Awakenings change results of nighttime ambulatory blood pressure monitoring

OBJECTIVE: Investigate the effect of distinguishing nighttime and sleep on nocturnal blood pressure results in ambulatory blood pressure monitoring. METHODS: We recruited 36 patients, 29 men, with suspected obstructive sleep apnea/hypopnea syndrome attending a sleep clinic for diagnostic polysomnography and who agreed to wear a Spacelabs 90207 ambulatory blood pressure monitor during polysomnography. Their mean age was 45+/-11 years; body mass index (BMI), 30.8+/-5.4 kg/m; apnea-hypopnea index, 35+/-29 AH/h; 13 had a history of hypertension. A microphone attached to the ambulatory blood pressure monitor recorded its sounds in the polygraph and allowed us to classify each ambulatory blood pressure monitoring measurement as being made in electrographically-determined wake (e-wake) or sleep state (e-sleep). RESULTS: Patients were asleep during (mean+/-SD) 61+/-24% (range 0-100%) of the 14+/-1 nighttime blood pressure measurements. Systolic and diastolic ambulatory blood pressure monitoring readings were significantly higher during e-wake (121+/-12/73+/-9 mmHg) than during total nighttime (119+/-11/70+/-8 mmHg) and e-sleep (116+/-13/68+/-9 mmHg). On the basis of nighttime measurements, 22 patients (61%) had nocturnal hypertension. On the basis of measurements made during e-sleep, nocturnal hypertension was diagnosed in 12 patients (33%; chi2=5.54; P=0.018). A multiple linear regression model showed that the percentage of measurements made in e-sleep was the only variable that significantly explained the difference between nighttime and e-sleep blood pressure figures, when controlling for sex, age, BMI, apnea-hypopnea index, and lowest SaO2. CONCLUSION: During ambulatory blood pressure monitoring, nighttime blood pressure readings are higher than during e-sleep and this changes dipping and nocturnal hypertension classification.     

HIV risk in Karachi and Lahore, Pakistan: an emerging epidemic in injecting and commercial sex networks

The objective of this study was to measure HIV prevalence and risk behaviour in injecting drug users (IDUs), male sex workers (MSWs), Hijras (transgenders), female sex workers (FSWs) and male truckers in Karachi and Lahore, Pakistan. The design was a linked-anonymous cross-sectional study of individuals identified at key venues or through peer referral. Approximately 400 respondents in each group (200 for Hijras) responded to a standardized questionnaire and were tested for HIV antibodies at each site. In Karachi, 23% of IDUs and 4% of MSWs were HIV positive, and HIV-positive individuals were identified in all risk groups in at least one city. Two-thirds of all IDUs used a shared needle in the previous week, and unprotected commercial sex activity with men and women was high. The HIV epidemic has entered IDU and male and female commercial sex networks in Karachi and Lahore. Targeted intervention services must be scaled up and risk group surveillance intensified.     

Haemoglobinuria in a 38-year-old French expatriate man living in Cameroon following artemisinin-based antimalarial treatment

Massive haemoglobinuria is encountered rarely during the course of malaria. It is usually considered a diagnostic criterion for severe malaria, together with anaemia, acute renal failure and jaundice. Haemoglobinuria can also present among expatriates travelling to endemic areas following repeated exposure to quinoline or arylaminoalcohol drugs. A case is described of haemoglobinuria developing in a 38-year-old French expatriate diagnosed concurrently with numerous tropical infections, and treated on presumptive basis with an antimalarial regimen containing artemisinin derivatives. Haemoglobinuria resolved spontaneously within a few days. Although this case does not definitely indicate a causal link between haemoglobinuria and artemisinin derivatives, the risk of such infrequent side-effects should be taken into account in pharmacovigilance monitoring. Moreover, the patient illustrates the multifaceted pathology that can be encountered with tropical infections.     

Soman poisoning induces delayed astrogliotic scar and angiogenesis in damaged mouse brain areas

