Merkel cell carcinoma of the eyelid is an aggressive, highly malignant tumor of the skin. Totaling approximately 0.5 % of all tumors of the eyelid, it constitutes a relatively small group of lid tumors. Nevertheless Merkel cell carcinoma is of significance to the ophthalmologist. Because of its clinical presentation it can be easily confused as a chalazion, a hordeolum or the lesser aggressive basal cell carcinoma. This often leads to delayed treatment. In this article we describe clinical aspects, which aim to help the ophthalmologist suspect Merkel cell carcinoma earlier. Additionally we outline a diagnostic and therapeutic workup taking into consideration the special anatomy of the eyelid.

Das Merkel-Zell-Karzinom des Augenlids ist eine aggressive, hochmaligne Neoplasie der Haut. Es stellt mit ca. 0,5 % eine kleine Gruppe der Lidtumoren dar. Dennoch ist das Merkel-Zell-Karzinom von Bedeutung für den Augenarzt, da durch sein klinisches Erscheinungsbild häufig eine Verwechslung mit einem Chalazion oder Hordeolum oder dem wesentlich weniger gefährlichen Basalzellkarzinom auftritt und somit die Behandlung verzögert wird. In diesem Beitrag werden klinische Aspekte genannt, die dem Augenarzt helfen sollen, ein Merkel-Zell-Karzinom früher in Erwägung zu ziehen. Zusätzlich wird eine diagnostische und therapeutische Aufarbeitung bei Merkel-Zell-Karzinomen unter Berücksichtigung der speziellen Lidanatomie besprochen.

Study Design. Case report.Objective. To report a patient with spinal tuberculosis (TB) and paravertebral abscess formation after kyphoplasty of L1. The literature is reviewed, and diagnostic options are discussed.Summary of Background Data. Kyphoplasty is a well-established procedure in the treatment of osteoporotic compression fractures and metastatic tumors of the vertebrae. Although complication rates are low, there is evidence for an increased risk of serious local infections after kyphoplasty in patients with any history of systemic infection. Spinal TB accounts for 2% of all TB cases with a trend toward an increased incidence in parallel with the growing number of immunocompromised patients. To our knowledge, only 1 article had reported a patient suffering from Pott disease after vertebroplasty.Methods. A 70-year-old patient with compression fracture of L1 underwent percutaneous kyphoplasty using polymethyl methacrylate.Results. Two weeks after kyphoplasty, the patient was readmitted with backache and signs of acute infection. Magnetic resonance imaging confirmed the diagnosis of spondylitis with paravertebral abscess formation. A tissue specimen obtained by computed tomography-guided percutaneous biopsy did not yield any pathogen. As broad-spectrum antibiotic therapy failed, combined surgery consisting of posterior instrumentation of Th11-L3 and anterior debridement, corporectomy of L1, and interposition of a titanium mesh cage filled with autologous rib graft was performed. Histologic examination of resected tissue and PCR and culture results confirmed diagnosis of spinal TB. Despite adequate antibiotic treatment and local surgical interventions, the patient died from septic multiple organ failure.Conclusion. Indication for kyphoplasty in patients with any history of local or systemic infection should be scrutinized rigorously. Symptoms of spinal TB are often nonspecific, and the clinician should be aware of this entity. Active investigation including microbiological and histologic examination is of utmost importance to avoid any delay in correct diagnosis and specific treatment.

