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Biomedical subjects

D Ofner

Publications and source records attributed to D Ofner.

At least 37 records · Page 2Linked to original sources

MIB1 in colorectal carcinomas: its evaluation by three different methods reveals lack of prognostic significance.

Immunohistochemically detected MIB1 has been determined in a series of 106 colorectal carcinomas with three different evaluation methods (semiquantitative estimation, evaluation by image analysis, and cell count). Although the semiquantitative estimation correlated significantly with results obtained by image analysis (R = 0.8), both methods were only poorly associated with MIB1 counts (R = 0.5). Additionally, all three methods revealed no statistical correlation of MIB1 with the clinical outcome of the respective patients. Our results indicate a pronounced heterogeneity of MIB1 in colorectal adenocarcinoma, thus leading, irrespectively of the evaluation method used, to non-representative results with lack of clinical relevance.

Adenocarcinoma

The effect of nephrectomy on the outcome of renal transplantation in patients with polycystic kidney disease.

Although various forms of polycystic kidney disease (PKD) account for up to 10% of patients requiring renal replacement therapy and severe complications may arise from these kidneys, no clear indications for pretransplant nephrectomy have been defined so far. A total of 104 renal transplants in three pediatric and 96 adult patients suffering from PKD were analysed retrospectively with regard to patient and graft survival in relation to pretransplant or posttransplant nephrectomy and no nephrectomy. Of these 99 patients, 25 had had either unilateral (19) or bilateral (6) nephrectomy sometime before transplantation and 10 patients between 3 and 81 months after transplantation. All patients received Cyclosporine-based immunosuppression. One-year patient and graft survivals for recipients of a first cadaveric renal graft (n = 91) were 94% and 92%, for recipients of second or third graft (n = 13) 89% and 78%. One- and five-year patient survival rates for patients with or without pretransplant nephrectomy were 100% and 100% vs 92% and 84%, respectively. One- and five-year graft survival rates were 100% and 93% for pretransplant nephrectomy patients vs 89% and 74% for the non-nephrectomy group (p < 0.05). Patients not undergoing nephrectomy sometime after transplantation had the same patient but better five-year graft survival when compared to the posttransplant nephrectomy group (89% vs 52%). In patients with early posttransplant urinary tract infection, which is considered in this analysis as a cyst-related complication, graft survival at one year was 77% but 97% in patients without this complication. From these data it is recommended that polycystic kidneys should be removed before transplantation if cyst-related complications occur repeatedly. Posttransplant nephrectomy can be performed with no mortality and should be carried out whenever clinically indicated.

Adolescent

Standardized staining and analysis of argyrophilic nucleolar organizer region associated proteins (AgNORs) in radically resected colorectal adenocarcinoma--correlation with tumour stage and long-term survival.

Quantification of silver-stained nucleolar organizer region associated proteins (AgNORs) was introduced in histopathology as a marker of cellular and nucleolar activity. However, due to the poor staining quality obtained on routinely processed archival material, the method yielded controversial and sometimes non-reproducible results. The recent introduction of wet autoclave pretreatment has reliably improved AgNOR staining quality on routinely formalin-fixed and paraffin-embedded tissues. In the present study, 92 routinely processed colorectal carcinomas were investigated, applying this novel staining technique. Subsequent standardized morphometric analysis revealed, irrespective of common tumour staging or grading classifications, a statistically highly significant correlation between AgNOR parameters and clinical course. The usefulness of standardized AgNOR parameters for the independent prediction of patient survival was proven by uni- and multivariate analysis.

Adenocarcinoma

Immunohistochemical detection of p53 protein in archival tissues from squamous cell carcinomas of the oral cavity using wet autoclave antigen retrieval.

