ABSTRACT
To assess the effect of a fermented rice-flour obtained from Lactobacillus paracasei CBA L74 in managing infants with moderate to severe atopic dermatitis. Infants with moderate to severe atopic dermatitis, aged 6-36 months, were randomly assigned to receive once-daily consumption of rice flour containing heat-killed probiotic Lactobacillus paracasei CBA L74 or placebo for 12 weeks as supplementary approach to topical treatment. Primary outcome was SCORAD index change from baseline to 12 weeks; secondary outcomes were gut microbiota composition, as evaluated by the analysis of fecal samples, and serum cytokines at baseline and at the end of the intervention period in both groups, and steroid usage over the treatment period and one month after stopping it. V3-V4 region of the 16S ribosomal RNA gene was sequenced to evaluate changes in the gut microbiota. SCORAD index decreased over the treatment period in both groups. The difference in the SCORAD change was -2.1 (-5.5 to 1.3; p = 0.223) for the experimental vs. the placebo group, not reaching the minimal clinical difference of 8.7 units. The use of topical steroids, measured as finger tips units, decreased from 4 to 16 weeks, in both groups; the reduction was significantly higher in experimental than in placebo group (p value from Wilcoxon rank sum test = 0.031). No significant differences were observed for cytokines levels between groups. The composition of gut microbiota at the phylum and class taxonomic levels resulted very similar, at baseline and after intervention, in both groups. Similarly, no significant differences were observed in the relative abundance of bacterial genera between groups. In conclusion, though the heat-killed Lactobacillus paracaseiwas not proved to be effective in reducing the severity of atopic dermatitis, it showed a steroid sparing effect the value of which needs to be further investigated.
Subject(s)
Dermatitis, Atopic/therapy , Flour/microbiology , Lacticaseibacillus paracasei , Oryza , Probiotics/therapeutic use , Bacteria/genetics , Child, Preschool , Cytokines/blood , Dermatitis, Atopic/blood , Dermatitis, Atopic/microbiology , Double-Blind Method , Feces/microbiology , Female , Fermentation , Gastrointestinal Microbiome/genetics , Humans , Infant , Male , RNA, Ribosomal, 16S , Severity of Illness IndexABSTRACT
Many potential therapeutic compounds for brain diseases fail to reach their molecular targets due to the impermeability of the blood-brain barrier, limiting their clinical development. Nanotechnology-based approaches might improve compounds pharmacokinetics by enhancing binding to the cerebrovascular endothelium and translocation into the brain. Adsorption of apolipoprotein E4 onto polysorbate 80-stabilized nanoparticles to produce a protein corona allows the specific targeting of cerebrovascular endothelium. This strategy increased nanoparticle translocation into brain parenchyma, and improved brain nanoparticle accumulation 3-fold compared to undecorated particles (119.8 vs 40.5 picomoles). Apolipoprotein decorated nanoparticles have high clinical translational potential and may improve the development of nanotechnology-based medicine for a variety of neurological diseases.
Subject(s)
Apolipoproteins/administration & dosage , Blood-Brain Barrier/drug effects , Brain/metabolism , Drug Delivery Systems , Nanoparticles/administration & dosage , Protein Corona/chemistry , Animals , Apolipoproteins/chemistry , Biological Transport , Brain/drug effects , Male , Mice , Mice, Inbred BALB C , Nanoparticles/chemistryABSTRACT
Inhibitors for the prevention of corrosion in reinforced concrete are chemical substances able to reduce carbon steel reinforcements corrosion without altering the overall properties of concrete. Today, many commercially available substances have a negative impact on human safety during either the inhibitor synthesis, their handling or application in field. Green corrosion inhibitors are nontoxic, biodegradable and environmentally biocompatible substances. They are generally made of extracts from natural plants or waste, which are abundantly available in several countries. The majority of green inhibitor molecules usually contain multiple bonds, aromatic rings, polar functional groups and electronegative atoms as P, N, S or O; the latter are able to coordinate with metal cations to form protective layers on the metallic surface of the reinforcements, so as to inhibit the development (initiation and/or propagation) of the corrosion process. In this review, the most recent achievements on the study and investigation of green corrosion inhibitors for concrete structures are presented and discussed. Inhibitors are classified based on their nature and inhibition mechanism. The inhibition effectiveness of the substances is compared with the well-established effective nitrite-based inhibitor, distinguishing between accelerated and long-term tests. Based on the available data, a summary of corrosion inhibitors efficiency is reported.
