Microglia-derived extracellular vesicles in homeostasis and demyelination/remyelination processes.

Microglia (MG) play a crucial role as the predominant myeloid cells in the central nervous system and are commonly activated in multiple sclerosis. They perform essential functions under normal conditions, such as actively surveying the surrounding parenchyma, facilitating synaptic remodeling, engulfing dead cells and debris, and protecting the brain against infectious pathogens and harmful self-proteins. Extracellular vesicles (EVs) are diverse structures enclosed by a lipid bilayer that originate from intracellular endocytic trafficking or the plasma membrane. They are released by cells into the extracellular space and can be found in various bodily fluids. EVs have recently emerged as a communication mechanism between cells, enabling the transfer of functional proteins, lipids, different RNA species, and even fragments of DNA from donor cells. MG act as both source and recipient of EVs. Consequently, MG-derived EVs are involved in regulating synapse development and maintaining homeostasis. These EVs also directly influence astrocytes, significantly increasing the release of inflammatory cytokines like IL-1ß, IL-6, and TNF-α, resulting in a robust inflammatory response. Furthermore, EVs derived from inflammatory MG have been found to inhibit remyelination, whereas Evs produced by pro-regenerative MG effectively promote myelin repair. This review aims to provide an overview of the current understanding of MG-derived Evs, their impact on neighboring cells, and the cellular microenvironment in normal conditions and pathological states, specifically focusing on demyelination and remyelination processes.

Pregnancy-associated plasma protein A mRNA expression as a marker for differentiated thyroid cancer: results from a "surgical" and a "cytological" series.

PURPOSE: Pregnancy-associated plasma protein A (PAPPA) is a metalloproteinase initially described for its role during pregnancy. PAPPA regulates IGF ligands 1 (IGF1) bioavailability through the degradation of IGF-binding protein 4 (IGFBP4). After the cleavage of IGFBP4, free IGF1 is able to bind IGF1 receptors (IGF1R) triggering the downstream signaling. Recently, PAPPA expression has been linked with development of several cancers. No data have been published on thyroid cancer, yet. METHODS: We evaluated PAPPA, insulin-like growth factor (IGF1), IGF1 receptors (IGF1R) and IGF-binding protein 4 (IGFBP4) mRNA expression levels in a "Surgical series" of 94 thyroid nodules (64 cancers, 16 follicular adenomas and 14 hyperplastic nodules) and in a "Cytological series" of 80 nodules from 74 patients underwent to fine-needle aspiration cytology (FNAC). In tissues, PAPPA was also evaluated by western blot. RESULTS: We found that PAPPA expression was increased in thyroid cancer specimen at mRNA and protein levels and that, adenomas and hyperplastic nodules had an expression similar to normal tissues. When applied on thyroid cytologies, PAPPA expression was able to discriminate benign from malignant nodules contributing to pre-surgical classification of the nodules. We calculated a cut-off with a good specificity (91%) which reached 100% when combined with molecular biology. CONCLUSION: These results show that PAPPA could represent a promising diagnostic marker for differentiated thyroid cancer.

Sapienza Global Bedside Evaluation of Swallowing after Stroke: the GLOBE-3S study.

BACKGROUND AND PURPOSE: Dysphagia occurs in up to 50% of all patients with acute stroke. There is debate regarding which is the most effective screening tool in identifying aspiration in patients with acute stroke. We assessed the accuracy of the Sapienza Global Bedside Evaluation of Swallowing after Stroke (GLOBE-3S), which combines the Toronto Bedside Swallowing Screening Test (TOR-BSST©) with oxygen desaturation and laryngeal elevation measurement during swallowing. METHODS: We prospectively enrolled consecutive patients with stroke within 72 h of symptom onset. All patients with stroke firstly underwent a standard neurological examination, then the GLOBE-3S evaluation and finally the fiberoptic endoscopic evaluation of swallowing (FEES). Two different assessors, a neurologist and a speech pathologist, blind to both the clinical data and each other's evaluation, administered the GLOBE-3S and FEES examination. We assessed the accuracy of the GLOBE-3S in detecting post-stroke swallow impairment with aspiration using the FEES as the standard. RESULTS: We enrolled 50 patients with acute stroke, 28 of whom (56%) had swallowing impairment with aspiration at FEES evaluation. A total of 33 patients (66%) failed the GLOBE-3S evaluation. The GLOBE-3S reached a sensitivity of 100% and a specificity of 77.3% (negative predictive value, 100%; positive likelihood ratio, 4.34). The median time required for the GLOBE-3S to be performed was 297 s. CONCLUSIONS: GLOBE-3S is quick to perform at the bedside and can accurately identify aspiration in patients with acute stroke. By including the measurement of laryngeal elevation and monitoring of oxygen desaturation, it could represent a highly sensitive instrument to avoid the misdiagnosis of silent aspirators.

