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Duchenne muscular dystrophy (DMD) is a genetic disorder in which the inherited absence of a muscle protein results in the progressive deterioration of muscle strength and eventual death. Research studies have suggested that the downward course of the illness may be slowed significantly by treatment with steroid drugs. In a previous study, it was not only demonstrated that prednisone was superior to placebo in maintaining muscle strength, but also that a daily dose of prednisone was superior to treatment every other day. When these findings became conclusive, 92 boys participating in the study were all placed on daily prednisone therapy. The results from two years of treatment (three, if counting the previous experimental period) now indicate that the steroid therapy has significantly slowed the progression of DMD. Data at the end of three years may indicate that improvement was related to several factors. The boys experienced an increase in muscle strength when they began prednisone treatment; it is possible that this temporary increase gave them an advantage, and that the rate of decline after the first six months has been about the same. Regular measurements of muscle strength and performance indicate that this is not the case. The boys experienced an increase in muscle strength which peaked by six months. However, the decline in muscle strength thereafter occurred at a slower rate than is generally observed among patients with DMD. Indeed, the expected annual decline in muscle performance scores is almost five times greater than the decline that has been observed among the prednisone-treated patients. These results confirm that prednisone slows the progression of DMD for at least three years. The benefits of prednisone must be weighed against the side effects of steroid treatment, which include weight gain and the typical puffiness of the skin. (Consumer Summary produced by Reliance Medical Information, Inc.)

Summary: Visual homing is a local navigation technique used to direct a robot to a previously seen location by comparing the image of the original location with the current visual image. Prior work has shown that exploiting depth cues such as image scale or stereo-depth in homing leads to improved homing performance. While it is not unusual to use a panoramic field of view (FOV) camera in visual homing, it is unusual to have a panoramic FOV stereo-camera. So, while the availability of stereo-depth information may improve performance, the concomitant-restricted FOV may be a detriment to performance, unless specialized stereo hardware is used. In this paper, we present an investigation of the effect on homing performance of varying the FOV widths in a stereo-vision-based visual homing algorithm using a common stereo-camera. We have collected six stereo-vision homing databases – three indoor and three outdoor. Based on over 350,000 homing trials, we show that while a larger FOV yields performance improvements for larger homing offset angles, the relative improvement falls off with increasing FOVs, and in fact decreases for the widest FOV tested. We conduct additional experiments to identify the cause of this fall-off in performance, which we term the 'blinder' effect, and which we predict should affect other correspondence-based visual homing algorithms. [ABSTRACT FROM AUTHOR]

A drug called prednisone improves the strength and ability to move about in patients with Duchenne's muscular dystrophy. The patients tested were all young boys, aged five to 15 years. Improvement began after as little as a month and peaked at three months. They became almost twice as fast at rising from a lying position to a standing position. They could walk short distances about a third again as fast as before. The could climb four stair steps nearly twice as fast and could breathe more deeply. Some boys received a higher dose of the drug and some a lower dose, but the size of the dose did not affect their rate of improvement. However, patients who needed braces or wheelchairs before treatment still needed them following administration of the drug. More of a substance called creatine, produced when muscles grow, was detected in their urine, suggesting that the drug helped their muscles to grow. Adverse side effects include weight gain, excessive hair growth, and an accumulation of fat on the face, neck and trunk.

Developing computer-aided approaches for cancer diagnosis and grading is currently receiving an increasing demand: this could take over intra- and inter-observer inconsistency, speed up the screening process, increase early diagnosis, and improve the accuracy and consistency of the treatment-planning processes.The third most common cancer worldwide and the second most common in women is colorectal cancer (CRC). Grading CRC is a key task in planning appropriate treatments and estimating the response to them. Unfortunately, it has not yet been fully demonstrated how the most advanced models and methodologies of machine learning can impact this crucial task.This paper systematically investigates the use of advanced deep models (convolutional neural networks and transformer architectures) to improve colon carcinoma detection and grading from histological images. To the best of our knowledge, this is the first attempt at using transformer architectures and ensemble strategies for exploiting deep learning paradigms for automatic colon cancer diagnosis. Results on the largest publicly available dataset demonstrated a substantial improvement with respect to the leading state-of-the-art methods. In particular, by exploiting a transformer architecture, it was possible to observe a 3% increase in accuracy in the detection task (two-class problem) and up to a 4% improvement in the grading task (three-class problem) by also integrating an ensemble strategy.

