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Rationale: Mechanical ventilation is a mainstay of intensive care but contributes to the mortality of patients through ventilator induced lung injury. Extracellular Cyclophilin A is an emerging inflammatory mediator and metalloproteinase inducer, and the gene responsible for its expression has recently been linked to COVID-19 infection. Objectives: Here we explore the involvement of extracellular Cyclophilin A in the pathophysiology of ventilator-induced lung injury. Methods: Mice were ventilated with low or high tidal volume for up to 3 hours, with or without blockade of extracellular Cyclophilin A signalling, and lung injury and inflammation were evaluated. Human primary alveolar epithelial cells were exposed to in vitro stretch to explore the cellular source of extracellular Cyclophilin A, and Cyclophilin A levels were measured in bronchoalveolar lavage fluid from acute respiratory distress syndrome patients, to evaluate clinical relevance. Measurements and Main Results: High tidal volume ventilation in mice provoked a rapid increase in soluble Cyclophilin A levels in the alveolar space, but not plasma. In vivo ventilation and in vitro stretch experiments indicated alveolar epithelium as the likely major source. In vivo blockade of extracellular Cyclophilin A signalling substantially attenuated physiological dysfunction, macrophage activation and matrix metalloproteinases. Finally, we found that patients with acute respiratory distress syndrome showed markedly elevated levels of extracellular Cyclophilin A within bronchoalveolar lavage. Conclusions: Cyclophilin A is upregulated within the lungs of injuriously ventilated mice (and critically ill patients), where it plays a significant role in lung injury. Extracellular Cyclophilin A represents an exciting novel target for pharmacological intervention.

BackgroundDespite advances in understanding the pathophysiology of acute respiratory distress syndrome, effective pharmacological interventions have proven elusive. We believe this is a consequence of existing preclinical models being designed primarily to explore biological pathways, rather than predict treatment effects. Here, we describe a mouse model in which both therapeutic intervention and ventilation were superimposed onto existing injury and explored the impact of β-agonist treatment, which is effective in simple models but not clinically.MethodsMice had lung injury induced by intranasal lipopolysaccharide (LPS), which peaked at 48 hours post-LPS based on clinically relevant parameters including hypoxaemia and impaired mechanics. At this peak of injury, mice were treated intratracheally with either terbutaline or tumour necrosis factor (TNF) receptor 1-targeting domain antibody, and ventilated with moderate tidal volume (20 mL/kg) to induce secondary ventilator-induced lung injury (VILI).ResultsVentilation of LPS-injured mice at 20 mL/kg exacerbated injury compared with low tidal volume (8 mL/kg). While terbutaline attenuated VILI within non-LPS-treated animals, it was ineffective to reduce VILI in pre-injured mice, mimicking its lack of clinical efficacy. In contrast, anti-TNF receptor 1 antibody attenuated secondary VILI within pre-injured lungs, indicating that the model was treatable.ConclusionsWe propose adoption of a practical framework like that described here to reduce the number of ultimately ineffective drugs reaching clinical trials. Novel targets should be evaluated alongside interventions which have been previously tested clinically, using models that recapitulate the (lack of) clinical efficacy. Within such a framework, outperforming a failed pharmacologic should be a prerequisite for drugs entering trials.