Bloodstream infections in haematological cancer patients colonized by multidrug-resistant bacteria.

Infections by multidrug-resistant (MDR) bacteria are a worrisome phenomenon in hematological patients. Data on the incidence of MDR colonization and related bloodstream infections (BSIs) in haematological patients are scarce. A multicentric prospective observational study was planned in 18 haematological institutions during a 6-month period. All patients showing MDR rectal colonization as well as occurrence of BSI at admission were recorded. One-hundred forty-four patients with MDR colonization were observed (6.5% of 2226 admissions). Extended spectrum beta-lactamase (ESBL)-producing (ESBL-P) enterobacteria were observed in 64/144 patients, carbapenem-resistant (CR) Gram-negative bacteria in 85/144 and vancomycin-resistant enterococci (VREs) in 9/144. Overall, 37 MDR-colonized patients (25.7%) developed at least one BSI; 23 of them (62.2%, 16% of the whole series) developed BSI by the same pathogen (MDRrel BSI), with a rate of 15.6% (10/64) for ESBL-P enterobacteria, 14.1% (12/85) for CR Gram-negative bacteria and 11.1% (1/9) for VRE. In 20/23 cases, MDRrel BSI occurred during neutropenia. After a median follow-up of 80 days, 18 patients died (12.5%). The 3-month overall survival was significantly lower for patients colonized with CR Gram-negative bacteria (83.6%) and VRE (77.8%) in comparison with those colonized with ESBL-P enterobacteria (96.8%). CR-rel BSI and the presence of a urinary catheter were independent predictors of mortality. MDR rectal colonization occurs in 6.5% of haematological inpatients and predicts a 16% probability of MDRrel BSI, particularly during neutropenia, as well as a higher probability of unfavourable outcomes in CR-rel BSIs. Tailored empiric antibiotic treatment should be decided on the basis of colonization.

Emerging resistant bacteria strains in bloodstream infections of acute leukaemia patients: results of a prospective study by the Rete Ematologica Lombarda (Rel).

Multiresistant bacterial infections are a potentially life-threatening condition in acute leukaemia (AL) patients. We aimed to better define the very recent epidemiology and outcome of bloodstream infections (BSIs) in a real-life setting. We prospectively collected all consecutive febrile/infectious episodes occurring in AL patients admitted to 9 haematology units. In 293 AL patients, 433 BSIs were diagnosed. Gram-positive (GP) bacteria were isolated in 44.8 % BSI and Gram-negative (GN) in 38.3 %, while polymicrobial aetiology- or fungi-related events were identified in 15.7 and 1.1 % of the cases, respectively. GP was observed more frequently in patients not in complete remission (p = 0.04), while GN during consolidation cycles (p = 0.003). Extended spectrum ß-lactamase-producing strains accounted for 23.2 % of enterobacteria. They were associated with previous antibiotic exposure, including fluoroquinolones prophylaxis (p = 0.01). Carbapenem-resistant (CR) strains occurred in 9 % of enterobacteria. Among Pseudomonas aeruginosa strains, 21.6 % were multiresistant. Overall 30-day mortality was 8.5 %. CR GN and multiresistant P. aeruginosa BSIs were independent predictors of death (p = 0.002), as well as relapsed/resistant AL (18.3 %; p = 0.0002) and the presence of pulmonary infiltrates (26.6 %; p < 0.001). Although GP still predominate over GN BSI, the percentage of antibiotic resistant GN strains is considerable in AL patients and it is associated with poor prognosis.

Comparison between azacitidine and decitabine as front-line therapy in elderly acute myeloid leukemia patients not eligible for intensive chemotherapy.

