Serological evidence for the co-circulation of two lineages of influenza D viruses in equine populations of the Midwest United States.

Influenza D virus (IDV) is a newly described influenza type of the Orthomyxoviridae virus family that was first isolated from diseased swine in 2011 and has subsequently been detected in cattle around the world in 2014. In addition, serological evidence for IDV infection in humans has been recently established. Despite all the progress, the full range of susceptible hosts for this novel virus has yet to be determined, but includes swine, bovine, small ruminants and human. This study was designed to determine if equine is a possible host to this newly emerging influenza virus. Three hundred and sixty-four equine serum samples were collected in 2015 from 141 farms within the Midwestern United States. Serum samples were examined using hemagglutination inhibition (HI) assay against two established IDV lineages (D/OK and D/660) and one IDV-related human ICV lineage (C/JHB). Results of this study showed 44 (44 of 364, 12%) samples positive for antibodies against D/OK, 39 (39 of 364, 11%) samples positive for antibodies against D/660, and 41 (41 of 364, 11%) samples positive for antibodies against C/JHB. A subset of these samples was further confirmed via microtitre neutralization (MN) assay. Our data demonstrated that horses are susceptible to two lineages of IDV, and that these viruses were present in equine populations throughout multiple Midwestern states of the United States. These findings continue to support the need for further surveillance of IDV viruses in agricultural species to work towards a better understanding of the full host range and natural reservoirs of influenza D virus.

Retinal nerve fiber layer thickness and neuropsychiatric manifestations in systemic lupus erythematosus.

Background Cognitive impairment is frequent in systemic lupus erythematosus. Atrophy of the corpus callosum and hippocampus have been reported in patients with systemic lupus erythematosus, and diffusion tensor imaging studies have shown impaired white matter integrity, suggesting that white matter damage in systemic lupus erythematosus may underlie the cognitive impairment as well as other neuropsychiatric systemic lupus erythematosus manifestations. Retinal nerve fiber layer thickness, as assessed by optical coherence tomography, has been suggested as a biomarker for white matter damage in neurologic disorders such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. Retinal nerve fiber layer thinning may occur early, even in patients with mild clinical symptoms. Aim The objective of this study was to assess the association of retinal nerve fiber layer thickness, as a biomarker of white matter damage in systemic lupus erythematosus patients, with neuropsychiatric systemic lupus erythematosus manifestations, including cognitive impairment. Methods Twenty-one consecutive patients with systemic lupus erythematosus underwent neuropsychological testing using a validated computerized battery of tests as well as the Rey-Auditory verbal learning test. All 21 patients, as well as 11 healthy, age matched controls, underwent optical coherence tomography testing to assess retinal nerve fiber layer thickness. Correlations between retinal nerve fiber layer thickness and results in eight cognitive domains assessed by the computerized battery of tests as well as the Rey-Auditory verbal learning test were assessed in patients with systemic lupus erythematosus, with and without neuropsychiatric systemic lupus erythematosus, and compared to retinal nerve fiber layer thickness in healthy controls. Results No statistically significant correlation was found between retinal nerve fiber layer thickness in patients with systemic lupus erythematosus as compared to healthy controls. When evaluating by subgroups, no correlation was found between patients with or without neuropsychiatric systemic lupus erythematosus or cognitive impairment and retinal nerve fiber layer thickness. Conclusion Retinal nerve fiber layer thickness of systemic lupus erythematosus patients was not found to be statistically different compared to controls. Within systemic lupus erythematosus patients there was no correlation between retinal nerve fiber layer thickness and cognitive impairment or other neuropsychiatric systemic lupus erythematosus manifestations.

Implementation of recommendations for the screening of hydroxychloroquine retinopathy: poor adherence of rheumatologists and ophthalmologists.

The American Academy of Ophthalmology published in 2011 revised recommendations regarding screening for hydroxychloroquine (HCQ) toxicity. We aimed to assess implementation of these recommendations by rheumatologists and ophthalmologists. A questionnaire regarding screening practices for HCQ toxicity was distributed among all members of the Israeli societies of Rheumatology and Ophthalmology. A total of 128 physicians responded to the questionnaire (rheumatologists: 60, ophthalmologists: 68). Only 5% of the rheumatologists and 15% of the ophthalmologists are aware of ophthalmologic assessments recommended for baseline and follow-up evaluation. When an abnormal test is detected, even if inappropriate for HCQ toxicity screening, 60% of the responders recommend cessation of therapy. Only 13% of the responders recommend first follow-up after five years for patients without risk factors; the remainder recommend more frequent testing. Ninety-six percent of the responders are not aware of all of the known risk factors for HCQ toxicity. Use of inappropriate tests to detect HCQ retinal toxicity may lead to unnecessary cessation of beneficial treatment with risk of disease flare, while lack of consideration of risk factors may put patients at risk for toxicity. These results emphasize the importance of implementing the recommendations to ensure safe and effective use of this drug.

