Could different aqueous humor and plasma cytokine profiles help differentiate between ocular sarcoidosis and ocular tuberculosis?

OBJECTIVE AND DESIGN: A cross-sectional single-center study was conducted to assess cytokine levels in aqueous humor (AH) and plasma of three different uveitis entities: definite ocular sarcoidosis (OS), definite OS associated with QuantiFERON®-TB Gold test positivity (Q + OS) and presumed tubercular uveitis (TBU). SUBJECTS: Thirty-two patients (15 OS, 5 Q + OS, 12 TBU) were included. METHODS: Quantification of selected cytokines was performed on blood and AH samples collected before starting any treatment. Statistical analysis was conducted using the Kruskal-Wallis test, the Mann-Whitney or Fisher test and the Principal Component Analysis (PCA). RESULTS: IL-6, IL-8 and IP-10 levels were higher in AH samples than in peripheral blood. In AH samples, BLC, IL-8 and IP-10 were significantly higher in definite OS than in presumptive TBU. There were no statistically significant differences in terms of cytokine levels between Q + OS and presumptive TBU. PCA showed a similar cytokine pattern in the latter two groups (IFNγ, IL-15, IL-2, IP-10, MIG), while the prevalent expression of BLC, IL-10 and MIP-3 α was seen in definite OS. CONCLUSIONS: The different AH and plasma cytokine profiles observed in OS compared to Q + OS and TBU may help to differentiate OS from TBU in overlapping clinical phenotypes of granulomatous uveitis (Q + OS).

Vogt-Koyanagi-Harada patients show higher frequencies of circulating NKG2Dpos NK and NK T cells.

Vogt-Koyanagi-Harada (VKH) is an autoimmune disease characterized by inflammation in tissues that contain melanocytes. We aimed to increase the knowledge regarding immunological pathways deregulated in VKH disease. We compared the percentages of circulating natural killer (NK), NK T and T cells expressing the activatory markers: CD16, CD69, NK group 2D (NKG2D), natural cytotoxicity triggering receptor 3 (Nkp30), natural cytotoxicity triggering receptor 1 (Nkp46) and the inhibitory marker: NK group 2 member A (NKG2A) in 10 active VKH patients, 20 control subjects (CTR) and seven patients with Behçet disease (BD) by flow cytometry. Cytotoxic potential of NK cells was determined through the degranulation marker CD107a expression after contact with K562 cells by flow cytometry. Moreover, plasmatic levels of 27 cytokines were determined with a multiplex bead-based assay. VKH patients showed higher percentages of NKG2Dpos NK and NK T cells versus CTR. The cytotoxic potential of NK cells induced by K562 cells was comparable between VKH patients and CTR. Finally, higher concentrations of interleukin (IL)-4, IL-5, IL-7, IL-17 and platelet-derived growth factor-subunits B (PDGF-bb) were detected in plasma of VKH patients versus CTR. The immune profile of VKH patients was similar to that of BD patients.

Exploiting within-breed variability in the autochthonous Reggiana breed identified several candidate genes affecting pigmentation-related traits, stature and udder defects in cattle.

Autochthonous cattle breeds constitute important reservoirs of genetic diversity. Reggiana is an Italian local cattle breed reared in the north of Italy for the production of a mono-breed Parmigiano-Reggiano cheese. Reggiana cattle usually have a classical solid red coat colour and pale muzzle. As part of the strategies designed for the sustainable conservation of this genetic resource, we investigated at the genome-wise level the within-breed detected variability of three pigmentation-related traits (intensity of red coat colour, based on three classes - light/diluted, normal and dark; spotted patterns/piebaldism that sometime emerge in the breed; muzzle colour - pink/pale, grey and black), stature, presence/absence and number of supernumerary teats and teat length. A total of 1776 Reggiana cattle (about two-thirds of the extant breed population) were genotyped with the GeneSeek GGP Bovine 150k SNP array and single-marker and haplotype-based GWASs were carried out. The results indicated that two main groups of genetic factors affect the intensity of red coat colour: darkening genes (including EDN3 and a few other genes) and diluting genes (including PMEL and a few other genes). Muzzle colour was mainly determined by MC1R gene markers. Piebaldism was mainly associated with KIT gene markers. Stature was associated with BTA6 markers upstream of the NCAPG-LCORL genes. Teat defects were associated with TBX3/TBX5, MCC and LGR5 genes. Overall, the identified genomic regions not only can be directly used in selection plans in the Reggiana breed, but also contribute to clarifying the genetic mechanisms involved in determining exterior traits in cattle.

