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Biomedical subjects

D Ofner

Publications and source records attributed to D Ofner.

At least 91 records · Page 5Linked to original sources
PubMed1993

[Proliferative activity and p53 expression in transitional cell carcinoma of the urinary bladder].

Mutations of the p53 gene are important mechanisms in malignant transformation and are associated with dysregulation of normal cell growth. In the present study the expression of mutated p53-protein and proliferating cell nuclear antigen (PCNA) was investigated in a series of 31 human transitional cell carcinomas (TCC) by immunohistochemistry (IHC). The number of PCNA-positive cells and the pattern of expression was distinct in normal urothelium being confined to the basal cell layer. In dysplastic urothelium and in Carcinoma in situ (CIS) PCNA-immunoreactive nuclei were irregularly distributed throughout all layers. In tumor cell complexes the pattern of PCNA-immunoreactivity was different in papillary and primary infiltrating TCCs. Densitometric quantification of the intensity of the PCNA-reactivity using image analysis revealed an increase from normal to dysplastic urothelium and from dysplastic urothelium to invasive tumors. 21/31 (68%) of the tumors and tumor-associated CIS showed overexpression of p53 varying in percentage, pattern and reaction intensity. The percentage of PCNA-positive cells was higher in tumors overexpressing p53. Double IHC showed colocalization of both molecules in a significant proportion of tumor cells suggesting a link of p53 overexpression and the abnormal proliferative activity. The present results show that p53 over-expression is found in a significant percentage of TCCs and indicate a close association with a defective growth regulation resulting in increased PCNA-levels and enhanced cellular proliferation.

Analysis of Variance↗
PubMed1993

[Pregnancy after kidney transplantation].

11 women gave birth to 13 live-born infants after a mean period of 39.6 months following transplantation, whereby one of these women had two successful pregnancies and one patient had a twin pregnancy. The highly premature twins, born after a complicated pregnancy with impaired renal graft function in the mother, died of respiratory insufficiency on the 13th day. All of these renal allograft recipients had to be delivered by caesarean section, either for nephrological or obstetric reasons. All graft with stable function prior to conception suffered no damage as a result of the pregnancy. In two women with already impaired function, pregnancy led to further deterioration and, eventually, graft loss. Because of the small numbers in this series no conclusions can be drawn with regard to the incidence of malformation of premature delivery. It is concluded that women with normal and stable renal graft function should be allowed to become pregnant. The risk for the graft as well as for the child does not seem to be increased under these circumstances. However, due to the complexity of the situation these patients should be cared for at specialized centres.

Adult↗
PubMed1993

Ultrasonography in the initial evaluation and follow-up of blunt abdominal injury.

BACKGROUND: Ultrasonography has been routinely performed in the assessment of blunt abdominal injury at our department of surgery since 1980. To establish its reliability, a retrospective study was carried out on 818 consecutive patients in the years 1980 to 1990. METHODS: Seven hundred twenty six patients underwent real-time ultrasonographic examination of the abdomen. Indication for ultrasonography included all cases evaluated for blunt abdominal trauma. Ninety two patients before 1985 were excluded. RESULTS: Two hundred seventy (37.2%) patients underwent laparotomy, 252 patients (34.7%) because of ultrasonographic diagnosis. Celiotomy was nontherapeutic in 28 patients; 26 of these patients had positive findings from ultrasonography (false positive, 3.6%). Eighteen patients with negative findings from ultrasonography also underwent laparotomy, which was nontherapeutic in two patients (false negative, 2.2%). Four hundred fifty six patients (62.8%) were managed without operation, relying on initial and follow-up ultrasonography, which was negative in 386 (53.2%) and positive in 70 patients (9.6%). The accuracy of ultrasonography was 94.2%, with 91.9% sensitivity, 96.0% specificity, and 94.9% predictive value. The rate of delayed recognition of documented visceral injury was 5.1%, but no false-negative findings from ultrasonography were noted among these patients. CONCLUSIONS: Ultrasonography has proved to be a thoroughly reliable, cost efficient, and noninvasive modality in primary evaluation and follow-up of blunt abdominal trauma.

Abdominal Injuries↗
PubMed1993

[The effect of various donor factors on primary and long-term function of the transplanted kidney].

