Reconstructing historical exposure to asbestos: the validation of 'educated guesses'.

BACKGROUND: In both the epidemiological and legal context, the causal attribution of asbestos-related lung diseases requires retrospective exposure assessment (REA). AIMS: To assess the correlation between the retrospective assessment of occupational and anthropogenic environmental exposure to asbestos and its content in the lung tissue. METHODS: Based on the available exposure information, a team of occupational physicians retrospectively assessed cumulative exposure to asbestos in 24 subjects who died of asbestos-related diseases. The asbestos lung content was analysed using analytical scanning electron microscope (SEM-EDS). The Log10 asbestos fibre count in the autoptic samples was predicted as a function of the Log10 estimated cumulative exposure using univariate regression analysis. RESULTS: The median count of asbestos fibres by grams of dry weight (ff/gdw) in the lung tissue was 81 339 (range 0-2 135 849.06); it was 287 144 (range 0-2 135 849.06) among the occupationally exposed, and 29 671 (range 0-116 891) among the subjects who only had anthropogenic environmental and/or household exposure. Amphiboles, and particularly amosite (52%) and crocidolite (43%), were detected in all the study subjects. Chrysotile was not detected in any of the samples. Overall, the retrospective estimate of lifetime cumulative exposure to asbestos showed a moderate correlation with the total asbestos fibre count in the autoptic lung, with the regression model explaining 38-55% of the total variance. CONCLUSIONS: Detailed information on occupational, environmental and household exposure circumstances would be indispensable for experienced industrial hygienists and/or occupational physicians to reliably assess past exposure to amphiboles or mixed types of asbestos.

Hypoalbuminemia in COVID-19: assessing the hypothesis for underlying pulmonary capillary leakage.

BACKGROUND: Since the first observations of patients with COVID-19, significant hypoalbuminaemia was detected. Its causes have not been investigated yet. OBJECTIVE: We hypothesized that pulmonary capillary leakage affects the severity of respiratory failure, causing a shift of fluids and proteins through the epithelial-endothelial barrier. METHODS: One hundred seventy-four COVID-19 patients with respiratory symptoms, 92 admitted to the intermediate medicine ward (IMW) and 82 to the intensive care unit (ICU) at Luigi Sacco Hospital in Milan, were studied. RESULTS: Baseline characteristics at admission were considered. Proteins, interleukin 8 (IL-8) and interleukin 10 (IL-10) in bronchoalveolar lavage fluid (BALF) were analysed in 26 ICU patients. In addition, ten autopsy ultrastructural lung studies were performed in patients with COVID-19 and compared with postmortem findings in a control group (bacterial pneumonia-ARDS and H1N1-ARDS). ICU patients had lower serum albumin than IMW patients [20 (18-23) vs 28 (24-33) g L-1 , P < 0.001]. Serum albumin was lower in more compromised groups (lower PaO2 -to-FiO2 ratio and worst chest X-ray findings) and was associated with 30 days of probability of survival. Protein concentration was correlated with IL-8 and IL-10 levels in BALF. Electron microscopy examinations of eight out of ten COVID-19 lung tissues showed loosening of junctional complexes, quantitatively more pronounced than in controls, and direct viral infection of type 2 pneumocytes and endothelial cells. CONCLUSION: Hypoalbuminaemia may serve as severity marker of epithelial-endothelial damage in patients with COVID-19. There are clues that pulmonary capillary leak syndrome plays a key role in the pathogenesis of COVID-19 and might be a potential therapeutic target.

Vaccination against seasonal influenza and socio-economic and environmental factors as determinants of the geographic variation of COVID-19 incidence and mortality in the Italian elderly.

BACKGROUND: A possible protective effect of seasonal influenza vaccination against the spread of the COVID-19 epidemic has been suggested. METHODS: We used publicly available data bases to explore the hypothesis as well as the effect of multiple social and environmental factors in the 20 Italian regions. RESULTS: Our results suggest that vaccination against seasonal influenza might beneficially impact on incidence and severity of the novel corona virus epidemic. Population density and vehicular traffic were also moderately associated with cumulative incidence of COVID-19. None of the other variables we considered showed an effect on cumulative incidence, case fatality rate or mortality from COVID-19. CONCLUSIONS: Extending influenza vaccination coverage particularly among the elderly, vulnerable individuals with specific chronic medical conditions, health care workers, and workers in other essential services, early in the upcoming 2020 influenza season, might help reduce the health impact of a second epidemic wave of COVID-19.

