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Tomas Gudbjartsson

Publications and source records attributed to Tomas Gudbjartsson.

At least 19 recordsLinked to original sources
PubMed2006

A genome-wide study of allelic imbalance in human testicular germ cell tumors using microsatellite markers.

Testicular germ cell tumors (TGCT) arise by multistep carcinogenesis pathways involving selective losses and gains of chromosome material. To locate cancer genes underlying this selection, we performed a genome-wide study of allelic imbalance (AI) in 32 tumors, using 710 microsatellite markers. The highest prevalence of AI was found at 12p, in line with previous studies finding consistent gain of the region in TGCTs. High frequency of AI was also observed at chromosome arms 4p, 9q, 10p, 11q, 11p, 13q, 16q, 18p, and 22q. Within 39 candidate regions identified by mapping of smallest regions of overlap (SROs), the highest frequency of AI was at 12p11.21 approximately p11.22 (62%), 12p12.1 approximately p13.1 (53%), 12p13.1 approximately p13.2 (53%), 11q14.1 approximately q14.2 (53%), 11p13 approximately p14.3 (47%), 9q21.13 approximately q21.32 (47%), and 4p15.1 approximately p15.2 (44%). Two genes known to be involved in cancer reside in these regions, ETV6 at 12p13.2 (TEL oncogene) and WT1 at 11p13. We also found a significant association (P = 0.02) between AI at 10q21.1 approximately q22.2 and higher clinical stage. This study contributes to the ongoing search for genes involved in transformation of germ cells and provides a useful reference point to previous studies using cytogenetic techniques to map chromosome changes in TGCTs.

Adolescent↗
PubMed2006

Testicular germ cell tumours in Iceland: a nationwide clinicopathological study.

The purpose of this study was to examine the pathology of all germ cell tumours of the testis diagnosed in Iceland 1955-2002. A total of 214 patients were included in the study. The current age-standardized incidence was found to be 6.1 per 100,000 and had increased almost fourfold during the study period. Seminoma was diagnosed in 55% of cases. Non-seminomas were diagnosed in 45%, and these were further classified as mixed germ cell tumours (33%), embryonal carcinoma (8%), teratoma (3%), and yolk sac tumour (n=1). The mean age at diagnosis was significantly higher for the seminomas than the non-seminomas (38 years versus 29 years) (p<0.001) and the non-seminomas were diagnosed at a significantly higher stage than the seminomas (p<0.001). Thus, in seminoma patients the tumour was localized to the testis (stage I) in 81% of cases, in 17% of patients the tumour had spread to the lymph nodes (stage II or III), and only 2% had extranodal metastasis at diagnosis (stage IV). In contrast, in the non-seminoma patients, the tumours were found to be stage I in 56%, stage II or III in 24%, and stage IV in 20% of cases. No significant difference in staging was found between non-seminoma subtypes. Identification of necrosis or vascular invasion was significantly associated with metastatic disease at diagnosis (p=0.002). During the study period a significant increase in stage I tumours was found as well as a decrease in the size of the tumours.

Adult↗
PubMed2006

Long-term outcome of the MitroFlow pericardial bioprosthesis in the elderly after aortic valve replacement.

BACKGROUND AND AIM OF THE STUDY: The current trend in Europe and the USA demonstrates an increased number of tissue valves being implanted. However, studies presenting long-term follow up of the Mitroflow pericardial bioprosthesis are relatively scarce. In the present study, the long-term outcome of the Mitroflow in the aortic position was analyzed in a geriatric population using actuarial statistics; risk factors for early and late mortality were also evaluated. METHODS: Between 1990 and 1993, 152 elderly (mean age 79.5 +/- 3.1 years; range: 75-91 years) patients each received a Mitroflow bioprosthesis implanted in the aortic position. A follow up was conducted in January 2003 and was 100% complete. Concomitant coronary artery bypass grafting was performed in 74 patients (49%). Valve-related outcomes were evaluated using actuarial statistics. Overall survival was compared to that in an age- and gender-matched population. A multivariate analysis of risk factors for mortality was also performed. RESULTS: Actuarial freedom from structural valve deterioration was 99% and 82% at five and 10 years, respectively. Actuarial freedom from stroke, bleeding, prosthetic valve endocarditis and valve explant at 10 years were 80 +/- 5%, 94 +/- 3%, 93 +/- 3% and 89 +/- 4%, respectively. Risk factors for mortality during follow up were male gender, small valves (< or = 21 mm), preoperative NYHA class III/IV, greater age, and long intraoperative perfusion time. CONCLUSION: The Mitroflow pericardial bioprosthesis demonstrated a good long-term performance after aortic valve replacement, suggesting it to be a feasible option in elderly patients.

