“Hearing voices” in schizophrenia: Who’s voices are they?

Paranoid schizophrenia is a subtype within the group of schizophrenia disorders. In the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), delusions and hallucinations are the first and second symptoms required for the diagnosis of schizophrenia. Empirical data and clinical observations allow us to present the hypothesis that paranoid schizophrenia can be divided into two subgroups: (1) Hallucinatory subgroup, patients with prominent hallucinations and delusions influenced by auditory hallucinations, (2) Delusional subgroup, patients with prominently impaired thought content, in which hallucinations are not significant clinical factors. Furthermore, we believe that auditory hallucinations are not disturbances of perception but rather of thought – or “pseudo-perceptions”.     

Tracing the origins of “fetal origins” of adult diseases: Programming by oxidative stress?

Too small size at birth (due to poor fetal growth and/or preterm delivery) has been associated with substantially elevated risks of the metabolic syndrome (dislipidemia, insulin resistance, hypertension), type 2 diabetes and cardiovascular disease in adulthood. The mechanisms of such "fetal origins" or "programming" of disease phenomenon remain unresolved. Too large size at birth seems also associated with an increased risk. Many known or suspected causes of or conditions associated with adverse (poor or excessive) fetal growth or preterm birth have been associated with oxidative stress. Plausibly, oxidative stress may be a common link underlying the superficial "programming" associations between adverse fetal growth or preterm birth and elevated risks of certain chronic diseases. The mechanisms of oxidative stress programming may be through directly modulating gene expression or indirectly through the effects of certain oxidized molecules. Experimental investigations have well demonstrated the role of redox balance in modulating gene expression, and recent studies indicate that both the insulin functional axis and blood pressure could be sensitive targets to oxidative stress programming. Adverse programming may occur without affecting fetal growth, but more frequently among low birth weight infants merely because they more frequently experienced known or unknown conditions with oxidative insults. As oxidative stress levels are easily modifiable during pregnancy and early postnatal periods (which are plausible critical windows), the hypothesis, if proved valid, will suggest new measures that could be very helpful on fighting the increasing epidemic of the metabolic syndrome, type 2 diabetes and cardiovascular disease. Currently, there are several ongoing large randomized trials of antioxidant supplementation to counter oxidative stress during pregnancy for the prevention of preeclampsia. It would be invaluable if long-term follow-ups of infants born to women in such trials could be realized to test the oxidative stress programming hypothesis in such experimental trial settings.     

Methotrexate for the treatment of rheumatoid arthritis in the biologic era: Still an “anchor” drug?

The improvement of rheumatoid arthritis (RA) management has been strictly related to methotrexate (MTX) long-term effectiveness, safety profile and its widespread use in clinical practice over the last decades. According to the results of several head-to-head comparative trials against other synthetic DMARDs, MTX has been recognised as the “anchor drug” for the treatment of RA at the end of the 1990s. The subsequent increasing knowledge in the area of RA pathophysiology has progressively expanded the arsenal of available therapeutic tools, especially by the introduction of novel drugs such as biological DMARDs. The introduction of therapies targeted to key molecules and cells involved in RA pathogenesis has significantly changed the strategies for disease management, possibly modifying the key role of MTX. This review first analyses data supporting the evolution of MTX towards the role of “anchor drug” for RA in the pre-biologic era. We will then examine how the introduction and progressive spreading of biological agents could have modified the central role of MTX in the approach to RA.     

Can children with autistic spectrum disorders perceive affect in music? An experimental investigation

BACKGROUND: Children with autistic spectrum disorders typically show impairments in processing affective information within social and interpersonal domains. It has yet to be established whether such difficulties persist in the area of music; a domain which is characteristically rich in emotional content. METHODS: Fourteen children with autism and Asperger syndrome and their age and intelligence matched controls were tested for their ability to identify the affective connotations of melodies in the major or minor musical mode. They were required to match musical fragments with schematic representations of happy and sad faces. RESULTS: The groups did not differ in their ability to ascribe the musical examples to the two affective categories. CONCLUSIONS: In contrast to their performance within social and interpersonal domains, children with autistic disorders showed no deficits in processing affect in musical stimuli.     

Recognition of emotional‐prosodic meanings in speech by autistic,schizophrenic, and normal children

The abilities of autistic, schizophrenic, and normal‐control children to label four emotional intonations (the emotional task) in speech were tested, along with a linguistic task. All stimuli were pretested on normal adults. Older (≥ 8 years of age) normal children performed as well as adults on both tasks; younger normal children and both younger and older autistic children performed poorly on the emotional task; children (all older) diagnosed as schizophrenic were not significantly impaired in either task. Mental age was not correlated with performance in autistic children. The relevance of these results to other findings regarding emotional and linguistic behaviors in normal and disabled children is considered.     

Apoptotic death by ceramide: will the real killer please stand up?

