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This article describes how the ideas promoted by the fundamental papers published by M. Frazier and B. Jawerth in the eighties have influenced subsequent developments related to the theory of atomic decompositions and Banach frames for function spaces such as the modulation spaces and Besov-Triebel-Lizorkin spaces. Both of these classes of spaces arise as special cases of two different, general constructions of function spaces: coorbit spaces and decomposition spaces. Coorbit spaces are defined by imposing certain decay conditions on the so-called voice transform of the function/distribution under consideration. As a concrete example, one might think of the wavelet transform, leading to the theory of Besov-Triebel-Lizorkin spaces. Decomposition spaces, on the other hand, are defined using certain decompositions in the Fourier domain. For Besov-Triebel-Lizorkin spaces, one uses a dyadic decomposition, while a uniform decomposition yields modulation spaces. Only recently, the second author has established a fruitful connection between modern variants of wavelet theory with respect to general dilation groups (which can be treated in the context of coorbit theory) and a particular family of decomposition spaces. In this way, optimal inclusion results and invariance properties for a variety of smoothness spaces can be established. We will present an outline of these connections and comment on the basic results arising in this context.

Hintergrund Infektionen mit Leishmanien sind vorwiegend in (sub)tropischen Regionen verbreitet, Berichte uber humane Leishmaniosen in Europa nehmen jedoch kontinuierlich zu. Die systemische, viszerale Form wird durch den Leishmania-donovani/infantum-Komplex verursacht und kann unbehandelt einen letalen Ausgang nehmen.

To analyze whether epidermal growth factor (EGF) exerts regulatory effects on proliferation and differentiation in ARPE19 cells after different incubation periods (24 vs. 48 h) for obtaining ideal conditions for feasible rejuvenation and autologous transplantation of retinal pigment epithelial cells (RPE cells). To evaluate gene expression patterns of RPE-specific differentiation and proliferation markers as well as transcriptional and translational changes of beta-catenin (s-catenin)-signaling markers by fluorescence activated cell sorting (FACS) and reverse transcription – polymerase chain reaction (RT-PCR) after 24 h of EGF treatment. After 24 h of EGF treatment, a significant decrease of retinal pigment epithelium-specific protein 65 (RPE 65), cellular retinaldehyde-binding protein (CRALBP) and cytokeratin 18 in ARPE-19 cells was scaled. In addition, an increase of cyclin D1 expression and a significant decrease of glycogen synthase kinase-3beta (GSK-3s) and beta-catenin (s-catenin) were equally observed after 24 and 48 h of EGF treatment. Cell-cycle studies revealed an increase of ARPE cells in S-G2/M phase after 24 h of EGF treatment. Our data demonstrate the induction of proliferation and upregulation of the s-catenin signaling pathway by EGF even after 24 h of incubation. As ideal cell culture conditions are essential for maintaining RPE-specific phenotypes, short incubation times enhance RPE cell quality for feasible rejuvenation and subsequent autologous transplantation of RPE cells.

BACKGROUND: An increase in corneal infiltrates and ulcers, especially among young contact lens users was noticed in our out-patient service over the last years. This prompted us to examine contact lens related corneal infiltrates and ulcers. PATIENTS AND METHODS: Retrospective study of 119 consecutive patients (134 eyes) who did wear contact lenses. 15 had problems in both eyes. We evaluated age of the patients, proportion of soft and hard contact lenses, number and location of infiltrates, the type of bacteria and the permanent corneal damage caused by scarring. RESULTS: Out of the 134 eyes evaluated 127 (94.8%) used soft contact lenses and 7 (5.2%) had used hard contact lenses for refractive correction. Mean age of patients was 28.4 years ± 12.9a. 80.6% (108 eyes) had central solitary infiltrates, 14.9% (20 eyes) had multiple peripheral infiltrates, and 4.5% (6 eyes) developed corneal ulcers. In 25.4% (34 eyes) we were able to isolate bacteria. Most of the bacteria were found in eyes with soft lenses (33 out of 34 eyes, 97%), in only one (3%) case a hard contact lens was used. Gram-negative bacteria such as serratia spp. (7 eyes), pseudomonas spp. (6 eyes), stenotrophomonas maltophilia (6 eyes) and klebsiella oxytoca (5 eyes) were predominantly isolated. 26 of 127 eyes (20.5%) with soft contact lens related keratitis healed with a corneal scar, resulting in permanent visual damage. CONCLUSION: The majority of keratitis was caused by wearing soft contact lenses. One fifth of these comparatively young patients retained a corneal scar. These findings should influence the information given to a patient concerning the choice of refractive correction.

Poor compliance or drug malabsorption are the most common reasons why an adequate TSH suppression is not achieved with oral levothyroxin in patients with hypothyroidism or thyroid carcinoma. When these conditions are excluded rare causes have to be considered. We report a female patient with follicular thyroid carcinoma in whom, under intended levothyroxin suppression therapy, a TSH-PRL-producing pituitary adenoma manifested by failure to achieve adequate TSH suppression, subtle signs of hyperthyroidism,and finally symptoms of elevated PRL.

Cells that are taken from the nucleus pulposus (NP) and that are allowed to proliferate in monolayer cultures often exhibit changes in their cell morphology and matrix-protein synthesis. However, whether concomitant alterations occur with respect to their mRNA levels for collagen I (CI), collagen II (CII) and aggrecan (AGG) is unclear. In this study, human NP cells from seven individuals were cultured in monolayers and specific mRNAs for CI, CII and AGG were quantified by real-time polymerase chain reaction in fresh NP tissue and during four passages of NP-cell culture. In addition, the presence of CI, CII and AGG protein was determined by immunofluorescence staining of NP cells. We found a significant reduction of CI, CII and AGG mRNA after the initiation of culture in DMEM compared with mRNA levels in fresh NP tissue. During passages 2--4, no further reduction of mRNA levels for CII and AGG was observed. The mRNA level for CI was reduced significantly with duration of culture. Immunofluorescence staining of cultured NP cells revealed expression of CI, CII and AGG protein during the whole culture period. Our data thus demonstrate a reduction of specific mRNA for matrix proteins during the initiation of NP-cell culture but the stable expression of the key matrix proteins, CII and AGG, during further expansion of the cells in monolayers, suggesting no functional changes occur in cultured NP cells.