Gliotic scar formation and angiogenesis are two biological events involved in the tissue reparative process generally occurring in the brain after mechanically induced injury, ischemia or cerebral tumor development. For the first time, in this study, neo-vascularization and glial scar formation were investigated in the brain of soman-poisoned mice over a 3-month period after nerve agent exposure (1.2 LD50 of soman). Using anti-claudin-5 and anti-vascular endothelial growth factor (VEGF) immunostaining techniques on brain sections, blood vessels were quantified and VEGF expression was verified to appraise the level of neo-angiogenesis induced in damaged brain areas. Furthermore, glial scar formation and neuropathology were estimated over time in the same injured brain regions by anti-glial fibrillary acidic protein (GFAP) immunohistochemistry and hemalun-phloxin (H&P) dye staining, respectively. VEGF over-expression was noticed on post-soman day 3 in lesioned areas such as the hippocampal CA1 field and amygdala. This was followed by an increase in the quantity of mature blood vessels, 3 months after soman poisoning, in the same brain areas. On the other hand, massive astroglial cell activation was demonstrated on post-soman day 8. Reactive astroglial cells were located only in damaged cerebral regions where H&P-stained eosinophilic neurons were found. For longer experimental times, astroglial response slowly decreased overtime but remained detectable on post-soman day 90 in some discrete brain regions (i.e. CA1 field and amygdala) evidencing the formation of a glial scar. In this study, we discuss the key role of VEGF in the angiogenic process and in the glial or neuronal response induced by soman poisoning.     

Induction of Ucp2 expression in brain phagocytes and neurons following murine toxoplasmosis: an essential role of IFN-gamma and an association with negative energy balance

A model of murine toxoplasmosis was used to study cellular and temporal expression of uncoupling protein-2 (Ucp2) in the brain. In situ hybridization indicated that Ucp2 was located in neurons. Nuclei structures involved in energy balance, in particular the nucleus of the solitary tract (NST), was shown to have a positive association between negative energy balance and Ucp2 levels. Infection-induced Ucp2 expression colocalized mainly with microglial cells, but also with infiltrating macrophages and neutrophils in the brain, which was evident from day 9 post-infection. Using cytokine knockout mice we demonstrate that microglial Ucp2 induction in the brain was largely dependant on interferon-gamma, but not interleukin-6 or tumour-necrosis-factor-alpha in response to infection. In summary, this study shows that Ucp2 is regulated in a different manner in neurons than in microglia/phagocytes following infection. Our study indicates that an association exists between negative energy balance and neuronal Ucp2 levels in the NST, in particular.     

Duane retraction syndrome: MRI features in two cases

PURPOSE: Neuroimaging findings in Duane's retraction syndrome (DRS), through magnetic resonance imaging (MRI), suggest that aplasia of the abducens nerve (VI) can be responsible for several forms of DRS. METHODS: Brain MRI was performed in two children of 2.5 and 7 years of age with left sided DRS type II and right sided DRS type I, respectively. 3D T2 weighted images through the brainstem were acquired in order to visualize the cranial nerves especially the abducens (VI) and oculomotor (III) nerves. RESULTS: The abducens nerve on the affected side could not be observed in these two different types of DRS with normal morphology of the third nerves. CONCLUSION: Absence of the VI nerve has been described recently in DRS types I and III only, while DRS type II is usually associated with normal VI nerve on MRI. However our results show that aplasia of the VI nerve can also be seen in DRS type II resulting in new insight of the pathogenesis of this clinical entity.     

The association of schizophrenia with split personality is not an ubiquitous phenomenon

A widely prevalent stereotype connected with schizophrenia is its misperception as split personality. We examine whether the popular meaning of the term schizophrenia differs in countries of different cultural imprint by conducting an international cross-cultural comparison of public associations with the word schizophrenia in a Western and a Non-Western industrialized country. We analyze data from two representative population surveys in Novosibirsk, Russia (n = 745), and large German cities (n = 952) that used identical questions and sampling procedures. Unprompted associations with schizophrenia are compared by assigning them to a differentiated categorical system. 31.6% of respondents in Germany associated split personality with schizophrenia, compared to 2.0% in Novosibirsk. Logistic regression analysis controlling for age, gender and educational achievement demonstrated that country differences were independent of socio-demographic variables. Mention of split personality increased significantly with higher education. In Novosibirsk, associations with abnormality and unpredictability prevailed. We hypothesize on those cultural particularities in both countries that have shaped the different public understanding of the term and discuss implications for anti-stigma interventions.     

Procognitive and antipsychotic efficacy of glycine transport 1 inhibitors (GlyT1) in acute and neurodevelopmental models of schizophrenia: latent inhibition studies in the rat

Rationale

SSR103800 and SSR504734 are novel glycine transport 1 (GlyT1) inhibitors with therapeutic potential for the treatment of schizophrenia.

Objective

The present studies investigated the effects of GlyT1 inhibitors in acute pharmacological and neurodevelopmental models of schizophrenia using latent inhibition in the rat; these latent inhibition (LI) models are believed to be predictive for treatments of positive, negative, and cognitive aspects of schizophrenia.

