Anterior Segment Optical Coherence Tomography in Uveitis-Glaucoma-Hyphema Syndrome.

PURPOSE: Uveitis-Glaucoma-Hyphema (UGH) syndrome results from contact between the intraocular lens (IOL) and the iris or ciliary body, leading to uveal structure erosion and blood-aqueous barrier breakdown. Treatment involves various drugs, with IOL removal often being necessary. Diagnosis relies on clinical signs, but imaging techniques like ultrasound biomicroscopy (UBM) or anterior segment optical coherence tomography (AS-OCT) are crucial. AS-OCT accurately depicts IOL position and potential contact, emerging as a primary alternative to UBM in the diagnosis. Our study aimed to correlate AS-OCT findings with clinically detectable iris atrophy in pseudophakic patients with IOL-iris chafing and UGH syndrome. METHODS: The study retrospectively analyzed patients diagnosed with UGH syndrome presenting at the Ocular Immunology Unit of Reggio Emilia, Italy, from January 2019 to August 2023. Patients' data were collected. Ophthalmological exams and imaging were performed. The peephole sign in AS-OCT images was evaluated. Statistical analyses were conducted, with a significance level of p ≤ 0.05. RESULTS: The study reviewed 22 eyes of 22 patients with UGH syndrome. Four eyes were excluded, leaving 18 patients (8 females, 10 males). Common misdiagnoses included idiopathic anterior uveitis (55.5%) and herpetic anterior uveitis (16.7%). All patients had iris transillumination defects, mostly focal (77.8%). AS-OCT revealed IOL chafing in all the eyes, with peephole sign correlation. More peephole signs occurred with IOL in the sulcus (p-value = 0.08). CONCLUSION: The study recommends AS-OCT for UGH syndrome confirmation and UBM when IOL-iris chafing is not observed on AS-OCT scans.

Microstructural Visual Pathway White Matter Alterations in Primary Open-Angle Glaucoma: A Neurite Orientation Dispersion and Density Imaging Study.

BACKGROUND AND PURPOSE: DTI studies of patients with primary open-angle glaucoma have demonstrated that glaucomatous degeneration is not confined to the retina but involves the entire visual pathway. Due to the lack of direct biologic interpretation of DTI parameters, the structural nature of this degeneration is still poorly understood. We used neurite orientation dispersion and density imaging (NODDI) to characterize the microstructural changes in the pregeniculate optic tracts and the postgeniculate optic radiations of patients with primary open-angle glaucoma, to better understand the mechanisms underlying these changes. MATERIALS AND METHODS: T1- and multishell diffusion-weighted scans were obtained from 23 patients with primary open-angle glaucoma and 29 controls. NODDI parametric maps were produced from the diffusion-weighted scans, and probabilistic tractography was used to track the optic tracts and optic radiations. NODDI parameters were computed for the tracked pathways, and the measures were compared between both groups. The retinal nerve fiber layer thickness and visual field loss were assessed for the patients with glaucoma. RESULTS: The optic tracts of the patients with glaucoma showed a higher orientation dispersion index and a lower neurite density index compared with the controls (P < .001 and P = .001, respectively), while their optic radiations showed a higher orientation dispersion index only (P = .003). CONCLUSIONS: The pregeniculate visual pathways of the patients with primary open-angle glaucoma exhibited a loss of both axonal coherence and density, while the postgeniculate pathways exhibited a loss of axonal coherence only. Further longitudinal studies are needed to assess the progression of NODDI alterations in the visual pathways of patients with primary open-angle glaucoma across time.

Interferon Alpha-2a Treatment for Post-Uveitic Refractory Macular Edema.

Purpose: To assess the efficacy of interferon (IFN) alpha-2a in the treatment of post-uveitic refractory macular edema (ME).Methods: Retrospective cohort of patients with post-uveitic refractory ME, who received subcutaneous IFN alpha-2a injections for at least 3 months. Baseline central macular thickness (CMT) and best-corrected visual acuity (BCVA) were compared with those at follow-up visits up to 12 months.Results: Thirty-seven patients were included. Treatment duration (median [interquartile range]) was 14[8-24] months with a follow-up of 17[10-38] months. CMT (mean [standard deviation]) decreased from 438[140] to 335[119] µm after 1 month (p < 0.0001) and remained significantly lower up to 12 months (286[98] µm, p = 0.001). BCVA (0.48[0.33] logMAR at baseline) improved by 0.26[0.33] logMAR (p = 0.001) at 12 months. There were 14 recurrences. Seven patients had treatment side effects, without serious adverse events.Conclusions: IFN alpha-2a was effective, safe, and well tolerated in treating post-uveitic refractory ME.

