Emmanouil Agapitos

Rosacea: A Clinicopathological Approach

Background: There are few reports of the histological changes in rosacea, and little attempt has been made to correlate such changes with clinical findings. In the present study, we describe in detail the histopathological features of rosacea in a large number of patients and simultaneously investigate the aetiopathogenesis of the disease based on the comparative assessment of epidemiological, clinical and histological findings. Methods: The study included 73 patients with rosacea. A skin biopsy with a 4-mm punch was performed in each case. All biopsy specimens included subcutaneous tissue. In 10 randomly selected patients, facial biopsy specimens were obtained from both involved and uninvolved (non-lesional) skin. Demodex mite presence was estimated semi-quantitatively under light microscopy. Patients with self-reported gastro-intestinal symptoms were submitted to upper gastro-intestinal endoscopy, and a rapid urease test was performed. Serological antibodies, IgG and IgA, against Helicobacter pylori were also detected. Results: The patients had a broad clinical spectrum of lesions. No specific histological features associated with either erythematous-telangiectatic or papulopustular clinical forms were noticed. Histological examination showed that there is no histological pattern unique to rosacea. Three different types of granulomas were observed: small palisaded ones around altered collagen and other granulomas of elastolytic and non-specific epithelioid type, all coexisting in 5 cases. The deep dermis and subcutis were frequently involved. Comparative study in 10 rosacea patients between lesional and non-lesional skin biopsies revealed almost the same histological changes to the latter biopsies, to a lesser degree though. Conclusion: Rosacea seems to be a reaction pattern to which a variety of pathogenetic routes may lead.

Variations in the origin and course of the posterior interventricular artery in relation to the crux cordis and the posterior interventricular vein: An anatomical study

Corrosion castings of 60 human hearts were used to demonstrate that the point of origin of the posterior interventricular artery (PIA), in relation to the crux cordis, is responsible for its subsequent course with respect to the posterior interventricular vein (PIV). In seven cases (12%), the PIA appeared as the continuation of the left circumflex, descending rightwards and on a deeper level of the PIV. In 53 cases (88%), the PIA arose from the right coronary artery (RCA) and 50 of these were selected to be classified into three groups, according to the PIAs origin and course. In group A (29 cases, 58%) and B (seven cases, 14%), the PIA emerged before the crux cordis and descended to the right or left of the PIV, respectively. In group C (14 cases, 28%), it originated at, or beyond, the crux cordis and descended along the left side of the PIV. Among the 50 cases, the PIA was found to be long in 34 (68%), large in 32 (64%), and long and large in 29 cases (58%). In 18 of the latter 29 cases (62%) or 36% of the 50 cases in total, the PIA arose as a continuation of the RCA (group A) and therefore these cases were easily accessible to interventional cardiologists and also to surgeons, since the PIA lay on the same or on a superficial level in relation to the PIV. This work describes and explains the variations of the PIA and concludes that at least 36% of these may be helpful in coronary artery angioplasty and bypass surgery. Anat. Rec. 252:413–417, 1998.

Ontogeny of Intrinsic Innervation in the Human Thymus and Spleen

The ontogeny of the innervation of human lymphoid organs has not been studied in detail. Our aim was to assess the nature and distribution of parenchymal nerves in human fetal thymus and spleen. We used the peroxidase immunohistochemical technique with antibodies specific to neuron-specific enolase (NSE), neurofilaments (NF), PGP9.5, S100 protein, and tyrosine hydroxylase (TH) and evaluated our results with image analysis. In human fetal thymus, NSE-, NF-, S100-, PGP9.5-, and TH-positive nerves were identified associated with large blood vessels from 18 gestational weeks (gw) onwards, increasing in density during development. Their branches penetrated the septal areas at 20 gw, reaching the cortex and the corticomedullary junction between 20 and 23 gw. Few nerve fibers were seen in the medulla in close association with Hassalls corpuscles. In human fetal spleen, NSE-, NF-, S100-, PGP9.5-, and TH-positive nerve fibers were localized in the connective tissue surrounding the splenic artery at 18 gw. Perivascular NSE-, NF-, S100-, PGP9.5-, and TH-positive nerve fibers were seen extending into the white pulp, mainly in association with the central artery and its branches, increasing in density during gestation. Scattered NSE-, NF-, S100-, PGP9.5-, and TH-positive nerve fibers and endings were localized in the red pulp from 18 gw onward. The predominant perivascular distribution of most parenchymal nerves implies that thymic and splenic innervation may play an important functional role during intrauterine life. (J Histochem Cytochem 55: 813–820, 2007)

Undiagnosed primary cardiac liposarcoma in an adult: a case report and review of the literature.

