamics of microparticles are important in a wide variety of technical and scientific fields including synthesis of semiconductor crystals from the vapour, heterogeneous chemistry in the stratosphere and the formation of cosmic dust surrounding the stars. Gravitational effects on particle formation from vapors include gas convection and buoyancy and particle sedimentation. These processes can be significantly reduced by studying condensation and agglomeration of particles in microgravity. In addition, to accurately simulate particle formation near stars, which takes place under low gravity conditions, studies in microgravity are desired. We report here the STARDUST experience, a recent collaborative effort that brings together a successful American program of microgravity experiments on particle formation aboard NASA KC-135 Reduced Gravity Research Aircraft and several Italian research groups with expertise in microgravity research and astrophysical dust formation. The program goal is to study the formation and properties of high temperature particles and gases that are of interest in astrophysics and planetary science. To do so we are developing techniques that are generally applicable to study particle formation and properties, taking advantage of the microgravity environment to allow accurate control of system parameters.

Biochemical adaptations in the black-tailed prairie dog (Cynomys ludovicianus) during long-term food and water deprivation.

1. Glucose and ketone body metabolism was studied in prairie dogs, which can withstand periods of food and water deprivation at near normal body temperatures without apparent utilization of body protein. 2. Plasma glucose concentrations decreased by 18% (from 8.39 to 6.83 mM) when animals were deprived of food and water for 14 days during winter, and 27% (from 7.89 to 5.78 mM) after similar treatment in summer. 3. Glucose utilization rates decreased by 33% (from 41.0 to 27.5 mumol/min/kg) during winter food and water deprivation, but changed little in summer animals (from 26.0 to 21.1 mumol/min/kg). 4. Glucose carbon recycling was 30-31% in winter animals, but essentially zero in summer animals and did not change due to food and water deprivation. 5. Analysis of the fatty acid composition of prairie dog adipose tissue showed no evidence of odd-number carbon fatty acids, a potential source of glucose carbon. No change in adrenal weights were noted. 6. Ketone body concentrations increased 16-fold (from 0.039 to 0.641 mM) after food and water deprivation in the winter, while utilization rates increased 12-fold (from 0.42 to 4.88 mumol/min/100 g). 7. These results are discussed in relation to the ability of the prairie dog to adapt to long-term food and water deprivation.

Valproate hepatotoxicity syndrome: hypotheses of pathogenesis.

Therapeutic use of the anticonvulsant valproate (VPA) has been associated with a rare, but severe and often fatal hepatotoxicity. Cases usually present with lethargy, anorexia, and vomiting with rapid progression to coma. Liver histopathology is characterized by steatosis with and without necrosis. In some instances only necrosis was present. Several hypotheses of pathogenesis have been postulated. These deal mainly with biochemical systems that are known to be affected by VPA, or with the possible idiosyncratic production of toxic VPA metabolites, especially delta 4-VPA. At present, no hypothesis entirely explains the diverse characteristics of the disorder.

Patients' reactions to psychiatric consultation.

Physicians are often concerned that patients will resent a request for psychiatric consultation. To investigate this problem, 60 patients undergoing psychiatric consultation in a general hospital were inverviewed 24 hours after the consultation. Nearly two thirds of these patients believed that the consultation was beneficial. Patients' attitudes were independent of their demographic characteristics, reason for referral, and hospital service involved. Patients with long-term illnesses more often had positive attitudes than patients with short-term illnesses. Patients who were initially hostile or ambivalent usually had positive attitudes 24 hours later. Substance abusers and patients who denied clearly recognizable psychiatric disorders often did not value the consultation. Even so, their physicians frequently believed that the consultation was useful. We attribute the positive attitudes of patients in our study largely to the referring physicians' preparing them for psychiatric consultation.

Splenic vein obstruction with bleeding gastric varices: a diagnostic approach.

It is important to separate splenic vein obstruction from other causes of variceal bleeding. The authors provide a diagnostic sequence for avoiding errors of management, citing a case to illustrate.