Shift rotation scheme, sleepiness and sleep quality in night-shift workers.

BACKGROUND: Shift rotation schemes can influence workers' tolerance of night-shift work and its impact on health. AIMS: This study was aimed to assess the influence of shift work rotation schemes on sleepiness and sleep quality. METHODS: We conducted a cross-sectional study of 145 male workers, 77 from a ceramic tile factory on a fixed, forward-rotating shift work scheme, and 68 from a dockyard company, working on-call night shifts. Participants self-administered the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI) questionnaires and provided data on demographic and lifestyle variables. We set two logistic regression models to predict the risk of daytime sleepiness and poor sleep quality as a function of night-shift work and on-call night shifts, adjusting for personal and lifestyle covariates. RESULTS: Marital status, body mass index, smoking and alcohol intake did not affect ESS and PSQI scores, nor did they differ between the two cohorts. Night-shift workers from both cohorts were more likely to have a PSQI score ≥6, suggestive of poor sleep quality, with no variation between the two cohorts. ESS scores suggestive of daytime sleepiness were strongly associated with on-call night shifts among dockyard workers for (odds ratio = 13.4; 95% confidence interval 2.9-63.9), in respect the regular, forward-rotating night-shift work among ceramic tile factory workers. DISCUSSION: Daytime sleepiness occurred more frequently among dockyard workers working on-call night shifts. Poor sleep quality occurred more frequently among night-shift workers, but it did not differ between the two companies.

Management of breast lobular carcinoma in situ: radio-pathological correlation, clinical implications, and follow-up.

PURPOSE OF INVESTIGATION: To show management of patients with breast lobular carcinoma in situ (LCIS). MATERIALS AND METHODS: This study is the retrospective review of 65 patients, between 1996 and 2012, with isolated LCIS of the breast, evaluated through clinical examination, ultrasound, and mammography at the first examination and follow-up. RESULTS: In 53 patients (81.54%), clinical examination was negative. In 14/65 (21.54%) cases, ultrasound was positive and led to biopsy. The clusters of tiny calcifications were the predominant mammographic pattern (45 cases, 69.23%). Forty-six patients (70.77%) underwent surgical biopsy after guided stereotactic placement of metallic marker (hook-wire), 12 (18.46%) by stereotactic vacuum biopsy (SVB), 5 (7.69%) by core needle biopsy (CNB) under ultrasound guidance, two (3.08%) patients CNB with clinically palpable nodules. Fourteen (21.54%) women underwent a quadrantectomy or total mastectomy after the first diagnosis; in this latter group follow-up was negative. Among the 51 patients (78.46%) who did not undergo quadrantectomy or total mastectomy, five relapses occurred, respectively, three LCIS and two infiltrating ductal carcinomas (IDC). Follow-up ranged from 12 to 144 months. CONCLUSION: LCIS is a risk factor for invasive carcinoma and should be managed with careful follow-up, but if there is a discrepancy between pathology and imaging, surgical excision is mandatory.

Effectiveness of multimodal exercises integrated with cognitive-behavioral therapy in working patients with chronic neck pain: protocol of a randomized controlled trial with 1-year follow-up.

