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Biomedical subjects

G Kovacs

Publications and source records attributed to G Kovacs.

At least 19 recordsLinked to original sources
PubMed2000

Allelic changes at multiple regions of chromosome 5 are associated with progression of urinary bladder cancer.

This study has analysed 65 urothelial carcinomas for allelic imbalance at 22 loci of chromosome 5 and has determined three regions of interest. A commonly duplicated region was mapped to chromosome 5p between loci D5S1473 and D5S819, one region of deletion to chromosome 5q22-23 between loci D5S2055 and D5S659, and another to chromosome 5q33-34 between loci D5S1456 and D5S1465. An allelic imbalance was detected in 54% of the cases. Only 10% of grade 1 tumours showed allelic changes at chromosome 5, whereas 60% and 63% of grade 2 and grade 3 cancers, respectively, had alterations of chromosome 5. The frequency of chromosome 5 changes increased from 24% in pTa tumours up to 72% in pT3-4 tumours. Of particular interest, ten out of 12 urothelial carcinomas showing metastatic growth in regional lymph nodes at the time of cystectomy had alterations at chromosome 5. No specific region, but genetic changes in general were associated with the grading and staging of bladder cancers.

Alleles↗
PubMed2000

Matrix metalloproteinase-1 and -3 and mast cells are present in the endometrium of women using progestin-only contraceptives.

Progestin-only contraceptives are associated with menstrual bleeding disturbances; a major reason why these agents are discontinued. The pathogenesis of such abnormal uterine bleeding associated with progestin-only contraceptives remains ill-defined. Matrix metalloproteinases (MMP)s and mast cells (MC)s are postulated to be involved in endometrial breakdown observed in normal menstruation. In this study comparisons were made of the immunolocalization of MMP-1 and -3 and MC in endometrium from women using Norplant or depot medroxyprogesterone acetate (DMPA) with normal controls. Positive MMP immunostaining was observed focally in stromal cells and adjacent extracellular matrix. Quantitative assessment revealed significantly higher MMP-1 immunostaining associated with the use of Norplant compared with DMPA or menstrual phase controls. Endometrial MMP-1 immunostaining in DMPA users was similar to that in menstrual controls. Positive MMP-3 immunolocalization was observed in a minority of endometrial samples. Activated MC, shown by the presence of extracellular MC tryptase, predominated in the endometrium of Norplant and DMPA users as also observed in menstrual phase controls. There was no correlation between MMP immunostaining, number of MC and number of bleeding days reported. These results indicate that in women using progestin-only contraceptives, endometrial MMP-1, -3 and MC demonstrate similarities to menstrual phase controls but also variation with different progestins.

Adult↗
PubMed1999

Microsatellite analysis reveals deletion of a large region at chromosome 8p in conventional renal cell carcinoma.

Loss of heterozygosity (LOH) at chromosome 8p is associated with the progression of conventional (non-papillary) renal cell carcinomas (RCC). To determine the tumor suppressor gene locus, we carried out a deletion mapping of chromosome 8p at 10 microsatellite loci in 96 RCCs. LOH occurred in 32% of the tumors. The smallest overlapping region of deletion at chromosome 8p11.2-p23.1 corresponds to approximately 34-cM genetic distance. No small interstitial deletion was seen.

Carcinoma, Renal Cell↗
PubMed1999

[Molecular genetics and diagnosis of renal cell tumors].