ABSTRACT
Excessive sedation is associated with poor outcome in critically ill acute respiratory distress syndrome (ARDS) patients. Whether this prognostic effect varies among ARDS patients with and without COVID-19 has yet to be determined. We compared the prognostic value of excessive sedationin terms of delirium, length of stay in intensive care unit (ICU-LOS) and ICU mortalitybetween COVID-19 and non-COVID-19 critically ill ARDS patients. This was a second analysis of prospectively collected data in four European academic centers pertaining to 101 adult critically ill ARDS patients with and without COVID-19 disease. Depth of sedation (DOS) and delirium were monitored through processed electroencephalogram (EEG) and the Confusion Assessment Method for ICU (CAM-ICU). Our main exposure was excessive sedation and how it relates to the presence of delirium, ICU-LOS and ICU mortality. The criterion for excessive sedation was met in 73 (72.3%) patients; of these, 15 (82.2%) and 58 (69.1%) were in non-COVID-19 and COVID-19 ARDS groups, respectively. The criteria of delirium were met in 44 patients (60.3%). Moreover, excessive sedation was present in 38 (86.4%) patients with delirium (p < 0.001). ICU death was ascertained in 41 out of 101 (41.0%) patients; of these, 37 (90.2%) had excessive sedation (p < 0.001). The distribution of ICU-LOS among excessive-sedated and non-sedated patients was 22 (16−27) vs. 14 (10.5−19.5) days (p < 0.001), respectively. In a multivariable framework, excessive sedation was independently associated with the development of delirium (p = 0.001), increased ICU mortality (p = 0.009) and longer ICU-LOS (p = 0.000), but only in COVID-19 ARDS patients. Independent of age and gender, excessive sedation might represent a risk factor for delirium in COVID-19 ARDS patients. Similarly, excessive sedation shows to be an independent predictor of ICU-LOS and ICU mortality. The use of continuous EEG-based depth of sedation (DOS) monitoring and delirium assessment in critically ill COVID-19 patients is warranted.
ABSTRACT
The topic of sustainability of reinforced concrete structures is strictly related with their durability in aggressive environments. In particular, at equal environmental impact, the higher the durability of construction materials, the higher the sustainability. The present review deals with the possible strategies aimed at producing sustainable and durable reinforced concrete structures in different environments. It focuses on the design methodologies as well as the use of unconventional corrosion-resistant reinforcements, alternative binders to Portland cement, and innovative or traditional solutions for reinforced concrete protection and prevention against rebars corrosion such as corrosion inhibitors, coatings, self-healing techniques, and waterproofing aggregates. Analysis of the scientific literature highlights that there is no preferential way for the production of "green" concrete but that the sustainability of the building materials can only be achieved by implementing simultaneous multiple strategies aimed at reducing environmental impact and improving both durability and performances.
ABSTRACT
Progesterone (Pg) and estrogen (E) receptors (PgRs and ERs) are expressed in normal and neoplastic adrenal cortex, but their role is not fully understood. In literature, Pg demonstrated cytotoxic activity on AdrenoCortical Carcinoma (ACC) cells, while tamoxifen is cytotoxic in NCI-H295R cells. Here, we demonstrated that in ACC cell models, ERs were expressed in NCI-H295R cells with a prevalence of ER-ß over the ER-α.Metastasis-derived MUC-1 and ACC115m cells displayed a very weak ER-α/ß signal, while PgR cells were expressed, although at low level. Accordingly, these latter were resistant to the SERM tamoxifen and scarcely sensitive to Pg, as we observed a lower potency compared to NCI-H295R cells in cytotoxicity (IC50: MUC-1 cells: 67.58 µM (95%CI: 63.22-73.04), ACC115m cells: 51.76 µM (95%CI: 46.45-57.67) and cell proliferation rate. Exposure of NCI-H295R cells to tamoxifen induced cytotoxicity (IC50: 5.43 µM (95%CI: 5.18-5.69 µM) mainly involving ER-ß, as their nuclear localization increased after tamoxifen: Δ A.U. treated vs untreated: 12 h: +27.04% (p < 0.01); 24 h: +36.46% (p < 0.0001). This effect involved the SF-1 protein reduction: Pg: -36.34 ± 9.26%; tamoxifen: -46.25 ± 15.68% (p < 0.01). Finally, in a cohort of 36 ACC samples, immunohistochemistry showed undetectable/low level of ERs, while PgR demonstrated a higher expression. In conclusion, ACC experimental cell models expressed PgR and low levels of ER in line with data obtained in patient tissues, thus limiting the possibility of a clinical approach targeting ER. Interestingly, Pg exerted cytotoxicity also in metastatic ACC cells, although with low potency.