Background Extralobar pulmonary sequestration is an uncommon congenital abnormality that is rarely diagnosed after the age of 40 years. We describe a 64‐year‐old woman with an intra‐abdominal sequestration of the lung and elevated carbohydrate antigen (CA) 19‐9 serum levels. Case outline On abdominal ultrasound a semi‐solid cystic tumour was demonstrated that showed tight connection to the tail of the pancreas according to computed tomography. Cytological examination of the percutaneous biopsy did not lead to a definitive diagnosis. CA 19‐9 serum levels were repeatedly elevated >250 IU/ml. With a tentative diagnosis of a tumour of the tail of pancreas the semi‐solid cystic mass was resected. Frozen section histology suggested the diagnosis of pulmonary sequestration, which was confirmed by definitive histological examination. Immunohistochemical staining of the specimen with a specific monoclonal antibody against CA 19‐9 showed strong immunoreactivity. Three months later the elevated CA 19‐9 serum levels returned to normal. Discussion Elevated CA 19‐9 serum levels have been described in benign pulmonary and mediastinal cystic lesions and in one case of extralobar intrathoracic lung sequestration. Although there is evidence that malignancies may arise in congenital lung cysts, CA 19‐9 serum levels have not been investigated in such cases. Based on our results elevated serum values of CA 19‐9 in combination with a cystic semi‐solid mass in the left subphrenic space should include the differential diagnosis of extralobar pulmonary sequestration.

Wir bemerkten in den letzten Jahren vor allem bei jungen Kontaktlinsentragern eine Zunahme von Hornhautinfiltraten und -geschwuren. Das veranlasste uns, das Patientengut mit Keratitis speziell auf Erkrankungsursachen zu untersuchen. Von Januar 1999 bis August 2000 wurden die Befunde von 210 konsekutiven Patienten (239 Augen) retrospektiv erfasst. Speziell ausgewertet wurden: Anteil der kontaktlinsentragenden Patienten, Patientenalter, Lokalisation und Zahl der Infiltrate, Art des Erregers sowie entstandene Dauerschaden durch Narbenbildung. Bei 134 (56%) von 239 Augen mit Keratitis wurden Kontaktlinsen als Sehhilfe benutzt, davon bei 127 (53%) weiche. Das Alter betrug bei diesen Patienten durchschnittlich 28,2 Jahre (±13,0 Jahre), die anderen Patienten waren deutlich alter(46,0 Jahre ±22,5 Jahre). Insgesamt lagen bei 71% (170 Augen) zentrale solitare Infiltrate vor, bei 19% (45 Augen) multiple Randinfiltrate und bei 10% (24 Augen) Hornhautulzera. Ein Erregernachweis gelang bei 33% (78 Augen), wobei der am haufigsten nachgewiesene Keim bei nicht kontaktlinseninduzierten Keratitiden Staphylococcus aureus (22 Augen) war. Bei den Augen mit weichen Kontaktlinsen wurden vorwiegend gramnegative Erreger wie Serratia spp. (7 Augen), Pseudomonas spp. (6 Augen), Stenotrophomonas maltophilia (6 Augen) und Klebsiella oxytoca (5 Augen) isoliert. 20% (26 von 127 Augen) der durch weiche Kontaktlinsen bedingten Keratitiden behielten eine Hornhautnarbe. Unsere Analyse zeigt, dass in unserem Patientengut der Grosteil der Keratitiden durch das Tragen von weichen Kontaktlinsen verursacht wurde. Ein Funftel dieser im Vergleich zum gesamten untersuchten Patientengut jungeren Patienten behielt eine Hornhautnarbe. Das Risiko, eine Keratitis zu entwickeln, ist somit bei weichen Kontaklinsen erhoht. Dies sollte im Hinblick auf Patientenaufklarung und Handhabung von weichen Kontaktlinsen berucksichtigt werden.

OBJECTIVE To investigate the retropubic space and attachments of the prostate and urethra, with special reference to radical perineal prostatectomy. MATERIALS AND METHODS Anatomical relationships were assessed intraoperatively in 60 patients, and in five cadavers after preparing the dorsal vein complex with coloured latex. Cross-sections of the area of interest were evaluated by microscopy. RESULTS The puboprostatic (pubovesical) ligaments could be clearly distinguished from the median part of the puboprostatic complex continuous with the urethral suspensory mechanism. The dorsal vein complex is integrated into this fibromuscular attachment of the prostate and male urethra. During the perineal approach, dissection in this region follows the so-called avascular plane. CONCLUSION With this new insight into the anatomical relationships the nomenclature derived from radical retropubic prostatectomy could be mirrored. In radical perineal prostatectomy, both the urethral suspensory mechanism and the dorsal vein complex can be preserved.

Hintergrund Die autologe Transplantation retinal er Pigmentepithelzellen (RPE) nach der Entfernung der choroidalen Neovaskularisationsmembran (CNV) im Rahmen der subretinalen Chirurgie ist eine zukunftsorientierte Behandlungsmethode der AMD. Ziel der vorliegenden Studie war die Untersuchung moglicher Zusammenhange zwischen den Eigenschaften der entfernten Membranen und der postoperativen Entwicklung der Sehscharfe bei den behandelten Patienten.