Aim of the Study Barrett's esophagus (BE) could be a rare late complication in children with repaired esophageal atresia, partly due to a long-term history of gastro-esophageal reflux disease (GERD). Radiofrequency ablation (RFA) is the best endoscopic technique in adults with BE and dysplasia. Guidelines do not support this approach for non-dysplastic BE. Aim of this study is to present our experience as Tertiary Gastroenterology referral Centers in the treatment of children and young adults with BE using RFA. Methods A multicenter retrospective study conducted on children with BE, subjected to RFA at the Digestive Surgery and Endoscopy Unit, Bambino Gesù Children's Hospital and the Department of General Surgery ‘Paride Stefanini’, Sapienza University of Rome, between June 2012 and December 2017.Demographic and clinical data were collected. BE characteristics according to Prague classification, presence and grade of dysplasia, number of RFA treatments, complications, clinic and endoscopic outcomes were described. All patients were treated with HALO RF BARRXtm (HALO 360 Covidien, Sunnyvale, California, USA). Endoscopic evaluation and treatment were performed every 3 months until complete eradication. Endoscopic follow-up was: 6 months after eradication, and then annually. Results Five patients were evaluated (M:5). Mean age at diagnosis was 14.4 years (range: 9–17); mean age at first treatment was 23 years (range: 13–36). Two patients presented with repaired esophageal atresia (long gap, type 3 atresia), 3 with peptic strictures. All patients exhibited a long-term history of symptomatic GERD and PPI dependency. Four patients underwent Nissen fundoplication before BE diagnosis. All patients presented with long segment BE (mean baseline length was 8,8 cm, range 7–10 cm). According to the Prague classification, patients were classified as follows: C0M7, C0M17, C8M10, C0M9 and C4M8. One patient presented with LGD. Patients received a mean of 3 HALO treatments (range 1–4 sessions). Eradication was 100% during 2- to 6-year follow-up (mean 4.5 year). No complications occurred. Conclusions Pediatric patients with EA present an high risk to develop early BE, therefore endoscopic surveillance is mandatory. RFA represents a safe and effective treatment option in patients with early onset BE. Treatment of BE with this technique could be a useful and minimal invasive strategy for dysplasia and cancer prevention.

Hand joint involvement in rheumatic diseases is often precocious and predominant as compared to other skeletomuscular regions. Clinical examination not always allows for easy detection of fluid outpouring and synovial involvement, and undoubtedly does not allow to diagnose pathognomonic bone alterations of several rheumatic conditions. Articular ultrasonography is an innocuous methodology, easily reproducible and directly applied by a rheumatologist. The aim of this vignette is to present ultrasonography elementary lesions of the hand for a prompt diagnosis.

To study heel fat pad (HFP) inflammatory-oedematous lesions in selected patients with rheumatoid arthritis (RA) using ultrasonography (US) and power Doppler US (PDUS), to describe and compare US features of these lesions with those obtained with magnetic resonance imaging (MRI), and to describe changes in the lesions after a short-term follow-up with conventional or anti-tumour necrosis factor-alpha (TNFalpha) therapy.Twelve heels of eight RA outpatients with HFP inflammatory-oedematous lesions were studied by US, PDUS, and unenhanced MRI. All the patients were followed up and US was performed after 3 months. Five patients started on anti-TNFalpha therapy.HFP lesions appeared at US as a heterogeneous and hypoechoic subcalcaneal mass, with loss of normal lobular structure and increased thickness of HFP, because of focal rupture of fibrous septae with oedema and fluid. PDUS showed peripheral vascularization of HFP lesions in 9/12 heels. In 3/12 heels some vascular signals was also detectable inside the lesion, always along the residual echoic septa. No detectable flow was observed within the central fluid-filled spaces. MRI of the HFP lesions showed areas of mean intensity in T1-weighted sequences and high intensity in T2-weighted sequences, with poorly or well-defined margins. After 3 months, PDUS showed reduction in HFP lesion vascularity (associated with reduction in pain) in 10/12 heels, while poor regression of grey-scale US abnormalities was observed.Both US and MRI are capable of demonstrating structural abnormalities in the HFP. PDUS is useful to assess and monitor inflammatory vascularization of the HFP lesions.

Heel fat pad inflammation and degeneration have been frequently proved to cause talalgia. Painful heel fat pad is often confused with plantar fasciitis, and only magnetic resonance imaging (MRI) or ultrasonography (US) can differentiate these conditions. Scanty data are available about heel fat pad involvement in the course of chronic polyarthritis.To investigate with US the heel fat pad involvement in patients with rheumatoid arthritis (RA) and spondyloarthropathies (SpA); to describe and compare the clinical and sonographic features of this lesion in the two groups.The heels of 181 consecutive outpatients with RA and 160 with SpA were studied by US and radiography. A control group of 60 healthy subjects was examined by US.Two different patterns of involvement of the heel fat pad were observed. The inflammatory-oedematous pattern was more frequent in patients with RA (6.6%) than in those with SpA (1.8%), and was associated with talalgia--even if it was not associated with plantar fasciitis or enthesophyte (bony spur). The degenerative-atrophic pattern was less frequent (1.1% in RA, 1.9% in SpA), and was associated with plantar fasciitis and subcalcaneal enthesophyte.The inflammatory-oedematous lesion of the heel fat-pad is relatively frequent in RA and causes subcalcaneal pain. Degenerative-atrophic changes of the heel fat pad can be observed in RA and SpA, and seem to be associated with chronic abnormalities of the plantar fascia and of its enthesis.

