Biomedical subjects

J Kovarik

Publications and source records attributed to J Kovarik.

At least 73 records · Page 4Linked to original sources

PubMed1993

Immunochemical analysis of the p53 oncoprotein in matched primary and metastatic human tumours.

There is much interest in the range of genetic aberrations which occur in human malignancies. An immunohistochemical study has been carried out to investigate the consistency of expression of abnormally accumulated p53 protein in paired samples of archival primary and metastatic carcinomas. The staining of methacarn-fixed tissue from 136 matched pairs of mammary carcinoma and 20 cancers from other sites was completed using antibody CM-1 and DO1 in a sensitive peroxidase-conjugated streptavidin-biotin technique. The majority of tumour cells were positive in 25% and the tumours were negative in 17% of the primary carcinomas; staining was heterogeneous in the remaining cases. Staining was identical in 180/186 (96%) metastatic lesions. An ELISA assay carried out on 12 matched pairs of the tumour specimens demonstrated that altered conformation of the aberrant p53 protein present in a primary lesion was maintained in its metastasis. These data indicate that alterations in the p53 gene result in a relatively stable phenotype and that progression of disease is not usually accompanied by either further mutation or loss of the mutant allele.

Breast Neoplasms↗

PubMed1993

The effects of lisinopril on renal function in proteinuric renal transplant recipients.

Renal transplantation is frequently accompanied by systemic hypertension. In the present study we evaluated the effect of 2.5 mg lisinopril in 12 hypertensive and proteinuric renal graft recipients with stable graft function over 3 months. Only patients with absence of renal artery stenosis, at least as judged by technetium-scan imaging, were included. Lisinopril was effective in lowering systemic blood pressure. Mean arterial pressure was unchanged despite reduction of concomitant antihypertensive medication. Mean serum creatinine was unchanged during the study (1.95 +/- 0.8 mg/dl in the pretreatment period vs. 1.77 +/- 0.76 mg/dl in the intervention period, n.s.). Glomerular filtration rate remained stable (62.75 +/- 21.96 vs. 60.17 +/- 18.27 ml/min/1.73 m2, n.s.) whereas renal plasma flow increased (224.75 +/- 91.66 vs. 244.92 +/- 94.13 ml/min/1.73m2, P < 0.01), leading to a drop in filtration fraction (31.4 +/- 12.4 vs. 26.8 +/- 8.6, n.s.). Renal vascular resistance was significantly reduced following angiotensin-converting enzyme (ACE) inhibitor therapy (26,447 +/- 14,574 vs. 23,425 +/- 12,430 dyne sec cm-5/1.73 m2, P < 0.01). Mean daily proteinuric decreased significantly (2.98 +/- 2.06 vs. 2.06 +/- 2.29 g, P < 0.01) whereas in a group of patients with comparable blood pressure but without ACE inhibitor therapy and similar degree of proteinuria, 24-hr proteinuria remained stable. No severe side effects were observed--in particular, mean serum potassium showed only a slight increase and no clinically significant hyperkalemic condition was observed. When lisinopril therapy was withdrawn after 3 months, blood pressure increased in all patients, requiring reinstitution of additional antihypertensive medication. Renal hemodynamic parameters and daily proteinuria returned to baseline values. We conclude that 2.5 mg lisinopril daily was safe and effective in this group of renal transplant recipients and showed a good antihypertensive as well as antiproteinuric effect.

Adult↗

PubMed1993

Secondary hyperparathyroidism and acute tubular necrosis following renal transplantation.

In the present study we investigated the relationship between secondary hyperparathyroidism in renal graft recipients and post-transplantation acute tubular necrosis (ATN). Patients were divided into two groups according to graft function: group A consisted of 28 patients who had an uneventful postoperative period and did not require haemodialysis. Group B comprised 26 patients with primary non-function of the graft due to biopsy-proven ATN who required continued haemodialysis for the first postoperative week or longer (mean 14.2 +/- 8.7 days). Both groups had comparable donor characteristics, HLA-matching and ischaemia times. All patients were given cyclosporin and low-dose prednisolone for immunosuppression. Pretransplant levels of intact PTH were significantly greater in group B than in group A (203.5 +/- 193.1 pg/ml versus 81.7 +/- 45.2 pg/ml, P < 0.01). Group B patients had more transplant biopsies (50 versus 7) and a longer hospitalization time (33.4 +/- 10.9 days versus 21.9 +/- 11.9 days, P < 0.01), although serum creatinine on the day of discharge was higher in group B (1.77 +/- 0.51 mg/dl versus 1.5 +/- 0.45 mg/dl, P < 0.05). We conclude that patients with secondary hyperparathyroidism as assessed by measuring circulating levels of intact PTH have an increased incidence of ATN.