Materials and methods

LI, the poorer conditioning to a previously irrelevant stimulus, was measured in a conditioned emotional response procedure in male rats. The effects of SSR103800 or SSR504734 (both at 1, 3, and 10 mg/kg, i.p.) were determined on amphetamine-induced disrupted LI, MK-801-induced abnormally persistent LI, and neurodevelopmentally induced abnormally persistent LI in adult animals that had been neonatally treated with a nitric oxide synthase inhibitor.

Results

SSR103800 (1 and 3 mg/kg) and SSR504734 (1 and 10 mg/kg) potentiated LI under conditions where LI was not present in nontreated controls and SSR103800 (1 mg/kg) reversed amphetamine-induced disrupted LI while not affecting LI on its own. Additionally, SSR103800 (1 and 3 mg/kg) and SSR504734 (3 and 10 mg/kg) reversed abnormally persistent LI induced by MK-801. In the neurodevelopmental model, SSR504734 (3 and 10 mg/kg) reverted the LI back to control (normal) levels.

Conclusions

These preclinical data, from acute and neurodevelopmental models, suggest that GlyT1 inhibition may exhibit activity in the positive, negative, and cognitive symptom domains of schizophrenia.     

Formic acid, a novel metabolite of chronic ethanol abuse, causes neurotoxicity, which is prevented by folic acid

Background: Methanol is endogenously formed in the brain and is present as a congener in most alcoholic beverages. Because ethanol is preferentially metabolized over methanol (MeOH) by alcohol dehydrogenase, it is not surprising that MeOH accumulates in the alcohol‐abusing population. This suggests that the alcohol‐drinking population will have higher levels of MeOH’s neurotoxic metabolite, formic acid (FA). FA elimination is mediated by folic acid. Neurotoxicity is a common result of chronic alcoholism. This study shows for the first time that FA, found in chronic alcoholics, is neurotoxic and this toxicity can be mitigated by folic acid administration. Objective: To determine if FA levels are higher in the alcohol‐drinking population and to assess its neurotoxicity in organotypic hippocampal rat brain slice cultures. Methods: Serum and CSF FA was measured in samples from both ethanol abusing and control patients, who presented to a hospital emergency department. FA’s neurotoxicity and its reversibility by folic acid were assessed using organotypic rat brain hippocampal slice cultures using clinically relevant concentrations. Results: Serum FA levels in the alcoholics (mean ± SE: 0.416 ± 0.093 mmol/l, n = 23) were significantly higher than in controls (mean ± SE: 0.154 ± 0.009 mmol/l, n = 82) (p < 0.0002). FA was not detected in the controls’ CSF (n = 20), whereas it was >0.15 mmol/l in CSF of 3 of the 4 alcoholic cases. Low doses of FA from 1 to 5 mmol/l added for 24, 48 or 72 hours to the rat brain slice cultures caused neuronal death as measured by propidium iodide staining. When folic acid (1 μmol/l) was added with the FA, neuronal death was prevented. Conclusions: Formic acid may be a significant factor in the neurotoxicity of ethanol abuse. This neurotoxicity can be mitigated by folic acid administration at a clinically relevant dose.     

Evaluation of a Solid Bolus Suitable for Esophageal Scintigraphy

This study was designed to select a suitable solid bolus for esophageal scintigraphy. Optimally, a bolus should leave minimal residual buccal and pharyngeal activity after being swallowed. We compared the oropharyngeal behavior of three boluses, i.e., omelette, egg white, and paté of 1- and 3-ml volume. Thirty patients without dysfunction of the upper esophageal sphincter were recruited for the study. Scintigraphy interpretation was based on the results of condensed images and time activity curves. A total of 108 oropharyngeal transits were analyzed. First we determined the most appropriate volume (1 or 3 ml) of paté, omelette, and egg white (i.e., the volume with the least residual oropharyngeal activity). Buccal or pharyngeal bolus retention occurred significantly less frequently with 1 ml paté than 3 ml (p = 0.03) and also less frequently with 3 ml egg white than with 1 ml egg white (p = 0.03), and the mean buccal bolus retention index was lower using 3 ml omelette than 1 ml omelette (p = 0.03). Then we identified the most suitable of the three selected boluses. Both oral and pharyngeal residues were higher for paté (1 ml) than for omelette (p = 0.02 and 0.05), and pharyngeal residue was significantly lower for omelette (3 ml) than for egg white (3 ml) (p = 0.02). In conclusion, a 3-ml bolus of radiolabeled omelette seems to be the most suitable bolus for exploration of esophageal transit, and its use could enhance the potential of scintigraphy in the assessment of esophageal disorders.