Renal cell tumors display notoriously an intra- and intertumoral morphological heterogeneity making a reproducible cytomorphological diagnosis impossible. To overcome the cytological heterogeneity, the "Heidelberg Classification of Renal Cell Tumours" is soundly based on the genetic lesions that underlie the formation of distinct tumors. Allelic loss of chromosome 3 p and mutation of the VHL gene specify conventional renal cell carcinoma. In addition duplication of chromosome 5 q as well as allelic losses of prognostic value at chromosomes 6 q, 8 p, 9 p and 14 q characterize conventional renal cell carcinomas. Papillary renal cell tumors, which display an adenoma-carcinoma sequence, are marked by trisomies of chromosomes 3 q, 7, 8 p, 12 q, 16 q, 17 q und 20 as well as loss of the Y chromosome in males. Chromophobe renal cell carcinoma shows a low chromosome number due to monosomy of chromosomes 1, 2, 6, 10, 13, 17, and 21. Benign tumors, such as renal oncocytoma and metanephric adenoma, can also be diagnosed by genetic means. The distinct types of tumors have different biological behaviour and therefore, an accurate classification is considered clinically important. We worked out a quick and reproducible fluorescent microsatellite assay for detecting allelic changes. This technique is useful for postoperative and retrospective diagnosis as well as for preoperative analysis of fine needle aspiration specimens.

Carcinoma, Renal Cell↗
PubMed1999

BCL10 is rarely mutated in human prostate carcinoma, small-cell lung cancer, head and neck tumours, renal carcinoma and sarcomas. MPT Collaborators, St George's Hospital Collaborators.

We have used single-strand conformation polymorphism (SSCP) analysis to screen for mutations in the BCL10 gene in 81 primary prostate carcinomas, 20 squamous cell cancers of the head and neck, 15 small-cell lung cancer cell lines, 24 renal carcinoma cell lines and 13 sarcoma cell lines. We failed to find evidence of somatically acquired mutations of the BCL10 gene suggesting that BCL10 does not play a major role in the development of these malignancies.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Laparoscopic replacement of urinary tract segments using biodegradable materials in a large-animal model.

OBJECTIVE: We elected to evaluate laparoscopic segmental bladder and ureteral replacement with free biodegradable graft materials in a large-animal model. MATERIALS AND METHODS: In 18 Yucatan minipigs, a 1.5- to 2.8-cm segment of the upper ureter was excised. In 15 study animals, the ureter was laparoscopically replaced: by a stinted (6F double-J stent) tube graft made of acellular matrix (AMX) prepared from minipig ureters (MUMX) in 6 animals, acellular matrix prepared from domestic pig ureters (DUMX) in 3, and small-intestinal submucosa (SIS) in 6. In 3 control animals, the ureteral gap was bridged only by an indwelling stent. The stent was removed at 6 weeks, and retrograde ureteropyelography was performed preoperatively and at 8 and 12 weeks postoperatively, when animals were sacrificed. In 18 Yucatan minipigs, 3 x 3-cm bladder dome segments were laparoscopically replaced: by acellular matrix prepared from minipig small bowel (MBMX) in 6 animals, and SIS in 6 animals. The bladder was closed primarily in 6 control animals. Bladder capacity was assessed preoperatively and at 6 and at 12 weeks, when the animals were sacrificed. RESULTS: The average operating time for ureteral replacement was 187 (range 105-360) minutes. At 12 weeks, all animals had complete obstruction at the level of the replacement, with fibrosis +/- bone formation at the level of the stricture. For the bladder replacement groups, the average operating time was 147 (range 85-200) minutes. At 12 weeks, the bladder capacity was 60% of the preoperative capacity in the control group, 118% in the MBMX group, and 142% in the SIS group. Histologic examination showed regeneration of urothelium and some muscle with both MBMX and SIS. CONCLUSIONS: We were able to develop a reliable laparoscopic technique for both segmental ureteral and partial bladder replacement in a porcine model. With AMX and SIS replacement, regeneration of urothelium occurred in both ureter and bladder. However, functional replacement was successful only in the bladder.

Absorbable Implants↗
PubMed1999

Cumulative pregnancy and live birth rates in women with antiphospholipid antibodies undergoing assisted reproduction.

