Development and results of valve replacement surgery at the Városmajor Clinic 1976-1990 (retorospective clinical analysis)]

In Hungary valve replacement is still a major indication for heart surgery in adults. In the Cardiovascular Surgical Clinic of Semmelweis Medical University of Budapest from 1976 to 1990 2435 patients were operated for valve disease. Majority of the cases had single (aortic n = 856, mitral n = 912) or double (aortic + mitral n = 513) valve replacement. Over this 15 years period there have been many alterations in patients characteristics and surgical technique as well. In spite of the increasing mean age of patients the operative mortality has decreased (in the last 5 years period it was 2.7%, 5.5% and 7.9% in the three groups respectively). At the same time the number of patients requiring valve re-replacement or combined valve + coronary procedure has increased. The use of bioprosthetic valves has fallen below 10 percent from the 60--80 percent observed between 1976--1980. The analysis showes excellent surgical results in the field of valve replacement in Hungary.     

Biological activity of the potent uridine phosphorylase inhibitor 5-ethyl-2,2'-anhydrouridine

5-Ethyl-2,2'-anhydrouridine (ANEUR) proved to be a potent inhibitor of uridine phosphorylase isolated from sarcoma 180 cells with an apparent Ki (Ki(app) value of 99 nM. Coadministration of ANEUR with 5-fluorouridine (FUR) resulted in increased toxicity of FUR. The LD50 value of FUR alone was 9 mg/kg (when administered for 5 consecutive days) while the LD50 was 3 mg/kg when FUR was administered together with ANEUR in vivo. There was no significant difference in mean tumor weight on day 10 between control animals and animals treated with FUR (5 mg/kg/day for 3 days) or ANEUR (280 mg/kg/day for 3 days). When FUR was coadministered with ANEUR, mean tumor weight was 91% less than that of the untreated controls, showing that ANEUR, the potent URPase inhibitor, increases the antitumor effect of FUR.     

Fibronectin on the surface of human lymphocytes

Fibronectin was detected by immunofluorescence technique on the surface of one part of separated normal peripheral blood lymphocytes by using FITC-conjugated anti-human fibronectin antibodies. Approximately one-fifth of isolated B cells and 7% of O cells contained surface-bound fibronectin but T cells failed to stain. There were no detectable free receptors for fibronectin on the surface of lymphocytes of different subsets as it was studied with FITC-labelled purified fibronectin. The percent of B and O cells bearing surface bound fibronectin was markedly decreased in patients with acute and chronic lymphocytic leukemias.     

Visual-perceptual dysfunctions are possible endophenotypes of schizophrenia: evidence from the psychophysical investigation of magnocellular and parvocellular pathways

Visual information processing is impaired in schizophrenia patients and their biological relatives. The authors measured vernier thresholds in 72 schizophrenia patients, their 86 siblings, and 60 healthy control subjects. Subjects were asked to detect the direction of the horizontal displacement of 2 stimuli (left or right). During magnocellular (M) pathway tests, stimuli were dots with low contrast (5%) or counterphase-modulated gratings (25 Hz). For parvocellular (P) pathway tests, isoluminant blue-red dots with yellow-green background were used. Results revealed that patients with schizophrenia and their siblings were more impaired in M pathway conditions than in P pathway conditions. There was no color-specific impairment. The patients and their siblings displayed lower performances on tests of executive functions, psychomotor speed, and verbal memory compared with the controls. Visual-perceptual and neuropsychological data did not correlate. In conclusion, M pathway dysfunction is a potential endophenotype of schizophrenia.     