Various factors such as cause of brain death, duration of intensive care, single or multiple organ procurement, renal function, heart rate, mean arterial blood pressure, requirement of catecholamines and metabolic derangement were investigated in 86 consecutive organ donors with respect to the possible influence on initial graft function in 86 kidney recipients. Donor conditioning and perioperative recipient management were standardized. Donors of kidneys with initial graft function (group I) showed a significantly higher incidence (80%) of brain death as a consequence of an isolated cerebral incident than donors of kidneys without initial graft function (group II), whereas the incidence of polytrauma (including cerebral) was much higher in donors of group II kidneys (42.9%). The donor requirement of catecholamines was higher in group II donors and the frequency of multiple organ donors was also higher in this group. Five-year graft survival was 80% for group I kidneys but only 62% for group II kidneys. The other factors had no influence on initial graft function. These data demonstrate that multiple injuries and multiple organ procurement have a negative impact on the initial function of the transplanted kidney, possibly due to prolonged ischemic insult.

Acid-Base Equilibrium↗
PubMed1992

Effects of interferons on the expression of the proto-oncogene HER-2 in human ovarian carcinoma cells.

The over-expression of the proto-oncogene HER-2 (c-erbB-2/neu) in ovarian, endometrial and mammary carcinoma is an important indicator for poor prognosis. We have previously shown in 3 out of 4 ovarian carcinoma cell lines an interferon-gamma (IFN-gamma)-mediated reduction in HER-2 specific protein and RNA levels. The oncogene expression was lowered only in the ovarian carcinoma cell lines but not in 3 IFN-gamma-sensitive human breast cancer cell lines. We extended our observations also to IFN type I, alpha and omega. The expression of the oncogene was measured by both the p185HER-2 ELISA and in selected cases by a living cell radioimmunoassay using the monoclonal antibody (MAb) 4D5 against the extracellular domain. Both IFN types reduced the expression of HER-2 in the ovarian carcinoma cell lines OVCAR-3, HTB-77, 2774 and SKOV-6, and in the SKUT-2 endometrial carcinoma cells. In contrast, SKOV-8 human ovarian carcinoma cells were sensitive for both IFN types regarding proliferation, but only IFN-gamma reduced proto-oncogene expression. In the SKBR-3 human mammary carcinoma cells, neither IFN type had an effect on HER-2 expression. The antibodies 4D5, 7C2, 3E8, and 3H4 which bind to the extracellular domain of p185HER-2 protein specifically inhibited anchorage-independent growth of SKBR-3 and HTB-77 cells. Expression of the oncogene HER-2 is the leading prognostic factor in ovarian cancer. Its modulation might represent a mechanism by which IFNs inhibit cell proliferation.

Antibodies, Monoclonal↗
PubMed1992

Immunohistochemical demonstration of chromogranins A and B in neuroendocrine tumors of the lung.

Fifty neuroendocrine tumors of the lung (16 carcinoids, two atypical carcinoids/well-differentiated neuroendocrine carcinomas [WDNCs], 13 neuroendocrine carcinomas of intermediate cell type [SCNCs], and 19 neuroendocrine carcinomas of small cell type [SCNs]) were immunohistochemically investigated with antibodies against chromogranins A and B. All carcinoids and WDNCs were positive for both chromogranins A and B, whereas in cases of ICNC and SCNC both markers were only expressed in six and five cases, respectively. One ICNC was only positive for chromogranin A. In cases of SCNC five tumors were exclusively positive for chromogranin A and six were positive only for chromogranin B. Chromogranins are therefore excellent markers for the immunohistochemical demonstration of carcinoids and WDNCs. It may be speculated that expression of chromogranins in cases of ICNC and SCNC represents a higher degree of differentiation in these tumors.

Carcinoid Tumor↗
PubMed1992

Deoxyribonucleic acid flow cytometry and semiquantitative histology of spermatogenesis: a comparative study.

OBJECTIVE: To compare deoxyribonucleic acid (DNA) flow cytometry with a semiquantitative histologic method for the assessment of spermatogenesis and to investigate the influence of various preparative techniques on the results of DNA measurements. DESIGN: Testicular tissue from 52 autopsies was examined for spermatogenesis by DNA flow cytometry and by conventional semiquantitative histology. Flow cytometry was performed on single nuclei suspensions from fine needle aspiration biopsies, resuspended imprints, as well as on specimens obtained by mechanical disaggregation of surgical biopsies of the same testis. RESULTS: In all cases, flow cytometry revealed a characteristic distribution pattern of haploid (n), diploid (2n), and tetraploid (4n) cells independent of the preparation technique used. The percentage of haploid cells of the testes showed statistically highly significant correlations (P = 0.0002) with the results of semiquantitative histology. Fine needle aspiration biopsy always contained more haploid cells compared with resuspended imprints and mechanically disaggregated samples. CONCLUSION: Our results confirm the suitability of DNA flow cytometry as a fast and reliable quantitative method for the assessment of spermatogenesis and demonstrate its optimal feasibility in combination with fine needle aspiration biopsy.