The aims of this study were to investigate the influence of antiphospholipid antibodies (APA) on cumulative pregnancy and live-birth rates in patients undergoing assisted reproductive treatment. Serum samples from 173 patients were collected prior to initiation treatment cycle and tested by enzyme-linked immunosorbent assay (ELISA) for the presence of immunoglobulin (Ig)G, IgM and IgA against cardiolipin, phosphoserine, phosphoethanolamine, phosphoinositol, phosphatidic acid, and phosphoglycerol. Fifty-six samples from patients who had at least two failed cycles by assisted reproductive treatment were also tested by a bioassay for the presence of lupus anticoagulants. Both cumulative pregnancy and live birth rates were not affected by the presence of any specific or any number of seropositive APA. There was no association between multiple assisted reproductive treatment failures and APA seropositivity. Neither the serum concentration of any of the 18 APA, nor the number of positive APA was correlated with the number of assisted reproductive treatment failed cycles or affected the probability of pregnancy. No patient was found to be positive for lupus anticoagulants. Using life table analyses, which has been recognized as the most appropriate method available to analyse assisted reproductive treatment results, we conclude that there is no relationship between circulating APA and assisted reproductive treatment outcome. APA do not affect the early process of implantation or maintenance of pregnancy among assisted reproductive treatment patients.

Abortion, Spontaneous↗
PubMed1999

Perinatal and obstetric outcomes of donor insemination using cryopreserved semen in Victoria, Australia.

This study compared the perinatal and obstetric outcomes of 1552 donor insemination pregnancies in Victoria, Australia, with a control group of 7717 normally conceived pregnancies from the general population. Data on the outcomes of pregnancies of at least 20 weeks gestation, for both groups, were obtained from the same population-based birth registry. The study showed that there were no significant differences between the donor insemination and control groups in the incidence of preterm birth, low birthweight, multiple birth, perinatal death and birth defects, or in the sex ratio. Pregnancies conceived by donor insemination were significantly more likely than controls to have an induced labour (OR = 1.6, 95% CI 1. 4-1.8), a forceps delivery (OR = 1.5, 95% CI 1.3-1.8) and/or a Caesarean section (OR = 1.6, 95% CI 1.4-1.9) and to develop pre-eclampsia (OR = 1.4, 95% CI 1.2-1.8) after adjusting for maternal age, multiple birth, parity and presentation. Reasons for the higher rate of induced and operative deliveries are not clear. Overall, the study's findings are reassuring for couples considering infertility treatment with donor insemination. The study illustrates the importance of complete follow-up in studies of pregnancy outcomes after assisted conception and the use of appropriate population-based control groups with comparable ascertainment of outcomes.

Case-Control Studies↗
PubMed1999

Oncocytoid renal cell carcinoma after neuroblastoma: a report of four cases of a distinct clinicopathologic entity.

Four children who developed oncocytoid renal cell carcinoma (RCC) after neuroblastoma are reported. One patient had multiple, bilateral RCCs. The mean age at time of diagnosis of RCC was 8.8 years (range, 5-13 years). The mean interval between neuroblastoma and RCC was 7.15 years (range, 3.1-11.5 years). The histologic findings of these RCCs did not fit within the spectrum of known renal epithelial neoplasms. Most of the neoplastic cells in all cases had eosinophilic, oncocytoid cytoplasm and were arranged in solid and papillary growth patterns. A subset of cells with reticular cytoplasm was also present. Immunohistochemical studies demonstrated keratins 8 and 18 in all neoplasms and keratin 20 in two cases. DNA ploidy analysis revealed that two of three neoplasms assessed were aneuploid. Cytogenetic studies revealed 45, XX, add or dup (7)(q32q36) in one neoplasm, and 83-89, XXXX, -1 ,-3, del (3)(q11.1q2?1), der(4)t(4;?22) (q32;q11.2), -14, -22 in a second tumor. Microsatellite polymerase chain reaction analysis detected no abnormalities in one neoplasm and allelic imbalance of chromosomes 2p31-32.2, 8p22, 9p22-24, 13q22, 20q13, and 22q11 in a second tumor. In case 4, two different RCCs excised 6 months apart were analyzed. The initial neoplasm showed allelic imbalance of chromosomes 2q31-32.2, 5q22, 5q31, 10p13-14, 13q22, 14q31, and 20q13. The subsequent neoplasm showed allelic imbalance of chromosomes 3p21.3, 14q31, and 20q13. The common presence of 14q31 and 20q13 abnormalities suggests that these two neoplasms were genetically related. In aggregate, these findings are distinctive, are not found in known types of RCC, and support the morphologic impression that oncocytoid RCC after neuroblastoma is a distinct clinicopathologic entity.