Mercury is a silvery white liquid metal that is volatile at room temperature due to its high vapour pressure. It exists in different oxidation states and can form a number of compounds. Mercury and its compounds can be absorbed into the human body by inhalation, ingestion, and through the skin. It is toxic when certain threshold values are exceeded. Acute toxicity is due to the inactivation of enzymes by the heavy metal, which leads to interstitial pneumonitis, ulcerative gastro-enteritis, or tubular necrosis, depending on the route of exposure. Long-term mercury poisoning affects mainly the central nervous system and the kidneys. In the latter case the nephrotoxicity is usually manifested as membranous glomerulonephritis (MGN) with nephrotic syndrome. Since 1920, numerous cases of nephrotic syndrome due to long-term contact with mercury and mercury compounds have been reported. Mercurial diuretics (Mersalyl), teething powders for young children, and mercury-containing ointments for psoriasis were the main sources of exposure in medicine w1,2x. In 1962, MGN was demonstrated by renal biopsy in five cases of nephrotic syndrome due to psoriasis ointments containing mercury w3x. MGN due to skin-lightening creams containing mercury was reported last in 1987 w4x. In industry, mercury is still used in gold mines, in chlor-alkali plants, and in the manufacture of batteries. In daily life, it occurs in technical and control instruments. Here we report for the first time two cases of membranous nephropathy due to occupational exposure to mercury vapour in the fluorescent-tuberecycling industry.

OBJECTIVES:This study examined the effects of endotoxin on cardiac contractility in human myocardium. BACKGROUND:In animal myocardium, endotoxin and cytokine treatment led to enhanced inducible nitric oxide synthase (iNOS) expression and contractile dysfunction. Effects in human myocardium are unknown. METHODS:Left ventricular myocardial preparations from failing (n = 18) and nonfailing (n = 5) human hearts were incubated for 6 and 12 h in tyrode solution or in tyrode plus lipopolysaccharides (LPS), with LPS plus N(G)-mono-methyl-L-arginine (L-NMMA), with LPS plus hemoglobin or with LPS plus the superoxide scavenger 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron). Force of contraction in response to isoprenaline (0.001 to 3 micromol/liter) was determined in electrically stimulated muscle preparations. The iNOS mRNA expression was examined by in situ hybridization and by polymerase chain reaction. The cyclic guanosine monophosphate (cGMP) levels were determined by radioimmunoassay. RESULTS:Isoprenaline concentration dependently increased force of contraction. Six and 12 hours of LPS treatment of failing myocardium decreased maximum inotropic response to isoprenaline by 54% (p = 0.009) and by 69% (p = 0.0023), respectively. In nonfailing myocardium, 12 h of LPS treatment decreased maximum inotropic effect of isoprenaline by 66% (p < 0.001). The LPS effects were attenuated by L-NMMA, hemoglobin and also Tiron. The iNOS mRNA was expressed in all LPS-treated preparations but also in most control myocardial preparations. In situ hybridization revealed iNOS expression within cardiac myocytes. There was no increase in myocardial cGMP content in response to endotoxin. CONCLUSIONS:Endotoxin exposure of human myocardium leads to a depression of cardiac contractility, which is mediated by enhanced iNOS activity and release of nitric oxide (NO). Consecutive reaction of NO with superoxide and formation of peroxynitrite may contribute to the decrease in force of contraction.

We applied a peroxidase-antiperoxidase technique to study the distribution pattern and binding characteristics of the lectin from the marine sponge Geodia cydonium (Geodia cydonium agglutinin; GCA) in various human tissues. This lectin has been shown to possess a broad reactivity, but there was a distinct distribution of binding sites within the different organs. In the histochemical system GCA displayed no blood group specificity and labeled red blood cells, the vascular endothelium, and epithelial cells showing blood group antigen expression independent of the ABH blood group status. However, inhibition of GCA reactivity by simple sugars and complex carbohydrates demonstrated tissue-specific differences of lectin binding related to the ABH blood group status of the tissue and revealed information on the structural requirements of the histological lectin binding site. Tissues that totally lacked blood group antigens or that expressed only the H-antigen disclosed a GCA reactivity which was completely inhibited by lactose. In contrast, tissues that expressed blood group A- or blood group B-antigen exhibited a lactose-resistant lectin binding which was inhibited only by water-soluble blood group substance A from peptone A and by bovine glycophorin but not by other complex carbohydrates, including human glycophorin and human asialoglycophorin. Competitive inhibition studies in situ revealed that GCA binding was not inhibited by blood group type I/II carbohydrate sequence-specific lectins or by lectins with other sugar specificities. Inhibition by lactose of GCA binding to some histological sites indicates that the binding site consists of a beta-linked galactose-containing disaccharide. However, periodate oxidation of tissue sections had no effect on lectin binding, pointing to a subterminal location of the relevant sequence. The results obtained from inhibition studies with simple saccharides and complex carbohydrates in relation to the expression of ABH blood group antigens suggest a complex lectin combining site(s) in histological specimens. The lectin may possess either one binding site with a range of affinities for different carbohydrates (besides beta-linked disaccharides the GCA binding site accommodates to carbohydrate determinants carrying the blood group A or blood group B determinant), or may possess two different binding sites. Besides an acceptor site for beta-linked disaccharides, an additional binding site may exist accommodating to extended carbohydrate sequences related to A or B blood group structures. In conclusion, GCA represents a blood group-nonspecific lectin whose binding affinities are determined by the ABH blood group status of the tissue.