Adult↗

PubMed1992

Distribution of individual components of basement membrane in human colon polyps and adenocarcinomas as revealed by monoclonal antibodies.

Double-label immunofluorescence was used to monitor basement-membrane composition and integrity in 22 human colon polyps, 36 adenocarcinomas and 2 metastases. Cryostat sections were stained with polyclonal anti-laminin anti-serum combined with monoclonal antibodies (MAbs) to all major basement-membrane components (laminin, entactin/nidogen, collagen type IV and large heparan sulfate proteoglycan), as well as to keratin 8. In all adenocarcinomas, including mucinous, basement membranes were altered more at the invasive front than in the parenchyma. The degree of this alteration was inversely correlated with the level of tumor differentiation. An uncoordinated loss of basement membrane components (dissociation of markers), previously described by us in rat colon adenocarcinomas, was also found in human tumors. In the great majority of adenocarcinomas a pronounced stromal reaction was seen. It was manifested by the presence of fibrillar deposits of basement-membrane components, mainly of collagen type IV and/or heparan sulfate proteoglycan. This reaction was never observed in polyps and may be derived from myofibroblasts reported to accumulate in colon cancer stroma. The combined use of antibodies to basement-membrane components and to a specific keratin may constitute an adequate immunohistochemical test for the presence of invasion, and may be useful in the histologic analysis of polyps, especially in dubious cases.

Adenocarcinoma↗

PubMed1992

Insensitivity to cyclosporine may explain the HLA-DRw6 recipient effect.

Clinical as well as experimental studies have found an interindividual variability in the immunosuppressive effect of cyclosporine (CsA). In renal transplant patients treated with CsA and prednisolone alone, biopsy-verified rejections were significantly more frequent in DRw6-positive than in DRw6-negative graft recipients. The relative risk for developing a graft rejection independently of the CsA blood levels increased in HLA-DRw6-positive transplant patients. Although no statistical significance of the CsA levels within different DR phenotypes could be assessed, HLA-DR2-positive graft recipients with biopsy-verified rejection episodes had significantly lower CsA levels than DR2-negative patients (P = 0.01). Our results would indicate a very low CsA sensitivity of HLA-DRw6-positive graft recipients and might explain previous results describing an increased incidence of rejection and decreased graft survival rates in these patients.

Antilymphocyte Serum↗

PubMed1992

Cytokine release and dynamics of leukocyte populations after CD3/TCR monoclonal antibody treatment.

Cytokine release and clinical side effects resulting from the use of OKT3 and BMA 031 monoclonal antibodies in the treatment of kidney graft recipients were evaluated and compared. The rise observed in serum levels of interferon gamma. TNF alpha, and IL-8 was similar after administration of either monoclonal antibody. Furthermore, both OKT3 and BMA 031 resulted in rapid disappearance not only of virtually all T cells, but also of substantial percentages of all major leukocyte populations from the circulation; this effect is probably due to cytokine release activating endothelial cells and thereby causing extravasation even of leukocytes not specifically recognized by the administered antibodies. Evidence has thus been obtained that BMA 031 is as potent as OKT3 in inducing unequivocal signs of T cell activation in vivo. However, while OKT3 therapy was accompanied by adverse side effects in our study as in previous ones, we saw no such reactions in any of the patients receiving BMA 031. This contrast might be due to different mechanisms of leukocyte activation possibly inducing other mediators in the case of OKT3, which then, in combination with the cytokines, could generate treatment-associated morbidity.

Antibodies, Monoclonal↗

PubMed1992

[Human papillomavirus infection of the uterine cervix in immune suppressed women after kidney transplantation].

In 23 women, who had immunosuppressive therapy following renal transplantation, routine cytology and colposcopy were performed. Colposcopically directed punch biopsies were taken from the most suspect area. If no pathologic finding was evident during colposcopy a random sample was taken from the transformation zone. Histology revealed condylomatous lesions in seven cases. In two of the lesions, a CIN II was detected. To each woman with a renal allograft and therefore immunosuppressive therapy, two cases were matched for age, parity, and histological finding as a control group. Human papillomavirus (HPV) detection was performed by in-situ hybridisation. HPV infection rate in women with renal allografts was higher in biopsy specimens with condylomatous lesion (86%), as well as in tissue without condylomatous lesions (25%), compared to controls (56% and 9%). The high prevalence of cervical dysplasia and high HPV infection rate in women with immunosuppressive therapy, indicates the need for accurate and regular cytologic and colposcopic examinations in these patients.

