Post-traumatic stress disorder and memory: prescient medicolegal testimony at the International War Crimes Tribunal?

The nature of remembrance of traumatic events has been particularly controversial during the past decade as vigorous new research has reshaped thinking about trauma and memory. Memory alterations in traumatized individuals have been investigated within both theoretical and biological frameworks. There are different types of memory, and empirical studies have associated post-traumatic stress disorder (PTSD) with a simultaneous weakening and a strengthening of memory. Memory deficiencies in PTSD have been found to be related to problems in new learning (explicit memory), but other specific deficiencies are unvalidated. Recently, accuracy of memory has received particular scrutiny because considerable importance is attached to victims' recollections. In 1998, at the International War Crimes Tribunal in The Hague, The Netherlands, a Bosnian-Croatian soldier was tried for aiding and abetting the rape of a Muslim woman. The defendant's lawyers suggested that the woman's memory was inaccurate, having been adversely affected by her traumatic experiences, and that the defendant whom she identified was not present during her interrogation and abuse. The prosecution disagreed and argued that memories of traumatic experiences in individuals with PTSD are characteristically hyperaccessible. Expert witnesses on both sides were brought in to provide medicolegal testimony about the scientific parameters of stress and its long-term effects on brain regions associated with memory. With the expert witness discussion as background, this article reviews the most recent research about the nature of memory in the aftermath of trauma and the politics of psychological trauma and the law.     

MR-based in vivo hippocampal volumetrics: 1. Review of methodologies currently employed

The advance of neuroimaging techniques has resulted in a burgeoning of studies reporting abnormalities in brain structure and function in a number of neuropsychiatric disorders. Measurement of hippocampal volume has developed as a useful tool in the study of neuropsychiatric disorders. We reviewed the literature and selected all English-language, human subject, data-driven papers on hippocampal volumetry, yielding a database of 423 records. From this database, the methodology of all original manual tracing protocols were studied. These protocols differed in a number of important factors for accurate hippocampal volume determination including magnetic field strength, the number of slices assessed and the thickness of slices, hippocampal orientation correction, volumetric correction, software used, inter-rater reliability, and anatomical boundaries of the hippocampus. The findings are discussed in relation to optimizing determination of hippocampal volume.     

MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders

Magnetic resonance imaging (MRI) has opened a new window to the brain. Measuring hippocampal volume with MRI has provided important information about several neuropsychiatric disorders. We reviewed the literature and selected all English-language, human subject, data-driven papers on hippocampal volumetry, yielding a database of 423 records. Smaller hippocampal volumes have been reported in epilepsy, Alzheimer's disease, dementia, mild cognitive impairment, the aged, traumatic brain injury, cardiac arrest, Parkinson's disease, Huntington's disease, Cushing's disease, herpes simplex encephalitis, Turner's syndrome, Down's syndrome, survivors of low birth weight, schizophrenia, major depression, posttraumatic stress disorder, chronic alcoholism, borderline personality disorder, obsessive-compulsive disorder, and antisocial personality disorder. Significantly larger hippocampal volumes have been correlated with autism and children with fragile X syndrome. Preservation of hippocampal volume has been reported in congenital hyperplasia, children with fetal alcohol syndrome, anorexia nervosa, attention-deficit and hyperactivity disorder, bipolar disorder, and panic disorder. Possible mechanisms of hippocampal volume loss in neuropsychiatric disorders are discussed.     

En bloc vs transhiatal esophagectomy for stage T3 N1 adenocarcinoma of the distal esophagus

HYPOTHESIS: En bloc esophagectomy (EBE) provides improved survival over transhiatal esophagectomy (THE) in patients with similarly sized transmural tumors (T3) and lymph node metastases (N1). DESIGN: A retrospective case-control study of 2 methods of esophageal resection for cancer. SETTING: University hospital (tertiary referral center for esophageal disease). PATIENTS: There were 49 patients (27 who underwent EBE and 22 who underwent THE) with similar T3 N1 disease and the following matched criteria: tumors of similar size and location, more than 20 lymph nodes in the surgical specimen, R0 resection, no previous chemotherapy or radiation therapy, and follow-up until death or for a minimum of 5 years.Main Outcome Measure Survival adjusted for differences in demographic and patient characteristics. RESULTS: The number of nodes harvested was greatest after EBE vs THE (median, 52 vs 29 [range, 21-85 vs 20-60]; P<.001). The median number of involved nodes was similar after EBE vs THE (median, 5 vs 7 [range, 1-19 vs 1-16]). The only 2 independent factors that affected survival in a Cox analysis were the number of involved lymph nodes (P =.01) and the type of resection (P =.03). Patients who underwent EBE had a survival benefit over those who underwent THE (P =.01). The survival benefit of EBE was seen only in patients with fewer than 9 involved lymph nodes (P<.001). CONCLUSION: En bloc esophagectomy confers a better survival than THE in patients with T3 N1 disease and fewer than 9 lymph node metastases.     