The occurrence and significance of bacterial carbohydrate recognition proteins (bacterial lectins) and endogenous carbohydrate binding proteins (endogenous lectins) of human urothelium as well as kidney tubulus epithelium was analyzed with respect to the adhesion of urotoxogenic Escherichia coli bacteria. Using biotinylated neoglycoproteins, we demonstrated a wide spectrum of endogenous lectins with Galactose-, Mannose-, Fucose-, N-Acetylgalactosamine-, and N-Acetylglucosamine binding activities in the urothelium. In the kidney the distal nephron and especially the medullar collecting ducts exhibited a similar spectrum of endogenous carbohydrate binding activities as detected for the urothelium. Adhesion- as well as inhibition-experiments with selective blocking of either bacterial lectins or endogenous lectins of the target cells by different carbohydrates both reduced the bacterial adhesion. However, maximal inhibition of bacterial adhesion was achieved by simultanous blocking of microbial and target cell lectins with mannose or mannan. From these results it is reasonable to conclude that specific adhesion which may result in an organotropism (urotropism) of E. coli infection is due to a dual recognition mechanism which is accomplished by the combined interaction of the bachterial and host cell lectins with the corresponding carbohydrates of E. coli and that of the target cells respectively. Further studies showed that normal human serum possesses natural antiadhesins which are represented by the glycan parts of the serum-glycoproteins.

The occurrence of the tumor-associated carbohydrate antigens defined by the monoclonal antibodies (moabs) C 50 and 19-9 has been studied by immunoperoxidase staining of formalin-fixed and paraffin-embedded tissue specimens from normal, hyperplastic, adenomatous, and carcinomatous thyroid tissues. Epithelial expression of these antigens was observed neither in normal nor in hyperplastic thyroid tissue. The antigens were expressed in only 1 of 26 follicular adenomas and the staining in this case was weak and restricted to a few cells. In contrast, the expression of this antigens is marked and progressive in carcinomatous tissues. A high proportion, 48 of 52 papillary carcinomas demonstrated C 50 reactivity, whereas 25 of these tumors expressed the CA 19-9 antigen. Of 25 follicular carcinomas, 15 gave a positive staining for the CA 50 and 6 for the CA 19-9 antigen. CA 50 antigen expression was still detected in tumor cells lacking the CA 19-9 antigen and C 50 reactive material was found in all tissue specimens from medullary carcinomas tested, whereas CA 19-9 antigen staining was consistently negative. This indicates that the moab C 50 which reacts, like the moab 19-9, with the sialylated Lewisa (Lea) blood group determinant also binds to other antigens apart from the sialylated Lea in CA 19-9 antigen negative tumor cells. Although, the functional significance of CA 50 and CA 19-9 antigen expression remains to be investigated, these results suggest that the demonstration of these antigens could provide additional differential diagnostic parameters for the characterization of hyperplastic and neoplastic lesions of the thyroid gland. Further clinical studies will show whether these carbohydrate antigens are useful serum markers for the monitoring of thyroid carcinomas.

