D., for his review and comments on the manuscript. The authors also thank Vikhyat Bebarta, M.D., for his insight into the issue of the quality of published case reports. Dr. Heard was supported by DA020573 from the National Institute on Drug Abuse. The funding agency had no role in the design, performance, manuscript preparation or decision Inhibitors,research,lifescience,medical to publish this information.
Intubation of

the trachea by paramedics in the pre-hospital setting may be lifesaving in severely ill and injured patients [1-3]. However, tracheal intubation is often difficult to perform in this setting, is associated with a lower success rate. Failed tracheal intubation in this setting constitutes an important cause of morbidity, arising from direct airway trauma and the systemic complications of hypoxia [4,5]. In Ireland, Advanced Paramedics (AP’s) Inhibitors,research,lifescience,medical are a subgroup of Emergency Medicine Technicians that are trained and certified as being competent in the skill of direct laryngoscopy and tracheal intubation. The recent development of a number of indirect laryngoscopes, which do not require alignment of the oral-pharyngeal-tracheal axes, may reduce

the difficult of tracheal intubation in the prehospital setting. Two portable indirect laryngoscopes, Inhibitors,research,lifescience,medical which could be included in ambulance equipment inventories, are the Glidescope® (Saturn Biomedical System Inc., Burnaby, Canada) (Figure ​(Figure1)1) and the AWS® (Hoya Corporation, Tokyo, Japan) (Figure ​(Figure2)2) laryngoscopes. Clinical studies have demonstrated advantages over the Macintosh laryngoscope for both the Glidescope® [6-9], and the AWS® [8,10] laryngoscopes. However, the efficacy of the Glidescope® and the AWS® when used by APs is not

known, and Inhibitors,research,lifescience,medical the relative efficacies Inhibitors,research,lifescience,medical of these devices in comparison to the Macintosh laryngoscope have not been compared in a single study. Figure 1 Photograph of the Glidescope laryngoscope. The device is held in the left hand and passed into the mouth over the tongue, and the tip Selleck AZD8931 placed in the vallecula or under the epiglottis. Figure 2 Photograph of the AWS® laryngoscope. The device is held in the left hand and Adenylyl cyclase passed into the mouth over the tongue, and the tip is placed under the epiglottis. We therefore wished to compare these two novel devices to the Macintosh laryngoscope when used by APs with demonstrated competence in the skill of tracheal intubation using the Macintosh laryngoscope. Methods Following ethical committee approval, and written informed consent, 25 Advanced Paramedics certified as competent to perform tracheal intubation consented to participate in this study. These participants constituted a convenience sample of AP’s that attended a Resuscitation Conference on the 11th June 2008 in Galway, Ireland, and represents more than 20% of all paramedics in Ireland. Each AP received a standardized training session with the Glidescope®, the AWS® and the Macintosh laryngoscopes.

157 The fourth, using a multistage design of discovery (479 cases, 2937 controls) and targeted replication (6666 cases, 9897 controls) samples, identified one genome-wide significant

SNP in the zinc-finger protein transcription factor ZNF804A gene,158 but only in the meta-analysis including the original sample. One independent replication attempt supported the association of ZNF804A, and showed that expression was increased from the associated haplotype.159 Three substantially larger GWAS of schizophrenia were published in 2009, in the SGENE+ sample160 (multiple European sites, 2663 cases/13498 controls), the International Schizophrenia Consortium (ISC) sample161 (multiple Inhibitors,research,lifescience,medical European sites, 3322 cases/3587 controls) and the Molecular Genetics of Schizophrenia (MGS) sample162 (multiple US sites, Inhibitors,research,lifescience,medical European ancestry: 2681 cases/2653 controls; African ancestry: 1286 cases/973 controls), analyzed both separately and together. The one region of the genome with www.selleckchem.com/products/gsk2656157.html significant overlap in signals from the 3 studies was the MHC region on chromosome 6p21.3-p22.1, site of some of the earliest genetic

evidence in schizophrenia discussed above. Inhibitors,research,lifescience,medical The SGENE+ sample detected significant association with several markers spanning the MHC region, as well as signals upstream of the neurogranin (NRGN) gene on 11q24.2 and in intron four of the transcription factor 4 (TCF4) gene on 18q21.2. The ISC sample detected association in ~450 SNPs spanning the MHC region and the myosin XVIIIB (MY018B) gene on 22q and supported ZNF804A. The MGS Inhibitors,research,lifescience,medical sample did not detect any individual genome-wide significant signals, but detected signals in the range of 10-5-10-7 in the CENTG2 gene (reported deleted in autism cases163) on chromosome 2q37.2 and JARID2 (the gene adjacent to DTNBP1) in Europeanancestry subjects, and in ERBB4 and NRG1 Inhibitors,research,lifescience,medical in AfricanAmerican subjects. Meta-analysis of data from all European-ancestry MGS, ISC and

