Effectiveness of Propranolol in the Treatment of Infantile Hemangioma Beyond the Proliferation Phase

During the last 5 years, many studies have shown the efficacy of propranolol as first‐line treatment for infantile hemangiomas (IHs), but not much has been written about the role of propranolol beyond the proliferation phase of IH (>1 year). Our aim was to assess propranolol efficacy and safety in the treatment of patients older than 1 year. A retrospective study of patients older than 1 year diagnosed with IH and treated in our vascular anomalies clinic between 2009 and 2013 was performed. Eighteen patients older than 1 year with a diagnosis of IH (15 girls, 3 boys) were identified. The mean age at the time of initiation of treatment was 25.7 months (range 13–72 mos). Single lesions were observed in 13 patients and multiple lesions in 5. Fifteen patients had focal lesions and three had segmental. The median duration of treatment with oral propranolol was 11.8 months (range 2–33 mos). Complete response was observed in 72.2% of the patients and partial response in 27.8%. Recurrence was observed in three patients 4.7 months after completion of therapy (range 0.3–8 mos). These patients required further therapy with propranolol for 6 more months. Bradycardia was documented in two patients and night terrors in one patient, which led to discontinuation of treatment. In our experience, propranolol may be useful in the treatment of IHs beyond the proliferation phase (>1 year old), but more studies are needed to support this observation.     

Thermoalgesic stimuli induce prepulse inhibition of the blink reflex and affect conscious perception in healthy humans

All sensory stimuli produce transient excitability changes in various central nervous system circuits. One example is prepulse inhibition (PPI), which is the inhibition generated by a preceding weak stimulus (prepulse) over the reflex response to a subsequent suprathreshold stimulus. The PPI is a ubiquitous phenomenon, common to many different sensory modalities. However, it has not yet been studied with thermoalgesic stimuli. These stimuli take a relatively long time to reach their peak, which implies some uncertainty in the exact timing of prepulse effects with respect to stimulus onset. In 20 healthy volunteers, we determined when thermoalgesic stimuli cause PPI of the blink reflex and measured conscious awareness (AW) of thermoalgesic stimulus perception using the Libet's clock. In this way, we determined the temporal relationship between AW and PPI. In a second experiment, we investigated whether prepulse effects on blink reflex also involved a change in conscious perception of the supraorbital nerve stimulus. Our results show that thermoalgesic stimuli generate PPI of the blink reflex long before subjects were consciously aware of the stimulus, confirming the already‐known principle that conscious perception is not required for PPI to take place, and that prepulse stimuli induce a change in the time of conscious perception of prepulse and pulse stimuli, in such a way that AW of both stimuli tended to become closer to each other.     

A miRNA signature for defining aggressive phenotype and prognosis in gliomas

Gliomas represent a disparate group of tumours for which there are to date no cure. Thus, there is a recognized need for new diagnostic and therapeutic approaches based on increased understanding of their molecular nature. We performed the comparison of the microRNA （miRNA） profile of 8 WHO grade II gliomas and 24 higher grade tumours （2 WHO grade III and 22 glioblastomas） by using the Affymetrix GeneChip miRNA Array v. 1.0. A relative quantification method （RT-qPCR） with standard curve was used to confirm the 22 miRNA signature resulted by array analysis. The prognostic performances of the confirmed miRNAs were estimated on the Tumor Cancer Genome Atlas （TCGA） datasets. We identified 22 miRNAs distinguishing grade II gliomas from higher grade tumours. RT-qPCR confirmed the differential expression in the two patients＇groups for 13 out of the 22 miRNAs. The analysis of the Glioblastoma Multiforme （GBM） and Lower Grade Glioma （LGG） datasets from TCGA demonstrated the association with prognosis for 6 of those miRNAs. Moreover, in the GBM dataset miR-21 and miR-210 were predictors of worse prognosis in both univariable and multivariable Cox regression analyses （ HR 1.19, P = O. 04, and HR 1.18, P = 0. 029 respectively）. Our results support a direct contribution of miRNAs to glioma cancerogenesis and suggest that miR-21 and miR-210 may play a role in the aggressive clinical behaviour of glioblastomas.     

A bibliography of cost-effectiveness practices in physical medicine and rehabilitation: AAPM&R white paper

Cost-effectiveness studies attempt to determine the ratio of costs to outcomes of a particular intervention or treatment and to compare a standard intervention with an alternative intervention to determine if the alternative is more cost effective. The goal is to establish priorities for the resources allocation and to decide among alternative interventions for the same medical condition. The global process of rehabilitation does not usually lend itself to cost-effective analysis (due to the complex set of treatments provided) but rather to specific interventions and specific aspects of outcome. The American Academy of Physical Medicine and Rehabilitation has published a cost effectiveness annotated bibliography on the Internet (http://www.aapmr.org/memphys/cebfinala.htm) that identifies 132 studies in the literature that meet specified criteria and are related to the field of rehabilitation. This White Paper attempts to interpret and synthesize the studies in that bibliography that relate to stroke, spinal cord injury (SCI), orthopedic conditions, pain syndromes, amputations, and traumatic brain injury (TBI). Most studies support the cost effectiveness of care for stroke and SCI in dedicated units or centers rather than in a general medical unit. Studies also support back programs and revascularization procedures in limb ischemia. Studies in TBI underscore the significant financial resources for the care of these patients as well as the potential benefit from rehabilitation services even in the most severely injured. Further high quality research in this area is needed.     