Association between ambient air pollution and birth weight in São Paulo, Brazil

Objectives: Previous studies have implicated air pollution in increased mortality and morbidity, especially in the elderly population and children. More recently, associations with mortality in infants and with some reproductive outcomes have also been reported. The aim of this study is to explore the association between exposure to outdoor air pollution during pregnancy and birth weight. Design: Cross sectional study using data on all singleton full term live births during a one year period. For each individual birth, information on gestational age, type of delivery, birth weight, sex, maternal education, maternal age, place of residence, and parity was available. Daily mean levels of PM₁₀, sulphur dioxide, nitrogen dioxide, carbon monoxide, and ozone were also gathered. The association between birth weight and air pollution was assessed in regression models with exposure averaged over each trimester of pregnancy. Setting: São Paulo city, Brazil. Results: Birth weight was shown to be associated with length of gestation, maternal age and instruction, infant gender, number of antenatal care visits, parity, and type of delivery. On adjusting for these variables negative effects of exposure to PM₁₀ and carbon monoxide during the first trimester were observed. This effect seemed to be more robust for carbon monoxide. For a 1 ppm increase in mean exposure to carbon monoxide during the first trimester a reduction of 23 g in birth weight was estimated. Conclusions: The results are consistent in revealing that exposure to air pollution during pregnancy may interfere with weight gain in the fetus. Given the poorer outlook for low birthweight babies on a number of health outcomes, this finding is important from the public health perspective.     

Calcium ionophoretic and apoptotic effects of ferutinin in the human Jurkat T-cell line

We have investigated the ionophoretic and apoptotic properties of the daucane sesquiterpene ferutinin and three related compounds, ferutidin, 2-alpha-hydroxyferutidin and teferin, all isolated from various species of plants from the genus Ferula. Ferutinin induced a biphasic elevation of intracellular Ca2+ in the leukemia T-cell line, Jurkat. First, a rapid calcium peak was observed and inhibited by BAPTA-AM. This initial calcium mobilization was followed by a sustained elevation, mediated by the entry of extracellular calcium through L-type calcium channels and sensitive to inhibition by EGTA. Moreover, ferutinin-induced apoptosis in Jurkat cells, and this event was preceded, in a cyclosporine-A sensitive manner, by a loss of mitochondrial transmembrane potential (DeltaPsim) and by an increase in intracellular reactive oxygen species. Ferutinin-induced DNA fragmentation was mediated by a caspase-3-dependent pathway, and was initiated independently of any specific phase of the cell cycle. The evaluation of ferutinin analogs in calcium mobilization and apoptosis assays showed strict structure-activity relationships, with p-hydroxylation of the benzoyl moiety being requested for activity.     

Cell-specific effects of RB or RB/p107 loss on retinal development implicate an intrinsically death-resistant cell-of-origin in retinoblastoma

Retinogenesis involves expansion of pluripotent progenitors, specification of postmitotic precursors, and terminal differentiation. Rb or Rb/p107 loss causes retinoblastoma in humans or mice, respectively. One model suggests that Rb- or Rb/p107-deficient retinal precursors have infinite proliferative capacity but are death-prone and must acquire an antiapoptotic mutation. Indeed, we show that Rb/p107 loss does not affect progenitor proliferation or precursor specification, but perturbs cell cycle exit in all seven retinal precursors. However, three precursors survive Rb/p107-loss and stop proliferating following terminal differentiation. Tumors arise from precursors that escape this delayed growth arrest. Thus, retinoblastoma arises from a precursor that has extended, not infinite, proliferative capacity, and is intrinsically death-resistant, not death-prone. We suggest that additional lesions common in retinoblastoma overcome growth arrest, not apoptosis.     

The effect of phosphate loading on erythrocyte 2,3-bisphosphoglycerate levels

BACKGROUND: Phosphate supplementation has been used in an effort to enhance athletic performance by increasing erythrocyte 2,3-bisphosphoglycerate levels ([2,3-BPG]) and hence improve oxygen offloading from haemoglobin. Claimed effects of phosphate loading upon both exercise performance and erythrocyte [2,3-BPG] are inconsistent, and the basis of any change in [2,3-BPG] is unknown. METHODS: We analysed plasma inorganic phosphate concentration ([P(i)]) and erythrocyte [P(i)] and [2,3-BPG] in venous blood samples from 12 healthy subjects. We re-examined a subset of five of these subjects after 7 days of phosphate loading. RESULTS: There were significant positive correlations between plasma [P(i)] and erythrocyte [P(i)] (r(2)=0.51, p=0.009) and between erythrocyte [P(i)] and [2,3-BPG] (r(2)=0.68, p<0.001). Following phosphate loading, there was a 30% increase in plasma [P(i)] (1.02+/-0.22 to 1.29+/-0.15 mmol/l (mean+/-S.D.), p=0.03) and a 25% increase in erythrocyte [2,3-BPG] (6.77+/-1.12 to 9.11+/-1.87 mmol/l cells, p=0.03). There is no relation between [2,3-BPG] and plasma [P(i)]. CONCLUSIONS: Phosphate loading increases both plasma and erythrocyte phosphate pools and the rise in [2,3-BPG] is probably a consequence of the rise in cell [P(i)].