Object. The authors compared the results of gamma knife radiosurgery in patients with uveal melanoma who underwent high-dose (treated from 1992–1995) and low-dose irradiation (treated from 1996–2002). Methods. Thirty-one patients with uveal melanomas were treated with a mean margin dose of 52.1 Gy (high dose) and 33 with a mean dose of 41.5 Gy (low dose), and results were compared between groups. The technical procedure was the same in each group except for radiation dose. In the low-dose group, complete tumor regression (scar formation) occurred in 12% and in the high-dose group in 26%. Partial regression (reduction of the tumor prominence between 50 and 80%) occurred in 81% of the low-dose group and in 58% of the high-dose group. Neovascular glaucoma as a severe complication developed in 9% of the low-dose group and in 48% of the high-dose group. Conclusions. Reduction of the margin dose from 52.1 to 41.5 Gy appears to achieve the same rate of tumor regression but is associated with a lower rate of severe side effects such as neovascular glaucoma. The follow-up period in the lowdose group, however, was much shorter.

PURPOSE: To describe the indications, surgical technique, and clinical results of 14 eyes in 13 patients with age-related macular degeneration and foveal choroidal neovascularization, in which subretinal surgery was combined with simultaneous transplantation of autologous retinal pigment epithelial cells. METHODS: Between March 1999 and February 2000, in a prospective study, 14 eyes (13 patients) with age-related macular degeneration underwent subretinal surgery because of foveal choroidal neovascularization with simultaneous transplantation of retinal pigment epithelium harvested from the nasal subretinal area of the same eye. Preoperatively, 1 month postoperatively, 3 months postoperatively and at 3-month intervals thereafter, examinations were performed including best-corrected visual acuity, visual field, biomicroscopy of anterior and posterior segment, tonometry, fluorescein and indocyanine angiographies, autofluorescence, scotometry, and fixation tests. RESULTS: Postoperatively, after median observation of 17 months (range, 12 to 24 months) best-corrected visual acuity was improved 2 or more lines in eight eyes (57.1%), remained the same (± 1 line) in five eyes (35%), and decreased by more than 2 lines in one eye (7.1%). Pairwise t test showed significant improvement after 1 month ( P = .0031, P = .0062) as well as 1 year ( P = .0066, P = .0105). Satisfactory reading vision between Jaeger 1 and 4 was achieved in three eyes (21.2%). No significant intraoperative or postoperative complications occurred in any eye. No recurrence of choroidal neovascularization was observed during the observation period. CONCLUSIONS: In eyes with age-related macular degeneration and foveal choroidal neovascularization, autotransplantation of retinal pigment epithelium was performed in addition to conventional removal of the choroidal neovascularization without significant intraoperative or postoperative complications. Visual acuity improvement of 2 or more lines in 57% of the eyes was achieved. No recurrent choroidal neovascularization formation was observed during the observation period. The results of this pilot study suggest that autologous transplantation of retinal pigment epithelium combined with submacular surgery might be a reasonable treatment option for patients with foveal choroidal neovascularization secondary to age-related macular degeneration.

Es wird uber den experimentellen Stand der retinalen Transplantation, den Hintergrund, Problematik der Abstosungsreaktion und die Entwicklung einer eigenen Technik der autologen RPR-Transplantation berichtet.

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly population. The prevalence is reported to be 1.2-1.4% in several population-based epidemiological studies. Currently 25-30 million people worldwide are blind due to AMD. With the aging world population it is bound to increase significantly, and could become a significant public health problem in next two decades, with serious socio-economic implications. Several strategies are today available to treat the wet form of AMD, which is responsible for significant visual loss. These were until recently confined to laser photocoagulation, and subretinal surgery, but today two other modalities, namely, radiation and photodynamic therapy, are available. These treatment modalities however, are aimed at preservation of vision only, and not at reversing the process of the disease. Further research on antiangiogenic drugs and gene therapy could significantly help AMD patients.

Der Alltag des Pathologen im Umgang mit Gewebeproben aus der Harnblase bei klinischem Tumorverdacht oder bei eindeutig verifizierten Neoplasien wird durch wenige, aber vielfach nicht einfach losbare Fragen und Probleme bestimmt, die fur den betroffenen Patienten von wesentlicher prognostischer und therapeutischer Bedeutung sind. Fur urotheliale Tumoren sind dies im wesentlichen die verbindliche histologische Diagnose des Wachstumsmusters, die Feststellung von Malignitatsgrad und Stadium und die Prasenz primarer oder tumorassoziierter intraurothelialer Neoplasien bzw. deren Abgrenzung von reaktiven Urothelveranderungen. Wahrend die Diagnose exophytischer, solid infiltrierender und flacher Urothellasionen zumeist wenig Schwierigkeiten bereitet, unterliegen das verlasliche und reproduzierbare Grading und Staging von Urothelkarzinomen oftmals mehr der Subjektivitat und Erfahrung des Befunders als nachvollziehbaren und standardisierten Kriterien. Die Art der Biopsie- bzw. Gewebeentnahme – in den meisten Fallen durch eine Elektroresektion der Lasion – macht diese Aufgaben nicht gerade leichter. Die gleichen Problemfelder ergeben sich ubrigens auch fur die histologische Diagnostik intraurothelialer Veranderungen, zusatzlich kompliziert durch eine verwirrende Terminologie. Der vorliegende Artikel versucht, einige dieser diagnostisch und klinisch relevanten Kontroversen aufzugreifen und zumindest fur die oben genannten Bereiche praktisch nutzliche Hinweise zu geben. Erganzt wird dieser Versuch durch eine knappe Zusammenfassung der Grundlagen und Wertigkeit der Urin- und Blasenspulzytologie, die weniger in der Primardiagnostik als vielmehr in der Nachsorge und Uberwachung von Tumorpatienten ihre sinn-volle Anwendung findet.