Spontaneous formation and relaxation of spin domains in antiferromagnetic spin-1 condensates.

Many-body systems at low temperatures generally organize themselves into ordered phases, whose nature and symmetries are captured by an order parameter. This order parameter is spatially uniform in the simplest cases, for example the macroscopic magnetization of a ferromagnetic material. Non-uniform situations also exist in nature, for instance in antiferromagnetic materials, where the magnetization alternates in space, or in the so-called stripe phases emerging for itinerant electrons in strongly correlated materials. Understanding such inhomogeneously ordered states is of central importance in many-body physics. Here we study experimentally the magnetic ordering of itinerant spin-1 bosons in inhomegeneous spin domains at nano-Kelvin temperatures. We demonstrate that spin domains form spontaneously, that is purely because of the antiferromagnetic interactions between the atoms and in the absence of external magnetic forces, after a phase separation transition. Furthermore, we explore how the equilibrium domain configuration emerges from an initial state prepared far from equilibrium.

Alpha tocopherol loaded chitosan oleate nanoemulsions for wound healing. Evaluation on cell lines and ex vivo human biopsies, and stabilization in spray dried Trojan microparticles.

An amphiphilic chitosan salt, chitosan oleate (CS-OA), was previously proposed for the physical stabilization of lemongrass antimicrobial nanoemulsions (NE) through a mild spontaneous emulsification process. As both chitosan and oleic acid are described in the literature for their positive effects in wound healing, in the present study CS-OA has been proposed to encapsulate alpha tocopherol (αTph) in NEs aimed to skin wounds. A NE formulation was developed showing about 220 nm dimensions, 36% drug loading, and αTph concentration up to 1 mg/ml. Both CS-OA and αTph NE stimulated cell proliferation on keratinocytes and fibroblast cell cultures, and in ex vivo skin biopsies, suggesting the suitability of CS-OA and of the antioxidant agent for topical application in wound healing. αTph stability was further improved with respect of encapsulation, by spray drying the NE into a powder (up to about 90% αTph residual after 3 months). The spray drying process was optimized, to improve powder yield and αTph recovery, by a design of experiments approach. The powder obtained was easily re-suspended to deliver the NE and resulted able to completely release αTph.

Stepwise Bose-Einstein Condensation in a Spinor Gas.

We observe multistep condensation of sodium atoms with spin F=1, where the different Zeeman components m_{F}=0,±1 condense sequentially as the temperature decreases. The precise sequence changes drastically depending on the magnetization m_{z} and on the quadratic Zeeman energy q (QZE) in an applied magnetic field. For large QZE, the overall structure of the phase diagram is the same as for an ideal spin-1 gas, although the precise locations of the phase boundaries are significantly shifted by interactions. For small QZE, antiferromagnetic interactions qualitatively change the phase diagram with respect to the ideal case, leading, for instance, to condensation in m_{F}=±1, a phenomenon that cannot occur for an ideal gas with q>0.

The Pathology of Aging 129S6/SvEvTac Mice.

