The trauma of first episode psychosis: the role of cognitive mediation

OBJECTIVE: First episode psychosis can be a distressing and traumatic event which has been linked to comorbid symptomatology, including anxiety, depression and PTSD symptoms (intrusions, avoidance, etc.). However, the link between events surrounding a first episode psychosis (i.e. police involvement, admission, use of Mental Health Act, etc.) and PTSD symptoms remains unproven. In the PTSD literature, attention has now turned to the patient's appraisal of the traumatic event as a key mediator. In this study we aim to evaluate the diagnostic status of first episode psychosis as a PTSD-triggering event and to determine the extent to which cognitive factors such as appraisals and coping mechanisms can mediate the expression of PTSD (traumatic) symptomatology. METHOD: Approximately 1.5 years after their first episode of psychosis, patients were assessed for traumatic symptoms, conformity to DSM-IV criteria for posttraumatic stress disorder (PTSD), and their appraisals of the traumatic events and coping strategies. Psychotic symptomatology was also measured. RESULTS: 31% of the sample of 35 patients who agreed to participate reported symptoms consistent with a diagnosis of PTSD. Although no relationship was found between PTSD (traumatic) symptoms and potentially traumatic aspects of the first episode (including place of treatment, detention under the MHA etc.), intrusions and avoidance were positively related to retrospective appraisals of stressfulness of the ward (i.e. the more stressful they rated it the greater the number of PTSD symptoms) and the patient's coping style (sealers were less likely to report intrusive re-experiencing but more likely to report avoidance). CONCLUSIONS: The results call into question whether it is possible to make claims for a simple causal link between psychosis and PTSD. Instead patients' appraisals of potentially traumatic events and their coping styles may mediate the traumatic impact of a first episode of psychosis.     

Relationship between damage accumulation and mechanical property degradation in cortical bone: microcrack orientation is important

The accumulation of damage and the associated degradation of the mechanical properties of cortical bone are postulated to contribute to age-, disease-, overuse-, and disuse-related skeletal fragilities. Therefore, gaining insight into the relationship between damage and degradation processes is essential in understanding the etiology of skeletal fractures. In investigating this relationship, the damage measure ideally needs to account for the size, the distribution density, and the orientation of microcracks. Existing measures of damage address the size and distribution density of microcracks; however, the orientation of cracks has not been well-investigated. Because the overall orientation of microcracks determines the material axis along which the greatest degradation will be experienced, we hypothesized that the incorporation of the relative orientation between microcracks and loading direction will improve the significance of the relationship between damage accumulation and material property degradation. A three-cycle damage protocol was used to induce tensile damage and to quantify the degradation of the elastic modulus of specimens from human donor femoral cortical bone (a 24-year-old and a 72-year-old man). Microcracks were evaluated by en bloc basic fuchsin staining of specimens after testing. The length (L(i)) and the orientation with respect to the loading direction (beta(i)) of each crack were quantified by a video microscopy system. Three damage measures were quantified for each specimen: the number of linear microcracks (Cr #), the sum of the crack lengths (SigmaL(i)) accounting for the microcrack size alone, and the sum of the projected crack length [SigmaL(Pi) = SigmaL(i)cos(beta(i))] accounting for both crack size and orientation. Inclusion of the orientation parameter improved the coefficient of determination between damage accumulation and the degradation of the elastic modulus: the coefficient of determination of the sum of the projected crack length (R(2) = 0.239) was 60% greater than that of the sum the projected crack length (R(2) = 0.149) and 33% greater than that of the number of linear microcracks (R(2) = 0.180). We conclude that microcrack orientation is an essential physical variable in the relationship between damage accumulation and degradation of mechanical properties of cortical bone tissue.     