We compared the efficacy of azacitidine (AZA) and decitabine (DEC) in elderly patients with untreated AML, diagnosed according to WHO criteria. In the two groups, we evaluated complete remission (CR), overall survival (OS) and disease free survival (DFS). The AZA and DEC groups included 139 and 186 patients, respectively. To minimize the effects of treatment selection bias, adjustments were made using the propensity-score matching method, which yielded 136 patient pairs. In the AZA and DEC cohort, median age was 75 years in both, (IQR, 71-78 and 71-77), median WBCc at treatment onset 2.5 × 109/L (IQR, 1.6-5.8) and 2.9 × 109/L (IQR, 1.5-8.1), median bone marrow (BM) blast count 30% (IQR, 24-41%) and 49% (IQR, 30-67%), 59 (43%) and 63 (46%) patients had a secondary AML, respectively. Karyotype was evaluable in 115 and 120 patients: 80 (59%) and 87 (64%) had intermediate-risk, 35 (26%) and 33 (24%) an adverse risk karyotype, respectively. Median number of cycles delivered was 6 (IQR, 3.0-11.0) and 4 (IQR, 2.0-9.0), CR rate was 24% vs 29%, median OS and 2-year OS rates 11.3 (95% CI 9.5-13.8) vs 12.0 (95% CI 7.1-16.5) months and 20% vs 24%, respectively. No differences in CR and OS were found within the following subgroup: intermediate- and adverse-risk cytogenetic, frequency of WBCc at treatment ≥ 5 × 10^9 L and < 5 × 10^9/L, de novo and secondary AML, BM blast count < and ≥ 30%. Median DFS for AZA and DEC treated patients was 9.2 vs 12 months, respectively. Our analysis indicates similar outcomes with AZA compared to DEC.

Dysfunctional DC subsets in RCC patients: ex vivo correction to yield an effective anti-cancer vaccine.

Dendritic cells (DCs) are potent antigen-presenting cells responsible for the activation and functional polarization of specific T cells. In patients with renal cell carcinoma (RCC) and other cancers, coordinate DC and T cell defects have been reported. In particular, DC and T cell functional subsets that are not conducive to tumor clearance are hypothesized to predominate in patients with advanced-stage disease. Two major peripheral blood DC subsets have been identified in humans: myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) that are believed to mediate contrasting effects on cancer immunity. Given the lack of information regarding DC subsets in patients with RCC, in the present study we have investigated the comparative frequencies and activation states of mDC and pDC in peripheral blood, cancer tissues and lymph nodes of patients with RCC using flow cytometry and immunohistochemistry. Three monoclonal antibodies (mAbs) reactive against specific DC subsets (BDCA-2 or BDCA-4 for pDC and BDCA-1 and BDCA-3 which represent two distinct subsets of mDC, mDC1 and mDC2, respectively) were employed. We observed a significant reduction of both DC subsets in the peripheral blood of patients as compared to normal donors. Similarly, both mDC and pDC were recruited in large numbers into RCC tumor tissues, where they displayed an immature phenotype (DC-LAMP(-)) and appeared unable to differentiate into mature DC (CD83(+)) that were competent to migrate to draining lymph nodes. However, we were readily able to generate ex vivo mDC from RCC patients. These DC stimulated robust anti-tumor CTL in vitro and would be envisioned for use in DC-based vaccines applied in patients with RCC whose existing immune system is judged dysfunctional, anergic or prone to undergo apoptosis.

Possible association between thyroid autoimmunity and Menière's disease.

Various aetiopathological mechanisms have been postulated to be at the root of Menière's disease (MD), and some data suggest that there may be also an underlying autoimmune factor. In fact, Menière patients manifest certain characteristics that are typical of autoimmune involvement association of particular human leucocyte antigen haplotypes, the presence of antibodies against internal ear antigens. In this study, we evaluated the association between thyroid autoimmunity and MD in a non-selected group of patients. We recruited 50 consecutive MD patients and two groups as controls: group A, 82 healthy volunteers; and group B, 50 subjects suffering from acute unilateral peripheral vestibulopathy. All subjects were submitted to instrumental assessment of cochlear-vestibular function and analysis of thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, anti-TSH receptor antibody (TR-Ab), anti-thyroperoxidase antibody (TPO-Ab) and anti-thyroglobulin antibody (Tg-Ab) in the blood. The prevalence of autoimmune thyroiditis in group B [6/50 (12%); 66.7% TPO-Ab and 33.3% Tg-Ab] was superimposable with the healthy controls [6/82 (7%); 66.7% TPO-Ab and 33.3% Tg-Ab]. In contrast, 38% of the MD patients (P = 0.0001 versus group A and group B) had significant autoantibody levels (68.4% TPO-Ab; 15.8% TPO-Ab + TR-Ab; 10.5% Tg-Ab; 5.2% TPO-Ab + Tg-Ab). Furthermore, 14% of the MD patients were hyperthyroid under l-thyroxine therapy, while no dysfunction was seen in the control groups. Overall, our data demonstrate a significant association between MD and thyroid autoimmunity, which suggests that an autoimmune factor is involved in the aetiopathogenesis of this disease. These findings suggest that it should be useful to submit MD patients to multi-disciplinary clinical investigation.