Subject(s)
Adrenal Cortex Neoplasms/pathology , Adrenocortical Carcinoma/pathology , Progesterone/pharmacology , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Tamoxifen/pharmacology , Adrenal Cortex Neoplasms/drug therapy , Adrenal Cortex Neoplasms/metabolism , Adrenocortical Carcinoma/drug therapy , Adrenocortical Carcinoma/metabolism , Antineoplastic Agents, Hormonal/pharmacology , Apoptosis , Cell Proliferation , Drug Therapy, Combination , Female , Humans , Male , Progestins/pharmacology , Tumor Cells, CulturedABSTRACT
BACKGROUND: Coping with end-stage pediatric cancer patients and the related bereavement is a challenge for all the caregivers involved. PROCEDURE: Forty-seven cancer patients who died in 2006 were assessed as concerns the main place of care in the end stage of their disease, their symptoms, the palliative treatments received, and the site of death. RESULTS: The end stage was managed at the Istituto Nazionale Tumori Pediatric Oncology Department in 61% of cases, at home in 26%, and in hospices or other hospital facilities in 11%. Pain was the most common symptom, followed by asthenia, anorexia, dyspnea, and nausea/vomiting. About half the patients died at home, 8.5% at our institute, 43% at other hospitals, and 8.5% in hospices. CONCLUSIONS: The care of pediatric cancer patients during the end stage of their disease is the responsibility of the caregivers who have followed them up since their diagnosis. However, it would be useful to establish an exchange of information and expertise between pediatric oncologists and the other facilities involved (hospices, other hospitals) or people assisting patients at home (family, family pediatrician/general practitioner GP).
Subject(s)
Caregivers/psychology , Neoplasms/psychology , Terminal Care/psychology , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Male , Neoplasms/therapy , Palliative Care , Quality of Life/psychology , Retrospective Studies , Young AdultABSTRACT
Cathodic protection (CP), in combination with an insulating coating, is a preventative system to control corrosion of buried carbon steel pipes. The corrosion protection of coating defects is achieved by means of a cathodic polarization below the protection potential, namely -0.85 V vs. CSE (CSE, copper-copper sulfate reference electrode) for carbon steel in aerated soil. The presence of alternating current (AC) interference, induced by high-voltage power lines (HVPL) or AC-electrified railways, may represent a corrosion threat for coated carbon steel structures, although the potential protection criterion is matched. Nowadays, the protection criteria in the presence of AC, as well as AC corrosion mechanisms in CP condition, are still controversial and discussed. This paper deals with a narrative literature review, which includes selected journal articles, conference proceedings and grey literature, on the assessment, acceptable criteria and corrosion mechanism of carbon steel structures in CP condition with AC interference. The study shows that the assessment of AC corrosion likelihood should be based on the measurement of AC and DC (direct current) related parameters, namely AC voltage, AC and DC densities and potential measurements. Threshold values of the mentioned parameters are discussed. Overprotection (EIR-free < -1.2 V vs. CSE) is the most dangerous condition in the presence of AC: the combination of strong alkalization close to the coating defect due to the high CP current density and the action of AC interference provokes localized corrosion of carbon steel.