Localization of postresection EGF receptor expression using laser capture microdissection

Background/Purpose: Epidermal growth factor (EGF) and its receptor (EGFR) are key components in the genesis of adaptation after small bowel resection (SBR). Within intestinal homogenates, EGFR expression is increased after SBR; however, the exact cells responsible for altered EGFR expression are unknown. In this study, laser capture microdissection (LCM) microscopy was used to elucidate the specific cellular compartment(s) responsible for postresection changes in EGFR expression. Methods: Male ICR mice underwent a 50% proximal SBR or sham operation. After 3 days, frozen sections were taken from the remnant ileum. Individual cells from villi, crypt, muscularis, and mesenchymal compartments were isolated by LCM. EGFR mRNA expression for each cell compartment was quantified using real-time polymerase chain reaction (PCR). Results: EGFR expression was increased after SBR within the crypt (2-fold) and muscularis compartments (3-fold). There were no changes detected after SBR in the villus tips or mesenchymal compartments. Conclusions: Increased expression of EGFR in crypts directly correlates with the zone of cell proliferation and supports the hypothesis that EGFR signaling is crucial for the mitogenic stimulus for adaptation. The finding of increased EGFR expression in the muscular compartment is novel and may implicate a role for EGFR as a mediator of the muscular hyperplasia seen after massive SBR. J Pediatr Surg 38:440-445.     

Sensorineural hearing loss and Kawasaki disease: a prospective study

PURPOSE: Kawasaki disease (KD) is an acute, self-limited vasculitis of infants and children that is now the most common cause of acquired heart disease in the pediatric age group in the United States and Japan. Reports have documented the association of acute KD with sensorineural hearing loss. To assess the prevalence of hearing loss following acute KD in a geographically and ethnically diverse population, a prospective, multicenter study of hearing loss in patients with KD was conducted. MATERIALS AND METHODS: Patients with acute KD were enrolled in 7 clinical centers and underwent a primary audiologic evaluation within 30 days of the onset of fever. Patients were subsequently reevaluated after resolution of the acute phase of the disease. A questionnaire assessing risk factors for hearing loss was also administered. RESULTS: A total of 62 patients were evaluated during the 29-month study period. At the first audiologic evaluation, 19 patients (30.6%) had sensorineural hearing loss, 6 patients (9.7%) had conductive hearing loss, 17 patients (27.4%) had normal hearing, and 20 patients (32.3%) had inconclusive studies. Overall, 2 of 36 patients (5.5%) had sensorineural hearing loss documented on their second audiologic evaluation. No risk factors for hearing loss were identified by the questionnaire. CONCLUSIONS: Transient sensorineural hearing loss (20 to 35 dB) is a frequent complication of acute KD and may be related to salicylate toxicity in some patients. Persistent sensorineural hearing loss is uncommon. Parents and primary care providers should be made aware of the potential for persistent sensorineural hearing loss following resolution of KD, but routine audiologic screening of this patient population does not appear to be warranted.     

Quantitative EEG in schizophrenia and in response to acute and chronic clozapine treatment

Topographic quantitative electroencephalographic (EEG) power and frequency indices were collected in 17 treatment refractory, DSM-III diagnosed schizophrenic patients, before and after acute (single dose) and chronic (six weeks) clozapine treatment, as well as in 17 healthy volunteers. Prior to treatment, patients exhibited greater overall absolute theta power, slower mean alpha frequency and elevated absolute delta and total power in anterior regions. Acute dosing increased total spectrum power globally, slow wave power posteriorally, mean alpha frequency and beta power anteriorally and decreased alpha power posteriorally. Six weeks of clozapine treatment significantly reduced clinical ratings of positive and negative symptoms as well as symptoms of global psychopathology. Chronic treatment resulted in EEG slowing as shown by decreases in relative alpha power, mean beta/total spectrum frequency and by widespread increases in absolute total and delta/theta power. The preliminary findings suggest that brain electric profiling may be a promising tool for assessing and understanding the central impact of pharmacotherapeutic interventions in schizophrenia.     