AbstractWell-differentiated liposarcomas are locally aggressive malignant mesenchymal neoplasms, which rarely metastasize to the heart and pericardium. Primary cardiac liposarcomas are extremely rare as well, and in both instances, symptoms are difficult to recognize. Therefore, accurate antemortem diagnosis seldom happens. A rare case of an undiagnosed, primary, well-differentiated cardiac liposarcoma is presented, in a 67-year-old man who suffered a sudden cardiac death. The tumor seemed to arise from the epicardium of the left ventricle and expand into the myocardium of the left ventricle and intraventricular septum. Macroscopic and histopathological findings are presented, as well as a short review of current literature.

Correlations between CCN1 immunoexpression and myocardial histologic lesions in sudden cardiac death.

AbstractCCN1 (CYR61) is a member of the CCN family of secreted matricellular proteins; it can regulate the expression of genes involved in angiogenesis and matrix remodeling. The latter mechanisms seem to be of vital importance in the pathophysiology of sudden cardiac death. We performed an immunohistochemical analysis on 62 cardiac tissue specimens derived from individuals of young and middle age who had died of sudden cardiac death. CCN1 immunopositivity was detected in 80.6% of all specimens. Semiquantitative statistical analysis of the staining results revealed that CCN1 immunoreactivity was significantly associated with ischemic morphology and hypertrophy of myocardial fibers, interstitial edema, and atheromatosis of coronary arteries in more than 10% of the myocardial fibers. Taking the previously mentioned correlations into account, ischemia seems to induce myocardial expression of CCN1; therefore, CCN1 immunostaining could be evaluated as a complementary tool in the assessment of ischemic areas when no tissue evidence of necrosis is available.

Prenatal diagnosis of a fetus with ring chromosome 15 characterized by array‐CGH

Emmanouil Manolakos1*, Annalisa Vetro2, Stylianos Kitmirides3, Ioannis Papoulidis4, Nadezda Kosyakova5, Kristin Mrasek5, Anja Weise5, Emmanouil Agapitos6, Sandro Orru7, Panagiotis Peitsidis8, Thomas Liehr5 and Michael B. Petersen9 1Laboratory of Molecular Cytogenetics, ‘Bioiatriki’ SA, Kifisias Ave. 132 and Papada, Athens, Greece 2Sezione di Biologia Generale e Genetica Medica, Dipartimento di Patologia Umana ed Ereditaria, Universita di Pavia, Italy 3Fetal Maternal Medicine Center, Athens, Greece 4‘Eurogenetica’ SA, Laboratory of Molecular Biology, Genetics, and Biotechnology, Technology Park, Thessaloniki, Greece 5Institut fur Humangenetik und Anthropologie, Universitatsklinikum Jena, Germany 6Department of Pathology, Medical School, University of Athens, Greece 7Department of Medical Genetics, University of Cagliari, Italy 8Department of Fetal Medicine, Royal Free Hospital, London, U.K 9Department of Genetics, Institute of Child Health, Athens, Greece

Metabolic effects of Crocus sativus and protective action against non-alcoholic fatty liver disease in diabetic rats