We applied a horseradish peroxidase-Erythrina cristagalli agglutinin (HRP-ECA) conjugate for histochemical staining of tissue sections from various formalin-fixed, paraffin-embedded human tissue specimens. The HRP-ECA conjugate showed broad reactivity, but there was a distinct distribution of native (not masked by sialic acid) and sialic acid-masked ECA binding sites in the various organs. Free ECA binding sites could be detected on red blood cells, lymphocytes of thymus, tonsil, lymph node, and in mucous substances of different organs. Independent of blood group type, the vascular endothelium exhibited strong ECA reactivity. Free ECA binding sites occurred in the cytoplasm of Kupffer's cells in liver, in histiocytic cells of thymus, lymph node, tonsil, and in bone marrow. Podocytes of kidney glomerulus, syncytiotrophoblasts of placenta, megakaryocytes in bone marrow, myelin sheath of nerve, medullary thymocytes, and hepatocytes, as well as islet cells of pancreas, contained only sialic acid-capped ECA binding sites. Inhibiting studies with galactose, lactose, and N-acetyl-lactosamine, as well as other sugars, revealed that this lectin is specific for galactosyl residues. In comparison to galactose and lactose, N-acetyl-lactosamine exhibited the highest inhibitory activity on lectin binding, supporting the concept that this lectin is most reactive with N-acetyl-lactosamine-type (type 2 chain) glycoconjugates.

Using a polyclonal antibody raised against bovine heart cytochrome c oxidase, the occurrence of this mitochondrial marker enzyme has been investigated in 63 kidney tumors (ten renal oncocytomas, 43 renal cell carcinomas and ten tubulopapillary adenomas) as well as in normal renal tissue by an immunoperoxidase method (PAP-technique). The differentiation between renal oncocytomas and mitochondria-rich carcinomas represents a problem of histopathology since these tumors have a different prognosis and require different patient managements. The strong immunoreactivity in renal oncocytomas contrasted with the much weaker reactivity in renal carcinomas and adenomas. Even mitochondria-rich (granular cell type) carcinomas exhibited only moderate staining intensity. Furthermore, single strongly stained oncocytes or small complexes were sometimes detected in normal renal tissue. The demonstration of marked differences in enzyme content between renal oncocytomas and granular cell carcinomas renders this method suitable for unequivocal distinction between these renal neoplasms. The antibody proved to be a valuable marker for detecting "true" oncocytic transformation in renal tumors and was useful in defining even single oncocytes or small oncocytic lesions.

The present study is aimed to gain more insight into the histochemical properties of renal oncocytomas. Ten oncocytomas and normal kidneys were investigated using several lectins (peanut agglutinin--PNA, Dolichos biflorus agglutinin--DBA and Ulex europaeus agglutinin--UEA) and antibodies against epithelial membrane antigen (EMA), Tamm-Horsfall glycoprotein (THG) and lysozyme. Lectin histochemistry revealed a characteristic binding pattern in renal oncocytomas, with strong DBA-binding and, in some cases, a weaker staining with UEA apparent in the cytoplasm of the oncocytes. PNA binding sites were evident only after enzymatic cleavage of sialic acid by neuraminidase. Comparative evaluation of normal kidneys exhibiting a strict compartmentalization of saccharide moieties in the various nephron segments revealed a similar binding pattern exclusively in interspersed collecting duct epithelium. This striking resemblance suggests that renal oncocytomas may originate from the collecting duct system. Further support for this assumption has been provided by the demonstration of strong cytoplasmic EMA reactivity in the oncocytes. In normal kidneys prominent labeling for EMA was apparent in the very same interspersed cells of the collecting ducts. THG and lysozyme failed to react in renal oncocytomas. In accordance with observations recently reported in the literature, these results clearly favor a histogenetic origin of renal oncocytomas from the collecting duct epithelium.