Toxicity of antiseptics against chondrocytes: What is best for the cartilage in septic joint surgery?

In septic joint surgery, the most frequently used antiseptics are polyhexanide, hydrogen peroxide and taurolidine. The aim of this study was to examine the effects of these antiseptics on viability of human chondrocytes. Our hypothesis was that antiseptics and supplemental irrigation with sodium chloride lavage are less toxic on human chondrocytes than treatment with antiseptics only. Primary human chondrocytes were isolated and cultured from six donated human knee joints. Polyhexanide, hydrogen peroxide or taurolidine were added to the cultures. Toxicity analysis was performed by visualisation of cell structure using light microscopy and LDH activity. The determination of vital cells and total cell numbers of chondrocytes treated with antiseptics partly followed by irrigation with sodium chloride solution was performed by using Casy Cell-Counter. Light microscopic data revealed a defect in cell structure after addition of antiseptics. We showed a significant increase of LDH enzyme activity after the treatment with polyhexanide or taurolidine. After treatment with antiseptics followed by sodium chloride solution a significant increase of vital and total cell numbers resulted in comparison with the chondrocytes that were only treated with antiseptics. The data show that treatment with polyhexanid, hydrogen peroxide or taurolidine induces cell death of human chondroctes in vitro. The application of sodium chloride solution after the treatment with polyhexanide and hydrogen peroxide possibly has a protective effect on chondrocyte viability.     

In silico modelling of physiologic systems

In silico modelling, in which computer models are developed to model a pharmacologic or physiologic process, is a logical extension of controlled in vitro experimentation. It is the natural result of the explosive increase in computing power available to the research scientist at continually decreasing cost. In silico modelling combines the advantages of both in vivo and in vitro experimentation, without subjecting itself to the ethical considerations and lack of control associated with in vivo experiments. Unlike in vitro experiments, which exist in isolation, in silico models allow the researcher to include a virtually unlimited array of parameters, which render the results more applicable to the organism as a whole. In silico modelling is best known for its extensive use in pharmacokinetic experimentation, the best-known example of which is the development of the three-compartment model. In addition, complex in silico models have been applied to pathophysiological problems to provide information which cannot be obtained practically or ethically by traditional clinical research methods. These experiments have led to the development of significant insights in subject matters ranging from pure physiology to congenital heart surgery, obstetric anaesthesia airway management, mechanical ventilation and cardiopulmonary bypass/ventricular support devices. The utility of these models is based on both the validity of the model framework as well as the corresponding assumptions. In vivo experimentation has validated some, but not all of the in silico strategies employed. We present a review illustrating by example how in silico modelling has been applied to a number of cardio-respiratory problems in states of health and disease, the purpose of which is to give the reader a sense of the complexity and assumptions which underlie this diverse and underappreciated research strategy, as well as an introduction to a research strategy that will likely continue to grow in importance.     

Nodular hemangiomatosis of pleura and peritoneum

Multiple, simultaneously occurring hemangiomas in one or more organs are known as hemangiomatosis syndromes in the context of phacomatosis manifesting in childhood. Nevertheless, hemangiomas of the serous membranes are extremely rare and often present as solitary lesions. We report the case of an elderly patient who suffered from diffuse hemangiomatosis of the visceral peritoneum and pleura and deceased due to acute respiratory distress syndrome following persistent and unmanageable pulmonary hemorrhage. We present an unusual case of a disseminated but histologically benign appearing hemangiomatosis of the serous membranes.     

Low glycemic index treatment for epilepsy in tuberous sclerosis complex

Retrospective chart review of 15 patients with tuberous sclerosis complex (TSC) who initiated the low glycemic index treatment (LGIT) for epilepsy management at Massachusetts General Hospital over a five-year period. Prior to dietary therapy, this cohort (average age: 8.5 years) had tried an average of 5.8 anti-epileptic drugs with incomplete seizure control. At 6 months on the LGIT, 7/15 (47%) patients experienced >50% reduction in seizure frequency.     

Low glycemic index treatment for seizures in Angelman syndrome

Purpose: The low glycemic index treatment (LGIT) is a high fat, limited carbohydrate diet used in the treatment of epilepsy. The purpose of this study was to assess the efficacy and tolerability of the LGIT for the treatment of refractory seizures in pediatric patients with Angelman syndrome. Methods: A pediatric Angelman syndrome cohort with refractory epilepsy was treated with the LGIT and followed prospectively over 4 months. Parents recorded a daily seizure log for a minimum of 1 month prior to the start of treatment as well as throughout the LGIT trial. Electroencephalography (EEG) and neuropsychological assessments (Scales of Independent Behavior‐Revised and the Vineland Adaptive Behavior Scales‐2nd Edition were obtained for each subject at both baseline and 4‐month follow‐up time points. Clinical evaluations of subjects were completed by a neurologist and dietitian at the time of enrollment, as well as following both the first and fourth months of dietary therapy. At each time point, blood for laboratory chemistries was drawn and anthropometric measures were obtained. Key Findings: Six children (mean age 3.3 years, range 1.1–4.8) with genetically confirmed Angelman syndrome initiated the LGIT, and completed the trial with no significant adverse events. Cohort averages for indices of seizure severity were as follows: age of 1.6 years at seizure onset, 3 lifetime antiepileptic drugs tried (range 1–6), and baseline seizure frequency of 10.1 events/week (range: 0.4–30.9). All subjects had a decrease in seizure frequency on the LGIT, with five of six exhibiting >80% seizure frequency reduction. All posttrial EEG studies showed improvement and three of four children with epileptiform activity on his or her baseline EEG had no discharges present on follow‐up EEG. Developmental gains were noted by parents in all cases, although few of these neurocognitive gains were statistically significant on neuropsychological assessment. Significance: This is the first prospective study assessing the LGIT for epilepsy. Our results indicate that this dietary therapy is highly effective in treating Angelman syndrome–related seizures. The diet was well tolerated by subjects as evidenced by five of six subjects remaining on the LGIT after completion of the trial. Beyond the prospective trial window, all five subjects who remained on the diet had >90% seizure reduction after 1 year of LGIT therapy. Despite the small sample size in this prospective study, the results indicate a potentially higher degree of efficacy of the LGIT for the Angelman syndrome population than that observed in the general epilepsy population. Although this study is too small to make definitive recommendations, these results suggest that the LGIT is a promising treatment option for Angelman syndrome–related epilepsy.     