Summary Background 138 infants and young children died from an endemic infantile liver cirrhosis in a circumscribed rural area of western Austria between 1900 and 1974. Frequency of the disease peaked between 1930 and 1960. It has disappeared from this area since 1974. Methods Clinical and genetic data on the patients was gathered; pedigrees analysed and ethnographic studies and interviews were undertaken. Findings The disease, which was clinically and pathologically indistinguishable from Indian childhood cirrhosis and hepatic copper toxicosis, was transmitted by autosomal recessive inheritance. Cow's milk, contaminated with copper from untinned copper or brass vessels, may have contributed to the development of copper toxicosis. Replacement of untinned copper cooking utensils by modern industrial vessels has eradicated the disease. Interpretation Our findings strongly suggest that the endemic Tyrolean childhood cirrhosis—and by analogy non-Wilsonian hepatic copper toxicosis occurring elsewhere—is an ecogenetic disorder requiring the involvement of both genetic and environmental factors for the disease to become manifest.

Zellzahl und Vitalitat der Zellen im zur Transplantation vorgesehenen RPE-Isolat sind kritische Faktoren bei der autologen RPE-Transplantation. Wir uberpruften diese beiden Parameter in RPE-Aspiraten unter Anwendung einer von uns beschriebenen Technik der lokalisierten Mobilisierung und Entnahme von RPE-Zellen vom nasalen Bereich der Netzhaut. Die Studie wurde an 14 Bulbi, die post mortem entnommen wurden, durchgefuhrt. Die Gewinnung der Zellen erfolgte nach Retinotomie und lokaler Abhebung der Netzhaut durch die subretinale Injektion von Ringer-Losung in einem umschriebenen Areal nasal des Sehnerveneintritts. Die RPE-Zellen wurden dabei von einer Flache, die in etwa 2 bis 4 Durchmessern des Discus n. optici entspricht, schonend mobilisiert, aspiriert und unmittelbar danach mit Trypanblau gefarbt und in der Zahlkammer ausgewertet. Die Evaluation der einzelnen Proben erfolgte nach Zellzahl pro Aspirat, Isolationseffizienz, i.e. Zellzahl pro Diskusoberflache, und Vitalitat. Die Gesamtzellzahl in den Aspiraten variierte zwischen 11.000 und 29.200 (19.976 ± 6.016) Zellen. Die Isolationseffizienz war mit 6.165 ± 746 RPE-Zellen bemerkenswert konstant. Die Vitalitatsrate lag zwischen 67 und 89%. Die beschriebene mikrochirurgische Technik erlaubt eine effiziente Gewinnung einer reproduzierbaren Menge vitaler RPE-Zellen zur weiteren, unmittelbaren Verwendung fur eine autologe Transplantation. A reproducible cell amount in the inoculate and its high viability are critical factors for autologous RPE transplantation. We therefore applied a technique of gentle mobilization and aspiration of RPE’s from the nasal area of the retina to 14 cadaver human eyes. The outcome was systematically evaluated for RPE cell counts and their viability. Briefly, after retinotomy the retina was locally detached nasally of the optic disc with a subretinal injection of Ringer’s solution. RPE cells were then gently mobilized over an area of 2–4 disc diameters, aspirated, stained with Trypan blue, and the dye exclusion immediately assessed. Total cell numbers ranged from 11.000 to 29.200 (19.976 ± 6.016), however, the harvesting efficacy (nr. of cells/disc area) was remarkably constant (6.165 ± 746). Cell viability was high (82.0 ± 6.9%). We conclude that reasonable cell numbers of high viability suitable for autologous RPE transplantation can be efficiently harvested even from small retinal areas.

Infections with Leishmania spp. are endemic in areas of the tropics and subtropics. An increased incidence of human infections has been reported in southern Europe, where zoonotic leishmaniasis is common. The systemic, visceral infection is caused by the Leishmania donovani/infantum complex and may be fatal when untreated.A 42-year-old man presented with a 6 week history of erythroderma, pancytopenia, hepatosplenomegaly and recurrent fever after a sojourn in Croatia. The patient's past history revealed a 10-year history of psoriasis and chronic obstructive pulmonary disease treated with methotrexate and prednisolone. Pathology was assessed by histology and molecular biologic analyses. RESULTS AND COURSE: A repeated bone marrow biopsy revealed multiple intracellular particles which were identified as Leishmania amastigotes. Indirect immunofluorescence as well as enzyme-linked immunosorbent assay (ELISA) of patient's serum showed specific anti-Leishmania antibodies. Despite rapid initiation of systemic therapy, the patient died of a secondary infection. Post mortem, PCR and sequencing revealed synchronous infection with Leishmania donovani/infantum complex and Leishmania major.Diagnosis of patients with complex clinical features is challenging even for experienced clinicians. Critical interpretation of findings and, if necessary, repetition of invasive examinations may be necessary for proper diagnosis. Increasing numbers of immunocompromised patients (iatrogenic, HIV) will expand the spectrum of rare infectious diseases including visceral leishmaniasis.

Great progress has been made in developing thermodynamic equations for high-nitrogen steels. Much of this work has centered on the effects of alloy composition on nitrogen concentration. Most of the currently produced high-nitrogen steels are formed by high-pressure melting. This joint U.S. Bureau of Mines, SRIM, and SIM study presents recent attempts to include the effects of pressure on the thermodynamic expressions used to determine the nitrogen concentration in Fe-Cr-Mn-Ni alloys.

The cell-cycle progression of germinating embryos of maize (Zea mays L.) was studied from 0 to 72 h after the start of imbibition using DNA flow cytometry on isolated nuclei, and analyses of thymidine kinase activity, histone biosynthesis and levels of proliferating cell nulcear antigen (PCNA). At the start of germination, 75% of the cells were in G1, but this population had decreased to 25% by 72 h. The concomitant increase of cells in S-phase did not occur continuously, but stepwise, indicating that during germination most of the cells enter S-phase as a partially synchronized population. Within the initial 60 h of embryo germination the cells passed through one S-phase; the start and duration of this period of replicative DNA synthesis was further substantiated by the analysis of S-phase-associated events, the biosynthesis of core histones and the enzyme activity of thymidine kinase, which both began to increase at about 12 h after the start of differentiation. Thymidine kinase fluctuated periodically during germination with a transient maximum at 30 h and a second peak at 72 h; histone biosynthesis was not detectable until 12 h after the start of germination. The levels of PCNA protein closely resembled the pattern of thymidine kinase during germination. Together with the cytometric data this allows a clear assignment of cell cycle events to different times of embryo differentiation.