Reggio Emilia (Northern Italy) Interdisciplinary Uveitis Clinic: What We Have Learned in the Last 20 Years.

PURPOSE: To analyze the referral patterns and the clinical and therapeutic features of patients diagnosed with uveitis in an Italian tertiary referral center to provide a comparison with previously published series from the same center. METHODS: Retrospective retrieval of data on all new referrals to the Ocular Immunology Unit in Reggio Emilia (Italy) between November 2015 and April 2022 and comparison with previously published series from the same center. RESULTS: Among the 1557 patients, the male-to-female ratio was 1:1.27. Anterior uveitis was the most common diagnosis (53.7%), followed by posterior (21.6%), pan- (18.5%), and intermediate (6.2%) uveitis. The most identifiable specific diagnoses were anterior herpetic uveitis (18.4%), Fuchs uveitis (12.8%), and tuberculosis (6.1%). Infectious etiologies were the most frequent (34.1%) and were more diffuse among non-Caucasian patients (p < 0.001), followed by systemic disease-associated uveitis (26.5%), and ocular-specific conditions (20%). Idiopathic uveitis accounted for 19.4% of cases. Fuchs uveitis presented the longest median diagnostic delay (21 months). Immunosuppressants were administered to 25.2% of patients. Antimetabolites, calcineurin inhibitors, and biologicals were prescribed to 18.4%, 3%, and 11.4% of cases, respectively. Compared to our previous reports, we observed a significant increase in foreign-born patients and in infectious uveitis, a decrease in idiopathic conditions, and an increasing use of non-biological and biological steroid-sparing drugs. CONCLUSIONS: The patterns of uveitis in Italy have been changing over the last 20 years, very likely due to migration flows. Diagnostic improvements and a more widespread interdisciplinary approach could reduce the incidence of idiopathic uveitis as well as diagnostic delay.

Intrahepatic lymphocyte phenotypes in hepatitis C virus infection: a comparison between cirrhotic and non-cirrhotic livers.

AIM: The pathogenesis of viral hepatitis involves the activation of cellular immunity, including intrahepatic lymphocytes (IHL). Lym-phocyte phenotypes play a fundamental role in the pathogenesis of chronic hepatitis C virus (HCV) infection, the progression of liver fibrosis and subsequent hepatocellular carcinoma. The aim of this study was to evaluate the frequency of intrahepatic mononuclear cell phenotypes in patients with chronic HCV. Another aim was to assess the relationship of nonparenchymal cells with liver fibrosis. METHODS: Liver fibrosis was evaluated with the Histologic Activity Index. Fourteen liver biopsies showed mild fibrosis (group 1), and 11 bridging fibrosis (group 2). Fourteen samples were explants from HCV patients who underwent liver transplantation (group 3). CD4 and CD8 T-lymphocytes, CD20 (B lymphocytes), CD16 (macrophage), and CD57 (NK) cells were detected using monoclonal antibodies on paraffin-embedded tissue. RESULTS: A minority of lobular cells stained for T- or B-lymphocytes. Most lobular cells stained with macrophage antibodies, and were more common in bridging fibrosis, compared to mild fibrosis. The percentages of lobular CD4 and CD8 cells were significantly lower in regenerative nodules of cirrhotic livers. There was a strong negative correlation between lobular CD8 and fibrosis score (R= -0.65), and a strong positive correlation between CD16-stained mononuclear cells (macrophages) and fibrosis score (R=0.66). In portal and periportal areas, CD4 but not CD8 lymphocytes decreased in parallel with fibrosis. B-lymphocytes were more commonly found in the portal areas than in the lobule. CD57-positive cells were rare in both lobule and portal areas, and their frequency was not different in the three groups studied. CONCLUSIONS: In hepatitis C, lobular mononuclear cells are mostly macrophages and appear associated with bridging fibrosis. Cirrhotic livers display significantly lower numbers of lobular CD4 and CD8 lymphocytes. This finding could help explain a decrease in immune surveillance and the promotion of neoplastic growth in HCV-associated cirrhosis.