The 129 mouse strain is commonly used for the generation of genetically engineered mice. Genetic drift or accidental contamination during outcrossing has resulted in several 129 substrains. Comprehensive data on spontaneous age-related pathology exist for the 129S4/SvJae substrain, whereas only limited information is available for other 129 substrains. This longitudinal aging study describes the life span and spontaneous lesions of 44 male and 18 female mice of the 129S6/SvEvTac substrain. Median survival time was 778 and 770 days for males and females, respectively. Tumors of lung and Harderian gland were the most common neoplasms in both sexes. Hepatocellular tumors occurred mainly in males. Hematopoietic tumors were observed at low frequency. Suppurative and ulcerative blepharoconjunctivitis was the most common nonneoplastic condition in both sexes. Corynebacteria (primarily Corynebacterium urealyticum and C. pseudodiphtheriticum) were isolated from animals with blepharoconjunctivitis and in some cases from unaffected mice, although a clear causal association between corynebacterial infections and blepharoconjunctivitis could not be inferred. Polyarteritis occurred only in males and was identified as the most common nonneoplastic contributory cause of death. Eosinophilic crystalline pneumonia occurred in both sexes and was a relevant cause of death or comorbidity. Epithelial hyalinosis at extrapulmonary sites was noted at higher frequency in females. This study contributes important data on the spontaneous age-related pathology of the 129S6/SvEvTac mouse substrain and is a valuable reference for evaluation of the phenotype in genetically engineered mice obtained with this 129 substrain.

Diffuse scaling dermatitis in an athymic nude mouse.

This report describes the clinicopathological features of a case of diffuse scaling dermatitis that occurred in a 16-week-old female athymic nude (CrTac:NCr-Foxn1(nu)) mouse. Gross presentation was suggestive of Corynebacterium bovis infection (scaly skin disease). However, C. bovis was not isolated from the skin of the affected animal or from the skin of unaffected CrTac:NCr-Foxn1(nu) mice housed in the same cage or room. Staphylococcus xylosus was instead isolated in high numbers from the skin lesion, whereas only a few colonies were recovered from the skin of unaffected mice. Microscopically, the affected skin was characterized by chronic hyperplastic and hyperkeratotic dermatitis with focal ulcerations, extensive serocellular crusts, and intralesional clusters of Gram-positive coccoid bacteria. Although gross presentation of the reported case was suggestive of C. bovis infection, epidemiological, histopathological, and bacteriological findings definitively ruled out an outbreak of scaly skin disease. A diagnostic hypothesis of hyperplastic and hyperkeratotic dermatitis associated with opportunistic S. xylosus infection was formulated based on increased bacterial burden and presence of intralesional Gram-positive coccoid bacteria.

Monoclonal antibody to fibulin-1 generated by genetic immunization.

Fibulin-1 (Fbln-1) is an extracellular matrix (ECM) and plasma glycoprotein. Considering the growing evidence indicating that Fbln-1 plays a role in cancer we sought to develop monospecific antibodies to better facilitate further studies of the function of Fbln-1 in breast cancer. Using a plasmid expression vector encoding full-length human Fbln-1D as an immunogen and CpG oligodeoxyribonucleotides as adjuvant a monoclonal antibody (MAb) against Fbln-1 was produced. This MAb, designated MEM-2 was of IgM isotype and reacted with bacterially expressed Fbln-1. Furthermore, MEM-2 reacted with Fbln-1 expressed in the ECM released by cultured human breast carcinoma SKBR-3 cells in ELISA, and also with Fbln-1 present in SKBR-3 cell extract in immunoprecipitation and Western blotting. MEM-2 also reacted with Fbln-1 in human breast carcinoma specimens. These findings illustrate the utility of genetic immunization as a means of generating monoclonal antibodies to tumor-related ECM proteins. MEM-2 represents a useful new tool for the study of Fbln-1 in breast cancer.

Prevention of spontaneous neu-expressing mammary tumor development in mice transgenic for rat proto-neu by DNA vaccination.

The HER-2/neu proto-oncogene is overexpressed in 20-30% of human breast cancers and is associated with high recurrence risk. The oncogenic potential of HER-2/neu, together with its elevated expression in tumors, cell surface localization, and immunogenicity in some patients, make this oncoprotein an ideal target for immunotherapeutic approaches. To test the efficacy of immune-based strategies in eliciting an antitumor response, we used the N#202 transgenic mouse model engineered to overexpress the rat neu proto-oncogene under the control of the mouse mammary tumor virus promoter; females of this line develop spontaneous focal mammary tumors by 6 months of age. Transgenic mice immunized intramuscularly with a HER-2 cDNA ligated into the VR1012 (VICAL) expression vector under the control of the cytomegalovirus promoter developed significantly fewer spontaneous tumors as compared with mice injected with the empty vector (P < 0.0001) or not injected (P = 0.0006). However, this protection was observed only when immunization was started in 3-month-old but not in 6-month-old mice. These data suggest that the xenogeneic HER-2 DNA sequence can break immune tolerance to rat neu in transgenic N#202 mice and induce protective immunity that impairs the neu oncogene-driven progression of mammary carcinogenesis. The preventive effect achieved by our immunological approach appeared not to be based on anti-neu specific B and T cell immune attacks but was more possibly based on different mechanisms including aspecific and inflammatory immunological responses.

p185(neu) protein is required for tumor and anchorage-independent growth, not for cell proliferation of transgenic mammary carcinoma.