Thirty-three out of 39 cynomolgus monkeys (Macaca fascicularis) infected with SIVsm (strain SMM-3) developed various pathologies similar to those seen in human AIDS. Lymphadenopathy was frequently seen (72%) and was characterized by hyperplasia followed by involution of follicle/germinal centres due to follicular dendritic cell (FDC) destruction corresponding to the degree of immunodeficiency. Various organs such as the lungs, liver, central nervous system, kidneys, gastrointestinal tract, cardiovascular system and adrenals showed histopathological changes with prominent monocyte/macrophage and multinucleated giant cell formation. Eighteen (54%) monkeys presented with extranodal malignant lymphoma (ML) associated with marked CD4 decrease and destruction of follicular architecture. The high frequency of ML, giant cell disease and lymph node changes seen in the present SIV model provides an attractive system to elucidate the role of FDC and monocytes/macrophages in the pathogenesis of these conditions in common with HIV infection and human AIDS.

A non-opportunistic, generalized giant cell disease (GCD) was found in 12 out of 25 (48%) cynomolgus monkeys infected with SIVsm. Most organs were affected notably the lymph nodes (LN), spleen, gut, liver, lungs and CNS. The multinucleated GC varied considerably in cell size and in the number and cytoplasmic distribution of the nuclei. Immunohistochemically most GC expressed SIV antigens and markers of mononuclear phagocytes (CD68), CD4 and also occasionally the T-cell markers CD45RO, CD43 and CD2. Monkeys with GCD had more pronounced immunosuppression with lower CD4-cell counts, more often demonstrable SIV antigen in the blood and LN and had been infected for a longer time oeriod, as compared to monkeys without GCD. These findings show that SIV infection in cynomolgus monkeys is frequently associated with extensive formation of multinucleated GC of macrophage origin, which appears to be related to the pathogenesis of the infection and the degree of immunosuppression.

We report two cases of cryptosporidiosis after CD34-selected PBSCT for lymphoma. While the first patient died of pulmonary cryptosporidiosis, treatment with paromomycin, azithromycin and subcutaneous low-dose rhIL-2 to improve numerical and functional T lymphocyte defects completely eliminated infection in the second patient. We conclude, that the removal of mature T lymphocytes by positive selection of CD34+ cells bears the risk of a delayed immune reconstitution resulting in an increased incidence of severe and sometimes fatal opportunistic infections. IL-2 might be useful in this situation by accelerating immune reconstitution and reducing the danger of opportunistic infections.

In 1988, a 27-year-old male patient received an allogeneic BMT for leukemic relapse 8 months after ABMT for AML (M2) in first complete remission. Because of chronic GVHD of the liver CsA was administered until 1994. Nine months after discontinuation of CsA, locally advanced gastric granulocytic sarcoma (GS) was diagnosed without evidence of systemic relapse. The patient was treated with two courses of polychemotherapy (ICE, NOVIA). Granulocyte colony-stimulating factor (G-CSF)-mobilized donor buffy coat cells were reinfused after each chemotherapy cycle in an attempt to accelerate hematopoietic regeneration and to induce a graft-versus-leukemia (GVL) effect. Local irradiation and surgical resection of residual leukemic cells resulted in complete remission. Seventeen months from diagnosis of GS the patient relapsed again with multiple lesions and died of generalized bleeding during aplasia after a third course of polychemotherapy (ICE). In our patient donor peripheral blood stem cell support did not accelerate hematopoietic regeneration (time to neutrophil recovery > 0.5 x 10(9) g/l from the start of chemotherapy was 27 days after ICE and 36 days after NOVIA) and did not result in long-term disease-free survival.

PURPOSE. To present the outcome of a consecutive series of patients who had foveal choroidal neovascularization (fCNV) in age-related macular degeneration (AMD) and were treated with subretinal surgery combined with simultaneous transplantation of autologous retinal pigment epithelial (RPE) cells. METHODS. Patients with fCNV who were not eligible for laser or photodynamic therapy were included in the study. They underwent subretinal membrane excision with simultaneous transplantation of autologous RPE cells. Eyes with membrane excision alone served as the control. Tests included best corrected visual acuity for far and near with Early Treatment Diabetic Retinopathy Study (ETDRS) and Jaeger charts, multifocal (mf)ERG, central visual field analysis, optical coherence tomography (OCT), and angiography, before surgery, and 1 month and 3 months after treatment, and at 3-month intervals thereafter. RESULTS. The results of final examinations of 53 eyes are presented. In 39 eyes, RPE transplantation was performed (group 1); 14 eyes had membrane excision alone (group 2). In group 1, visual acuity improved significantly, two or more lines in 21 (53.8%) patients; remained stable in 12 patients (30.8%); and decreased two or more lines in 6 patients (15.4%; P 0.0062). In group 2, the corresponding values were 21.1%, 57.8%, and 21.1% (P 0.5377 NS). Statistical analysis of results in the two groups showed a trend in favor of group 1 (P 0.9714). The difference in reading acuity was significant between the two groups (mean change in group 1: 1.85 0.42 vs. 0.43 0.47 in group 2; P 0.0001). mfERG response density changes were significantly different between groups 1 and 2 (P 0.0094). No significant decreases in central visual field defects were detected. OCT showed the postoperative median retinal thickness in the lesion area in group 1 to be higher (242.31 12.30 m) than in group 2 (202.07 10.68 m), showing a trend (P 0.0682). CONCLUSIONS. Patients undergoing fCNV removal with autologous transplantation of RPE reached significantly better reading acuity and higher mfERG-response density than control subjects. The results provide evidence that autologous transplantation of RPE is a beneficial supplement to membrane excision alone in patients with fCNV in AMD and may be regarded as a reasonable treatment option. (Invest Ophthalmol Vis Sci. 2004;45:4151‐4160) DOI:10.1167/iovs.04-0118

