Respiratory function in recent pulmonary sarcoidosis with special reference to small airways

This study was designed to evaluate airway dysfunction in relation to duration of disease in patients with pulmonary sarcoidosis for less than two years. Twenty four subjects with recent disease were compared with nine subjects with disease of more than two years' duration. They underwent lung function testing (lung volumes, lung transfer factor for CO and pulmonary mechanics). Small airway function was assessed using frequency dependence of compliance, closing volume, nitrogen single breath test and flow-volume curves breathing air and helium-oxygen mixture. Airway dysfunction was seen in pulmonary sarcoidosis even in some patients with recent disease and it became more evident in disease of longer duration. The results suggest small airway involvement. The frequency of airway dysfunction is difficult to evaluate, varying from estimates of 0% using flow-volume curves to 79% with frequency dependence of compliance. This apparent discrepancy could be explained by the consequences of parenchymal involvement leading to inhomogeneities in distribution of compliance, and of elastic lung recoil. We conclude that patients with recent sarcoidosis are probably affected by intrinsic small airway disease, but an increase in elastic recoil often conceals its consequences. The airway disease may not be apparent using conventional function tests and published predicted values.     

Conservative Treatment of Ankle Osteoarthritis: Can Platelet-Rich Plasma Effectively Postpone Surgery?

Osteoarthritis is the most common and disabling of the orthopedic diseases. Currently, the conservative treatment of osteoarthritis is limited to symptomatic treatment, whose goal is to improve function and pain control. Ankle osteoarthritis is relatively uncommon, in contrast to osteoarthritis of the hip and knee, and the therapeutic options (both pharmacologic and surgical) are limited, with surgery providing poorer and less predictable results. The effectiveness of platelet-rich plasma injections for osteoarthritis is still controversial, especially so for ankle arthritis, owing to the lack of evidence in the present data. We retrospectively evaluated the mid- to long-term clinical results (mean follow-up of 17.7 months) for platelet-rich plasma injections in 20 patients (20 ankles) with ankle osteoarthritis. We evaluated the presence of pain using the visual analog scale, function using the Foot and Ankle Disability Index, and subjective satisfaction. The pre- and post-treatment scores, obtained from the clinical records and from telephone interviews during the follow-up period, were compared using the Student t test. We found a strong positive effect for 4 platelet-rich plasma injections (injected once a week) on pain (p = .0001) and function (p = .001), with 80% of patients very satisfied and satisfied, and only 2 patients (10%) required surgery because of early treatment failure. These results suggest that the use of platelet-rich plasma injection is a valid and safe alternative to postpone the need for surgery.     

Autoimmune-like pancreatitis in thymoma with myasthenia gravis

A patient with thymoma and myasthenia gravis admitted for surgery presented increased serum levels of pancreatic amylase and lipase. Suspecting a thymoma-related autoimmune disorder, autoantibody serum titers were determined: increased autoantibody titers to acetylcholine receptors, thyroglobulin, thyroperoxidase and pancreatic insulin were detected. After thymectomy the serum levels of pancreatic enzymes decreased rapidly. Myasthenia gravis symptoms also improved. To the best of our knowledge no similar cases have been reported in the literature.     

Plasticity in the adult brain: lessons from the visual system

While cortical circuits display maximal sensitivity to sensory experience during critical periods of early postnatal development, far less plasticity is present in the mature brain. Ocular dominance shift of visual cortical neurons in response to eye occlusion and recovery of visual functions from a period of sensory deprivation are two classical models in the study of critical period determinants in the visual cortex. Recent papers employing various pharmacological and environmental strategies have shown that it is possible to reinstate much greater levels of plasticity in the adult visual cortex than previously suspected. These studies point toward intracortical inhibition as a crucial determinant for critical period regulation in the visual system and have a great potential for therapeutic rehabilitation and recovery from injury in the adult brain. M. Spolidoro and A. Sale have equally contributed to this work.     

Intensity-modulated proton therapy versus helical tomotherapy in nasopharynx cancer: planning comparison and NTCP evaluation

PURPOSE: To compare intensity-modulated proton therapy (IMPT) and helical tomotherapy (HT) treatment plans for nasopharynx cancer using a simultaneous integrated boost approach. METHODS AND MATERIALS: The data from 6 patients who had previously been treated with HT were used. A three-beam IMPT technique was optimized in the Hyperion treatment planning system, simulating a "beam scanning" technique. HT was planned using the tomotherapy treatment planning system. Both techniques were optimized to simultaneously deliver 66 Gy in 30 fractions to planning target volume (PTV1; GTV and enlarged nodes) and 54 Gy to PTV2 subclinical, electively treated nodes. Normal tissue complication probability calculation was performed for the parotids and larynx. RESULTS: Very similar PTVs coverage and homogeneity of the target dose distribution for IMPT and HT were found. The conformity index was significantly lower for protons than for photons (1.19 vs. 1.42, respectively). The mean dose to the ipsilateral and contralateral parotid glands decreased by 6.4 Gy and 5.6 Gy, respectively, with IMPT. The volume of mucosa and esophagus receiving >/=20 Gy and >/=30 Gy with IMPT was significantly lower than with HT. The average volume of larynx receiving >/=50 Gy was significantly lower with HT, while for thyroid, it was comparable. The volume receiving >/=30, >/=20, and >/=10 Gy in total body volume decreased with IMPT by 14.5%, 19.4%, and 23.1%, respectively. The normal tissue complication probability for the parotid glands was significantly lower with IMPT for all sets of parameters; however, we also estimated an almost full recovery of the contralateral parotid with HT. The normal tissue complication probability for the larynx was not significantly different between the two irradiation techniques. CONCLUSION: Excellent target coverage, homogeneity within the PTVs, and sparing of the organs at risk were reached with both modalities. IMPT allows for better sparing of most organs at risk at medium-to-low doses.     