Transgenic FVB-NeuN mice (N202) bearing the rat neu protooncogene driven by the mouse mammary tumor virus promoter/enhancer develop focal mammary carcinomas overexpressing the neu-encoded p185(neu) protein. In vitro expression of p185(neu) among mammary carcinoma cultures was heterogeneous, and we could establish some cell lines and clones displaying a complete loss of p185(neu) expression, along with others with very high p185(neu) protein level. Upon in vivo injection, p185(neu)-positive cells gave rise to fast-growing tumors with a short latency, while p185(neu)-negative cells required a very long latency time, and the resulting tumors were invariably p185(neu)-positive. The lower growth ability of p185(neu)-negative cells in vivo was also confirmed in athymic nude mice. In vitro, analysis of anchorage-independent growth in soft agar revealed colony formation from p185(neu)-positive but not p185(neu)-negative cells. The direct involvement of p185(neu) in clonogenicity was demonstrated by the inhibition of p185(neu)-positive colony growth in soft agar in the presence of an anti-p185(neu) monoclonal antibody. By contrast, a higher level of anchorage-dependent clonogenic growth and proliferation was observed in p185(neu)-negative cells as compared to p185(neu)-positive cells, thus explaining the relative ease with which p185(neu)-negative cell lines and clones were established in vitro. Together, the results indicate that p185(neu) expression can lead to tumor formation and metastasis through the modification of intrinsic properties of cells related to anchorage-independent growth ability rather than to proliferation or host-dependent mechanisms.

Ectopic expression of pRb2/p130 suppresses the tumorigenicity of the c-erbB-2-overexpressing SKOV3 tumor cell line.

We investigated the in vitro and in vivo effects of the ectopic expression of the pRb2/p130 cell cycle regulator on c-erbB-2-associated tumorigenicity. SKOV3 ovarian cancer cells, which display c-erbB-2 gene amplification and oncoprotein (p185HER2) overexpression, were stably transfected with a plasmid containing the coding sequence for human wild-type pRb2/p130 (wtRb2), or with pcDNA3 empty vector. Three wtRb2-transfected clones (cl. 24, ci. 49, cl. 100) and one empty vector-transfected clone (cl. mock) were randomly picked and further analysed. Western blot analysis revealed high levels of pRb2/p130 in the three clones compared to mock cells. Levels of p185HER2 and the extent of its tyrosine phosphorylation were similar in all transfectant clones, as were levels of pRb1 and p107. In anchorage-independent growth assays, the number of colonies from wtRb2 clone-transfectants was about 90% less than that arising from mock cells (P<0.001). Tumor take rates of the three wtRb2-transfected clones xenografted in nu/nu mice were much lower than those of mock cells, and tumor volume was decreased by 80% (P<0.001). A mutant version of pRb2/p130 deleted of the pocket region (mut-Rb2) was also transfected into SKOV3 cells and studied in parallel with the wtRb2-transfected and pcDNA empty vector-transfected bulk populations. mut-Rb2 transfected cells showed no inhibition of in vitro colony formation and were fully tumorigenic. Together, these findings indicate that Rb2 acts as a tumor suppressor gene in vivo and in vitro in SKOV3 cells and that the intact pocket region is required for the suppressor activity.

Macrophage infiltrate and prognosis in c-erbB-2-overexpressing breast carcinomas.