Clinical applications of oro-pharyngo-oesophageal scintigraphy in the study of dysphagia.

The diagnostic approach to patients with dysphagia is well established and relies mainly on videofluoroscopy and endoscopy. Oro-pharyngo-oesophageal scintigraphy permits both a functional and a semi-quantitative study of the various stages of swallowing. Moreover, by means of this investigation, it is possible to estimate the amount of inhaled bolus. Oro-pharyngo-oesophageal scintigraphy with 99mTc-nanocolloid has been found to be easy to use, economical, well tolerated and, supplying precise indications regarding the extent of the swallowing disorder, then permits a better clinical definition of the patient. The limitations of swallowing scintigraphy are: poor definition in visualizing anatomic structures and low specificity when used as the only diagnostic test. Scintigraphy plays an important role in the diagnosis and follow-up of dysphagia, and its use, together with other diagnostic techniques, increases diagnostic accuracy. In this study, the role of oro-pharyngo-oesophageal scintigraphy has been analysed in patients with post-surgical, neurological and oesophageal dysphagia.

The relationship between motor proficiency and mental health outcomes in young adults: A test of the Environmental Stress Hypothesis.

Growing evidence has highlighted the importance of motor proficiency in relation to psychosocial outcomes including self-perceived competence in various domains, perceived social support, and emotional areas such as anxiety and depression. The Environmental Stress Hypothesis-elaborated (Cairney, Rigoli, & Piek, 2013) is a proposed theoretical framework for understanding these relationships and recent studies have begun examining parts of this model using child and adolescent populations. However, the extent to which the relationships between these areas exist, persist or change during early adulthood is currently unclear. The current study aimed to investigate the Environmental Stress Hypothesis in a sample of 95 young adults aged 18-30years and examined the mediating role of physical self-worth and perceived social support in the relationship between motor proficiency and internalising symptoms. The McCarron Assessment of Neuromuscular Development (McCarron, 1997) was used to assess motor proficiency, the Depression Anxiety Stress Scale (Lovibond & Lovibond, 1995) provided a measure of internalising symptoms, and the Physical Self Perceptions Profile (Fox & Corbin, 1989) and the Multidimensional Scale of Perceived Social Support (Zimet, Dahlem, Zimet, & Farley, 1988) were used to investigate the possible mediating role of physical self-worth and perceived social support respectively. Potential confounding variables such as age, gender and BMI were also considered in the analysis. Structural Equation Modelling revealed that perceived social support mediated the relationship between motor proficiency and internalising symptoms, whereas, the mediating role of physical self-worth was non-significant. The current results provide support for part of the model pathways as described in the Environmental Stress Hypothesis and suggest an important relationship between motor proficiency and psychosocial outcomes in young adults. Specifically, the results support previous literature regarding the significant role of perceived social support for mental well-being and suggest that an intervention that considers social support may also indirectly influence mental health outcomes in young adults who experience movement difficulties.

Chitosan and Laminarin as Alternatives to Copper for Plasmopara viticola Control: Effect on Grape Amino Acid.

Copper fungicide use is limited by the European regulation; therefore, new strategies have been developed to prevent grapevine downy mildew (GDM). However, there is poor information about their effects on grape amino acid composition. This field trial aimed to evaluate the effect on grape amino acid composition of chitosan and of a mixture of laminarin and Saccharomyces extracts (LamE), applied in different strategies with copper hydroxide. The results showed that all the treatments applied to grapevines decreased the concentration of several amino acids. Moreover, treatments that have mostly decreased these compounds are those with copper hydroxide, especially when applied individually. LamE applied individually or alternately with copper hydroxide had the least negative effect on grape amino acid content. These results provide further information about the negative effects of copper on grape quality, which can be reduced when it is used in strategy with LamE or chitosan in GDM control.

Stabilometric findings in patients affected by organic dysphonia before and after phonomicrosurgery.