BACKGROUND: The etiology of neck pain is multifactorial and includes personal and work-related factors such as age, sex, wrong postures, and repeated strains. Studies based on bio-psychosocial model also link chronic neck pain to psychological factors. Over time, the use of multidisciplinary interventions for chronic neck pain has grown in order to improve disability, pain, and adaptive cognitions and behaviors towards patients' problems. The objective is to evaluate the effectiveness of an individual-based multidisciplinary rehabilitation program that integrates cognitive-behavioral therapy focused on kinesiophobia with specific exercises in the treatment of patients with chronic neck pain, employed in different working activities. METHODS: A randomized, parallel-group superiority-controlled trial will be conducted with 1-year follow-up. One hundred seventy patients engaged in several working activities (blue collar and white collar workers) will be randomly allocated to either the experimental (receiving a multidisciplinary rehabilitation program combining multimodal exercises with psychologist-lead cognitive-behavioral therapy sessions) or the control group (receiving general care physiotherapy). Both groups will follow individual-based programs once a week for 10 weeks. The main outcome measures will be the Neck Disability Index, the Tampa Scale for Kinesiophobia, the Pain Catastrophizing Scale, a pain numerical rating scale, the Short-Form Health Survey, and the Work Ability Index. Participants will be evaluated before, after training, and after 12 months. DISCUSSION: Findings may provide empirical evidence on the effectiveness of an individual-based multidisciplinary rehabilitation program on inducing clinically significant and long-term improvements in the disability, pain, psychological factors, and quality of life of workers with chronic neck pain and that these would be maintained in the long term. Hence, this trial might contribute towards refining guidelines for good clinical practice and might be used as a basis for health authorities' recommendations. TRIAL REGISTRATION: ClinicalTrials.gov NCT04768790 . Registered on 24 February 2021.

Differential expression of circulating miRNAs after alemtuzumab induction therapy in lung transplantation.

Alemtuzumab is a monoclonal antibody targeting CD52, used as induction therapy after lung transplantation (LTx). Its engagement produces a long-lasting immunodepletion; however, the mechanisms driving cell reconstitution are poorly defined. We hypothesized that miRNAs are involved in this process. The expression of a set of miRNAs, cytokines and co-signaling molecules was measured with RT-qPCR and flow cytometry in prospectively collected serum samples of LTx recipients, after alemtuzumab or no induction therapy. Twenty-six LTx recipients who received alemtuzumab and twenty-seven matched LTx recipients without induction therapy were included in the analysis. One year after transplantation four miRNAs were differentially regulated: miR-23b (p = 0.05) miR-146 (p = 0.04), miR-155 (p < 0.001) and miR-486 (p < 0.001). Expression of 3 miRNAs changed within the alemtuzumab group: miR-146 (p < 0.001), miR-155 (p < 0.001) and miR-31 (p < 0.001). Levels of IL-13, IL-4, IFN-γ, BAFF, IL-5, IL-9, IL-17F, IL-17A and IL-22 were different one year after transplantation compared to baseline. In no-induction group, concentration of sCD27, sB7.2 and sPD-L1 increased overtime. Expression of miR-23b, miR-146, miR-486, miR-155 and miR-31 was different in LTx recipients who received alemtuzumab compared to recipients without induction therapy. The observed cytokine pattern suggested proliferation of specific B cell subsets in alemtuzumab group and co-stimulation of T-cells in no-induction group.

Virologic and immunologic monitoring of cytomegalovirus to guide preemptive therapy in solid-organ transplantation.

Control of human cytomegalovirus (HCMV) infection during the posttransplant period was investigated in 134 solid-organ transplant recipients by monitoring in parallel virologic and immunologic parameters for at least 1 year of follow-up. Virologic monitoring was achieved by determining HCMV DNAemia with real-time PCR, using the threshold of 300 000 DNA copies/mL blood as a cutoff for starting preemptive therapy. Immunologic monitoring included measurement of HCMV-specific CD4+ and CD8+ T cells by cytokine flow cytometry, using HCMV-infected dendritic cells as a stimulus. HCMV infection was diagnosed in 110 (82%) and required treatment in 49 (36%) patients. At 12 months after transplantation 'protective' immunity (≥0.4 CD4+ and CD8+ HCMV-specific T cells/µL blood) was achieved in 115/129 (89%) patients. During the entire study period, 122 patients reconstituting HCMV-specific CD4+ and CD8+ T-cell immunity at 60 days posttransplant onward were able to control HCMV infection, except for one patient who developed HCMV disease because of a rejection episode. Patients reconstituting HCMV-specific CD8+ only did not control HCMV infection. In conclusion, the presence of both HCMV-specific CD4+ and CD8+ T cells ≥ 0.4/µL blood appears to be protective against HCMV disease. This result does not apply to patients undergoing antirejection treatment, or reconstituting HCMV-specific CD8+ T cells only.