Acute toxic exposures in childhood are quite a frequent event in Paediatric Emergency Medicine. Despite that, there are few papers about clinical toxicology in children, at least in Italy. This paper is the first that takes into account both epidemiological aspects and clinical features of acute poisoning in children on a national basis. Collected data show the increased use of activated charcoal as a treatment and the use of the short stay observation unit as an appropriate answer to the real clinical situation, although some aspects are still controversial. It will be necessary to reconsider the whole matter widening the number of participating centres, so that the most controversial aspects may be clarified.

Unlabelled: The objective of this study was to evaluate retention of ALS knowledge and performance among anaesthesiologists, who, in Italy, respond to in-hospital emergencies as team leaders., Methods: 47 anaesthesiologists (23 consultants and 24 residents) were invited at one weeks notice to attend a re-evaluation session, 6 months after successful completion of an ERC ALS course. Knowledge retention was assessed by a multiple choice question test, and skills and management by evaluation of performance as team leader in one of the six standardized CAStest scenarios. During the performance, the timeliness of first defibrillation, completion of the three shock sequence, adrenaline (epinephrine) administration and intubation were recorded. Results were compared between consultants and residents., Results: Compared to the results at the end of the ALS course, the percent of correct answers to the multiple choice question test decreased from 85.89 +/- 5.28% to 79.45 +/- 6.62% (P < 0.001), the number of candidates achieving a pass performance decreased from 47/47 to 30/47 (P < 0.001). Time to first defibrillation was 73.38 +/- 18.72 s, time for completion of the third defibrillation was 113.04 +/- 35.58 s and subsequent ALS interventions were very delayed or forgotten. Comparison between consultants and residents showed that consultants retained knowledge information better, skills decreased comparably in both groups and residents performed tasks faster., Conclusions: The significant decay of ALS skills 6 months post-ALS recorded among anaesthesiologists supports the need for periodical reinforcement during intervals before recertification.

Data collection at Emergency Departments (ED), especially with regard to toxicological aspects, is usually incomplete; they further deteriorate following the recent diffusion of data processing and retrieval systems, possibly different from region to region. The present paper deals with the setting of a computer program, specific for toxicological patients, easy to access from the general data collection system.

Rationale: In the body, heroin is rapidly transformed to 6-acetylmorphine (6-AM) and then to morphine, that in turn is mainly metabolized to morphine-3-glucuronide (M3G) and, at lesser extent, to morphine-6-glucuronide (M6G). Unlike M3G, M6G is a potent opioid agonist. Intravenous heroin abusers (IHU) are exposed to a wide array of drugs and contaminants that might affect glucuronidation., Objectives: We assessed plasma and urine concentrations of M3G and M6G in four groups of subjects: the first two included long-term IHU either exposed to street heroin ( n=8) or receiving a single IV injection of morphine ( n=4), while the other two groups included non-IHU patients receiving acute IV ( n=8) or chronic oral ( n=6) administrations of morphine., Methods: After solid phase extraction plasma and urine concentrations of morphine metabolites were determined by HPLC analyses., Results: M3G accounted for the greater part of morphine glucuronides detected in body fluids of non-IHU patients treated with morphine. This pattern of metabolism remained stable across 15 days of oral administration of incremental doses of morphine. In contrast, the two groups of IHU (street heroin taking or morphine-treated subjects) showed a reduction of blood and urine M3G concentrations in favor of M6G. Consequently, M6G/M3G ratio was significantly higher in the two IHU groups in comparison with the non-IHU groups., Conclusions: Chronic exposure to street heroin causes a relative increase in concentrations of the active metabolite, M6G. Since the pattern of M6G action seems closer to heroin than to morphine, the increased synthesis of M6G observed in IHU may prolong the narrow window of heroin effects.