Pathogenesis of hepatitis C virus infection.

The hepatitis C virus (HCV) is a single stranded RNA virus. In 60-80% of patients, it is able to escape innate and adaptive immune surveillance. Thus it establishes itself as an agent of chronic hepatitis. Cytotoxic lymphocytes then contribute to liver injury in an attempt to eradicate the virus. On the other hand, strong multispecific T-lymphocyte reaction against HCV proteins is associated with viral clearance. Both CD4+ and CD8+ lymphocyte functions are important to effect this outcome. In chronic infection, genetic and environmental factors determine the progression of inflammation and fibrosis in individual patients. Of these factors, age, gender, race and alcohol use are the most established ones. The development of hepatocellular carcinoma is mainly restricted to patients with cirrhosis.

Esophageal disease in human immunodeficiency virus infection.

Up to 40% of patients with the acquired immunodeficiency syndrome may develop symptoms of esophageal disease. Candida esophagitis is responsible for the majority of the cases of esophageal disease; cytomegalovirus, herpes simplex, idiopathic esophageal ulcers, and Kaposi's sarcoma account for most of the remaining cases. Although endoscopy with esophageal biopsy and brushing is the gold standard for the diagnosis of esophageal disease in the acquired immunodeficiency syndrome, we generally recommend initial empiric therapy with an antifungal agent in patients with esophageal symptoms. Since effective treatment is available for most cases of esophageal disease in the acquired immunodeficiency syndrome, we recommend endoscopic evaluation in patients who do not respond to empiric therapy within 1 to 2 weeks.

Hepatitis C in patients with human immunodeficiency virus infection: diagnosis, natural history, meta-analysis of sexual and vertical transmission, and therapeutic issues.

Hepatitis C (HCV) infection occurs in as many as 33% of the patients with human immunodeficiency virus (HIV) infection. In view of their improved survival, liver disease will become more clinically significant in patients coinfected with HIV/HCV. Several studies in patients with hemophilia have shown that coinfected patients develop earlier and more severe liver disease, including hepatocellular carcinoma. In nonhemophilic cohorts, lower CD4 counts are associated with an increased prevalence of cirrhosis. However, HCV infection does not seem to alter the natural history of HIV infection in most cases. Human immunodeficiency virus coinfection in pregnant women increases the risk of perinatal HCV transmission 2-fold, with more than 25% of occurrences involving transmission of both viruses: cesarean delivery significantly decreases this risk. The expanded use of highly active antiretroviral therapy may lead to further improvement in morbidity and mortality from HIV infection. Thus, the management of coexistent HCV liver disease will need to be formulated. We suggest that alcohol be disallowed. Interferon and ribavirin in combination are likely to become the therapy of choice, particularly in coinfected patients with higher CD4 counts, lower HCV viremia, and non-1 genotype. During treatment, complete blood cell counts need to be closely monitored. Future controlled trials will determine the efficacy and safety of long-acting interferon preparations. Administration of highly active antiretroviral therapy, with the intent to prevent decreases in CD4 counts, seems crucial in stemming liver disease progression. However, some drugs have clear-cut hepatotoxic potential and patients with known liver disease should be closely monitored. Arch Intern Med. 2000;160:3365-3373.

The causes of esophageal symptoms in human immunodeficiency virus infection. A prospective study of 110 patients.