Using a panel of four anti-p53 antibodies (CM-1, PAb 1801, DO7, and PAb 240), the phenotypic characteristics of p53 protein overexpression were investigated in 22 routinely formalin-fixed and paraffin-embedded squamous cell carcinomas of the oral cavity. Conventional immunohistochemical staining without pretreatment for antigen retrieval was compared with wet autoclaving (AC) and microwave irradiation (MW). Applying AC or MW, p53 immunoreactivity was demonstrated in 9/22 cases with PAb 1801 and DO7 antibodies and in 8/22 cases with the CM-1 antibody. Immunostaining with the PAb 240 antibody after AC pretreatment showed p53 positivity in 8/22 tumours, but in only 4/22 following MW pretreatment. Immunostaining without pretreatment revealed only 2/22 p53-positive cases using CM-1, 4/22 with PAb 1801, and 3/22 with DO7. Without pretreatment, the PAb 240 antibody was consistently negative. Wet autoclave pretreatment was significantly superior for all the antibodies used in this study when compared with conventional immunohistochemistry without pretreatment (P < 0.005). It yielded better results than microwave irradiation for antigen unmasking in relation to the PAB 240 antibody (P < 0.05). Wet autoclave pretreatment is recommended as a reliable and highly reproducible method for p53 antigen retrieval in routinely processed archival material. The advantages over microwave pretreatment include simple handling and good preservation of morphology.

Carcinoma, Squamous Cell

Immunohistochemical distribution of chromogranins A and B and secretogranin II in neuroendocrine tumours of the gastrointestinal tract.

The aim of the present study was to investigate immunohistochemically the distribution of chromogranin A, chromogranin B, and secretogranin II in a series of 152 neuroendocrine tumours of the gastrointestinal tract. Tumour tissues from 25 argyrophil gastric carcinoids, 18 gastrin and 5 somatostatin-producing tumours, 4 'gangliocytic paragangliomas', 49 classical argentaffin and 2 L cell appendiceal carcinoids, 27 classical ileal carcinoids, 17 rectal carcinoids, and 5 poorly differentiated neuroendocrine tumours of the stomach and rectum were immunostained with antibodies against chromogranin A, chromogranin B, and secretogranin II. Chromogranin A was the major granin expressed in gastric carcinoids and in serotonin-producing carcinoids of the appendix and the ileum. In contrast, strong chromogranin B and secretogranin II immunoreactivity was found in rectal carcinoids, in which chromogranin A was rarely expressed. Since chromogranin A is a widely used marker for neuroendocrine differentiation, it is of diagnostic importance that some gastrin-producing tumours, 'gangliocytic paragangliomas', poorly differentiated neuroendocrine carcinomas, and appendiceal L cell carcinoids completely lacked chromogranin A positivity. It is concluded that the various neuroendocrine tumours of the gastrointestinal tract show distinctly different patterns of granin expression, probably reflecting their histogenetical origin.

Chromogranin A

Wet autoclave pretreatment for immunohistochemical demonstration of oestrogen receptors in routinely processed breast carcinoma tissue.

The immunohistochemical demonstration of oestrogen receptor (OR) was performed on 32 randomly selected and routinely processed breast carcinomas after wet autoclave pretreatment of sections. The autoclave method was compared to the OR status found on frozen sections as well as to alternative pretreatment methods such as enzymatic predigestion and microwave irradiation. Using four different monoclonal antibody clones (H222, LH1, CC4-5, 1D5.26), the OR status was evaluated for each of the various pretreatment methods applied. All cases with a high OR content on frozen sections (n = 11) also showed a high OR status on wet autoclave-pretreated paraffin tissues using antibody clones 1D5.26 and CC4-5; in cases with low OR content on frozen sections, no false-negative cases were recorded using only the antibody 1D5.26 neither after wet autoclave nor microwave pretreatment. In addition, with this antibody, OR was detectable after autoclave pretreatment in two cases which were considered to be OR-negative even on frozen sections. When the primary antibody was omitted, no false-positive cases were observed after wet autoclave pretreatment. Thus, in our hands, wet autoclave pretreatment, in combination with the antibody 1D5.26, offers a highly sensitive method for the immunohistochemical demonstration of OR in routinely formalin-fixed, paraffin-embedded sections of breast carcinomas.

Antibodies, Monoclonal

Fulminant hepatic failure in a child as a potential adverse effect of trimethoprim-sulphamethoxazole.

