Olanzapine compared to lithium in mania: a double-blind randomized controlled trial

Neuroleptics are of established efficacy in mania. Controlled data on the use of olanzapine in mania is however, absent. In this study, 30 patients meeting DSM-IV criteria for mania were randomly allocated to receive either olanzapine or lithium in a 4 week double-blind randomized controlled design. There were no significant outcome differences between the two groups on any of the primary outcome measures, the Brief Psychiatric Rating Scale (lithium 28.2; olanzapine 28.0; P = 0.44); Clinical Global Impression (CGI) improvement scale (lithium 2.75, olanzapine 2.36; P = 0.163) or the Mania Scale (lithium 13.2, olanzapine 10.2; P = 0.315). Olanzapine was however, significantly superior to lithium on the CGI-severity scale at week 4 (lithium 2.83, olanzapine 2.29; P = 0.025). Olanzapine did not differ from lithium in terms of treatment emergent extrapyramidal side-effects as measured by the Simpson-Angus Scale. Olanzapine appears to be at least as effective as lithium in the treatment of mania.     

The King is Dead, Long Live the King: Entering A New Era of Stem Cell Research and Clinical Development

With the approval of the first therapeutic cancer vaccines for veterinarian and human use, the field reached a significant milestone after a considerable interval of tumultuous research and development marked by numerous ups and downs. As the mechanism of action and clinical benefit afforded by this class of agents are starkly different from that of conventional or small targeted therapies for cancer, there are still numerous hurdles that need to be overcome to fully unleash their potential. These challenges and efforts are illustrated in a book just published on this subject, a non-exhaustive yet representative synopsis of the latest advances in cancer vaccine technologies in various stages of development. Major lessons resulting from clinical testing of cancer vaccines and other immune interventions, are being integrated in novel, cutting edge platform technologies that blur the distinction between passive and active immunotherapies as well as carry the promise of fundamentally changing and improving the management of patients with cancer.     

Measuring Intraoral Pressure: Adaptation of a Dental Appliance Allows Measurement During Function

This article introduces a new way of recording intraoral pressures from a range of locations within the oral cavity. To measure pressure flow dynamics during swallowing, we fitted eight miniature pressure transducers capable of measuring absolute pressures to a chrome-cobalt palatal appliance with a labial bow. Unlike previous devices, our design provides a rigid, custom-fitted platform for the simultaneous recording of pressures at eight locations within the oral cavity during function. We placed an anterior pair of gauges to measure lingual and labial contact against the left central incisor tooth, and two pairs of gauges to measure pressure contributions of the lateral tongue margin and cheeks on the canine and first molar teeth. Finally, lingual pressure on the midline of the palate was measured by two gauges, one at the position of the premolars and one on the posterior boundary of the hard palate. We then recorded intraoral pressures in five adult volunteers seated in an upright position and asked to swallow 10 ml of water. Labial pressures on the canine rose rapidly from a resting level of 10 kPa to 33 kPa, while pressure profiles from the labial aspects of the incisor and first molar teeth followed a negative pattern, peaking at -12 kPa for the incisor and -15 kPa for the molar sensor. Pressure profiles recorded from the palatal aspects of the first molar and the canine appeared to be similar, but the former fell to -13 kPa before rising to 9 kPa, and the canine pressure rapidly increased to 22 kPa before returning to its resting level of 4 kPa. The pressure profile of the palatal aspect of the central incisor was strikingly different; at the start of the swallow, pressure dropped precipitously to -20 kPa, before slowly rising to 10 kPa. It then followed the general pattern of the other two sensors, before peaking again at 10 kPa and then returning to a resting level of 4 kPa. We also showed that there were significant negative pressures in the mouth during function, and that pressure profiles varied markedly between individuals.     

Chemical resistance of the gram-negative bacteria to different sanitizers in a water purification system

Background  

Purified water for pharmaceutical purposes must be free of microbial contamination and pyrogens. Even with the additional sanitary and disinfecting treatments applied to the system (sequential operational stages), Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas alcaligenes, Pseudomonas picketti, Flavobacterium aureum, Acinetobacter lowffi and Pseudomonas diminuta were isolated and identified from a thirteen-stage purification system. To evaluate the efficacy of the chemical agents used in the disinfecting process along with those used to adjust chemical characteristics of the system, over the identified bacteria, the kinetic parameter of killing time (D-value) necessary to inactivate 90% of the initial bioburden (decimal reduction time) was experimentally determined.     

Tongue contractions during speech may have led to the development of the bony geometry of the chin following the evolution of human language: a mechanobiological hypothesis for the development of the human chin

One of the most fundamental yet unanswered questions of human evolution is that of the development of the chin. Whereas it is known that the chin, or mentum osseum, is an unique anatomical feature of modern humans that emerged during the Middle and Late Pleistocene, its origin and biomechanical significance are the subjects of intense controversy. Theories range from the suggestion that the chin evolved as a result of progressive reduction of the dental arch, which left it as a protrusion, to the hypothesis that it provided resistance to mandibular bending during mastication. Until now however, no accepted functional explanation of the human chin has emerged. Here, we develop the hypothesis that the actions of the tongue and non-masticatory orofacial muscles may have played a significant role on the development of the human chin. We report numerical simulations of the forces and resultant stresses developed in hypothetical chinned and non-chinned mandibles. Using empirical data and estimates of the forces generated by the human tongue during speech, our hypothesis suggests that the chin might in fact have developed as a result of the actions of the tongue and perioral muscles, rather than as a buttress to withstand masticatory induced stress. This provides a new perspective on the generation of the chin and importantly, suggests that its appearance may be causally related to the development of the human language.     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

Efficacy of mirtazapine add on therapy to haloperidol in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled study

The negative symptoms of schizophrenia remain a major clinical challenge. Mirtazapine is an antidepressant with antagonist properties at 5-HT2A, 5-HT3 and alpha 2 receptors as well as indirect 5-HT1a agonist effects. Many of these pharmacological actions have clinical or preclinical evidence of efficacy in schizophrenia. This study was a 6-week randomized placebo-controlled trial of mirtzepine or placebo add on to haloperidol 5 mg in the treatment of 30 patients with DSM-IV schizophrenia. The primary finding of the trial was a 42% reduction in Positive and Negative Syndrome Scale (PANSS) negative symptom scores in the mirtazapine group compared to placebo at the end of 6 weeks (mirtazapine 13.9, SD 1.56; placebo 23.9, SD 1.56; P = 0.000, F = 20.31, d.f. = 1). The PANNS total scores, Clinical Global Impression severity and improvement scales in addition showed superiority of mirtazapine over placebo. There was no difference between the groups on the Hamilton depression scale at endpoint, suggesting that the improvement in negative symptoms was not an artifact of mood improvement. These results suggest a potential role for mirtazapine in the negative symptoms of schizophrenia.