Many studies have shown that the addition of ceramide to an incubation medium, or procedures that lead to increased ceramide concentrations, can begin a process that leads to slowing of cell growth or apoptotic cell death. Only a few studies have examined the nature of the accumulating ceramide: is it composed of a fatty acid and sphinganine, or a fatty acid and sphingosine? Of the studies involving addition of ceramide to a cell culture, almost all have found that the sphingosine amide is active, not the sphinganine amide. Nearly all of these studies have utilized the rare form of ceramide, containing an acetyl group rather than the commonly found palmitoyl, stearoyl, or longer group. Acetyl sphingosine produces some unexpected effects with cells, the most striking being the formation of reactive oxygen species and mitochondrial damage. This mitochondrial damage appears to be an essential step in apoptosis. The possibility should be considered that the reactive oxygen species appear as the result of oxidation of the allylic alcohol group in unsaturated ceramides. This question is very relevant to a host of ceramide functions, particularly cancer chemotherapy and cell growth.     

Is there a role for atrial peptides in the labyrinthine “disease”?

The important role of atrial natriuretic peptides (ANP) in regulating blood pressure and changing vascular permeability has been widely studied and assessed during the last ten years. Considering the characteristics of this mechanism, which is responsible for a hypotensive and hypovolemic effect, and the possible role of hypotension associated with a default of autoregulatory sympathetic reactions in inner ear unexplained disorders, it seems reasonable to hypothesize a possible involvement of ANP system in the genesis of such disorders. As a matter of fact, the presence of specific receptors for ANP in the inner ear has been widely reported in studies concerning both rat and human inner ear, although their precise role in the labyrinthine homeostasis has not been satisfactory explained until now. Some aspects concerning vascular and fluid regulation of the inner ear under different conditions still remain not totally clear, and consequently a detailed explanation to the possible mechanism causing inner ear disorders of functional origin is lacking; from this point of view, an investigation on the serum level of ANP in subjects with labyrinthine affections of uncertain origin could be of some utility in contributing to assess the role of this system in the inner ear fluid regulation and in the inner ear perfusion and to investigate on the possible influence of an abnormal ANP release in some kind of inner ear damage.     

Is the prevalence of wheeze in children altered by neonatal BCG vaccination?

BACKGROUND: The prevalence of asthma and atopic disease has increased in recent decades, but precise reasons for this increase are unknown. BCG vaccination is thought to be among a group of vaccines capable of manipulating the immune system toward T(H)1 dominance and therefore reducing the likelihood of atopic disease. OBJECTIVE: The aim of this study was to determine the influence of neonatal BCG vaccination on the prevalence of wheeze in a large community population of children. METHOD: In a historical cohort study, a parent-completed questionnaire was used to identify the prevalence of wheeze in BCG-vaccinated and nonvaccinated children in Manchester, England. RESULTS: There were 2414 participants aged between 6 and 11 years. In a univariate analysis neonatal BCG vaccination was associated with a significantly lower prevalence of wheeze (odds ratio, 0.69; 95% CI, 0.55-0.86), and statistical significance was retained when the analysis was adjusted for potential confounders (odds ratio, 0.68; 95% CI, 0.53-0.87). CONCLUSION: These results demonstrate an association between asthma symptom prevalence and neonatal BCG vaccination, relating to a possible 27% reduction in prevalence, and are therefore of considerable public health importance. CLINICAL IMPLICATIONS: The capacity of neonatal BCG vaccination to reduce the prevalence of respiratory symptoms in children warrants further investigation.     

“Killing the Blues”: A role for cellular suicide (apoptosis) in depression and the antidepressant response?

Apoptosis or programmed cell death is a critical regulator of tissue homeostasis and emerging evidence is focused on the role of apoptosis mechanisms in the central nervous system. Generally, apoptosis is necessary to prevent cancerous growths. However, excessive apoptosis in post-mitotic cells such as neurons leads to neurodegeneration. Chronic stress, which can precipitate depression, has been shown to increase the susceptibility of certain populations of neurons to cell death while antidepressant treatment, in general, shows the ability to oppose these effects and promote neuroprotection. Here, we discuss the major players in cell death pathways, the physiological implications of chronic stress and depression, chronic stress models in animals which result in cell death and the different classes of antidepressants and mood stabilizers that have been shown to prevent cell death. We discuss the cellular effects of antidepressants and possible modes of action in preventing apoptosis. Investigations on the role of apoptosis in mediating the molecular, physiological and behavioural effects of antidepressants may help gain a better mechanistic insight into drug action and allow refinement of current therapeutics in order to target these pathways in a specific manner.     

Does the meniscus exist in the elbow joint in children?

The authors report a case of meniscus at the elbow joint in a 15-month-old infant causing a limitation of elbow extension. Histological examination demonstrated that this tissue was not a synovial fold or a chondroid metaplasia of the synovial fold. As a meniscus does not appear at any stage of the embryological evolution of the elbow joint, it has been concluded that the presence of the meniscus can be considered as an abnormal condition.     

