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Mammary gland development is dependent upon insulin-like growth factors (IGFs) as survival factors. The actions of the IGFs are modulated by a family of IGF-binding proteins (IGFBP1-6). Expression of the IGFBPs is both time-dependent and cell-specific during both the developmental phases and the involution of the mammary gland. Although studied extensively in vitro, understanding the roles of IGFBPs in vivo has been difficult, largely due to the fact that IGFBP knock-out mice have no dramatic phenotypes. This review examines the evidence from in vitro studies and the attempts to examine in vivo actions utilising models with IGFBP deficiency or over-expression. In vitro studies demonstrate that IGFBPs can act by inhibition of the survival effects of IGFs, as well as by enhancing the effects of IGFs. Because the IGFBPs are found associated with the extracellular matrix, a role for IGFBPs as a reservoir of IGFs or, alternatively as a potential barrier to IGFs, thereby restricting their entry into particular tissues or cellular compartments was postulated. We also provide evidence with respect to the IGF-independent actions of the IGFBPs which include receptors, nuclear localization, and interaction with the extracellular matrix and cell surface proteins including integrins. We believe that recent findings place some of the IGFBPs in a larger family of extracellular proteins, the secreted cysteine-rich protein (CCN) family, which have similar structural domains (involved in binding to IGFs, extracellular matrix and integrins) and are heavily implicated in tissue re-modeling and morphogenesis. [ABSTRACT FROM AUTHOR]

Summary: This prospective, open-label study evaluated the efficacy and safety of adjunctive levetiracetam (LEV) in Korean adults with uncontrolled partial epilepsy. Study patients had to have an average of at least 1 and not more than 14 partial seizures per month (averaged over a 3-month historical baseline) despite the use of one or two AEDs. Patients initially received LEV 1000mg/day (administered bid) and could increase to 2000mg/day after 2 weeks, and to 3000mg/day after another 2 weeks, to obtain adequate seizure control. During the 12-week maintenance period, the dose of LEV could be increased or decreased once if seizure control was insufficient or tolerability warranted, respectively. Seizure count and adverse events (AEs) were recorded by patients. Global evaluation scale (GES) and quality of life (QOLIE-31) were also evaluated. A total of 100 patients were enrolled and 92 patients completed the study. The median percent reduction in weekly seizure frequency over the treatment period was 43.2%. The ≥50% and ≥75% responder rates were 45.4% and 36.1%, respectively. Seizure freedom throughout the 16-week treatment period was observed in 17 patients. On investigator''s GES, 81 patients were considered improved, with 41 patients showing marked improvement. Most QOLIE-31 scales improved significantly. Treatment-emergent AEs were reported in 59 patients. Three most common AEs were somnolence (36%), dizziness (12%), and headache (8%). Adjunctive LEV therapy was effective and well-tolerated in Korean adults with refractory partial epilepsy. [Copyright &y& Elsevier]

The article explores the philosophical convergence between Sigmund Freud, founder of psychoanalysis, and Jeremy Bentham, founder of utilitarianism in the concept of panopticism and super-ego. Both thinkers believed that man was driven by two fundamental forces. The article states that the structure and function of the super-ego is reflected by the structure and function of the Panopticon, and it is founded upon Freud's and Bentham's views of the nature of humanity.

PURPOSE OF REVIEW: Propofol infusion syndrome is a rare but often fatal syndrome, characterized by lactacidosis, lipaemic plasma and cardiac failure, associated with propofol infusion over prolonged periods of time. As propofol is used worldwide, knowledge of propofol infusion syndrome is essential for all anaesthesiologists and intensive care physicians. This review will provide an update on reported cases, and describe recent findings relevant to the pathophysiology and clinical presentation of propofol infusion syndrome. RECENT FINDINGS: Case reports of propofol infusion syndrome have contributed new pathophysiological evidence. Reported cases of similar syndromes may represent initial propofol infusion syndrome, and may help to identify further risk factors such as low carbohydrate supply and early warning signs such as lactacidosis. Newly identified gene defects mimicking propofol infusion syndrome may elicit the underlying genetic susceptibility. Recommendations for the limitation of propofol use have been devised by various institutions. SUMMARY: Propofol infusion syndrome must be kept in mind as a rare but highly lethal complication of propofol use, not necessarily confined to the prolonged use of propofol. Dose limitations must be adhered to, and early warning signs such as lactacidosis should lead to the immediate cessation of propofol infusion. [ABSTRACT FROM AUTHOR]

Due to increasing life expectancy and a rising elderly population in Europe, the incidence of mild cognitive impairment which may predict diseases like Alzheimer''s Disease or Vascular Dementia, is rising. Neurophysiological techniques are simple and inexpensive tools for early diagnosis and provide useful and objective correlates of cognitive activity both in normal subjects and patients suffering from the above conditions. Cognitive impairment due to different mental disease is characterized by decreased power and coherence in the alpha/beta band, which suggests functional disconnection among cortical areas, whereas both power and coherence in the delta and theta bands increase as a sign of cortical deafferentation from subcortical structures. Quantification of power and phase relationship by bispectral analysis suggests the Bispectral Index could be a useful but simple tool for early diagnosis of mental disease. [Copyright &y& Elsevier]