ABSTRACT
Titanium is well known as one of the most corrosion-resistant metals. However, it can suffer corrosion attacks in some specific aggressive conditions. To further increase its corrosion resistance, it is possible either to modify its surface, tuning either thickness, composition, morphology or structure of the oxide that spontaneously forms on the metal, or to modify its bulk composition. Part 2 of this review is dedicated to the corrosion of titanium and focuses on possible titanium treatments that can increase corrosion resistance. Both surface treatments, such as anodization or thermal or chemical oxidation, and bulk treatments, such as alloying, are considered, highlighting the advantages of each technique.
Subject(s)
Alloys/chemistry , Titanium/chemistry , Corrosion , Surface PropertiesABSTRACT
Titanium has outstanding corrosion resistance due to the external natural oxide protective layer formed when it is exposed to an aerated environment. Despite this, titanium may suffer different forms of corrosion in severe environments: uniform corrosion, pitting and crevice corrosion, hydrogen embrittlement, stress-corrosion cracking, fretting corrosion and erosion. In this first review, forms of corrosion affecting titanium are analyzed based on a wide literature review. For each form of corrosion, the mechanism and most severe environment are reported according to the current understanding.In the second part, this review will address the possible surface treatments that can increase corrosion resistance on commercially pure titanium: Electrochemical anodizing, thermal oxidation, chemical oxidation and bulk treatments such as alloying will be considered, highlighting the advantages of each technique.
Subject(s)
Environment , Titanium/chemistry , Alloys/chemistry , Animals , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacokinetics , Corrosion , Humans , Oxidation-Reduction , Oxides/chemistry , Stress, Mechanical , Surface Properties , Titanium/pharmacokineticsABSTRACT
BACKGROUND: In patients polysensitized to pollen allergens, the priming effect, by which the sensitivity of the nasal mucosa to an allergen is increased by the previous exposure to another allergen, is a known phenomenon. This study was aimed at evaluating the degree of nasal inflammation, assessed by nasal cytology, in children with allergic rhinitis (AR) from ragweed pollen according to being monosensitized or polysensitized. METHODS: The study included 47 children. Of them, 24 suffered from AR caused by sensitization to grass pollen and ragweed pollen (group A) and 23 were sensitized only to ragweed pollen (group B). In all patients, the severity of AR was assessed according to the Allergic Rhinitis and Its Impact on Asthma guidelines, and comorbidities were also evaluated. RESULTS: In group A, 16.7% of children had a mild intermittent AR, 4.2% a moderate-to-severe intermittent, 33.3% a mild persistent, and 45.8% a moderate-to-severe persistent; in group B, 26.1% of children had a mild intermittent AR, 0% a moderate-to-severe intermittent, 52.2% a mild persistent, and 21.7% a moderate-to-severe persistent. No significant difference was detected in the number of the considered comorbidities between the two groups. The cell counts of neutrophils, eosinophils, lymphocytes/plasma cells, and mast cells were high but not significantly different in the two groups. CONCLUSION: These findings show that the degree of nasal inflammation found in children with ragweed-induced AR is not influenced by additional allergy to grass pollen and confirm the previously reported absence of priming effect in ragweed allergy.
ABSTRACT
CONTEXT: Recombinant human GH (rhGH) reduces excess accumulation of intraabdominal adipose tissue (IAT) in lipodystrophic HIV-infected adults, whereas data in pediatric patients are lacking. OBJECTIVE: The objective of this study was to assess the efficacy of rhGH treatment on lipodystrophy in HIV-infected adolescents. DESIGN: The study is a prospective, 24-wk open-label study of rhGH. SETTING: The study was conducted at a referral center for pediatric HIV infection. PATIENTS AND OTHER PARTICIPANTS: Eight HIV-infected adolescents (ages, 13.7-18.5 yr), with abnormal IAT accumulation (>41 cm(2) at L4-magnetic resonance imaging) and 97 healthy controls (HC) (ages, 9.5-19.9 yr) were enrolled. INTERVENTION: rhGH was given by sc injection at a daily dose of 0.028 mg/kg. MAIN OUTCOME MEASURES: The main outcome was change in IAT at L4-magnetic resonance imaging. Body composition by dual-energy x-ray absorptiometry, glucose and lipid metabolism, and IGF-I changes were also evaluated. RESULTS: All patients completed the study period; none of them showed adverse event, and no change in the daily dose of rhGH was required. The treatment was associated with a mean height increase of 2.4 cm. From baseline to wk 24, IAT area decreased significantly by a median of 34.5% (-19.2 to -70%). Fat mass decreased significantly in patients, compared with HC, with a median loss of total, trunk, and arm and leg fat mass of 10.4, 10.9, 12.7, and 5.4%, respectively. Total, arm, and leg lean masses increased significantly, compared with HC. IGF-I increased significantly, but supraphysiological values of mild degree (2-23% over the upper normal limit) were detected in only nine of 24 samples. No significant effects on glucose metabolism, triglyceride, and cholesterol levels were observed. CONCLUSIONS: Our data showed that rhGH 0.028 mg/kg daily for 24 wk in HIV-infected adolescents reduces IAT, trunk, and also limb fat and increases lean mass. Overall, short-term rhGH is well tolerated and is not associated with a worsening of glucose and lipid metabolism.