Background: Previous studies have shown that a profound suppression of immune function transiently occurs in patients who undergo surgery under general anesthesia. The decline in the absolute counts of peripheral blood lymphocytes constitutes a major factor accounting for this immune defect, and recent evidence indicates that apoptosis plays a crucial role in determining postsurgical lymphocytopenia., Hypothesis: An altered oxidation-reduction status of mitochondria may contribute through apoptosis to the loss of lymphocytes following surgical trauma and general anesthesia., Design: We studied 16 patients with American Society of Anesthesiologists' physical status I or II who underwent elective surgery under general anesthesia. The data were collected prospectively., Setting: University hospital., Main Outcome Measures: Samples of peripheral blood were drawn on the day before surgery and at 24 and 96 hours after the operation. Following lymphocyte isolation, the mitochondrial transmembrane potential was assessed by flow cytometry using 3,3'-dihexylocarbo-cyanine iodide, and stains with hydroethidine and 2'-7'-dichlorofluorescein diacetate were used to determine the generation of reactive oxygen species. The labeling of lymphocytes with monobromobimane was used to assess the presence of reduced glutathione., Results: At 24 hours after surgery, we detected a significantly elevated frequency of peripheral blood lymphocytes (P =.002), which incorporated low levels of 3,3'-dihexylocarbo-cyanine iodide, compared with the preoperative period. At this same time point, the frequency of lymphocytes with the hydroethidine- and 2'-7'-dichlorofluorescein diacetate-positive phenotype was elevated compared with baseline levels. Conversely, at 24 hours after surgery, the frequency of cells that stained positive for glutathione was strongly decreased compared with preoperative values. Overall measurements returned to the baseline levels at 96 hours after surgery., Conclusion: The strict association we observed between the overproduction of reactive oxygen species and the disruption of the mitochondrial transmembrane potential supports the view that alterations in mitochondrial energy metabolism, paralleled by the presence of a pro-oxidant oxidation-reduction status, could be involved in the accelerated apoptotic loss of lymphocytes following surgical trauma and general anesthesia.

From 1 January 1998 to 31 October 1999 the two Poison Control Centres active in Rome provided 923 telephone consultations for individuals and health care providers on suspected poisonings involving pesticides. Exposures more frequently reported in association with suspected cases were insecticides (n. 636), including organophosphates (n. 300), carbamates (n. 155), pyrethroids (n. 102), and organochlorines (n. 79). Children aged 1-4 years accounted for 22% of all suspected poisonings (n. 200). Each case was classified as to the likelihood of a relationship between the reported pesticide exposure and the occurrence of health effects. Around 18% of suspected pesticide poisonings (n. 168) were subsequently classified as definite, around 43% (n. 390) as possible, and around 37% were considered unlikely (n. 344).

Background: Surgery and anesthesia cause depression of cell-mediated immunity in the postoperative period, including a reduction in the numbers of circulating lymphocytes. It has been claimed that this immunosuppression is associated with an increased incidence of postoperative infections., Hypothesis: Lymphocytopenia following surgical trauma depends on a dysregulated expression of death/and survival factors associated with apoptosis that, in turn, interferes with the occurrence of postsurgical infections., Design: Fifteen subjects undergoing elective surgery under general anesthesia entered the study. The data of the patients who had infections during the postoperative outcome were compared with the data of those who did not. The data were collected prospectively., Main Outcome Measures: Peripheral blood samples were drawn before the operation, and 24 hours and 96 hours after the operation. Lymphocytes were isolated and examined for quantification and phenotypic analysis of apoptosis using the 7-amino-actinomycin D method, as well as for Fas and Fas ligand, interleukin 1-converting enzyme p20/caspase-1, Bcl-2, and p35 expression. The rate of apoptotic cells was correlated with the incidence of postoperative infections., Setting: University hospital., Results: Twenty-four hours after surgery, CD4(+) and CD8(+) cells exhibited a significantly higher frequency of apoptosis as well as of Fas and Fas ligand and interleukin 1-converting enzyme p20/caspase-1 expressions than preoperatively. This increase was paralleled by a significant down-regulation of antiapoptotic factors such as Bcl-2. However, the expression of the proapoptotic factor p35 was reduced. In addition, we found a relationship between the rate of the apoptotic CD8(+) subset and the occurrence of infectious complications during the postoperative course. At 96 hours after surgery, the variables studied returned to the baseline levels., Conclusions: In the early postoperative period, surgical trauma under general anesthesia induces an intracellular perturbation on peripheral lymphocytes, resulting in both up-regulation of death-signaling factors and down-regulation of survival-signaling factors. The increased apoptosis of CD8(+) lymphocytes, but not of CD4(+) cells, seemed to be associated with a greater risk of postsurgical infections.