UNLABELLED: Trimethoprim-sulphamethoxazole (TMP-SMZ) is considered a safe drug for treatment of infectious bacterial diseases in children. Side-effects are rare and generally take the form of a hypersensitivity reaction to the sulphamethoxazole component of the drug. Hepatic injury usually presents as a transient elevation of liver enzymes, which is of little clinical relevance. Fulminant liver failure due to TMP-SMZ has been reported in only six adults and never in children. We here report a 5-year-old girl who developed fulminant liver failure 3 weeks after her third exposure to TMP-SMZ. After a biphasic clinical course she underwent successful liver transplantation. CONCLUSION: Trimethoprim-Sulphamethoxazole may cause fulminant liver failure in children. The disease can run a biphasic clinical course and liver transplantation must be considered as the therapeutic option for these patients.

Biopsy

Prognosis and life expectancy in chronic liver disease.

The aim of the present was to define prognosis and life expectancy in patients with chronic liver disease of different etiologies and to relate them to an age- and sex-matched normal population. After a follow-up of 15 years, life expectancy of 620 patients with chronic liver disease was retrospectively calculated and compared with an age- and sex-matched normal population. Among patients with cirrhosis, prognosis was dependent upon Child classification (P = 0.001). Patients with alcoholic cirrhosis and fatty liver disease were younger (P = 0.01) and had a lower life expectancy than patients with other causes of chronic liver disease (P = 0.004). Patients with hepatitis B and hepatitis C cirrhosis showed a comparable prognosis and a significantly lower life expectancy than the age- and sex-matched population. Cryptogenic and autoimmune liver diseases showed a comparable life expectancy but a significantly shorter life expectancy than the normal population. In patients with alpha 1-antitrypsin deficiency-associated cirrhosis, a high viral coinfection rate was found (P = 0.01). For patients with noncirrhotic hemochromatosis, prognosis was poorer than that for the age- and sex-matched population. In patients with asymptomatic primary biliary cirrhosis, chronic persistent hepatitis B, and alpha 1-antitrypsin deficiency without cirrhosis, life expectancy was equal to that of the normal population. Prognosis and life expectancy in chronic liver disease depend on stage, cause, and symptoms of chronic liver disease; age; and possibilities of treatment. In patients with hereditary liver disease, additional viral infection of alcohol abuse lead to a significant deterioration of life expectancy. Patients with alcoholic chronic liver disease have the poorest prognosis.

Autoimmune Diseases

The impact of jejunal transplant peristalsis on enteric flora.

The importance of phase III of the migrating myoelectric complex (MMC) for homeostasis of enteric flora is well documented. The goal of this study was to evaluate in an isogeneic rat model the effect of MMC changes on the self-purging capacity of the jejunal graft. The proximal 25% of the entire jejunoileum of Lewis rats was transplanted orthotopically. Electrodes were then fixed to the graft. Native bowel of five rats and five rats with analogue jejunal segmentation served as controls. Myoelectric recordings were carried out until day 21, when animals were killed for bacteriologic analysis of the segments analyzed myoelectrically and the of neighboring gut. MMCs were observed in all animals during all recordings. Phase III was irregular in transplants because of long-lasting periods of phase III absence alternating with phase III occurring more frequently. The variation coefficient of phase III periodicity calculated for grafts was 48.74, for native bowel 14.79, and for segmented jejunum 22.9. Enteric flora found in all specimens consisted of colonic-like microorganisms. Titers of microorganisms in grafts did not differ from control segments. These findings show that phase III periodicity is severely altered in jejunal grafts. Homeostasis of enteric flora, however, is not influenced by the transplant procedure.

Animals

Immunohistochemically detectable bcl-2 expression in colorectal carcinoma: correlation with tumour stage and patient survival.