Subject(s)
Adipose Tissue/drug effects , Growth Hormone/therapeutic use , HIV Infections/complications , Lipodystrophy/drug therapy , Adipose Tissue/metabolism , Adolescent , Antiretroviral Therapy, Highly Active , Body Composition/drug effects , Cholesterol/blood , Female , HIV Infections/drug therapy , HIV Infections/metabolism , Humans , Insulin-Like Growth Factor I/analysis , Male , Pilot Projects , Triglycerides/bloodABSTRACT
OBJECTIVE: To assess the impact on immunological, virological and metabolic parameters of replacing protease inhibitors (PIs) with efavirenz and replacing stavudine with tenofovir in HIV-infected children. METHODS: A 48-week prospective evaluation of 28 HIV-infected children, with stable undetectable HIV-1 loads, who were taking highly active antiretroviral therapy (HAART) containing lamivudine, stavudine and a PI. Individuals were randomized to switch PI to efavirenz and stavudine to tenofovir at baseline (Group 1) or at week 24 (Group 2). Patient assessment included: clinical evaluation, viral load, CD4+ T-cell count, fasting blood levels and urine samples. RESULTS: All individuals maintained HIV RNA <50 copies/ml and unchanged CD4+ T-cell count through week 48. In Group 1 individuals, a significant decrease in cholesterol (P < 0.05), cholesterol:high-density lipoprotein (HDL) ratio (P < 0.01) and triglycerides (P < 0.05) was observed 24 and 48 weeks after the switch of HAART. The percentage of Group 1 children with increased cholesterol and triglycerides markedly decreased over the study period (from 43% to 0% and from 36% to 7%, respectively). In Group 2 individuals, unchanged lipids in the 24 weeks prior to the switch of HAART and a significant improvement on cholesterol (P < 0.05), cholesterol:HDL ratio (P < 0.01) and triglycerides (P < 0.05) were observed 24 weeks after the switch of HAART. The percentage of Group 2 children with increased cholesterol and triglycerides markedly decreased 24 weeks after the switch of HAART (from 46% to 7% and from 54% to 0%, respectively). Proteinuria and glucosuria were not detected in any individual. The mean values of serum creatinine, serum phosphorus, serum bicarbonate, estimated glomerular filtration rate, urinary microalbumin/creatinine, alpha-1-microglobulin/creatinine ratio and maximal tubular phosphate reabsorption remained unchanged in both groups. CONCLUSIONS: In HIV-infected children, switching PI to efavirenz and stavudine to tenofovir is virologically and immunologically safe, is not associated with renal impairment and provides a significant improvement in lipid profile.
