Psychotic depression and mortality

OBJECTIVE: Major depressive disorder is associated with elevated mortality rates that increase with the severity of depression. The authors hypothesized that patients with psychotic depression would have higher mortality rates than patients with nonpsychotic depression. METHOD: Survival analytic techniques were used to compare the vital status of 61 patients with psychotic major depression with that of 59 patients with nonpsychotic major depression up to 15 years after hospital admission. Medical status was assessed with the Cumulative Illness Rating Scale. Dexamethasone suppression test (DST) data were available for 101 patients. RESULTS: The mortality rate for subjects with psychotic depression was significantly greater than that for those with nonpsychotic depression, with 41% versus 20%, respectively, dying within 15 years after hospital admission. A proportional hazards model with age and medical status entered as covariates confirmed a significantly higher mortality rate in patients with psychotic depression (hazards ratio=2.31). A positive DST result was associated with psychotic depression but was not related to vital status. CONCLUSIONS: Patients with psychotic depression have a two-fold greater risk of death than do patients with severe, nonpsychotic major depression.     

Positron emission tomography in female patients with borderline personality disorder

The pathology of Borderline personality disorder (BPD) is poorly understood and its biological basis remains largely unknown. One functional brain imaging study using [(18)F]Deoxyglucose-PET previously reported frontal and prefrontal hypometabolism. We studied brain metabolism at baseline in 12 medication-free female patients with BPD without current substance abuse or depression and 12 healthy female controls by [(18)F]Deoxyglucose-PET and statistical parametric mapping. We found significant frontal and prefrontal hypermetabolism in patients with BPD relative to controls as well as significant hypometabolism in the hippocampus and cuneus. This study demonstrated limbic and prefrontal dysfunction under resting conditions in patients with BPD by FDG-PET. Dysfunction in this network of brain regions, which has been implicated in the regulation of emotion, may underlie symptoms of BPD.     

Homograft conduit failure in infants is not due to somatic outgrowth

OBJECTIVE: It has been assumed that the need for homograft replacement is due to somatic outgrowth, but this has not been adequately studied. Our objective was to identify reasons for homograft conduit failure. METHODS: The records and imaging studies of 40 patients undergoing homograft conduit replacement of the right ventricular outflow tract from 1996 to 2000 were retrospectively reviewed. RESULTS: The majority of patients had a diagnosis of tetralogy of Fallot (n = 20) and truncus arteriosus (n = 13). The median age at the initial operation was 8 months (0.25-108 months). The initial homograft sizes ranged from 9 to 22 mm, and 28 conduits were of pulmonary origin. When comparing size of the initial homograft with patients' expected pulmonary valve diameter (z = 0), oversizing was noted to be +3 (range, 0.83-5.4). Median interval to conduit failure was 5.3 years (0.83-11.3 years). At homograft replacement, only 12 patients had an existing conduit that was 1 SD below the homograft conduit size needed (z < or = -1). Most conduits had important regurgitation, but this was rarely a primary reason for reintervention (n = 1). Reoperation was usually required for stenosis, with a median gradient of 53 mm Hg (20-140 mm Hg). Stenosis was further categorized angiographically as follows: homograft valvular stenosis (shrinkage; 21/40 [53%]), distal anastomotic stenosis (4/40 [10%]), conduit kinking (3/40 [8%]), sternal compression (3/40 [8%]), posterior shelf impingement (2/40 [5%]), and somatic outgrowth (3/40 [8%]). Replacement in 2 patients was for proximal hood aneurysm. Several patients (7/40 [18%]) had stenosis at multiple levels. The average decrease in conduit diameter was 47% (28%-73%). CONCLUSIONS: Somatic outgrowth is seldom a primary reason for homograft conduit replacement of the right ventricular outflow tract. The most common cause for failure is conduit obstruction with thickening and shrinkage at the annular area. Conduit stenosis was responsible for failure in 53% of patients, technical issues were responsible for 30%, and only 8% failed as a result of somatic outgrowth. Placement of a smaller homograft (z = 0) at the initial operation may decrease the incidence of conduit kinking, sternal compression, and posterior shelf impingement.     

