Isolation rearing significantly perturbs brain metabolism in the thalamus and hippocampus.

Psychosocial neglect during childhood severely impairs both behavioral and physical health. The isolation rearing model in rodents has been employed by our group and others to study this clinical problem at a basic level. We previously showed that immediate early gene (IEG) expression in the hippocampus and medial prefrontal cortex (mPFC) is decreased in isolation-reared (IR) compared to group-reared (GR) rats. In the current study, we sought to evaluate: (1) whether these changes in IEG expression would be detected by the measurement of brain glucose metabolism using positron emission tomography (PET) with fluorodeoxyglucose (FDG) and (2) whether PET FDG could illuminate other brain regions with different glucose metabolism in IR compared to GR rats. We found that there were significant differences in FDG uptake in the hippocampus that were consistent with our findings for IEG expression (decreased mean FDG uptake in IR rats). In contrast, in the mPFC, the FDG uptake between IR and GR rats did not differ. Finally, we found decreased mean FDG uptake in the thalamus of the IR rats, a region we had not previously examined. The results suggest that PET FDG has the potential to be utilized as a biomarker of molecular changes in the hippocampus. Further, the differences found in thalamic brain FDG uptake suggest that further investigation of this region at the molecular and cellular levels may provide an important insight into the neurobiological basis of the adverse clinical outcomes found in children exposed to psychosocial deprivation.

Isolation rearing impairs wound healing and is associated with increased locomotion and decreased immediate early gene expression in the medial prefrontal cortex of juvenile rats.

In addition to its maladaptive effects on psychiatric function, psychosocial deprivation impairs recovery from physical illness. Previously, we found that psychosocial deprivation, modeled by isolation rearing, depressed immediate early gene (IEG) expression in the medial prefrontal cortex (mPFC) and increased locomotion in the open field test [Levine JB, Youngs RM, et al. (2007) Isolation rearing and hyperlocomotion are associated with reduced immediate early gene expression levels in the medial prefrontal cortex. Neuroscience 145(1):42-55]. In the present study, we examined whether similar changes in behavior and gene expression are associated with the maladaptive effects of psychosocial deprivation on physical injury healing. After weaning, anesthetized rats were subjected to a 20% total body surface area third degree burn injury and were subsequently either group or isolation reared. After 4 weeks of either isolation or group rearing (a period that encompasses post-wearing and early adolescence), rats were killed, and their healing and gene expression in the mPFC were assessed. Locomotion in the open field test was examined at 3 weeks post-burn injury. We found that: 1) gross wound healing was significantly impaired in isolation-reared rats compared with group-reared rats, 2) locomotion was increased and IEG expression was suppressed for isolation-reared rats during burn injury healing, 3) the decreased activity in the open field and increased IEG expression was greater for burn injury healing group-reared rats than for uninjured group-reared rats, 4) the degree of hyperactivity and IEG suppression was relatively similar between isolation-reared rats during burn injury compared with uninjured isolation-reared rats. Thus, in the mPFC, behavioral hyperactivity to novelty (the open field test) along with IEG suppression may constitute a detectable biomarker of isolation rearing during traumatic physical injury. Implications of the findings for understanding, assessing, and treating the maladaptive effects of psychosocial deprivation on physical healing during childhood are discussed.

Isolation rearing and hyperlocomotion are associated with reduced immediate early gene expression levels in the medial prefrontal cortex.

Environmental deprivation contributes in important ways to the development of a wide range of psychiatric disorders. Isolation rearing of rodents, a model for environmental deprivation in humans, consistently produces hyperlocomotion, which provides a measurable parameter to study the underlying mechanisms of early adverse psychosocial stressors. Male Sprague-Dawley rat pups were separated from dams at postnatal (PN) day 20 and reared either in groups of three or in isolation. On PN 38, locomotion was assessed in the open field. On PN 46, rats were killed and gene expression patterns examined in the medial prefrontal cortex (mPFC). Isolation-reared rats displayed increased locomotor activity and decreased resting time in the open field. Specific gene expression patterns in the mPFC were associated with both isolation rearing and hyperlocomotive behavior in the open field. Genes involved in these expression patterns included immediate early genes (IEGs) and genes that regulate cell differentiation and apoptosis. The study of these genes could provide important insights into how abnormal early psychosocial events affect brain function and behavior.

Astrocytes interact intimately with degenerating motor neurons in mouse amyotrophic lateral sclerosis (ALS).

Astrocytic proliferation and hypertrophy (astrogliosis) are associated with neuronal injury. However, neither the temporal nor the spatial relationship between astrocytes and injured neurons is clear, especially in neurodegenerative diseases. We investigated these questions in a mouse amyotrophic lateral sclerosis (ALS) model. The initial increase in astrogliosis coincided with the onset of clinical disease and massive mitochondrial vacuolation in motor neurons. After disease onset, astrogliosis increased further in parallel with the number of degenerating motor neurons. Examination of individual astrocytes by three-dimensional reconstruction revealed that astrocytes extended their processes toward, wrapped around, and sometimes penetrated vacuoles derived from neuronal mitochondria. These results show a close temporal correlation between the onset of neuronal degeneration and the beginning of astrogliosis in this neurodegenerative disease and reveal a novel spatial relationship that is consistent with the view that astrocytes play an active role in the neuronal degeneration process.