Aged↗
PubMed2005

Histological subtyping and nuclear grading of renal cell carcinoma and their implications for survival: a retrospective nation-wide study of 629 patients.

OBJECTS: The aim of this study was to evaluate the prognostic significance of the current WHO histological subtyping and Fuhrman nuclear grading on the survival of patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: A retrospective population-based study was carried out on all patients with a histopathologically confirmed diagnosis of RCC in Iceland between 1971 and 2000. Fuhrman grade, TNM stage, and survival were evaluated and multivariate analysis applied in order to determine prognostic factors. RESULTS: Out of 629 patients (387 males, 242 females, mean age 64 years), 558 (88.7%) had clear cell, 53 (8.4%) papillary, and 13 (2.1%) chromophobe RCC. Patient demographics were comparable for the two major subtypes, but chromophobe RCCs were larger in size and were diagnosed at a younger age. Clear cell RCCs were more often of higher grades (G3+G4, 48.4%) and at advanced TNM stages (III+IV, 59.3%) than papillary RCCs (22.6% and 34% respectively, p<0.001). Linear regression analysis showed a strong correlation between grade, tumor size, and stage (p<0.001). Chromophobe RCCs had a better survival in univariate analysis than both papillary and clear cell RCCs (84.6% vs. 66.5% and 54.9% 5-year disease specific survival, p<0.001). However, in the multivariate analysis, only the patient's age, calendar year of diagnosis, TNM stage, and nuclear grade were independent prognostic factors of survival. CONCLUSION: In this complete nation-wide series nuclear grading is important in predicting survival of patients with RCC. It is strongly related to both tumor size and stage, with stage being by far the strongest prognostic factor. Different histological subtypes confer different survival. However, in spite of the distinctive cytogenetic and molecular characteristics of the subtypes, the survival difference is to a large extent due to differences in grade and particularly stage.

Adenocarcinoma, Clear Cell↗
PubMed2005

Effect of incidental detection for survival of patients with renal cell carcinoma: results of population-based study of 701 patients.

OBJECTIVES: To conduct a population-based study to evaluate the effect of incidental detection of renal cell carcinoma (RCC) on survival. Incidental detection of RCC has increased significantly in recent years because of widespread use of abdominal imaging. The patients with incidentally diagnosed RCC have better survival; however, because of possible "lead time" bias and stage migration, the real implications of incidental detection on survival have been a matter of debate. METHODS: All living patients diagnosed with RCC in Iceland between 1971 and 2000 were included (n = 701). The histologic findings were verified, the stage (extent) of the disease was determined, and the incidence, mortality, and survival were evaluated. RESULTS: The strongest predictors of mortality were stage and nuclear grade. After correcting for these factors in the multivariate analysis, incidental diagnosis, histologic subtype, and gender lost their significance as independent prognostic factors of death. However, the incidentally diagnosed tumors were 2.3 cm smaller on average and at a lower stage and grade than symptomatic tumors, with significantly better patient survival than those with symptomatic tumors on univariate analysis (76% versus 44% 5-year disease-specific survival). An increased incidence of RCC was only seen in men, but incidental detection increased threefold during the study period in both sexes, with significant improvement in survival for the whole group as a result. CONCLUSIONS: The increased frequency of incidental detection has improved the survival of patients with RCC in Iceland. Incidental detection was not an independent prognostic factor of death, indicating that these tumors are of a similar biologic nature as symptomatic RCCs, only diagnosed earlier.