Adenoma, Oxyphilic↗
PubMed1999

Evaluating procedural skills competence: inter-rater reliability of expert and non-expert observers.

PURPOSE: To examine the inter-rater reliability of expert and non-expert observers when they used objective structured checklists to evaluate candidates' performances on three simulated medical procedures. METHOD: Simulations and structured checklists were developed for three medical procedures: endotracheal intubation, application of a forearm cast, and suturing a simple skin laceration. Groups comprised of two expert and two non-expert observers scored the performances of 101 procedures by 38 medical trainees and practitioners of varying skill levels. Inter-rater reliability was assessed using Pearson correlation coefficients. RESULTS: Inter-rater reliability was good for expert/expert, expert/non-expert, and non-expert/non-expert pairings in all three skills simulations. CONCLUSION: Both expert and non-expert observers demonstrated good inter-rater reliability when using structured checklists to assess procedural skills. Further study is required to determine whether this conclusion may be extrapolated to other study groups or procedures.

Clinical Competence↗
PubMed1999

Clinical decision making: an emergency medicine perspective.

Clinical decision making (CDM) describes a form of qualitative inquiry that examines the thought processes involved in making medical decisions. A significant body of literature exists on the orderly "hypothetico-deductive" model of clinical decision making. However, very little has been written on how CDM differs in the acute setting. This paper reviews the common methods of CDM and their relevance to emergency medicine (EM). The concept of diagnostic uncertainty and the utility of the diagnosis of unknown etiology in the disposition phase of the emergency patient visit are discussed. Finally, a unique EM perspective on clinical decision-making errors is presented.

Adult↗
PubMed1999

Duplications of DNA sequences between loci D20S478 and D20S206 at 20q11.2 and between loci D20S902 and D20S480 at 20q13.2 mark new tumor genes in papillary renal cell carcinoma.

Trisomy of chromosome 20 is associated with the progression of papillary renal cell carcinomas (RCC). To define the gene loci, we have analyzed 40 tumors by applying 18 polymorphic microsatellite markers. An allelic imbalance at all informative loci was seen in 14 cases. Partial duplications of chromosome 20 in 14 tumors delineated four nonsyntenic regions: region A at chromosome 20p12-p13, regions B and C at chromosome 20q11.2, and region D at chromosome 20q13.2. Region B was bracketed by loci D20S206 and D20S478, both mapped to 54 cM and both excluded. The smallest overlapping duplication at region D was scaled down to the region between loci D20S480 and D29S902 marking approximately 100-kb genomic sequences. Allelic duplication in papillary RCC was confirmed by fluorescence in situ hybridisation analysis by using BAC clones 441o14 and 354n14 positive for the flanking loci at region B. Altogether 70% of papillary RCC showed genetic changes at least at one of the four regions, but coalteration of two or more regions was seen in most cases.

Alleles↗
PubMed1999

Renal cell carcinoma of end-stage renal disease: an analysis of chromosome 3, 7, and 17 abnormalities by microsatellite amplification.