To establish by ultrasonography (US) the frequency of calcaneal entheses involvement in erosive osteoarthritis (EOA), nodal osteoarthritis (NOA), RA and PsA, and to compare these results in order to aid clinicians in the differential diagnosis among these diseases. A comparison between US results and radiography was also made.The heels of 56 consecutive outpatients with EOA, 209 with NOA, 158 with RA and 125 with PsA were studied by US and radiography. A control group of 50 subjects was examined by US.US showed no significant difference in inferior calcaneal enthesophytosis among the four diseases. The frequency of posterioinferior enthesophytosis was lower in RA (34%) in comparison with the other diseases (57% in EOA, 47% in NOA, 49% in PsA). Achilles enthesitis was found in 8% of PsA and in 2% of RA. Retrocalcaneal bursitis was found in 18% of RA and in 6% of PsA. Posterior erosions were present in 12% of RA and 5% of PsA. Inferior erosions were present in 6% of RA and in 1% of PsA. Plantar fasciitis was found in 26% of RA, in 37% of PsA, and in 15% of NOA and 12% of EOA. Subcalcaneal panniculitis was observed in 10% of RA and in 1% of PsA. In the control group, only posterioinferior and inferior enthesophytosis (22% and 18% respectively) were found. Kappa statistics show excellent agreement between US and radiography in detecting posterioinferior (kappa = 0.89) and inferior enthesophytosis (kappa = 0.83), and entheseal erosions (kappa = 0.86).The calcaneal lesions that could be found in EOA are similar to those observed in NOA. The frequency of calcaneal enthesophytosis is similar in EOA, NOA, and PsA, but inflammatory lesions of calcaneal entheses and of the adjacent bursae are more frequent in RA and in PsA. In terms of heel involvement, EOA seems to be similar to NOA. US shows an excellent concordance with radiography in detecting entheseal cortical bone abnormalities.

Enthesitis is an inflammatory lesion of the tendon, ligament and capsular insertions into the bone, and it is a fundamental element in the diagnosis of spondyloarthropathies. Sonography is the method of choice for studying periarticular soft tissues because it is capable of detecting both the early (oedema, thickening) and the late alterations (erosions and enthesophytes); it is also an inexpensive, biologically harmless and easily repeatable technique. The aim of this study was to compare the prevalence of quadricipital enthesitis in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients, and to document any clinical and echostructural differences in this lesion between the two diseases. The results show that enthesitis is more frequent in PsA patients, more than half of whom are asymptomatic. Knee inflammation was found in the PsA patients with enthesitis regardless of the concomitant presence of joint effusion; none of the RA patients suffered from enthesitis alone. Quadricipital enthesitis is more frequent in male patients. There was no significant correlation between the presence of peripatellar psoriatic lesions and enthesitis. Sonographic examinations of patients with enthesitis revealed that those with RA had dominantly inflammatory lesions, whereas PsA patients also showed major new bone deposition.

Objective: to study the frequence of deltoideal proximal insertion enthesitis (DPIE) in patients affected with spondyloarthritis (SpA) and to evaluate its clinical, sonographic and radiological characteristics. Methods: a retrospective study of clinical, sonographic and radiological examinations of the shoulders of 100 symptomatic consecutive outpatients with SpA, compared to 4 groups of control patients: 100 with Rheumatoid Arthritis, 100 with Osteoarthritis, 100 with Painful Shoulder, and 50 with shoulders undamaged by local pathological processes. Results: the frequence of DPIE in the course of SpA was 9%. DPIE appears most frequently in Psoriatic Arthritis (PsA) (17%, 7/41). DPIE does not appear to be related to the sex or the age of the patient. The clinical signs and symptoms are similar to those of an impingement syndrome. Sonography reveals thickening and hypoechogenicity of the enthesis, associated or not to the subchondral osseous rearrangement and enthesophytosis. Radiology only reveals the ent...