Aged↗
PubMed2005

Renal oncocytoma: a clinicopathological analysis of 45 consecutive cases.

OBJECTIVE: To evaluate the clinical behaviour and pathology of renal oncocytoma in a well-defined population over a 30-year period. PATIENTS AND METHODS: In a retrospective population-based study we assessed relevant clinical and pathological factors in 45 patients (31 men and 14 women) diagnosed with renal oncocytoma in Iceland between 1971 and 2000. Clinical presentation, pathology, survival and causes of death were evaluated. RESULTS: The age-standardized incidence was 0.3 per 100,000 per year for both men and women, the incidence of oncocytomas being 5.5% of renal cell carcinomas (RCCs) diagnosed during the same period in Iceland. Fourteen patients were diagnosed at autopsy for an unrelated disease. Of 31 living patients (mean age 70.5 years), seven were diagnosed incidentally (23%), and the others had presented with haematuria (32%), abdominal pain (29%), and weight loss (10%). All the patients had a radical nephrectomy, except for one with bilateral oncocytoma who had a partial nephrectomy. The mean (range) tumour size was 5.7 (0.9-12) cm. Eighteen patients (58%) were diagnosed at Tumour-Node-Metastasis stage I, 10 at stage II (32%) and three at stage III (10%), all of those at stage III having renal capsular penetration or tumour invasion into perirenal fat tissue (T3aN0M0). No patients were diagnosed with lymph node or distant metastasis. Two cases of coexisting RCC were detected. After a median follow-up of 8.3 years there were no recurrences or deaths from oncocytoma (100% disease-specific survival). The overall 5-year survival was 63%, with most patients dying from cardiovascular diseases or nonrenal cancers. CONCLUSIONS: In most cases renal oncocytoma behaves like a benign tumour; the long-term prognosis is excellent. Thus, in the present patients, radical nephrectomy could be regarded as an over-treatment and nephron-sparing surgery as more appropriate, especially in patients with small tumours. However, both coexisting RCC and perirenal fat invasion, a hallmark of malignant behaviour, might indicate that more radical surgery is warranted in some of these patients.

Adenoma, Oxyphilic↗
PubMed2004

ADP receptor P2Y12 is expressed in vascular smooth muscle cells and stimulates contraction in human blood vessels.

OBJECTIVE: ADP plays an important role in platelet aggregation by activating P2Y12 receptors. We assessed the hypothesis that P2Y12 receptors are expressed in vascular smooth muscle cells (VSMC). METHODS AND RESULTS: P2Y12 receptor mRNA was found to have a high expression among the P2 receptors in human VSMC, significantly higher than the other 2 ADP receptors (P2Y1 and P2Y13, real-time polymerase chain reaction). Western blots gave a band of 50 kD, similar to that in platelets. To unmask a P2Y12 receptor-mediated vasoconstriction by simulating the in vivo situation, vessels were precontracted to a submaximal level. 2-MeSADP stimulated contractions in vessel segments from internal mammary artery (IM), IM branches and small veins (Emax=15+/-6% of 60 mmol/L K+ contraction, pEC50=5.6+/-0.6, Emax=21+/-1%, pEC50=6.8+/-0.1, and Emax=48+/-9%, pEC50=6.6+/-0.4). The selective P2Y12 antagonist AR-C67085 blocked 2-MeSADP contractions. The contraction was not reduced in patients using clopidogrel, a drug inhibiting ADP-induced platelet aggregation by blocking the P2Y12 receptor. This may be explained by the high instability of the active clopidogrel metabolite that never reaches the systemic circulation. CONCLUSIONS: ADP acting on P2Y12 receptors not only is important for platelet activation but also stimulates vasoconstriction. Stable drugs with antagonistic effects on P2Y12 receptors, affecting both platelets and VSMC, could be of double therapeutic benefit in their prevention of both thrombosis and vasospasm.

Adenosine Diphosphate↗
PubMed2003

Hypothermic circulatory arrest for the surgical treatment of complicated adult coarctation of the aorta.