Angiocentric lymphomatoid granulomatosis and severe hypogammaglobulinaemia

Angiocentric lymphomatoid granulomatosis is a rare lymphoproliferative disease, mainly associated with pulmonary manifestation. Its origin is unknown, but Epstein-Barr virus may be one of the etiological factors. A 51-year-old male had an abdominal laparotomy in 1994 and a large granulomatous mass was removed from behind the cecum. No specific therapy was administered. In February 1998 multiple pulmonary lesions were found by X-ray and thoracoscopic biopsy was made. The histopathological diagnosis was angiocentric lymphomatoid granulomatosis. The patient received 6 cycles of CHOP chemotherapy, with which a complete remission was achieved. A consistent severe hypogammaglobulinaemia was detected, so the diagnosis of common variable immunodeficiency (CVID) was established. The diagnosed CVID was the probable causative factor of the angiocentric lymphomatoid granulomatosis. After the CHOP treatment, the patient is on intravenous immunoglobulin substitution and is well up to today.     

Outcomes of unrelated umbilical cord blood transplantation for X-linked adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an X-linked disorder caused by a defect in the metabolism of long chain fatty acids leading to demyelination, neurodegeneration, and death. The disease typically presents in young boys and adolescent boys. Allogeneic bone marrow transplantation has been used to halt progression of the disease. However, many patients lack suitable HLA- matched related donors and must rely on unmatched donors for a source of stem cells. The purpose of this study was to evaluate outcomes of unrelated donor umbilical cord blood transplantation after chemotherapy-based myeloablative conditioning and retrospectively determine if baseline studies correlate and help predict outcome. Between November 22, 1996, and November 3, 2005, 12 boys with X-linked ALD who lacked HL- matched related donors were referred to Duke University Medical Center for transplantation. These children were conditioned with myeloablative therapy including busulfan, cyclophosphamide, and antithymocyte globulin before receiving umbilical cord-blood transplants from unrelated donors. Baseline studies of neurophysiologic, neuroimaging, and neurodevelopmental status were performed and patients were subsequently evaluated for survival, engraftment, graft-versus-host disease, and neurodevelopmental outcomes. A substudy evaluated whether baseline neuroimaging and neurophysiologic studies correlated with cognitive and motor function and if these studies were predictive of posttransplantation outcomes. The umbilical cord blood grafts had normal levels of very long chain fatty acids. They delivered a median of 6.98 x 10(7) nucleated cells per kilogram of recipient body weight and were discordant for up to 4 of 6 HLA markers. Neutrophil engraftment occurred at a median of 22.9 days after transplantation. Three patients had grade II-IV acute graft-versus-host disease; 2 had extensive chronic graft-versus-host disease. Cumulative incidence of overall survival of the group at 6 months is 66.7% (95% confidence interval 39.9-93.3%). Median follow-up was 3.3 years (range 12 days to 6.3 years). As previously reported with bone marrow transplantation, symptomatic patients faired poorly with lower survival and rapid deterioration of neurologic function. This study included 3 patients transplanted at a very young age (2.6-3.5 years) before the onset of clinical symptoms who continue to develop at a normal rate for 3-5 years posttransplant. Although baseline Loes scores correlated with cognitive and motor outcome, neurophysiologic studies failed to show statistically significant differences. Transplantation of boys with X-linked ALD using partial HLA-matched umbilical cord blood yields similar results to those previously reported after bone marrow transplantation. Superior outcomes were seen in neurologically asymptomatic boys less than 3.5 years of age at the time of transplantation. Baseline Loes scores were a strong predictor of cognitive and motor outcome.     

Theory of mind and motion perception in schizophrenia

This study investigated the relationship between theory of mind (ToM) deficits and visual perception in patients with schizophrenia (N=52; 17 remitted and unmedicated) compared with healthy controls (N=30). ToM was assessed with the Eyes Test, which asked participants to choose which of 4 words best described the mental state of a person whose eyes were depicted in a photograph. Visual perception was evaluated with form and motion coherence threshold measurements. Results revealed that patients with schizophrenia (both remitted and nonremitted) showed deficits on the Eyes Test and the motion coherence task. ToM dysfunctions were associated with higher motion coherence thresholds and more severe negative symptoms. This suggests that ToM deficits are related to motion perception dysfunctions, which indicates a possible role of motion-sensitive areas in the pathophysiology of schizophrenia.     

