Classical and new proving methodology: provings of Plumbum metallicum and Piper methysticum and comparison with a classical proving of Plumbum metallicum

OBJECTIVE: To study the reliability of a proving methodology and the reproducibility of proving symptoms. METHODS: Two homeopathic medicines and placebo were given, in a double-blind randomized design, to 31 healthy volunteers (13 Piper methysticum 30C, 11 placebo and 7 Plumbum metallicum 30C), 5 drops 4 times daily, until the onset of unbearable symptoms, or at most for 1 week. The primary outcome measure was the number of phrases containing unusual or new symptoms selected by supervisors (SEL) from unstructured diaries and the number of these symptoms (SYM) present in SELs. The secondary outcome measures were the number of symptoms with modalities of both verum groups concordant with symptoms reported in a previous proving of Plumbum 12C. Other parameters evaluated were repeated and crossed symptoms in SELs. RESULTS: Both medicines showed qualitative and quantitative differences from placebo. Piper: 146 SELs (median: 5), Plumbum: 118 SELs (16), placebo: 48 SELs (2), containing 260 (8), 199 (29) and 58 (2) SYMs, respectively. There was a significant difference from placebo in Plumbum but not in Piper SELs and SYMs (P < 0.05). 31, 24 and 4 'repeated' and 18, 22 and 2 'crossed' symptoms were found in Piper, Plumbum and placebo. 8 and 30 symptoms concordant with the classical proving of Plumbum were found for Piper and Plumbum, corresponding to about 10% and 45% of their total SELs. CONCLUSIONS: Open diaries, supervision and double-blind placebo are useful methods in homeopathic pathogenetic trials. Estimates of concordance should be introduced in proving methodology.     

Noninvasive Ventilation in Postoperative Care of Lung Transplant Recipients

Noninvasive positive pressure ventilation (NIPPV), which provides consolidated treatment of both acute and chronic respiratory failure, is increasingly being used in the postoperative care of lung transplant patients. Graft- and patient-related respiratory insufficiency requiring mechanical ventilation are common features in the postoperative period; they may persist for hours to days. Prolonged intubation, particularly in these immunocompromised patients, has been considered one of the main predisposing factors for developing nosocomial pneumonia. It has been associated with increased length of intensive care unit (ICU) stay as well. Noninvasive mechanical ventilation is nowadays an attractive choice to shorten weaning time and avoid reintubation following lung transplantation.Rapid extubation plus prompt NIPPV application is a useful strategy for lung recipients who do not completely fulfill the criteria for safe extubation. Unloading respiratory muscles, decreasing respiratory rate and sensation of dyspnea, improving ventilation/perfusion abnormalities, decreasing the heart rate, and improving hemodynamics are among the recognized benefits. Adding a noninvasive inspiratory support plus positive end-expiratory pressure (PEEP) to lung transplant recipients has been helpful to prevent airway injury and infections, avoiding the need for reintubation in cases of extubation failure, facilitating nocturnal sedation, treating the post-reimplantation syndrome and postoperative phrenic nerve dysfunction, and preventing reintubation in cases of readmission to the ICU. In our practice, the helmet system has emerged as the preferred interface; in cases of dyshomogeneous dorsobasal lung infiltrates, it allows effective ventilatory support in the prone position as well.     

Report from the fifth National Cancer Institute Mouse Models of Human Cancers Consortium Nervous System Tumors Workshop

Cancers of the nervous system are clinically challenging tumors that present with varied histopathologies and genetic etiologies. While the prognosis for the most malignant of these tumors is essentially unchanged despite decades of basic and translational science research, the past few years have witnessed the identification of numerous targetable molecular alterations in these cancers. With the advent of advanced genomic sequencing methodologies and the development of accurate small-animal models of these nervous system cancers, we are now ideally positioned to develop personalized therapies that target the unique cellular and molecular changes that define their formation and drive their continued growth. Recently, the National Cancer Institute convened a workshop to advance our understanding of nervous system cancer mouse models and to inform clinical trials by reconsidering these neoplasms as complex biological systems characterized by heterogeneity at all levels.     

Remodelling and overgrowth after conservative treatment for femoral and tibial shaft fractures in children

One thousand nine hundred and eighty-four children who had received conservative treatment for shaft (diaphyseal and metadiaphyseal) fractures of lower limbs (1162 femoral, 822 tibial fractures) at an average age of 8.5 years (range 0–14 years) were reviewed by clinical and radiographic investigations at an average follow-up of 6.6 years (1–15 years). Particularly, two main features were evaluated: remodelling of (angular and rotational) deformities and post-traumatic overgrowth. Mechanisms underlying these processes are discussed, based on a review of the literature, and parameters conditioning their evolution are analysed. Finally, criteria for an acceptable reduction (and limits for residual deformities that may be tolerated) at the time of conservative treatment are proposed.     

Isolated fracture of the malleus handle: A video clip

Isolated malleus fracture is a rare clinical entity, and usually the handle of the malleus is involved. We report a video, to our knowledge the first in the literature, of a diagnostic otoscopy of a malleus fracture showing the movement of a left fractured malleus handle during a Valsalva maneuver (see the video online at www.laryngoscope.com ). Laryngoscope, 2010     

Epidermal growth factor receptor as a molecular determinant of glioblastoma response to dopamine receptor D2 inhibitors

BackgroundThere are ongoing clinical trials exploring the efficacy of dopamine receptor D2 (DRD2) inhibition against glioblastomas, the most common primary brain tumor. Here we examine potential molecular determinants of this efficacy.MethodsThe Cancer Genome Atlas glioblastoma database and other published mRNA profiles were used to analyze the DRD2 and epidermal growth factor receptor (EGFR) expression pattern. In vitro and in vivo responses to DRD2 inhibitors were determined using patient-derived xenograft (PDX) glioblastoma models. Immunohistochemical studies were performed on clinically annotated glioblastoma samples derived from patients treated with ONC201.ResultsAnalysis of clinical glioblastoma specimens derived from independent patient cohorts revealed an inverse correlation between EGFR and DRD2 mRNA expression, with implication that signaling mediated by these proteins shares overlapping functions. In independent panels of PDX glioblastoma lines, high EGFR expression was associated with poor in vitro and in vivo response to DRD2 inhibitors, including haloperidol and ONC201. Moreover, ectopic expression of a constitutively active EGFR, variant (v)III, suppressed glioblastoma sensitivity to ONC201. DRD2 expression positively correlated with expression of rate-limiting enzymes for dopamine synthesis as well as dopamine secretion, suggesting contribution of autocrine DRD2 signaling. Analysis of specimens from patients treated with ONC201 (n = 15) showed an inverse correlation between the intensity of EGFR staining and clinical response. The median overall survival for patients with high and low EGFR staining was 162 and 373 days, respectively (0.037).ConclusionsHigh EGFR expression is a determinant of poor glioblastoma response to DRD2. This finding should inform future clinical trial designs.     

Application of the concept of traceability to the management of nuclear data

The connotations of the quality of nuclear data in the quality of experimental results are discussed. The authors show the analogies existent between metrological standards and literature data and propose the adoption of the concept of traceability of nuclear data. The conditions to be fulfilled for the publication of nuclear data, concerning the establishment of traceability, are discussed. Criteria for renormalization are presented. The requirements of nuclear data in neutron activation analysis and the role of the analyst are discussed.