The bcl-2 gene encodes for a mitochondrial membrane proto-oncoprotein, the expression of which is known to suppress programmed cell death (apoptosis). In the present study the prognostic value of bcl-2 proto-oncoprotein was immunohistochemically investigated in a series of 104 colorectal carcinomas. The bcl-2 staining patterns were semiquantitatively assessed and correlated with the pTNM stage, Dukes' classification, lymphocytic infiltration (Jass classification) and tumour grade as well as parameters not associated with prognosis (gender, age, tumour site, histological tumour type). Statistical analysis was carried out using the Kaplan-Meier method, the log-rank test, hazard ratios and their confidence intervals. Fifty-five out of 104 cases completely lacked immunohistochemical bcl-2 expression. Fewer than 5% of bcl-2-positive cells were found in 25, 5-50% in 17 and more than 50% in five cases. The extent of bcl-2 expression by tumour cells decreased significantly with respect to increasing tumour size (P < 0.05), decreasing lymphocytic infiltration (P < 0.05) and chance of poor clinical outcome (P < 0.05), but not with worsening of Dukes stages. In multivariate analysis (Cox regression model) bcl-2 expression remained as an independent prognostic parameter with Dukes' classification as stratification factor (P < 0.001). Although the biological functions of bcl-2 protein are not yet well understood, our results provide further evidence that bcl-2 oncoprotein appears to be associated with favourable clinical outcome. Thus immunohistochemical bcl-2 phenotyping of colorectal carcinoma may contribute in future to the clinical management of these patients.

Adult

Statistical modelling in analysis of outcome after trauma Glasgow-Coma-Scale and Innsbruck-Coma-Scale.

AIM OF THE STUDY: The current study investigated the Glasgow-Coma-Scale (GCS) and the Innsbruck-Coma-Scale (ICS) for accuracy and reliability of prehospital prediction of non-survival. METHODS: 254 patients were scored immediately after trauma. RESULTS: Both scales equally predicted non-survival with low scores (p < 0.001). The ICS was slightly better in overall prediction of patient outcome (ICS: 84.98%; GCS: 82.68%), but more importantly, statistical analysis (logistic regression model) showed a greater distance between the median scores of survivors and non-survivors, when scored with the ICS (survival: 12; non-survival: 3) than when scored with the GCS (survival: 7; non-survival: 4). CONCLUSION: The results of the present study not only suggest that it is possible to predict mortality prior to therapy for any individual GCS and ICS coma score, but also indicated the ICS to be safer to use than the GCS because of the greater distance of the median scores for survivors and non survivors.

Adolescent

Secretoneurin in bronchopulmonary carcinoids--immunohistochemical comparison with chromogranins A and B and secretogranin II.

Ninety-nine classical and 11 atypical bronchopulmonary carcinoids were investigated immunohistochemically with an antibody against secretoneurin, a peptide proteolytically processed from secretogranin II (chromogranin C), as well as antibodies against chromogranin A and B and secretogranin II. Secretoneurin was immunolocalized in 86 tumours (78 classical and eight atypical carcinoids); secretogranin II was found in the same tumours in a similar distribution, whereas chromogranin A was present in all 100 and chromogranin B in 106 tumours investigated. Bronchopulmonary carcinoids are usually not associated with clinically or biochemically distinct syndromes. Although we found bronchial carcinoids with different immunohistochemical chromogranins/secretogranin patterns, no correlation with the biological behaviour of these tumours could be demonstrated.

Carcinoid Tumor

Atrophic variants of dermatofibroma and dermatofibrosarcoma protuberans.

Dermal atrophy of more than 50% of the locoregional dermis may be the predominant histopathological feature in dermatofibroma and dermatofibrosarcoma protuberans. This may cause diagnostic difficulties. In the present study 26 cases of atrophic dermatofibroma were compared with three cases of atrophic dermatofibrosarcoma protuberans. Clinically, both conditions mostly occurred on the (upper) trunk of females. While atrophic dermatofibroma usually presented as a reddish, umbilicated lesion (0.5-1cm), often suspected to be a basal cell carcinoma, atrophic dermatofibrosarcoma protuberans showed irregularly arranged tan-brown plaques (3-6 cm). Histologically, atrophic dermatofibroma showed a regular silhouette with a smooth nodular (9/26) or scalloped lower margin with an intervening lace-like pattern of superficial fatty tissue infiltration (17/26) and variable sclerosis: atrophic dermatofibrosarcoma protuberans showed a deep, irregular infiltration of fatty tissue in a lacelike/honeycomb and/ or multilayered pattern, but no sclerosis. Immunohistochemically, atrophic dermatofibroma was mostly negative with QBEnd 10 (CD34;24/26), variably positive for factor XIIIa (20/26) and metallothionein (11/26). Labelling for factor XIIIa and metallothionein was usually seen in 'early' (metabolically active) lesions, while 'late' sclerotic ones were negative. In contrast to atrophic dermatofibroma all three atrophic dermatofibrosarcoma protuberans showed a consistently uniform profile: CD34 positive, factor XIIIa and metallothionein negative. Our study delineates atrophic dermatofibroma and atrophic dermatofibrosarcoma protuberans as distinct entities clearly distinguishable from each other by clinicopathologic criteria.