PURPOSE: Experiments were designed to investigate the association between tumor leukocytic infiltrates with other pathologic and biologic variables in primary tumors and with prognosis, and to define the phenotype of the infiltrating leukocytes. PATIENTS AND METHODS: A retrospective series of 1,207 primary breast carcinomas was studied according to different prognostic variables, including the presence of lymphoplasmacytic infiltrate (LPI). LPI was analyzed in association with other variables and survival. Additionally, a small prospective series of surgical specimens from 75 primary breast carcinomas with infiltrating leukocytes was tested by immunohistochemistry on frozen sections to phenotypically characterize the infiltrate, using anti-CD reagents, and the tumor, using anti-c-erbB-2 oncoprotein monoclonal antibody. RESULTS: In the retrospective series, menopausal status, nodal status, tumor size, stage, grade, and p185HER2 overexpression but not LPI were found to be associated with prognosis and maintained their prognostic significance in a multivariate analysis. LPI was significantly associated with some of these independent prognostic factors, such as tumor size (P = .03), stage (P = .004), grade III carcinomas (P < .000001), and overexpression of the p185HER2 (P < .000001). In some subgroups of patients in whom LPI was found more frequently, such as grade III cases or N- and c-erbB-2-positive cases, LPI was found to be indicative of a good prognosis (P = .008 and P = .03, respectively). Phenotypic analysis of the infiltrating leukocytes revealed a preponderance of macrophages in high-grade (P = .05) or c-erbB-2-positive (P = .008) tumors, whereas T cells constituted most of the infiltrate in the other tumors. CONCLUSION: Our data demonstrate different leukocytic types in the infiltrate of breast tumors with different prognostic significance.

[Exclusive radiotherapy of pyriform sinus carcinomas. Retrospective analysis of 90 cases]. / La radioterapia esclusiva dei carcinomi del seno piriforme. Analisi retrospettiva di 90 casi.

In the present study 90 patients affected with pyriform sinus carcinomas are analyzed. They underwent irradiation alone from 1970 to 1986. All cases were staged according to TNM criteria (UICC 1982): 7 were T1, 16 T2, 40 T3, 27 T4, 36 N0, 18 N1, 3 N2, 33 N3. Radiotherapy was performed with 60Co. In all cases doses of 60-70 Gy were delivered to T and N1 and doses of 45-50 Gy to N0. Locoregional control obtained in 35 patients (38.9%): 6/7 T1 (85.7%), 9/16 T2 (56.2%), 15/40 T3 (37.5%), 5/27 T4 (18.5%) and 20/36 N0, 8/18 N1, 1/3 N2, 6/33 N3. The overall and NED 3-year survival rates are 23.3% (21/90) and 20.0% (18/90), respectively; at 5 and 10 years all patients alive are NED, with survival rates of 12.2% (11/90) and 9.8% (5/51) respectively. Locoregional failures were observed in 12/35 cases (34.3%); 91% of them occurred within the first two years of follow up (mean: 10 months). Distant metastases appeared in 26/90 patients (28.9%) and secondary tumors occurred in 10/90 cases (11.1%). Our experience confirms radiotherapy to be an effective alternative treatment to surgery in the early stages (I-II) of pyriform sinus carcinomas, but no more than only a palliative treatment in stage III-IV cancers.

[Radiotherapy in the treatment of carcinomas of the base of the tongue. Analysis of the literature and personal experience]. / La radioterapia nel trattamento dei carcinomi della base della lingua. Analisi della letteratura ed esperienza personale.

Carcinoma of the base of the tongue is usually treated with radiation therapy. After a review of the literature, the findings are reported of 129 patients with squamous cell carcinoma of the base of the tongue treated in 1979-1983, with a minimum of a 3-year follow-up: 8 T1, 40 T2, 60 T3 and 21 T4 were found; only 48 cases were N0. Advanced stages (stage III and stage IV) were 83% of the total. External photon irradiation (Cobalt-60) was used in all cases; 33 patients underwent chemotherapy or surgery as additional treatment. The overall local control rate was 45.7%. Local control decreased as T stage advanced: T1 62.5%, T2 55%, T3 41.7% and T4 33.3%. The overall regional control rate for lymph nodes clinically palpable was 51.8%. The overall actuarial 5-year survival rate was 29.1%. The 5-year survival rate according to the N-staging varied from 37% for N0-stage to 17.4% for N3-stage. The majority of failures (92.8%) occurred within 2 years since the end of the therapy. Treatment complications, secondary carcinomas and causes of death are also discussed. Radiation therapy has proven to be effective for early-stage carcinoma of the base of the tongue; in more extensive lesions results are poor. Improved results could be obtained by optimal application of radiotherapeutic techniques. Knowledge of the various prognostic factors is essential to administer the therapeutic regimen for a given patient by the characteristics of his particular tumor.