OBJECTIVES: This study was designed to evaluate the surgical treatment of recurrent coarctation by a new technique. BACKGROUND: Recurrent coarctation either from aneurysm or recurrent constriction is a difficult problem in the adult because of the possible interruption of important collateral circulation. METHODS: We reviewed four patients who underwent recurrent coarctation surgery with the use of deep hypothermic circulatory arrest (HCA). RESULTS: All four patients survived. Deep HCA facilitated precise surgical resection and there was no postoperative paraplegia, stroke, or myocardial infarction. CONCLUSIONS: Deep HCA and resection and grafting of the coarctation is indicated for complicated adult coarctations, particularly when the collateral circulation is in doubt.

Adult↗
PubMed2003

Contractions in human coronary bypass vessels stimulated by extracellular nucleotides.

BACKGROUND: The present study was designed to evaluate the relative contribution of different contractile P2 receptors in human saphenous vein compared with internal mammary artery obtained during coronary artery surgery. METHODS: The isometric tension in endothelium-denuded isolated vessel segments was recorded in vitro. The P2 receptor mRNA expression was quantified by real-time polymerase chain reaction. RESULTS: The P2X(1) receptor agonist, alphabeta-MeATP (alphabeta-methylene-adenosine triphosphate), was the most potent vasoconstrictor, with more efficacious contractions in the saphenous vein than in the internal mammary artery. The selective P2Y(6) receptor agonist, UDPbetaS (uridine 5'-O-thiodiphosphate), stimulated more potent contractions in saphenous vein compared with internal mammary artery. Furthermore, UDPbetaS induced long-lasting contractions for more than 2 hours, explained by the low desensitization rate of the P2Y(6) receptor. The ATP-induced vasoconstriction could not be abolished by desensitization of P2X(1) receptors with alphabeta-MeATP, or P2Y(2/4) receptors with UTPgammaS (uridine 5'-O-3-thiotriphosphate), indicating the presence of yet another contractile ATP receptor. Based on quantification with real-time polymerase chain reaction, the P2Y(11) receptor could be responsible for this ATP contraction. CONCLUSIONS: The P2X(1) and P2Y(6) receptors elicit more prominent contractions in the saphenous vein as compared with the internal mammary artery. These results may present one explanation for the differences in the two conduits. It is possible that selective antagonists of P2X(1) and P2Y(6) receptors could be used to prevent vasospasm and restenosis in the saphenous vein during and after revascularization surgery.

Aged↗
PubMed2003

Biological vs. mechanical aortic root replacement.

OBJECTIVES: Although age and co-existing coronary disease are major determining factors when deciding valve choice (mechanical vs. biological) in simple aortic valve replacement, no studies have documented selection criterion for biological (BIO) vs. mechanical (MECH) aortic root prosthesis. METHODS: Two hundred and twenty-one consecutive patients underwent elective aortic root replacement with either BIO (homograft, n=111, Freestyle, n=25) or MECH composite grafts (n=85). Median age in BIO was 53 years and in MECH 54 years (P=NS). Groups were similar in gender, NYHA class and ejection fraction (BIO, EF=59% vs. MECH, EF=55%), but the need for concomitant coronary artery bypass grafting (CABG) did differ between groups (MECH=35% vs. BIO=17%, P=0.003). Mean follow-up was 42+/-28 months for mortality and 39+/-28 months for morbidity. RESULTS: Full root replacement was performed in 213 patients (96%) and hemi-root in eight (4%). The most common underlying etiologies were annulo-aortic ectasia (n=82, 37%), calcified-degenerative (n=73, 33%) and bicuspid/congenital aortic valve disease (n=39, 18%). Operative mortality was 1.5% for BIO and 2.4% for MECH (P=0.5). By univariate analysis there was a trend towards greater 5-year survival in BIO (92.4% vs. 88.2%, P=0.068). By multivariate analysis, increasing age (HR=2.4, P=0.003), previous valve replacement (HR=4.7, P=0.024), concomitant CABG (HR=3.7, P=0.032), and perioperative stroke (HR=9.9, P=0.0005) were all independent predictors of late death. The 5-year freedom from valve-related complications was similar in both groups (BIO=93% vs. MECH=86%, P=0.5). CONCLUSIONS: Elective aortic root replacement is an exceedingly safe operation. At mean follow-up of 4 years, there is no meaningful difference in early or mid term valve-related results between BIO and MECH aortic root replacement. Continued evaluation for late valve-related complications in this cohort will be necessary to determine the advantages, if any, of one prosthesis over the other.