Adult

Expression of p53 protein in oral squamous cell carcinomas and adjacent non-tumorous mucosa of the floor of the mouth: an archival immunohistochemical study using wet autoclave pretreatment for antigen retrieval.

Routinely formalin-fixed and paraffin-embedded material of 22 squamous cell carcinomas of the floor of the mouth (T2NoMo, Ro), together with adjacent dysplastic or normal mucosa, were immunohistochemically investigated using a panel of four anti-p53 antibodies (CM1, PAb1801, DO7, PAb240) subsequent to wet autoclave pretreatment for antigen retrieval. p53 immunoreactivity was detected in 9/22 (40%) carcinomas with PAb1801 and DO7 antibodies, and in 8/22 cases using CM1 and PAb 240. p53-positive tumour cells accumulated predominantly at the invasive front of the carcinomas. A focal or scattered p53 immunoreactivity was observed in the adjacent normal and/or dysplastic mucosa in 17/22 (77%) cases using both CM1 and PAb1801 antibodies, in 10/22 with DO7, and in 8/22 with PAb240. This study has demonstrated examples of different p53 immunophenotypes in the non-tumorous and neoplastic oral mucosa of the same patient without significant correlation to the clinicopathological parameters studied.

Antibodies, Monoclonal

Prognosis and life expectancy on alpha-1-antitrypsin deficiency and chronic liver disease.

BACKGROUND: Alpha-1-antitrypsin deficiency is a common autosomal recessive disorder associated with early development of emphysema, liver cirrhosis, and hepatocellular carcinoma. The aim of the present study was to define prognosis and life expectancy in patients with alpha 1-antitrypsin deficiency with and without chronic liver disease. METHODS: After a follow-up of 15 years the estimated life table analysis of mortality of 160 patients with alpha 1-antitrypsin deficiency was retrospectively calculated. The survival time was estimated using the Kaplan-Meier survival curves and was compared with the life expectancy of the age- and sex-matched population of west Austria. RESULTS: Fifty-four patients with alpha 1-antitrypsin patients had evidence of chronic liver disease; of these, 78% showed positive viral markers. Of the 106 patients with alpha 1-antitrypsin deficiency without chronic liver disease none had evidence of additional viral infection. Life expectancy in patients with alpha-1 antitrypsin deficiency and chronic liver disease was significantly lower than in patients with alpha 1-antitrypsin deficiency without chronic liver disease (p = 0.001). No difference in life expectancy in alpha 1-antitrypsin deficiency without chronic liver disease was found in comparison with that of the normal population. CONCLUSIONS: We suggest that in alpha 1-antitrypsin deficiency-associated chronic liver disease it is the high coinfection rather than the inborn error of metabolism itself that is responsible for a deterioration of life expectancy or for the poor prognosis of the disease.

Chronic Disease

Pentoxifylline as an adjunct to cyclosporine-based immunosuppression does not improve the outcome of renal transplantation.

The adjunct of PTX to the therapeutic regimen after renal transplantation had no effect on the incidence of ATN, immunologic or infectious complications, or CyA toxicity. Also, patient and graft survival was not affected. The four deaths in the study group can probably not be attributed to PTX therapy. From these data it is concluded that PTX is not able to improve the outcome of renal transplantation.

Adult