Molecular effects of calcium binding mutations in Marfan syndrome depend on domain context

Mutations in the human fibrillin-1 (FBN-1) gene cause Marfan syndrome (MFS), an autosomal dominant disease of connective tissue. Fibrillin-1, a 350 kDa extracellular calcium binding protein, is a major structural component of 10-12 nm microfibrils and consists predominantly of two repeated module types: the calcium binding epidermal growth factor-like (cbEGF) domain and the transforming growth factor beta1 binding protein-like (TB) domain. A group of reported FBN-1 mutations is predicted to reduce calcium binding to cbEGF domains by removal of a side chain ligand for calcium. These mutations occur in two protein domain contexts, either in a cbEGF preceded by a TB domain or in a cbEGF preceded by another cbEGF domain. In this study we have used three proteases to probe structural changes caused by an N2144S MFS calcium binding mutation in a TB6-cbEGF32 and a cbEGF32-33 domain pair, and an N2183S mutation in the cbEGF32-33 pair. N-terminal sequence analysis of domain pairs digested in the presence and absence of calcium show that: (i) domain interactions between TB6 and cbEGF32 are calcium independent, despite the presence of a calcium binding site in cbEGF32; (ii) domain interactions between cbEGF32 and cbEGF33 are calcium dependent; and (iii) an N-->S mutation causes increased proteolytic susceptibility only when located in cbEGF33, consistent with a key role for interdomain calcium binding in rigidifying cbEGF domain linkages. These data demonstrate for the first time that the structural consequences of calcium binding mutations in fibrillin-1 cbEGF domains can be influenced by domain context.     

Acute nicotine effects on auditory sensory memory in tacrine-treated and nontreated patients with Alzheimer's disease: an event-related potential study

The auditory mismatch negativity (MMN) event-related brain potential (ERP) reflects the storage of information in acoustic sensory memory. Thirteen patients with Alzheimer's disease (AD), 6 receiving treatment with the cholinesterase inhibitor, tacrine [tetrahydroaminoacridine (THA)], and 7 receiving no treatment, were administered 2 mg of nicotine polacrilex and placebo. MMNs were recorded with 1- and 3-s interstimulus intervals (ISIs) during pre- and post-placebo/nicotine administration. Amplitudes decreased from pre- to post-placebo recordings in nontreated patients but remained stable in THA-treated patients. Comparison of pre- and post-nicotine MMNs found amplitude increases with nicotine in nontreated but not in THA-treated patients. MMN latencies were shortened by nicotine in both treatment groups. These exploratory findings suggest that nicotine-improved strength of acoustic sensory memory traces and speed of acoustic sensory discrimination in AD are differentially affected by chronic tacrine treatment.     

Effects of lactate-induced panic attacks on brain stem auditory evoked potentials

As the clinical symptomatology of panic attacks may be conceivably related to abnormal brain stem activity, the present study examined the effect of lactate-precipitated panic on brain stem auditory evoked potentials (BSAEPs). The subjects were 27 patients who met DSM-III criteria for panic disorder (Pd), agoraphobia with panic attacks (AgPa) or agoraphobia (Ag). Following drug washout, patients were tested in two separate sessions, in a double-blind randomised controlled design in which each session involved two sequentially ordered BSAEP collection periods - a baseline period with no infusion followed by an intravenous infusion of 5% dextrose in water or 1.0 M sodium lactate (5 ml/kg in 5% dextrose/water) over a 20-min period. Of the 27 patients, 17 were clear responders, reporting panic attacks and self-report changes under lactate similar to those occurring during spontaneous panic. Of the remaining 10 patients, 6 were pseudo-responders, reporting panic symptoms under both dextrose and lactate, and 4 were non-responders. In the clear responders, lactate did not alter electrical events of the BSAEP, but further analysis within the clear responders, comparing AgPa patients with Pd patients, yielded a significant effect with lactate resulting in a prolonged III-V inter-peak interval in the AgPa group. It is suggested that the increased III-V interval in the AgPa group may be reflective of hyperactivity of brain stem noradrenergic nuclei.