Objectives: To investigate the concentrations of mononuclear cell-associated ceramide and serum tumor necrosis factor-alpha (TNF-alpha) in patients with sepsis and to assess their predictive value for the development of multiple organ dysfunction syndrome (MODS)., Design: Prospective, cohort study., Setting: Intensive care unit and two research laboratories at a university hospital., Patients: Twenty-three adult patients admitted to an intensive care unit meeting the criteria for diagnosis of sepsis., Interventions: Blood samples were collected at the time when diagnosis of sepsis was made., Measurements and Main Results: Mononuclear cell-associated ceramide and serum TNF-alpha were significantly elevated in the samples from the septic patients compared with the control individuals (318.01+/-270.15 pmol/10(6) cells vs. 99.90+/-52.75 pmol/10(6) cells; p<.001, and 28.52+/-18.77 pg/mL vs. 10.43+/-3.37 pg/mL; p<.0001, respectively), and a direct correlation linked ceramide and TNF-alpha concentrations (r2 = .90, p<.00001). In the septic patients who went on to develop MODS, ceramide and TNF-alpha were significantly higher compared with the no MODS patients (489.22+/-264.93 pmol/10(6) cells vs. 131.23+/-99.02 pmol/10(6) cells; p<.0001, and 40.96+/-18 pg/mL vs. 14.95+/-5.60 pg/mL; p<.001, respectively). The receiver operating characteristic curves demonstrated that both TNF-alpha and ceramide were prognostic of MODS, but ceramide concentrations were more efficient predictors., Conclusions: These observations suggest that mononuclear cells of peripheral blood from patients with sepsis are committed to undergo apoptosis, because there is evidence that ceramide acts as an endogenous mediator of apoptosis. The strong correlation we found between cell-associated ceramide and serum TNF-alpha supports the hypothesis that this cytokine plays an important role in activating the sphingomyelin pathway and ceramide generation in patients with sepsis. In addition, this study provides evidence that consistent concentrations of mononuclear cell-associated ceramide may predict progression toward MODS in septic patients.

To verify the impact on stress response and the influence of anesthesia on endocrine/immunologic changes, we have investigated the plasma level of norepinephrine, cortisol, TNFalpha, and IL-6 in 46 patients scheduled for laparotomy and laparoscopic cholecystectomy at 2, 6, 12, and 24 h after the operation. Among subjects who underwent open approach, 9 received fentanyl anesthesia and 13 received isoflurane anesthesia. In the laparoscopy group, 14 patients were given fentanyl anesthesia and 10 were given isoflurane anesthesia. The results obtained confirmed that laparoscopic cholecystectomy is associated with a lesser immunoendocrine response, and the two anesthesia models do not interfere with plasma changes of the assessed hormones and cytokines.

In this study we tested for TNF alpha concentrations 45 subjects undergoing elective prostatectomy performed under two different anaesthetic regimens. In addition, given the influence of neuroendocrine axis on immunological homeostasis, we also determined post surgery cortisol and norepinephrine levels. The patients were randomly assigned to one of two groups: group 1 (no. = 24) received NLA general anaesthesia, whereas group 2 (no. = 21) received spinal analgesia. Blood samples were drawn the day before surgery (t0), at two (t1), at 24 (t2), at 48 (t3) and 72 (t4) hours from the completion of operation. In the patients assigned to the general anaesthesia group an increase of circulating TNF alpha was detected through t1 to t4. In the spinal group TNFa values did not change in t1 and t2, whereas enhanced levels of the cytokine--overlapping with those of group 1--were observed at 48 and 72 hrs following surgery. Cortisol response increased in both the groups, peaking at t1 but, at this time patients undergoing spinal anaesthesia were found to have significantly lower circulating cortisol. A rise of plasma norepinephrine was observed at t1 in the general anaesthesia group alone. For the early TNF alpha increase, observed in group 1 only, we hypothesize that anaesthetics, such as NLA agents, may trigger a TNF alpha release in vivo. Alternatively TNF alpha production may represent the result of the neuroendocrine response such as cortisol and norepinephrine, to the surgical/anaesthetic trauma which could be blocked by subarachnoid anaesthesia. Conversely, the late TNF alpha increase found in all the patients studied might be explained by postoperative infections as well as by inflammation of the injured tissues and/or normal wound healing.