The present multicenter double-blind placebo-controlled trial evaluates the therapeutic effectiveness of small-volume daily doses of an isosmotic polyethylene glycol (PEG) electrolyte solution in the treatment of chronic nonorganic constipation. After a complete diagnostic investigation, patients still constipated at the end of a four-week placebo-treatment run-in period were enrolled and randomized to receive either placebo or PEG solution 250 ml twice a day for the following eight weeks. Patients were assessed at four and eight weeks of treatment, and they reported frequency and modality of evacuation, use of laxatives, and relevant symptoms daily on a diary card. Oroanal and segmental large-bowel transit times were assessed with radiopaque markers during the fourth week of the run-in period and the last week of the treatment period. During the study period, dietary fiber and liquids were standardized and laxatives were allowed only after five consecutive days without a bowel movement. Of the 55 patients enrolled, five dropped out, three because of adverse events and two for reasons unrelated to therapy; another two were excluded from the efficacy analysis because of protocol violation. Of the remaining 48 patients (37 women, age 42 +/- 15 years, mean +/- SD), 23 were assigned to placebo and 25 to PEG treatment. In comparison to placebo, PEG solution induced a statistically significant increase in weekly bowel frequency at four weeks and at the end of the study (PEG: 4.8 +/- 2.3 vs placebo: 2.8 +/- 1.6; P0.002) and a significant decrease in straining at defecation (P0.01), stool consistency (P0.02), and use of laxatives (P0.03). Oroanal, left colon, and rectal transit times were significantly shortened by PEG treatment. There was no difference between controls and PEG-treated patients as far as abdominal symptoms and side effects were concerned. In conclusion, PEG solution at 250 ml twice a day is effective in increasing bowel frequency, accelerating colorectal transit times, and improving difficult evacuation in patients with chronic nonorganic constipation and is devoid of significant side effects.

Volume guarantee ventilation (VGV) is an optional ventilation mode which has become the most widely and extensively studied in the last 10 years in premature infants. Nonetheless, theoretical expected endpoints are intriguing and even though VGV has not yet become 'the' standard ventilation mode, a great deal of information has been acquired and stored. In our experience, VGV during the course of respiratory distress syndrome is useful and can be considered a standard ventilation mode. Weaning occurs in real time as described earlier, and synchronized intermittent positive pressure ventilation and pressure support ventilation (PSV) seem to be the preferred combined modes. Management during the acute phase requires more care since several sudden changes take place in both the lung mechanics and clinical behavior. The software is designed to protect the lung, and subsequently, sudden changes in lung compliance following iatrogenic procedures such as surfactant administration are powerfully counteracted. VGV has been extensively studied and the proposed algorithm has been found to function as planned. Although the 'superiority' of one method over another cannot be demonstrated, the use of new technologies require 'a staff learning curve' and homogeneity of treatment, while at the same time other factors, such as patient heterogeneity or illness phase, should be taken into due account.

JIA is a chronic disease that can involve many different joints including TMJ. TMJ involvement leads to: chewing function alteration due to synovial membrane thickening, masticator muscle weakness and facial pain; craniofacial growth disturbance (micrognathia or facial asymmetry). The aim of our study is to evaluate the TMJ in people affected by JIA for early diagnosis of TMJ arthritis. Our series included 51 consecutive patients with JIA, 16 males and 35 females (age range 4 – 19 years), that were evaluated through a rheumatologic and dentist examination. Clinically suspected cases were studied with Magnetic Resonance Imaging (MRI). Our results showed that 19/51 patients (37%) (age range 9 – 19 years) had TMJ alterations, 10/19 (19,6%) concerning the left one while 7/19 (13,7%) the right one. Only 2/19 (4%) had a bilateral involvement. TMJ arthritis can severely affect the growth of mandibular, it can be asymptomatic in the majority of cases but it is present in about 50% of children with JIA. MRI is useful to evidence the assessment of disease activity with precious informations about its evolution. Besides, this imaging technique allows to eliminate X-rays exposure and, in according to its high definition, can show early joints alterations also in apparently asymptomatic children. In our patients, MRI was the gold standard for an early diagnosis showing that 37% of cases had TMJ involvement.