CT-guided cryoablation of both breast cancer and lymph node axillary metastasis.

Breast conservation is a major goal of cancer treatment. Many different minimally invasive options have been considered such as cryoablation. This technique is the best visualized of all ablation techniques due to the phase change during ice formation. We describe a case of breast cancer with lymph node axillary metastasis treated by CT-guided cryoablation. Cryoablation may have unique benefits for cost-effective outpatient breast cancer therapy using only local anesthesia and/or mild sedation.

Preemptive therapy for systemic and pulmonary human cytomegalovirus infection in lung transplant recipients.

The incidence and treatment of both systemic and pulmonary human cytomegalovirus (HCMV) infection as well as HCMV-specific T-cell immune responses were investigated in 57 consecutive lung transplant recipients (LTR) by using as cutoffs for preemptive therapy: 300 000 DNA copies/mL whole blood for systemic infections and 100 000 DNA copies/mL bronchoalveolar lavage fluid for lung infections. Results showed that out of 29/57 LTR (50.9%) needing preemptive antiviral therapy, 15 (51.7%) reached the blood cutoff, 8 (27.6%) the pulmonary cutoff and 6 (20.7%) both the blood and the lung cutoff (3 simultaneously and 3 subsequently). Recovery of HCMV-specific T-cell immune responses was achieved much earlier for CD8+ than CD4+ T cells. However, protection from HCMV reactivation was conferred by the presence of both arms of the T-cell response. In two LTR reaching the pulmonary cutoff and not preemptively treated, a full HCMV-specific CD4+ and CD8+ T-cell response was associated with resolution of lung infection. Antirejection steroid therapy suppressed T-cell immune responses, thus facilitating HCMV reactivation. In conclusion, in LTR, monitoring HCMV infection in both blood and lungs, may improve preemptive therapy efficacy. In addition, monitoring the HCMV-specific T-cell immune response appears useful for predicting control of HCMV infection in the posttransplant period.

Correlation of rhinovirus load in the respiratory tract and clinical symptoms in hospitalized immunocompetent and immunocompromised patients.

While human rhinoviruses (HRVs) are well accepted as a major cause of common cold syndromes (rhinitis), their role in the etiology of lower respiratory tract infections is still controversial, and their detection in asymptomatic patients is relatively common. The HRV pathogenic role in four groups of hospitalized patients (pediatric immunocompetent and immunocompromised patients, and adult immunocompetent and immunocompromised patients) was investigated by quantifying HRV load in nasopharyngeal aspirates or bronchoalveolar lavage samples by real-time reverse transcription PCR (RT-PCR). Real-time RT-PCR was performed in duplicate on all respiratory samples resulting positive by qualitative RT-PCR. In addition, molecular typing allowed detection of all known HRV species (A, B, and C). In immunocompetent pediatric patients HRVs were mostly associated with lower respiratory tract infections (in the absence of other viral agents) and wheezing, when viral load was > or =10(6) RNA copies/ml. In young immunocompromised patients (stem cell transplantation recipients), an inverse correlation between HRV persistence over time and time at which the infection occurred after transplantation was observed, whereas in adult immunocompromised patients (lung transplant recipients) HRVs could be detected at a medium-low level (<10(5) RNA copies/ml) in bronchoalveolar lavage samples taken routinely from asymptomatic patients. In conclusion, when detected at high viral load, HRVs may cause severe upper and lower respiratory tract infections, whereas when detected at a medium-low viral load, an event more frequent in immunocompromised subjects, they may represent only bystander viruses.

Frequency of Th1, Th2 and Th17 producing T lymphocytes in bronchoalveolar lavage of patients with systemic sclerosis.