Histopathology of cryptococcosis and other fungal infections in patients with acquired immunodeficiency syndrome.

OBJECTIVE: To gain insight into the histopathologic characteristics of fungal infection in acquired immunodeficiency syndrome (AIDS). METHODS: A review was conducted of the histopathology for 162 patients with evident fungal infection. RESULTS: The microscopic appearance of esophageal candidiasis that was common in patients with single organ involvement revealed necrotic debris containing proliferating hyphae at the site of mucosal erosions without fungal invasion of underlying tissue. The incidence of oral and esophageal candidiasis was followed by that of pulmonary aspergillosis and Candida infection. Eighteen patients had generalized cryptococcosis, representing the commonest generalized fungal disease. The essential histologic features of the disease consisted of yeast cell proliferation with a histiocytic response, but only minor lymphocytic and neutrophilic components. This was different from the manifestations of both Candida and Aspergillus infections. The two histologic patterns recognized in the pulmonary cryptococcal lesions could be graded with respect to the degree and type of inflammatory reaction. The milder one consisted of small scattered foci of intra-alveolar cryptococcal proliferation with a histiocytic response. Another pattern involved massive cryptococcal infection, which might be simply more extensive than that in the former. Capillary involvement of alveolar septa was an important common finding in all 18 patients.

The influence of time on human breast capsule histology: smooth and textured silicone-surfaced implants.

Although the histology of capsular tissue is well described in the literature, most studies in humans do not correlate histologic findings with implant age (number of years an implant was in place before sampling). As such, questions regarding the long-term histology in humans remain. The microanatomy of 93 human periprosthetic capsular tissues surrounding 22 textured and 71 smooth silicone-surfaced prostheses was studied. The implants were divided into two groups according to the time between implantation and capsulectomy: between 0 and 5 years or more than 5 years. Hematoxylin and eosin and Masson trichrome-stained sections were analyzed by light microscopy, with and without polarization. Eighteen of the textured implants contained silicone gel and four contained saline. Sixty of the smooth implants contained silicone gel, eight contained saline, and in three, the filler type was not known. For the majority of patients, surgery was performed for augmentation mammaplasty, and the implants were removed because of capsular contracture. The following histologic features were assessed: synovial-like metaplasia, villous hyperplasia, density of the collagenous capsule, alignment of collagen fibers within the capsule, and the presence of foreign material and of a foreign body reaction. The following trends were observed. In smooth implants, increasing implant duration was associated with a decrease in the presence of synovial-like metaplasia (p = 0.003) and villous hyperplasia; there was no significant difference in the presence of a dense collagenous capsule, the orientation of collagen fibers, or the presence of a foreign body reaction. An increase was observed in the presence of foreign material (p = 0.01). In textured implants, increasing implant duration was associated with a decrease in the presence of synovial-like metaplasia, villous hyperplasia (p = 0.003), dense collagenous architecture, and parallel orientation of collagen fibers (p = 0.017). An increase in the presence of a foreign body type reaction and foreign material (p = 0.024) was observed. In comparing textured and smooth-surfaced implants, synovial-like metaplasia was observed more often in the textured group, both at 0 to 5 years (p = 0.01) and at greater than 5 years (p < 0.01). Textured implants more often had villous hyperplasia at 0 to 5 years (p = 0.03) but not beyond 5 years. Smooth implants more often had a dense collagenous capsule than textured implants after 5 years. No significant difference was seen in the orientation of collagen fibers in capsules around smooth and textured implants at 0 to 5 years. After 5 years, the incidence of capsules with collagen fibers arranged parallel to the implant surface was significantly greater in the smooth group than in the textured group (p = 0.01). The presence of a foreign body type reaction was seen more often in the textured group between 0 and 5 years (p = 0.01) and at greater than 5 years (p < 0.01), and the presence of foreign material was more often seen in the textured group between 0 and 5 years (p = 0.06) and at greater than 5 years (p < 0.01). In summary, the cytologic changes around implants seem to be dynamic in nature, and implantation duration and shell type play a significant role. Synovial-like metaplasia, villous hyperplasia, and foreign material were more often observed in the textured group within the 0 to 5 year interval. Beyond 5 years, synovial-like metaplasia, a foreign body type reaction, and foreign material were more often observed in the textured group. Differences in the density of collagenous capsules were not significant at any time point, and collagen fibers oriented parallel to the implant surface were more often observed in the smooth group after 5 years. The significance of these findings awaits further investigation.