Sedation and analgesia are important components of care for critically ill patients. Avoiding over- as well as undersedation is of utmost importance as both states carry considerable risks and may influence outcome. The management of sedation has changed dramatically over the past two decades from providing a dosage level by which the patient was kept in a deep stage of anaesthesia to a current dosing strategy allowing the administration of drugs in line with individual need, resulting in most cases in a slightly sedated, cooperative patient. The importance of monitoring the level of sedation and analgesia has only recently been realised. Most importantly, regularly determining the appropriate level of sedation and analgesia as well as monitoring the desired level of sedation will help to minimise the adverse effects of sedation. Clinical sedation scales are, however, subjective, and most lack proper validation. Thus, an objective measure of sedation, such as the use of processed electroencephalogram (EEG) parameters is desirable. Processed EEG algorithms such as the bispectral index were initially introduced into clinical practice as a tool to assess the depth of anaesthesia objectively in the operating room. However, patients under general anaesthesia differ from those in an intensive care unit. Accordingly, most results from studies evaluating the performance of processed EEG parameters in critically ill patients have not been satisfactory. At present, monitoring sedation with processed EEG parameters cannot generally be recommended. However, in special situations such as deep sedation and neuromuscular blockade, in which clinical sedation scales are prone to failure, the bispectral index may help to assess the level of sedation. [Copyright &y& Elsevier]

Even today many anaesthesiologists rely on parameters of the autonomic nervous system, such as blood pressure and heart rate to decide if a patient is adequately anaesthetized. It is thought that the electroencephalogram (EEG) may provide more information on the state of anaesthesia. Because full EEG analysis is not possible in the operating room, processed EEG parameters have been developed comprising complex information into a single value. Time and frequency domain parameters are calculated. The power spectrum results from a Fourier analysis and can be described by parameters such as median frequency, spectral edge frequency and others. It was noted, however, that anaesthetics at low doses increase frequency of the EEG, whereas at high doses the EEG is depressed. This biphasic response makes it difficult to clearly distinguish the exact anaesthetic state of a patient. Median frequency and spectral edge frequency have been studied in numerous studies. However, no sole indicator has been derived from the EEG that could serve as a descriptor of anaesthetic depth. [Copyright &y& Elsevier]

An ‘ideal’ anaesthetic can be approached by using a combination of different compounds. A variety of anaesthetic techniques has been described to ensure safe administration and an early recovery with high patient satisfaction. In particular, the inhalational anaesthetics desflurane and sevoflurane, with their rapid pharmacokinetics, re-established the notion of balanced anaesthesia as an equivalent, well-controllable technique. With the choice of anaesthetics and anaesthetic adjuvants clinically available today, especially the combination of a volatile anaesthetic with a short-acting opioid, balanced anaesthesia represents a big step towards an ideal anaesthetic. [Copyright &y& Elsevier]

PURPOSE OF REVIEW: The development of dexmedetomidine, a potent and highly selective a2-adrenoceptor agonist, has created new interest in the use of a2-adrenoceptor agonists, and has led to its evaluation in various yet non-approved perioperative settings. The current review focuses on the usefulness of dexmedetomidine in anaesthesia practice. RECENT FINDINGS: Recently acquired knowledge and experience with dexmedetomidine in perioperative use will be presented and discussed in the context of known pharmacological properties. SUMMARY: Dexmedetomidine offers beneficial pharmacological properties, providing dose-dependent sedation, analgesia, sympatholysis and anxiolysis without relevant respiratory depression. The side-effects are predictable from the pharmacological profile of (2-adrenoceptor agonists. In particular, the unique sedative properties of dexmedetomidine resulted in several interesting applications in anaesthesia practice, promising benefits in the perioperative use of this compound. However, dexmedetomidine was approved for sedation in the intensive care unit in the USA in 1999, and administration in anaesthesia practice remains an off-label use. Further studies are needed to establish the role of dexmedetomidine in the perioperative period. [ABSTRACT FROM AUTHOR]

PURPOSE OF REVIEW Sedation and analgesia are important means of providing care for the critically ill patient.RECENT FINDINGS It is now clear that posttraumatic stress disorders resulting from an intensive care unit stay may be prevented by the right level of sedation. New drug developments but also recent findings in new ventilation strategies allow for a sedation management that is better tailored to an individual's need. Most importantly, regular definition of the appropriate level of sedation and analgesia as well as monitoring of the desired level will help to avoid over- and undersedation and may ultimately improve the outcome of the patient and reduce costs.SUMMARY Sedation and analgesia are now regarded as an integral part of treatment on the intensive care unit instead of being an unpleasant but necessary and minor issue. The importance of monitoring the level of sedation and analgesia has only recently been realized. It remains to be shown that new management strategies including an evaluation of the patient, planned interventions and the choice of drugs will further improve the care for the critically ill. [ABSTRACT FROM AUTHOR]