Objective: To assess the efficacy of Cellfood®’s therapy in the treatment of fibromyalgia. Methods: This study was a single-blind, cross-over, randomized placebo-controlled trial. Fourty female were selected from 320 cases investigated in the period 2003-2005 of june. To be included in this study, it was required that the diagnosis of fibromyalgia was made by a specialist in according to the ACR classification criteria of 1990. The patient’s age was between 35-47 years, the choice of criteria were the absence of improvements with the conventional therapy and the normality of medical check-up. The patients were divided into two different-groups of thirty-one and nine subjects, each-one (group A) treated with Cellfood® for six months in according to the Eurodream’s scheme, and each-other (group B) treated with placebo for three months and successively with Cellfood® for three months.Besides we have estimated the tender points with algometer and the health status of women with the Fibromyalgia Impact Questionnaire (FIQ) at the baseline (T0) and at three (T1) and six month (T2). Result: The group A had an appreciable improvement of the parameters at T1 statistically significant compared to the group B, while we observed a stability of they at T2 on the group A and an improvementof the parameters of the group B statistically non significant compared to each-one. Conclusion: Our result suggest that the Cellfood®’s therapy improve fibromyalgia symptoms and health-related quality of life.

Bisphosphonates (BPs) are pharmacological compounds widely used in the treatment of a variety of bone-related diseases, particularly where the bone-turnover is skewed in favour of osteolysis. The mechanisms by which BPs reduce bone-resorption directly acting on osteoclasts (OCs) are now largely clarified even at molecular level. The researches concerning the BPs effects on osteoblasts (OBs) have instead shown variable results. Objectives: We have investigated the efficacy of neridronate (NER), an amino-BP, as anabolic agent on human OBs. Moreover, we have tried to verify if NER is able to negatively modulate the production of IL-6 on OBs stimulated or not by the pro-inflammatory cytokine Il-1b. Methods: We have tested if different concentrations of NER (from 10-11M to 10-3M), added to primary human OB cultures, could affect the cells number, the endogenous cellular alkaline phosphatase (ALP) activity, the collagen I (COLI) synthesis, the formation of mineralized nodules and the IL-6 production. Our experimental approach was performed testing a wide range of NER concentrations because, under physiological conditions, OBs seems to be exposed to variable and transient levels of the drug. Results: Our results show that NER doesn’t negatively affect in vitro the viability, proliferation and cellular activity of human OBs, even after 20 days of exposure to concentrations ²10-5 M (therapeutic dose). In addition, NER seems to enhance the differentiation of cultured OBs in mature bone-forming cells. A maximum increase of COL-I synthesis (+25% after 4 days; p

According to the criteria proposed by Ryan and McCarty,1 the diagnosis of calcium pyrophosphate dihydrate (CPPD) deposition disease has been based on radiological evidence of the characteristic calcifications and on verification of the synovial liquid of CPPD crystals. Joint ultrasonography is an innocuous diagnostic technique that is well tolerated by patients, and is the elected method for observing calcified deposits in soft tissues.2 We carried out a longitudinal study, enrolling patients affected with ultrasonographic chondrocalcinosis according to previously proposed criteria3 from a sample of consecutive patients that came to our joint ultrasonography department for gonalgia (fig. 1). A total of 47 patients were identified, of which 14 had joint effusion. Figure 1 Hyperechoic deposits. Deposits (arrows) are shown that are compatible with calcium pyrophosphate dihydrate (CPPD) calcifications in the context of the synovial membrane (1), hyaline cartilage of the …

Objective: To investigate by high frequency ultrasonography the appearance of calcium pyrophosphate dihydrate (CPPD) calcifications, in the most commonly affected sites in CPPD disease, and the relationship between ultrasonographic CPPD deposits and the presence of CPPD crystals in synovial fluid. Methods: Three ultrasonographic patterns of CPPD calcification were identified and 11 patients enrolled. A control group comprised 13 patients with no evidence of CPPD deposits. Synovial fluid was aspirated from all patients and controls and examined for identification of crystals. All patients underwent a standard radiography examination at the same sites investigated by ultrasound. Results: In all patients with ultrasonographically defined CPPD deposits, CPPD crystals were found in the synovial fluid. In two cases, standard radiographic examination did not show evidence of the calcific deposits that were identified by ultrasonography. CPPD crystals were not found in the synovial fluid of controls. In four control group patients, ultrasonography identified calcifications defined as deposits of another nature. Conclusions: The ultrasonographic pattern used in this study for the diagnosis of CPPD disease demonstrated a very high correlation with the presence of CPPD crystals in synovial fluid. Ultrasonography demonstrated a sensitivity and specificity at least equal to that of radiography in identifying CPPD crystal calcifications.