Adolescent↗

PubMed1992

[Renal osteodystrophy: the spectrum of the x-ray symptoms in modern forms of kidney transplantation and long-term dialysis therapy].

Plain film radiography and microradioscopy represent standard imaging for diagnosis and grading of renal osteodystrophy. The aim of this retrospective study was to evaluate the effects of modern therapeutic regimens on skeletal abnormalities as diagnosed radiographically. 198 patients were investigated. X-ray findings of 38 patients from 1981-1983 (16-66 years, 40.1 +/- 13.4; 23 male, 15 female) were compared with those of 160 patients from 1991 (20-71 years, 48.4 +/- 12.5; 98 male, 62 female). We found significant differences in respect of the spectrum and the degree of skeletal abnormalities. The prevalence of phalangeal resorptions lowered from 87 to 50%, the prevalence of soft tissue calcification from 68 to 57%. Therefore, renal osteodystrophy is not as extensive as it was ten years ago, but it still continues to be an unavoidable complication of renal insufficiency.

Adolescent↗

PubMed1992

Evidence that sensitivity to cyclosporine is influenced by the HLA-DR phenotype of kidney graft recipients.

Clinical as well as experimental studies have shown a great interindividual variability in the immunosuppressive efficacy of CsA. Evaluating previous in vitro findings of a correlation between sensitivity of alloresponsiveness to CsA and the HLA-DR phenotype CsA levels were compared in kidney transplant recipients with and without rejections during the early posttransplant period and tested for a possible relationship to the HLA-DR phenotype of the recipient. In patients treated with CsA and prednisolone only, rejection frequency was significantly higher in HLA-DRw6 positive than in DRw6 negative graft recipients (77% vs. 53%, P = 0.045). In the DRw6 positive group incidence of rejection was independent of CsA blood levels, whereas in DRw6 negative patients frequency of rejection episodes decreased as a function of increasing CsA levels. Therefore the relative risk in developing graft rejection continuously increased in HLA-DRw6 positive patients. In HLA-DR2 positive graft recipients, however, a decrease in the relative risk could be observed with increasing CsA levels. Within patients with bioptically verified rejection episodes HLA-DR2 positive recipients had significantly lower CsA levels than DR2 negative patients (P = 0.01). In other HLA-DR phenotypes no association with CsA blood levels could be assessed. Also no statistically significant difference could be found in nonrejecting patients. These clinical findings demonstrate an association of sensitivity to immunosuppressive treatment and the HLA-DR phenotype of the graft recipient. Our results would indicate a very low CsA sensitivity of HLA-DRw6 positive graft recipients and thus might offer an explanation for previous findings about an increase in the incidence of rejection reported on those patients.

Adult↗

PubMed1992

Treatment of hyperlipidemic kidney graft recipients with lovastatin: effect on LDL-cholesterol and lipoprotein (a).

An increased incidence of hyperlipidemia places kidney graft recipients at increased risk for cardiovascular disease and may contribute to a decline in graft function. A study was undertaken to evaluate the safety and efficacy of lovastatin in these patients. Twelve kidney graft recipients with stable graft function and a cholesterol (chol) level over 250 mg/dl (6.46 mmol/l) were included. The lipid-lowering treatment consisted of 20 mg lovastatin daily, and all patients received immunosuppression with ciclosporin (CS) and prednisolone. Total chol decreased by 27% (300 +/- 56 to 219 +/- 28 mg/dl; 7.76 +/- 1.45 to 5.66 +/- 0.72 mmol/l; p < 0.01), LDL-chol by 35% (220 +/- 38 to 143 +/- 17 mg/dl; 5.69 +/- 0.98 to 3.70 +/- 0.44 mmol/l; p < 0.01) and triglycerides by 33% (207 +/- 127 to 138 +/- 56 mg/dl; 2.36 +/- 1.44 to 1.57 +/- 0.64 mmol/l; p < 0.05). HDL-chol increased by 10% (57 +/- 11 to 63 +/- 13 mg/dl; 1.47 +/- 0.28 to 1.63 +/- 0.34 mmol/l; NS). The ratio of total chol/HDL-chol, a generally accepted risk predictor of atherosclerosis, fell from 5.4 +/- 1.3 to 3.3 +/- 1.2, p < 0.01. Lipoprotein (a) [lp(a)], an independent risk predictor for atherosclerosis, was also evaluated at baseline and after 6 months of lovastatin treatment and showed a decrease of 39% (32.9 +/- 27.6 to 19.9 +/- 22.9 mg/dl; 0.85 +/- 0.71 to 0.51 +/- 0.59 mmol/l; p < 0.05). No adverse side effects were seen at this dosage, and hepatic and renal parameters remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992