Building memories: remembering and forgetting of verbal experiences as predicted by brain activity

A fundamental question about human memory is why some experiences are remembered whereas others are forgotten. Brain activation during word encoding was measured using blocked and event-related functional magnetic resonance imaging to examine how neural activation differs for subsequently remembered and subsequently forgotten experiences. Results revealed that the ability to later remember a verbal experience is predicted by the magnitude of activation in left prefrontal and temporal cortices during that experience. These findings provide direct evidence that left prefrontal and temporal regions jointly promote memory formation for verbalizable events.     

Should third-generation cephalosporins be the empirical treatment of choice for severe community-acquired pneumonia in adults?

The choice of empirical treatment for community-acquired pneumonia (CAP) is highly controversial. Our survey of 42 Australian emergency department doctors showed that monotherapy with a third-generation cephalosporin was the preferred regimen for severe CAP (14/42; 33%). We argue that cheaper regimens with a narrower spectrum are likely to be just as effective as third-generation cephalosporins and will have fewer adverse effects on the microbial ecology of hospitals. We suggest penicillin or ampicillin (to cover pneumococci--even if penicillin "resistant"--and Haemophilus influenzae), plus a macrolide (e.g., azithromycin or erythromycin; to cover Legionella and other "atypical" pathogens), plus a single large dose of an aminoglycoside (e.g., gentamicin; to cover gram-negative bacilli such as Klebsiella pneumoniae) as empirical therapy for severe CAP.     

Pediatric hepatic trauma: does clinical course support intensive care unit stay?

PURPOSE: The objective of this study is to determine if grade of liver injury predicts outcome after blunt hepatic trauma in children and to initiate analysis of current management practices to optimize resource utilization without compromising patient care. METHODS: A retrospective review of 36 children who had blunt hepatic trauma treated at a pediatric trauma center from 1989 to present was performed. Hepatic injuries graded (AAST Organ Injury Scaling) ranged from grade I to IV. Injury Severity Score (ISS), Glasgow Coma Score (GCS), transfusion requirements, liver transaminase levels, associated injuries, intensive care unit (ICU) length of stay, and survival were analyzed. RESULTS: Mean (+/-SEM) age was 6.6+/-0.8 years, mean grade of hepatic injury was 2.4+/-0.2, mean ISS was 17+/-2.6, mean GCS was 13+/-1, and mean transfusion was 15.4 mL/kg of packed red blood cells (PRBC). There were three deaths with a mean ISS of 59+/-9 and a mean GCS of 3+/-0. Death was not associated with a high-grade liver injury, survivors versus nonsurvivors, 2.3+/-0.2 versus 2.7+/-0.3, but was associated with ISS, 13+/-1.4 versus 59+/-9 (P = .005) and GCS, 14+/-1 versus 3+/-0 (P = .005). Only one patient (grade III, ISS = 43) underwent surgery. There were no differences in mean ISS or GCS between grades I to IV patients. The hepatic injury grades of patients requiring transfusion versus no transfusion were significantly different, 3.4+/-0.2 versus 2.2+/-0.2 (P = 0.04). Abused patients had high-grade hepatic injuries and significant laboratory and clinical findings. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly higher in grade III and IV injuries than in grades I and II, 1,157+/-320 versus 333+/-61 (P= .02) and 1,176+/-299 versus 516+/-86 (P= .04), respectively. No children with grade I or II injury had a transfusion requirement or surgical intervention. There were no liver-related complications. CONCLUSIONS: Mortality and morbidity rates in pediatric liver injuries, grades I to IV, correlate with associated injuries not the degree of hepatic damage. ALT, AST, and transfusion requirements are significantly related to degree of liver injury. Low-grade and isolated high-grade liver injuries seldom require transfusion. Blunt liver trauma rarely requires surgical intervention. In retrospect, the need for expensive ICU observation for low-grade and isolated high-grade hepatic injuries is questionably warranted.     

The alcohol deprivation effect in the alcohol-preferring P rat under free-drinking and operant access conditions

The alcohol-deprivation effect (ADE) was examined under 4-hr operant and 24-hr free-choice alcohol access in the alcohol-preferring (P) rat after deprivation intervals from 2 to 4 weeks. Results indicated that adult male P rats responding for 6 weeks on a concurrent FR-5/FR-1 schedule of reinforcement for alcohol and water, respectively, and then deprived of alcohol for 2 weeks, demonstrated a 40% increase in alcohol responding during the first 60 min of alcohol reinstatement. The alcohol deprivation effect was temporary, however, as responding did not differ from baseline levels on the second day of reinstatement. In a second experiment, weanling male and female P rats received 7 weeks of continuous access to alcohol, beginning at 21 days of age, and were then deprived of alcohol for 4 weeks. On the first day of alcohol reinstatement, P rats exhibited a 40% to 45% increase from baseline alcohol drinking levels, with alcohol intake returning to baseline levels by the 3rd day of reinstatement. Although alcohol intake was higher in females than in males when adjustment was made for body weight, there were no gender differences in the magnitude of the alcohol deprivation effect. Taken together, these results indicate that the ADE is a long-lasting phenomenon that occurs under both operant and continuous access conditions in the P rat, and thus these rats may be useful models for the study of factors involved in relapse of alcohol drinking.     