STUDY OBJECTIVES: --To determine the prevalence of infectious agents in patients with human immunodeficiency virus infection and odynophagia or dysphagia; the utility of endoscopic, histologic, cytologic, and virologic testing for the diagnosis of esophagitis; and the yield of blind brushings of the esophagus in this setting. DESIGN: --Prospective clinical case study. SETTING: --Urban county hospital. PATIENTS: --One hundred ten consecutive patients with esophageal symptoms and documented human immunodeficiency virus infection. INTERVENTION: --Blind brushing of the esophagus via orogastric tube followed by endoscopy with esophageal brushing for fungal stain, Papanicolau smear, and viral cultures and esophageal biopsies for histologic examination and viral culture. MAIN RESULTS: --Seventy-two (65%) of the 110 patients had a total of 100 esophageal infections. Thirty-three (30%) had Candida alone, 22 (20%) had Candida and cytomegalovirus, two (1.8%) had Candida with cytomegalovirus and herpes simplex virus, seven (6%) had cytomegalovirus alone, six (5%) had herpes simplex virus alone, and two (1.8%) had both viruses. Fifty of 55 patients with plaques alone had Candida, and two (4%) had only viral infection. Of 19 patients with erosions or ulcers, 11 (58%) had a viral infection, two (11%) had Candida alone, and six (30%) had no etiologic agent identified. The sensitivity of endoscopic brushings (95%) was better than that of histologic examination (70%) in the diagnosis of Candida esophagitis. Likewise, viral cultures of brushings or biopsy specimens were more sensitive (67%) than histologic examination (35%) for viral esophagitis. Blind brushing of the esophagus had a sensitivity and specificity for infectious esophagitis of 84% and 75%, respectively. Oral thrush had a sensitivity of 53% and a positive predictive value of 77% for Candida esophagitis.

Cytomegalovirus and Candida esophagitis in patients with AIDS.

We define the clinical importance of cytomegalovirus (CMV) in the natural history of patients with concomitant candida and CMV infection of the esophagus. Prospective evaluation was made of patients with Candida and CMV esophagitis enrolled in a trial of antifungal therapy for Candida esophagitis. Retrospective review was also made of the course of patients who had been found to have both Candida and CMV infection during a previous prospective endoscopic study investigating the etiology of esophageal symptoms in HIV infection. Ten (21%) of 48 patients with Candida esophagitis in the prospective study had evidence of esophageal CMV (nine by culture, one by histology). One died after 4 weeks of therapy, with minimal retrosternal pain. None of the remaining nine had any symptoms or gross CMV esophagitis after antifungal therapy. Thirteen other patients with CMV and Candida were included in the retrospective review (mean follow-up of 8 months). Eight patients received antifungal therapy alone: six (CMV determined by histology in three and by culture in three) had symptomatic resolution; one (CMV by culture) had ongoing symptoms, and a second endoscopy showed an esophageal ulcer due to CMV (histology and culture); and one had ongoing symptoms but a negative repeat endoscopy. Two died without receiving treatment, and three were treated with antifungal and anti-CMV therapy together because of concurrent CMV retinitis (esophageal symptoms resolved in all three). Thus, CMV was of clinical importance in the esophagus in only one of 18 patients with CMV and Candida who received antifungal therapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Right posterior brain-damaged patients are poor at assessing the age of a face.

The ability to order unknown faces by age was investigated in right and left brain-damaged patients, divided into posterior and non-posterior groups on the basis of CT scan findings. A face recognition test and a figure ground discrimination test were also given. All three tests were affected by brain damage, but their sensitivity to the locus and side of lesion varied. While no hemispheric difference was found on the figure ground discrimination test, the face age test significantly discriminated patients with right posterior injury from any other brain-damaged group. The face recognition test occupied an intermediate position, with right posterior patients significantly impaired in comparison with right non-posterior patients and marginally impaired with respect to left posterior patients. Aphasia did not affect the performance of left brain-damaged patients on any of the tests. The findings are interpreted as evidence that damage of the right posterior hemisphere areas disrupts the structural encoding of visual information. Four prosopagnosic patients were also tested. Only those showing signs of apperceptive agnosia failed on the face age test.

Hepatobiliary complications in patients with human immunodeficiency virus infection.