Adult↗
PubMed2003

A population-based analysis of increased incidence and improved survival of testicular cancer patients in Iceland.

OBJECTIVE: For unknown reasons the incidence of testicular cancer has risen dramatically in many industrialized countries. At the same time, the prognosis for these patients has improved even more significantly. This has mostly been explained by the introduction of an effective cisplatin-based multidrug chemotherapy regimen for patients with metastatic or recurrent disease, but better diagnostic tools and surveillance may also play a role. In this population-based study the clinical behaviour of testicular cancer cases (n = 198) in Iceland between 1955 and 1999 was investigated, with a special emphasis on changes in incidence, staging and survival. MATERIAL AND METHODS: The tumours were staged and pathologically classified and the crude probability of survival evaluated. The incidence was calculated for the whole period and further clinical evaluation was done for all the patients diagnosed after 1970 (n = 172). RESULTS: Of 198 patients, 111 (58%) were diagnosed with seminomas and 82 with non-seminomas (42%). Age-adjusted incidence increased from 2.2 per 100,000 men between 1955 and 1959 to 5.3 per 100,000 men between 1995 and 1999 (p < 0.01). More patients were diagnosed with localized disease (stage I) in the second compared to the first time period of the study: 71% vs 52% respectively (p < 0.01). After the introduction of cisplatin-based multidrug chemotherapy in Iceland in 1978, 5-year survival has increased from 67% in the period 1955-77 to 96% in the period 1978-99. CONCLUSIONS: During the study period the incidence of testicular cancer in Iceland increased almost threefold. After multidrug chemotherapy was introduced in 1978 only two patients have died from the disease. Since 1987, patients with stage I disease have been followed with surveillance after orchiectomy, without any deaths. Our population-based findings of increased incidence, lower staging and improved survival of patients with testicular cancer in Iceland are important for planning future treatment strategies. The availability of effective treatment, even for patients with advanced disease, stresses the importance of reducing treatment-related morbidity (infertility and secondary malignancies).

Adolescent↗
PubMed2003

Operative mortality after nephrectomy for renal cell carcinoma.

OBJECTIVE: To study the rate and causes of operative and treatment-related mortality after nephrectomy for renal cell carcinoma (RCC) in Iceland. MATERIAL AND METHODS: This retrospective population-based study included all patients who underwent nephrectomy for RCC in Iceland between 1971 and 2000. Patients who died <30 days after the operation were analyzed and compared to those who survived surgery. Disease stage, tumor size, patient age and preoperative American Society of Anesthesiologists classification were compared between the two groups. Autopsy records were examined to determine the causes of death. RESULTS: During the study period 880 patients were diagnosed with RCC and 575 (65%) of them underwent a nephrectomy, 116 (20%) with palliative intent. Operative mortality (OM) was 2.8% and did not change during the 30-year period. Patients with OM were significantly older than those without (73 vs 64 years, respectively) but disease stage, tumor size, ASA classification and gender were comparable between the groups. OM was comparable for patients operated on with palliative (3.4%) vs. curative (2.6%) intent (ns). Median time of death was 10 days postoperatively but no patient died intraoperatively. Causes of death were peri- and postoperative bleeding in five patients, infection/sepsis in four, arrhythmia in three, acute renal failure in two, pulmonary embolism in one and multiorgan failure in one. CONCLUSIONS: OM after nephrectomy for RCC has remained low during the past three decades in Iceland. It is most often caused by perioperative bleeding and infections. We find that the low OM in patients with metastases gives support to the use of palliative nephrectomy as a treatment option when other forms of treatment have failed.

Adult↗
PubMed2003

[The results of surgical treatment for cryptorchidism at Landspitalinn, 1970-1993.].