SGENE samples detected genome-wide significant association signals for 7 SNPs spanning 209 Kb of the MHC region. LD is high between the 7 SNPs and extends over a region of 1.5 Mb on chromosome 6p22.1, making it difficult to determine if the signal is driven by one or many genes. The genic content of this region is not limited to histocompatibility loci, and also includes genes involved in transcriptional regulation, DNA repair, chromatin structure, G-protein-coupled-receptor signaling Adenylyl cyclase and the nuclear pore complex. Meta-analyses of schizophrenia linkage and association data The strongest linkage meta-analysis approach ranks 30 cM bins of the genome from most positive to least positive for each study, and then sums the ranks for each bin. Significance levels are calculated by simulation, and this method can identify regions of the genome where modest positive results occur across many studies.

In contrast to crosslinking in the core or periphery of the micelle, Intezyne has developed pH-reversible crosslinking technology in the middle block of the triblock copolymer. Crosslinking of this middle layer of the micelle is advantageous since it does not click here interfere with the core region, which is where the drug resides. The chemistry utilized to crosslink the polymer chains together,

and thus stabilizes the micelle, is based on metal acetate chemistry (Figure 2). It is well known that a number of metal ions can interact with carboxylic acids to form metal-acetate bonds [26]. Inhibitors,research,lifescience,medical It is also understood that these ligation events form rapidly when the carboxylic acid is in the carboxylate form (e.g., high pH, pH ~ 7-8) yet only weakly interact when the carboxylic acids are fully protonated (e.g., low pH, pH 4-5), therefore Inhibitors,research,lifescience,medical allowing release of the drug in low-pH environments, such as regions surrounding the tumor, and the endosomes of tumor cells following endocytosis of micelles. The poly(ethylene glycol) block (Figure 1, shown in gray) allows for water solubility and provides “stealth” properties to the micelle in order to avoid protein opsonization and the reticuloendothelial system [2]. Figure 1 The IVECT polymer micelle. Drugs are loaded into the core hydrophobic block (yellow). The crosslinking

Inhibitors,research,lifescience,medical block (green) provides stability to the Inhibitors,research,lifescience,medical micelle by forming pH-reversible metal-acetate bonds that allow for triggered drug release near the tumor. The … Figure 2 Metal-acetate crosslinking chemistry for stabilization of polymer micelles. While the drug is localized in the core block, the poly(aspartic acid) block of the middle block reacts with metals to form metal acetate bonds. Bonds are Inhibitors,research,lifescience,medical formed at high pH and … As an initial study, the triblock copolymer was used to encapsulate several different small molecule drugs with varying hydrophobicities. A trend was discovered such that the ability of the triblock to encapsulate a drug was dependent on the drug’s

LogP value. Effective encapsulation was achieved with molecules having a Log P > 1.4 (Figure 3). The weight loadings of the formulations ranged between 1 and 20%. Molecules that were encapsulated were subsequently crosslinked by the addition of iron chloride. The addition of iron chloride to the micelle did not affect the drug and oxyclozanide did not result in generation of polymer-drug conjugates. To test stability of the crosslinked micelle, the in vitro stability of the micelle below the CMC was determined using a dialysis assay. In contrast to the encapsulation retention, there was no clear correlation between the LogP value and crosslinking retention (Table 1). The particle sizes of crosslinked micelles, as determined by dynamic light scattering, also did not seem related to the LogP value.