Obsessive-compulsive disorder among schizophrenic patients: an exploratory study using functional magnetic resonance imaging data.

Despite the growing research on the etiology of obsessive-compulsive disorder (OCD), and schizophrenia, the clinical distinction between the two disorders is not clearly understood. In the present investigation, we sought to better understand the relationship between OCD and psychotic disorders by examining functional magnetic resonance imaging (fMRI) data from a group of schizophrenic patients with varying degrees of OCD symptomatology, based on results of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the National Institute of Mental Health (NIMH) rating scales of OCD. While subjects performed a cognitive challenge paradigm that included a verbal fluency task, activation data from the left dorsolateral prefrontal cortex were collected and analyzed. We hypothesized that the fMRI signal patterns in schizophrenic patients with high levels of OCD symptomatology would differ from that of schizophrenic patients with a low level of OCD. For the group as a whole, no significant relationship was found for scores of either rating scale and fMRI signal change; however, a significant association was found for a subgroup of patients. For these schizophrenics, there was a negative relationship between OCD symptomatology and activation of the left dorsolateral prefrontal cortex. These results support the suggestion of several researchers that a relationship between OCD severity and neurophysiological activity exists in schizophrenia.

Psychological predictors of subsequent medical care among patients hospitalized with cardiac disease.

BACKGROUND: There have been numerous reports indicating a relation between psychological distress and coronary artery disease. The authors tried to determine whether psychological distress in patients hospitalized for coronary artery disease is associated with the amount of medical care required after discharge. METHODS: Using a prospective clinical cohort, 210 patients who had been admitted for myocardial infarction (n = 67), percutaneous transluminal coronary angioplasty (n = 75), or coronary artery bypass grafting (n = 68) were followed for 6 months. Index psychological status was determined from questionnaires measuring depression and anxiety. Disease severity was assessed by the index hospitalization medical record of left ventricular ejection fraction, number of stenotic vessels, and number of noncardiac comorbidities. The amount of subsequent medical care delivered was based on the number of days of rehospitalization for cardiac-related illness and for any reason within 6 months after discharge. This was determined from a combination of computer medical record and patient self-report. RESULTS: The authors first determined that both psychological depression and disease severity each predicted days of rehospitalization. (Anxiety was not predictive of rehospitalization.) Next, disease severity was controlled for using partial correlation, and depression was still predictive of rehospitalization. Finally, the authors combined the predictor variables using a regression model to predict rehospitalization. Depression was a significant main effect in all models predicting rehospitalization. CONCLUSIONS: Psychological depression appears to be an important predictor of rehospitalization among persons who have been admitted with coronary artery disease.

Extraintestinal considerations in inflammatory bowel disease.

If one reviews the literature with zeal, it is increasingly apparent that few organs escape recruitment when IBD is chronic or progressive. Insights into mucosal pathophysiology have helped with understanding the more frequent extraintestinal manifestations, but the mechanisms attendant to the development of less common events (e.g. acute pancreatitis, concurrent gluten sensitive enteropathy, or active pulmonary disease) remain either poorly studied or obscure. It is particularly interesting, however, to read reports of abnormal pulmonary function, generally of the obstructive type, correlated to measurements of abnormal intestinal permeability in patients with either active pulmonary sarcoid or pulmonary involvement in Crohn's disease. It has been further speculated that similarities in the mucosal immune system of the lung and intestine are responsible for evidence of bronchial hyperreactivity in patients with active IBD. Finally, it is important to recognize that extensions of the inflammatory process are not restricted to the development of organ-based events but may be responsible for some of the most frequent systemic abnormalities detected in IBD patients. It is now also well confirmed that the cytokine environment in IBD can support activated coagulation and, in some clinical situations, overt vascular thrombosis. The cerebrovascular complications of IBD are well recognized and range from peripheral venous thrombosis to central stroke syndromes and pseudotumor cerebri. Reports of focal white matter lesions in the brains of patients with IBD or an increased incidence of polyneuropathy may be other clinical examples of regional microvascular clotting. Microvascular injury appears to be more ubiquitously present, with reports ranging from a speculated primary causative role (e.g., granulomatous vasculitis in the mesenteric circulation) to the utility of nailbed vasospasm, in Crohn's disease, as a clinical marker for disease activity. It is also reported that IL-6 suppression of erythropoietin production is a major feature of the chronic anemia seen in active IBD. Moreover, the capacity of peripheral monocytes from active IBD patients to secrete TNF and IL-8 is reported predictive for the degree of therapeutic response from recombinant erythropoietin. These collected observations constitute another excellent example of the symmetry between basic science and clinical utility. It is from the context of applied basic science that many future therapies will arise. Empiricism will lose much of its appeal as clinical observations will be increasingly translated into cellular language. Already in animal models, elemental diets diminish IL-6-related acute inflammatory injury, and reductions in dietary lipid alter the antigenicity of bacteria. Provocatively, in humans, unconfirmed reports have even associated diet therapy with the resolution of uveitis and pyoderma gangrenosum. It is likely that efforts will also be made to induce oral tolerance if specific triggering proteins are discovered or to alter bowel flora if such an arcane area of investigation becomes resurgent.