Non-small cell lung cancer cyclooxygenase-2-dependent regulation of cytokine balance in lymphocytes and macrophages: up-regulation of interleukin 10 and down-regulation of interleukin 12 production.

Tumor-derived prostaglandin E2 (PGE2) modifies cytokine balance and inhibits host immunity. We hypothesized that a high level of PGE2 production by lung tumor cells is dependent on tumor cyclooxygenase (COX)-2 expression. We found that PGE2 production by A549 non-small cell lung cancer (NSCLC) cells was elevated up to 50-fold in response to interleukin (IL)-1beta. Reversal of IL-1beta-induced PGE2 production in A549 cells was achieved by specific pharmacological or antisense oligonucleotide inhibition of COX-2 activity or expression. In contrast, specific COX-1 inhibition was not effective. Consistent with these findings, IL-1beta induced COX-2 mRNA expression and protein production in A549 cells. Specific inhibition of COX-2 abrogated the capacity of IL-1beta-stimulated A549 cells to induce IL-10 in lymphocytes and macrophages. Furthermore, specific inhibition of A549 COX-2 reversed the tumor-derived PGE2-dependent inhibition of macrophage IL-12 production when whole blood was cultured in tumor supernatants. Our results indicate that lung tumor-derived PGE2 plays a pivotal role in promoting lymphocyte and macrophage IL-10 induction while simultaneously inhibiting macrophage IL-12 production. Immunohistochemistry of human NSCLC tissues obtained from lung cancer resection specimens revealed cytoplasmic staining for COX-2 within tumor cells. This is the first description of functional COX-2 expression by NSCLC cells and the definition of a pathway whereby tumor COX-2 expression and a high level of PGE2 production mediate profound alteration in cytokine balance in the lung cancer microenvironment.

Human non-small cell lung cancer cells express a type 2 cytokine pattern.

In addition to infiltrating inflammatory cells, tumors also produce cytokines and growth factors that may alter tumor growth, tumor immunogenicity, and the host immune response. To characterize the expression profile of human non-small cell lung cancer (NSCLC)-derived cytokines, the mRNA expression of type 1 and type 2 cytokines in five human NSCLC lines was analyzed by reverse transcriptase-PCR. Expression of interleukin 5 (IL-5) and IL-10 was demonstrated in all tumor lines evaluated, whereas IL-4 was present in three of five lines and IL-13 was present in two of five lines. In contrast, none of the tumor lines expressed IL-2 and IFN-gamma. Type 2 cytokine protein production by NSCLC lines was confirmed by immunoprecipitation and cytokine specific ELISA. Tumor-derived IL-10 secretion was significantly augmented by exogenous recombinant cytokines including IL-4 and tumor necrosis factor-alpha. To evaluate whether fresh NSCLC nodules also express a type 2 cytokine pattern, the content of type 1 and type 2 cytokines in tissue homogenates from 13 fresh NSCLC nodules and normal lung surgical specimens was assessed. Human NSCLC nodules contain significantly more type 2 cytokines than does normal lung tissue when corrected for total protein concentration. To identify the cellular source of type 2 cytokine production in tumor nodules, immunohistology was performed on sections from 5 lung squamous cell carcinomas and 5 adenocarcinomas. All of the specimens revealed positive staining for type 2 cytokines within tumor cells. In summary, we report that human NSCLC cells produce type 2 cytokines both in situ and in vitro, which may play an active immunoregulatory role in the lung cancer microenvironment.

Mammography of the male breast.

Mammography of the male breast accounts for less than 1% of mammographic examinations done in breast imaging centers [1]. The purpose of this pictorial essay is to familiarize readers with diseases of the male breast and their mammographic manifestations that were observed during a 40-month period at the VA Medical Center, West Los Angeles. The most common presenting signs and symptoms that lead to a request for a mammograph in these men included an enlarging breast, a palpable lump, and breast tenderness.

Enhanced healing of large cranial defects by an osteoinductive protein in rabbits.