Central neuropeptide Y modulates binge-like ethanol drinking in C57BL/6J mice via Y1 and Y2 receptors

Frequent binge drinking has been linked to heart disease, high blood pressure, type 2 diabetes, and the development of ethanol dependence. Thus, identifying pharmaceutical targets to treat binge drinking is of paramount importance. Here we employed a mouse model of binge-like ethanol drinking to study the role of neuropeptide Y (NPY). To this end, the present set of studies utilized pharmacological manipulation of NPY signaling, immunoreactivity (IR) mapping of NPY and NPY receptors, and electrophysiological recordings from slice preparations of the amygdala. The results indicated that central infusion of NPY, a NPY Y1 receptor (Y1R) agonist, and a Y2R antagonist significantly blunted binge-like ethanol drinking in C57BL/6J mice (that achieved blood ethanol levels >80?mg/dl in control conditions). Binge-like ethanol drinking reduced NPY and Y1R IR in the central nucleus of the amygdala (CeA), and 24?h of ethanol abstinence after a history of binge-like drinking promoted increases of Y1R and Y2R IR. Electrophysiological recordings of slice preparations from the CeA showed that binge-like ethanol drinking augmented the ability of NPY to inhibit GABAergic transmission. Thus, binge-like ethanol drinking in C57BL/6J mice promoted alterations of NPY signaling in the CeA, and administration of exogenous NPY compounds protected against binge-like drinking. The current data suggest that Y1R agonists and Y2R antagonists may be useful for curbing and/or preventing binge drinking, protecting vulnerable individuals from progressing to the point of ethanol dependence.     

Ability of the Masimo pulse CO-Oximeter to detect changes in hemoglobin

The decision to administer blood products is complex and multifactorial. Accurate assessment of the concentration of hemoglobin [Hgb] is a key component of this evaluation. Recently a noninvasive method of continuously measuring hemoglobin (SpHb) has become available with multi-wavelength Pulse CO-Oximetry. The accuracy of this device is well documented, but the trending ability of this monitor has not been previously described. Twenty patients undergoing major thoracic and lumbar spine surgery were recruited. All patients received radial arterial lines. On the contralateral index finger, a R1 25 sensor (Rev E) was applied and connected to a Radical-7 Pulse CO-Oximeter (both Masimo Corp, Irvine, CA). Blood samples were drawn intermittently at the anesthesia provider’s discretion and were analyzed by the operating room satellite laboratory CO-Oximeter. The value of Hgb and SpHb at that time point was compared. Trend analysis was performed by the four quadrant plot technique, testing directionality of change, and Critchley’s polar plot method testing both directionality and magnitude of the change in values. Eighty-eight samples recorded at times of sufficient signal quality were available for analysis. Four quadrant plot analysis revealed 94% of data within the quadrants associated with the correct direction change, and 90% of data points lay within the analysis bounds proposed by Critchley. Pulse CO-Oximetry offers an acceptable trend monitor in patients undergoing major spine surgery. Future work should explore the ability of this device to detect large changes in hemoglobin, as well as its applicability in additional surgical and non-surgical patient populations.     

Surface and intracardiac ECG for discriminating conduction disorders after CoreValve implantation

Background

Transcatheter aortic valve implantation (TAVI) has been developed to minimize operative morbidity and mortality in high-risk symptomatic patients unfit for open surgery. With the proximity of the aortic valve annulus to the conduction system there is, however, an unknown risk of conduction disturbances necessitating monitoring and often cardiac pacing.

Materials and methods

We enrolled 50 consecutive patients from January 2007 to 2008 in our prospective evaluation of conduction disturbances measured by surface and intracardiac ECG recordings. Baseline parameters, procedural characteristics as well as twelve-lead surface ECG and intracardiac conduction times were revealed pre-interventionally, after TAVI and at 7-day follow-up.

Results

TAVI was performed successfully in all patients. During 7?days of follow-up the rate for first-degree AV block raised from 14% at baseline to 44% at day 7 (p?p?p?p?p?p?Conclusion Cardiac conduction disturbances were common in the early experience with CoreValve implantation necessitating close surveillance for at least 1?week.