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Biomedical subjects

H Steininger

Publications and source records attributed to H Steininger.

At least 19 recordsLinked to original sources

Suppression of HHV-8 viremia by foscarnet in an HIV-infected patient with Kaposi's sarcoma and HHV-8 associated hemophagocytic syndrome.

Human herpes virus 8 (HHV-8) seems to be involved in the pathogenesis of Kaposi s sarcoma. In vitro, antiviral drugs with activity against herpes viruses also can suppress HHV-8, however, little is known about the antiviral activity against HHV-8 in vivo. In this report we describe the effects of foscarnet on HHV-8 viremia in an HIV-infected patient with disseminated Kaposi s sarcoma and a presumably HHV-8 associated hemophagocytic syndrome. HHV-8 DNA could be detected in this patient by PCR in peripheral blood mononuclear cells (PBMC), in bronchoalveolar fluid and tumor biopsies. After initiation of foscarnet because of a severe hemophagocytic syndrome HHV-8 PCR turned negative in PBMC, but stayed positive in pleural effusions and in a tumor biopsy. After termination of foscarnet therapy HHV-8 DNA in PBMC persistently reappeared. Under treatment with foscarnet the hemophagocytic syndrome dramatically improved, suggesting that HHV-8 had a pathogenetic role in this syndrome.

AIDS-Related Opportunistic Infections

Apoptosis in chronic gastritis and its correlation with antigastric autoantibodies.

In the course of time, chronic gastritis may result in gastric atrophy, as in type A gastritis, where autoimmune reactions against parietal cells result in a loss of corpus glands. Two antigastric autoantibodies have been detected in Helicobacter pylori gastritis and are described as anti-luminal and anti-canalicular autoantibodies. The aim of this study was to determine whether increased apoptosis may be responsible for the loss of gastric epithelium and whether this apoptosis is correlated with antigastric autoimmunity. Gastric biopsies from normal mucosa and Helicobacter pylori gastritis were analysed for the presence of apoptosis using the TUNEL method. Helicobacter pylori gastritis was divided into cases (1) without autoantibodies, (2) with anti-luminal, and (3) with anti-canalicular autoantibodies. Apoptotic cells of the foveolar and of the glandular epithelium in the antrum and corpus were counted. The number of apoptotic cells in the gastric mucosa was significantly increased in all cases of gastritis. The highest number of apoptotic cells was observed in the gastric glands of the corpus mucosa in Helicobacter pylori gastritis with anti-canalicular autoantibodies. Apoptosis contributes to the development of gastric atrophy and there are various types of Helicobacter pylori gastritis. The positive correlation between apoptotic cell loss in the glandular zone of the corpus mucosa and the presence of anti-canalicular autoantibodies indicates a possible link between anti-gastric autoimmunity and atrophy in this type of Helicobacter pylori gastritis--similar to that in classic type A gastritis.

Adult

Nodal CT density and total tumor volume as prognostic factors after radiation therapy of stage III/IV head and neck cancer.

PURPOSE: To determine whether the immunohistochemical expression of proliferation-associated antigens (proliferating cell nuclear antigen, MIB1) and the nuclear p53 reactivity in addition to total tumor volume, nodal CT density and T and N category are predictive for overall survival and locoregional tumor control in patients with squamous cell carcinoma of the head and neck region. MATERIALS AND METHODS: Between October 1989 and September 1993, 87 patients with biopsy proven head and neck cancer were randomly allocated to receive radiation alone or simultaneous radiation and chemotherapy as part of a multicenter trial with a total of 298 randomized patients. There were only inoperable lesions in UICC (1992) stage III (8%) and IV (92%). Radiotherapy was delivered with 180 cGy twice daily up to a total dose of 7020 cGy in 51 days. Three cycles of 2340 cGy each were separated by a rest period of 11 days. Chemotherapy consisted of cis-DDP, 5-fluorouracil and leucovorin and was repeated on days 22 and 44. Routinely-processed paraffin-embedded sections were stained using monoclonal antibodies for detection of proliferation-associated antigens (MIB1 and PCNA) and p53 oncoprotein to determine the labeling index (LI). In addition, the total tumor volume and the percentage of necrosis were measured using CT data. The median follow-up was 3.9 years (range 1.9-5.0 years). RESULTS: The overall survival and locoregional control for all 87 patients were 34 and 39% at 3 years, respectively. The addition of chemotherapy resulted in a better overall survival (27 versus 47%, P = 0.03) but did not influence locoregional control (31 versus 47%, P = 0.08). In univariate analysis, nodal CT density (P < 0.0001), total tumor volume (P < 0.0001), age (P = 0.001) and the MIB1-LI (P = 0.04) had a significant impact on overall survival. However, in the final Cox model only the nodal CT density (P = 0.0003) and age (P = 0.05) were independent prognostic factors for survival and only the nodal CT density (P = 0.0006) was an independent prognostic factor for locoregional control. The expression of the p53 oncoprotein was not found to have a clear predictive value. CONCLUSION: Nodal CT density, total tumor volume and age will remain the relevant prognostic factors in stage III/IV head and neck cancer.