The apolar distal histidine mutant (His69-->Val) of the homodimeric Scapharca hemoglobin is in an R-like conformation

The effect of the apolar mutation of the distal histidine (His69-->Val) has been studied in the cooperative homodimeric hemoglobin from the mollusc Scapharca inaequivalvis. Absorption, circular dichroism, and resonance Raman spectroscopy point to a more symmetric heme structure of the deoxy derivative, which is indicative of an R-like conformation of the deoxy heme. Resonance Raman spectroscopy also brings out alterations in the geometry and interactions of the bound CO molecule. The iron-carbon stretching frequency is decreased by about 30 cm-1 with respect to the native protein, while the diatomic ligand stretching frequency is increased by about the same degree. Consistent with the structural changes, the ligand binding properties are significantly altered. In the mutant the overall rate and the affinity for CO binding are increased about 100-fold with respect to the native protein, and cooperativity is abolished. In addition, the amplitude and the rate of the geminate rebinding process increase significantly. This finding may be correlated to the longer average residence time of the photolyzed CO molecule within the heme pocket of the H69V mutant, as indicated by molecular dynamics simulations.     

Comparative analysis of Haemophilus influenzae hifA (pilin) genes

Adherence of Haemophilus influenzae to epithelial cells plays a central role in colonization and is the first step in infection with this organism. Pili, which are large polymorphic surface proteins, have been shown to mediate the binding of H. influenzae to cells of the human respiratory tract. Earlier experiments have demonstrated that the major epitopes of H. influenzae pili are highly conformational and immunologically heterogenous; their subunit pilins are, however, immunologically homogenous. To define the extent of structural variation in pilins, which polymerize to form pili, the pilin genes (hifA) of 26 type a to f and 16 nontypeable strains of H. influenzae were amplified by PCR and subjected to restriction fragment length polymorphism (RFLP) analysis with AluI and RsaI. Six different RFLP patterns were identified. Four further RFLP patterns were identified from published hifA sequences from five nontypeable H. influenzae strains. Two patterns contained only nontypeable isolates; one of these contained H. influenzae biotype aegyptius strains F3031 and F3037. Another pattern contained predominantly H. influenzae type f strains. All other patterns were displayed by a variety of capsular and noncapsular types. Sequence analysis of selected hifA genes confirmed the 10 RFLP patterns and showed strong identity among representatives displaying the same RFLP patterns. In addition, the immunologic reactivity of pili with antipilus antisera correlated with the groupings of strains based on hifA RFLP patterns. Those strains that show greater reactivity with antiserum directed against H. influenzae type b strain M43 pili tend to fall into one RFLP pattern (pattern 3); while those strains that show equal or greater reactivity with antiserum directed against H. influenzae type b strain Eagan pili tend to fall in a different RFLP pattern (pattern 1). Sequence analysis of representative HifA pilins from typeable and nontypeable H. influenzae identified several highly conserved regions that play a role in bacterial pilus assembly and other regions with considerable amino acid heterogeneity. These regions of HifA amino acid sequence heterogeneity may explain the immunologic diversity seen in intact pili.     

Catastrophic falls in patients who have fibrodysplasia ossificans progressiva

There have been numerous anecdotal reports of catastrophic falls in patients with fibrodysplasia ossificans progressiva. To determine the incidence of serious morbidity and mortality associated with falls in this patient population, the authors surveyed the 135 patient members of the International Fibrodysplasia Ossificans Progressiva Association and an age and gender matched control group. Eighty-one percent of the fibrodysplasia ossificans progressiva population suffered a fall resulting in injury compared with 44% of the controls. Sixty-seven percent of the falls initiated a painful flareup of fibrodysplasia ossificans progressiva leading to permanent loss of movement in almost all patients. Fifty-four percent of all falls suffered by the fibrodysplasia ossificans progressiva group led to permanent disability compared with 4% of all falls in the control group. Although trauma to the head was a common site of injury in both groups, the injury profile in the fibrodysplasia ossificans progressiva group included traumatic brain injuries, intracranial hemorrhage and death whereas the control group suffered mostly minor soft tissue lacerations. Deficiencies in coordinate gait and protective function likely accounted for the severity of injuries especially to the head in the fibrodysplasia ossificans progressiva population. Precautions are recommended that are intended to minimize the risk of injury without compromising a patient's functional level and independence. These recommendations include limitation of high risk activities, protective head gear, safety improvements in living environments, and augmentation of stabilizing and protective functions.     

Statistical issues in biological radiation dosimetry for risk assessment using stable chromosome aberrations

Biological dosimeters are useful for epidemiologic risk assessment in populations exposed to catastrophic nuclear events and as a means of validating physical dosimetry in radiation workers. Application requires knowledge of the magnitude of uncertainty in the biological dose estimates and an understanding of potential statistical pitfalls arising from their use. This paper describes the statistical aspects of biological dosimetry in general and presents a detailed analysis in the specific case of dosimetry for risk assessment using stable chromosome aberration frequency. Biological dose estimates may be obtained from a dose-response curve, but negative estimates can result and adjustment must be made for regression bias due to imprecise estimation when the estimates are used in regression analyses. Posterior-mean estimates, derived as the mean of the distribution of true doses compatible with a given value of the biological endpoint, have several desirable properties: they are nonnegative, less sensitive to extreme skewness in the true dose distribution, and implicitly adjusted to avoid regression bias. The methods necessitate approximating the true-dose distribution in the population in which biological dosimetry is being applied, which calls for careful consideration of this distribution through other information. An important question addressed here is to what extent the methods are robust to misspecification of this distribution, because in many applications of biological dosimetry it cannot be characterized well. The findings suggest that dosimetry based solely on stable chromosome aberration frequency may be useful for population-based risk assessment.