In our outpatient service the number of corneal infiltrates and ulcers associated with contact lens wear in young patients increased during the last years. Therefore we evaluated all patients with keratitis regarding to the reason.From January 1999 to August 2000 the medical charts of 210 consecutive patients and 239 eyes were reviewed. We evaluated the percentage of contact lens wearers. Patient age, localisation and number of infiltrates, bacteria and healing results were also evaluated.In 134 of 239 eyes (56%) keratitis was caused by contact lenses, 127 eyes (53%) with soft lenses. The mean age of soft contact lens wearing patients was 28,2 +/-13,0 years. Mean age in other reasons was 46,0 +/-22,5 years. 71% (170 eyes) had single central infiltrates, 19% (45 eyes) multiple peripheral infiltrates and 10% (24 eyes) corneal ulcers. Bacteria were found in 33% (78 eyes). The most frequent isolated bacteria in non contact lens induced keratitis was staphylococcus aureus (22 eyes). In those eyes with soft contact lenses we found mostly gram negative bacteria such as serratia spp. (6 eyes), pseudomonas spp. (6 eyes), stenotrophomonas maltophilia (6 eyes) and klebsiella oxytoca (5 eyes). 20% (26 of 127 eyes) of contact lens induced corneal infection healed with a scar.Our analysis shows, that the major part of keratitis was induced by soft contact lenses. One fifth of these very young patients retained a corneal scar. There is a higher risk to suffer a keratitis when using soft contact lenses. This should influence especially patients information regarding choice and use of soft contact lenses.

A reproducible cell amount in the inoculate and its high viability are critical factors in autologous RPE transplantation. We therefore applied a technique of gentle mobilization and aspiration of RPE-s from the nasal area of the retina to 14 cadaver human eyes. The outcome was systematically evaluated for RPE cell amounts and their viability. Briefly, after retinotomy the retina was locally detached nasally of the optic disc with a subretinal injection of Ringer’s solution. RPE cells were then gently mobilized over an area of 2–4 disc diameters, aspirated, stained with Trypan blue, and the dye exclusion immediately assessed. Total cell numbers ranged from 11.000 to 29.200 (19.976 ± 6.016), however, the harvesting efficacy (nr. of cells/disc area) was remarkably constant (6.165 ± 746). Cell viability was high (82,0 ± 6,9%). We conclude that reasonable cell numbers of high viability suitable for autologous RPE transplantation can be efficiently harvested even from small retinal areas.

Because of the higher life expectancy in the industrial world and increasing demands on life quality age related macular degeneration (AMD) has become one of the most important diseases in ophthalmologic research. While about 85% of patients are diagnosed with the “dry” atrophic form of AMD, 15% suffer from the “wet” form, which is responsible for the highest percentage of visual loss in these patients and mainly characterised by the development of choroidal neovascularisation [1]. Treatment modalities usually used f.e. laser photocoagulation, photodynamic therapy (PDT), or transpupillary therapy (TTT) are vasodestructive methods and have therefore a very limited potential to improve the retinal situation [2, 3, 4]. These methods also do not allow any visionary aspect for the treatment of the large group of patients with dry AMD.

Purpose: We have recently described combined subretinal surgery and simultaneous autologous transplantation of RPE as a therapeutic option for the treatment of CNV in patients with advanced AMD. The purpose of the present study was to determine whether the size and morphology of the membranes were correlated with patient outcome.

The authors compared the results of gamma knife radiosurgery in patients with uveal melanoma who underwent high-dose (treated from 1992-1995) and low-dose irradiation (treated from 1996-2002).Thirty-one patients with uveal melanomas were treated with a mean margin dose of 52.1 Gy (high dose) and 33 with a mean dose of 41.5 Gy (low dose), and results were compared between groups. The technical procedure was the same in each group except for radiation dose. In the low-dose group, complete tumor regression (scar formation) occurred in 12% and in the high-dose group in 26%. Partial regression (reduction of the tumor prominence between 50 and 80%) occurred in 81% of the low-dose group and in 58% of the high-dose group. Neovascular glaucoma as a severe complication developed in 9% of the low-dose group and in 48% of the high-dose group.Reduction of the margin dose from 52.1 to 41.5 Gy appears to achieve the same rate of tumor regression but is associated with a lower rate of severe side effects such as neovascular glaucoma. The follow-up period in the low-dose group, however, was much shorter.

Recently, 138 cases of infantile cirrhosis originating in several families in the Austrian province of the Tyrol were reported. This endemic Tyrolean infantile cirrhosis (ETIC) is indistinguishable from Indian childhood cirrhosis (ICC), idiopathic copper toxicosis (ICT), and resembles the early forms of Wilson's disease (WND). It has been argued that ETIC might represent an allelic variant of the WND gene, which is a copper transporting P-type ATPase (ATP7B). Assuming that ETIC results from a founder effect, a possible role for ATP7B in ETIC was investigated by association studies and haplotype sharing. Because of its lethality, the mapping of ETIC was focused on obligate gene carriers, i.e. the patients' parents. Our data indicate that ETIC is a separate genetic entity, distinct from WND.