The purpose of this study is to understand if there is any alteration in the posture of patients affected by organic dysphonia and describe possible postural modifications after phonomicrosurgery on the vocal folds. Forty subjects (22 males, 18 females; mean age 32.6 ± 7.5 years) suffering from organic dysphonia (15 cases of polyps, 11 submucosal retention cysts, 10 bilateral fibrous vocal fold nodules and 4 bilateral Reinke's oedema) were examined by open-eye and closed-eye posturography while breathing spontaneously before surgery, 24 hours after surgery and after 6 months. The variables taken into account were: the coordinates of the centre of pressure on both frontal and sagittal planes, length and surface of the track, mean velocity of the oscillations and relative standard deviations, spectral analysis of oscillation frequency, statokinesigram and stabilogram values. No characteristic pathological pattern was seen in basal stabilometry in any of the subgroups (polyps, cysts, Reinke's oedema). Only the subgroup of patients with fibrous vocal fold nodules (8/10; 80%) showed a slight forward shift from the centre of gravity when analysed in both open-eye and closed-eye posturography. A comparison performed within the same subgroup using open-eye and closed-eye posturography before and after surgery revealed no significant difference in any of the parameters being studied. The use of static stabilometry in this study demonstrates the absence of characteristic postural alterations in patients affected by organic dysphonia and also excludes that simple removal of the vocal fold lesion can change posture.

Solid papillary carcinoma of the nipple: an in situ carcinoma or an expansive growth tumor?

Papillary breast lesions are a heterogeneous group of tumors which mainly arise in the central mammary region, ranging from benign to malignant. Among them, solid papillary carcinoma (SPC) represents a very uncommon variant with indolent clinical behavior and excellent prognosis. The categorization of papillary lesions as benign, atypical or malignant is often difficult even for experienced pathologists. Furthermore, for prognostic purposes, to decide whether to consider a lesions as in situ when it is not associated with frank invasive foci of carcinoma may be problematic. We present a case of solid papillary carcinoma arising in the nipple with an expansive and circumscribed growth, mimicking an in situ lesion of the breast on the hematoxylin and eosin stained sections, but in which a myoepithelial layer around neoplastic nodules could not be detected by using immunohistochemistry. To the best of our knowledge, primary origin in the nipple is very rare for SPCs and it has been described only once in the literature. The case we herein illustrate is of interest not only because of its origin in the nipple, but also because of its not in situ, but invasive, although expansive and not infiltrative growth. In the differential diagnosis, nipple disorders as adenoma and syringomatous adenoma, usual ductal hyperplasia (UDH), papilloma, intracystic papillary carcinoma, lobular carcinoma in situ, ductal carcinoma in situ and skin adnexal tumors are considered.

Comparison between videofluoroscopy, fiberoptic endoscopy and scintigraphy for diagnosis of oro-pharyngeal dysphagia.

The purpose of this study was to compare videofluoroscopy (VFS), fiberoptic endoscopic evaluation of swallowing (FEES) and oro-pharyngo- oesophageal scintigraphy (OPES) with regards to premature spillage, post-swallowing residue and aspiration to assess the reliability of these tests for detection of oro-pharyngeal dysphagia. Sixty patients affected with dysphagia of various origin were enrolled in the study and submitted to VFS, FEES and OPES using a liquid and semi-solid bolus. As a reference, we used VFS. Both the FEES and the OPES showed good sensitivity with high overall values (≥ 80% and ≥ 90% respectively). The comparison between FEES vs VFS concerning drop before swallowing showed good specificity (84.4% for semi-solids and 86.7% for liquids). In the case of post-swallowing residue, FEES vs VFS revealed good overall validity (75% for semi-solids) with specificity and sensitivity well balanced for the semi-solids. OPES vs. VFS demonstrated good sensitivity (88.6%) and overall validity (76.7%) for liquids. The analysis of FEES vs. VFS for aspiration showed that the overall validity was low (≤ 65%). On the other hand, OPES demonstrated appreciable overall validity (71.7%). VFS, FEES and OPES are capable of detecting oro-pharyngeal dysphagia. FEES gave significant results in the evaluation of post-swallowing residues.

Significance of Epstein-Barr virus (EBV) load and interleukin-10 in post-transplant lymphoproliferative disorders.

The complex relationship between EBV, IL-10 and lymphomagenesis has been widely investigated and several studies have highlighted the diagnostic value of EBV DNA copies and serum IL-10, that may be considered as tumor markers. Notwithstanding the great number of data published in the last few years on the behavior of EBV DNA copies in the peripheral blood of transplanted patients, a threshold value significant for impending or overt post-transplant lymphoproliferative disorder (PTLD) has not yet been defined. Too many factors, both technical and clinicopathological, may affect the results of clinical studies, making their comparison difficult. On the contrary, although the role of IL-10 in PTLDs has been well documented, a sufficient number of studies exploring sensitivity and specificity of serum IL-10 measurement is lacking. The aim of this review is to summarise data on EBV load quantification and serum IL-10 detection in transplanted patients, providing clinicians with wide and useful information in order to improve bedside management of transplanted patients with regard to PTLDs occurrence and treatment.