Non-alcoholic fatty liver disease (NAFLD) is the result of the accumulation of adipose tissue deposits in the liver and it is associated with type 2 diabetes. Crocus sativus (saffron) is known for its antioxidant and its potential hypoglycemic effects. We investigated the role of saffron on NAFLD in diabetic rats. Thirty adult male rats were allocated into three groups; control (n=10), which received normal diet; streptozotocin (STZ) group (n=10), which received normal chow diet, 10% fructose in their drinking water and STZ (40 mg/kg body weight; STZ-saffron group (n=10), which followed the same dietary and pharmacological pattern as STZ group and were additionally supplemented with saffron (100 mg/kg/day). Metabolic profile was measured and histopathological examination of the liver was evaluated. STZ group exhibited the highest glucose levels at the end of the experiment (P<0.05), while there was no difference between control and STZ-saffron group (584 vs. 213 mg/dl vs. 209 mg/dl, respectively). STZ group revealed higher percentage of steatosis (5–33%) when compared to the other two groups (P<0.005). Saffron exhibits both hypoglycemic and hepatoprotective actions. Yet, further studies enlightening the exact mechanisms of saffrons mode of actions are required.

Retinal Toxicity of Intravitreal Trastuzumab in a Rabbit Model: Preliminary Results of an Experimental Study

PURPOSE To evaluate the retinal toxicity of intravitreal trastuzumab in a rabbit model. METHODS Fourteen New Zealand albino rabbits, weighing between 2.5 and 3 kg were used for this study. In the first group (n=6), 0.1 mL trastuzumab 10 mg/mL was injected into the vitreous. In the second group (n=6), the same volume of sterile balanced saline solution was injected intravitreally (sham injection). Additionally, 0.1 mL of 2 other concentrations of trastuzumab (7.5 and 5 mg/mL, respectively), was injected into the vitreous of 2 rabbits. Slit-lamp and funduscopic examinations were performed and the animals were observed for 2 weeks for signs of inflammation, infection, and toxicity. An electroretinogram (ERG) was performed at baseline and 14 days after the injection. The animals were killed on day 14 and a histological examination was performed in the enucleated eyes. RESULTS The clinical examination was unremarkable on either sham or intravitreal injection of trastuzumab. Conversely, the ERG was greatly affected and in 2 cases extinguished 14 days after trastuzumab injection. Consistent with electrophysiological abnormalities of the retina, signs of retinal edema in experimented eyes, suggesting morphologic retinal damage, were observed. In contrast, in the sham injected eyes, the ERG was normal without histopathologic retinal changes. CONCLUSIONS Intravitreal trastuzumab seems to be toxic to the retina in albino rabbits even at a concentration of 5 mg/mL. Further studies are needed to evaluate the safety of intravitreal trastuzumab in models of choroidal neovascularization, as well as to obtain experience concerning the intravitreal toxicity of trastuzumab in primates too and not only in rabbits.

Abruptio placentae and idiopathic arterial calcification in a stillborn

We report a case of idiopathic arterial calcification in a stillborn of 22 weeks gestational age. The pregnancy was complicated by abruptio placentae and the postmortem examination showed widespread arterial calcification in the placenta, as well as in the pulmonary, renal, cerebellar, and brain arteries.

Effect of Saffron on Metabolic Profile and Retina in Apolipoprotein E–Knockout Mice Fed a High-Fat Diet

ABSTRACT Saffron is a spice that has been traditionally used as a regimen for a variety of diseases due to its potent antioxidant attributes. It is well documented that impaired systemic oxidative status is firmly associated with diverse adverse effects including retinal damage. The aim of this study was to investigate the role of saffron administration against the retinal damage in apoE −/− mice fed a high-fat diet, since they constitute a designated experimental model susceptible to oxidative stress. Twenty-one mice were allocated into three groups: Group A (control, n = 7 c57bl/6 mice) received standard chow diet; Group B (high-fat, n = 7 apoE −/− mice) received a high-fat diet; and Group C (high-fat and saffron, n = 7 apoE −/− mice) received a high-fat diet and saffron (25 mg/kg/d) through their drinking water. The duration of the study was 20 weeks. Lipidemic profile, glucose, C-reactive protein (CRP), and total oxidative capacity (PerOX) were measured in blood serum. Histological analysis of retina was also conducted. Administration of saffron resulted in enhanced glycemic control and preservation of retinal thickness when compared with apoE −/− mice fed a high-fat diet. The outcomes of the study suggest the potential protective role of saffron against retinal damage induced by oxidative stress. Nevertheless, verification of these results in humans is required before any definite conclusions can be drawn.