Subject(s)
Adenine/analogs & derivatives , Anti-HIV Agents/therapeutic use , Dyslipidemias/chemically induced , HIV Infections/drug therapy , HIV-1 , Organophosphonates/therapeutic use , Oxazines/therapeutic use , Protease Inhibitors/therapeutic use , Stavudine/therapeutic use , Adenine/therapeutic use , Adolescent , Alkynes , Antiretroviral Therapy, Highly Active , Benzoxazines , CD4 Lymphocyte Count , Child , Cyclopropanes , Female , HIV Infections/blood , HIV Infections/immunology , HIV Infections/virology , HIV-1/isolation & purification , Humans , Lipids/blood , Male , Protease Inhibitors/adverse effects , Stavudine/adverse effects , Tenofovir , Treatment Outcome , Viral LoadABSTRACT
Anti-Ro antibodies appear to represent a direct pathogenic factor in neonatal lupus (NL) neutropenia. Resolution of NL neutropenia is expected when anti-Ro antibodies are cleared. In this report, we describe a case of persistent neutropenia in a baby born to an anti-Ro-positive mother. The initial diagnosis of NL neutropenia was later called into question due to the identification of positive anti-neutrophil antibodies and transient hypogammaglobulinemia of infancy. The patient seemed to have had overlapping causes of her hematologic manifestations. To our knowledge, no other similar cases have been previously reported in the literature. Newborns are not routinely tested for white blood cell count, and several neutropenia cases remain undetected.
ABSTRACT
Chlorpromazine is a well-known antipsychotic agent that binds with a variety of receptors in the central nervous system. To date, chlorpromazine has never been associated with onset of hearing disorders and tinnitus. We report on an unexpected suspect adverse reaction to chlorpromazine that occurred in a 12-year-old boy, affected by severe generalized anxiety disorder. After treatment with chlorpromazine, the patient experienced an enhanced sensitivity to sounds accompanied by perception of noises of the buzzing or ringing type. This clinical case is of great clinical interest as chlorpromazine is not currently included among potentially ototoxic drugs.
ABSTRACT
OBJECTIVE: To gain information on safety of drugs used in pediatrics through a 4-year post-marketing active pharmacovigilance program. The program sampled the Italian population and was termed 'Monitoring of the Adverse Effects in Pediatric population' (MEAP). RESEARCH DESIGN AND METHODS: Adverse drug reactions (ADRs) were collected for individuals aged 0 - 17 years treated in hospitals and territorial health services in Lombardy, Tuscany, Apulia and Campania; located to gain an appropriate sampling of the population. ADRs were evaluated using the Adverse Drug Reaction Probability Scale (Naranjo) and analyzed with respect to time, age, sex, category of ADR, seriousness, suspected medicines, type of reporter and off-label use. RESULTS: We collected and analyzed reports from 3539 ADRs. Vaccines, antineoplastic and psychotropic drugs were the most frequently pharmacotherapeutic subgroups involved. Seventeen percent of reported ADRs were serious; of them fever, vomiting and angioedema were the most frequently reported. Eight percent of ADRs were associated with off-label use, and 10% were unknown ADRs. Analysis of these revealed possible strategies of therapy optimization. CONCLUSIONS: The MEAP project demonstrated that active post-marketing pharmacovigilance programs are a valid strategy to increase awareness on pediatric pharmacology, reduce underreporting and provide information on drug actions in pediatrics. This information enhances drug therapy optimization in the pediatric patients.
Subject(s)
Adverse Drug Reaction Reporting Systems/statistics & numerical data , Drug-Related Side Effects and Adverse Reactions/epidemiology , Pharmacovigilance , Product Surveillance, Postmarketing/methods , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Italy/epidemiology , Male , Off-Label Use/statistics & numerical data , Prospective StudiesABSTRACT
We assessed the presence of lung dysfunction in children with type 1 diabetes, evaluated as reduced diffusing capacity of the lung for carbon monoxide (DLCO), and its components: membrane diffusing capacity (DM) and pulmonary capillary blood volume (Vc). A total of 42 children, aged 15.6 ± 3.8 years, with type 1 diabetes for 8.3 ± 5.5 years, and 30 healthy age and sex-matched peers were recruited for the study. Lung volumes and spirometric dynamic parameters were assessed by plethysmography. Single-breath DLCO was measured according to international recommendation. DM and Vc volume were calculated. Lung volumes were significantly reduced in young patients with type 1 diabetes when compared to controls. Moreover, DLCO was reduced in patients compared to controls (78% ± 16% vs. 120% ± 1%, P = 0.0001). However, when differentiating DM and Vc compartments, we observed a significant impairment only about Vc (34 ± 20 ml vs. 88 ± 18 ml; P = 0.0001), while no difference was observed about DM compartment (23 ± 4 vs. 26 ± 3 ml/min/mmHg, P = 0.798). Whether this might be seen as the "first" sign of microangiopathic involvement in patients with type 1 diabetes has to be confirmed on larger groups but is still fascinating. Meanwhile, we suggest to screen DLCO in all patients with type 1 diabetes.