Perforating Barrett's ulcer resulting in a life-threatening esophagobronchial fistula

Perforating benign ulcer is a very rare complication of Barrett's esophagus. This report presents the management of a patient with a Barrett's ulcer that penetrated into the left mainstem bronchus resulting in a life-threatening bronchial esophageal fistula. This rare complication was successfully managed by using a staged surgical approach, which combined the principles used for treating benign esophagorespiratory fistulas and perforating Barrett's ulcers.     

Neuroimaging of childhood trauma

Childhood abuse is a major public health problem affecting as many as a third of children in this country today at some point before their 18(th) birthday. The effects of childhood trauma on the brain are increasingly an area of interest. In trying to understand the effects of early stressors on the brain we use animal models of early stress to guide the development of hypotheses. An important potential tool in understanding the effects of abuse on the brain is neuroimaging. Neuroimaging studies in traumatized children are in a relative state of infancy. A number of methodological and ethical issues make this a difficult area for research, including problems ranging from patient motion during scanning to the ethical issues of the duty to report abuse and working with child protective services. Some studies have shown that adults abused as children have smaller volume of the hippocampus, a brain area involved in learning and memory, as measured with magnetic resonance imaging (MRI). One study in children with posttraumatic stress disorder (PTSD) did not find smaller hippocampal volume, but did find smaller brain volume and corpus callosum. Functional neuroimaging studies are consistent with alteration in function and structure of medial prefrontal cortex and hippocampus in patients with childhood sexual trauma and PTSD. These initial results suggest that childhood abuse in the setting of PTSD is associated with long-term changes in brain structure and function.     

Iatrogenic secondary post‐partum haemorrhage: Apropos of two uncommon cases

In this article we would like to highlight uterine pseudoaneurysm as a cause of secondary post‐partum haemorrhage following Caesarean section. We would like to stress Doppler ultrasound scan as the initial screening modality for this condition. We also describe angioembolization as the prudent treatment option for this condition rather than resorting to surgery.     

Structural determinants in adenovirus 12 E1A involved in the interaction with C-terminal binding protein 1

The interaction between the C-terminal binding protein 1 (CtBP-1) and purified Ad12 E1A protein has been examined through the use of a combination of biophysical techniques. A fragment equivalent to the 77 C-terminal amino acids of Ad12 E1A (Ad12 77-a.a. E1A) was generated by limited proteolysis of Ad12 266-a.a. E1A at Phe(187) and/or Tyr(189) using chymotrypsin. The impact of deletion of the 189 N-terminal amino acids from E1A on the equilibrium dissociation constant K(d) for binding to CtBP was assessed using ELISA in vitro binding assays and intrinsic fluorescence spectroscopy. Values of K(d) of 4.0 and 38 nM were determined for full-length and truncated forms of E1A, respectively. Circular dichroism spectroscopic studies revealed that the conformation adopted by these polypeptides is dependent on the surrounding environment, which is predominately randomly folded when free in solution, but adopting a more ordered alpha-helical secondary structure in the presence of trifluoroethanol. Using nuclear magnetic resonance (NMR) spectroscopy to examine the interaction between Ad E1A and CtBP it was observed that the chemical shift positions of individual backbone amide nitrogen atoms were well resolved in (15)N-(1)H-HSQC NMR spectra performed on samples of isotopically (15)N-labeled Ad12 77-a.a. E1A. In the presence of CtBP, signals of backbone amide nitrogen atoms displayed increased linewidth consistent with an increase in molecular mass upon binding CtBP. In addition, some signals that have been attributed to Val(254/256) and Leu(259), and reside within the binding site for CtBP on E1A, are shifted in the (15)N- and/or (1)H-dimensions, defining specific contacts between E1A and CtBP. These data suggest that structural determinants in the C-terminal PXDLS binding motif in the rest of exon 2 and in exon 1 all contribute to optimizing the conformation of the binding site on Ad12 E1A for CtBP. However, no interaction was observed between CtBP and truncated Ad12 E1A, which no longer contained the C-terminal binding motif.     