The primary difference between genome-wide linkage studies and genome-wide association studies (GWASs) is that with linkage the investigator is looking for cotransmission of a specific DNA marker within a family, while in a genome -wide association study the investigator is looking for a population association between a DNA marker and disease. Linkage studies are better Inhibitors,research,lifescience,medical suited to identifying genes that have large effects, and GWASs are better

when attempting to identify genes that have relatively small effects on the phenotype. These GWASs should examine both common markers as well a copy number variants and other rare genetic events. It is becoming evidence that complex disorders may be “caused” by both rare genes of major effect and a combination of common genes Inhibitors,research,lifescience,medical of lesser effect. Given the limited state of knowledge about the Selleckchem CP-868596 pathophysiological pathways important for the manifestation of OCD, it is premature at this time to restrict focus on the association of specific candidate genes with OCD. Instead, a GWAS with a sample of sufficient size is the most promising approach for the identification of genomic regions that most likely harbor OCD risk Inhibitors,research,lifescience,medical genes. Once these regions have been identified, then

more informed candidate gene studies could be undertaken. Given the variability of recurrence risks and the results from the most recent twin study, it is clear that, like other neuropsychiatric conditions, Inhibitors,research,lifescience,medical OCD is etiologically heterogeneous. Given this high likelihood

of etiologic heterogeneity, it is critical to study a sufficiently large sample of affected individuals so that homogeneous clinical subgroups more likely to be etiologically homogenous can be identified from within the larger sample.140-141 In order to obtain these large samples, it Inhibitors,research,lifescience,medical is imperative that investigators interested in the genetics of OCD collaborate. A collaboration of this type (the International OCD Foundation Genetics Collaborative) is currently conducting a GWAS of OCD on samples contributed from 21 different research sites from around the world. Acknowledgments The work was supported in part by NIH grants NS016648, NS-040024, and MH079489.
Our knowledge of psychiatric Sodium butyrate and substance-use genetics comes from two key fields of research, both dynamic areas in rapid change. First, genetic epidemiology asks whether there is risk in excess of the population baseline in the relatives of cases, and, if so, whether the excess risk is attributable to the genetic factors or the environments they share. Beyond simply estimating heritability, genetic epidemiology has evolved to address more sophisticated questions, such as whether liability genes have the same effects across the lifespan, how they may influence multiple disorders, and how they might interact with environmental risks.

Conventional 2DE, being confined to several predefined views, actually shows only a very limited part of the whole LV myocardium (Fig. 11). Conversely, 3DE can display

the entire myocardial volume in a multi-slice panel, allowing a comprehensive assessment of the whole LV circumference (Fig. 6). This display modality can improve the accuracy of visual regional wall motion assessment, because even limited wall motion abnormalities, localized in regions that are not apparent in conventional 2D views, Inhibitors,research,lifescience,medical can be visualized. Furthermore, with 3DE, a quantitative www.selleckchem.com/products/SB-202190.html analysis of LV regional functional is possible by comparing regional volume variation of each pyramidal-shaped LV segment during the cardiac cycle (Fig. Inhibitors,research,lifescience,medical 8). A good correlation of quantitative 3DE analysis with 2DE regional wall motion score10) and CMR32) has been reported. Fig. 11 Schematic representation of the position of 3 apical views of left ventricle obtainable with conventional 2D echocardiography. As shown, the 3 longitudinal slices cover only a very limited part of left ventricular circumference and cannot be changed anymore … Very recently 3D speckle-tracking technology has been validated for regional wall motion analysis,33) providing an Inhibitors,research,lifescience,medical additional quantitative tool to objectively assess segmental myocardial

deformation. A more accurate evaluation of regional wall motion improves the diagnostic accuracy of pharmacological stress echocardiography in ischemic heart disease.34),35) Inhibitors,research,lifescience,medical In addition, since the recovery of wall motion abnormalities has been shown to occur fast in patients with limited coronary disease, the rapid acquisition of peak stress images is of paramount importance to detect single-vessel disease.

Latest generation 3DE scanners allow a rapid image acquisition during peak stress, which may decrease the potential risk of missing transitory ischemia.35) Using 3DE, the operator is able to acquire all views from a single transducer location, significantly shortening the acquisition time. The views obtained by automatically slicing the 3D data sets acquired Inhibitors,research,lifescience,medical at different steps of the stress echocardiographic protocol can be re-aligned at any moment after acquisition and automatically displayed side-by-side to allow an easier detection of new wall motion abnormalities or of changes in wall motion abnormalities detected at baseline. Casein kinase 1 Aggeli et al.34) and Badano et al.35) have reported an increased sensitivity of 3D stress echo to detect inducible ischemia in the territory of left anterior descendent coronary artery. 3DE is emerging as a promising tool to assess intraventricular mechanical dyssynchrony, to improve the selection of patients with heart failure who will benefit from biventricular pacing and to monitor post-implant LV remodeling.36),37) A systolic dyssynchrony index is calculated as the standard deviation of the time to minimum systolic volume of each LV segment (Fig. 8).

