The stress cascade and schizophrenia: etiology and onset

Psychosocial stress is included in most etiologic models of schizophrenia, frequently as a precipitating factor for psychosis in vulnerable individuals. Nonetheless, the stress-diathesis model has not been tested prospectively in prodromal patients as a predictor of psychosis. The biological effects of stress are mediated by the hypothalamic-pituitary-adrenal (HPA) axis, which governs the release of steroids, including cortisol. The past few decades have witnessed an increased understanding of the neural effects of stress and cortisol, including both normal and abnormal diatheses. As few biological markers have been evaluated as risk factors for psychosis in prodromal patients, the HPA axis and its interaction with intervening life events are apt candidates for study. In this article, we review the HPA axis and its neural effects, present a model for how stress might precipitate psychosis in vulnerable individuals, review the empirical evidence of a link between stress and schizophrenia symptoms, and propose a research design and appropriate statistical models to test the stress-diathesis model for psychosis onset in prodromal patients.     

Patterns of swallowing failure following medialization in unilateral vocal fold immobility

OBJECTIVE: To quantify the incidence of penetration and aspiration following medialization for unilateral vocal cord immobility (UVCI) and determine patterns of failure. STUDY DESIGN: Blinded analysis consecutive case series. METHODS: Prospective blinded analysis of videofluoroscopic swallowing studies of patients who had received a medialization procedure was conducted, determining the incidence of penetration and aspiration by using the Penetration-Aspiration Scale. Pharyngeal transport measures were also assessed. Associations between clinical factors and penetration-aspiration were statistically determined. RESULTS: Sixty-seven videofluoroscopic swallowing studies were reviewed in patients (mean age, 63.3 y) who had undergone vocal fold medialization (14 laryngoplasties and 53 vocal cord injections) for UVCI. Unilateral vocal cord immobility was left-sided in 56 patients (83.6%), and 50 patients (74.6%) had a postsurgical etiologic factor for their immobility. Thirty (44.8%) and 16 (23.9%) patients demonstrated penetration and aspiration, respectively. Penetration most often occurred during the swallow, but aspiration was equally likely to occur during or after the swallow. No differences in the incidence of penetration or aspiration were noted according to the side of vocal fold paralysis ( P=.20, chi test) or etiologic factor ( P=.69). Further analysis found that swallow factors significantly associated with penetration and aspiration were swallow delay ( P=.001, Wilcoxon ranked pairs test) and reduced laryngeal elevation ( P=.001), as well as bolus residues in the valleculae (P =.002), piriform sinus ( P=.001), or posterior pharynx (P =.008). CONCLUSIONS: Many patients demonstrate significant radiographic aspiration even after medialization procedures for UVCI. Although glottal incompetence is a known risk factor for aspiration, other factors including pharyngeal bolus transport are important in determining an effective swallow in UVCI.     

Ultrasonography: Its role in nodular thyroid disease

Objective The objective was to correlate the number, size and extent of the nodules as determined during the preoperative clinical examination of the thyroid gland, USG, intra-operative examination and histopathology. Also, FNAC (with or without USG guidance) and USG findings suggestive of malignancy were correlated with the final histopathology. Setting Tertiary referral centre Patients A retrospective chart review was done for 106 patients who underwent surgery for benign or malignant nodular thyroid disease in our center, between Jan 2004–Dec 2006. Results USG has 7 times higher predictive value than clinical examination in detecting number of nodules and determining size of nodules. USG guided FNAC has a sensitivity of 85.71% and specificity of 90.0% in detecting malignancy in nodular thyroid disease. However for predicting malignancy in thryoid nodules, this study shows that USG has a sensitivity of 20.0% and specificity of 97.67%. Conclusion In patients with nodular thyroid disease, USG can accurately determine the number and the size of the nodules. It is extremely useful in guiding FNAC; However its role in predicting malignancy is doubtful. We therefore recommend that USG guided FNAC be carried out as a routine in the evaluation of thyroid nodules.     