Esthetic diagnosis.

To ensure esthetic success, dental practitioners must respond to patient inquiries with a codiagnostic approach, allowing the clear identification of esthetic problems and the visualization of solutions. This structured approach involves a therapeutic mind set whereby a common esthetic language is established, and a communication triangle is formed between the patient, the dentist, and the technicians. The problem is clearly identified through the use of the esthetic evaluation form, diagnostic casts, and computer imaging. The solutions are visualized and treatment methods established through a diagnostic wax-up and computer imaging. This approach works by building a high-energy, high-trust relationship between the doctor and the patient, which serves to increase the probability of successful and consistent treatment and improves the dentist's general understanding of esthetic concepts.

Psychometric properties of the Separation-Individuation Test of Adolescence within a clinical population.

Completed forms of the Separation Individuation Test of Adolescence (SITA) and the Millon Adolescent Personality Inventory were obtained from 117 clinical subjects. In addition, clinicians who were working with the subjects rated them on the SITA's subscale dimensions. The results were compared with those previously found for a nonclinical population. Moderately strong internal-structural properties were attained for six of the nine SITA subscales. Personality external criteria correlations showed a great deal of convergence with findings previously obtained from a nonclinical sample and were consistent with the theoretical foundations of the SITA subscales. Clinician ratings did not tend to correlate with the complementary SITA subscales, although they did with SITA subscales that were conceptually similar.

Safety profile of H2-receptor antagonists: current status of famotidine.

An assessment of the adverse reactions associated with H2-receptor blockers is presented, with particular emphasis towards famotidine. Post-marketing studies on the H2-receptor blockers have shown that they have a low incidence of adverse reactions (1-2% of patients) and are very effective in the treatment of peptic ulcers. The most common adverse reactions are gastro-intestinal, although central nervous system, cardiovascular, haematological, endocrine and hepatic disturbances may occur. Drug interactions and the considerable amount of post-marketing surveillance data, spanning over a decade of use, are also assessed.

Activation of blood coagulation in Crohn's disease. Increased plasma fibrinopeptide A levels and enhanced generation of monocyte tissue factor activity.

We have examined the relationships among activation of blood coagulation, generation of monocyte procoagulant activity, and clinical activity in patients with Crohn's disease. Subclinical activation of blood coagulation was measured using a radioimmunoassay for fibrinopeptide A. Fibrinopeptide A levels were strongly correlated with the level of disease activity as measured by the Crohn's disease activity index. Patients with active disease who were successfully treated either medically or surgically demonstrated a reduction of fibrinopeptide A levels. Failure of fibrinopeptide A to return to the normal range predicted an early relapse. Monocyte tissue factor generation was assessed in both unstimulated and lipopolysaccharide-stimulated mononuclear cell cultures obtained from the peripheral blood of patients with Crohn's disease. A strong correlation (r = 0.89) was observed between plasma fibrinopeptide A levels and monocyte tissue factor generation. These results suggest that monocyte procoagulant generation may contribute to the activation of blood coagulation in this inflammatory bowel disease. Moreover, fibrinopeptide A levels in Crohn's disease may provide a useful quantitative measure of inflammatory activity.

The Separation-Individuation Test of Adolescence.

The procedures undergone to establish the validity of the Separation- Individuation Test of Adolescence (SITA) are described. The test consists of six scales designed to measure key dimensions of adolescent separation-individuation. Each scale was subjected to three stages of validation: theoretical-substantive, internal-structural, and external-criterion. The results of data with 305 adolescents are reported. Although particular modifications from the original form are planned, appreciative levels of validity were established for the SITA's various scales.

Chemical and clinical evaluation of the random access analyzer "RA-1000".

In the RA-1000, a random-access discrete analyzer, an inert fluorocarbon fluid is used to prevent interaction and carryover. Production-model instruments were evaluated in two laboratories with respect to determination of glucose, creatinine, total protein, inorganic phosphorus, cholesterol, alkaline phosphatase, lactate dehydrogenase, creatine kinase, gamma-glutamyltransferase, and aspartate and alanine aminotransferases. Within-run, among-run, and day-to-day (for 15 days) precision was assessed, and results were correlated with those obtained by the methods routinely in use in our departments. Precision was excellent, correlation acceptable.

Filiform polyposis of the colon presenting as massive hemorrhage: an uncommon complication of Crohn's disease.

A case of localized filiform polyposis of the colon is presented. This lesion was part of a more generalized inflammatory bowel disease with clinicopathological features indicative of Crohn's disease. An unusual feature of this case was profuse rectal bleeding, initially from a solitary sigmoid ulcer and later from the area of filiform polyposis. A step by step clinicopathological follow-up emphasizing the development of filiform polyps is provided.