Analysis of CD154 and CD40 expression in native coronary atherosclerosis and transplant associated coronary artery disease

T cells have roles in the pathogenesis of native coronary atherosclerosis (CA) and transplant-associated coronary artery disease (TCAD). The mechanisms by which T cells interact with other cells in these lesions are not fully known. CD154 is an activation-induced CD4⁺ T cell surface molecule that interacts with CD40⁺ target cells, including macrophages and endothelial cells, and induces the production of pro-inflammatory molecules, including CD54 (ICAM-1) and CD106 (VCAM-1). To investigate whether CD154-CD40 interactions might be involved in the pathogenesis of CA or TCAD we performed immunohistochemical studies of CD154 and CD40 expression on frozen sections of coronary arteries obtained from cardiac allograft recipients with CA (n=10) or TCAD (n=9). Utilizing four different anti-CD154 mAb we found that CD154 expression was restricted to infiltrating lymphocytes in CA and TCAD. CD40 expression was markedly up-regulated on intimal endothelial cells, foam cells, macrophages and smooth muscle cells in both diseases. Dual immunolabeling demonstrated many CD40⁺ cells co-expressed CD54 and CD106. The extent of CD40, CD54 and CD106 expression showed statistical significant correlation with the severity of disease and the amount of intimal lymphocytes. Together these studies demonstrate the presence of activated CD154⁺ and CD40⁺ cells in both CA and TCAD lesions and suggest that CD154-mediated interactions with CD40⁺ macrophages, foam cells, smooth muscle cells and/or endothelial cells may contribute to the pathogenesis of these diseases. Received: 17 December 1999 / Accepted: 20 January 2000     

Immunohistochemical and ultrastructural analysis of a mammary cystic hypersecretory carcinoma

Cystic hypersecretory carcinoma (CHC) is a rare variant of intraductal carcinoma. A CHC in a 50-year-old woman was excised and processed for light and electron microscopy and immunohistochemistry. The tumor had a marked cystic appearance. The walls of the cysts consisted of epithelial and myoepithelial cells and a well-developed basement membrane. The epithelial cells contained well-developed rough-surfaced endoplasmatic reticulum and Golgi apparatus. Secretory granules were not detected, with the exception of a few mucus-producing cells. The secretion was predominantly homogenous, reminiscent of thyroid colloid, and demonstrated distinct PAS positivity. The cells displayed a strong labeling with epithelial membrane antigen (EMA) and EMA-positive structures were observed within the intraluminal secretion, too. Some of these were stained by alcian blue. In addition, the colloid-like material was admixed with mucus showing a filamentous internal structure and lipid droplets resulting in some heterogenity of the secretion. Intraductal micropapillary proliferation in some of the cysts and adjacent nondistended ducts was a further defining feature of the tumor. Steroid hormone receptor and Ki-67 proliferation marker immuno his Tochemistry showed scattered positivity among the tumor cells. These results are in agreement with previous observations and further clarify the nature of this low-grade in situ cancer.     

Ganglioneuroma of the adrenal gland]

149 patients with adrenal incidentalomas were examined. Sixty-eight cases were histologically confirmed, five of them had ganglioneuromas. On the basis of these patients history current knowledge of this benign tumour was summarized. Histological and pathological characteristics of one tumour suggest that ganglioneuromas may develop by maturing of malignant neuroblastic tumours. The clinical symptoms (abdominal pain, meteorism) were local. In 2 of 5 cases mildly elevated levels of urinary vanillylmandelic acid and catecholamine could be measured. One patient had persisting hypertension after surgery. In an other patient previous diarrhoea stopped after the removal of tumour. On the basis of ultrasound and computertomographic features, the size and origin of a tumour and its relation to the surrounding organs can be well characterized. One patient was inoperable because of an infiltratively spreading tumour, but during five years of follow-up no tumour progression could be observed with computertomography. After surgery we could follow only 2 of 4 patients. Until now no recurrence of tumour were detected.