OBJECTIVE: Cryptorchidism is a common congenital genito-urological anomali in males with increased risk of infertility and testicular cancer. In this retrospective study the results of operations for undescended testis at Landspitalinn University Hospital were reviewed with special emphasis on patients diagnosed with testicular cancer later in life. MATERIAL AND METHODS: The study includes 593 males with undescended testis who were operated on between 1970 and 1993. Information was gathered from hospital records, including birth-weight, age at diagnosis and operation, localization of the testes and complications to surgery. Information on patients diagnosed with testicular cancer was aquired from the Icelandic Cancer Registry. RESULTS: The average birth-weight was 3461 g, including 58 boys (10%) with low birth-weight (</=2500 g). Age at diagnosis was 3.0 year (range 0-14 year) and at operation 7.5 year (range 0-51 year). The undescended testis was more common on the right side (61%) (p<0.01) and 18% had bilateral undescended testis. In 50% of the cases the testis was located in the inguinal canal, intra-abdominal in 10% and 34% were ectopic. Complications to surgery was seen in 29 patients (5%), with hematoma (2.7%) and wound infection (1.2%) as the most common ones. Majority (52%) of the boys had inguinal hernia. Out of 593 males in this study, two have been diagnosed with testicular cancer (mean follow-up time 23 years), both with embryonal carcinoma, 13 and 14 years efter surgery (0.3%). CONCLUSION: The surgical results are good in this study with a low complication-rate. Age at diagnosis is still high (3.0 year) but is decreasing. Age at operation is even higher (7.5 year) underscoring a significant delay in treatment, but only 5.4% of patients were operated on before the age of two as international guidelines recommend. In our cohort the frequency of testicular cancer was only 0.3% which is very low. Informations about infertility was not available in this study.

English Abstract↗
PubMed2003

[Pulmonary sequestration - a case report and review of the litterature.].

Pulmonary sequestration is an uncommon congenital malformation where non-functioning lung tissue is separated from the normal bronchopulmonary tree and vascularized by an aberrant systemic artery. We describe a previously healthy 17 year old girl who was diagnosed with intralobar sequestration following a pneumonia and pulmonary abscess. The diagnosis was made with on CT-scan and confirmed by MRI angiography. A right lower lobectomy was performed and six months later the patient was without symptoms. The case is discussed and the literature reviewed.

English Abstract↗
PubMed2002

P2 receptor expression profiles in human vascular smooth muscle and endothelial cells.

P2 receptors mediate the actions of the extracellular nucleotides ATP, ADP, UTP, and UDP, regulating several physiologic responses including cardiac function, vascular tone, smooth muscle cell (SMC) proliferation, platelet aggregation, and the release of endothelial factors. P2 receptor characterization has been hampered by the lack of selective antagonists. The aim of the current study was to investigate the mRNA and protein expression of P2X and P2Y receptors in human SMC and in endothelial cells (EC). Smooth muscle cells were obtained from human mammary artery and EC from human umbilical vein. Using real-time PCR, the authors established quantitative mRNA assays. Protein expression was studied using Western blotting with recently developed antibodies. The P2X1 receptor was highly specific for human SMC, while the P2X4 was the highest expressed receptor in EC. The P2Y2 receptor was present in both SMC and EC. UTP-mediated effects in these cells are likely to be mediated by P2Y2 and not P2Y4 receptors since the latter had considerably lower expression. The P2Y6 receptor was expressed in both SMC and EC. The P2Y1 and surprisingly the P2Y11 receptors were the most abundantly expressed P2Y receptors in the endothelium. Overall, Western blotting confirmed the mRNA findings in most aspects, and most interestingly, indicated oligomerization of the P2Y1 receptor that may be important for its function. In conclusion, P2X1, P2Y2, and P2Y6 are the most expressed P2 receptors in SMC and are thus probably mediating the contractile and mitogenic actions of extracellular nucleotides. The P2X4, P2Y11, P2Y1, and P2Y2 are the most expressed P2 receptors in EC, and are most likely mediating release of nitric oxide, endothelium-dependent hyperpolarizing factor (EDHF), and t-PA induced by extracellular nucleotides. These findings will help to direct future cardiovascular drug development against the large P2 receptor family.

Animals↗