Adult↗
PubMed1992

Relationship between quantity of silver stained nucleolar organizer regions associated proteins (Ag-NORs) and population doubling time in ten breast cancer cell lines.

Using a one-step silver staining technique ten human breast cancer cell lines were investigated, determining by means of automated image analysis the mean area of Ag-NORs per nucleus, the total number of Ag-NORs, and the so-called "scattered" and "clustered" Ag-NORs. These parameters were statistically correlated with the population doubling time (PDT) of the various carcinoma cell lines of this series. Our results show that the mean area of Ag-NORs per nucleus (p less than 0.001) is highly significantly correlated to the PDT, whereas all other parameters were less or not significant. It is concluded that the assessment of the area of Ag-NORs by automated image analysis is a simple and reliable method for the determination of cell duplication rates.

Breast Neoplasms↗
PubMed1992

Classic, atypical, and anaplastic meningioma: three histopathological subtypes of clinical relevance.

This study correlates the histopathological classification of meningiomas with clinicopathological features of biological activity. A retrospective evaluation of 1799 surgical specimens of meningiomas from 1582 patients was made. The classic histopathological type, atypical meningiomas defined by increased cellularity and at least five mitotic figures in 10 high-power fields, anaplastic (malignant) meningiomas, and hemangiopericytic or papillary meningiomas were seen in 87.6%, 7.2%, 2.4%, and 2.8% of operations, respectively. The rates of recurrence in surgically treated patients with classic, atypical, anaplastic, and hemangiopericytic or papillary meningiomas were 6.96%, 34.6%, 72.7%, and 68.2%, respectively. The extent of surgery and the tumor size and site were studied in detail in 252 tumors of all histopathological types. Recurrences were rare in classic meningiomas after complete resection, whereas atypical and anaplastic tumors recurred after complete resection much more frequently. Classic meningiomas, hemangiopericytomas, and papillary meningiomas were smaller at surgery than atypical and malignant meningiomas. Atypical and malignant tumors were operated on more often in falcine and lateral convexity regions than were classic meningiomas. To support the authors' subjective categorization by a quantitative parameter related to proliferation, 112 meningiomas comprising all histopathological subtypes were investigated for staining of argyrophilic nucleolar organizer region proteins (Ag-NOR's). The Ag-NOR counts showed significant differences between classic, atypical, and anaplastic tumors but no significant differences between primary and recurrent tumors. Hemangiopericytomas and papillary meningiomas had lower Ag-NOR values than anaplastic meningiomas. A correlation of Ag-NOR numbers with the authors' histopathological scale of malignancy supports the introduction of atypical meningiomas with intermediate biological behavior on the classification scale between classic and anaplastic meningiomas. Overlapping of Ag-NOR numbers among all groups of malignancy may restrict the prognostic value of Ag-NOR counting in the individual case.

Aged↗
PubMed1991

Does pancreas transplantation influence the course of diabetic retinopathy?

Between March 1983 and December 1989 a total of 57 pancreas transplants were performed in 54 patients, of whom 49 also received a kidney for end-stage diabetic nephropathy. Of the surviving 44 patients, 39 had regular pre-operative and post-operative ophthalmological examinations. Diabetic retinopathy was classified according to the original "Early treatment diabetic retinopathy study" (ETDRS) protocol. At the time of this analysis a total of 25 patients had a functioning pancreas transplant and 23 of them also a functioning renal allograft after a mean observation time of 43.2 months (Group 1). They were all free of exogenous insulin, HbA1c being 6.2% (5.1-6.9%; normal value 4.2-5.9%). Fourteen patients in Group 2 lost their pancreas transplant during the first four years. Six of them still have a functioning renal allograft, four patients regularly undergo hemodialysis. Mean HbA1c is 7.5% (5.7-9.2%). Before transplantation, grade of retinopathy according the ETDRS protocol was 6.7 (2-10) in group 1 patients and 7.9 (3-10) in group 2. In group 1 patients stabilisation of retinopathy was observed in 33 eyes (73.3%) and clear improvement achieved in 4 eyes (8.8%). Detoriation occurred in 8 eyes (17.7%) only. In group 2, 14 eyes (54%) remained stable, whereas progression of the disease continued in 12 eyes (46%). From these results it is concluded that the course of diabetic retinopathy is positively influenced by successful pancreas transplantation.

Adult↗
PubMed1991

Small bowel transplantation in the rat: impact of various immunosuppressive regimens on graft-versus-host reaction.