Members of the lipocalin protein family are characterized by their ability to bind small hydrophobic molecules. Some of them are known to be produced by various glands and secretory cells. Under certain conditions, these proteins would be ideally suited for clearance of lipophilic, potentially harmful substances and might also act as protection factors in airway secretions. We therefore used RT-PCR analysis with a set of oligonucleotide primers deduced from conserved regions of lipocalin members to identify specific RNA isolated from human trachea. With two of these oligonucleotide primers, a positive result was obtained. Sequencing of the RT-PCR products revealed that the DNA fragments were identical to the lipocalin 1 (LCN1) encoding cDNA. LCN1 is an unusual lipocalin member that binds a variety of lipophilic compounds and exhibits cysteine proteinase inhibitor and antimicrobial activities. The local production and topographic distribution of LCN1 in the human tracheobronchial tree was then investigated by immunoperoxidase staining on thin-layer sections using a specific antiserum. LCN1 was detectable in the acini of serous mucosal glands and sometimes within the glandular lumen, suggesting excretion of the protein. The latter finding was tested and verified by Western blot analysis of bronchial secretions of healthy individuals. Furthermore, the results of SDS-PAGE and Western blot analysis of bronchial secretions from patients with cystic fibrosis (CF), which are usually characterized by an increase of airway lipids, suggested that LCN1 secretion was enhanced. Northern blot analysis of RNA from normal trachea and RNA isolated from tracheal biopsies of patients with CF indicated that induced secretion was due to an up-regulated expression of the LCN1 gene. Thus, our investigations present the first clear evidence that LCN1 is induced in infection or inflammation and support the idea that this lipocalin functions as a physiologic protection factor of epithelia in vivo.

The surgical pathology of biopsies or electroresection specimens taken from clinically suspicious or overt tumors in the urinary bladder encompasses the evaluation of a few parameters. This should allow the segregation of bladder tumor patients into subgroups with distinct clinical features and biological behavior, thus providing a rationale for choosing the best available therapy. In essence, the pathologist's role entails a careful morphologic assessment of the primary tumor, including evaluation of the histologic type, the growth pattern, the tumor grade, the tumor stage, and finally the presence and type of primary or tumor-associated flat intraurothelial lesions. Whereas the growth pattern of a lesion can be readily recognized, the correct grading and staging of papillary tumors are often more dependent on the complexity of the individual case and the experience of the pathologist due to the inherent subjectivity of the field and a lack of standardized criteria. These problems of intra- and interobserver variability are intimately coupled with the characteristics of the material, that is, bad orientation and tangential sectioning, thermal injury, crush and fixation artifacts, and limitations of the size of the samples. The correct evaluation and interpretation of flat intrauorothelial lesions suffer from similar difficulties and are further complicated by a confusing categorization and terminology. Although new modalities and molecular approaches have been introduced in recent years in an effort to overcome some of these obstacles, morphology still remains the most effective means to assess the biological behavior and prognosis of urothelial bladder cancer. The present article therefore addresses some of the diagnostically and clinically most relevant controversies and aims to give some useful hints for the evaluation of the above-mentioned morphological parameters. In addition, it adds some remarks on the morphological basis and diagnostic validity of urinary cytology in primary diagnosis and, more importantly, monitoring of bladder cancer patients.

Liver diseases of infancy and childhood are generally rare and within the spectrum of these disorders, only a few subtypes are related to abnormal hepatic copper accumulation. Idiopathic copper toxicosis has been defined as such a subtype; although this disease is characterized by distinct clinical and pathologic features, its exact etiology is still controversial. On the basis of a review of the literature, supplemented by our own observations of 138 cases endemic to western Austria, we hypothesize that idiopathic copper toxicosis is caused by a synergy of an autosomal-recessive inherited defect in copper metabolism and excess dietary copper. Increased awareness of the disease should enable early diagnosis and lead to successful treatment, thereby improving the overall poor prognosis of affected patients.

Twenty-eight histologically proven severe acute vascular rejection episodes in renal grafts were reversed in 22/28 (78%) cases by extensive plasma exchange, which was well-tolerated by all but one patient. CMV infection was the most frequent complication. As 1-year survival of 93% (patient) and 71% (graft) is considered a good result in this severe immunological complication, the extensive plasma exchange can be recommended for the treatment of acute vascular rejection.

Twenty-eight histologically proven severe acute vascular rejection episodes in renal grafts were reversed in 22/28 (78%) cases by extensive plasma exchange, which was well-tolerated by all but one patient. CMV infection was the most frequent complication. As 1-year survival of 93% (patient) and 71% (graft) is considered a good result in this severe immunological complication, the extensive plasma exchange can be recommended for the treatment of acute vascular rejection.

Blood group antigens traditionally have been associated with a risk of developing peptic ulcer and gastric cancer. Helicobacter pylori is a bacterium associated with chronic active gastritis and ulcer disease, and its attachment to gastric mucosa was recently shown in vitro to be mediated by blood group Lewisb and H antigens. This study was designed to test the clinical relevance of this laboratory observation in patients undergoing endoscopy and gastric biopsy.Blood group phenotypes and gastric biopsies for H. pylori and histology were determined and correlated in 384 patients undergoing upper endoscopy. Blood from healthy blood donors was tested for the same blood group antigens and used as a control group.The distribution of blood groups ABO, Lewis, Rhesus, and MN was similar among the patients undergoing endoscopy and a control group of 2369 healthy blood donors from the same geographic area. There was no correlation between H. pylori infection or the H. pylori-associated diseases, peptic ulcer or chronic active gastritis, with any blood group phenotype, including Lewisb, blood group O, or both.No in vivo correlation between H. pylori infection or disease and Lewisb or H antigen could be demonstrated. Moreover, patients with H. pylori infection and disease have a distribution of blood group antigens similar to a control population.