Antineoplastic Combined Chemotherapy Protocols

Oral squamous cell carcinomas are characterized by a rather uniform pattern of genomic imbalances detected by comparative genomic hybridisation.

Total genomic DNA sampled from 20 oral squamous cell carcinomas (SCCs) and from four SCC cell lines, was examined for genomic imbalances using comparative genomic hybridisation (CGH). Gains and losses of DNA copy number aberrations (CNAs) were found in the primary tumours, but also in the cell lines at a varying number. The patterns of CNAs proved to be rather peculiar in oral SCCs, gains of genetic material clearly dominating compared with losses, and a rather high uniformity of these patterns was an impressive finding. Hypersomies of whole chromosomes, e.g. numbers 17 and 19 or of whole chromosome arms, e.g. 20q, were particularly evident. The segments most frequently gained in oral SCCs were 3q26-q27, 5p15 and 9q34 (16 of 20 tumours each), as well as 1p36.3, 8q24, 10q26, 19 and 20q (15/20 each). Among the 15 tumours with more than 10 CNAs, all showed these imbalances. 11q13 was a band often involved in increases (14/20 tumours), but in several tumours was involved in amplification of DNA copy number. Several other chromosomal segments over represented in more than 60% of the tumours, as, for example, 12q24, 15q22-q24, 16p13.2 and 17q (14/20 tumours each), 6q26-qter, 7p22, 12p12.2-p13, 14q31-q32.2 (13/20) and 1q32-q41, 2q37, 16q23-q24 (12/20 each). In contrast, loss of material affected only a few chromosomal segments, as, for example, 3p12 (12 of the 20 tumours), 5q21 (10/20), 6q13 (8/20). The peculiarities of these findings, in some respect, differ from those found in other epithelial tumours, suggesting a high impact of environmental factors in the generation and progression of these tumours.

Adult

Antigastric autoantibodies and gastric secretory function in Helicobacter pylori-infected patients with duodenal ulcer and non-ulcer dyspepsia.

BACKGROUND: Autoantibodies against epitopes located at the canaliculi of human parietal cells occur in about 30% of Helicobacter pylori-infected patients. This has led to the hypothesis that gastric secretory function could be inhibited by anticanalicular autoantibodies in H. pylori gastritis. METHODS: Forty-four H. pylori-infected patients with and without duodenal ulcers were screened for anticanalicular autoantibodies by means of immunohistochemistry. Plasma gastrin levels and basal and maximal gastric acid output were determined. RESULTS: Fasting gastrin levels were significantly increased in the group with anticanalicular autoantibodies. In the group of patients with non-ulcer dyspepsia the presence of anticanalicular autoantibodies was significantly correlated with an impaired basal acid secretion. CONCLUSIONS: Antigastric autoimmunity in H. pylori gastritis seems to be relevant for gastric hyposecretion either directly by inhibiting the proton pump or indirectly through the development of gastric mucosa atrophy.

Adult

Evidence of novel pathogenic pathways for the formation of antigastric autoantibodies in Helicobacter pylori gastritis.