The effect of ciclosporin (CS) and methotrexate (MTX) on the development of graft-versus-host (GvH) disease was examined after small bowel allotransplantation in the rat. The drugs were tested either alone or in combination. Lewis small bowel allografts were transplantated into Brown Norway recipients in a heterotopic position. The native small bowel, spleen, liver, skin, mesenteric lymph nodes and the kidney of the recipients were examined histologically 5, 10 and 20 days after allotransplantation. Intraepithelial lymphocyte numbers were determined quantitatively in the native small bowel. The relative spleen weight of the host was determined after sacrifice for estimation of the severity of GvH disease. Grade I GvH reaction of the native small bowel occurred in the animals without immunosuppression, but graft rejection predominated in this group. Treatment with CS was effective in the early postoperative periods; after 10 and 20 days GvH lesions in the native small bowel were comparable to those observed in the allogeneic combinations. MTX had a detrimental effect on the allografts and the GvH reaction was augmented. When CS and MTX were combined, GvH lesions were comparable to those in the animals treated solely with CS. Animals, however, suffered from heavy side effects. The spleen, liver, lymph nodes and kidney exhibited only unspecific histologic changes, which could not unequivocally be recognized as a GvH reaction. This was true for all groups. As a conclusion it can be said that GvH reaction occurs in the early postoperative period in a fully allogeneic model and cannot be prevented by CS in the dosae used. MTX was not seen to be of any value in this regard.

Animals↗
PubMed1990

[Intestinal angiodysplasia as a cause of severe intestinal hemorrhage--report of 4 cases].

Angiodysplasia of the small intestine alone cannot be differentiated histologically from hereditary hemorrhagic telangiectasia (Morbus Rendu-Osler-Weber). Isolated localisation in the small intestine is rare and requires surgery in the event of massive bleeding. Four cases of bleeding from angiodysplasias of the small intestine in patients having undergone surgery at our institution over a ten-year period are presented. In three patients the particular intestine was resected. Two of these patients had an uneventful follow-up of even and ten years, one patient relapsed and was rehospitalized for surgical treatment. The fourth patient, who showed angiodysplasias scattered over the entire small intestine, had no further bleeding over a three-year period after transmural ligations of the lesions found by intraoperative endoscopical diaphany.

Adult↗
PubMed1990

Silver stained nucleolar organizer region proteins (Ag-NORs) as a predictor of prognosis in colonic cancer.

Using a one-step silver nitrate staining technique, routinely processed tumour tissues of 49 carcinomas of the colon were investigated to demonstrate silver-stained nucleoli (Ag-nus) and argyrophilic proteins associated with the so-called nucleolar organizer regions (Ag-NORs). Patients with attempted curative resections and tumour stages Dukes' A, B, C1 and C2, with an uneventful follow-up period of at least 48 months (N = 17), showed a statistically significant (P = 0.0001) lower mean number of scattered Ag-NORs (3.04; SD: 1.08) compared to patients who developed metastases during their follow-up period (N = 15; 5.40; SD: 1.28), as well as to patients who underwent palliative surgical treatment (N = 17; 4.48; SD: 1.67). Mean numbers of scattered Ag-NORs per nucleus and staging of the tumour were strongly related (P = 0.0001) to cancer-specific survival. The results indicate that the evaluation of silver-stained particles according to their different distribution patterns is of great value with regard to the clinical outcome of colonic carcinoma and may even allow a more accurate prognostic assessment of these patients than the WHO grading system, UICC staging system, the so-called Jass-scoring system, and Dukes' classification.

Adult↗
PubMed1990

Argyrophilic nucleolar organizer region proteins (Ag-NORs) in human brain tumors: relations with grade of malignancy and proliferation indices.

Proliferation indices and mean number of silver-stained nucleolar organizer region-associated proteins (Ag-NORs) are compared in 65 brain tumors, including 34 gliomas, 8 meningiomas, 17 metastatic tumors, and 6 other tumors. Immunocytochemical investigations include labeling with the monoclonal antibody Ki-67 which identifies the whole growth fraction, and with a monoclonal antibody against bromodeoxyuridine (BrdUrd) which detects cells in the S phase of the cell cycle after in vitro incubation with BrdUrd. When all types of tumors are collectively considered, mean numbers of Ag-NORs did not correlate with Ki-67 and Brd-Urd labeling indices (LIs) and mitotic index. Among tumor subtypes, only meningiomas showed significant correlations between Ag-NOR counts, LIs, and malignancy. Mean number of Ag-NORs did not correlate with proliferation indices and tumor grade in low-grade and high-grade gliomas. However, recurrent high-grade gliomas showed a tendency to higher Ag-NOR counts than primary tumors. This study indicates that counting of Ag-NORs in paraffin sections is of limited value in tumor neuropathology. Correlations found in meningeal tumors should be substantiated in larger series.

Adult↗