Medical hypotheses
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We hypothesize that supplemental inhaled nitric oxide (iNO) will improve outcomes in children with severe malaria receiving standard antimalarial therapy. The rationale for the hypothesized efficacy of iNO rests on: (1) biological plausibility, based on known actions of NO in modulating endothelial activation; (2) pre-clinical efficacy data from animal models of experimental cerebral malaria; and (3) a human trial of the NO precursor l-arginine, which improved endothelial function in adults with severe malaria. iNO is an attractive new candidate for the adjunctive treatment of severe malaria, given its proven therapeutic efficacy in animal studies, track record of safety in clinical practice and numerous clinical trials, inexpensive manufacturing costs, and ease of administration in settings with limited healthcare infrastructure. We plan to test this hypothesis in a randomized controlled trial (ClinicalTrials.gov Identifier: NCT01255215).
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Fibromyalgia (FM) is a condition of chronic generalized musculoskeletal pain that is thought to be a disorder of central pain sensitization. A number of neurotransmitters in the ascending and descending pain pathways have been implicated in FM including glutamate and GABA. Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme in the conversion of glutamate to GABA and decreased expression or activity of this enzyme could result in an imbalance of excitatory and inhibitory neurotransmission in the ascending and descending pain pathways. ⋯ These six general lines of evidence suggest that GAD expression and/or activity might underlie the pathophysiology of FM. If this hypothesis is supported by future empirical studies, our understanding of the etiology of FM could be greatly improved. Moreover, behavioral and pharmacological therapies that modulate or mimic the effects of GAD might hold promise for the treatment of this debilitating and poorly understood disorder.
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The innovative concept of transnasal evaporative cooling for therapeutic hypothermia in cardio-pulmonary-cerebro-resuscitation has therapeutic implications with evidence of rapid and selective brain cooling; however, this author wants to elicit that this concept may hold answers for many physiological phenomena which have not been explored or completely understood up till now. To affirm the physiological role of transnasal cooling, the innovative non-invasive brain temperature monitoring can help the investigators to explore and understand the following transnasal pathophysiological phenomena: (1) understanding correlation of brain temperature and sinus headache secondary to nasal blockade, (2) exploring the therapeutic role of nasal oxygen for prevention of delirium in intubated patients, (3) realizing the impact of controlled enclosed environments on the mood and affect of the inhabitants, (4) understanding the etio-pathogenesis of claustrophobia after excluding the confounding factors of morbid obesity, severe cardiopulmonary disease and incapacitating musculoskeletal diseases, (5) exploring the anthropological role of male pattern of moustache, beard and hair loss, and (6) possible development of a coolant moustache as proposed by the author. In summary, transnasal pathophysiology offers many promising lines of fruitful research to explore the non-olfactory physiological functions of nose in human beings.
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We previously found that a blood urea nitrogen/creatinine (BUN/Cr) ratio>15 is an independent predictor of early neurological deterioration after acute ischemic stroke, which suggests that dehydration may be a cause of early deterioration. The aim of this study was to determine whether urine specific gravity, which is another indicator of hydration status and one that is more easily obtained, is also an independent predictor of early deterioration or stroke-in-evolution (SIE). Demographic and clinical data were recorded at admission from patients with acute ischemic stroke who were prospectively enrolled from October 2007 to June 2010. ⋯ After adjusting for age and gender, patients with a urine specific gravity>1.010 were 2.78 times more likely to develop SIE (95% CI=1.11-6.96; P=0.030). Urine specific gravity may be useful as an early predictor of early deterioration in patients with acute ischemic stroke. Patients with urine specific gravity ≤ 1.010 therefore may have a reduced likelihood of early neurological deterioration.
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Normal brain function is facilitated by a highly organized and interconnected structure allowing complex integration of sensory information and motor responses. The acute confusional state of delirium is characterized by a fluctuating disturbance in consciousness, arousal level and cognition-memory; as such, delirium represents a failure in the integration and appropriate processing of information. The pathogenesis of this cognitive disintegration is unclear; herein a hypothesis is proposed that delirium results from an acute breakdown in network connectivity within the brain. ⋯ An important role for GABAergic neurotransmission is implicated in increasing the inhibitory tone to produce delirium. This theory accounts for the various forms of delirium, hypoactive, hyperactive and mixed. The form of delirium that ensues will depend upon how and which networks breakdown (dependent on both the individual's baseline network connectivity and the degree change in inhibitory tone produced).