Clinical pharmacology research in the pediatric patient: the challenge continues

For most of the 20th century, most drugs labeled by the United States Food and Drug Administration (USFDA) have not been adequately studied in the pediatric population. This lack of data has necessitated the continued dependence of practitioners on sub-optimal prescribing data placing pediatric patients at great risk of serious therapeutic misadventures. Recently, the USFDA has enacted and begun to enforce the Final Rule of 1997 which became effective on 1 April 1999. This rule is the culmination of the persistent efforts of numerous professional organizations, clinicians, academicians, the USFDA and others, to ensure the ready availability of appropriate data for medications intended for or that will be used in children. Unlike the 1994 Rule which voluntarily required pharmaceutical manufacturers to submit pediatric data, the Final Rule mandates submission of such data and, most importantly, empowers the USFDA to afford incentives and penalties for non-compliance including possible removal of already marketed products. This overview addresses many of the important components which must be included in the performance of a comprehensive clinical pharmacologic evaluation serving as the foundation for optimal dosing across the broad age range encompassing pediatric practice. Furthermore, the possible risk and/or benefits of the study must be reasonably defined prior to undertaking the study and clearly shared with the patient's caregivers. Consent should always be obtained from the caregiver and, when appropriate, assent obtained from the underage child. To facilitate such clinical investigations and to foster collaborative efforts with innovators and clinical research programs, the National Institutes of Health through the National Institute of Child Health and Human Development of the NIH established a network of Pediatric Pharmacology Research Units. These units have worked closely together and with other pediatric research centers to facilitate USFDA labeling of a number of commonly used medications. All of these very positive efforts highlight the many challenges that remain for the pediatric investigator and practitioner while underscoring the very positive environment in support of these efforts.     

Transepithelial paracellular leakiness induced by chronic phorbol ester exposure correlates with polyp-like foci and redistribution of protein kinase C-alpha

Although exposure of LLC-PK1 epithelial cell sheets to phorbol esters (TPA) causes a near immediate and total decrease of transepithelial electrical resistance (TER), continuation of exposure for 3 to 4 days results in a tachyphylactic response as TER begins to return to control levels. Recovery of TER is maximal by 5 to 6 days, but reaches only 70 to 80% of control level. A reciprocal change in the transepithelial flux of D-mannitol indicates that the TER decrease is indicative of an increase in tight junction permeability. Exposure of cell sheets to TPA for several days also results in the appearance of multilayered polyp- like foci (PLFs) across the otherwise one cell layer thick cell sheets. The pattern of penetration of the electron dense dye, ruthenium red, from the apical surface, across the tight junction and into the lateral intercellular space indicates that the tight junctions of the cell sheet become uniformly leaky after acute exposure to TPA. However, when exposure is continued for several days, only the junctions of cells in the PLFs manifest leakiness. The decrease in TER following acute TPA exposure correlates with the translocation of protein kinase C-alpha (PKC alpha) into a membrane-associated compartment. With exposure of several days, only a trace of PKC alpha is visible by Western immunoblot, and this is in the membrane-associated compartment. Immunofluorescent microscopy indicates that the trace of PKC alpha seen in the Western immunoblots is ascribable distinctly to cells of the PLFs. Monolayer areas between PLFs show no discernible immunofluorescent signal. The data therefore indicate that tight junction barrier function may be restored in certain areas by the down regulation of PKC alpha from the membrane-associated compartment. Failure to down regulate may result in the paracellular leakiness and abnormal cell architecture of the PLFs. Possible implications of this model for in vivo epithelial tumor promotion are discussed.