Obsessive-compulsive disorder: A “sensory-motor” problem?

Obsessive–compulsive disorder (OCD) is a clinically heterogeneous condition. Although its pathophysiology is not completely understood, neurophysiologic and neuroimaging data have disclosed functional abnormalities in the networks linking frontal cortex, supplementary motor and premotor areas, striatum, globus pallidus, and thalamus (CSPT circuits). By means of transcranial magnetic stimulation (TMS) it is possible to test inhibitory and excitatory circuits within motor cortex.     

The Genus Streptococcus – Part I: Emerging Pathogens in the “Pyogenic Cocci” and the “Streptococcus bovis” Groups

In this first part of a two-part update on the streptococci, new and emerging pathogens in the “pyogenic cocci group” and the “Streptococcus bovis group” are addressed. Among the pyogenic cocci, several new species have been described, and some of these are becoming relevant agents of human disease. Streptococcus porcinus and Streptococcus pseudoporcinus are β-hemolytic streptococci that are found in swine and humans, respectively. S. pseudoporcinus has been isolated primarily from the female genital tract and may play a role in genitourinary tract infections, wound infections, and adverse pregnancy outcomes. Streptococcus iniae, Streptococcus hongkongensis, and Streptococcus ictaluri are fish pathogens, and S. iniae, in particular, has been isolated from several human infections in persons who handle raw seafood or experience penetrating injuries from fish spines or crab pincers. Streptococcus gallolyticus subspecies (i.e., the former “S. bovis group”) are well-recognized causes of bacteremia, meningitis, and endocarditis. S. gallolyticus subsp. gallolyticus is known to be associated with colon cancer, and current studies suggest that other S. gallolyticus subspecies (particularly S. gallolyticus subsp. pasteurianus) may also be associated with meningitis and other digestive tract malignancies. In this review, current research on S. gallolyticus subspecies and proposed mechanisms for their involvement in the pathogenesis of colonic carcinoma are also briefly addressed.     

Value of magnetic resonance enterography in diagnosis and treatment follow up in Crohn’s disease in children

PurposeCrohn’s disease (CD) is a chronic inflammatory disease which can affect all parts of the gastrointestinal tract. Magnetic resonance enterography (MRE) enables detection of pathologic changes in the small intestine, which are not accessible by conventional endoscopy. The aim of the study was to assess the value of MRE in imaging of small bowel lesions, their location and extent, in CD patients and its correlation with clinical and endoscopic activity.Materials and methodsMRE was performed in 108 children with CD, aged 5.5 to 18 years. The diagnosis was based on the Porto criteria. Location and clinical manifestation was evaluated according to the Paris classification. Clinical CD activity was assessed with PCDAI and endoscopic activity with SES-CD. In 36 children, control MRE was performed.ResultsThe most common endoscopic location of the disease was the colon (41.7%), terminal ileum and colon (24.1%). Inflammation as the main clinical manifestation was dominant (81.5%). In MRE, inflammatory changes were found in 40.8% of children, strictures in 11.1%. The EIA value (activity in MRE) increased along with PCDAI score and SES-CD. MRE performed during follow up, showed transmural healing in 16.7% of patients and improvement in 55.5%.ConclusionsMRE is an efficient diagnostic tool in proper characterization of disease location in pediatric CD. As positive correlation of the results of MRE with the endoscopic and clinical activity has been found, taking into account good tolerance and non-invasiveness of the procedure it can be recommended to be used in reassessment.     

‘Bipolar disorder’ in the elderly: What's in a name?

Bipolar disorder is a chronic disorder of mood which leads to episodes of either elevated mood or depression in a sizable number of adults in the community (1%). Though the prevalence rates in the elderly are lower in the community (up to 0.1%), there is significantly higher morbidity in protected environments like care homes and hospital settings where prevalence rates may be as high as 10%. Bipolar disorder in the elderly is probably heterogenous and its etiopathogenesis is complex. Bipolar disorder may be divided into two distinct subtypes, the late onset bipolar (LOB) and the early onset bipolar (EOB) groups. LOB patients tend to have a milder illness in terms of manic severity but they have higher medical and neurological burden. They also have lower familial burden of bipolar illness as compared to EOB patients. There is an increased risk of dementia and stroke in patients with late life bipolar disorder (and there may be a protective effect of lithium in preventing dementia). White matter changes, as seen by increased white matter hyperintensities on neuroimaging, are also increased, providing further evidence of cerebrovascular disease. Treatment of late life bipolar is currently based on guidelines drawn up for younger bipolar disorder patients. Good quality intervention studies are needed to estimate the possible protective effect of cognitive enhancers and/or vascular prevention strategies. This review suggests that late life bipolar disorder, particularly late onset bipolar disorder, is probably a distinct diagnostic entity compared to the younger bipolar patients as it has a different presentation, etiology and hence perhaps needs different treatment strategies.