2. Materials and Methods 2.1. Materials Olmesartan medoxomil was received as a gift sample from Alembic Pharma Ltd., Baroda, India. The following materials were gifted by Abitec Corp., USA and were used as received: Capmul MCM (Glyceryl monocaprylate), Acconon C-80 (Polyoxyethylene 80 coconut glycerides), Captex 200 (Propylene glycol dicaprylocaprate),

and Captex 355 (Glyceryl tricaprylate). Plurol Oleique (Polyglyceryl-3 Inhibitors,research,lifescience,medical dioleate), Labrafil M 2125CS (Linoleyl macrogol-6 glycerides), and Lauroglycol 90 (Propylene glycol monolaurate) were received as gift sample from Gattefosse, France. Acrysol K 140 (Polyoxyl 40 hydrogenated castor oil) and Acrysol EL 135 (Polyoxyl 35 castor oil) were procured as a gift Inhibitors,research,lifescience,medical samples from Corel Pharma Chem., Ahmedabad, India. Fujicalin (Dibasic calcium phosphate anhydrous) and Neusilin (Magnesium aluminometasilicate) were obtained as gift sample from Fuji Chemical Industry Co. Ltd., Japan. 2.2. Solubility Studies Solubility of olmesartan medoxomil was determined Inhibitors,research,lifescience,medical in various nonvolatile solvents. Two mL of each component was taken in screw cap vials with known quantity (200mg) of excess drug. After sealing, vials were kept on isothermal mechanical shaker at 37 ± 2°C for 72 hours. After equilibrium, each test tube

was centrifuged at 6000rpm for 20 minutes. Supernatant was filtered through membrane filter using 0.45μm filter Inhibitors,research,lifescience,medical disk. Filtered solution was appropriately diluted with methanol, and UV absorbances were measured at 257nm wavelength. Concentration of dissolved drug was determined using standard equation. 2.3. Measuring Angle of Slide This experiment was designed to measure the flowable liquid retention potential (-value)

for Avicel PH 102, Fujicalin and Neusilin (carrier Inhibitors,research,lifescience,medical material, Ca), and Aerosil (coating material, Co) and the optimum liquid load factor (Lf). The -value of a powder is the maximum amount of given nonvolatile liquid that can be retained inside powder bulk (w/w) while maintaining acceptable flowability, whereas Lf is the mass ratio (w/w) of the liquid medication to the carrier powder in the liquisolid formulation. Powder admixtures containing 5g of either carrier or coating with increasing quantity of nonvolatile liquid vehicle (Acrysol EL 135) were mixed Ketanserin using a mortar and pestle. Each admixture was then placed on a shiny metal plate; the plate was then tilted until the admixture slides. The angle formed between the plate and the PF-01367338 chemical structure horizontal surface, at which admixture slides were measured as angle of slide (θ). The flowable liquid retention potential was calculated using the following equation: φ-Value=Weight  of  nonvolatile  liquidWeight  of  carrier  or  coat. (1) Each admixture has specific -values which were determined and plotted against respective measured angle of slide for all nonvolatile liquid vehicles.

The median duration of hospital stay in this study was found to be longer than that reported by other authors [3,9]. This can be explained by large number of patients with postoperative complications which usually need long duration of hospitalization. The present study had a mortality rate of 11.2%, which is higher than the rate quoted by Manilal Inhibitors,research,lifescience,medical et al. [9]. Factors responsible for the high mortality rate in our study were associated co-morbidities, delayed presentation and presence of complications. In our study, the cut throat injuries were successfully without complications in 89.7% of cases which is similar to other studies reported elsewhere [9,11]. Self discharge by

patient against medical advice is recognized problem in our setting and this is rampant, especially Inhibitors,research,lifescience,medical amongst surgical patients. Similarly, poor follow up visits