[Chemo-radiotherapeutic treatment of non-seminoma germ cell tumors of the testis in the advanced stage]. / Trattamento chemio-radioterapico dei tumori germinali del testicolo non seminomi in fase avanzata.

The results obtained in 18 patients suffering from non seminomatous germ cell tumours of the testis (stage IIC, IID, III), treated at the Division of Radiotherapy-Ospedale Maggiore Novara with chemotherapy and radiotherapy are presented. The radiotherapy technique is described particularly with reference to the use of large fields. CR and PR were obtained in 83.3% and 16.7% of the patients respectively. After a follow up from 13 to 60 months (median 40 months), the total survival is 88.9% and the NED survival is 77.8%.

[Carcinoma of the paranasal sinuses. Results with radiotherapy alone or with a radio-surgical combination]. / Carcinomi dei seni paranasali. Risultati del trattamento con radioterapia sola o con associazione radio-chirurgica.

The authors evaluate 117 patients affected by paranasal sinuses carcinoma treated by radiation therapy alone or by post-operative irradiation, from 1976 to 1984. Among these: 4 T1, 21 T2, 48 T3 and 44 T4; 66 cases were squamous cell carcinomas, 23 adenocarcinomas, 16 undifferentiated carcinomas and 12 adenoid cystic carcinomas. The overall 3 and 5 years actuarial survival rates were, respectively, 46% and 27%. The survival rates for stages T1 and T2 were 82 and 48% at 3 and 5 years; for stages T3 and T4 were 36% and 21%. According to the hystological type the survival rate varied from 50% for adenoid cystic carcinomas to 0% for undifferentiated carcinomas at 5 years. The survival rate for the group of patients treated with post-operative irradiation was 37% at 5 years, versus 10% for the group treated by radiotherapy alone. Complications have been minimal. Causes of failure are discussed. In conclusion, the authors consider a multicentric study as necessary to determine the efficacy of various schedules of treatment.

Comparison of pharmacokinetics of sodium and lysine cephalexin in calves.

The pharmacokinetics of sodium and lysine cephalexins were investigated after intravenous and intramuscular administration of a single dose rate of 30 mg.kg-1 body weight in calves. The data for the two salts administered intravenously were pooled, the resulting pharmacokinetic disposition of cephalexin indicating a distribution half-time (t1/2 alpha) and an elimination half-time (t1/2 beta) of 9.78 and 62.0 min, respectively. Following intramuscular administration some pharmacokinetic differences were recorded between the cephalexin preparations: lysine cephalexin was more rapidly eliminated (t1/2kel = 55.2 min) than sodium cephalexin (t1/2kel = 89.8 min), although the peak blood level was higher and attained after a longer time with lysine cephalexin.

[Curie therapy with 192 iridium on a moulded apparatus in the treatment of tumors of the hard palate]. / La curieterapia con 192iridio su apparecchio modellato nel trattamento dei tumori del palato duro.

Complete regression of the primary tumour was observed when a shaped apparatus loaded with 192Ir wires was used in the treatment of 6 patients with neoplasia of the hard palate, whereas very slight changes were noted in another subject. Fatal locoregional adenopathy appeared after 6 months in one of these 6 patients without prejudice to the cure obtained in the primary site.

Effects of Caerulein on exocrine pancreatic secretion in sheep.

caerulein administered by slow intravenous infusion at increasing dosage rates (0.1, 1.0, 5.0 and 10.0 ng/kg/min X 30 min) stimulated pancreatic juice production in sheep as well as the protein content, the amylolytic, the lipolytic and proteolytic activities of pancreatic juice samples collected at 30 min intervals. A long lasting (300 min) infusion of a high dose of Caerulein by subcutaneous route elicited stimulatory effects with reduced intensities, slower onsets but more sustained durations than those produced by the same dose level administered intravenously.