Generalised radiological osteopenia has been seen to occur in a significant percentage of patients with systemic sclerosis (SSc).1,2 Bone mineral content was found to be reduced at the radius,3–5 lumbar spine, and the total body.5 No data are available on quantitative ultrasound (QUS) evaluation of bone in patients with SSc. In this study, bone mineral density (BMD) and stiffness index (SI) were measured in patients with SSc not treated with steroids to investigate the presence of systemic osteoporosis. Forty seven women (mean age 53.9 years (range 32–77)) affected with SSc were investigated: 20 were premenopausal (preSSc) and 27 postmenopausal (postSSc). All the patients satisfied the preliminary American Rheumatology Association criteria indicated in the classification of progressive SSc. The control group consisted of 50 healthy female subjects: 23 premenopausal (prenorm) and 27 postmenopausal (postnorm). The exclusion criteria …

The aim of this placebo-controlled study was to determine whether once-weekly clodronate could prevent osteoporosis in patients with arthritis at the start of corticosteroid therapy. One hundred sixty-three patients, 18 to 90 years of age, with rheumatoid or psoriatic arthritis, were randomly assigned to receive either clodronate (100 mg im/week) plus calcium and vitamin D (1000 mg and 800 UI, respectively) or calcium and vitamin D alone. Patients had started therapy with prednisone or its equivalent within the previous 100 days and had bone mineral density

Objective—To evaluate the eYcacy of extracorporeal shock wave treatment (ESWT) in calcaneal enthesophytosis. Methods—60 patients (43 women, 17 men) were examined who had talalgia associated with heel spur. A single blind randomised study was performed in which 30 patients underwent a regular treatment (group 1) and 30 a simulated one (shocks of 0 mJ/mm 2 energy were applied) (group 2). Variations in symptoms were evaluated by visual analogue scale (VAS). Variations in the dimension of enthesophytosis were evaluated by x ray examination. Variations in the grade of enthesitis were evaluated by sonography. Results—A significant decrease of VAS was seen in group 1. Examination by x ray showed morphological modifications (reduction of the larger diameter >1 mm) of the enthesophytosis in nine (30%) patients. Sonography did not show significant changes in the grade of enthesitis just after the end of the treatment, but a significant reduction was seen after one month. In the control group no significant decrease of VAS was seen.No modification was observed by x ray examination or sonography. Conclusion—ESWT is safe and improves the symptoms of most patients with a painful heel, it can also structurally modify enthesophytosis, and reduce inflammatory oedema. (Ann Rheum Dis 2001;60:1064‐1067) Painful heel is a common syndrome characterised by severe pain in the inferior or posterior aspect of the heel, which is aggravated by weight bearing, becoming progressively worse and often incapacitating, with evidence of a spur in about 50% of cases. 1 Until now the cause of the condition has been obscure, but numerous factors have been claimed to produce painful heel with a bony spur: functional overuse, degenerative diseases, inflammatory diseases, and metabolic diseases. 2

Manometry is an important tool in the diagnosis of oesophageal motility disorders, but proper instruments and methods are needed to obtain useful clinical information. The authors reviewed the minimal technical requirements, operative aspects, which information the final report should contain as well as indications and contraindications of the text itself. Technical requirements: At least a three-channel, multiple-lumen catheter perfused with a pneumo-hydraulic capillary infusion system which ensures ΔP/ΔT> 150–200 mmHg/sec.; data should be recorded at a sampling rate of >-8 Hz to study the oesophageal body and lower oesophageal sphincter; lower oesophageal sphincter tonic (pressure) and phasic activity (relaxations) and oesophageal body amplitude and peristaltic activity should be recorded. The final report must contain the patient's details, the indication for the test and a manometric diagnosis. Indications for manometry: Dysphagia (after ruling out any organic pathology); non- cardiac chest pain (after ruling out any cardiopulmonary involvement); systemic collagenosis (to investigate oesophageal involvement); gastro-oesophageal reflux disease (if surgery is planned). Contraindications are limited to: pharyngeal or upper oesophageal obstructions, oesophageal bullous disorder, cardiac conditions in which vagal stimulation may not be tolerated, severe coagulopathy and patient non-compliance.