Two experimental bone-graft substitutes, one composed of a porous hydroxyapatite plus an osteoinductive protein and the other composed of lactomer beads (copolymers of polylactic acid and polyglycolic acid) plus an osteoinductive protein, were evaluated as a means of reconstructing a large cranial defect model created in the rabbit. Twenty-five rabbits underwent a 16 x 20 x 1.5 mm full-thickness (extradural) excision of the parietal bone, were divided into different groups of five rabbits each, and were reconstructed by (1) hydroxyapatite, (2) hydroxyapatite plus protein, (3) lactomer beads, and (4) lactomer beads plus protein, and (5) one group consisted of nonreconstructed controls. The implants were harvested at 12 weeks and analyzed for percentage of bone ingrowth by histologic examination of decalcified mid-coronal sections stained with hematoxylin and eosin. The groups reconstructed with protein-treated implants demonstrated significantly greater amounts of ingrowth than those with untreated implants. Both protein-treated hydroxyapatite and lactomer bead groups had more than twice the amount of bone ingrowth than their respective untreated groups (29.0 versus 12.8 percent, p < 0.005, and 27.0 versus 10.0 percent, p < 0.001, respectively). The new bone found in the protein-treated and untreated implants was quite different: lamellar and woven, respectively. The results strongly suggest a clinical role for the combination of the mechanisms of osteoconduction and osteoinduction in the treatment of bone defects.

Ultrasonic-pathological comparison of the human arterial wall. Verification of intima-media thickness.

Recent intravascular ultrasound experience challenges the accuracy of ultrasonic measurement of arterial wall thickness. We reevaluated the correlation between histological and sonographic measurements of intima-media thickness using standard transcutaneous vascular technology. Carotid and femoral arterial segments were imaged before and after fixation using a 7-MHz linear-array vascular transducer. Log compression and beam orientation were varied. Mean intima, media, and adventitia thicknesses were measured and compared with corresponding histological tunica. Tissue processing caused 2.5% shrinkage. Intraobserver reading error was 0.7% for histology and 5.4% for sonography. Ultrasound overestimated the thickness of the intima and adventitia and underestimated the thickness of the media. For combined intima-media thickness, the differences between histology and imaging were insignificant, averaging 4% for the carotid artery and 9% for the femoral artery in the far-wall projection. In the near-wall projection, sonographic intima-media thickness was 20% less than that determined histologically. We conclude that ultrasonography is limited mainly by axial resolution in quantifying the dimensions of individual arterial tunica but is capable of accurately measuring far-wall intima-media thickness.

Sebaceous carcinoma of the head and neck. Case report and literature review.

Sebaceous carcinoma is uncommon, with fewer than 400 cases reported. Usually, lesions arise in the meibomian glands of the eyelid; however, extraocular lesions within the head and neck have been reported. Regardless of the location, sebaceous malignancies must be considered aggressive neoplasms with a potential for regional and distant metastasis. Diagnosis may be difficult, given the low incidence and inconsistencies in histopathologic classification. Recently, needle aspiration cytologic characteristics have been delineated, with this procedure becoming increasingly useful in establishing the diagnosis. Treatment requires wide surgical excision with removal of involved regional lymph nodes. Opinions are divided regarding the use of postoperative irradiation or chemotherapy. Records of all patients with sebaceous carcinoma of the head and neck treated at UCLA Medical Center, Los Angeles, over the last 35 years were reviewed. The clinical and pathologic features are discussed, and the literature is summarized.

The induction of bone by an osteogenic protein and the conduction of bone by porous hydroxyapatite: a laboratory study in the rabbit.

The influence of the addition of an osteoinductive protein, capable of inducing extraskeletal ossification, on bone ingrowth into coralline porous hydroxyapatite was evaluated in the rabbit using a calvarium onlay model. Twenty-three rabbits received hydroxyapatite implants (10 x 10 x 2 mm) prepared with and without osteoinductive protein. These were implanted on the frontal bone and secured by wire fixation after 0.25 mm of the cortical surface was abraded. The implants were harvested at 3 and 4 months and analyzed for percentage of bone ingrowth by histologic examination of decalcified H&E sections and by scanning electron microscope backscatter image analysis. The osteoinductive protein-treated implants demonstrated significantly greater amounts of bone ingrowth at both 3 (52.0 versus 10.3 percent; p less than 0.001) and 4 months (66.1 versus 39.2 percent; p less than 0.005) than the untreated implants. The type of bone found in all osteoinductive protein-treated implants was predominantly lamellar. Untreated implants contained mostly woven bone at 3 months, with increasing amounts of lamellar bone appearing at 4 months. These results suggest that the combination of a bone-inducing protein and a suitable osteoconductive matrix may provide an alternative to bone grafting.

Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis.