OBJECTIVE: The pathophysiology of the lung fibrotic process in systemic sclerosis (SSc) is not fully elucidated. Since this pattern represents the leading cause of death in SSc, the knowledge of its actual pathophysiology is basic to prevent and stage pulmonary damage. In this study, we aimed to further investigate the relationship between the functional profiles of bronchoalveolar lavage (BAL) T cells and the pulmonary manifestation of the disease. METHODS: With this aim, we assessed the frequency of Th1, Th2 and Th17 producing T-lymphocytes and their effector cytokines in BAL of SSc patients without signs or symptoms of lung interstitial involvement (SScFib-) and with interstitial lung fibrosis (SScFib+). We also study as control groups: patients with usual interstitial pneumonia (UIP), patients with sarcoidosis and 9 healthy controls (NHCs). RESULTS: SScFib- showed an increase in BAL Th1/Th2 balance compared to NHCs, which was even higher than that observed in sarcoidosis. SScFib+ showed a shift towards a lower Th1/Th2 ratio as compared to SScFib-. The frequency of Th17 BAL T cells did not change among study groups. CONCLUSION: Our data confirm the Th1/Th2 imbalance hypothesis on the pathogenesis of interstitial fibrosis in SSc patients, and suggest a possible utility in the assessment of BAL Th1/Th2 ratio.

Is contrast-enhanced US alternative to spiral CT in the assessment of treatment outcome of radiofrequency ablation in hepatocellular carcinoma?

PURPOSE: The present study was conducted to assess the efficacy of contrast-enhanced ultrasound with low mechanical index in evaluating the response of percutaneous radiofrequency ablation treatment of hepatocellular carcinoma by comparing it with 4-row spiral computed tomography. MATERIALS AND METHODS: 100 consecutive patients (65 men and 35 women; age range: 62 - 76 years) with solitary hepatocellular carcinomas (mean lesion diameter: 3.7 cm +/- 1.1 cm SD) underwent internally cooled radiofrequency ablation. Therapeutic response was evaluated at one month after the treatment with triple-phasic contrast-enhanced spiral CT and low-mechanical index contrast-enhanced ultrasound following bolus injection of 2.4 ml of Sonovue (Bracco, Milan). 60 out of 100 patients were followed up for another 3 months. Contrast-enhanced sonographic studies were reviewed by two blinded radiologists in consensus. Sensitivity, specificity, NPV and PPV of contrast-enhanced ultrasound examination were determined. RESULTS: After treatment, contrast-enhanced ultrasound identified persistent signal enhancement in 24 patients (24 %), whereas no intratumoral enhancement was detected in the remaining 76 patients (76 %). Using CT imaging as gold standard, the sensitivity, specificity, NPV, and PPV of contrast enhanced ultrasound were 92.3 % (95 % CI = 75.9 - 97.9 %), 100 % (95 % CI = 95.2 - 100 %), 97.4 % (95 % CI = 91.1 - 99.3 %), and 100 % (95 % CI = 86.2 - 100 %). CONCLUSION: Contrast-enhanced ultrasound with low mechanical index using Sonovue is a feasible tool in evaluating the response of hepatocellular carcinoma to radiofrequency ablation. Accuracy is comparable to 4-row spiral CT.

A rare case of oncocytic Schneiderian papilloma with intradural and intraorbital extension with notes of operative techniques.

Epithelial cells of cylindrical cell papilloma are oncocytes, which arise from the sinonasal respiratory epithelium, hence the term Oncocytic Schneiderian papilloma.This is a rare and benign neoplasm of the nose and paranasal sinuses and it should be considered in the work-up of all unilateral nasal polypoid lesions. Clinically behaviour is comparable to inverted papillomas for local recurrence and malignancy coexistence. We report a case arisen from the nasoethmoidal space that extended to the anterior skull base through a bone dehiscence with intradural invasion and orbital space involvement. Surgical therapy is the treatment of choice, the endonasal endoscopic approach can be used in most of the cases and this surgical technique is safe and suitable also in presence of an extra nasal extension. We describe our experience for management of this kind of lesions and some notes on our operative technique.

[Regulatory T cells in kidney transplant recipients]. / Cellule T-regolatorie nel trapianto di rene.

