Neuroprotective and symptomatological action of memantine relevant for alzheimer’s disease — a unified glutamatergic hypothesis on the mechanism of action

The involvement of glutamate mediated neurotoxicity in the pathogenesis of Alzheimer's disease is finding increasingly more acceptance in the scientific community. Central to this hypothesis is the assumption that in particular glutamate receptors of the N-methyl-D-aspartate (NMDA) type are overactivated in a tonic rather than a phasic manner. Such continuous mild activation leads under chronic conditions to neuronal damage. Moreover, one should consider that impairment of plasticity (learning) may result not only from neuronal damage per se but also from continuous activation of NMDA receptors. To investigate this possibility we tested whether overactivation of NMDA receptors using either non-toxic doses/concentrations of a direct NMDA agonist or through an indirect approach--decrease in magnesium concentration--produces deficits in plasticity. In fact NMDA both in vivo (passive avoidance test) and in vitro (LTP in CA1 region) impaired learning and synaptic plasticity. Under these conditions memantine which is an uncompetitive NMDA receptor antagonist with features of "improved magnesium" (voltage dependence, affinity) attenuated the deficit. The more direct proof that memantine can act as a surrogate for magnesium was obtained in LTP experiments under low magnesium conditions. In this case as well, impaired LTP was restored in the presence of therapeutically relevant concentrations of memantine (1 microM). In vivo, doses leading to similar brain/serum levels produce neuroprotection in animal models relevant for neurodegeneration in Alzheimer's disease such as neurotoxicity produced by inflammation in the NBM or beta-amyloid injection to the hippocampus. Hence, we postulate that if in Alzheimer's disease overactivation of NMDA receptors occurs indeed, memantine would be expected to improve both symptoms (cognition) and slow down disease progression because it takes over the physiological function of magnesium.     

Acute Lymphoblastic Leukemia as a Second Malignant Neoplasm in a Child with Medulloblastoma

Second malignant neoplasm in childhood is increasing due to advances in therapy modalities. Acute lymphoblastic leukemia as a second malignancy following the treatment of medulloblastoma is a very rare condition. A 13-year-old boy was diagnosed as acute lymphoblastic leukemia following radiotherapy and chemotherapy for treatment of medulloblastoma.     

An unexpected complication of acute pancreatitis: Intra-cardiac thrombus

Left atrial thrombus after acute pancreatitis (AP) is a rare clinical statement. Because of induction of systemic prothrombotic process by AP; some patients with underlying risk factors may develop an intra-cardiac thrombus. We present a 53 years-old-woman with moderate mitral stenosis and atrial fibrillation. However the patient was under warfarin treatment, she developed a big left atrial big thrombus which was originated from left atrial appendage after she was suffered from AP.     

Labial Adhesion with Acute Urinary Retention Secondary to Bartholin's Abscess

Labial adhesions are usually seen in early childhood or in the postmenopausal years, but this clinical entity is rarely seen in the reproductive years. We report a case of labial adhesion with acute urinary retention secondary to Bartholin's abscess in a reproductive‐aged woman with normal menstrual periods. We emphasize the possible occurrence of labial adhesion following Bartholin's abscess in the reproductive years with normal estrogen levels.     

Gender differences in randomised,controlled trials in intensive care units

There is a male dominance among patients in intensive care units (ICUs). Potentially, this will increase the risk of a skewed male/female distribution in randomised, controlled trials (RCTs). We have evaluated if this has in fact happened when randomising and whether the authors have been aware of that. We performed a systematic search on PubMed from 1 January 2011 to 31 May 2012 using the mesh terms ‘randomized controlled trial’ and ‘intensive care unit’. Twenty‐five RCTs with a total of 12,788 patients met the inclusion criteria, with an overall male dominance of 63.6% (P < 0.0001). Eighteen of the 25 papers had an individually statistically significant gender difference in their total trial population. None of the 18 trials with a significant gender difference in their overall trial population had calculated the P‐value for this overall difference. In the randomised groups, there was a significant gender difference in five papers. Seventeen had no significant gender difference in the randomised groups, and three papers did not state gender in the randomised groups. This study show that there is a marked male dominance in RCTs conducted in ICUs. We recommend that when planning future RCTs, the authors contemplate if their results can be used indiscriminately among ICU patients if the distribution of males and females is much skewed. It is relevant to determine if ones endpoint can be influenced by gender differences and if there is a risk of gender influence on data, proportional allocation or stratification should be considered.