Epidural lysis of adhesions and myeloscopy

Chronic low back pain is one of the most common ailments in modern medicine, with as many as 79% of patients with acute pain continuing to suffer with chronic or recurrent low back pain 1 year after its onset. Lumbar epidural fibrosis and post-lumbar laminectomy syndrome are increasingly recognized as being responsible for persistent low back pain. Estimations show that approximately 5% to 40% of lumbar surgeries result in failed back surgery syndrome. Epidural adhesiolysis with myeloscopy is an interventional technique based on the premise that the three-dimensional visualization of the contents of the epidural space provides the physician with the ability to directly visualize the structures, perform appropriate adhesiolysis, and administer drugs specifically to the target. This review describes pathophysiologic aspects, purposes and goals, rationale and indications, complications, and effectiveness of epidural lysis of adhesions with myeloscopy.     

Mifepristone pretreatment overcomes resistance of prostate cancer cells to tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL)

Examination of the effects of TRAIL (tumor necrosis factor alpha-related apoptosis-inducing ligand) showed higher apoptotic response in LNCaP C4-2, whereas LNCaP were resistant. However, treatment of LNCaP with Mifepristone, an antiprogestin, before TRAIL induced significant apoptosis, similar to the levels observed in LNCaP C4-2. Experiments to determine the reasons for altered response of the cell lines showed no significant differences in death/decoy receptors and caspase-8 activity. However, treatment induced increased truncation of Bid and activation of caspases -9, -7, and -3 in LNCaP C4-2. Time course experiments showed that caspase-8 was activated before the involvement of mitochondrial pathway, and caspase-9 was responsible for activation of caspases -7 and -3. Use of specific caspase inhibitors demonstrated the presence of a short-loop feedback activation of Bid. Published reports suggested that increased phosphorylation of Akt was responsible for resistance of LNCaP to TRAIL. However, no significant differences were noticed in the levels of phosphorylated Akt in TRAIL-resistant LNCaP and TRAIL-sensitive LNCaP C4-2. On the basis of our results, it is suggested that the differences in response of the two cell lines to TRAIL is at the mitochondrial level.     

Hyperhomocysteinemia and the risk of thromboembolic phenomenon in patients with chronic renal failure

Thromboembolic phenomena are a major cause of morbidity and mortality in patients with end-stage renal disease. Studies in patients with chronic renal failure (CRF) have demonstrated an increased relative risk of coronary artery disease (CAD) in association with hyperhomocysteinemia (HHe). However, very little data exist about the causal relationship between HHe and cerebrovascular diseases (CVA) in patients with CRF. We report the results of our observational retrospective study to determine the effect of HHe on CVA and CAD in patients with CRF (defined as creatinine clearance <50 ml/min). One hundred ten male patients were eligible for our study performed at a Veterans Affairs Medical Center. Age range was 36-86 years (median age 67 years). A fasting plasma HC level >15 micromol/l was considered as HHe. Thirty-four patients were on dialysis. Eight patients were postrenal transplantation. Our study results showed that a homocysteine (HC) level greater than 15 micromol/l was an independent predictor of CVA, after adjusting for potential confounders. Adjusted odds ratio (OR) for CVA was 10.9 (CI: 1.8-67.2, p=.01). Although our study results suggest a strong relationship between HHe and CVA, they failed to demonstrate an association between HHe and CAD. There exists a need for larger prospective randomized clinical trials to evaluate the effect of HHe on the incidence of CVA and CAD in patients with CRF.     

Central and peripheral chemoreflexes in panic disorder

Klein (Arch Gen Psychiatry, 50, 1993, 306-317) has suggested that panic disorder patients have a false suffocation alarm that may be associated with a lowered threshold for carbon dioxide detection. We compared the thresholds and sensitivities of the central and peripheral chemoreflexes between panic disorder patients and age- and sex-matched healthy volunteers to test this aspect of the hypothesis. We used a modified version of Read's rebreathing technique in 11 panic disorder patients and 10 healthy volunteers to examine the peripheral and central chemoreflex characteristics in these two populations. Subjects were examined during three rebreathing tests: training, hyperoxic (central chemoreflex alone) and hypoxic (combined central and peripheral chemoreflex). Panic symptoms were retrospectively assessed between groups using a DSM-IV derived Panic Symptom Scale. Comparisons of panic disorder patients with agoraphobia and healthy volunteers showed no significant differences in sensitivities or thresholds. Klein's hypothesis is not supported by these data. If a false suffocation alarm exists, its triggering may not be implemented within the respiratory chemoreflexes.