Subject(s)
Carbon Monoxide/metabolism , Diabetes Complications/diagnosis , Diabetes Complications/metabolism , Diabetes Mellitus, Type 1/complications , Pulmonary Diffusing Capacity , Adolescent , Case-Control Studies , Child , Cohort Studies , Diabetes Complications/etiology , Diabetes Complications/physiopathology , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 1/physiopathology , Diffusion , Female , Humans , Lung/metabolism , Lung/physiopathology , Male , Young AdultABSTRACT
PURPOSE: To evaluate morphologic changes in meibomian glands (MGs) and the status of periglandular inflammation in patients with primary and secondary Sjögren's Syndrome (SS) using in vivo confocal laser microscopy (LSCM). METHODS: Twenty patients with primary SS (SSI), 25 with secondary SS (SSII), 20 with MG dysfunction (MGD), and 25 age- and gender-matched control subjects were enrolled consecutively. Each participant completed an Ocular Surface Disease Index questionnaire and underwent a full eye examination, including tear film break-up time (BUT), fluorescein and lissamine green staining, Schirmer test, and an LSCM examination of the MGs, the last to determine acinar unit density and diameter, glandular orifice diameters, meibum secretion reflectivity, inhomogeneous appearance of glandular interstice, and acinar wall. RESULTS: All parameters indicated statistically significant differences among groups (P < 0.001, Kruskal-Wallis test). LSCM demonstrated no differences between SSI and SSII (Mann-Whitney U test). Compared with control subjects, SS subjects' MGs showed more periglandular inflammation and higher secretion reflectivity (P < 0.001, Mann-Whitney U test). Compared with MGD patients, SS patients' MGs had higher acinar density, smaller diameters, greater density of periglandular inflammatory cells, and lower secretion reflectivity (P < 0.001, Mann-Whitney U test). In SS patients, the two measured confocal signs of inflammation were significantly interrelated and correlated with corneal fluorescein staining (P ≤ 0.01, Spearman correlation coefficient). Acinar density and diameters were strongly correlated among themselves (P < 0.001) and with BUT (P < 0.05). CONCLUSIONS: LSCM is capable of effectively revealing morphologic and inflammatory changes in MGs and showed discernible patterns of MG abnormalities in SS and MGD not easily distinguishable by the usual clinical exams.
Subject(s)
Blepharitis/diagnosis , Eyelid Diseases/diagnosis , Meibomian Glands/pathology , Microscopy, Confocal , Sjogren's Syndrome/diagnosis , Adult , Aged , Aged, 80 and over , Cell Count , Female , Fluorescein , Humans , Lissamine Green Dyes , Male , Middle Aged , Staining and Labeling/methods , Surveys and QuestionnairesABSTRACT
PURPOSE: To investigate by laser scanning confocal microscopy (LSCM) the density of presumed epithelial, presumed goblet, and presumed inflammatory cells in the tarsal conjunctiva of healthy young and older subjects and in patients with Sjögren's syndrome (SS). To evaluate the interobserver variability and to compare the measured densities with known age-related and SS-related changes. METHODS: The authors studied 24 eyes of 12 healthy young subjects (8 women, 4 men; average age, 26 years; age range, 21-30 years), 24 eyes of 12 healthy older subjects (10 women, 2 men; average age, 68 years; age range, 67-74 years), and 24 eyes of 12 patients with SS (10 women, 2 men; average age, 62 years; age range, 49-72 years). The inferior tarsal conjunctiva of each patient was examined in vivo by LSCM. The density of the three cell types was independently analyzed by two masked investigators. RESULTS: The density of presumed epithelial, presumed goblet, and presumed inflammatory cells was significantly higher in SS patients than in both control groups (P < 0.001; Mann-Whitney U test). The densities for presumed goblet cells calculated by the two investigators were significantly different from one another (P < 0.01, Mann-Whitney U test) and were not correlated. CONCLUSIONS: LSCM is a promising tool that should profoundly change the study of the ocular surface, but it requires accurate standardization before it is used in clinical practice.