Human immunodeficiency virus (HIV) infection has been associated with a number of hepatic and biliary tract disorders. Case reports, series of liver biopsies, and postmortem studies that examined the hepatobiliary system were retrieved with a MEDLARS search and form the basis of this review. The liver and biliary tract are frequently involved with opportunistic infections (most commonly mycobacteria and cytomegalovirus) and neoplasms (mainly Kaposi's sarcoma) in patients with HIV infection. The patients are often asymptomatic but may have elevated levels of serum liver enzymes. These abnormalities are nonspecific. Sulfa drugs, pentamidine, and ketoconazole are the medications used in HIV-related infections that are most likely to result in abnormalities on liver tests. Acalculous cholecystitis and sclerosing cholangitis also occur in HIV infection. Cytomegalovirus and Cryptosporidium are the organisms most commonly associated with these conditions. Imaging studies of the liver may detect parenchymal abnormalities and guide liver biopsy. The role of this procedure in the diagnosis of opportunistic infections and neoplasms is controversial because these lesions are generally disseminated at the time liver abnormalities are evident. A liver biopsy is best used when other less invasive procedures have failed to provide a diagnosis. Endoscopic retrograde cholangiopancreatography is a useful diagnostic procedure with therapeutic potential in patients with abdominal pain, fever, or an elevated serum alkaline phosphatase level.

Location and severity of cortical opacities in different regions of the lens in age-related cataract.

PURPOSE: To examine the distribution of cortical opacities across the lens in the Italian-American Natural History Study of Age-Related Cataract and to study the association between an index of sunlight exposure and the location of cortical cataract within the lens. METHODS: Lens photographs of one eye of 731 persons with cortical opacities (503 with pure and 228 with mixed types of opacity) were included in the analysis. A radial grid superimposed on the photographs was used to assess presence, location, and severity of wedge-shaped cortical opacities. RESULTS: Both the prevalence and the extent of cortical opacities were highest in the inferior-nasal quadrant and lowest in the superior-nasal quadrant of the lens. In polychotomous logistic regression, persons with the greatest excess areal involvement in the inferior half of the lens were more likely to have high exposure to sunlight, as measured by a sunlight index, than persons with excess involvement in the superior half of the lens (odds ratio, 1.73; 95% confidence interval 1.03, 2.93). Excess areal involvement of the inferior lens also was associated with the pure type of cortical cataract and with the total extent of the opacity. CONCLUSIONS: Age-related cortical opacities occur more frequently inferiorly than superiorly and, to a lesser extent, nasally than temporally. Possibly higher exposure of these lens segments to sunlight may explain this preferential location of cortical opacities.

The effect of cataract severity and morphology on the reliability of the Lens Opacities Classification System II (LOCS II).

Data collected from 3646 eyes in the Italian-American Natural History Study of Age-Related Cataract were used to investigate whether the reliability of the Lens Opacities Classification System II (LOCS II) by the severity of the opacity that is being graded or is influenced by the presence and severity of coexisting opacities. Reliability was assessed by comparing the slit-lamp gradings of two clinical examiners (346 eyes) and the gradings performed at the slit lamp with gradings of photographs (3646 eyes). The severity of cortical and nuclear opacities did not affect the reproducibility of slit-lamp gradings, but clinical grading of posterior subcapsular opacities became more reliable as the severity of the posterior subcapsular opacities increased. More advanced coexisting opacities decreased the agreement in the slit-lamp diagnosis of nuclear, but not cortical or posterior subcapsular, opacities. Comparisons of clinical and photographic gradings showed very good to excellent agreement for nuclear and cortical opacities, regardless of the severity of the specific opacity or the severity of the coexisting opacities. Agreement in diagnosing posterior subcapsular opacities was decreased in eyes with milder posterior subcapsular opacities and in eyes with more severe coexisting nuclear and/or cortical opacities. The effect of the severity of the opacity being graded and the severity of coexisting opacities on the reliability of the LOCS II must be considered in studies that use the system to classify and grade cataracts.

Influence of type and severity of pure forms of age-related cataract on visual acuity and contrast sensitivity. Italian American Cataract Study Group.