A Histology Activity Index has been developed which generates a numerical score for liver biopsy specimens obtained from patients with asymptomatic chronic active hepatitis. Biopsies are graded in four categories: periportal necrosis, intralobular necrosis, portal inflammation, and fibrosis. Under code, three pathologists and three hepatologists evaluated 14 liver biopsy specimens obtained from five patients with asymptomatic chronic active hepatitis. Good correlation was seen between severity of liver biopsy lesions as judged by conventional histological descriptions and Histology Activity Index scores. Significant differences in Histology Activity Index score occurred in only 2 or 28 duplicate scorings of biopsy specimens by two observers. This system provides definitive endpoints for statistical analysis of serial changes in liver histology and offers an alternative to the use of conventional pathological descriptions in following the natural history and treatment responses of asymptomatic chronic active hepatitis.

Anal cloacogenic carcinoma: classification and clinical behavior.

A retrospective study of 35 patients with anal cloacogenic carcinomas showed that the histological characteristics of the tumors were correlated with their biological behavior. The basaloid squamous type of cloacogenic carcinoma was more common in women (3.6:1) and had a more favorable course in both men and women, with a mean survival of 5.0 years. Glandular variants of these tumors, with an adenocystic or mucoepidermoid pattern, occurred predominantly in men and had a more aggressive course, manifested by early metastases to inguinal and mesenteric lymph nodes, liver, and lung, with mean survival limited to 2.5 years. Nine of the 11 patients who survived longer than five years had the basaloid squamous histological pattern and were treated by abdominoperineal resection or pelvic exenteration; five of these patients also received postoperative therapy with radiation. The overall actual five-year survival for patients with anal cloacogenic carcinoma was 41% in this study. The histological pattern of anal cloacogenic carcinoma provides useful prognostic information to the clinician.

Significance of microscopic cholangitis in alcoholic liver disease.

Marked biochemical cholestasis mimicking extrahepatic obstruction may occur in alcoholic liver disease. Twenty-three consecutive hyperbilirubinemic alcoholics who underwent liver biopsy were studied. Comparison of the clinical, laboratory, and histological features was made between patients with no or rare intraductal polymorphonuclear leukocytes, group A (19 cases), and those with polymorphonuclear leukocytes in multiple bile ducts ("microscopic cholangitis"), group B (4 cases). Extrahepatic biliary obstruction was excluded in group B by cholangiography. Group B had significantly higher serum SGOT, bilirubin, alkaline phosphatase, and cholesterol than group A. All group B patients had periductal acute inflammation and severe panlobular cholestasis. However, there was no significant histological difference comparing group A patients with alkaline phosphatase greater than 300 mIU per ml and group B patients, except for the presence of intraductal polymorphonuclear inflammation. Therefore, we conclude that microscopic cholangitis is a feature of severe cholestasis which may accompany alcoholic liver injury.

Effect of high-oleic and high-linoleic safflower oils on mammary tumors induced in rats by 7,12-dimethylbenz(alpha)anthracene.

A mutant safflower oil, rich in oleic acid, was used for a critical test of the hypothesis that polyunsaturated fats act as co-carcinogens. Weanling female rats were each given 5 mg of 7,12-dimethylbenz(alpha)anthracene. They were then pair-fed diets containing 20%, by weight, of conventional high-linoleic safflower oil; a mutant high-oleic safflower oil; or coconut oil. Half of each group received supplementary DL-alpha-tocopherol. Tumors were identified by two observers, by palpation. Data on incidence of tumors and on numbers of tumors per affected rat led to similar conclusions. At 16 weeks, there were significant differences when supplementary tocopherol was included in the diet: the group fed high-oleic safflower oil had more tumors than the group fed coconut oil. This difference was not seen in the absence of supplementary tocopherol. When the data for tocopherol-supplemented and unsupplemented subgroups were combined, the high-oleic safflower oil group had significantly more tumors than did the coconut oil group. The high-linoleic safflower oil group was not significantly different from either of the other groups. In all groups, histologic examination of the largest tumor in each rat revealed more benign tumors, mostly duct papillomas, than carcinomas.

Malignant teratoma of the nasal cavity.

A case of malignant teratoma of the nasal cavity in an adult is presented. Histologically, the tumor consisted of mesenchymal malignant structures in addition to entodermal and ectodermal malignant elements. Whereas surgical treatment of the primary tumor has been generally considered preferred, this patient was given a full course of radiation therapy alone to the primary lesion. There is no clinical evidence of tumor 5 years following diagnosis. Three years following treatment of the primary tumor, neck lymph node metastasis appeared contralaterally. Management of this problem was with radical neck dissection followed by postoperative radiotherapy. Function of the eyes, nose, and paranasal sinuses remains normal. A review of the literature suggests that radiotherapy is of little value in the management of malignant teratomas. This case demonstrates an opposite point of view.