after discharge from hospitals remain a cause for concern. In the present study, only 36.8% of survivors were available for follow up which is in keeping with other studies done in developing countries [3,9,11]. The potential limitation of this study is the fact that information about some patients was incomplete in view of the retrospective nature of the study. This might have introduced some bias in our buy BIBR 1532 findings. Conclusions Cut throat injuries have become a major cause of morbidity and mortality among young Inhibitors,research,lifescience,medical males in our society where resources for prehospital and hospital trauma care Inhibitors,research,lifescience,medical are limited. High rates of unemployment, poor socio-economic status, poor education, poverty and substance abuse have been reported to be responsible for these injuries in our society. Addressing the root causes of violence such as poverty, unemployment, Inhibitors,research,lifescience,medical and substance abuse will reduce the incidence of cut throat injuries in our environment. Establishment of efficient emergency health

care services for pre-hospital care and effective ambulance system for rapid transport of injured victims to hospital will reduce morbidity and mortality associated with these injuries. Competing interests The authors declare that they have no competing interests. Authors’ contributions JMG conceived the study, participated in the design and coordination of the study and drafted the manuscript. KAH and PLC of contributed in study design, literature search, data analysis, manuscript writing and editing. In addition PLC submitted the manuscript. All the authors read and approved the final manuscript. Pre-publication history The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-227X/14/1/prepub Acknowledgements We are grateful to the Senior House Officers in the department of Surgery for their support in data collection. We also like to thank all members of staff in Medical Record department for their cordial help and support in data collection during this study.

In an attempt to overcome these flaws, Frank et al2 proposed a set of definitions which they referred to as longitudinal studies of mood disorders, but, may entail more general applicability in psychiatry. Remission (which is differentiated into partial and full remission) is a relatively brief period during which an improvement, of sufficient magnitude is OSI906 observed and the individual no longer meets syndromal criteria for the disorder. Recovery implies a more

sustained remission, and raises the possibility that treatment can be discontinued or prolonged with the aim of prevention. Relapse is a return Inhibitors,research,lifescience,medical of symptoms satisfying the full syndromal criteria during the period of remission, whereas recurrence can occur only during a recovery. The development of these criteria provides helpful ground for decreasing inconsistencies among research reports, yet, it does not, touch some key issues in the conceptualization of these terms. First, according

to these definitions,2 recovery occurs Inhibitors,research,lifescience,medical when the number and severity of symptoms fall below the threshold used for defining onset, and this Inhibitors,research,lifescience,medical subthreshold level of symptomatology remains for a specified period of time. However, this state cannot be equated with being asymptomatic, and provides room for a wide range of subclinical conditions. Second, the definition of remission parallels the traditional medical concept, of convalescence, a transitional period of reintegration after illness.

The trajectory of such a process is thus an important additional dimension Inhibitors,research,lifescience,medical which requires a longitudinal consideration of the development of disorders, encompassing the prodromal phase, the fully developed disorder, and residual states. Not only the duration of the acute phase of illness -as is widely acknowledged- may affect, the rate of recovery, but also the characteristics of prodromes, the Inhibitors,research,lifescience,medical amount, of residual symptomatology not alleviated by specific treatments, and the level of premorbid functioning may influence the course of recovery.3,4 Finally, either the distinction between recovery and full remission is made on temporal grounds only. They are not, differentiated by whether active treatment, is associated, even though recovery implies the possibility that therapy can be discontinued. A recovered depressed patient who is currently drug-free is thus equated to another patient, who is receiving long-term, high-dose antidepressant, treatment. The aim of this review is to analyze some issues which would help to define the psychosocial determinants of recovery in depression. The inadequacies of standard clinical assessment The staging method, whereby a disorder is characterized according to seriousness, extent, and features, has achieved wide currency in medicine, but, is currently neglected in psychiatry.

There is no doubt that the problem of scientific misconduct and breach of publishing ethics is common at present, and possible explanations might be the author’s failure to peruse the ethical standards stated in instructions to authors and the author’s failure to comply with such guidelines. More research is required to shed further light on the reasons for violations of publication ethics. Conflict of Interest:

None declared.
Stroke is an important medical problem that requires good management. In medicine, stroke is the most common cause of disability around the world. The recent report on infective stroke is Inhibitors,research,lifescience,medical very interesting.1 Moghtaderi and Alavi-Naini1 pointed out many interesting issues and mentioned a large Selleckchem SCH727965 number of tropical infections that can cause infective stroke. According to this report, malaria, tuberculosis, cysticercosis, syphilis, Inhibitors,research,lifescience,medical and Chagas disease are important examples of infective stroke.1 In fact, several kinds of tropical infections (i.e. parasitic, bacterial, viral, or fungal infections) can lead to stroke. Moghtaderi and Alavi-Naini

also noted that “Lack of human as well as financial Inhibitors,research,lifescience,medical resources makes it difficult to control and treat the disease properly.”1 Indeed, the epidemiology of stroke in tropical countries is interesting. Gomes and Chalela et al.2 noted that “Cerebrovascular disease is a leading cause of morbidity and mortality in tropical countries.” The authors also added to classical etiologies by mentioning “unusual causative mechanisms”. Tropical Inhibitors,research,lifescience,medical infections comprise an important group that merits due consideration. It has been noted that tropical infections accumulate “up to 10% of the cases of strokes in adults” in tropical countries.3 The predominant tropical infections that can lead to tropical stroke might be different

in different settings. For example, Chagas disease is predominant in South America, whereas gnathostomiasis is predominant in Southeast Asia.3 However, Inhibitors,research,lifescience,medical some tropical infections that can cause stroke such as malaria and cysticercosis can be seen in many tropical as well as non-tropical areas.3 Oxalosuccinic acid Of interest, the clinical problems are sometimes underdiagnosed. For sure, this leads to the high mortality among the patients with specific tropical strokes.3 As evidence, del Brutto et al.4 mentioned that “The severity of the neurological picture makes it impossible to identify an specific stroke syndrome and cerebrovascular complications are only recognized on neuroimaging studies or autopsy.” This fact calls for medical attention to the forgotten problem of tropical stroke. Of interest, the problem of cryptogenic stroke still exists and incomplete investigation has been cited as the most important cause of it.5 There is no doubt that those cryptogenic cases can have the exact underlying etiologies as tropical infections.

In case 2 valproic acid was not able to stop rapid recurrences due to lithium discontinuation. The rapid cycling was stopped with the addition of memantine. In case 3 the patient had a rapid cycling bipolar II disorder treated with lithium and lamotrigine with poor response. She had to discontinue both drugs because of adverse

reactions. The rapid cycling course was stopped with memantine and a small dose of valproic acid. Moreover, we previously observed that the drug might be effective Inhibitors,research,lifescience,medical also as monotherapy in the prevention of affective recurrences occurring after lithium discontinuation [Serra et al. 2013]. Although we observed a good response to memantine administration 4 months after lithium discontinuation (case 2), the mood-stabilizing effect of memantine seems to be more effective (as a monotherapy [Serra et al. 2013]) when it is administered before lithium discontinuation Inhibitors,research,lifescience,medical (case 3: 9 months before). In case 1 memantine was added immediately after lithium discontinuation and the stabilization of the rapid cycling bipolar course was

obtained with the reinstatement of a subtherapeutic dose of lithium (serum level 0.2 mmol/L). Although Inhibitors,research,lifescience,medical memantine is used in learn more combination with another mood stabilizer, it does not diminish the clinical relevance of our observations. In our patients lithium discontinuation led to a malignant course that did not respond to valproic acid as monotherapy. We observed a potent mood-stabilizing action of the combination of memantine with lamotrigine or valproic acid, drugs that usually are not able to stop the rapid Inhibitors,research,lifescience,medical cycling course when used as monotherapy [Kemp et al. 2012]. Moreover, even lithium, before its discontinuation and the addition of memantine, was administered in combination with another mood stabilizer,

because of the severity of the bipolar disorder course. These case histories are consistent with our previous observations suggesting that memantine has a long-lasting Inhibitors,research,lifescience,medical mood-stabilizing effect. As to the mechanism of action, we have observed that memantine prevents the bipolar-like behaviour induced by antidepressants in rats [Demontis et al. 2012], and suggested that the prevention of dopamine antagonist receptor sensitization (mania) by memantine results in an antimanic effect, which, in turn, prevents the following desensitization associated TCL with depression [Serra, 2010]. Regardless of the mechanism of action, these case reports confirm our previous observations, and suggest that memantine may be considered a useful replacement for lithium in the prevention of affective recurrences observed in patients who have to discontinue long-term lithium prophylaxis because of severe medical complications. Acknowledgments The authors would like to thank Denis Greenan for his valuable contribution to the drafting of the paper.