Ovarian cancer arises mostly from the ovarian surface epithelium. The aim of our study was to compare the effects of cytokines in ovarian surface epithelial (OSE) cells and in ovarian carcinoma cells. Proliferation and expression of surface antigens (CA-125 and classes I and II antigens of the major histocompatibility complex [MHC]) were measured in OSE cells obtained from 7 different patients and 7 ovarian carcinoma cell lines. Proliferation of OSE cells remained unaffected by interferon (IFN)-alpha or IFN-gamma, whereas interleukin-1 (IL-1) and tumor necrosis factor (TNF) increased cell growth. Proliferation of ovarian carcinoma cells was reduced by both types of IFN as well as TNF but was not affected by IL-1. Expression of the tumor marker CA-125 was increased by IFN-gamma in ovarian carcinoma cells but not by any other treatment. None of the cytokines affected CA-125 surface expression in OSE cells. Expression of MHC-I was augmented in OSE and in carcinoma cells by both IFNs but not by the other cytokines. Both types of cell were negative for MHC-II, but IFN-gamma induced its expression in both OSE and carcinoma cells. Significant concentrations of the cytokines evaluated here have been measured in blood and follicular fluid by several authors. The different actions of these cytokines in OSE and carcinoma cells could therefore be important in understanding the role of such molecules in the regulation of physiological and pathological processes in the ovary, such as ovulation or malignant proliferation.

Peritoneal mesothelial cells are uniquely located to regulate cellular events in the peritoneal cavity and are a potentially important source for various cytokines. The present study was designed to elucidate the capacity of human peritoneal mesothelial cells (HPMCs) to synthesize and secrete the transforming growth factor (TGF)-beta isoforms 1, 2, and 3 and to characterize their regulation by inflammatory cytokines. HPMCs constitutively released appreciable amounts of TGF-beta 1 and low amounts of TGF-beta 2 as detected by specific immunoassays. TGF-beta 1 levels secreted within 48 hours (45 +/- 8.9 pg/10(5) cells) were 60-fold higher than TGF-beta 2 levels (0.9 +/- 0.1 pg/10(5) cells), respectively. Treatment of HPMCs with interleukin (IL)-1 beta (10 ng/ml) resulted in a significant increase of both TGF-beta 1 (mean, 5-fold; P < 0.001) and TGF-beta 2 (mean, 6-fold; P < 0.01) generation. After 48 hours of IL-1 beta treatment the levels were 185 +/- 17.1 pg/10(5) cells for TGF-beta 1 and 5.3 +/- 1.5 pg/10(5) cells for TGF-beta 2, respectively. Neither tumor necrosis factor (TNF)-alpha nor interferon (IFN)-gamma (both 10 ng/ml) affected TGF-beta 1 or TGF-beta 2 synthesis by HPMCs. TGF-beta 3 could not be detected in any of the supernatant media. Stimulation of HPMCs with IL-1 beta increased steady-state levels of TGF-beta 1- and TGF-beta 2-specific mRNA. Western blot analysis of supernatants revealed the presence of an immunoreactive band at 25 kd. Indirect competition assays confirmed receptor-binding activity of HPMC-derived TGF-beta. Appreciable amounts of TGF-beta were present in a bioactive form. Our results demonstrate that HPMCs synthesize the TGF-beta isoforms 1 and 2 and that the levels of mRNA and protein release can be up-regulated by the proinflammatory cytokine IL-1 beta.

Ki-ras mutations and DNA aneuploidy are common findings in human pancreatic ductal adenocarcinomas. An altered p53 tumor-suppressor gene has been suggested to cooperate with activated Ki-ras in malignant cellular transformation and could enhance genomic instability. We have investigated a panel of well-documented pancreatic carcinomas with defined ploidy and Ki-ras mutations for the presence and pattern of genetic alterations of the p53 gene, their coincidence with Ki-ras point mutations, and their correlation with DNA ploidy, tumor pathology, and clinical course. DNA was isolated from formalin-fixed and paraffin-embedded tumor tissue and polymerase-chain-reaction-amplified fragments of the p53 gene exons 5 to 9 were screened by the single-strand conformation polymorphism method. The positive cases were further examined for mutations by direct sequencing. Twenty-nine of seventy-one (41%) tumors showed mutations of the p53 gene, however, five tumors carried two mutations resulting in a total of 34/71 (48%) genetic alterations of the p53 gene. The majority were missense point mutations and distributed primarily within the evolutionary conserved domains (62%). Ten of Thirty-four (29%) affected the hotspot codons 248, 273, and 282, respectively, and 21/34 (62%) of the p53 gene mutations clustered on exons 7 and 8. Transitions (71%) predominated over transversions (15%), deletions were identified in 7/34 (21%) tumors. One third of the carcinomas showed both Ki-ras codon 12 and p53 gene mutations. p53 mutations correlated with distant metastasis (p0.05) and survival (p0.05). DNA triploidy was associated with a mutated Ki-ras gene (p0.05) as well as with double mutations of c-Ki-ras and p53 (p0.05). Unlike most other malignant tumors pancreatic ductal adenocarcinomas exhibit a significantly higher incidence of c-Ki-ras than p53 gene mutations. However, like other neoplasms p53 gene mutations seem to be associated with a metastatic phenotype possibly acquired during tumor progression.

Distinct ploidy patterns of germ cell tumors and aneuploidy of classic seminoma are of central importance in a current concept designating seminoma as a stage in tumor evolution preceding all nonseminomatous germ cell tumors. Whereas cytogenetic studies almost constantly revealed numerical chromosomal aberrations in seminomas in line with this pathogenetic model, ploidy determination by DNA cytometry yielded highly controversial results on the frequency of diploid seminomas.Twenty-two classic seminomas were investigated in a comparative manner by DNA flow and DNA image cytometry on nuclei isolated from fresh as well as formalin-fixed tumors. The cellular composition of the tumors, i.e., the number of neoplastic, interstitial, and lymphoid cells was quantified in each case.Irrespective of the tissue preparation and fixation method, all of the tumors that were analyzed were aneuploid by image cytometry. Diploid cases were only found by flow cytometry. Thus, 1/22 cases from paraffin-embedded and 4/11 cases of native tumors showed a single diploid stemline by flow cytometry, however, they exhibited aneuploidy by image cytometry. The quantity of tumor infiltrating lymphocytes was clearly correlated with false diploidy detected by flow cytometry.Classic testicular seminomas are aneuploid tumors. Previous reports on diploid cases detected by flow cytometry have most likely been caused by extensive lymphocytic infiltration.