PURPOSE: To compare the relationship between logMAR visual acuity (VA) and cataract severity and between contrast sensitivity (CS) and cataract severity in pure types of age-related lens opacities. METHODS: Analysis included patients followed in the ongoing Italian-American Study of the Natural History of Age-Related Cataract. Lens opacities were classified and graded according to the Lens Opacities Classification System II (LOCS II). Visual acuity was measured with the Early Treatment Diabetic Retinopathy Study Chart. Contrast sensitivity was measured with the Pelli-Robson chart. RESULTS: Data from 1,076 eyes were used for the analysis (366 clear lenses; 550, 124, and 36 eyes with cortical, nuclear and posterior subcapsular cataract, respectively). In age-adjusted analyses, increasing severity of all three cataract types was associated with progressively higher logMAR VA, which translates into poorer acuity, and lower CS scores. For both VA and CS, the effect of increasing severity was greatest for nuclear and least for cortical opacities. After adjusting for age and VA, CS scores were no longer associated with cataract type and severity, with the exception of advanced cortical opacities. CONCLUSIONS: Increased cataract severity, as determined by LOCS II grading, is strongly associated with both VA and CS scores. Contrast sensitivity scores obtained from testing at low spatial frequency do not seem to offer additional information over standard VA testing in early cortical and posterior subcapsular opacities nor in nuclear cataracts.

Pleurodesis in metastatic pneumothorax.

A 57-year-old woman with bilateral pneumothoraces secondary to pulmonary metastases from leiomyosarcoma of the uterus was treated successfully by intrapleural instillation of tetracycline.

Vitreous fluorophotometry in juvenile diabetics after oral fluorescein.

Vitreous fluorophotometry was performed in young patients (8 to 19 years old) affected by insulin-dependent diabetes mellitus, with no signs of diabetic retinopathy. Oral fluorescein was administered, and measures were used to prevent hypoglycemia during the examination. The results showed a breakdown of the blood-retinal barrier in nine (43%) of the 21 patients. The oral fluorescein method allows a satisfactory evaluation of ocular fluorescence profiles, with minimal risk of systemic side effects.

Preliminary evaluation of a simple photographic cataract classification for epidemiological surveys.

A preliminary evaluation of the agreement between clinical and photographic cataract classification and its reproducibility by utilizing a very simple classification system is presented. Photographic classification was based on color Zeiss 75-SL transparencies. Results indicate that photo-derived cataract classification based on slitlamp photographs has good validity for nuclear opacities but tends to underestimate posterior subcapsular cataracts.

Esophageal disease in patients with AIDS: diagnosis and treatment.

Patients with HIV infection often present with symptoms suggesting esophageal disease: these include odynophagia (pain with swallowing), dysphagia (difficulty in swallowing), and retrosternal chest pain. Esophageal symptoms rank second only to diarrhea in frequency of gastrointestinal complaints among patients with AIDS. Also, esophageal opportunistic infections have been associated with a poor outcome, the mean survival after diagnosis being less than 6 months in one study. Such short survival may be explained by the underlying immunosuppression, as well as a decrease in nutritional intake due to difficulty swallowing.

Pruritus in patients with chronic human immunodeficiency virus, hepatitis B and C virus infections.

AIM: The prevalence of pruritus was prospectively determined in 310 patients of whom 119 had hepatitis C virus infection, 91 hepatitis C virus and human immunodeficiency virus, 51 human immunodeficiency virus infection alone, 31 hepatitis B virus and human immunodeficiency virus coinfection and 18 were HBsAg carriers. RESULTS: Patients in the first three groups were more likely to complain of itching (22%, 28% and 25%, respectively) than HBsAg carriers (8.2%, p=0.01. Laboratory data were not different between groups, except for the human immunodeficiency virus group, whose alkaline phosphatase levels were highest, and CD4 counts were lowest (median 30 cells/mm3). Patients with hepatitis C, including those with human immunodeficiency virus, had similar hepatitis C virus RNA levels in patients with or without pruritus. There was no difference in hepatic inflammation or fibrosis between those with and those without pruritus. CONCLUSION: 20% of patients with chronic hepatitis C and 8% of hepatitis B patients complain of pruritus. Patients with pruritus have laboratory and histologic parameters comparable to those without.