Identification of Candida species in the clinical laboratory: a review of conventional,commercial, and molecular techniques

In healthy individuals, Candida species are considered commensal yeasts of the oral cavity. However, these microorganisms can also act as opportunist pathogens, particularly the so‐called non‐albicans Candida species that are increasingly recognized as important agents of human infection. Several surveys have documented increased rates of C. glabrata, C. tropicalis, C. guilliermondii, C. dubliniensis, C. parapsilosis, and C. krusei in local and systemic fungal infections. Some of these species are resistant to antifungal agents. Consequently, rapid and correct identification of species can play an important role in the management of candidiasis. Conventional methods for identification of Candida species are based on morphological and physiological attributes. However, accurate identification of all isolates from clinical samples is often complex and time‐consuming. Hence, several manual and automated rapid commercial systems for identifying these organisms have been developed, some of which may have significant sensitivity issues. To overcome these limitations, newer molecular typing techniques have been developed that allow accurate and rapid identification of Candida species. This study reviewed the current state of identification methods for yeasts, particularly Candida species.     

The Irish potato famine pathogen Phytophthora infestans originated in central Mexico rather than the Andes

Phytophthora infestans is a destructive plant pathogen best known for causing the disease that triggered the Irish potato famine and remains the most costly potato pathogen to manage worldwide. Identification of P. infestan’s elusive center of origin is critical to understanding the mechanisms of repeated global emergence of this pathogen. There are two competing theories, placing the origin in either South America or in central Mexico, both of which are centers of diversity of Solanum host plants. To test these competing hypotheses, we conducted detailed phylogeographic and approximate Bayesian computation analyses, which are suitable approaches to unraveling complex demographic histories. Our analyses used microsatellite markers and sequences of four nuclear genes sampled from populations in the Andes, Mexico, and elsewhere. To infer the ancestral state, we included the closest known relatives Phytophthora phaseoli, Phytophthora mirabilis, and Phytophthora ipomoeae, as well as the interspecific hybrid Phytophthora andina. We did not find support for an Andean origin of P. infestans; rather, the sequence data suggest a Mexican origin. Our findings support the hypothesis that populations found in the Andes are descendants of the Mexican populations and reconcile previous findings of ancestral variation in the Andes. Although centers of origin are well documented as centers of evolution and diversity for numerous crop plants, the number of plant pathogens with a known geographic origin are limited. This work has important implications for our understanding of the coevolution of hosts and pathogens, as well as the harnessing of plant disease resistance to manage late blight.The potato pathogen Phytophthora infestans, the causal agent of potato late blight, is the plant pathogen that has most greatly impacted humanity to date. This pathogen is best known for its causal involvement in the Irish potato famine after introduction of the HERB-1 strain to Ireland from the Americas in the 19th century (1). To this day, potato late blight remains a major threat to food security and carries a global cost conservatively estimated at more than $6 billion per year (2). In the 1980s, a single asexual lineage named US-1, possibly derived from the same metapopulation as HERB-1 (1), dominated global populations, whereas a genetically diverse and sexual population of P. infestans in central Mexico led to formulation of the hypothesis identifying Mexico as this pathogen’s center of origin (3, 4). A competing hypothesis argues that the center of origin of the potato, the South American Andes, is the center of origin of P. infestans (5). This hypothesis recently gained prominence after an analysis demonstrated ancestral variation in Andean lineages of P. infestans (5). Other evidence supporting this hypothesis includes infection of native Solanum hosts and an Andean distribution for Phytophthora andina, a phylogenetic relative of P. infestans (6).Evidence supporting a Mexican center of origin is substantial, but inconclusive (4). Two close relatives of P. infestans, Phytophthora ipomoeae and Phytophthora mirabilis, are endemic to central Mexico (7, 8). P. ipomoeae and P. mirabilis cause disease on two endemic plant host groups, Ipomoea spp. and Mirabilis jalapa, respectively. Populations of P. infestans in the Toluca Valley, southwest of Mexico City, are genetically diverse, are in Hardy–Weinberg equilibrium, and contain mating types A1 and A2 in the expected 1:1 ratio for sexual populations (9, 10). Before a migration event from Mexico to Europe in the 1970s (11, 12), only A1 mating types of P. infestans were found worldwide outside of central Mexico, limiting other populations to asexual reproduction (13). Tuber-bearing native Solanum species occur throughout the Toluca Valley (14). Of the R genes that have been used to confer resistance to strains of P. infestans in potato, the majority described to date originated from Solanum demissum or Solanum edinense in the Toluca Valley, with some discovered in South America (15).Support for the alternate hypothesis that P. infestans originated in the Andes is based on a coalescent analysis conducted by Gómez-Alpizar et al. (5). This analysis used the nuclear RAS locus and the mitochondrial P3 and P4 regions to infer rooted gene genealogies that showed ancestral lineages rooted in the Andes. Furthermore, the Mexico sample harbored less nucleotide diversity than the Andean population. P. andina was identified as the ancestral lineage for the mitochondrial genealogy; however, P. mirabilis and P. ipomoeae were not included in that study. P. andina has since been shown to be a hybrid species derived from P. infestans and a Phytophthora sp. unknown to science (16). Surprisingly, populations of P. infestans and P. andina are clonal in South America and are not in Hardy–Weinberg equilibrium (6, 17–19). Thus, the question of whether P. infestans originated in the Andes or central Mexico remained unresolved.Powerful approaches for determining the demographic and evolutionary history of organisms are now available (20). Many of these approaches rely on the power of coalescent theory for inferring the genealogical history of a species based on a representative population sample (21–23). Bayesian phylogeography uses geographic information in light of phylogenetic uncertainty to provide model-based inference of geographic locations of ancestral strains (24). The isolation with migration (IM) model and associated software uses likelihood-based inference to infer divergence time between evolutionary lineages (25). Approximate Bayesian computation (ABC) makes use of coalescent simulations and likelihood-free inference to contrast complex demographic scenarios. Each of these methods has proven useful in reconstructing the demography of pests and pathogens (24, 26–29).The objective of the present study was to reconcile the two competing hypotheses on the origin of P. infestans using Bayesian phylogenetics and ABC. We sampled key populations of P. infestans from central Mexico and the Andes and expanded on the analysis of Gómez-Alpizar et al. (5) by sequencing additional nuclear loci to assess support for the center of origin across multiple loci. To determine ancestral state, we added sequences from the sister taxa P. andina, P. mirabilis, P. ipomoeae, and Phytophthora phaseoli, all of which belong to Phytophthora clade 1c (30, 31). Finally, we aimed to reconcile the biology of P. infestans in Mexico with the findings of Gómez-Alpizar et al. (5) of ancestral variation in the Andes.     