Autoantibodies against gastric epithelial cells are detectable in up to 50% of patients with chronic, active Helicobacter pylori gastritis. Presence of autoantibodies against canalicular structures within human parietal cells (anticanalicular autoantibodies) correlate with gastric mucosa atrophy. It has been suggested, that molecular mimicry between H pylori and the host on the level of Lewis X and Lewis Y blood group antigens leads to these autoantibodies. This study aimed at analysing whether antigastric antibodies can be absorbed to Lewis X or Y positive H pylori strains. Sera from 14 H pylori infected patients with anticanalicular autoantibodies were effectively absorbed to H pylori. Immunohistochemical studies of the absorbed sera showed no decrease of antigastric autoreactivity. Pathogenic mechanisms other than molecular mimicry lead to the formation of antigastric autoantibodies, and epitopes other than Lewis antigens are the autoimmune targets.

Autoantibodies

Gain of DNA copy number on chromosomes 3q26-qter and 5p14-pter is a frequent finding in head and neck squamous cell carcinomas.

Comparative genomic hybridization (CGH) was used to study genomic imbalances in 77 squamous cell carcinomas of the head and neck (HNSCC) and in four cell lines derived from oral carcinomas. Particular attention was paid to all tumors characterized by a gain of two specific chromosomal segments, i.e. 3q26-qter and 5p14-p15. The 57 tumors containing both or one of the two imbalances were compared with 20 tumors lacking both with regard to genomic complexity, as well as to associated genomic, histopathologic and clinical peculiarities. 60% of the oral, and 66% of the non-oral cancers exhibited a gain of 3q26-qter, while a gain of 5p14-p15 was found in 66% of the oral, but only in 48% of the non-oral tumors. 48% of all tumors were characterized by both gains together, 26% exhibited only one of the two alterations. It could be shown that presence of both, gain of 3q26-qter and 5p14-p15, was clearly associated with a significantly higher complexity of genomic changes which was not only expressed as a high frequency of DNA copy number alterations (CNAs) but was also connected with a considerable number of additional amplifications of various chromosomal segments and a high conformity of the patterns of genomic imbalances in these tumors. Clear differences of the extent and of the patterns of genomic imbalance could be observed between oral and non-oral tumors. With respect to histopathological parameters, no clear association could be found for specific imbalances to the grade of differentiation, nor the invasiveness or metastatic status of the tumors. However, a higher number of patients with tumors characterized by gain of 3q26-qter plus 5p14-p15 died within a short period (i.e. less than 15 months) after excision of the tumor compared to the group without these imbalances. The implications of these findings are discussed from the oncogenetic and clinical aspects and in comparison with other reports.

Journal Article

Pattern of genomic imbalances in oral squamous cell carcinomas with and without an increased copy number of 11q13.

Among 23 squamous cell carcinomas (SCC) of the oral cavity which were screened for DNA copy number alterations (CNAs) using comparative genomic hybridization, 14 showed a gain of, and 5 of these 14 even an amplification of band 11q13. Amplification of 11q13 was also detected in three of the four studied SCC cell lines and was confirmed by interphase FISH. The number of CNAs in addition to 11q13 varied from 14 to 47 in these carcinomas. All these tumors had seven other specific CNAs in common, i.e. gain on 1p36.3-36.6, 5p15, 9q34, 12p12-13, 14q32, 19 and 20q, all but one showed also an increase of copy number in 7p22, 8q24, 10q26, 12q26, 15q24-25, 16p, 16q23-24, 17q and 22q12-qter. These imbalances were distinctly rarer in the tumors without CNA in 11q13. Loss of material apparently played a minor role in these tumors with gain of 11q13, the most frequent losses (3p12-14 and 5q21) being present in 10 of the 14 cases and loss of 9p13-21 in 5/14 tumors. The three tumors with the highest number of CNAs in addition to 11q13, were histologically classified as pT4, three of the five tumors with 11q13 amplification were highly node-positive (pN 2b-2c). Two of the pT4 tumors shared as many as 23 specific chromosomal segments affected by CNA. Thus, gain of 11q13, though being found at different stages of karyotypic evolution, is apparently associated with a rather specific pattern of other CNAs and involved in progressed stages of malignancy in oral squamous cell carcinoma. In addition, the proportion of patients deceased within one year after diagnosis was clearly higher in the group whose tumors showed an increased 11q13 copy number as compared to the group without this increase. This could point to an association of gain in 11q13 and aggressiveness of the respective tumor.