Quantitative performance of E-Scribe warehouse in detecting quality issues with digital annotated ECG data from healthy subjects

The US Food and Drug Administration recommends submission of digital electrocardiograms in the standard HL7 XML format into the electrocardiogram warehouse to support preapproval review of new drug applications. The Food and Drug Administration scrutinizes electrocardiogram quality by viewing the annotated waveforms and scoring electrocardiogram quality by the warehouse algorithms. Part of the Food and Drug Administration warehouse is commercially available to sponsors as the E-Scribe Warehouse. The authors tested the performance of E-Scribe Warehouse algorithms by quantifying electrocardiogram acquisition quality, adherence to QT annotation protocol, and T-wave signal strength in 2 data sets: "reference" (104 digital electrocardiograms from a phase I study with sotalol in 26 healthy subjects with QT annotations by computer-assisted manual adjustment) and "test" (the same electrocardiograms with an intentionally introduced predefined number of quality issues). The E-Scribe Warehouse correctly detected differences between the 2 sets expected from the number and pattern of errors in the "test" set (except for 1 subject with QT misannotated in different leads of serial electrocardiograms) and confirmed the absence of differences where none was expected. E-Scribe Warehouse scores below the threshold value identified individual electrocardiograms with questionable T-wave signal strength. The E-Scribe Warehouse showed satisfactory performance in detecting electrocardiogram quality issues that may impair reliability of QTc assessment in clinical trials in healthy subjects.     

Prion protein potentiates acetylcholine release at the neuromuscular junction.

Cellular prion protein (PrP(c)), the normal isoform of the pathogenic peptide (PrP(sc)) responsible of the transmissible spongiform encephalopaties (TSEs), is present in many neural tissues, including neuromuscular junctions (NMJ). To analyze if this protein could influence the synaptic transmission, we performed an electrophysiological approach to study the effect of cellular prion protein on a mammalian neuromuscular junction. The loose patch clamp (LPC) technique enables the study of the whole preparation including the pre- and the post-synaptic domains. In a mouse phrenic-diaphragm preparation, nanomolar concentrations of cellular prion protein were able to induce a very striking potentiation of the acetylcholine (ACh) release. The effect was mainly pre-synaptic with an increase of the amplitude of the miniature end-plate currents, probably calcium dependent. Moreover, an apparent facilitation of the synaptic transmission was noted. The results clearly indicate that cellular prion protein may play a key role in the function of the neuromuscular junction.     

Wollastonite Fibers in Vitro Generate Reactive Oxygen Species Able to Lyse Erythrocytes and Activate the Complement Alternate Pathway

Wollastonite fibers were tested in vitro for their ability toproduce reactive oxygen species (ROS) with two different systems:a cell-free reactive mixture containing deoxyribose and a polymorphonuclearleukocyte suspension. After adding the fibers, we measured thethiobarbituric acid-reactive substances pduced by deoxyribosedegradation and luminol-enhanced chemiluminescence, respectively.Compared with asbestos, wollastonite fibers produced higherROS levels both in the PMN suspensions and in the cell-freereactive mixtures. A large amount of these ROS were not hydroxylradicals. Indeed we obtained remarkable differences in ROS generationbetween unground and ground wollastonite fibers and negativeresults with fibers modified with ferric chloride and dithionite.In addition, ROS generation was partially inhibited (by 46–54%)in the reactions performed in the presence of 1,3-dimethyl-2-thiourea(DMTU), a strong hydroxyl radical scavenger. Wollastonite fiberswere also analyzed for their ability to lyse erythrocytes andactivate complement. Hemolytic potency was about twice thatof chrysotile and half that of crocidolite. The levels of complementactivation (via the alternate pathway) were about four-fifthsof those measured in zyrnosan-activated plasma (a typical stimulusused to activate the alternate pathway), equal to those obtainedwith crocidolite, and two-thirds of those found with chrysotile.The addition of DMTU markedly reduced both these activities.Since asbestos fiber toxicity is mainly due to hydroxyl radicalgeneration, our results indicate that wollastonite fibers areprobably less toxic than asbestos fibers.