Osborn waves in sepsis

A patient with severe sepsis, who presented with moderate hypothermia and the classical electrocardiographic findings that have been described in patients with accidental hypothermia is presented. Rewarming was associated with proportional improvement of the initial electrocardiographic abnormalities. A brief discussion is included about the electrophysiologic mechanisms of Osborn waves, the differential diagnosis of this electrocardiographic finding as well as other findings described in patients with hypothermia.     

Satisfaction with, and the beneficial side effects of, hypnotic analgesia

Case study research suggests that hypnosis treatment may provide benefits that are not necessarily the target of specific suggestions. To better understand satisfaction with and the beneficial "side effects" of hypnosis treatment, questions inquiring about treatment satisfaction and treatment benefits were administered to a group of 30 patients with chronic pain who had participated in a case series of hypnotic analgesia treatment. The results confirmed the authors' clinical experience and showed that most participants reported satisfaction with hypnosis treatment even when the targeted symptom (in this case, pain intensity) did not decrease substantially. Study participants also reported a variety of both symptom-related and nonsymptom-related benefits from hypnosis treatment, including decreased pain, increased perceived control over pain, increased sense of relaxation and well-being, and decreased perceived stress, although no single benefit was noted by a majority of participants.     

Treatments for chronic pain associated with spinal cord injuries: many are tried,few are helpful

OBJECTIVE: The objective was to investigate, in two community samples of people with spinal cord injuries, the frequency of use of different pain treatments and the perceived helpfulness of these treatments. DESIGN AND SETTING: A postal survey was conducted in the community. PARTICIPANTS: The participants were 471 persons aged 18 years or older who had spinal cord injuries and pain. There were 2 separate samples (n = 308 and n = 163). OUTCOME MEASURES: The pain treatments used, the helpfulness of these treatments, and the Chronic Pain Grade questionnaire answers were assessed. RESULTS: Respondents reported multiple pain treatments (range of 0-14 and median of 4 in sample 1; range of 0-16 and median of 4 in sample 2). The most commonly reported treatments were oral medications and physical therapy. Medication types most commonly reported were nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and opioids. The treatments rated as most helpful were opioid medications, physical therapy, and diazepam therapy, and those rated as least helpful were spinal cord stimulation, counseling or psychotherapy, administration of acetaminophen, and administration of amitriptyline. Alternative treatments reported as most helpful were massage therapy and use of marijuana. Acupuncture was tried by many but was rated as only moderately helpful. CONCLUSIONS: This survey of two large samples of community-dwelling individuals with spinal cord injury-related chronic pain indicates that multiple pain treatments are tried but only a few are rated as more than somewhat helpful. Furthermore, the treatments that are most commonly reported are not always those that are rated as most helpful. The findings point to a number of potentially fruitful directions for future research.