To evaluate the prognostic value of DNA content-ploidy, agoraphilic nucleolar organizing regions (AgNORs) and proliferating cell nuclear antigen (PCNA) for survival among patients with choroidal melanoma choroidal melanomas managed by enucleation in 55 patients with a follow-up of 5 years were studied. AgNor counts were evaluated by two examiners after sections were specifically processed. Immunohistochemistry was performed to evaluate PCNA expression. Kaplan-Meier estimation of survival curves, the log-rank test, and Cox regression analysis were used to compare survival according to the above mentioned factors. Five years after enucleation 62% of patients had died. Patients with spindle cell type melanomas had the best and those with epithelioid cell type had the worst survival (p=0.004). Patients with small tumors had better survival than those with medium or large tumors (p=0.02). Patients having tumors with aneuploid nuclear DNA content had worse survival than those having tumors with diploid DNA content (p=0.004). A high PCNA level correlated with lower survival rates (p=0.02). Patients having a high AgNor count had a worse survival than those with lower counts (p=0.02). DNA content, PCNA level, and AgNOR count each showed a clinically significant influence on patient survival. However, each of these new evaluated prognostic factors was strongly related to one or both of the classic prognostic factors. It is therefore difficult to separate the effects of the two categories of prognostic factors. Results of the Cox regression analysis suggested that these newer evaluated prognostic factors provided little additional information about patient prognosis.

We reviewed 55 consecutive cases of rhegmatogenous retinal detachment treated with pneumatic retinopexy as a primary procedure and followed up for a minimum of 1 year. 40 eyes were phakic, 11 aphakic and 4 pseudophakic. 0.6 ml of sulfur hexafluoride were injected into 42 eyes, while 0.3 ml of perfluoropropane were introduced into 13. Transconjunctival cryotherapy was performed in 51 eyes, while light coagulation was used as retinopexy after the retina was reattached in the remaining 4 cases. Of the 55 eyes undergoing treatment, 46 (83.6%) retinas were reattached with one operation. The benefits, complications and disadvantages of the procedure are reported.

Retinitis pigmentosa (RP) is the most common form of hereditary retinal degeneration, affecting approximately 1 in 3500 individuals.1,2 Classical RP is characterised by progressive night blindness and constriction of the peripheral visual fields, ultimately causing deterioration of the central vision in many patients. These symptoms are accompanied by ophthalmoscopically detectable degenerative and pigmentary changes of the retinal tissue and by reductions of the electrical retinal response to flashes of light using an electroretinogram (ERG). ERG abnormalities are typically present before any detectable retinal change becomes visible to clinical examination. RP can be transmitted by all inheritance modes, with X linked recessive RP (XLRP) accounting for 10–20% of genetically identifiable cases and being reportedly among the most severe forms.1,2 To date, two of the genes responsible for XLRP have been cloned: RP2 3 and the retinitis pigmentosa GTPase regulator, RPGR .4,5 RPGR accounts for the majority of XLRP.6,7 RP or RP-like retinopathies can also be part of syndromic conditions—that is, associated with extra-ocular manifestations. The most common are Bardet-Biedl and Usher syndromes.1,8–11 Usher syndrome is characterised by the association of RP with sensorineural hearing loss of variable severity, and has three broad clinical phenotypes, with types I and II being the most common.9,11 Type I is characterised by profound congenital non-progressive hearing loss, marked speech impediment, and vestibular dysfunction. The hearing loss of Usher syndrome type II is typically mild to moderate, limited to high frequencies, non-progressive in nature, associated with speech abnormalities commensurate to the hearing defect, and with normal or minimally abnormal vestibular function. Usher syndrome is inherited as an autosomal recessive trait, although a pseudo-dominant Usher syndrome-like phenotype due to a mutation in the mitochondrial MTTS2 gene has been described.12,13 Some reports have …

In the past some studies have been carried out to investigate the melt strength of polymers with the purpose of comparing the results obtained with different materials and at different temperatures. In those experimental activities, once that the testing instrument had been chosen, the polymers were considered the object of the investigation and the attention was rarely focused on the testing geometry. The present work, instead, intends to analyze the influence that the geometry of the extrusion die has on the melt strength of polymers. In particular, attention is focused on the analysis of the differences produced on the melt strength of a material, when the extruded filament is subjected, via the use of two different dies specifically designed, to two distinct temperature profiles along the stretching axis. This investigation highlights that the testing geometry chosen for an experimental activity based on melt tension tests, via haul-off measurements, plays a fundamental role in the correct interpretation of the results. In fact it is demonstrated that the correct choice of the extrusion die allows one to obtain results much more similar to the real processing type that, using melt tension tests, has to be analyzed.