Purpose: This study investigates heat shock protein 70 (HSP70) expression by peripheral blood mononuclear cells (PBMCs) of septic patients admitted to an intensive care unit and examines the possibility of a correlation between HSP70 levels and plasma tumor necrosis factor alpha (TNF-alpha) concentrations. Additionally, we evaluated whether the HSP70 production could be regarded as a prognostic factor for the development of septic shock as well as for patient survival., Materials and Methods: Blood samples of 29 patients were taken 24 hours after the diagnosis of sepsis. HSP70 expression and TNF-alpha level were measured using indirect immunofluorescent analysis and a commercially available enzyme-linked immunosorbent assay method, respectively., Results: PBMCs expressed significantly high levels of HSP70 (11.9 +/- 5.6 [sd]) compared with those of the healthy control group (3.2 +/- 2.1% positive cells). Such enhanced levels were correlated to plasma TNF-alpha concentrations (r = .99, P < .01). This study failed to demonstrate a relationship between HSP70 production and clinical outcome., Conclusion: These findings give further evidence that also in humans, heat shock response is activated during sepsis. The correlation observed between HSP70 overproduction and TNF-alpha plasma concentrations suggests that HSP70 exerts a possible protective effect against TNF-alpha cytotoxicity. Such hypothesis has not been confirmed by our clinical data.

Objective: Evaluation of respiratory function after 24 hours from intervention related to two different surgical techniques of cholecistectomy., Patients and Methods: Thirty patients submitted to cholecystectomy, nine by laparotomy and twenty-one by video-laparoscopy. The ventilatory parameters considered are as follows: CV, FCV, VEF1, FEF25-75%; and moreover also some variables of acid-base balance: pH, paCO2 e paO., Results: In all cases was evidenced a decrease of respiratory activity. This phenomenon was more evident in the laparotomy group (CV = 37, 35, FCV = 41, 47, VEF1 = 40, FEF25-75% = 36.62% related to preoperative values versus 71.20, 80.88, 79.29, 77.91% in the videolaparoscopic group. No significative differences were registered between the two groups as to postoperative paO2, which was moderately lower in all patients, while no variation was observed for pH and paCO2., Conclusions: Data collected confirm that after laparoscopic cholecystectomy the ventilatory respiratory capacity is better conserved, that clinically means lower incidence of postoperatory pulmonary complications.

The authors report a case of ethanol-induced coma treated successfully with naloxone, in a subject undergoing liver metastasis alcoholization. A dose of ethanol 95 degrees (150 ml) was injected intraoperatively into the hepatic tumor with ultrasound monitoring, in a 55-year old woman which underwent mastectomy two years ago for breast cancer. At the end of operation that went on for 128 minutes, the patient maintained during surgery with standard NLA II anaesthesia did not awake. Toxicologic testing of blood showed an alcohol concentration of 1.9 g/l. Intra-venous naloxone 2 mg was given in boluses of 0.4 mg, through a time of 30 minutes. The patient became progressively responsive with complete recovery 20 minutes later. Since fentanyl doses administered during general anaesthesia were very low, the authors believe that the postoperative coma was due to ethanol overdose. They suggest naloxone as effective treatment to reverse the depressant effects of ethanol following ultrasonically guided alcohol injection therapy.