Aged

[Hyperferritinemia in Still syndrome in the adult and reactive hemophagocytic syndrome].

This report describes the fatal outcome of a case of adult onset Still's disease in a 46-year old man. The diagnosis was made according to the 1992 criteria, proposed by Yamaguchi. Nine months after the initial disease manifestations a rapid deterioration with progressive hepatosplenomegaly developed. In parallel, pancytopenia and marked hyperferritinemia could be detected. Transjugular liver biopsy revealed the presence of a hemophagocytic syndrome. The course of the disease was refractory to any form of treatment and the patient died from disseminated intravascular coagulation, hepatic and pulmonary failure. Pathogenetic mechanisms and possible associations between Still's disease and reactive hemophagocytic syndrome are discussed.

Adult

Lipogranulomas as complications of septorhinoplasty.

BACKGROUND: Nasal tumors caused by lipogranulomas are a rare complication of a rhinoplasty; only 1 report of this occurrence was found in the literature. OBJECTIVE: To present a series of 4 patients with subcutaneous nasal tumors after each had undergone a rhinoplasty, together with a review of the literature and the clinical consequences. DESIGN: Case series. SETTING: Hospitalized care at a university ear, nose, and throat department. PATIENTS: Four patients were referred within 6 months from a single department for consultation because of broad nasal pyramids after each patient had undergone a rhinoplasty. The origin of the deformities was not known. INTERVENTIONS: Ear, nose, and throat and ultrasound examinations and computed tomography (ie, bone and soft tissue examinations). Two patients had undergone revision surgery and histological examinations of subcutaneous fibrous tissue. MAIN OUTCOME MEASURE: Search for the origin of the nasal deformity. RESULTS: All 4 patients had wide nasal pyramids. One of the 4 patients also had subcutaneous tumors of the nasal dorsum, glabella, and medial canthus area; this patient had subcutaneous cystic lesions on computed tomography and ultrasound examination and a foreign body reaction around "empty spaces" on histological examination. The tumorlike lesions were the result of displaced ointment from the endonasal packings. Two of the 4 patients with minor deformities did not undergo any surgical revision, and they still had some moderate reduction of the cystic lesions within 1 year after the rhinoplasty. CONCLUSIONS: Lipogranulomas caused by ointments that are used together with nasal packings are most often reported in the orbit after endonasal sinus surgery. The incidence should be more frequent in patients who undergo a rhinoplasty because connections between the endonasal cavity and the extranasal subcutaneous layer are created routinely by osteotomies or removal of a hump. Thus, postoperative deformities (eg, inadequate narrowing of the bony pyramid or supratip thickening [permanent swelling of the nasal tip]) should be examined by use of computed tomography, if lipid ointments were used endonasally. For prevention, no lipid substances should be applied together with pressure from packings. In the case of a lipogranuloma, surgical removal via an open approach is the treatment of choice.

Adult

Antigastric autoantibodies in Helicobacter pylori infection: implications of histological and clinical parameters of gastritis.

BACKGROUND: It has recently been shown that humoral antigastric autoreactivities occur in a substantial number of Helicobacter pylori infected patients. AIMS: To analyse the relevance of such antigastric autoantibodies for histological and serological parameters of the infection as well as for the clinical course. METHODS: Gastric biopsy samples and sera from 126 patients with upper abdominal complaints were investigated for evidence of H pylori infection using histology and serology. Autoantibodies against epitopes in human gastric mucosa were detected by immunohistochemical techniques. Histological and clinical findings of all patients were then correlated with the detection of antigastric autoantibodies. RESULTS: H pylori infection was significantly associated with antigastric autoantibodies reactive with the luminal membrane of the foveolar epithelium and with canalicular structures within parietal cells. The presence of the latter autoantibodies was significantly correlated with the severity of body gastritis, gastric mucosa atrophy, elevated fasting gastrin concentrations, and a decreased ratio of serum pepsinogen I:II. Furthermore the presence of anticanalicular autoantibodies was associated with a greater than twofold reduced prevalence for duodenal ulcer. CONCLUSION: The data indicate that antigastric autoantibodies play a role in the pathogenesis and outcome of H pylori gastritis, in particular in the development of gastric mucosal atrophy.