End-stage renal disease (ESRD) patients have an increased risk of carcinoma of the kidney, thought to result from development of a disproportionately high number of papillary renal cell carcinomas. This study was undertaken to discover whether these renal carcinomas have a deletion of the short arm of chromosome 3, which characterizes conventional (clear cell) carcinomas, or trisomies of chromosomes 7 and 17, which characterize the majority of sporadic papillary renal cell neoplasms. Archival specimens from 17 end-stage kidneys containing renal cell carcinomas were collected from 16 ESRD patients. DNA was extracted from paraffin blocks of tumor and nontumorous tissue. Microsatellites on the long and short arm of chromosomes 3, 7, and 17 were amplified in paired "normal" tumor samples. Heterozygous loci were analyzed for loss of heterozygosity, indicating a deletion, and for allele ratio differences, indicating a duplication. Successful microsatellite studies were obtained on 18 tumors (2 conventional carcinomas, 14 papillary carcinomas, 2 unclassified [solid, eosinophilic cell] carcinomas). Of the papillary carcinomas, none had a 3p deletion, five had trisomies of both chromosomes 7 and 17, six had no changes in chromosomes 7 and 17, and three had either trisomy 7 or trisomy 17 but not both. A 3p deletion was present in one of two conventional carcinomas. No chromosome 3, 7, or 17 changes were identified in the unclassified carcinomas. The genetic abnormalities in 6 of 18 ESRD tumors seemed to be the same as those found in sporadic papillary or conventional renal cell carcinomas. Nine of 14 papillary carcinomas did not show allelic duplications of chromosomes 7 and 17. This is uncharacteristic of the findings reported for most of the sporadic forms of the neoplasm and suggests that the genetic mechanism underlying the development of many papillary renal cell carcinomas in ESRD patients might be different than that of the general population.

Adolescent↗
PubMed1999

Mapping the papillary renal cell carcinoma gene between loci D17S787 and D17S1799 on chromosome 17q21.32.

Trisomy of chromosome 17 is associated with the development of papillary renal cell tumors (RCT). We have analyzed 37 papillary RCT by applying 25 polymorphic microsatellite markers and found an overlapping duplication including loci D17S1795 and D17S1306 on chromosome 17q21. This region was then analyzed in additional 118 sporadic and hereditary papillary RCT. Overlapping partial duplications at the chromosome 17q21.32 region localized the papillary RCT gene to an approximately 300 kb genomic sequences flanked by loci D17S787 and D17S1799. Altogether, 92% of the 100 papillary RCT showed allelic duplication at this region. We did not find mutation in coding sequences or altered expression of the hepatic leukemia factor gene, which is mapped the smallest duplicated interval, in any type of RCT. Therefore, another gene within the 300 kb region might be responsible for the development of papillary RCT.

Base Sequence↗
PubMed1998

Duplication and overexpression of the mutant allele of the MET proto-oncogene in multiple hereditary papillary renal cell tumours.

Previous karyotyping showed a combined trisomy of chromosome 7 and 17 in sporadic and hereditary papillary renal cell tumours (RCT). A recent molecular analysis revealed a mutation in the MET tyrosine kinase (chromosome 7q31) in the germline of four out of seven families with hereditary papillary RCT (HPRCT). We have analysed germline cells as well as multiple tumours obtained from HPRCT families and sporadic cases for alteration of the MET tyrosine kinase and for allelic duplication at chromosome 7 and 17. We have detected a germ line mutation in the MET tyrosine kinase in one of the two families with HPRCTs and also found the same mutation in the germ line of one patient with clinically recognized multiple, bilateral papillary RCTs but without family history. The mutant MET allele is consequently duplicated and overexpressed in tumour cells indicating that duplication of the mutant MET allele is necessary before cells enter the tumorigenic pathway. The lack of germline mutation in two members of another HPRT family and duplication of the same parental allele of chromosome 7 in multiple tumours suggests that a germ line event other than mutation of MET tyrosine kinase is involved in the development of these tumours. Duplication of different alleles of chromosome 7 in sporadic and of chromosome 17 in both types of tumours excludes a germline mutation at these chromosomal sites.

Adenoma↗