Immunosuppressive drugs are essential for the prevention of acute transplant rejection but some may not promote long-term tolerance. Tolerance to self-antigens is ensured naturally by several mechanisms; one major mechanism depends on the activity of regulatory T lymphocytes (Treg), particularly CD4+CD25+ T cells. The transcription factor forkhead box protein 3 (Foxp3) has been identified as a molecular marker for Treg cells. The direct effects of immunosuppressive drugs on CD4+CD25+ cells are uncertain. In the clinical setting, basiliximab used in the induction phase of immunosuppression effectively reduced the number of acute rejection episodes. We studied the effects of the most widely used immunosuppressive induction regimens including cyclosporine, mycophenolate mofetil, steroids, and anti-CD25 monoclonal antibody (basiliximab) on the capacity to regulate human Treg in vivo. Twenty first cadaveric kidney transplant recipients (14 men, 6 women) were enrolled in the study. Blood samples were collected before kidney transplant and after one month. Blood sampling was done immediately before the administration of immunosuppressive therapy after an overnight fast. None of the transplant recipients presented laboratory or clinical signs of infection or acute rejection. The number and percentage of CD4+CD25+ and Foxp3+ T cells were determined by fluorescence activated cell sorter (FACS) analysis. Our results showed absence of both CD4+CD25+ and CD4+CD25+ Foxp3+ T cells one month after transplant. Peripheral CD4+CD25-Foxp3+ T cells significantly decreased after transplant but did not disappear. These preliminary data suggest that immunosuppressive induction therapy with basiliximab completely suppresses CD4+CD25+ regulatory cells and significantly reduces the total number of Foxp3+ lymphocytes.

Lung Allocation Score System: First Italian Experience.

BACKGROUND: Lung transplantation is an established therapeutic option for patients with end-stage pulmonary disease. In May 2005, the lung allocation score (LAS) was introduced in the United States to maximize the benefit to the recipient population and reduce waiting list mortality. The LAS has been applied in a region of Italy since March 2016 on a provisional basis. The aims of the study were describing waiting list characteristics and short-term outcomes after lung transplantation before and after LAS introduction. METHODS: All the patients who received transplants between January 1, 2011, and March 15, 2017, were included in our retrospective study. The study population was divided into 2 cohorts (historical cohort and post-LAS cohort) and a comparison among the main perioperative data was performed. RESULTS: The historical cohort consisted of 415 patients on the waiting list with 91 deaths and 199 lung transplants; the post-LAS cohort consisted of 134 patients with 10 deaths on the waiting list and 51 transplants. Median waiting time and mortality on the list decreased from 223 to 106 days (P = .03) and from 11.2% to 7.5% (P > .05), respectively. The transplantation rate increased from 25% to 38% (P = .001) and the probability to receive a transplant in the first year in the post-LAS era increased significantly (P = .004). CONCLUSIONS: The results of the introduction of the LAS system in our region are encouraging and have not shown any adverse short-term effects. The regional coordination decided to prolong the experimental application of LAS in order to accumulate more data and to evaluate medium-term outcomes.

Lung transplantation: the role of azithromycin in the management of patients with bronchiolitis obliterans syndrome.

Bronchiolitis obliterans syndrome (BOS) is the leading cause of death in lung transplant recipients (LTR). BOS is thought to result from chronic immunologic/inflammatory insults leading to peri-bronchiolar leukocyte infiltration, with a subsequent exuberant tissue re-modelling and fibro-obliteration of the luminal space of the allograft airways. Diagnosis is based on functional criteria and severity is graded on the degree of Forced Expiratory Volume in 1 second (FEV1) impairment. Current strategies to improve pulmonary function once BOS is established have demonstrated little or no impact on disease progression and re-transplantation remains the only therapeutic option. Among the alternative treatments which have been attempted in the last few years, long-term azithromycin treatment seems to be the most promising therapeutic device for BOS treatment. Azithromycin is a macrolide antibiotic, endowed with a broad spectrum of anti-inflammatory/immunomodulatory activities. Long-term oral azithromycin therapy can significantly improve FEV1 in about 42% of patients with established BOS. Moreover, reduced neutrophilia, chemokine release and bacterial exacerbations have been demonstrated. These observations suggest that the drug can down-regulate pulmonary inflammation, even if the precise underlying mechanisms still need to be determined.

Chemokine redundancy in BOS pathogenesis. A possible role also for the CC chemokines: MIP3-beta, MIP3-alpha, MDC and their specific receptors.