Adolescent

Congenital microvillous atrophy: report of two cases.

2 infants with chronic severe diarrhoea from birth and with lethal outcome have been studied. Small intestinal biopsies were examined by light and electron microscopy. Severe villous atrophy, complete loss of microvilli or rudimentary forms, intracytoplasmic vesicles, and microvillous inclusions are the characteristic features of the disease. The etiology is unknown. A disturbance in the transport of brush-border proteins to the cell surface is assumed to be the reason for congenital microvillous atrophy.

Atrophy

Antigastric autoantibodies in Helicobacter pylori gastritis: prevalence, in-situ binding sites and clues for clinical relevance.

Colonization of human gastric mucosa with Helicobacter pylori leads to chronic active gastritis and induces the occurrence of an acquired mucosa-associated lymphoid tissue (MALT) in the stomach. This remodelling of the gastric mucosa together with chronic antigen persistence may induce autoimmune reactions. The aim of this study was to investigate humoral autoimmune reactions to human gastric mucosa in H. pylori gastritis and their clinical relevance. Sera from patients with dyspeptic symptoms were tested for presence of IgG immunoglobulins against H. pylori. Gastric infection with H. pylori and alterations of gastric mucosa were demonstrated by histological examination of gastric biopsy specimens. All sera were tested for reactivity against human gastric mucosa by immunohistochemistry. Two different in-situ binding sites of antigastric autoantibodies were observed. Binding to canalicular structures within parietal cells was significantly correlated with antibodies to H. pylori, elevated basal gastrin levels and atrophy of gastric corpus glands. Our data indicate that autoimmune reactions to antigens in the human gastric mucosa occur in H. pylori gastritis and that they may play a role in the pathogenesis of the disease.

Adult

Therapy with CD7 monoclonal antibody TH-69 is highly effective for xenografted human T-cell ALL.

Human T-cell acute lymphocytic leukaemia (ALL) was established in athymic nude or severe combined immunodeficient (SCID) mice by injecting CEM or MOLT-16 cells. When nude mice bearing approx. 2 g of tumour were treated with a single injection of CD7 antibody TH-69, 82.6% reached complete remission within 10 d whereas 13.0% showed partial remission. Similarly, in SCID mice with advanced disease a significant prolongation of survival was seen. The therapeutic effects were dependent upon dose and affinity of the antibody. TH-69 is a high-affinity antibody (7.6 x 10(9) M-1) that rapidly induced modulation during treatment. The Fc-portion of the antibody was required for effective tumour cell killing. Complement deposition was found on tumour sections after TH-69 treatment and in part may account for tumour destruction. There was no evidence for antibody-dependent cellular cytotoxicity (ADCC). The kinetics of tumour disappearance suggested the initiation of a programmed cell death (PCD), despite the lack of significant DNA fragmentation. Unmodified high-affinity antibodies to the T-cell antigen CD7 have potential for T-cell ALL therapy.

Animals

[To what extent do patients with coronary heart disease want to be informed?].

To what extent do patients suffering from coronary heart disease want to be informed? New legislation on patients' rights, passed in Austria in 1993, laid down what information patients are entitled to received. This raises dilemmas. On the one hand the patient has the right to be fully informed about his condition, on the other hand, disclosure could cause sufficient stress to impair the prognosis. The doctor must balance his duty to inform against the therapeutic reasons not to inform, in his duty to care. The empirical part of this research is concerned with the wish to be informed, of patients with coronary heart disease. A questionnaire was administered to patients after bypass operation. It is hoped that the results will be helpful to doctors. Nurses, who are not legally entitled to give information may, nevertheless, find it helpful to know about patients' individual needs for information, when they deliver professional nursing care.

Aged