Background: Myoblast transfer has been proposed as a technique to replace dystrophin, the skeletal-muscle protein that is deficient in Duchenne's muscular dystrophy. Donor myoblasts injected into muscles of affected patients can fuse with host muscle fibers, thus contributing their nuclei, which are potentially capable of replacing deficient gene products. Previous controlled trials involving a single transfer of myoblasts have been unsuccessful., Methods: We injected donor muscle cells once a month for six months to the biceps brachii muscles of one arm of each of 12 boys with Duchenne's muscular dystrophy. The opposite arms served as sham-injected controls. In each procedure 110 million cells donated by fathers or brothers were transferred. The patients were randomly assigned to receive either cyclosporine or placebo. Strength was measured by quantitative isometric muscle testing. Six months after the final myoblast transfer, the presence of dystrophin was assessed with the use of peptide antibodies specific to the deleted exons of the dystrophin gene., Results: There was no significant difference in muscle strength between arms injected with myoblasts and sham-injected arms. In one patient, 10.3 percent of muscle fibers expressed donor-derived dystrophin after myoblast transfer. Three other patients also had a low level of donor dystrophin (< 1 percent); eight had none., Conclusions: Myoblasts transferred once a month for six months failed to improve strength in patients with Duchenne's muscular dystrophy. The value of exon-specific peptide antibodies in the interpretation of myoblast-transfer results was demonstrated in a patient with Duchenne's muscular dystrophy who had a high percentage of donor-derived dystrophin. Specific variables affecting the efficiency of myoblast transfer need to be identified in order to improve upon this technique.

Purpose: This study aimed to investigate the predictive value of neopterin and soluble interleukin-2 (IL-2) receptor for shock occurrence in gram-negative sepsis., Methods: We examined 57 patients admitted to an intensive care unit with gram-negative sepsis diagnosed according to preestablished criteria. Blood samples were collected every 24 hours and neopterin and soluble IL-2 receptor were measured by using commercially available test kits. To judge the predictive significance of these analyses the Cox proportional hazards regression model was used., Results: Both neopterin (P < .05) and soluble IL-2 receptor (P < .01) were identified as significant predictors of a shock state, but the prognostic strength of neopterin exceeded that of soluble IL-2 receptor. To further assess if other factors could interfere with the predictive significance of both compounds, we also investigated other clinical and laboratory variables but these candidate predictors did not contribute any additional significant predictive information., Conclusion: The measurement of serum neopterin and soluble IL-2 receptor concentrations has predictability for identifying patients with gram-negative sepsis at risk for progression toward the syndrome of septic shock.

Removal of acoustic neuromas may often imply anesthesiological as well as surgical problems, especially in the case of large tumors (> 3 cm) which may have come into contact with vital neighbouring structures (brain stem, cerebellum). In this paper the use of two different anesthesiological methods during the translabyrinthine approach is analyzed and discussed in the light of the different needs in this type of surgery. More specifically, anesthesia maintenance was assured by constant infusion of either Propofol (4 mg/kg/h) or Isoflurane (1-1.5%). Withdrawal of curarization was also planned in order to allow the surgeon to take advantage of routine intraoperative facial nerve monitoring. Arterial pressure, CO2 and O2 were assessed at prefixed phases of the operation. Both anesthesiologic methods proved to be satisfactory during the entire surgical procedure. During dissection of the tumoral capsule, an increased heart rate (7% of the initial value) was noticed, whilst in only three patients (with tumors larger than 3.5 cm) a severe bradycardia, which did not respond to Atropine administration and which subsided spontaneously during temporary suspension of surgical manoeuvres, occurred. After this preliminary experience, the Authors believe that both techniques could have a major role in translabyrinthine acoustic tumor surgery and auspicate their further application.

In 67 patients submitted to surgical procedures serum neopterin (NPT) and Interleukin 2 soluble receptors (IL2R) were evaluated at the end of the operation as well as 24, 48, 72 hours later. Thirty seven of the subjects (Group B) had undergone minor surgery (average time of operation: 40 +/- 10 min.), thirty (Group A) had undergone major surgery (average time: 180 +/- 30 min.). The results showed elevated NPT and IL2R levels in the latter cases and, in particular, 48 and 72 h after surgery. Neopterin levels were positively correlated with IL2R (r = 0.548 p < 0.01). These data suggest an activation of the cellular immune response which parallels the magnitude and length of surgical trauma. Thus NPT and IL2R levels could represent biochemical markers of postoperative disorders of the immune homeostasis.