Bronchiolitis obliterans syndrome (BOS) is one of the most important factors limiting the long-term survival of lung transplant recipients (LTR), however its pathogenesis still remains unclear. We hypothesized that an increased production of certain specific proinflammatory mediators in the first post-transplant year would predispose to BOS. We retrospectively evaluated temporal kinetics of some CC chemokines that have not yet been evaluated, including CCL3/MIP1-alpha, CCL4/MIP1-beta, CCL17/TARC, CCL19/MIP3-beta, CCL20/MIP3-alpha, CCL22/MDC and CCL26/eotaxin, in broncho-alveolar lavage fluid (BAL-f) in the first post-transplant year in a cohort of 8 LTR before the development of BOS (pre-BOS LTR) and 8 LTR with long-term stable clinical conditions (stable LTR). Chemokine levels were assayed by means of a multiplex sandwich ELISA. Furthermore, for those ligands which resulted significantly predictive of BOS onset, we analyzed the expression of specific receptors (CCR) on BAL cells. The proportion of CCR-expressing BAL cells was assessed by flow cytometry. We demonstrated that MIP3-beta/CCL19, MIP3-alpha/CCL20, MDC/CCL22 levels at 6 months post-transplant significantly predicted BOS onset. In addition, the temporal behavior of these factors resulted significantly different in pre-BOS patients as compared to stable LTR. Finally the expression of CCR was documented on BAL lymphocytes and macrophages, and, in some cases, their expression was found to vary between the two groups. Within the complexity of the chemokine network, these three CCL factors could play an additive role in the pathogenesis of the inflammatory process leading to bronchiolar fibro-obliteration.

Clinical evaluation of sodium hyaluronate in the treatment of patients with sopraspinatus tendinosis under echographic guide: experimental study of periarticular injections.

PURPOSE: The purpose of this study was to examine the effect of periarticular injection of hyaluronate into shoulders with supraspinatus tendinosis under echographic guide. METHODS AND MATERIALS: The subjects were 56 patients with clinical, echographic and magnetic resonance diagnosis of supraspinatus tendinosis. They were divided in two groups by random sampling; 28 patients were assigned in SH group (sodium hyaluronate) and 28 patients in SC group (sodium chloride). The test drug was 20mg sodium hyaluronate (2ml, Hyalgan, Fidia SpA, Abano T., P.M. 500-700.000, 20mg/2ml). RESULTS: Preliminary results showed that sodium hyaluronate presented the highest efficacy in the improvement of clinical symptoms and recovery of functional status in patients with supraspinatus tendinosis in fact the mean V.A.S. score (Visual Analogue Scale) at 1 month after the end of the infiltrative cycle was 8.0 in the SC group vs. 2.8 in SH group and these numerical data were substantially unchanged also after 3 and 4 months. CONCLUSION: Hyaluronate injection under echographic guide should be use not only as a lubricant but also to prevent articular cartilage degeneration and cover and protect the articular cartilage; indeed sodium hyaluronate can decrease inflammatory joint process.

Complementary DNA cloning of the alternatively expressed endothelial cell glycoprotein Ib beta (GPIb beta) and localization of the GPIb beta gene to chromosome 22.

Glycoprotein Ib beta (GPIb beta) exists in platelets disulfide-linked to glycoprotein Ib alpha (GPIb alpha), a major receptor for von Willebrand factor. Both GPIb alpha and GPIb beta are expressed in endothelial cells (EC). While the GPIb alpha mRNA and protein appear similar in platelets and EC, EC GPIb beta mRNA is larger than platelet GPIb beta and encodes a larger protein. We have cloned and sequenced EC GPIb beta cDNA and report a 2793-nucleotide sequence which contains a 411-amino acid open reading frame. The EC sequence contains all of the platelet cDNA sequence and all but three amino acids of the primary translation product. Like the genes encoding GPIb alpha, GPIX, and GPV, the GPIb beta gene appears simple in structure. Using human hamster hybrids, we have localized the GPIb beta gene to chromosome 22pter-->22q11.2. When we examined poly (A)+ RNA from several human tissues for GPIb beta mRNA expression, we found that GPIb beta mRNA was expressed in a variety of tissues but was most abundant in heart and brain, while GPIb alpha and GPIX mRNA expression was found only in lung and placenta at very low levels. The broad distribution of GPIb beta mRNA suggests that it may be playing a role different than or additional to its function in platelets.