In a 6 to 12-week double-blind trial, the effect of cisapride (10 mg q.i.d.) was compared with that of placebo in 63 patients with esophagitis confirmed by endoscopy and/or biopsy. In only one patient (3%) in the cisapride group but in 43% of the placebo patients (p = 0.001), symptoms had not improved after 6 weeks. Forty patients continued treatment until week 12. At that time, control endoscopy showed a significantly (p = 0.005) higher rate of healing (no erosions, ulcers, or bleeding mucosa) in the cisapride patients (63%) than in the placebo patients (12%). At week 12, only three of the 21 cisapride patients still had moderate reflux symptoms, whereas eight of the 19 placebo patients had moderate or severe symptoms (p less than 0.05). Cisapride patients also took significantly (p less than 0.001) less antacids during the trial. These results show that cisapride, 10 mg q.i.d., heals esophagitis lesions and greatly reduces associated symptoms. The treatment was well tolerated.

In 28 postmenopausal women with rheumatoid arthritis, serum osteocalcin (OC) concentration decreased from 5.2 +/- 1.9 ng/ml to 3.0 +/- 1.6 ng/ml after 6 months therapy with corticosteroids (p less than 0.005). No differences, however, were found in a control group of 13 patients treated for 6 months with nonsteroidal anti-inflammatory drugs. In those patients with serial OC measurements, changes in serum OC were already evident within the first month of therapy. This suggests that a suppressed osteoblast function may be detectable early during corticosteroid therapy in rheumatoid arthritis. Fifteen patients treated with prednisone (5-25 mg once daily, mean 12.33 mg/day) showed a more marked decrease in serum OC than 13 patients treated with equivalent doses of deflazacort (p less than 0.005). Prednisone therapy at doses higher than 10 mg/day resulted in a severe suppression of OC values in most cases. The effect of deflazacort was, however, mild in the majority of patients treated with doses of up to 30 mg/day.

The onset of symptoms in patients with gastroesophageal reflux (GER) is usually thought to be associated with the occurrence of GER. However, esophageal acid perfusion does not always elicit the symptoms in the patients (Kjellen and Tib-bling 1985). Moreover, data regarding the association between reflux and symptoms on the basis of prolonged pH measurements are lacking. The aim of our study was thus to verify the existence of a relationship between these events in a group of patients with GER disease.

Cystic fibrosis is characterized by an abnormally high electrolyte concentration in exocrine secretions. The authors performed the tear mucus ferning test in 26 eyes of children with cystic fibrosis and compared the results to those in an equal number of age-matched normals. The results suggest that the increased electrolyte concentration could be responsible for the increased hyperviscosity of mucus. The tear mucus ferning test appears to be a suitable diagnostic test for the assessment of cystic fibrosis.

Background. Chronic persistent cough is a common and disabling disorder and gastro-oesophageal reflux disease is considered to be the third leading cause, after asthma and postnasal drip. Therefore, patients with unexplained chronic persistent cough usually undergo a stepwise evaluation to establish the existence of a reflux disease. Aim. To identify the most cost-effective diagnostic approach to assess gastro-oesophageal reflux disease in patients with unexplained chronic persistent cough. Methods. Direct and indirect costs associated with six diagnostic strategies using 24-h oesophageal pH-metry, oesophago-gastroduodenoscopy and the proton pump inhibitors test in different sequences, were evaluated using a decision tree model. If the first test was positive, the diagnostic work-up was stopped, if negative the patient proceeded to the second test, and so on. Clinical data from an observational prospective trial conducted in 51 patients with unexplained chronic persistent cough were used in the economic model. Results. All six strategies had the same clinical effectiveness (78.4%). The diagnostic work-up with the lowest cost was the proton pump inhibitors test followed by pH-metry and then oesophago-gastroduodenoscopy with a total cost of EURO211.08 (direct EURO142.93, indirect EURO68.15). Conclusions. This study shows that the lowest cost is the strategy where proton pump inhibitors test is performed as first investigation. Implementation of this diagnostic work-up may lead to cost savings in the management of patients with chronic persistent cough. (c) 2006 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.