Suprapubic-assisted Transurethral Excision of a Vaginal Mesh Eroded Into the Bladder.

A 56-year-old woman with irritative voiding symptoms and recurrent urinary infections was found to have erosion into the bladder of a tension-free vaginal tape placed 61 months before. To achieve radical excision, a 26Fr Amplatz sheath was placed suprapubically under endoscopic vision. A rigid nephroscope with grasping forceps was used to pull the eroded mesh out of the bladder wall while excising it transurethrally with a resectoscope. Postoperative course was uneventful; 12 months after surgery the patient remains asymptomatic. This novel technique provides an effective means of radically removing a mesh eroded into the bladder either transurethrally or suprapubically.

Enhanced expression of transforming growth factor beta1 in rat thyroid hyperplasia is thyrotropin induced and time dependent.

Forty-three 8-week-old male Wistar rats were studied to evaluate temporal changes of transforming growth factor beta1, (TGF-beta1) mRNA levels in thyroid tissue during pharmacologically induced goiter. Four rats were treated with purified bovine thyrotropin (TSH; Ambinon, 2 mU/day sc) for 7 days before being sacrificed. Thirty-one were treated with propylthiouracil (PTU), added to their drinking water at a concentration of 0.2 g%, and subsequently were sacrificed as follows: five after 1 week (PTU-1): five after 2 weeks (PTU-2); five after 4 weeks (PTU-4); five after 8 weeks (PTU-8); five after 12 weeks (PTU-12). In six rats, after 12 weeks of treatment. PTU was withdrawn for 2 months and subsequently started again in three rats which were sacrificed after 2 weeks (PTU-R); the remaining three rats were sacrificed without any further treatment (PTU-R control). Eight rats (control rats) were never treated and served as controls. After sacrifice, blood was drawn for determination of total thyroxine and the thyroid was excised and subdivided into two lobes. Northern analysis for TGF-beta1 was performed in one lobe. while histological and immunohistochemical studies were performed in the other lobe. Gene expression of TGF-beta1 was induced in TSH- and PTU-treated rats. In TSH-treated rats TGF-beta1 gene expression was less detectable than in PTU-treated rats, where it became evident after 2 weeks and remained through weeks 4-8. Gene expression of TGF-beta1 wits also seen in PTU-R rats, but not in the control and in the PTU-R control. Immunohistochemical analysis showed a different presence and location for the TGF-beta1 protein, which appears to be dependent on the time of exposure to mitogenic stimulus. In conclusion, TGF-beta1 is produced in response to both a direct (TSH by itself) and indirect (TSH induced by PTU-induced hypothyroidism) cellular proliferative stimulus and is not linked to an adaptative phenomenon secondary to hypothyroidism. The immunohistochemical location of TGF-beta1 within the thyrocytes is influenced by mitogen exposure time. A TGF-beta1 immunohistochemical evaluation may be important to define exposure time and activity of goitrogenic stimuli.

Bacterial isolates and cigarette smoking in patients with chronic bronchitis: results from an Italian multicenter survey.

Patients who were cigarette smokers suffering exacerbations of chronic bronchitis were examined in eight outpatient clinics in five regions of Italy, three from the South (Campania, 82 patients; Sicily, 82 patients; and Puglia, 29 patients) and two from North (Lombardy, 33 patients; and Liguria, 50 patients). Haemophilus influenzae was the most frequently isolated bacterium in the patients' sputum (in 30% of the total group), followed by Streptococcus pneumoniae (in 20%), Staphylococcus aureus (in 25%), and Branhamella catarrhalis (in 7%). H. influenzae was the most common bacterium in the South (in 37%) and S aureus in the North (in 13%). Smoking index scores (number of cigarettes smoked daily x years of smoking) were 827 in patients in whom H influenzae was isolated; 691 in patients with S aureus; 599 in patients with S pneumoniae; 542 in patients with B catarrhalis; and 446 in patients in whom no isolates were found. Pulmonary function was most severely decreased in patients positive for H influenzae and S aureus. The results indicate an association between heavy cigarette smoking and lower respiratory tract infections that is influenced by regional differences.